Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA. Conclusion: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its effect on DN. In our study we used five groups of rats; control, DN, DN treated with exosomes, DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy) and DN treated with 3-methyladenine (3-MA) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Background: Impairment of testicular function is one of complications of Diabetes mellitus (D.M) and this may result from increased oxidative stress. Vitamin E (Vit E) has antioxidant properties. Objective: To determine the microscopic changes in the diabetic testis with metformin alone or with Vit E and which of them are better to preserve the testicular structure. Materials and Methods: Fifty adult albino rats, were equally divided into five groups: Group 1: control group; group 2: diabetic group (diabetes was induced by (65 mg/kg; i.p) single dose of streptozotocin (STZ); group 3: vit.E-treated diabetic group (200 mg/kg/day) ip; group 4: Metformin-treated diabetic group (100 mg/kg/day) and group 5 Metformin and vit.E-treated diabetic group for eight weeks. Levels of testosterone, insulin and blood sugar were analyzed and testes specimens were prepared for light microscope and immunohistochemical detection of androgen receptor (AR) and caspase-3. Results: In diabetic group showed irregular seminiferous tubules with depletion, separation, vacuolation of the spermatogenic cells with perivascular and intertubular fibrosis also, the mean diameter of tubules significantly decreases. There are negative immunoexpressions of AR with positive caspase-3. Sections of metformin treated diabetic group showed incomplete or partial regeneration of germ cells while in group 4 and 5 showed almost complete regeneration of spermatogenic cells with increase in mean diameter of tubules, significantly

Background: Deltamethrin (DLM) is class II synthetic pyrethroid used worldwide as pesticides in agriculture, household pest control, protection of foodstuff, and disease vector control. Exposures occur mainly from the household application, contaminated food or water. Although initially thought to be least toxic, a number of recent studies revealed its toxic effects in different animal species. Aim: The current study aimed to evaluate oxidative stress effect due to DLM exposure on brain tissues of adult albino rats, and whether co-administration of pomegranate (PM) molasses can ameliorate this oxidative damage. Materials & Methods: Thirty adult experimental Albino rats were divided into five groups:-ve control group (6 rats), +ve control group (6 rats) (received 1ml corn oil once daily, orally), diluted PM molasses [(0.5ml (PM) molasses+(0.5ml) distilled water] treated group (6 rats), DLM (6mg/kg) treated group (6 rats), DLM (6mg/kg) + diluted PM molasses[(0.5ml (PM) molasses+(0.5ml) distilled water] treated group (6 rats). These doses were given once daily, orally for seven days. By the end of the expirement, blood sample were obtained for estimation of plasma cholinesterase (PCHE) level and oxidative stress parameters) malondialdehyde [MDA], glutathione [GSH], and catalase [CAT] (, then rats were sacrificed. The brains were excised, prepared for estimation of oxidative stress parameters in tissue, histopathological changes and immunohistochemical examination. Results: revealed that DLM caused neurotoxicity in albino rats as there was a significant increase in serum & brain tissues MDA, reduction of both GSH & CAT, decrease in PCHE level & pathological changes in brain included, neuronal degeneration, apoptotic bodies, neuropil vacuolizations, proliferated and dilated blood vessels beside strong positive immunreaction for bax when compared with both control groups & PM molasses treated groups. While, there was significant reduction in serum & brain MDA, significant increase in both GSH &CAT and also decrease in PCHE level. Mild pathological changes in brain of albino rats beside mild positive immunreaction for bax in DLM + PM molasses treated group as compared to DLM treated group. Conclusion: deltamethrin can induce oxidative damage in the experimental albino rat brain & pomegranate molasses as an antioxidant has an ameliorative effect against this damage.

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.

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Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), it is used in the treatment of depression; it has a toxic effect on the testis. Major depressive disorder is a pathological disorder associated with increased levels of the inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β). Fluoxetine increase in malondialdehyde (MDA) and decrease in antioxidant enzyme activity SOD superoxide dismutase and catalase (SOD and CAT) and reduced glutathione (GSH). The study aimed to investigate whether vitamin D can reduce the oxidative damage caused by fluoxetine. Thirty -two adult male rats are divided into four groups and are included in the analysis. Animals in Group I (control group) were administered distilled water by gavage. Groups II: animals were given a dose of 10 mg/kg of fluoxetine (fluoxetine treated group) orally by gavage daily for 4 weeks. Group III (vitamin D group) animals received intramuscular VD (1,000 IU/kg; 3 days/week for 4 weeks. Group IV (fluoxetine+ vitamin D): drugs were given in the same previous doses for 4weeks. Blood samples were obtained 24 hours after the last dose of each drug. The biochemical results showed that fluoxetine significantly increased oxidative stress in testicular tissue and inflammatory markers in serum. The in-depth investigations supported that administering the fluoxetine combined with vitamin D reduced the testicular damage to a marked level and normalized all relevant markers. It was concluded that the oxidative stress induced by fluoxetine administration in rats could be reduced by vitamin D supplementation.

Preimplantation genetic diagnosis (PGD) offers couples who need to avoid having a child affected with a severe genetic disease, an alternative to prenatal diagnosis and termination of an existing pregnancy. One of the main indications of PGD is sex selection to avoid sex-linked genetic disorders. The main objective of the present study was to investigate the feasibility of whole genome amplification (WGA) and real time PCR for sexing of single human blastomere and to confirm the results by sequencing. Forty non-viable embryos were selected for analysis. WGA technique was employed on single blastomeres that were biopsied from embryos and on buccal mucosal cells obtained from five men and five women as positive and negative controls respectively. Whole genomic DNA amplification efficiency from a single human blastomere and from optimized buccal cells was 100 % and the level of amplification reached hundreds fold. The obtained genomic DNAs were then subjected to PCR amplification of the SRY, DYS14 and DAZ genes for gender determination. DAZ sequences correctly identified the gender of all male and female embryos with 100% sensitivity and specificity. However, the obtained sensitivity and specificity for SRY sequences were 92.6% and 100% respectively and the obtained sensitivity and specificity for DYS14 sequences were 100% and 93.8% respectively. The results of the present study prove the feasibility of WGA PCR assay for the detection of specific DNA fragments from single cells and the real-time PCR assay of the multicopy DAZ sequence in single human blastomeres detected correctly the embryo's gender. This will pave their use in preimplantation gender determination genetic diagnosis.. Keywords  Preimplantation genetic diagnosis  Embryo sexing  Single human blastomere  Whole genome amplification  Real time PCR. Bull. of Egyp. Soc. Physiol. Sci.