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Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000 C-kit+ cells, and (4) Diabetic + C-kit− cells (D + C-kit neg), intravenously injected C-kit− cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MET) is one of the most important chemotherapy agents used against various tumors and cancer diseases. One of the critical side effects of MET is inducing male infertility. Objective: The current study aimed to investigate Sertoli cell culture-conditioned medium (SCM) recovery effects on MET-induced conditions in rats. Materials and Methods: 30 mature male Wistar rats were randomly divided into 3 groups (n = 10). In the first group, rats received normal saline intraperitoneally. In the second group, animals received MET (10 mg/kg; intraperitoneally) once a week for 2 wk. The rats in the third group (MET+SCM) received MET and a single injection of SCM for 56 days post-MET administration. 56 days later, serum, epididymis, and testicular tissue samples were collected, and the animals were euthanized. Sperm parameters, serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone were examined. The testicular tissues were stained using hematoxylin and eosin solution, and histopathological changes were analyzed. Results: The MET-induced condition resulted in significant pathological changes in the testis, decreased hormone levels, and downregulated sperm parameters. However, SCM injection improved hormonal levels, testicular changes, and sperm parameters. Conclusion: It can be concluded that a single intra-testicular SCM injection accelerates male reproductive system recovery post-MET treatment. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats. Materials and Methods: Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-a using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis. Results: Diabetes reduced the IL-10, IL-11, and Nrf2 levels (P<0.001 to P<0.01) and increased the levels of TNF-a and NF-κB compared to the Col group (P<0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (P<0.001 to P<0.05), however; the TNF-a and NF-κB levels decreased (P<0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (P<0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group. Conclusion: These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions. [ABSTRACT FROM AUTHOR]

Objective(s): Although various studies have revealed the beneficial effects of crocin (derived from saffron), such as anti-inflammatory, anti-cancer, antioxidant, and immune modulator, however, its exact mechanism is unknown. The present study aimed to investigate the effect of crocin on the expression ratio of T-bet/GATA-3 as an indicator of altered immune responses in the lung tissue of ovalbumin (OVA)-sensitized mice. In addition, the effect of crocin on the expression level of miR- 146a and miR-106a in the lung tissue OVA-sensitized mice was investigated. Materials and Methods: Mice were randomly divided into five groups (n=6): Control; OVA, OVA + Crocin 25, OVA + Cro 50, and OVA + Cro100 groups. Crocin was administrated intraperitoneally at doses of 25, 50, and 100 mg/kg for five consecutive days. One day after asthma induction, animals were euthanized, and lungs were sampled for pathological and gene expression analysis. Results: OVA-sensitization led to increased inflammation and histopathological changes in the lung tissue of mice. In addition, GATA-3 expression increased (P<0.001) and T-bet expression decreased (P<0.001) in OVA-sensitized groups. The T-bet/GATA3 ratio was also reduced markedly in asthma groups (P<0.001). Furthermore, increased expression of miR-146a and miR-106a levels was evident in the lung tissue of OVA-sensitized mice (P<0.001 for both). Intervention with high concentrations of crocin (50 and 100 mg/kg) significantly reduced airway inflammation, GATA-3 expression, miR-146a expression, and miR-106a expression and corrected the T-bet/GATA-3 ratio (P<0.05 to P<0.001). Conclusion: Treatment with crocin led to a decrease in the severity of lung inflammation in OVAsensitized mice, which is probably through the reduction of the T-bet/GATA-3 ratio, and mir-146a and mir-106a expression level. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is one of the leading causes of death globally. The development of cellular injuries and impaired energy metabolism are involved in the pathogenesis of diabetes mellitus, leading to severe diabetic complications in different tissues such as the pulmonary tissue. Autophagy is a double-edged sword mechanism required for maintaining cell survival and homeostasis. Any abnormalities in autophagic response can lead to the progression of several diseases. Here, we aimed to assess the effect of diabetic conditions on the autophagic response and exosome secretion in a rat model of type 2 diabetes mellitus. The experimental diabetic group received 45.00 mg kg-1 streptozocin (STZ) dissolved in 0.10 M sodium citrate. After 4 weeks, we monitored autophagic response and exosome biogenesis in the pulmonary tract using immunohistochemistry (IHC) and Real-time polymerase chain reaction analyses, respectively. Histological examination revealed the interstitial bronchopneumonia indicating enhanced immune cell infiltration into the pulmonary parenchyma. Immunohistochemistry staining displayed an enhanced autophagic response through the induction of microtubleassociated protein light chain 3 (LC3) and protein sequestosome 1 (P62) compared to the control rats. These changes coincided with significant induction of tetraspanin CD63 in STZinduced diabetic rats relative to control rats. In conclusion, a diabetic condition can increase the autophagic response in pulmonary tissue. The accumulation of P62 in the pulmonary niche exhibits an incomplete autophagic response. The abnormal autophagy response can increase pulmonary cell sensitivity against injuries. [ABSTRACT FROM AUTHOR]

Background: To circumvent some pitfalls related to acute status, chronic model of asthma is conceived to be more suitable approach to guarantee the conditions which are similar to human pulmonary disease. Here, possible therapeutic mechanisms were monitored by which c-kit+ bone marrow cells can attenuate vascular inflammation in rat model of chronic asthma. Results: Data revealed c-Kit+ cells could significantly reduce pathological injures in asthmatic rats via modulating the expression of IL-4, INF-γ, ICAM-1 and VCAM-1 in lung tissues and TNF-α, IL-1β and NO levels in BALF (p < 0.001 to p < 0.05). Besides, c-Kit+ cells reduced increased levels of VCAM-1 evaluated by immunohistochemistry staining. In contrast to c-Kit+ cells, c-Kit− cells could not exert beneficial effects in the asthmatic conditions. Conclusion: Overall, we found that systemic administration of C-kit positive cells can diminish pulmonary and vascular inflammation of chronic asthmatic changes in a rat model. These cells are eligible to suppress inflammation and nitrosative stress in lung tissue coincides with the reduction of pathological changes. These data indicate that C-kit positive cells be used as an alternative cell source for the amelioration of asthmatic changes. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The aim of the experiment was to highlight the regenerative capacity of bone marrow Kit+ cells in the restoration of asthmatic pulmonary function in the rat model.What is the main finding and its importance?Data showed that these cells were recruited successfully to the asthmatic niche after intratracheal administration and accelerated the regeneration of asthmatic lungs by the modulation of inflammation via the control of Gata3 and Tbx21 expression, leading to decreased tracheal responsiveness to methacholine and reduction of pathological remodelling. Allergic asthma is a T helper (Th) 2 immunological disorder with consequential uncontrolled inflammatory responses. There is an increasing demand to use new methods for the treatment of asthma based on modulation of the Th2‐to‐Th1 ratio in favour of the Th1 population. Accordingly, we decided to evaluate the effects of intratracheal administration of Kit+ bone marrow cells on tracheal responsiveness and the expression of Gata3 and Tbx21 genes. Forty male Wistar rats were allocated randomly into four experimental groups: healthy rats (control group), sensitized rats (OVA group), sensitized rats receiving Kit− cells (OVA+Kit− group) and sensitized rats receiving Kit+ cells (OVA+Kit+ group). Total and differential white blood cell counts, tracheal responsiveness to cumulative methacholine concentrations and histopathological analysis were evaluated. The results showed a statistically significant increase in total white blood cell, eosinophil and neutrophil counts, tracheal contractility, Gata3 expression and prototypical histopathology of asthma. Along with these conditions, we found that the number of lymphocytes was decreased and expression of Tbx21 diminished in sensitized rats compared with control animals. Monitoring of labelled tagged cells confirmed successful engraftment of transplanted cells in pulmonary tissue. Juxtaposition of Kit+ cells changed the blood leucogram closer to the control values. Kit+ cells increased the expression of Tbx21 and suppressed Gata3 (P < 0.05). In the OVA+Kit+ group, tracheal responsiveness was improved coincident with increased pulmonary regeneration. In conclusion, this study showed that intratracheal administration of bone marrow‐derived Kit+ cells, but not Kit− cells, could be effective in the alleviation of asthma, presumably by the modulation of Gata3 and Tbx21. [ABSTRACT FROM AUTHOR]