Bone Marrow-Derived C-Kit+ Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats.

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.

Swimming training reduced inflammation and apoptotic changes in pulmonary tissue in type 1 diabetic mice.

Background: Despite the vulnerability of pulmonary tissue to diabetic conditions, there are few reports related to the detrimental effects of hyperglycemia and therapeutic modalities on lung parenchyma. Here, the apoptotic changes were monitored in the diabetic pulmonary tissue of mice (DM1) subjected to a four‒week swimming plan. Methods: The mice were randomly allocated into Control; Control + Swimming (S); Diabetic group (D); and Diabetic + Swimming (D + S) groups (each in 8 mice). In the D and D + S groups, mice received intraperitoneally 50 mg/kg of streptozotocin (STZ). After 14 days, swimming exercise was done for four weeks. The expression of il-1ß, bcl-2, bax, and caspase-3 was investigated using real-time PCR analysis. A histological examination was performed using H&E staining. Results: DM1 significantly upregulated il-1ß, bax, and caspase-3, and down-regulated bcl-2 compared to the non-diabetic mice (p < 0.05). We noted that swimming exercises reversed the expression pattern of all genes in the diabetic mice and closed to basal levels (p < 0.05). Data indicated that swimming exercise could diminish emphysematous changes, and interstitial pneumonitis induced by STZ. Along with these changes, swimming exercise had protective effects to reduce the thickness of the inter-alveolar septum and mean alveolar area in diabetic mice. Conclusion: These data demonstrated that swimming exercises could decrease DM1-related pathologies in mouse lungs by regulating apoptosis and inflammatory response.

Can troxerutin pretreatment prevent testicular complications in prepubertal diabetic male rats?

OBJECTIVE: The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system's impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats. METHODS: Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2-4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed. RESULTS: The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group. CONCLUSION: Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.

Swimming Impacts on Pancreatic Inflammatory Cytokines, miR-146a and NF-кB Expression Levels in Type-2 Diabetic Rats.

BACKGROUND: Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and type-2 diabetes Objective: This study aimed to evaluate the effect of swimming exercise on pancreatic expression levels of inflammatory cytokines, miR-146a and NF-кB in type-2 diabetic male rats. METHODS: Twenty- eight male Wistar rats were divided into four groups: control (Con), exercise, diabetes and diabetic exercise (n = 7). Diabetes induction performed by the combination of high-fat diet (HFD, 4 weeks) and streptozotocin (35 mg/kg. ip). After induction of diabetes, the rats swam in the exercise groups for 12 weeks. Then, blood and tissue samples were collected. RESULTS: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1ß) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group. CONCLUSION: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1ß) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.

Prophylactic furosemide infusion decreasing early major postoperative renal dysfunction in on-pump adult cardiac surgery: a randomized clinical trial.

INTRODUCTION: Acute renal dysfunction is a common complication of cardiac surgery. Furosemide is used in prevention, or treatment, of acute renal dysfunction. This study was conducted to evaluate the protective effects of intra- and early postoperative furosemide infusion on preventing acute renal dysfunction in elective adult cardiac surgery. METHODS: Eighty-one patients, candidates of elective cardiac surgery, were enrolled in this study in either the furosemide (n=41) or placebo (n=40) group. Furosemide (2 mg/h) or 0.9% saline was administered and continued up to 12 hours postoperatively. We measured serum creatinine (Scr) at preoperative and on the second and fifth postoperative days. Then calculated estimated glomerular filtration rate (eGFR) at these times. An increase in Scr of >0.5 mg/dL and/or >25%-50%, compared to preoperative values, was considered as acute kidney injury (AKI). In contrast, an increase in Scr by >50% and/or the need for hemodialysis was regarded as acute renal failure (ARF). At the end we compared the AKI or ARF incidence between the two groups. RESULTS: On the second and fifth postoperative days, Scr was lower, and the eGFR was higher in the furosemide group. AKI incidence was similar in the two groups (11 vs 12 cases; P-value 0.622); however, ARF rate was lower in furosemide group (1 vs 6 cases; P-value 0.044). During the study period, Scr was more stable in the furosemide group, however in the placebo group, Scr initially increased and then decreased to its preoperative value after a few days. CONCLUSION: This study showed that intra- and early postoperative furosemide infusion has a renal protective effect in adult cardiac surgery with cardiopulmonary bypass. Although this protective effect cannot be discovered in mild renal dysfunctions, it apparently reduces the rate of the more severe renal dysfunctions. A more multidisciplinary strategy may be needed in reducing the milder renal damage.