Endoplasmic reticulum stress PERK-ATF4-CHOP pathway is involved in non-alcoholic fatty liver disease in type 1 diabetic rats: The rescue effect of treatment exercise and insulin-like growth factor I.

Endoplasmic Reticulum Stress (ERS) is a key factor in the development of Non-Alcoholic Fatty Liver Disease (NAFLD) in diabetes. The current study aimed to examine the effects of exercise and IGF-I on ERS markers in liver tissue. Rats were divided into five groups (n = 8 per group), including control (CON), diabetes (DIA), diabetes + exercise (DIA + EX), diabetes + IGF-I (DIA + IGF-I), and diabetes + exercise + IGF-I (DIA + EX + IGF-I). Type 1 diabetes was induced by an I.P. injection of streptozotocin (60 mg/kg). After 30 days of treatment with exercise or IGF-I alone or in combination, liver tissue was assessed for caspase 12, 8, and CHOP protein levels, and expression of ERS markers (ATF-6, PERK, IRE-1A) and lipid metabolism-involved genes (FAS, FXR, SREBP-1c) by western immunoblotting. In addition, for the evaluation of histopathological changes in the liver, Hematoxylin - Eosin and Masson's Trichrome staining were done. Compared to the control group, diabetes significantly caused liver fibrosis, induced ERS, increased caspase 12 and 8 levels in the liver, and changed expression levels of genes associated with lipid metabolism, including FAS, FXR, and SREBP-1c. Treatment with either exercise or IGF-I reduced fibrosis levels suppressed ER stress markers and apoptosis, and improved expression of genes associated with lipid metabolism. In addition, simultaneous treatment with exercise and IGF-I showed a synergistic effect compared to DIA + E and DIA + IGF-I. The results suggest that IGF-1 and exercise reduced liver fibrosis possibly by reducing ERS, creating adaptive ER stress status, and improving protein folding.

Cell-mediated barriers in cancer immunosurveillance.

The immune cells within the tumor microenvironment (TME) exert multifaceted functions ranging from tumor-antagonizing or tumor-promoting activities. During the initial phases of tumor development, the tumor-antagonizing immune cells in the TME combat cancer cells in an immune surveillance process. However, with time, cancer cells can evade detection and impede the immune cells' effectiveness through diverse mechanisms, such as decreasing immunogenic antigen presentation on their surfaces and/or secreting anti-immune factors that cause tolerance in TME. Moreover, some immune cells cause immunosuppressive situations and inhibit antitumoral immune responses. Physical and cellular-mediated barriers in the TME, such as cancer-associated fibroblasts, tumor endothelium, the altered lipid composition of tumor cells, and exosomes secreted from cancer cells, also mediate immunosuppression and prevent extravasation of immune cells. Due to successful clinical outcomes of cancer treatment strategies the potential barriers must be identified and addressed. We need to figure out how to optimize cancer immunotherapy strategies, and how to combine therapeutic approaches for maximum clinical benefit. This review provides a detailed overview of various cells and molecules in the TME, their association with escaping from immune surveillance, therapeutic targets, and future perspectives for improving cancer immunotherapy.

Cellular junction dynamics and Alzheimer's disease: a comprehensive review.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive neuronal damage and cognitive decline. Recent studies have shed light on the involvement of not only the blood-brain barrier (BBB) dysfunction but also significant alterations in cellular junctions in AD pathogenesis. In this review article, we explore the role of the BBB and cellular junctions in AD pathology, with a specific focus on the hippocampus. The BBB acts as a crucial protective barrier between the bloodstream and the brain, maintaining brain homeostasis and regulating molecular transport. Preservation of BBB integrity relies on various junctions, including gap junctions formed by connexins, tight junctions composed of proteins such as claudins, occludin, and ZO-1, as well as adherence junctions involving molecules like vascular endothelial (VE) cadherin, Nectins, and Nectin-like molecules (Necls). Abnormalities in these junctions and junctional components contribute to impaired neuronal signaling and increased cerebrovascular permeability, which are closely associated with AD advancement. By elucidating the underlying molecular mechanisms governing BBB and cellular junction dysfunctions within the context of AD, this review offers valuable insights into the pathogenesis of AD and identifies potential therapeutic targets for intervention.

The effects of forced exercise and zinc supplementation during pregnancy on prenatally stress-induced behavioral and neurobiological consequences in adolescent female rat offspring.

Prenatal manipulations can lead to neurobehavioral changes in the offspring. In this study, individual and combined effects of forced exercise and zinc supplementation during pregnancy on prenatally restraint stress (PRS)-induced behavioral impairments, neuro-inflammatory responses, and oxidative stress have been investigated in adolescent female rat offspring. Pregnant rats were divided into five groups: control; restraint stress (RS); RS + exercise stress (RS + ES), RS + zinc supplementation (RS + Zn); and RS + ES + Zn. All the pregnant rats (except control) were exposed to RS from gestational days 15 to 19. Pregnant rats in ES groups were subjected to forced treadmill exercise (30 min/daily), and in Zn groups to zinc sulfate (30 mg/kg/orally), throughout the pregnancy. At postnatal days 25-27, anxiety-like and stress-coping behaviors were recorded, and the gene expressions of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and the concentration of total antioxidant capacity were measured in the prefrontal cortex. PRS significantly enhanced anxiety, generated passive coping behaviors, increased IL-1ß and TNF-α expression, and decreased the antioxidant capacity. ES potentiated while zinc reversed PRS-induced behavioral impairments. Prenatal zinc also restored the anti-inflammatory and antioxidant capacity but had no effect on additive responses imposed by the combination of RS and ES. Suppression of PRS-induced behavioral and neurobiological impairments by zinc suggests the probable clinical importance of zinc on PRS-induced changes on child temperament.

Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise.

OBJECTIVES: Exercise is assumed to attenuate age-related neuronal apoptosis, but the detailed mechanism(s) is not fully understood. α1-Adrenergic receptors (ARs) can either trigger or suppress apoptosis, therefore, here we determined the impact of treadmill exercise on the expression of the apoptosis regulatory proteins as well as α1-AR subtypes α1A- and α1B-ARs, in order to elucidate a possible association between apoptosis and the hippocampal expression of α1-ARs in aged male rats. METHODS: Twenty-one male Wistar rats were divided into 3 groups (n=7): young control, aged sedentary, and aged + exercise. Western blot for α1A- and α1B-ARs as well as pro-(Bax and p53) and anti-apoptotic (Bcl2) proteins was conducted. An 8-week regular moderate-intensity treadmill exercise intervention was carried out in exercise group. RESULTS: In aged rats, α1A-AR expression in the hippocampus was significantly increased, and exercise markedly prevented this event. While α1B-AR expression was no altered with aging, a marked reduction in α1B-AR level was detected in exercise group when compared to aged group. Furthermore, pro-apoptotic protein levels of Bax and p53 were upregulated and anti-apoptotic protein Bcl2 was downregulated in the aging hippocampus, but could be reversed by treadmill exercise. In the present research, exercise-induced reduction in α1A- and α1B-ARs was associated with an obvious downregulation of Bax/Bcl2 ratio in aged rats, suggesting that exercise may inhibit apoptosis through regulating α1-ARs, particularly α1A-AR. CONCLUSIONS: Our study suggests that manipulations attenuating α1-AR activity, including nonselective α1-adrenergic antagonists, may protect against hippocampal neurodegeneration in aging brains.

Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats: Rescue Effects of IGF-1 and Exercise.

Purpose: Reduced angiogenesis in the heart tissue is a primary risk factor for heart disease in the diabetes condition. This study was aimed to evaluate the changes of two main angiogenesis mediators, NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) protein levels in the heart of diabetic rats and the impact of Insulin-like growth factor 1 (IGF-1) and exercise on these proteins. Methods: Injection of 60 mg/kg of streptozotocin in 40 male Wistar rats led to the induction of type 1 diabetes. Angiogenesis was detected in the hearts by immunostaining for PECAM-1/ CD31 after 30 days of treatment with IGF-1 (2 mg/kg/day) and exercise. ELISA technique was utilized to establish the expression levels of NOX4 and SIRT-1 within the heart. Results: The results revealed a significant increase in HbA1c and a significant decrease in SIRT1, NOX4 levels and angiogenesis grade in the heart of diabetes group compared to control group. Meanwhile, IGF-1 and exercise alone or in combination completely masked these effects. Additionally, synergistic effect on SIRT-1, HbA1c levels and angiogenesis grade is evident when IGF-1 and exercise are applied simultaneously. Conclusion: Our findings suggest that reduction in angiogenesis in the heart of diabetic rats may be mediated by down expression of NOX4 and SIRT-1 protein levels. It was also displayed that IGF-1 and exercise as novel therapies increase NOX4 and SIRT-1 protein levels within the hearts of diabetic rats.

Melatonin/nicotinamide mononucleotide/ubiquinol: a cocktail providing superior cardioprotection against ischemia/reperfusion injury in a common co-morbidities modelled rat.

BACKGROUND: The metabolic and intracellular abnormalities in aging and diabetes cause loss of cardioprotection by routine interventions against myocardial ischemia/reperfusion (I/R) injury. We aimed to evaluate the possible interaction of aging and type-2 diabetes mellitus with cardioprotection and the potential protective effect of a mitochondrial cocktail (melatonin/nicotinamide mononucleotide (NMN)/ubiquinol) on myocardial I/R injury in aged diabetic rats. METHODS: Male Wistar rats (n = 108, 22-24 months old, 400-450 g) received high-fat diet/low dose of streptozotocin to induce type-2 diabetes, then were randomized into 9 groups of 12 rats each with/without I/R and/or melatonin, NMN, and ubiquinol, alone or in dual or triple combinations. Myocardial I/R was induced by LAD occlusion for 30 min followed by 24 h reperfusion. NMN (100 mg/kg/48 h, intraperitoneally) was administered for 28 days before I/R operation. Melatonin (10 mg/kg, intraperitoneally) and/or ubiquinol (30 mg/kg, intravenously) were administered at early reperfusion. Finally, hemodynamic index changes, infarct size, CK-MB levels, mitochondrial functional endpoints, and expression of mitochondrial biogenesis genes (SIRT-1/PGC-1α/NRF-2/TFAM) were assessed. RESULTS: The solo and dual applications of melatonin, NMN, and ubiquinol did not exert remarkable cardioprotective impacts. However, the triple combination improved myocardial function and decreased infarct size and CK-MB levels following myocardial I/R (P < .05 to P < .01). It also improved mitochondrial function and restored mitochondrial biogenesis genes (P < .01). CONCLUSIONS: Combination therapy with melatonin, NMN, and ubiquinol exerted significant cardioprotection and improved mitochondrial function and biogenesis via upregulation of SIRT-1/PGC-1α/NRF-2/TFAM profiles in aged diabetic rats and, thus, offers a promising strategy for providing noticeable cardioprotection against I/R injury also in aged diabetic patients.

Exercise may alleviate age-related spatial memory impairment by rescuing ß-adrenergic receptor dysregulation via both G protein-dependent and ß-arrestin-dependent mechanisms in rat hippocampus.

Hippocampal-dependent memory abilities including spatial memory decline with age. Exercise improves memory decline in aging brain, but, the precise mechanisms are still unknown. Learning and memory are recently hypothesized to be mediated by a ß-arrestin (ßArr)-dependent ß-adrenergic pathway. Hence, we examined the effect of 8 weeks of treadmill exercise on hippocampal expression of ß-adrenergic receptors (ß-ARs; members of the G protein-coupled receptor family), and ßArrs as well as spatial learning and memory in aged male rats to determine whether ß-AR/ßArr pathway could be involved in age-related memory decline. A total of 24 young (3-month-old) and aged (18-month-old) male Wistar rats were divided into young control, aged sedentary, and aged + exercise (n = 8 for each). Western blot for ß1- and ß2-ARs as well as ßArr1 and ßArr2 was performed. Spatial learning and memory were evaluated with the Morris water maze. The results showed significant up-regulation of ß1-ARs as well as significant down-regulation of ß2-AR and ßArrs (ßArr1 and ßArr2) in the hippocampus of aged rats. Spatial memory, but not spatial learning, was impaired in aging, and treadmill exercise improved it. Notably, the improvement in spatial memory was accompanied by amelioration of ß-ARs dysregulation and increase in ßArr2 levels after exercise. There was a negative association between the expression of ßArr2 and ß1-AR, but not ß2-AR, such that an increase in ßArr2 by exercise was associated with reduced ß1-AR expression, suggesting ßArr2 may contribute to posttranslational down-regulation of ß1-ARs. These data suggest that both G protein-dependent and ß-arrestin-dependent ß-AR pathways may regulate spatial learning and memory in aging brain.

IGF-I combined with exercise improve diabetes-induced vascular dysfunction in heart of male Wistar rats.

Introduction: This research investigates the impact of insulin-like growth factor-I (IGF -I)and exercise on mediators associated with angiogenesis (VEGF-A, TSP-1, and NF-кß) and capillarization status of the diabetic rats' hearts. Methods: Splitting of forty Wistar male rats into five groups occurred as following: control,diabetes, diabetes+IGF-I, diabetes+exercise, and diabetes+exercise+IGF-I.Through intraperitoneal administration of 60 mg/kg streptozotocin, the condition of Type 1diabetes was escalated. After four weeks of treatment with IGF-I (2 mg/kg/day) or treadmill exercise (17 m/min, zero degrees slope, 30 min/day), in the heart, microvascular density and protein levels of VEGF-A, TSP-1, and NF-Ðºß were determined by H&E staining and ELISA,respectively. Results: Within the diabetic group, observations present a significant decrease in VEGF-A and MVD levels, whereas an increase in the TSP-1 and NF-Κb levels. While these impacts were reversed by either IGF-I or exercise treatments, simultaneous treatment had synergistic effects. Moreover, among diabetic rats, undesirable histologic alterations of the heart were demonstrated, including myonecrosis, interstitial edema, hemorrhage, and mononuclear immune cell infiltration, whereas treatments improved these changes. Conclusion: These data manifest that IGF-I and exercise can increase the cardiac angiogenesis of diabetic rats through increasing expression of VEGF-A, and decreasing TSP-1 and NF-кßproteins level, also can improve myocardial tissue damages.

Effect of exercise and curcumin on cardiomyocyte molecular mediators associated with oxidative stress and autophagy in aged male rats.

AIM: Aging can origin changes in the heart that may increase risk of developing cardiovascular disease. This study aimed to characterize autophagy alterations and related molecular mediators in the heart tissue in the aging alone or in combination with exercise and curcumin treatment. METHODS: Seven young and twenty-eight elderly male Wistar rats were assigned into five groups, namely: young control, age, exercise, curcumin, and curcumin+exercise. Aged rats in exercise group run on treadmill (17 m/min) and in the curcumin group received curcumin (50 mg/kg) by gavage daily for 8 weeks for 2 months. At the end, heart samples were collected and used for determination of autophagy by immunostaining for LC3-phosphatidylethanolamine conjugate (LC3-II), apoptosis by TUNEL assay, Malondialdehyde (MDA) level by enzymatic assay and determination of mediators' molecules by ELISA for NADPH Oxidase 4 (NOX4), sirtuin 1 (SIRT-1), phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-Ƙb) protein levels and Sequestosome-1 (P62). Also, histological changes such as fibrosis evaluated by Masson trichrome staining. RESULTS: Our results showed that autophagy, SIRT-1 level were significantly decreased and MDA, NOX4, p-NF-Ƙb and P62 levels were significantly increased in heart of aged group compared to young group. Also, significant increased apoptosis and fibrosis levels in the heart of aged rats were observed compared with young rats, whereas, these undesirable changes were improved by exercise and curcumin. Also, combination therapy of aged rats with curcumin and exercise showed more significant prominent effect on molecular mediators and histological changes in the heart compared with monotherapy. CONCLUSION: These findings indicate that stress oxidative increase and autophagy decrease in the heart tissue of aged rats. The age induced the mentioned changes in the heart may in part be associated with down-expression of SIRT-1 and overexpression of NOX4 proteins. It was also showed that these age induced effects can be alleviated by treatment with exercise and curcumin. Since NF-Ƙb increased in both the age and treatment groups, it seems the age heart increased NF-Ƙb to be due to a compensatory mechanism.

Rheumatoid arthritis: current therapeutics compendium.

Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.

The impact of zinc on the molecular signaling pathways in the diabetes disease.

Since there's been an upsurge in people with diabetes or pre-diabetes conditions, many studies have been conducted to evaluate approaches for reducing the complications of diabetes. One of the most common therapeutic elements suggested for this purpose is zinc (Zn). Zn has long been shown to positively improve complications of both type 1 and type 2 diabetes. This review aims to provide comprehensive information about the influence of Zn on the various signaling pathways in multiple tissues with diabetic conditions, with great attention to the treatment period and effective dose of Zn.

Crocin attenuates inflammation of lung tissue in ovalbumin-sensitized mice by altering the expression of endoplasmic reticulum stress markers.

Endoplasmic reticulum (ER) stress plays a pivotal role in the pathogenesis of asthma. The present study aimed to investigate the reducing or suppressing effects of crocin in ovalbumin (OVA)-sensitized mice on ER stress markers. Mice were divided into six groups (n = 5 per group) including control, OVA-sensitized (OVA), OVA-treated crocin (OVA-Cr25, OVA-Cr50, and OVA-Cr100 mg/kg), and OVA-treated dexamethasone (1 mg/kg), (OVA-Dexa) groups. Animals 5 later groups were sensitized to OVA and the treatment groups received intraperitoneally crocin/dexamethasone in the last 5 days of the model. At the end of the study, lung tissue was evaluated for airway inflammation, caspase 12 and CHOP protein levels, and expression of ER stress markers using real-time-PCR. Sensitization with OVA significantly caused airway inflammation and induction of ER stress in mice compared to the control group based on the elevated inflammatory cells and ER stress markers in the lung tissue. Treatment with crocin and dexamethasone reduced airway inflammation and suppressed ER stress markers. Interestingly, in the OVA-Cr100 group, the suppressive effects on ER stress apoptotic markers were comparable to the OVA-Dexa group. The results suggest that crocin mediates maladaptive ER stress conditions possibly by creating adaptive ER stress status and driving protein folding correctly.

Curcumin improves angiogenesis in the heart of aged rats: Involvement of TSP1/NF-κB/VEGF-A signaling.

BACKGROUND: Cardiac aging is an irreversible process that is determined by a number of slowly deleterious changes in morphological and physiological properties of the heart. We investigated the effects of curcumin on cardiac angiogenesis, in old male rats. MATERIALS AND METHODS: Rats randomly divided into young, age (rats of 26-28 months of age) and curcumin-age (rats of 26-28 months of age treatment with curcumin 50mg/kg). Finally, the expression of VEGF, NF-κB, and TSP-1 were assessed by ELISA in cardiac tissue. Also, angiogenesis was determined by immunostaining for PECAM-1/CD31 and apoptosis was evaluated by TUNEL. RESULTS: After 2 months, curcumin-age had significantly higher cardiac VEGF-A and NF-κB and lower cardiac TSP-1 expression levels in comparison with age and young. A significant increase in levels of NF-κB and TSP-1 were observed in the age group. CONCLUSION: Results suggest that curcumin through regulation of cardiogenic mediators and improving cardiac angiogenesis can promote heart performance in the senescent rats.

Targeting Mitochondrial Biogenesis with Polyphenol Compounds.

Appropriate mitochondrial physiology is an essential for health and survival. Cells have developed unique mechanisms to adapt to stress circumstances and changes in metabolic demands, by meditating mitochondrial function and number. In this context, sufficient mitochondrial biogenesis is necessary for efficient cell function and haemostasis, which is dependent on the regulation of ATP generation and maintenance of mitochondrial DNA (mtDNA). These procedures play a primary role in the processes of inflammation, aging, cancer, metabolic diseases, and neurodegeneration. Polyphenols have been considered as the main components of plants, fruits, and natural extracts with proven therapeutic effects during the time. These components regulate the intracellular pathways of mitochondrial biogenesis. Therefore, the current review is aimed at representing an updated review which determines the effects of different natural polyphenol compounds from various plant kingdoms on modulating signaling pathways of mitochondrial biogenesis that could be a promising alternative for the treatment of several disorders.

Effect of moderate exercises and curcumin on hepatic transcriptional factors associated with lipid metabolism and steatosis in elderly male rat.

BACKGROUND AND PURPOSE: The specific molecular mediators involved in dyslipidemia in older people are not yet clearly understood. The current study was, thus, an attempt to investigate whether moderate aerobic exercises and curcumin administration alleviates the abnormalities caused by aging in the rats' liver. EXPERIMENTAL APPROACH: Thirty-two eight-year-old young rats were classified into five groups, namely, young control, aged control, aged-curcumin, aged-exercise, and aged-curcumin-exercise co-treatment. The rats in the exercise groups were trained on an animal treadmill for 60 min/day five times per week for eight weeks. FINDINGS/RESULTS: The results revealed a significant increase in FAT/CD36, PTP1B, significantly decreased HNF4α genes expression, increase in LDL and cholesterol in the aged group compared to the young control. Compared to those in the young control group, no significant changes in HDL and TG amounts in the aged control were observed. Moreover, compared to the young control, the aged group showed liver histological changes such as fibrosis and mild or grade 1 steatohepatitis. Moderate aerobic exercise and curcumin alone or in combination completely masked this effect. CONCLUSION AND IMPLICATIONS: The findings revealed dyslipidemia and liver steatosis related to aging might be partly associated with changes in hepatic transcriptional factors which can be mitigated via moderate aerobic exercise and curcumin.

The protective effect of zinc on morphine-induced testicular toxicity via p53 and Akt pathways: An in vitro and in vivo approach.

BACKGROUND: Chronic use of morphine is associated with reproductive complications, such as hypogonadism and infertility. While the side effects of morphine have been extensively studied in the testis, much less is known regarding the effects of morphine on Sertoli cells and the effects of zinc on morphine-induced testicular injury as well as their underlying mechanisms. Therefore, the purpose of this study was to investigate the effect of morphine (alone and co-administered with zinc) on cell viability and apoptosis of the testicular (Sertoli) cells as well as the tumor suppressor p53 and phosphorylated-protein kinase B (p-Akt) protein levels in both in vitro and in vivo models. METHODS: Cultured Sertoli cells were exposed to morphine (23 µM), zinc (8 µM), and zinc prior to morphine and their effects on Sertoli cell viability and apoptosis were investigated. Morphine (3 mg/kg) and zinc (5 mg/kg, 1 h before morphine) were also injected intraperitoneally to rats and then the apoptotic changes in the testis were evaluated. RESULTS: Cell viability and p-Akt protein levels decreased in morphine-treated cells, while apoptosis and p53 protein expression increased in these cells. Pretreatment with zinc recovered morphine-induced apoptotic effects, as well as over-expression of p53 and down-regulation of p-Akt. These findings were supported by a subsequent animal study. CONCLUSION: The present data indicated the protective effect of zinc against morphine-induced testicular (Sertoli) cell toxicity via p53/Akt pathways in both in vivo and in vitro models and suggested the clinical importance of zinc on infertility among chronic opioid users and addicted men.

A Comprehensive Review of Detection Methods for SARS-CoV-2.

Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of SARS-CoV-2 infection, with various advantages and weaknesses to each. In this paper, we summarize promising methods, such as reverse transcription-polymerase chain reaction (RT-PCR), serological testing, point-of-care testing, smartphone surveillance of infectious diseases, nanotechnology-based approaches, biosensors, amplicon-based metagenomic sequencing, smartphone, and wastewater-based epidemiology (WBE) that can also be utilized for the detection of SARS-CoV-2. In addition, we discuss principles, advantages, and disadvantages of these detection methods, and highlight the potential methods for the development of additional techniques and products for early and fast detection of SARS-CoV-2.

Stem cell-derived biofactors fight against coronavirus infection.

Despite various treatment protocols and newly recognized therapeutics, there are no effective treatment approaches against coronavirus disease. New therapeutic strategies including the use of stem cells-derived secretome as a cell-free therapy have been recommended for patients with critical illness. The pro-regenerative, pro-angiogenic, anti-inflammatory, anti-apoptotic, immunomodulatory, and trophic properties of stem cells-derived secretome, extracellular vesicles (EVs), and bioactive factors have made them suitable candidates for respiratory tract regeneration in coronavirus disease 2019 (COVID-19) patients. EVs including microvesicles and exosomes can be applied for communication at the intercellular level due to their abilities in the long-distance transfer of biological messages such as mRNAs, growth factors, transcription factors, microRNAs, and cytokines, and therefore, simulate the specifications of the parent cell, influencing target cells upon internalization and/or binding. EVs exhibit both anti-inflammatory and tolerogenic immune responses by regulation of proliferation, polarization, activation, and migration of different immune cells. Due to effective immunomodulatory and high safety including a minimum risk of immunogenicity and tumorigenicity, mesenchymal stem cell (MSC)-EVs are more preferable to MSC-based therapies. Thus, as an endogenous repair and inflammation-reducing agent, MSC-EVs could be used against COVID-19 induced morbidity and mortality after further mechanistic and preclinical/clinical investigations. This review is focused on the therapeutic perspective of the secretome of stem cells in alleviating the cytokine storm and organ injury in COVID-19 patients.

Testosterone Combined with Voluntary Exercise Attenuates Diabetes-induced Pancreatic Apoptosis in Castrated Diabetic Rats Induced by HFD/STZ

Abstract Increased apoptosis in the pancreas and beta cell death causes reduced insulin secretion in type 2 diabetes. This study was aimed to evaluate the effects of exercise training and testosterone administration on apoptosis marker (p53 protein) in the pancreas tissue in animal with diabetes. Type 2 diabetes was induced by high fat diet and injection of low dose STZ (35mg/kg; ip). After 2 months of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, apoptosis (tunnel assay) and p53 protein (ELISA method) were measured. Testosterone and exercise decreased the blood glucose, HbA1c levels, HOMA-IR, p53 protein expression and increased insulin level in treated diabetic and diabetic castrated groups. Simultaneous treatment of these groups with testosterone together voluntary exercise had an additive effect on reducing p53 expression, blood glucose, HbA1c levels, HOMA-IR and subsequently decreasing apoptosis. Our results suggest that the apoptosis decreasing effect of testosterone and voluntary exercise is associated with the reduced levels of blood glucose, HbA1c and HOMA-IR that subsequently decreased the expression of p53 level.