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What Is Arthritis? Arthritis Symptoms, Types, Causes, Treatments – Prevention Magazine

Bending your knees to climb the stairs. Moving your fingers to button a shirt. Swaying your hips to a favorite song. Most of us dont give much thought to these simple movements, unless they start to become painful or difficult. That can happen when a person has arthritis.

Arthritis is a progressive condition marked by pain or stiffness in the jointsparts of the body where two or more bones meet (like the elbow, wrist, or knee). It can be caused by simple wear and tear or by an overactive immune system, depending on the type of arthritis. But in both cases, the condition can make it harder to carry out everyday activities and have a major impact on a persons quality of life.

Roughly 58.5 million US adults have been diagnosed with arthritis, and that number is expected to jump to 78 million by 2040, according to the Centers for Disease Control and Prevention. Its the leading cause of work disability, and may increase a persons risk for problems like excess body fat and depression.

With arthritis, even the simplest tasks can become monumental. Whether its knitting, hiking, cycling, or just playing with a beloved pet, the pain, stiffness and limitations that come with arthritis can render these activities difficult, says Elizabeth Ortiz, M.D., a Dallas-based rheumatologist in private practice and medical director of Motto Health.

The condition doesnt have to sideline you, though. With the right care plan, you can keep your arthritis symptoms in check and find ways to do more of the things you love with less pain.

You might be surprised to hear that there are more than 100 types of arthritis. While each kind has its own specific symptoms, most can be lumped into one of two big categories.

Osteoarthritis or OA is the most common type of arthritis. Its sometimes called degenerative arthritis, since it happens when wear and tear (from repeatedly using a joint or injuring it) causes damage to a joints cartilage. Cartilage is the smooth, flexible tissue that cushions the ends of your bones, allowing your joints to move without friction. Once it becomes damaged or roughened, the joint bones begin to grind directly on each other, causing pain and stiffness that typically gets worse with activity or as the day goes on.

OA can happen in any joint, but it most often involves weight-bearing joints like the knees or the hips and typically affects them asymmetrically. Experts dont fully know why, but each joint is an independent variable with OA. One could easily have mild OA in the left knee, severe OA in the right hip, and no OA at all in other joints, says Benjamin Bengs, M.D., an orthopedic surgeon at Providence Saint Johns Health Center in Santa Monica, CA.

Simply getting older is a major risk factor, since age alone can cause joint cartilage to wear down. Youre even more prone if youve regularly engaged in high-impact sports (like running, dancing, or basketball), have a job that requires a lot of bending or squatting, or if youve sustained a joint injury (from playing sports or from a car accident, for instance). Women are also significantly more likely to develop OA than men, though experts dont fully understand why.

While osteoarthritis develops from wear and tear, inflammatory arthritis is an autoimmune condition where the immune system mistakenly attacks healthy joint tissue. This, too, can cause pain, stiffness, swelling, and inflammation that tends to get worse with activity and ease up when a person rests. The pain and stiffness can also be intense first thing in the morning.

The most common type of inflammatory arthritis is rheumatoid arthritis or RA. Joints on both sides of the body are typically affected, especially those in the hands, wrists, fingers, knees, ankles, and feet. But RAs problems can also be more far-reachingespecially when the condition isnt well-managedincreasing the risk for fatigue, dry mouth, digestive trouble, hives, or slow-to-heal wounds, as well as lung scarring and heart disease. Its immune system ties also mean that RA also makes people more prone to complications from illnesses like the flu or COVID-19, research shows.

Unlike osteoarthritis, aging isnt a risk factor for RA. In fact, it most often develops in a persons 30s, 40s, or 50s, and can even develop in kids and teens. It tends to run in families, and again, is significantly more common in women than in men.

There are other types of inflammatory arthritis too, including:

Different types and the potential to affect different joints means that arthritis symptoms tend to be pretty individualized. One person with osteoarthritis in their knee might hear cracking or popping when they bend down to grab something or feel like the knee might buckle when they try to stand back up. Another with rheumatoid arthritis in their fingers might find it difficult to write a check or a grocery list and struggle with chronic fatigue or brain fog, for instance.

But some arthritis symptoms tend to show up across the board. Though the severity isnt always the same, most people will experience:

Arthritis can affect your mood too. In fact, up to 1 in 5 people with the condition have symptoms of depression or anxiety. When faced with chronic joint pain and an inability to do the activities we once loved, it is only natural for our mood to be impacted, Dr. Ortiz says. Problem is, these feelings can end up zapping a persons motivation to manage their arthritis, which can lead to a cycle of worsening symptoms and worsening mood.

Osteoarthritis and inflammatory arthritis stem from different causes. OA happens when cartilage surrounding the joint starts to break down, leading the bones surrounding the joint to grind against each other. Its often the result of age-related wear and tear, but can be exacerbated by joint injuries or years of performing high-impact activities.

Inflammatory forms of arthritis like RA occur when the immune system mistakenly attacks the lining of the joints, causing the joints to become swollen and inflamed. Experts dont fully understand what triggers this immune response, but it likely has to do with genes (youre more likely to get RA if close family members have it) and environmental factors like exposure to certain viral infections.

Women are at higher risk for developing both OA and RA. Being overweight or obese can also make a person more prone to arthritis. Excess weight puts more pressure on joints, but there may be more to it. Fat cells can give off inflammatory signals, and simply having more of them may increase inflammation throughout the body, including inflammation around the joints, explains Micah Yu, M.D., an integrative rheumatologist in private practice in Newport Beach, CA.

The goal of arthritis care is to limit a persons pain and improve their function so they can do more of their everyday activities. For RA, its also about controlling inflammation and slowing the diseases progression. That usually involves a combo of medication, therapy, and lifestyle changes, and in some cases, surgery.

Both oral and topical meds can help manage osteoarthritis pain. Some people rely on OTC pain relievers like acetaminophen or NSAIDs ibuprofen, but when thats not enough, prescription NSAIDs or chronic pain meds like duloxetine can offer more relief.

OTC or prescription pain relievers such as NSAIDs can also be helpful for rheumatoid arthritis. But disease-modifying drugs (DMARDs) and biologics such as hydroxychloroquine, methotrexate, adalimumab, or rituximab also play an important role, since they can help prevent or delay the onset of worsening symptoms and permanent joint damage.

Injectable meds may be another option when oral or topical treatments arent doing enough. Your doctor might recommend a corticosteroid injection to temporarily relieve intense pain or inject a lubricant like hyaluronic acid to provide extra cushioning around a painful joint.

During sessions with a physical or occupational therapist, youll learn stretching and strengthening exercises that can go a long way towards reducing your joint pain and making movement easier and more comfortable. In fact, one study found that adults with knee osteoarthritis who participated in regular physical therapy experienced less pain and disability after one year compared to those who received steroid injections.

Healthy habits wont make arthritis go away. But when adopted as part of a comprehensive treatment plan, youll likely notice that you have less joint discomfort and more energy, so you feel better overall. Some behaviors to consider:

You and your doctor might decide to consider surgery to repair or restore damaged joints when other treatment options havent delivered the relief youre looking for. Depending on your symptoms, the procedure might involve removing inflamed joint linings, repairing tendons, fusing or realigning joints, or replacing joints that are badly damaged.

Aches or pains that last a day or two generally arent cause for concern. But you should let your doctor know if youre experiencing persistent joint pain, stiffness, or swelling, or if youre experiencing joint symptoms that are getting in the way of your everyday activities. Rheumatoid arthritis needs to be treated early in order to stave off permanent joint damage. And regardless of your arthritis type, getting care sooner can help you feel better.

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What Is Arthritis? Arthritis Symptoms, Types, Causes, Treatments - Prevention Magazine

Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 … – Hindawi

Although plenty of drugs are currently available for type 2 diabetes mellitus (T2DM), a subset of patients still failed to restore normoglycemia. Recent studies proved that symptoms of T2DM patients who are unresponsive to conventional medications could be relieved with mesenchymal stem/stromal cell (MSC) therapy. However, the lack of systematic summary and analysis for animal and clinical studies of T2DM has limited the establishment of standard guidelines in anti-T2DM MSC therapy. Besides, the therapeutic mechanisms of MSCs to combat T2DM have not been thoroughly understood. In this review, we present an overview of the current status of MSC therapy in treating T2DM for both animal studies and clinical studies. Potential mechanisms of MSC-based intervention on multiple pathological processes of T2DM, such as -cell exhaustion, hepatic dysfunction, insulin resistance, and systemic inflammation, are also delineated. Moreover, we highlight the importance of understanding the pharmacokinetics (PK) of transplanted cells and discuss the hurdles in MSC-based T2DM therapy toward future clinical applications.

Diabetes mellitus (DM) consists of an array of dysfunctions characterized by hyperglycemia and has become one of the most prevalent chronic diseases worldwide. Diabetes has afflicted more than 436 million people in 2019, and this number is estimated to reach 700 million by 2045. Type 1 diabetes mellitus (T1DM) is caused by a deficiency of insulin production, while type 2 diabetes mellitus (T2DM) is linked to insulin resistance. Precisely, more than 90% of diabetic patients are affected by T2DM and, to a large extent, associated with obesity, lack of exercise, poor diet, and heredity [1, 2]. Insulin resistance occurs when cells in the muscle, adipose tissue, and liver insensitively respond to the action of insulin, thus engendering numerous pathogeneses that encompass the accumulation of ectopic lipid metabolites, activation of unfolded protein response (UPR) pathways, and activation of innate immune pathways [2]. Insulin resistance is primarily compensated by elevated insulin secretion, which eventually leads to T2DM due to the exhaustion of pancreatic -cells [3]. Therefore, insulin resistance has become the most prominent predictor of T2DM progression, as well as a potential therapeutic target once hyperglycemia is present [4].

Besides hyperglycemia, most diabetic patients are apt to suffer from various life-threatening complications (e.g., cardiovascular diseases and stroke) that reduce their quality of life and could even inflict fatal outcomes, which further highlights the necessity of suitable pharmacological intervention for the prevention and treatment of diabetes. In conformity with the American Diabetes Association (ADA), the regular treatment of T2DM is based on lifestyle interventions, including a healthy diet, weight loss, and regular practice of physical activity [5]. Nonetheless, these efforts should be performed in concert with antidiabetic drugs for consolidated maintenance of normoglycemia. To date, eight classes of antidiabetic drugs have been approved by the Food and Drug Administration (FDA), including the first-line drug metformin and newly developed glucagon-like peptide-1 receptor agonists (GLP-1RAs) [6], along with versatile medication protocols such as monotherapy, dual therapy, and multiagent therapy to improve the efficacy of T2DM treatment [7]. However, certain pathologies of T2DM, such as -cell exhaustion, hepatic dysfunction, insulin resistance, and systemic inflammation, remain refractory with the employment of conventional medications. Besides, these medications are associated with a myriad of risks and side effects, including hypoglycemia, diarrhea, and liver damage, signifying the indispensability of developing an antidiabetic drug ideal for the augmentation of insulin sensitivity and reversal of pancreatic -cell failure [7].

Recently, cell-based therapies have emerged as the next-generation medicine to address intricate physiopathologies of T2DM [810]. Mesenchymal stem/stromal cells (MSCs) have demonstrated their therapeutic effects in both animal studies and clinical studies, thus offering adept modalities in treating T2DM. In brief, MSCs are capable of self-renewal and differentiating into multiple mesenchymal lineages, such as adipogenic, chondrogenic, and osteogenic lineages in vitro. Moreover, they exhibit low immunogenicity due to the intermediate expression of major histocompatibility complex (MHC) class I, as well as the absence of MHC class II and costimulatory molecules on their cell surfaces [11, 12]. Besides, the plethora of cytokines, growth factors, and exosomes secreted by MSCs play a pivotal role in the regulation of insulin sensitivity and -cell dysfunction [13, 14]. Most significantly, previous studies have indicated that MSCs are capable of exerting certain antidiabetic effects, as supported by the evidence that multiple infusions of MSCs may reverse hyperglycemia instead of single-dose infusion [15, 16]. In this review, we summarize various animal and clinical studies of MSC therapy in treating T2DM. Next, we shed light on the possibility of MSC-based therapy as a novel antidiabetic treatment, with a focus on its potential therapeutic mechanisms. Finally, critical challenges toward the clinical translation of MSC therapy for T2DM are discussed through the viewpoint of cellular pharmacokinetics (PK) and safety considerations.

The multiplexed ability of MSCs to ameliorate T2DM-associated metabolic syndromes such as hyperglycemia, insulin resistance, and systemic inflammation has heretofore been delineated by numerous animal studies. The MSC sources, animal models, delivery routes, and interventions used in these research studies have been summarized in Table 1. Briefly, the main sources of MSCs include the umbilical cord, adipose tissue, and bone marrow from autologous, allogeneic, and xenogeneic origins [1719]. Interestingly, several publications that involved human-derived MSCs revealed that xenogeneic cells conferred suboptimal therapeutic effects in T2DM animal models and did not lead to severe graft rejection [17, 1921].

Furthermore, the most widely used T2DM models in these studies can be stratified into the high-fat diet- (HFD-) induced model, fat-fed/streptozocin- (STZ-) induced model, and leptin receptor-deficient (db/db) model. However, the duration of obesity and T2DM induction varies between different studies, thus causing different pathological stages of T2DM. Generally, a longer time is needed to induce -cell dysfunction than insulin resistance and hyperlipidemia, while 30 weeks were taken to induce nonalcoholic steatohepatitis (NASH) syndrome in small animals [18]. Moreover, STZ is usually injected intrapancreatically into animals after 10 weeks of HFD treatment in order to accelerate the induction of -cell dysfunction [19, 22]. Besides, the db/db model, which is characterized by the deficiency in leptin receptors, is also well adopted owing to the steadily high plasma glucose level [23].

According to Table 1, the majority of researchers deliver therapeutic MSCs through the intravenous tail vein despite the fact that MSCs would be trapped within the lung capillaries and eliminated rapidly within hours postadministration [18, 2225]. On the other hand, a single administration of MSCs has been proved to provide potent therapeutic effects on glucose tolerance and insulin tolerance in diabetic animals [18, 22]. However, only a limited number of articles summarize the versatile therapeutic effects of MSCs among diverse formulation and dosing regimens on T2DM animal models. Therefore, further studies should be carried out to establish the standard guidelines to be implemented in MSC therapy.

In addition to optimizing the MSC sources, animal models, administration routes, and dosages, cell engineering strategies have been scrutinized to improve the therapeutic outcomes of MSCs. In particular, genetically modified MSCs were exploited to induce the secretion of rarely expressed or nonnative therapeutic proteins with the advent of gene-editing tools such as CRISPR-Cas9, viral and nonviral vectors. For instance, Xu et al. have exemplified that the overexpression of insulin-producing genes in mouse MSCs significantly sustained their antidiabetic effects in vivo after intrahepatic administration [26]. Karnieli et al. also reported that MSCs transfected with pancreatic and duodenal homeobox-1 (PDX-1) can reduce blood glucose in STZ-diabetic severe combined immunodeficient (SCID) mice after 5 weeks [27], accompanied with some drawback as the mice developed abnormal glucose tolerance after 6-8 weeks of transplantation. In addition, Milanesi et al. used human bone marrow mesenchymal stem cells (hBM-MSCs) to coexpress the vascular endothelial growth factor (VEGF) and PDX-1 transiently and were able to reverse hyperglycemia in more than half of the diabetic mice, denoting that MSCs improved their overall survival and body weight [28]. However, discrepant effects were observed between mice treated with hBM-MSCs with dual and single gene expressions. Aside from insulin-producing genes, PDX-1, VEGF, and interfering neurogenin 3 (Ngn3) have also been integrated into MSCs to augment their antidiabetic effects [29]. In our recent research, we genetically engineered MSCs with Exendin-4 (MSC-Ex-4) and demonstrated their boosted cellular function and antidiabetic efficacy in the T2DM mouse model. The Exendin-4 secreted by MSC-Ex-4 improved MSC survival under high glucose stress via autocrine activation of the GLP-1R-mediated AMPK signaling pathway, as well as suppressed senescence and apoptosis of pancreatic -cells through endocrine effects. We also showed that the amplified secretion of bioactive factors (e.g., IGFBP2 and APOM) of MSC-Ex-4 paracrinely augments insulin sensitivity and decreases lipid accumulation in hepatocytes through PI3K-AKT activation [30]. Indisputably, the functional proteins secreted by genetically modified MSCs may be useful to mitigate NASH and metabolic-associated fatty liver disease (MAFLD) concomitantly, concerning that diabetes is intimately associated with these complications. In concise detail, the antidiabetic GLP-1RA commercialized by Novo Nordisk, namely, semaglutide, has shown encouraging effects in resolving the symptoms of NASH in phase 2 trials [31].

Nevertheless, these genetically engineered MSCs still exhibited numerous setbacks, which lead to the underwhelming therapeutic effects of MSCs. Firstly, transient transfection is extremely unstable, thus resulting in short-lasting therapeutic effects. Secondly, most viral vectors are not desirable in clinical settings due to the possibility of causing carcinogenesis and immune responses, which indicates a demand for other cell engineering modalities in order to enhance the MSC potency. Simultaneously, maintaining the low generation of MSCs and reducing the cell damage during cell transfection and chemical (e.g., puromycin) selection are challenging tasks. Meanwhile, the ethical concerns involving gene manipulation face a considerable degree of skepticism. However, with the continuous advancement of gene-editing tools with unprecedented spatiotemporal control, we believe that the genetic manipulation techniques are prompt to have enhanced precision, efficacy, and safety [32, 33].

According to the data published by the National Institutes of Health (NIH), current clinical trials of MSCs involved in the treatment of diabetes mainly focus on T1DM patients. In 2008, the University of Miami has started MSC therapy on T2DM patients by using bone marrow stem cells (BM-SCs), which were harvested from the patients iliac crest bone marrow [38]. Although this study did not authenticate the identity of isolated cells, most of these cells were claimed to be MSCs according to the isolation method. The metabolic panels showed significant improvement in T2DM patients when comparing baseline data with 12 months of follow-up data. Furthermore, combinatorial therapy of intrapancreatically infused autologous stem cells (ASCs) and hyperbaric oxygen therapy (HBO) can improve the metabolic and insulin control of T2DM patients. Still, further randomized and controlled clinical trials are necessary to validate these findings.

According to Table 2, although human umbilical cord mesenchymal stem cells (hUC-MSCs), BM-MSCs, and bone marrow mononuclear cells (BM-MNCs) are the mostly used cell types in clinical trials, some infrequently used cell types or conditions, such as hypoxia preconditioned mesenchymal stem cells (HP-MSCs) and bone marrow-derived mesenchymal precursor cells (BM-MPCs), also show their therapeutic effects. Besides, MSC therapy was applied as an adjuvant to strengthen the efficacy of antidiabetic drugs. In a Chinese clinical trial, 12 T2DM patients who failed to reinstate normal glycemic control after liraglutide treatment were treated with cells/kg of hUC-MSCs via pancreatic artery infusion on the first day, with another cells/kg of cells infused through the peripheral vein on days 8, 15, and 22. On the contrary, control subjects were infused with saline, while both groups were treated with liraglutide for 24 weeks. The result demonstrated that the fasting plasma glucose (FPG), postload glucose (2hPG), and hemoglobin A1c (HbA1c) levels were significantly decreased in subjects who received MSC therapy in comparison with control groups [39], indicating that MSCs can improve glucose metabolism and -cell function in T2DM patients in combination with other medications or therapies.

In addition, intrapancreatic and intravenous infusion methods are generally used in clinical studies due to safety concerns. In 2014, Liu et al. found that subcutaneous hematoma was developed at the injection site of a patient during the first day of intrapancreatic injection, which was resolved subsequently after seven days. Besides, nausea, vomiting, and headache also occurred in another patient, who recovered spontaneously within one week. Therefore, although previous clinical trials showed that intravenously injected MSCs can cause pulmonary microembolism, no serious adverse reactions have been indicated so far [40]. In addition, the therapeutic effects of MSCs can be enhanced when combined with biological materials, such as collagen and hydrogels. A clinical study that was aimed at improving the erectile function of men with diabetes by the injection of collagen hydrogel and hUC-MSC mixture into the cavernous body was recruiting in 2015. Since a collagen scaffold has been demonstrated to prolong the lifetime and maintain the stemness of MSCs, we can assume that the combination of stem cell therapy and tissue engineering can further augment the therapeutic efficacy of MSCs.

Although the therapeutic efficacy of MSC therapies for T2DM has been postulated decades ago, their underlying mechanisms remain elusive. Therefore, multiple potential mechanisms of MSCs in various pathological processes of T2DM, such as -cell exhaustion, hepatic dysfunction, insulin resistance, and systemic inflammation, are envisaged here.

MSCs promote insulin production by facilitating the regeneration of endogenous pancreatic islet -cells, and several hypotheses about their fundamental mechanisms have been reported. Although previous studies have proved that MSCs can differentiate into -cells or insulin-producing cells in vitro [4850], it is increasingly evidenced that limited transdifferentiation of the infused MSCs could occur in vivo to facilitate the process of pancreas regeneration and ameliorate hyperglycemia in T2DM models. For example, Hess et al. discovered that despite the elevated insulin production of streptozotocin- (STZ-) induced mice at 42 days after the intravenous injection of hBM-MSCs, the majority of the transplanted cells migrated to ductal and islet structures, and only a minority of transplanted cells are labeled with insulin [51]. Therefore, although MSCs can initiate endogenous insulin production and stimulate the proliferation of -cells, transdifferentiation of MSCs into -cells and transplantation engraftment may not significantly contribute to the restoration of pancreas function.

Moreover, MSCs demonstrate their repairing potential through the secretion of versatile cytokines and growth factors, including transforming growth factor- (TGF-) , interleukin- (IL-) 6, and VEGF, which participate through both the paracrine and autocrine actions to enhance the islet function [52] and facilitate the vascularization process (Figure 1) [53]. In addition, some researchers correlated the islet repairing potential of MSCs to their antiapoptotic effects. Briefly, Borg et al. proved that BM-MSCs could reduce islet cell apoptosis as decreased cleavage of caspase 3 in vivo was observed after MSC treatment [54]. Chandravanshi and Bhonde further proved the antiapoptotic effect of MSCs by downregulating reactive oxygen species (ROS), nitric oxide, superoxide ions, caspase 3, caspase 8, and p53 and upregulating Bcl2 under hypoxia circumstances [55]. Besides, BM-MSCs are able to alleviate endoplasmic reticulum stress- (ERS-) induced apoptosis by overexpressing Myc through stromal cell-derived factor- (SDF-) 1 signaling or cell-cell interaction (Figure 1) [56].

Besides, MSCs are capable of enhancing the formation of autophagosomes by clearing impaired mitochondria and increasing the number of insulin granules (Figure 1) [22]. Mitochondria are key players in energy production, signaling, and apoptosis in cells, and their dysfunction has become the hallmark of various diseases, including diabetes, ischemia, inflammation, and aging. An increasing number of studies have revealed that MSC-mediated mitochondrial transfer is a mainstay to rescue injured cells and restore mitochondrial functions [57, 58]. Rackham et al. demonstrated that mitochondria of MSCs could be transferred to -cells under hypoxia conditions for replenishment. Consequently, the oxygen consumption rate and insulin secretion rate of islet cells were enhanced after being cultured with MSCs, indicating that mitochondrial transfer could respond to and alleviate hypoxic and oxidative stress caused by excessive ROS production from damaged mitochondria [59]. Considering that mitochondria play a central role in energy metabolism, their intercellular transfer may partially explain the therapeutic mechanism of MSCs in improving -cell regeneration. Besides, an increasing number of studies have postulated that mitochondrial donation by MSCs can also ameliorate other diabetic complications, including diabetic nephropathy and inflammation [58, 60, 61].

T2DM is strongly associated with hepatic dysfunction, provided that around 57% to 80% of T2DM patients are suffering from MAFLD. In short, the relationship between MAFLD and T2DM is intricate and bidirectional, as they share similar features and metabolic syndromes, such as the accumulation of hepatic lipids, oxidative stress, and glucose tolerance [62]. In 2012, Ezquer et al. found that intravenously transplanted MSCs could significantly lower a panel of disordered biochemical markers of liver function caused by HFD, for instance, alkaline phosphatase (AKP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), implying that MSCs could improve liver function of T2DM patients (Figure 1) [18].

PPARs are the major regulators of lipid metabolism, which help to control the balance of fatty acid uptake, adipogenesis, and -oxidation. After MSC administration, PPAR- was upregulated while PPAR- was downregulated in the liver of HFD mice, denoting that PPAR signaling pathways modulated by MSCs implicitly influence hepatic metabolism [17]. Besides, the expression of enzymes associated with hepatic glycolysis, including glucokinase (GCK), liver pyruvate kinase (L-PK), and 6-phosphofructo-1-kinase (PFK), was greatly elevated. Meanwhile, enzymes involved in gluconeogenesis, such as peroxisome proliferator -activated receptor coactivator 1- (PGC-1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase), were reduced [24]. Evidence shows that the infusion of MSCs will activate protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling pathways, which play indispensable roles in cell metabolism (Figure 1) [24, 25].

Furthermore, oxidative stress caused by mitochondrial dysfunction will also lead to liver metabolic imbalance [63]. The glutathione (GSH)/oxidized glutathione (GSSG) ratio was reduced, and the amount of superoxide dismutase, which is inversely proportional to systemic ROS levels, was increased after MSC treatment (Figure 1) [64, 65], postulating that the therapeutic effect of MSCs is highly associated with metabolic homeostasis. Meanwhile, treatment using an MSC-conditioned medium exhibited similar effects, suggesting that paracrine effects significantly contribute to the reparation process in T2DM [25]. In our recent work, we demonstrated that the intravenously injected MSCs resided in the liver on day 5 postadministration and persisted for 15 days. Besides, bioactive factors (e.g., IGFBP2 and APOM) secreted by MSCs paracrinely augmented insulin sensitivity and decreased lipid accumulation in hepatocytes through PI3K-AKT activation [30].

Insulin resistance, which is a distinctive hallmark of T2DM, describes the failure of cells to respond to insulin during disease progression. Lately, Si et al. revealed that intravenously injected BM-MSCs could increase GLUT expression and elevate phosphorylation of insulin receptor substrate-1 (IRS-1) and AKT in the target tissues of insulin [66], delineating that MSCs are capable of alleviating insulin resistance of diabetic patients. Furthermore, Deng et al. also showed that Mitsugumin 53 (MG53), an E3 ligase that promotes the ubiquitinoylation of IRS-1 in skeletal muscles, was inhibited by MSCs (Figure 2) [67]. Akin to the skeletal muscle that accounts for 70%-80% of insulin-stimulated glucose disposal, inhibition of the IRS-1 ubiquitin pathway may also engage in alleviating insulin resistance [68]. Moreover, insulin resistance in MAFLD and subsequent hepatic diseases is associated with the overproduction of inflammatory mediators and their downstream signaling molecules, with evidence suggesting that NOD-like receptor protein 3 (NLRP3) inflammasomes play an important role in obesity-induced insulin resistance [21]. The application of MSCs in T2DM treatment exemplifies that NLRP3 formation was inhibited through immune response regulation of MSCs, thus enhancing the function of IRS-1 and GLUT4 in hepatic cells (Figure 2) [35].

Besides, exosomes, which are nanoscale extracellular vesicles, also show broad prospects in tissue regeneration and damage reparation. In vivo experiments have further demonstrated the therapeutic effects of intravenously injected MSC exosomes in reducing the blood glucose level, as well as restoring the phosphorylation of IRS-1 and AKT signaling pathways in insulin target tissues [20]. The latest study confirmed that exosomal miR-29b-3p can regulate cellular insulin sensitivity via sirtuin- (SIRT-) 1 (Figure 2) [14], which is a class III histone deacetylase deeply involved in apoptosis, genomic stability, and gene expression regulation, indicating that histone modification related to insulin resistance is one of the treatment approaches of MSCs. Moreover, the clearance of dysfunctional mitochondria, alleviation of ERS, and diminishment of ROS may ameliorate insulin resistance [69].

It is notorious that the pathogenesis of obesity-related insulin resistance includes chronic low-grade inflammation and activation of the immune system [21, 70]. Therefore, overexpression of systemic inflammatory cytokines, such as tumor necrosis factor- (TNF-) , interleukin- (IL-) 1, and IL-6, is accompanied by the pathogenesis of metabolic syndromes, including insulin resistance, atherosclerosis, and MAFLD (Figure 2). Likewise, the abnormal changes in peripheral or tissue-resident immune cells and their regulatory function always accompany the development of diabetes, indicating that immune cells such as T lymphocytes (T cells), macrophages, and natural killer cells (NK cells) are considered to participate in the progression of T2DM concomitantly [21].

It has been a prevailing dogma that MSCs have immune privilege properties. This is exemplified by the immunomodulatory effects of MSCs on T cells, B lymphocytes (B cells), dendritic cells (DCs), and NK cells, mainly via paracrine effects that involve the secretion of enzymes, chemokines, cytokines, anti-inflammatory mediators, growth factors, and extracellular vesicles [71, 72]. Briefly, MSC activation is subjected to the stimulation of a multitude of inflammatory cytokines, including TNF- and interferon- (IFN-) , which in turn shift to an immunosuppressive phenotype by inducing the secretion of soluble factors that mediated immunomodulatory activities, such as prostaglandin E2 (PGE2), hepatocyte growth factor (HGF), indoleamine-pyrrole 2,3-dioxygenase (IDO), and IL-10 [73, 74]. Additionally, the paracrine immunomodulatory properties of MSCs are highly mediated by versatile signaling pathways like the telomerase-associated protein Rap1/NF-B pathway [75]. Although we do not have a comprehensive understanding of the precise mechanism of MSC-based immunomodulation, MSCs have been harnessed for the treatment of immune-mediated disorders [76, 77], including graft-versus-host disease (GvHD) and diabetes.

To date, experimental results showed that the inflammatory status of STZ-diabetic animal models contributes to the modification of the pancreatic microenvironment, while the administration of MSCs promoted the proliferation of regulatory T cells (Tregs) to provide long-term immunoregulatory effects [78]. Consequently, Th2 cytokines (IL-10 and IL-13) secreted by Tregs seem to play a key role in -cell activation and survival through their anti-inflammatory effects, where the definitive mechanism of action remains to be an enigma (Figure 2) [19]. Besides, the mobilization of MSCs by inflammatory factors under specific microenvironments has been demonstrated, illustrating that MSCs can elicit the transition of macrophages into an anti-inflammatory phenotype to alleviate insulin resistance in T2DM rats [34, 36]. In brief, classically activated macrophages (M1) could stimulate MSCs to overexpress IL-6 and MCP-1, thus converting M1 into an alternatively activated phenotype (M2) (Figure 2). Meanwhile, IL-4R expression was upregulated in macrophages, which sensitizes them to the IL-4 stimulus. Moreover, MSCs can downregulate the systemic inflammatory cytokines to impair insulin receptor action and respective downstream signaling pathways by preventing the formation of NLRP3 in the adipose tissue and liver [35]. Wang et al. demonstrated that IL-1 and TNF- secreted by the T2DM islet could stimulate MSCs to secrete IL-1Ra, which could ameliorate islet inflammation (Figure 2) [37]. In conclusion, the above mechanistic investigation provides a theoretical basis for the clinical application of MSCs in the treatment of T2DM along with its associated complications.

Although MSCs have shown their potential in treating T2DM both in vitro and in vivo, we have not thoroughly understood their in vivo behavior, which hampers further progress for clinical investigation in the field of MSC-based T2DM therapy [79]. It is generally known that there is often a discrepancy in the kinetics of MSCs among different cell sources, T2DM models, and routes of administration [80]. Therefore, the ability to determine the dose, in vivo distribution, and extended viability of MSCs in patients is crucial in developing MSC-based therapies and elucidating the in vivo therapeutic mechanism of administered MSCs for T2DM treatment [81]. Furthermore, increased knowledge of MSC distribution after delivery could allow researchers to estimate cellular pharmacokinetics, thus identifying the dosing scheme required to achieve optimal therapeutic effects [82]. Akin to the use of a PK model for drug development, which delineated the time course of drug absorption, distribution, metabolism, and excretion (ADME), an effective in vivo kinetic model of administered MSCs and their released factors should be adapted and applied to allow clinical translation of therapeutic MSCs in treating T2DM. If robust pharmacokinetic models of MSCs can be developed, the therapeutic efficacy of MSCs in various treatment conditions can be predicted, thus informing the optimal administration regimes of the cells and hastening the progression of clinical research [80].

Despite the rapid progress in using MSCs as a safe and effective treatment of T2DM, the in vivo PK of administered MSCs is rarely reported. Sood et al. labeled BM-MNCs with a positron emission tomography (PET) tracer, namely, fluorine 18-fluorodeoxyglucose (18F-FDG), to track the biodistribution of cells in vivo. BM-MNCs were administered to diabetic patients through three different routesperipheral intravenous, superior pancreaticoduodenal artery, and splenic artery injectionwith the in vivo biodistribution of cells tracked and quantified at 30 and 90 minutes after administration. More BM-MNCs were retained in the pancreas after being administered through the superior pancreaticoduodenal artery, while no discernible cell was observed after splenic artery and intravenous injection. Besides the pancreas, the spleen also showed an intense FDG signal after splenic artery injection. On the contrary, the lung showed retention of cells within 30 minutes, with a significant clearance in 90 minutes after intravenous injection [83]. The study by Sood et al. did not track the BM-MNCs for a longer time. Furthermore, Yaochite et al. generated adipose-derived- (AD-) MSCsLuc+ that expressed luciferase and administered the cells to STZ-induced diabetic mice through intrasplenic or intrapancreatic injection. Following intrasplenic transplantation, AD-MSCsLuc+ were mainly observed in the liver and pancreas until day 8 after intrasplenic and intrapancreatic injection, respectively. However, these injection routes are rarely used in clinical trials, denoting that the long-term distribution of MSCs after intravenous injection should be further compared with the above administration routes in diabetic mice and patients [84].

Although the biodistribution of cells can be quantified by various experiment techniques, the PK of administered cells has not been studied systematically through a PK model. During the past 30 years, many PK models have been developed to describe the ADME of conventional drugs, which were successfully applied to predict the safety and efficacy of therapeutic agents, including biologics and small-molecule drugs [80]. Studying the PK aspects of MSCs is difficult but critical in the development of MSC therapy, which could assist in the optimization of the cell dosage, mode of injection, course treatment, and targeting strategies to achieve maximum efficiency with the lowest risk [85]. To simplify the explanation of the in vivo kinetics of therapeutic cells, the dynamics of systematically administered cells have been considered similar to those of inert micrometer-scale particles injected into the bloodstream of animals [83, 86, 87]. To date, the only published PK model of MSCs was developed in 2016 [79]. Wang et al. established a physiological-based (PB) PK model based on the anatomical structure of the body, which separates every important organ in the body as an individual compartment, and each of them is interconnected by blood vessels. In this simplified model, the whole body was divided into eight interconnected compartments, which were the arterial blood, lungs, liver, spleen, kidneys, heart, venous blood, and the rest of the human body (Figure 3) [37]. Once administered intravenously, most of the MSCs were rapidly transferred to the blood vessels of each organ through systemic blood flow. MSCs that reached the organs were either passively entrapped in the microvessels or actively adhered to the endothelial cells. The entrapped MSCs were either released back into the blood circulation or eliminated after depletion (Figure 3). Therefore, , , and were used to represent the rate constants of the arrest, release, and depletion processes, respectively, along with other key parameters, including species-specific physiological parameters (body weight, organ volume, and blood flow) and MSC-specific parameters (partition coefficient, arrest rate constant, release rate constant, and depletion rate constant). Through this PBPK model, the time course of MSC concentration in blood and individual organs can be predicted across species, such as mice, rats, and humans. However, the model only predicts a fast distribution process of MSCs in the body within 24 hours, implying that optimization of the current model is imperative, as the slow biological process such as proliferation, senescence, and differentiation of the arrested MSCs should be incorporated into the model [88].

Besides, it is well established that MSCs can play their therapeutic roles beyond what is conveyed by the transplanted cells alone, mainly through the secretion of bioactive products, namely, the secretome [89]. Therefore, the PK of these factors, which are constantly secreted by MSCs, should be considered in a similar way to common pharmaceutical drugs [80]. Salvadori et al. used the approach described by Parekkadan and Milwid [86] to establish a new pharmacokinetic-pharmacodynamic (PK-PD) model, namely, the two-functional-compartments PK-PD model [82]. In this model, the cell-related biomarkers released by MSCs, which are capable of influencing bystander cells (e.g., macrophages), can secrete specialized bioactive substances that play a main role in the PD of administered cells [90]. Accordingly, they described that MSCs can attenuate sepsis by releasing PGE2, which binds to PGE2 receptors of activated macrophages and provokes the release of IL-10 that in turn reduces inflammation by acting on immune cells [86]. Moreover, other supporting data on this concept have been reported [91]. Nevertheless, the present models are still unable to represent the long-term in vivo kinetics of MSCs and their secretomes adequately.

In short, understanding the in vivo kinetics of administered drugs can be challenging, especially for nontraditional drugs such as MSCs. A functional PK-PD model may begin to predict the pharmacokinetics of MSC therapies through a specific formulation and administration pathway by utilizing both in silico modeling and empirical analysis. Besides, studies of the pharmacokinetic model have the ability for interspecies scaling, allowing us to predict the in vivo kinetics of therapeutic MSCs in humans through animal data. However, it is indefinite how well the findings in animals can be quantitatively transferred to humans. Despite the use of MSCs in clinical trials, many details still need to be discussed as their biodistribution varies under different treatment conditions. Therefore, combined PK-PD modeling describing both the biodistribution and the functional secreted factors of MSCs should be unraveled to achieve more efficacious MSC therapeutics in the future.

According to the summarization of preclinical and clinical results in the aforementioned studies, MSC-based therapy has made tremendous progress in T2DM treatment in both animal studies and clinical trials. Aside from the necessity of developing a robust PK-PD model, there are still many encumbrances for MSCs to transit out of the laboratory stage and be launched as therapeutic products in the pharmaceutical industry. Some of these impediments have become a mutual subject in the field of cell therapy, but some necessitate particular considerations due to the special characteristics of T2DM that are distinct from other diseases. Therefore, various challenges in the clinical development of MSC therapy for T2DM are discussed here, which include but are not restricted to the limited therapeutic effects caused by the lung barrier, the capillary blockage caused by microthrombus, and the selection of diverse cell sources.

The delivery routes of MSCs have been shown to dramatically influence the therapeutic effects of MSCs. In small animal and clinical studies, intravenous injection is the most frequently used administration route and the bioluminescence imaging system is widely accepted to track the in vivo biodistribution of MSCs. Impoverished cell survival was discovered as most of the MSCs were trapped within the lung capillaries and eliminated within hours posttail vein injection [92]. Still, the fate of MSCs in the lung is controversial as the fluorescence signal gradually disappeared during long-term tracking [93]. Furthermore, microthrombus that contributes to the blockages in lung capillaries also arises as a potential safety issue in cell therapy. According to previous studies, intravenous infusion of MSCs will lead to a reduced blood flow velocity in the lung capillaries, which resulted in the formation of local thrombus in the blood vessels [94]. In order to resolve this drawback, heparin was mixed with cell suspension by Liao et al. during systemic injection [95], while MSCs were pretreated with hypertonic solution by Leibacher et al. to reduce the cell size [96]. Besides, Leibacher et al. also suggested that the size of MSCs would gradually increase with prolonged culture passage [96], indicating that the infusion of MSCs with lower passage will reduce the formation of microthrombus.

Although MSCs derived from various sources such as the umbilical cord, adipose tissue, and bone marrow have shown efficacy in relieving T2DM in preclinical and clinical studies, the clinical success of MSC therapy is still facing great challenges due to their compromised expansion potential and age-associated functional decline, as well as the setbacks in the standardized and large-scale manufacture of therapeutic MSCs [97, 98]. Primary MSCs isolated from different donors, tissue sources, cell separation methods, or culture conditions show natural heterogenicity, which causes batch-to-batch variation and diverse differential and therapeutic efficacy [97, 98]. Therefore, the production of MSCs complying with the current good manufacturing practice (cGMP) standards becomes a prerequisite to ensure the standardization and reproducibility, as well as the quality and safety of MSCs for clinical use [99]. Besides, although MSCs have been considered safe with minimal tumorigenicity after transplantation, genetically modified MSCs are facing safety concerns, including the immunogenic toxicity of viral vectors, insertional oncogenesis, and mutational integration [97].

To date, there are insufficient studies that have compared the therapeutic effects of MSCs from different sources and engineering methods systematically. Therefore, the selection of MSCs that can achieve the best prognosis effect under diverse clinical circumstances remains an arduous task to be investigated concertedly. Particularly, the ability of AD-MSCs to improve glucose tolerance effectively is evidenced by both animal studies and preclinical studies. However, despite the lower production cost, higher feasibility, and superior in vitro expansion ability of AD-MSCs, research shows that adipose tissue in T2DM patients is in an inflammatory state and is accompanied by a certain degree of cell aging [100]. Aging cells will disrupt tissue function through their senescence-associated secretory phenotype (SASP), which contains a large number of inflammatory factors, thus contributing significantly to systemic inflammation in T2DM patients [101]. Furthermore, SASP can cause insulin resistance in liver cells and apoptosis of islet cells, given that transplanting senescent adipose tissue will affect the animals behavioral ability and accelerate the aging of mice [102]. Therefore, it is still questionable whether autologous AD-MSCs are suitable for the treatment of T2DM, concerning that the adipocytes in diabetic patients are in an inflammatory state. Besides, autologous cells are hard to be developed as off-the-shelf products due to their longer processing duration after being extracted from patients. On the other hand, although studies have shown that MSCs exhibit immunoregulatory effects, it remains elusive as to what degree the allogeneic cells trigger immune responses in vivo after the administration [103].

Aside from primary tissue-derived MSCs, the employment of MSCs differentiated from human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), may potentially be more desirable choices as safer and more effective MSC medications against T2DM [104]. In particular, iPSCs based on cell reprogramming technology have provided unprecedented opportunities to expedite the development of human cell therapies, without involving the ethical issues of ESCs. Briefly, the advantages of iPSC-derived MSCs (iMSCs) include their potential to produce infinite donor-related sources of specific stem cells with improved homogeneity, stability, controllability, and scalability, thus becoming a preferential commercial candidate for clinical applications [97, 98]. Besides, it is increasingly appreciated that human iMSCs exhibit higher proliferative potential and display potent immunomodulatory properties [105, 106]. To date, Cymerus MSCs (CYP-001), which are derived from adult iPSCs produced by an optimized GMP-compliant manufacturing process, have been characterized by Cynata Therapeutics and received approval to launch the worlds first formal trial for the treatment of acute steroid-resistant GvHD [107, 108]. However, it is worth noting that there are still a few hurdles, such as potential tumorigenicity, immunogenicity, and heterogeneity, which remain to be overcome when using iMSCs for downstream applications, including T2DM therapy in the future [104].

Although the therapeutic success is substantiated by MSCs in preclinical and clinical studies, their mechanisms of action in the progression of T2DM become the foremost issue to be thoroughly elucidated. Meanwhile, although researchers reach a consensus on the immunosuppressive effect of MSCs [32], the mechanism that describes how MSCs can affect systemic inflammation has not been thoroughly clarified. Galleu et al. investigated the therapeutic effects of MSCs on GvHD and suggested that those MSCs that resided in the lung were attacked by cytotoxic T cells and NK cells, thus leading to cell apoptosis [109]. Consequently, fragments produced by apoptotic MSCs are phagocytosed by macrophages to produce indoleamine 2,3-dioxygenase, which helps to mediate systemic inflammation inhibition. However, it remains unclear whether apoptotic MSCs contribute to the same therapeutic mechanism in treating T2DM. In addition, Akiyama et al. believe that MSCs can induce T cell apoptosis through their production of the Fas ligand, and the apoptotic fragments are swallowed by macrophages to trigger systemic immune regulation [110], suggesting that the diverse roles of MSCs might lead to potential safety risks in clinical use. Therefore, uncovering the fate of MSCs in vivo will pave the way for the understanding of therapeutic mechanisms to accelerate the progress of their clinical translation.

Despite the complexity involved in the pathological process of diabetes, various conventional drugs are capable of lowering blood sugar levels through different mechanisms. However, it is uncertain whether antidiabetic drugs can reverse the pathological progression of T2DM. Thiazolidinedione, which possesses the potential to increase liver insulin sensitivity, has a risk of inducing heart failure or hepatic dysfunction [111]. GLP-1RAs have shown a broad range of therapeutic effects in various diseases aside from their antidiabetic effects. Recent studies have proved that liraglutide, exenatide, and semaglutide show promises in treating cardiovascular diseases [112, 113], MAFLD [114], obesity [115], ischemic stroke [112, 116, 117], Parkinsons disease [118, 119], and Alzheimers disease [120]. Therefore, combinatory administration of GLP-1RAs and MSCs is expected to augment the therapeutic efficacy of both the antidiabetic drugs and the MSCs.

In conclusion, the therapeutic effects of MSCs on T2DM are multifaceted [121] and the possible therapeutic mechanisms have been summarized here. MSCs can improve the systemic inflammatory state through their immunosuppressive functions, reduce the apoptosis of islet -cells to augment insulin secretion, and improve the metabolic state of the liver. However, further in-depth clarifications regarding the mechanisms of action of MSCs in treating T2DM are still a requisite. Therefore, whether it is possible for MSCs or novel MSC-assisted therapeutics to surpass traditional medicines in reversing the progression of T2DM remains an engrossing question to be explored in the future.

The references used to support the findings of this study are included within the article.

All authors declare that they have no conflicts of interest.

Shuang Gao, Yuanyuan Zhang, and Kaini Liang contributed equally to this work under the supervision of Yanan Du. All authors read and approved the final manuscript.

All authors would like to thank all members of Du Lab for their great support. This work is financially supported by the National Key Research and Development Program of China (2017YFA0104901), the Beijing Municipal Science and Technology Commission (Z181100001818005), and the China Postdoctoral Science Foundation (043220012).

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Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 ... - Hindawi

All Puppies Have Been Adopted and This One Was Left Behind – K945

A couple of months ago a momma dog and her companion were dumped on Westport road in Shreveport. They made their way along I-20 and by some miracle, these dogs weren't hit.

What started off as a "Let me take these dogs in for the week until we figure out what's going to happen with the dogs" turned into a "This momma dog is going to give birth in 7 to 10 days. We have puppies on the way."

Krystal Montez, Canva

Highway is the shy one of the crew and he really just wants to cuddle and hide under a blanket. He is already a professional cuddler so if you love puppy breath and puppy cuddles he wants to go home with you.

Krystal Montez

If you are interested in adoptingHighway he is ready to gohome.He has gotten his first round of puppyshots and it's a $120 adoption fee to cover all of the expenses. You must have a vet reference or good standing with an animal rescue. We want to make sure all these pups end up in the best homes as we have grown to love these little dudes already. To apply to adopt this sweet pup or if you have any questions email jackie.whaley@townsquaremedia.com with the subject "Highway Puppy".

Check out these 50 fascinating facts about dogs:

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

Does your loyal pup's breed make the list? Read on to see if you'll be bragging to the neighbors about your dog's intellectual prowess the next time you take your fur baby out for a walk. Don't worry: Even if your dog's breed doesn't land on the list, that doesn't mean he's not a good boy--some traits simply can't be measured.

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All Puppies Have Been Adopted and This One Was Left Behind - K945

Tanya Dorff, MD, Speaks to the Development of CAR T-Cell Therapy in Prostate Cancer – Cancer Network

At 2022 ASCO, Tanya Dorff, MD, reviewed the use of CAR T cells in the treatment of prostate cancer.

CAR T cells are typically used in the treatment of hematologic malignancies, but recent studies have shown they may also be used to combat prostate cancer. A recent panel discussion by Tanya Dorff, MD, from the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting shed light on this potential addition to the prostate cancer treatment paradigm.

Several trials are underway assessing the use CAR T cells targeted to prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and KLK2. Dorff emphasized the importance of educating oncologists who treat solid malignancies to identify adverse effects and mechanisms associated with CAR T-cell therapies that those specializing in hematologic malignancies may be more familiar with.

A big part of our education focus was just to help familiarize solid tumor oncologists with things like cytokine release syndrome and macrophage activation and the ways these present and how to manage them. Thats the long-term implementation of making sure the community is educated as a whole so these treatments can be widely accessed, Dorff, an associate professor in the Department of Medical oncology and Therapeutics Research, and section chief of the Genitourinary Disease Program at City of Hope, said in an interview with CancerNetwork.

Dorff also discussed highlights in prostate cancer from the 2022 ASCO Annual Meeting, including the use potential treatment intensification with triplet regimens up front and the efficacy of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

Dorff: I was part of an educational session discussing CAR T-cell therapy and bispecific T-cell engaging therapy for advanced prostate cancer. It was a case-based approach helping oncologists get a sense of how these treatments that are traditionally used in hematologic malignancies are being studied in prostate cancer, what to expect from them, how things are going, what kind of results were seeing, and where were going next with the field.

We have a long way to go to get CAR T-cell therapy into practice for prostate cancer, but weve been excited that even within the first handful of patients treated on the various trials, we are seeing responses. At the 2022 ASCO Genitourinary Symposium (ASCO GU), a poster was presented for POSEIDAs PSMA CAR T product by Susan F. Slovin, MD, PhD, of Memorial Sloan Kettering,1 showing this beautiful response in a patient and a fairly robust PSA [prostate specific antigen] response waterfall from that early experience with the CAR T-cell [study. Findings using] our PSCA-targeted CAR T from City of Hope that our scientists have developed and we produce here were also presented a ASCO GU showing, again, a robust response early on. However, the toxicity was considerable.2 Were just learning what the [adverse] effect [AE] profile will look like in [patients with] prostate cancer vs hematologic malignancies. Taking a step back, were still sorting out optimal dosing and whether were going to need adjunctive strategies or multiple doses to get a higher rate of nice, durable remissions with these therapies.

Multiple trials are open and accruing. We have 3 of them open here at City of Hope, 1 with our own PSCA-targeted CAR T-cell product. Were just finishing up phase 1 study and expect to open the phase 1b study later this summer where were going to be testing multiple dosing and radiation prior to CAR T-cell administration, which in the lab seems to augment responsiveness; a good number of patients already have been treated. The PSMA targeted CAR T from POSEIDA is still accruing. Weve treated 7 [patients] here. Its a multi-site study, so there are many other sites that have treated patients as well, and thats still ongoing. Then there's the KLK2 targeted CAR T-cell study [NCT04898634] from Janssen. Thats a little earlier along but theyve treated a fair number of patients at this point; its a multicenter study. This is already a reality in terms of clinical trials, but still far from practice.

There are 2 big topics that came out of ASCO for prostate cancer this year. One was the up-front intensification study using triplet combinations where were not only adding chemotherapy up front or an androgen targeted agent like abiraterone [Yonsa], enzalutamide [Xtandi], apalutamide [Erleda], or darolutamide [Nubeqa], but using all the above. The important message to get out is for community oncologists and urologists to act on this and implement this in their own practices. Newly diagnosed [patients with] metastatic prostate cancer should not get just castration monotherapy. They will benefit tremendously from having up-front intensification with either doublet or in some cases triplet therapy.

The other big story is the 177Lu-PSMA-617 which was recently approved by the FDA based on the [phase 3] VISION trial [NCT03511664].3 Theres a lot of information coming out at some of these meetings about differences between the VISION trial and the [phase 2] TheraP trial [NCT03392428], in which the control arm was cabazitaxel [Jevtana], which helps us benchmark the efficacy and start to think about sequencing. Also, what PSMA PET characteristics might help us optimally select patients for this treatment, because the criteria have been different [across] trials. There has been all kinds of practical and helpful information presented at ASCO and a lot of buzz and talking among attendees about those topics.

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Tanya Dorff, MD, Speaks to the Development of CAR T-Cell Therapy in Prostate Cancer - Cancer Network

Airdrie’s Greg Roberts Memorial walk returning this weekend to raise awareness of myeloma – Airdrie Today

Murray said when she went into remission, she vowed to live every day to the fullest, and to do whatever she can to help others living with multiple myeloma.

The seventh annual Greg Roberts Memorial Myeloma Walk/Run will be raising awareness and funds to support research to help cure the potentially deadly blood cancer on Sept. 25 in Airdries East Lake Regional Park.

According to Myeloma Canada, about 11 Canadians are diagnosed with myeloma one of the most common blood cancers every day in this country, and that number has been rising every year. Myeloma Canada facilitates the Multiple Mylemoa March every year, with walks taking place around the country.

Rocky View County resident Trish Murray is organizing Airdrie local march on behalf of Myeloma Canada this Sunday.

Its a cause that is highly personal for Murray, who was diagnosed with an even rarer and more aggressive form of the disease called multiple myeloma two years ago. The disease caused painful outbreaks in both her spine and her jaw.

After aggressive radiation treatment and a stem cell transplant, Murray is grateful the disease is now in remission. However, Murray admitted the long-term prognosis for the disease is still not very good, with a high chance of recurrence. It is a reality she has learned to accept over the past two years.

I still take immuno-therapy drugs to keep the myeloma away, and there is no cure at the moment for myeloma, Murray said. So, as much as I try to stay positive about it, there is always the chance it will relapse some time in the future.

Nobody knows what tomorrow holds. Its an unknown for everyone; so I try not to dwell on it. I try to live every day as healthy as possible, and do whatever I can to do what the doctors say to do and hope.

Murray said when she went into remission, she vowed to live every day to the fullest, and to do whatever she can to help others living with the disease.

I am at a point in my treatment where I am feeling good and have lots of energy, she explained. So, I did want to do something for the myeloma community, and I contacted Myeloma Canada.

According to Murray, it just so happened the national organization didnt have anyone to organize the Airdrie version of the Multiple Myeloma March this year.

That is why I took it on, but, ultimately, it is raising awareness about what multiple myeloma is, she said.

The Airdrie march named after resident Greg Roberts, who passed away from multiple myeloma in 2014 benefits those suffering in three different ways, according to Murray. First and foremost, she said, it helps raise awareness of what is a misunderstood and relatively unknown form of blood cancer.

Because (myeloma) doesnt get the publicity the other (blood) diseases do, (the Airdrie march) is relatively small, she said. My goal is to get more people out to raise awareness by talking about it and to increase understanding of what it actually is.

The second benefit of the Greg Roberts Memorial Myeloma Walk/Run, explained Murray, is the funds it raises to help fund myeloma research in Canada.

In the last 15 years, there have been so many advances in treatment, she said. Its amazing. The life expectancy of a myeloma patient has tripled now compared to what it was in the early 2000s. Any money that is going toward research, clinical trials, will hopefully one day lead to a cure.

And the third, more personal, reason, said Murray, is the spiritual and emotional boost it gives to those suffering in the community with myeloma, as well as their families and caregivers.

It makes me very emotional, because it is overwhelming the support (the march receives) from family, friends and community, she explained. They want to do everything they can to help.

For local residents coming out on Sept. 25 for the five-kilometre walk/run in Airdries East Lake Regional Park, Murray promises a family- and pet-friendly event focused on fun and community. The walking part is optional, she stressed, as the most important thing is just being present.

Chances are (the readers) will know somebody who has myeloma one day, if they dont already, she said. Not to sound too dismal about it, but it is starting to become more common. Any way they could help the (myeloma) community would be really appreciated.

For more information on the seventh annual Greg Roberts Memorial Myeloma Walk/Run, visit myelomamarch.ca. Registration takes place on Sunday at 9:30 a.m.

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Airdrie's Greg Roberts Memorial walk returning this weekend to raise awareness of myeloma - Airdrie Today

Loveland K9 Officer Saves the Day in Stolen License Plate Case – Townsquare NoCo

There's a member of the Loveland Police Department (LPD) that you need to meet andStyng is his name.

Styng is a part of the Loveland Police Canine Unit. According to the LPD, Styng and his fellow K9 officers Shadow, Jojo, Pako, and Nazar work tirelessly to assist police with arrests, narcotics seizures, safety sweeps, criminal tracking, and locating missing persons.

"Each canine is assigned to the individual handler and are sworn Officers of the Loveland Police Department," said LPD. "Currently, the unit has Belgian Malinois, Dutch Shepherd, and Labrador Retriever breeds in service."

On Monday (Sept. 13), Styng got a special shoutout for his work on a recent case.

In a Facebook post, LPD said that Styng and his handler responded to a suspicious vehicle call after officers determined that the car had a stolen license plate. The male suspect in the case had taken off running and that's when the K9 officer saved the day.

Styng began to track the suspect and alerted his handler that the perpetrator was hiding in a closed trash can. Thanks to the K9's skills, police safely took the man into custody.

"Officers got into a safe position and called the male out," read the post. "He had multiple warrants including weapons charges and was arrested without incident. Good boy, Styng!"

Styng, a 3-year-old Belgian Malinois, joined the LPD in February of 2021 after graduating from their K9 Academy. See more of Northern Colorado's K9 officers in the gallery below.

Northern Colorado Law Enforcement K-9 Dogs

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

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Loveland K9 Officer Saves the Day in Stolen License Plate Case - Townsquare NoCo

DiMethyl Sulfoxide (DMSO) Market to Touch US$ 838.6 Million in 2032 Owing to its Widespread Application in End-Use Industries & Anti-Inflammatory…

Future Market Insights Global and Consulting Pvt. Ltd.

In 2022, North America will have 27.2% of the worldwide DiMethyl Sulfoxide (DMSO) Market. Asia Pacific is expected to procure 20% market share for DiMethyl Sulfoxide (DMSO) market in the assessment period 2022-2032

NEWARK, Del, Sept. 13, 2022 (GLOBE NEWSWIRE) -- The global DiMethyl Sulfoxide (DMSO) market is estimated to showcase a steady growth rate throughout the projection period from 2022 to 2032 with a CAGR of about 5.4%. The market was valued at US$ 495.6 Million in 2022 and is estimated to be worth US$ 838.6 Million in 2032. According to the historical forecast (2016 to 2021), the global DiMethyl Sulfoxide (DMSO) Market sales witnessed significant growth, registering a CAGR of 4.2%.

Dimethyl Sulfoxide (DMSO), is known as a dipolar aprotic solvent containing high flash and boiling points, it also has excellent miscibility with polar and non-polar solvents. Black liquor is used to make DMSO which is a by-product of paper mills. There are several applications of DMSO in various industries including healthcare, agrochemicals, fine chemicals & materials. With continuous research and development in this field, utilization of DMSO in the pharmaceutical sector has seen an impressive hike in the global demand over the assessment period.

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Being a solvent with several medicinal applications, DiMethyl Sulfoxide (DMSO) is used as a key component in many medicinal and agrochemical products. In recent years, several government restrictions have been loosened, due to which the worldwide DiMethyl Sulfoxide (DMSO) market is expected to expand rapidly over the projected period.

Key Takeaways

Amidst the pandemic, the pharmaceutical business expanded significantly. Owing to peoples widened awareness of health and safety has grown the demand for healthcare items. In several nations, DiMethyl Sulfoxide (DMSO) has been licensed for its use in medicines, as it has several medical benefits. DiMethyl Sulfoxide (DMSO) is now one of the most important solvents utilized in the pharmaceutical sector.

Owing to its membrane penetrating capabilities, DiMethyl Sulfoxide (DMSO) is excessively used in several medical treatments. It has also been employed as a medication carrier. It aids in the penetration of the medications into the human skin and brings more effective results of the medication. Owing to these factors, DiMethyl Sulfoxide (DMSO) market is expected to surge over the forecast period.

Because DiMethyl Sulfoxide (DMSO) is able to transport drugs that are unable to cross cell membranes on their own, it is frequently utilized as a component in a variety of anti-bacterial treatments. Backed by such crucial properties, sales in DiMethyl Sulfoxide (DMSO) market are expected to rise exponentially.

In the formulation of antifungal medicines that are used in eye care, the employment of DiMethyl Sulfoxide (DMSO) is significant. In addition to that, it has also been noticed that DMSO is an ingredient mentioned on various anti-fatigue skincare products as well. Such diverse applications are generating cash for producers of DiMethyl Sulfoxide (DMSO).

Equipped with high anti-inflammatory effects, DiMethyl Sulfoxide (DMSO) acts as an antioxidant in order to decrease inflammation. It reduces or fully stops the development of swelling and inflammation by preventing the oxidation of free radicals such as oxygen molecules produced by biological processes.

DiMethyl Sulfoxide (DMSO) has been recently used in steroids due to its membrane penetration and anti-inflammatory effects. In order to preserve bone marrow and stem cells, DiMethyl Sulfoxide (DMSO) has been employed as a cry protective agent. It has been considered one of the oldest applications of DMSO.

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Competitive Landscape

The prominent competitors in the worldwide DMSO market are developing new technologies that enable biopharmaceutical businesses to accelerate clinical manufacturing while decreasing process development time and costs

The Major Keyplayers are Arkema Group, Gaylord Chemical Corporation, Toray Fine Chemicals Co. Ltd., Hubei Xingfa Chemicals Group, Sigma-Aldrich Co. LLC., and Parchem Fine & Specialty Chemicals are some of the prominent competitors in the worldwide DMSO market.

More Insights into the DiMethyl Sulfoxide (DMSO) Market

The North American region is expected to dominate the global DiMethyl Sulfoxide (DMSO) market by accounting for 27.2% of the worldwide market in 2022. Owing to its widespread application and it is favored by many end users due to its ecologically friendly production technique and low toxicity.

Due to its employment in various medicinal and agrochemical applications in the region, the Dimethyl Sulfoxide (DMSO) is predicted to exhibit robust growth over the years. It is also well-acclaimed for its anti-inflammatory qualities and is commonly utilized in drugs that aid in body absorption.

The Asia Pacific is expected to witness positive growth opportunities throughout the assessment period due to its large demand in the pharmaceutical and electronics sectors. Developing economies like China have a hold over half of the Asia Pacific dimethyl Sulfoxide market. Thus, Asia Pacific is expected to procure a 20% market share for DiMethyl Sulfoxide (DMSO) market in the assessment period 2022-2032.

DiMethyl Sulfoxide (DMSO) Market Key Segments

DiMethyl Sulfoxide (DMSO) Market by Raw Materials:

Black Liquor

Sulphur

Raw Cotton

Lignin

DiMethyl Sulfoxide (DMSO) Market by Application:

Pharmaceuticals

Agrochemicals

Electronics

Fine Chemicals

Coatings

Cleaning Applications

DiMethyl Sulfoxide (DMSO) Market by Region:

North America DiMethyl Sulfoxide (DMSO)Market

Latin America DiMethyl Sulfoxide (DMSO)Market

Europe DiMethyl Sulfoxide (DMSO)Market

Asia Pacific DiMethyl Sulfoxide (DMSO)Market

Middle East & Africa DiMethyl Sulfoxide (DMSO)Market

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Table of Content

1. Executive Summary

1.1. Global Market Outlook

1.2. Demand-side Trends

1.3. Supply-side Trends

1.4. Technology Roadmap Analysis

1.5. Analysis and Recommendations

2. Market Overview

2.1. Market Coverage / Taxonomy

2.2. Market Definition / Scope / Limitations

3. Market Background

3.1. Market Dynamics

3.1.1. Drivers

3.1.2. Restraints

3.1.3. Opportunity

3.1.4. Trends

3.2. Scenario Forecast

3.2.1. Demand in Optimistic Scenario

3.2.2. Demand in Likely Scenario

3.2.3. Demand in Conservative Scenario

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Explore FMIs related ongoing Coverage onChemicals & MaterialsDomain

Dimethyl Disulphide (DMDS) Market Segment : The globaldimethyl disulphide (DMDS) marketsize is anticipated to be evaluated atUS$ 218.6 Mnin 2022.

Dimethylolpropionic Acid (DMPA) Market Growth : Dimethylolpropionic acid is a crystalline compound that is increasingly gaining traction for its extensive use in the development of aqueous urethane dispersions, which are ideal for high gloss waterborne coating offerings with superior flexibility and free-flow characteristics.

Dimethyl Terephthalate Market Analysis : Dimethyl terephthalate, also known as dimethyl 1, 4-benzenedicarboxylate is used as a feedstock in production ofpolyethylene terephthalate(PET) and polybutylene terephthalate (PBT).

Dimethylformamide (DMF) Market Size : The globaldimethylformamide (DMF) marketleads to an estimated CAGR of4.7%in the global market during the forecast period and registers a revenue valued atUS$ 374.88 Mnin 2022, and is expected to crossUS$ 593.4 Mnby 2032.

Lauryl Dimethyl Amine Oxide Market Outlook: Lauryl dimethyl amine oxide is a typefatty aminederivative. Lauryl dimethyl amine oxide is also known as N-lauryl-N,N-dimethylamine oxide, dodecyl dimethylamine oxide (DDAO) and N,N-Dimethyl-1-Dodecylamine N-Oxide.

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DiMethyl Sulfoxide (DMSO) Market to Touch US$ 838.6 Million in 2032 Owing to its Widespread Application in End-Use Industries & Anti-Inflammatory...

Stem cell therapy cost panama – grret.fitclub-rv.de

Aug 06, 2019 A culture-expanded stem cell procedure $$$. Numbers 1 and 2 here are procedures where all of the injections are performed on the same day, while number 3 takes a few weeks to grow cells. The advertised cost of birth tissue procedures and same-day bone marrow or fat procedures are similar, usually in the 4-8K USD range.. "/>

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level 1. 2 yr. ago. Since the beginning of this stem cell craze, Latin American countries are very open when it comes to stem cell regulations. Therefore, most clinics set up shop in Mexico, Brazil, Costa Rica, Panama and the Bahamas. In general, processed stem cells are considered drugs in the U.S. as is in South Korea.

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No, the cost of treatment at the Stem Cell Institute of Panama is very similar to Costa Rica. The experts at the Stem Cells Institute in Costa Rica use state-of-the-art technology and provide high quality care at a reasonable price. Do treatments in Costa Rica differ from the treatments at the Stem Cell Institute of Panama in terms of efficacy?.

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A physician expert discusses Panama stem cell clinic reviews and how that site compares to other clinics like Cayman and Mexico. About Us. Our Approach; Doctor Directory; ... (from the patient) or allogeneic (from a donor). The only therapy in the US that has real stem cells and that's currently permitted by US law is bone marrow concentrate.

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MediGlobus enlist only the top hospitals in Israel for Stem cell therapy. Compare clinics, read reviews, check cost and get a free quote. | MediGlobus ... Procedure Cost Oncologist consultation $650 Urologist consultation $650 Neurologist consultation $650 Radiologist consultation $580 Surgeon's consultation $750 Gastroscopy $800 Biopsy $1,500.

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Jun 30, 2021 The post by Bioinformant about the cost of stem cells describes a clinic called The Stem Cell Institute in Panama ( which sells unproven stem cell injections including into children) this way: Founded by Dr. Neil Riordan, the Stem Cell Institute in Panama is one of the worlds most trusted stem cell therapy centers...

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Oct 14, 2020 The Stem Cell Institute, located in Panama, is clearly a quack stem cell clinic. Its website advertises stem cells to treat autism, cerebral palsy, heart failure, multiple sclerosis, osteoarthritis, rheumatoid arthritis, spinal cord injury, and autoimmune diseases, complete with very little actual science but a whole lot of testimonials.. Aug 27, 2022 Stem Cell Cancer Treatment in Panama City, Panama - July 13th, 2018; Stem Cell Therapy for Autism in Panama - Medical Tourism - July 4th, 2018; Stem Cell Therapy A Rising Tide Neil H. RIordan, PA ... - June 20th, 2018; Stem Cell Cancer Treatment in Panama - health-tourism.com - September 20th, 2017.

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June 14, 2022; pros and cons of stem cell therapy for knees;. 2022 World Series 8u, 10u, 12u. July 17th thru 23rd. We are offering A,B and C classifications for all age groups. This week is for the 14u,16u, and 18u. This week also features the College Showcase. Many signings every year from a variety of Colleges at all levels.. 2022 sanctions.

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Aug 27, 2022 Stem Cell Cancer Treatment in Panama City, Panama - July 13th, 2018; Stem Cell Therapy for Autism in Panama - Medical Tourism - July 4th, 2018; Stem Cell Therapy A Rising Tide Neil H. RIordan, PA ... - June 20th, 2018; Stem Cell Cancer Treatment in Panama - health-tourism.com - September 20th, 2017.

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Fetal stem cells are the cellular building blocks of the 220 cell types within the body. Uniquely, they are the only stem cell that can repair and regenerate damaged cells and tissues, including for conditions such as Parkinson's, MS, Lupus and traumatic brain injury, among others.

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Knee Stem Cell Therapy. Shoulder Stem Cell Therapy. MS Stem Cells. Congestive Heart Failure Stem Cell Therapy. 833-445-9089 Joya Hospital - Paseo de los Cocoteros 55 Int ... anti-inflammatory benefits. I got an email quote of $23,150 from Dr. Neil Riordan's clinic in Panama for this treatment and understand that Dream Body's top IV price is.

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Jun 30, 2021 The post by Bioinformant about the cost of stem cells describes a clinic called The Stem Cell Institute in Panama ( which sells unproven stem cell injections including into children) this way: Founded by Dr. Neil Riordan, the Stem Cell Institute in Panama is one of the worlds most trusted stem cell therapy centers... Nov 18, 2019 By Chris Centeno, MD / Nov 18, 2019. Yesterday I flew down to Grand Cayman to once again allow some of my patients access to advanced cultured stem cells. This morning I would also like to compare and contrast what we do here from whats done in Panama. Hence, this will be one of my first official Panama stem cell clinic reviews..

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If you have decided to have Stem Cell Treatment for Hair Loss in Panama City, Panama you should know that the average price is $75. The final cost will depend on the type of procedure.

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Stem cell therapy for autism, cerebral palsy, heart failure, multiple sclerosis, osteoarthritis, rheumatoid arthritis, and spinal cord injury.

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Stem cell therapy cost panama - grret.fitclub-rv.de

More Pets up for Adoption in Maine After Animal Refuge Rescue – WJBQ

We all know the importance of Adopt Dont Shop! and rescuing furry friends that are in shelters. We have many incredible shelters around Maine with high volume, allowing our residents to have ample opportunities and options for bringing a pet home in the most benevolent way.

If youve been in the market for a new four-legged friend, Maine now has 61 new cats and dogs that just got rescued from Puerto Rico and are ready to be adopted!!

Animal Refuge League of Greater Portland recently sent over volunteers on a Freedom Flight with nonprofit Wings of Rescue to rescue more than 300 cats and dogs from Puerto Rico. Of those animals, 61 have been brought to Maine with the rest being housed in shelters in New York.

As the Refuge shared with News Center Maine, a lot of locations where the pets were rescued are still damaged by Hurricane Maria and there are more than 500,000 stray dogs on the island right now due to most of them not being fixed.

The most touching part was when the director of community engagement shared with the outlet that when they first met the animals, they were really timid, shy, and scared; In just a matter of two days, they watched the animals get comfortable in the feeling of safety and start to play, run around and snuggle.

There are now even more animals to choose from to save from shelters here in Maine that meet your needs. You can visit the Animal Refuge League in person in Westbrook or visit their website to learn more about how to adopt or get involved.

Regardless, you should definitely follow their Instagram so you can see the adorable pictures of the rescued furry friends!! Plus, sharing the content can help these guys get adopted.

KEEP LOOKING: See What 50 of America's Most 'Pupular' Dog Breeds Look Like as Puppies

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

View post:
More Pets up for Adoption in Maine After Animal Refuge Rescue - WJBQ

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice | Scientific Reports – Nature.com

Apperley, L. J. & Ng, S. M. Increased insulin requirement may contribute to risk of obesity in children and young people with type 1 diabetes mellitus. Diabetes Metabol. Syndrome-Clin. Res. Rev. 13, 492495. https://doi.org/10.1016/j.dsx.2018.11.005 (2019).

Article Google Scholar

Scherm, M. G. et al. Beta cell and immune cell interactions in autoimmune type 1 diabetes: How they meet and talk to each other. Mol. Metab. 2022, 101565. https://doi.org/10.1016/j.molmet.2022.101565 (2022).

CAS Article Google Scholar

Tisch, R. & McDevitt, H. Insulin-dependent diabetes mellitus. Cell 85, 291297. https://doi.org/10.1016/s0092-8674(00)81106-x (1996).

CAS Article PubMed Google Scholar

Shao, L. et al. The role of adipose-derived inflammatory cytokines in type 1 diabetes. Adipocyte 5, 270274. https://doi.org/10.1080/21623945.2016.1162358 (2016).

CAS Article PubMed PubMed Central Google Scholar

Viehmann-Milam, A. A. et al. A humanized mouse model of autoimmune insulitis. Diabetes 63, 17121724. https://doi.org/10.2337/db13-1141 (2014).

CAS Article PubMed PubMed Central Google Scholar

Martins, C. P. et al. Glycolysis inhibition induces functional and metabolic exhaustion of CD4(+) T cells in type 1 diabetes. Front. Immunol. 12, 669456. https://doi.org/10.3389/fimmu.2021.669456 (2021).

CAS Article PubMed PubMed Central Google Scholar

Lichtnekert, J., Kawakami, T., Parks, W. C. & Duffield, J. S. Changes in macrophage phenotype as the immune response evolves. Curr. Opin. Pharmacol. 13, 555564. https://doi.org/10.1016/j.coph.2013.05.013 (2013).

CAS Article PubMed PubMed Central Google Scholar

Sugg, K. B., Lubardic, J., Gumucio, J. P. & Mendias, C. L. Changes in macrophage phenotype and induction of epithelial-to-mesenchymal transition genes following acute Achilles tenotomy and repair. J. Orthopaed. Res. 32, 944951. https://doi.org/10.1002/jor.22624 (2014).

CAS Article Google Scholar

Saltiel, A. R. & Olefsky, J. M. Inflammatory mechanisms linking obesity and metabolic disease. J. Clin. Investig. 127, 14. https://doi.org/10.1172/jci92035 (2017).

Article PubMed PubMed Central Google Scholar

Coope, A., Torsoni, A. S. & Velloso, L. A. Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes. Eur. J. Endocrinol. 174, R175R187. https://doi.org/10.1530/eje-15-1065 (2016).

CAS Article PubMed Google Scholar

Zhang, C. et al. Circular RNA circPPM1F modulates M1 macrophage activation and pancreatic islet inflammation in type 1 diabetes mellitus. Theranostics 10, 1090810924. https://doi.org/10.7150/thno.48264 (2020).

CAS Article PubMed PubMed Central Google Scholar

Calderon, B., Suri, A. & Unanue, E. R. In CD4+ T-cell-induced diabetes, macrophages are the final effector cells that mediate islet beta-cell killing: Studies from an acute model. Am. J. Pathol. 169, 21372147. https://doi.org/10.2353/ajpath.2006.060539 (2006).

CAS Article PubMed PubMed Central Google Scholar

Wang, F. et al. Loss of ubiquitin-conjugating enzyme E2 (Ubc9) in macrophages exacerbates multiple low-dose streptozotocin-induced diabetes by attenuating M2 macrophage polarization. Cell Death Dis. 10, 892. https://doi.org/10.1038/s41419-019-2130-z (2019).

CAS Article PubMed PubMed Central Google Scholar

Arnush, M., Scarim, A. L., Heitmeier, M. R., Kelly, C. B. & Corbett, J. A. Potential role of resident islet macrophage activation in the initiation of autoimmune diabetes. J. Immunol. 160, 26842691 (1998).

CAS PubMed Google Scholar

Apaolaza, P. S., Petropoulou, P. I. & Rodriguez-Calvo, T. Whole-slide image analysis of human pancreas samples to elucidate the immunopathogenesis of type 1 diabetes using the QuPath software. Front. Mol. Biosci. 8, 689799. https://doi.org/10.3389/fmolb.2021.689799 (2021).

CAS Article PubMed PubMed Central Google Scholar

Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K. & Morgan, N. G. Analysis of islet inflammation in human type 1 diabetes. Clin. Exp. Immunol. 155, 173181. https://doi.org/10.1111/j.1365-2249.2008.03860.x (2009).

CAS Article PubMed PubMed Central Google Scholar

Wherrett, D. K. et al. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: A consensus report. Diabetes Care 38, 19751985. https://doi.org/10.2337/dc15-1429 (2015).

CAS Article PubMed PubMed Central Google Scholar

Mahon, J. L. et al. The TrialNet natural history study of the development of type 1 diabetes: Objectives, design, and initial results. Pediatr. Diabetes 10, 97104. https://doi.org/10.1111/j.1399-5448.2008.00464.x (2009).

Article PubMed Google Scholar

Bang, J. I. et al. Blood pool activity on F-18 FDG PET/CT as a possible imaging biomarker of metabolic syndrome. Sci. Rep. 10, 17367. https://doi.org/10.1038/s41598-020-74443-9 (2020).

ADS CAS Article PubMed PubMed Central Google Scholar

Luo, B. et al. Characterization and immunological activity of polysaccharides from Ixeris polycephala. Int. J. Biol. Macromol. 113, 804812. https://doi.org/10.1016/j.ijbiomac.2018.02.165 (2018).

CAS Article PubMed Google Scholar

Yang, H. et al. Tim-3 aggravates podocyte injury in diabetic nephropathy by promoting macrophage activation via the NF-B/TNF- pathway. Mol. Metabol. 23, 2436. https://doi.org/10.1016/j.molmet.2019.02.007 (2019).

CAS Article Google Scholar

Zhao, N. et al. Molecular network-based analysis of guizhi-shaoyao-zhimu decoction, a TCM herbal formula, for treatment of diabetic peripheral neuropathy. Acta Pharmacol. Sin. 36, 716723. https://doi.org/10.1038/aps.2015.15 (2015).

CAS Article PubMed PubMed Central Google Scholar

Gao, P. et al. Risk variants disrupting enhancers of T(H)1 and T(REG) cells in type 1 diabetes. Proc. Natl. Acad Sci. USA 116, 75817590. https://doi.org/10.1073/pnas.1815336116 (2019).

CAS Article PubMed PubMed Central Google Scholar

Yu, H., Hu, W., Song, X. & Zhao, Y. Immune modulation of platelet-derived mitochondria on memory CD4(+) T cells in humans. Int. J. Mol. Sci. 2020, 21. https://doi.org/10.3390/ijms21176295 (2020).

CAS Article Google Scholar

Qi, Z. et al. Characterization of susceptibility of inbred mouse strains to diabetic nephropathy. Diabetes 54, 26282637. https://doi.org/10.2337/diabetes.54.9.2628 (2005).

CAS Article PubMed Google Scholar

Zhou, D. et al. Critical involvement of macrophage infiltration in the development of Sjgrens syndrome-associated dry eye. Am. J. Pathol. 181, 753760. https://doi.org/10.1016/j.ajpath.2012.05.014 (2012).

CAS Article PubMed PubMed Central Google Scholar

Frikke-Schmidt, H. et al. Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice. Mol. Metabol. 6, 317326. https://doi.org/10.1016/j.molmet.2017.02.004 (2017).

CAS Article Google Scholar

Mndez-Snchez, N. et al. The cellular pathways of liver fibrosis in non-alcoholic steatohepatitis. Ann. Transl. Med. 8, 400. https://doi.org/10.21037/atm.2020.02.184 (2020).

CAS Article PubMed PubMed Central Google Scholar

Felton, J. L., Conway, H. & Bonami, R. H. B Quiet: Autoantigen-specific strategies to silence raucous B lymphocytes and halt cross-talk with T cells in type 1 diabetes. Biomedicines 9, 42. https://doi.org/10.3390/biomedicines9010042 (2021).

CAS Article PubMed PubMed Central Google Scholar

Kakoola, D. N., Lenchik, N. I., Curcio-Brint, A. & Gerling, I. C. Transcriptional profiling of CD4 T-lymphocytes reveals abnormal gene expression in young prediabetic NOD mice. BMC Bioinform. 10, A15. https://doi.org/10.1186/1471-2105-10-s7-a15 (2009).

Article Google Scholar

Enk, J. & Mandelboim, O. The role of natural cytotoxicity receptors in various pathologies: Emphasis on type I diabetes. Front. Immunol. 5, 4. https://doi.org/10.3389/fimmu.2014.00004 (2014).

CAS Article PubMed PubMed Central Google Scholar

Pichler, R., Afkarian, M., Dieter, B. P. & Tuttle, K. R. Immunity and inflammation in diabetic kidney disease: Translating mechanisms to biomarkers and treatment targets. Am. J. Physiol. Renal Physiol. 312, F716-f731. https://doi.org/10.1152/ajprenal.00314.2016 (2017).

CAS Article PubMed Google Scholar

Zhang, H., Shih, D. Q. & Zhang, X. Mechanisms underlying effects of 1,25-Dihydroxyvitamin D3 on the Th17 cells. Eur. J. Microbiol. Immunol. 3, 237240. https://doi.org/10.1556/EuJMI.3.2013.4.1 (2013).

Article Google Scholar

Sadeqi Nezhad, M. et al. Chimeric antigen receptor based therapy as a potential approach in autoimmune diseases: How close are we to the treatment?. Front. Immunol. 11, 603237. https://doi.org/10.3389/fimmu.2020.603237 (2020).

CAS Article PubMed PubMed Central Google Scholar

Cho, H. J. & Cheong, J. Y. Role of immune cells in patients with hepatitis B virus-related hepatocellular carcinoma. Int. J. Mol. Sci. 22, 8011. https://doi.org/10.3390/ijms22158011 (2021).

CAS Article PubMed PubMed Central Google Scholar

Zhao, Y., Xie, Y. & Li, W. Liraglutide exerts potential anti-inflammatory effect in type 1 diabetes by inhibiting IFN- production via suppressing JAK-STAT pathway. Endocr. Metab. Immune Disord. Drug Targets 19, 656664. https://doi.org/10.2174/1871530319666190301115654 (2019).

CAS Article PubMed Google Scholar

Shao, F., Zheng, P., Yu, D., Zhou, Z. & Jia, L. Follicular helper T cells in type 1 diabetes. FASEB J. 34, 3040. https://doi.org/10.1096/fj.201901637R (2020).

CAS Article PubMed Google Scholar

Ye, L. et al. Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res. Ther. 8, 90. https://doi.org/10.1186/s13287-017-0542-1 (2017).

CAS Article PubMed PubMed Central Google Scholar

Kornete, M. et al. Th1-Like ICOS+ Foxp3+ Treg cells preferentially express CXCR3 and home to -islets during pre-diabetes in BDC25 NOD mice. PLoS ONE 10, e0126311. https://doi.org/10.1371/journal.pone.0126311 (2015).

CAS Article PubMed PubMed Central Google Scholar

Qiao, Y. C. et al. Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis. Clin. Immunol. (Orlando, Fla) 170, 6169. https://doi.org/10.1016/j.clim.2016.08.004 (2016).

CAS Article Google Scholar

Prasanna, S. J., Gopalakrishnan, D., Shankar, S. R. & Vasandan, A. B. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS ONE 5, e9016. https://doi.org/10.1371/journal.pone.0009016 (2010).

ADS CAS Article PubMed PubMed Central Google Scholar

Li, R. et al. PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice. Diabetes 64, 529540. https://doi.org/10.2337/db13-1737 (2015).

CAS Article PubMed Google Scholar

Fiorina, P. et al. Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes. J. Immunol (Baltim., Md.: 1950) 183, 9931004. https://doi.org/10.4049/jimmunol.0900803 (2009).

CAS Article Google Scholar

Zazzeroni, L., Lanzoni, G., Pasquinelli, G. & Ricordi, C. Considerations on the harvesting site and donor derivation for mesenchymal stem cells-based strategies for diabetes. CellR4 Repair Replace. Regener. Reprogram. 5, 6 (2017).

Google Scholar

Guillot, A. & Tacke, F. Liver macrophages: Old dogmas and new insights. Hepatol. Commun. 3, 730743. https://doi.org/10.1002/hep4.1356 (2019).

Article PubMed PubMed Central Google Scholar

Shao, B. Y., Zhang, S. F., Li, H. D., Meng, X. M. & Chen, H. Y. Epigenetics and inflammation in diabetic nephropathy. Front. Physiol. 12, 649587. https://doi.org/10.3389/fphys.2021.649587 (2021).

Article PubMed PubMed Central Google Scholar

Guo, J. et al. Accelerated kidney aging in diabetes mellitus. Oxid. Med. Cell. Longev. 2020, 1234059. https://doi.org/10.1155/2020/1234059 (2020).

CAS Article PubMed PubMed Central Google Scholar

Tesch, G. H. Diabetic nephropathyis this an immune disorder?. Clin. Sci. (Lond. Engl. 1979) 131, 21832199. https://doi.org/10.1042/cs20160636 (2017).

CAS Article Google Scholar

Qian, J. et al. An Indole-2-carboxamide derivative, LG4, alleviates diabetic kidney disease through inhibiting MAPK-mediated inflammatory responses. J. Inflamm. Res. 14, 16331645. https://doi.org/10.2147/jir.S308353 (2021).

Article PubMed PubMed Central Google Scholar

Lv, J., Chen, J., Wang, M. & Yan, F. Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization. Aging (Albany NY) 12, 91399150. https://doi.org/10.18632/aging.103183 (2020).

CAS Article Google Scholar

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Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice | Scientific Reports - Nature.com

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