BackgroundMesenchymal stem cells (MSCs) are valuable for cell-based therapy. However, their application is limited owing to their low survival rate when exposed to stressful conditions. Autophagy, the process by which cells recycle the cytoplasm and dispose of defective organelles, is activated by stress stimuli to adapt, tolerate adverse conditions, or trigger the apoptotic machinery. This study aimed to determine whether regulation of autophagy would affect the survival of MSCs under stress conditions.MethodsAutophagy was induced in bone marrow-derived MSCs (BM-MSCs) by rapamycin, and was inhibited via shRNA-mediated knockdown of the autophagy specific gene, ATG7. ATG7 expression in BM-MSCs was evaluated by reverse transcription polymerase chain reaction (RT-PCR), western blot, and quantitative PCR (qPCR). Cells were then exposed to harsh microenvironments, and a water-soluble tetrazolium salt (WST)-1 assay was performed to determine the cytotoxic effects of the stressful conditions on cells.ResultsOf 4 specific ATG7-inhibitor clones analyzed, only shRNA clone 3 decreased ATG7 expression. Under normal conditions, the induction of autophagy slightly increased the viability of MSCs while autophagy inhibition decreased their viability. However, under stressful conditions such as hypoxia, serum deprivation, and oxidative stress, the induction of autophagy resulted in cell death, while its inhibition potentiated MSCs to withstand the stress conditions. The viability of autophagy-suppressed MSCs was significantly higher than that of relevant controls (P<0.05, P<0.01 and P<0.001).ConclusionAutophagy modulation in MSCs can be proposed as a new strategy to improve their survival rate in stressful microenvironments.

Background: Since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic there have been contradictions and speculations about the relationship between vitamin D and COVID-19. Given that there is an association between vitamin D deficiency and some diseasesincluding cancer, autoimmune disease and some infectious diseasesa higher incidence and mortality rate in the vitamin-D-deficient COVID-19 population was not a surprise; conversely, some research would argue this relationship. Considering these contradictions, this study aimed to determine the relationship between prognosis and vitamin D level in cases with COVID-19. Methods: In this cross-sectional study, 329 confirmed cases of COVID-19who were admitted to Kamkar-ArabNia Hospital in Qom city, Iran from March-July 2020were categorized into three groups according to vitamin D serum levels (ng/ml): sufficient (>30), insufficient (20-30) and deficient (<20). Prognosis was determined across the groups. Results: There was a significant difference in hospital stay between patients with sufficient and insufficient vitamin D levels (P = 0.007). Adjusting vitamin D levels for confounding variables, linear regression underscored significant differences in the association between length of hospitalization and lower vitamin D levels, with a longer stay noted in insufficient groups (P = 0.002). However, there was no significant difference in the time interval to return to normal oxygen level (from SpO2 < 93%) or death rate between groups (P > 0.05). Conclusion:There was a significant association between hospital stay and lower serum vitamin D levels. However, the relationship between vitamin D status and death rate or the time interval to return to normal oxygen levels was not significant.

Background: Immobilization has been used extensively and accepted widely for studying stress-induced alterations. To determine the protective effects of Aloe vera leaf extract, we evaluated the effects of co-administration of immobilization stress and Aloe vera leaf extract on serum level of carcinoembryonic antigen (CEA) tumor marker in male rats. Materials and Methods: In this experimental study, 45 male Wistar rats were randomly divided into 9 groups of 5 rats in each including: 1) control, 2) normal saline receiving, 3) Aloe vera extract receiving, 4) acutely immobilized, 5) chronically immobilized, 6) acutely immobilized+Aloe vera extract, 7) chronically immobilized+Aloe vera extract, 8) acutely immobilized+normal saline and 9) chronically immobilized+normal saline. The animals were exposed to chronic or acute immobilization stress for 2 h/day or 8 h/day for a period of 3 weeks or one week, respectively. Aloe vera extract (300 mg/kg/day) was fed by gavage feeding orally. Blood samples were collected and following serum collection, CEA level was determined by radioimmunoassay method. Data were compared statistically between groups using ANOVA. Results: Serum CEA level was significantly increased in acutely (0.640±0.025 ng/mL) or chronically immobilized (0.647±0.023 ng/mL) rats compared with control animals group (0.564±0.014 ng/mL) (p<0.001). However, there was no significant difference between serum CEA levels of acutely or chronically immobilized Aloe vera extract received animals compared with control rats (0.622±0.027 ng/m and 0.616±0.044 ng/mL, respectively). Conclusion: Our findings indicate that immobilization stress enhances serum CEA level, however, intake of Aloe vera extract can withstand against.

Background: Various studies indicate that life style may influence serum enzyme levels. Objectives: The aim of this study was to evaluate the effects of waterpipe smoking, immobilization and darkness stress on serum creatine kinase (CK) and alkaline phosphatase (ALP) levels in female rats. Materials and Methods: Female Wistar rats were divided into control, waterpipe smoking, immobilized, under darkness stress, immobilized waterpipe smoking, under darkness stress waterpipe smoking, under darkness stress immobilized and under darkness stress immobilized waterpipe smoking of 7 each. Waterpipe smoking exposure was 10 th /day for 10 minutes of each with 5 minutes resting time; chronically immobilization was applied 4 hours/day (twice a day for 2 hours with 2 hours resting time) and darkness stress for 6 hours/day in dark situation. Following 7 weeks experiment, serum enzyme levels were measured and compared statistically between groups using ANOVA. Results: The results indicated enhanced serum CK and ALP levels in all groups compared with control (P < 0.05). Also, there was a significant difference in serum CK levels between all the groups including different types or multiplicity of stress (P < 0.05). Serum ALP levels were found less affected by these factors; where darkness or immobilization have shown semi-equal effect on these enzyme levels with no significant difference. Besides, under darkness immobilized waterpipe smoking, ALP levels have no significant difference compared to immobilized waterpipe smoking or under darkness stress waterpipe smoking animals. Conclusions: Our findings clearly indicate a synergistic effect of waterpipe smoke, immobilization and darkness stress on serum CK levels, whereas serum ALP levels of experimental groups have shown no significant synergism for the mentioned factors.

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