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Objectives: 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-α 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-α 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-α 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., Competing Interests: No potential conflicts of interest were reported by the authors.

Objectives: The exact role of the progenitor cell types in the dynamic healing of asthmatic lungs is lacking. This investigation was proposed to evaluate the effect of intratracheally administered rat bone marrow-derived c-kit + cells on ovalbumin-induced sensitized male rats., Materials and Methods: Forty rats were randomly divided into 4 groups; healthy rats received phosphate-buffered saline (PBS) (C); sensitized rats received PBS (S); PBS containing C-kit- cells (S+C-kit - ); and PBS containing C-kit + cells (S+C-kit + ). After two weeks, circulatory CD4 + /CD8 + T-cell counts and pulmonary ERK/NF-ƙB signaling pathway as well as the probability of cellular differentiation were assessed., Results: The results showed that transplanted C-Kit + cells were engrafted into pulmonary tissue and differentiated into epithelial cells. C-Kit + cells could increase the number of CD4 + cells in comparison with the S group ( P <0.001); however, they diminished the level of CD8 + cells ( P <0.01). Moreover, data demonstrated increased p-ERK/ERK ratio ( P <0.001) and NF-ƙB level ( P <0.05) in sensitized rats compared with the C group. The administration of C-kit + , but not C-Kit - , decreased p-ERK/ERK ratio and NF-ƙB level compared with those of the S group ( P <0.05)., Conclusion: The study revealed that C-Kit + cells engrafted into pulmonary tissue reduced the NF-ƙB protein level and diminished p-ERK/ERK ratio, leading to suppression of inflammatory response in asthmatic lungs., Competing Interests: The authors declare that no conflict of interest exists.

Objectives: Most male patients with type 2 diabetes mellitus (T2DM) experience infertility. It is well established that regular physical activity could alleviate diabetic infertility symptoms. This study was designed to determine the effect of voluntary exercise on sperm malformation., Materials and Methods: Thirty-two male Wistar rats were randomly divided into control (C), diabetic (D), voluntary exercise (Ex), and diabetic-voluntary exercise (D-Ex) groups. Diabetes was induced by an intraperitoneal injection of streptozotocin (35 mg/kg) followed by a high-fat diet for four weeks. Voluntary exercise was performed by placing the animals in the rotary wheel cages for ten weeks. Sperm malformations were analyzed. Moreover, the hypothalamic leptin, kisspeptin, kisspeptin receptors (KissR), as well as plasma LH, FSH, testosterone, and leptin levels were evaluated., Results: Results showed that induction of T2DM caused increased sperm malformation, plasma, and hypothalamic leptin as well as decreased hypothalamic kisspeptin, KissR, and plasma LH levels compared with the C group ( P <0.001 to P <0.01). Voluntary exercise in the Ex group increased hypothalamic KissR, plasma FSH, LH, and testosterone levels compared with the C group; however, it decreased sperm malformation and hypothalamic leptin levels ( P <0.001 to P <0.05). Voluntary exercise in the D-Ex group reduced sperm malformation, hypothalamic leptin, and plasma testosterone while elevated hypothalamic kisspeptin and KissR protein levels compared with the D group ( P <0.001 to P <0.01)., Conclusion: The results illustrated voluntary exercise reduces sperm malformations by improving the HHG axis and kisspeptin/leptin signaling in rats with T2DM.

Objectives: There are still challenges regarding c-kit+ cells' therapeutic outcome in the clinical setting. Here, we examined the c-kit+ cell effect on the alleviation of asthma by modulating miRNAs expression., Materials and Methods: To induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (6 rats each). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) was assessed by real-time PCR analysis., Results: Pathological examination and Th1 and Th2 associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group ( P <0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had the potential to change INF-γ/IL-4 ratio close to the normal values compared with matched-control asthmatic rats ( P <0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by an increase of miRNA-133 and decrease of miRNA-126 compared with cell-free sensitized groups ( P <0.05)., Conclusion: c-kit- cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.

Objectives: This research was designed to demonstrate the impact of voluntary exercise on sperm parameters including sperm count, morphology, motility, viability, testicular apoptosis, oxidative stress, and the mir-34a/SIRT1/p53 pathway in type 2 diabetic rats., Materials and Methods: 32 Wistar male rats were separated into four groups: control (C), voluntary exercise (VE), diabetic (D), and diabetic rats that performed voluntary exercise (VED). To induce diabetes, animals were injected with streptozotocin (35 mg/kg) after receiving a high-fat diet. The testicular protein levels of SIRT1 and P53, miR-34a expression, MDA, GPx, SOD, catalase, and sperm parameters were evaluated., Results: Diabetes caused increased testicular MDA content, miR-34a expression, acetylated p53 protein expression, and the percent of immotile sperm ( P <0.01 to P <0.001) as well as reduced testicular GPx, SOD and catalase activities, SIRT1 protein expression, and sperm parameters ( P <0.05 to P <0.001). Voluntary exercise reduced testicular MDA content, miR-34a, and acetylated p53 protein expression compared with the D group ( P <0.001), however, GPx, SOD, catalase activities, and sperm parameters in voluntarily exercised rats were elevated compared with diabetic rats ( P <0.05 to P <0.001)., Conclusion: It seems that voluntary exercise has significant positive impacts that can be employed to reduce the complications of type 2 diabetes in the testis of male rats.

Objectives: Diabetes can gradually cause damage to the function and structure of male gonads. This survey was conducted to investigate the effect of troxerutin on hormonal changes, serum oxidative stress indices, and testicular function and structure in prepubertal diabetic rats., Materials and Methods: Fifty prepubertal (6 weeks old) male Wistar rats were divided into five groups including Control, Troxerutin, Diabetic, Diabetic+Troxerutin, and Diabetic+Insulin. Type I diabetes was induced by 55 mg/kg of streptozotocin intraperitoneally. The groups were treated with 150 mg/kg/day troxerutin via oral gavage or 4-6 IU/day insulin via subcutaneous injection for 4 consecutive weeks. Blood sugar (BS) and serum levels of insulin, FSH, LH, testosterone, glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were analyzed. Testis and epididymis were removed for histopathologic study and analysis of sperm parameters., Results: Troxerutin significantly reduced the BS in the diabetic group similar to insulin but could not affect insulin, FSH, or LH significantly. Troxerutin caused a significant increase in testosterone and GPX but had no significant effect on serum MDA, TAC, and SOD levels. In addition, troxerutin had a better effect than insulin on diabetes-induced testicular structural damage. Sperm analysis results also revealed that troxerutin and insulin could improve sperm number, motility, and viability in diabetic rats., Conclusion: According to these results, it can be derived that administration of troxerutin is a suitable protective strategy for side effects of diabetes in testis of prepubertal diabetic male rats., Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Objectives: Human and animal studies have shown a close relationship between obesity and asthma severity. Here, we examined the effects of diet-induced obesity (DIO) on the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA in male Wistar rats tracheal after sensitization with ovalbumin (OVA)., Materials and Methods: Twenty male Wistar rats divided to four groups, included, control group with normal diet (C+ND), OVA-sensitized group with normal diet (S+ND), control group with high-fat diet (C+HFD), and OVA-sensitized group with high-fat diet (S+HFD). All animals fed for 8 weeks with standard pelts or high-fat diet, and then were sensitized and challenged with OVA or saline for another 4 weeks with designed regimens. At the end of study, trachea isolated and examined for expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA with RT-PCR method., Results: Diet-induced obesity groups developed increased weight, obesity indexes and lipid profiles (P<0.05 to P<0.001). The expression levels of IL-1β mRNA in OVA-sensitization groups (S+ND and S+HFD) showed a significantly increased when compared with control group. Also in S+HFD group, expression level of TRAF-6 mRNA was higher than other groups (P<0.001). IRAK-1 expression level was high in S+HFD compared with control group.IL-1β and TRAF-6 mRNA correlated positively with obesity indexes., Conclusion: The results showed that DIO causes overexpression of IL-1β, IRAK-1 and TRAF-6 mRNA in an experimental model of asthma. Our results suggested that in obese-asthmatic conditions locally production and activation of pro-inflammatory agents can be increased. These findings showed that possible mechanism for obesity-asthma relationships.

Nigella sativa (N. sativa) is a spice plant which has been traditionally used for culinary and medicinal purposes. Different therapeutic properties including the beneficial effects on asthma and dyspnea, digestive and gynecology disorders have been described for the seeds of N. sativa. There is evidence of the relaxant effects of this plant and some of its constituents on different types of smooth muscle including rabbit aorta, rabbit jejunum and trachea. The relaxant effect of N. sativa could be of therapeutic importance such as bronchodilation in asthma, vasodilation in hypertension and therapeutic effect on digestive or urogenital disorders. Therefore in the present article, the relaxant effects of N. sativa and its constituents on smooth muscles and its possible mechanisms as well as clinical application of this effect were reviewed.

Objectives: For determining the mechanism of anti-asthmatic effect of thymoquinone, this investigation evaluated the effect of thymoquinone in the presence of selective A2A and A2B adenosine receptor antagonists (ZM241385 and MRS1706, respectively)., Materials and Methods: Seventy guinea pigs were randomly divided to 7 groups; control (C), sensitized with ovalbumin (S), sensitized groups pretreated with thymoquinone (S+TQ), ZM241385 (S+Anta A2A), MRS1706 (S+Anta A2B), thymoquinone and antagonists (S+Anta A2A+TQ and S+Anta A2B+TQ). Thymoquinone and each of these antagonists with 3 mg/kg dose were injected i.p. on 10(th) day of sensitization protocol. Tracheal responsiveness (TR) to methacholine and ovalbumin (OA), and total and differential cell count in lung lavage fluid (LLF) in different groups were measured., Results: Increased EC50 and LLF neutrophil count and decreased TR to methacholine and OA, LLF eosinophil and basophil counts were observed in S+TQ group compared to S group (P<0.001 to P<0.05). Significant decrease in EC50 (P<0.01), LLF neutrophil, lymphocyte and monocyte count (P<0.001 for all) and significant increase in TR to OA (P<0.01), LLF total WBC (P<0.01) and eosinophil count (P<0.001) were observed in S+A2A group compared to S+TQ group. There was significant increase in LLF eosinophil and monocyte counts in S+Anta A2B group compared with S+TQ group (P<0.001 for both). In S+TQ+Anta A2A group, there was significant increase in LLF eosinophil (P<0.001) and significant decrease in LLF neutrophil (P<0.01) and monocyte (P<0.001) counts compared with S+TQ group., Conclusion: Thymoquinone affects adenosine receptors, which suggest that some of its anti-inflammatory effects may be mediated by these receptors.

Objective(s): In regard to the high incidence of asthma and the side-effects of the drugs used, finding novel treatments for this disease is necessary. Our previous studies demonstrated the preventive effect of Nigella sativa extract on ovalbumin-induced asthma. In addition, water-soluble substances of N. sativa extract and methanol fraction of this plant were responsible for the relaxant effect of this plant on tracheal chains of guinea pigs. Therefore, for the first time, in the present study, in order to identify main constituents of the methanolic extract, the relaxant effects of five different methanolic fractions (20%, 40%, 60%, 80%, and 100%) of N. sativa on tracheal chains of guinea pigs were examined., Materials and Methods: The relaxant effects of four cumulative concentrations of each fraction (0.8, 1.2, 1.6, and 2.0 g%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6, and 0.8 mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 µM methacholine (group 2)., Results: In group 1, all concentrations of only theophylline showed significant relaxant effects but all concentrations of these methanolic fractions showed significant contractile effects compared with that of saline (P<0.001 to P<0.05). However, in group 2, all concentrations of theophylline and these methanolic fractions showed significant relaxant effects compared with that of saline (P<0.001 to P<0.05)., Conclusion: These results showed a potent relaxant effect of 20% methanolic fractions from N. sativa on tracheal chains of guinea pigs that were higher than that of theophylline at the used concentrations.