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Trastuzumab (Trz) is a humanized monoclonal antibody targeting epidermal growth factor receptor 2 (HER2; ErbB2). The combined administration of Trz and doxorubicin (DOX) has shown potent anti-cancer efficacy; however, this regimen may be accompanied by severe cardiac toxicity. Mesenchymal stem cells (MSCs)-derived exosomes are nanosized vesicles that play a crucial role in cell–cell communication and have shown efficacy in the treatment of various diseases. In this study, we aim to investigate the cardioprotective effects of MSCs-derived exosomes in a DOX/Trz- mediated cardiotoxicity model, and the possible mechanisms underlying these effects are elucidated. Forty-nine male rats were randomly assigned into four groups: Group I (control); Group II (Dox/Trz); Group III (protective group); and Group IV (curative group). Cardiac hemodynamic parameters, serum markers of cardiac injury, oxidative stress indices, and cardiac histopathology were investigated. Further, transcript profile of specific cardiac tissue injury markers, apoptotic markers, and fibrotic markers were analyzed using qRT-PCR, while the protein expressions of pAkt/Akt, pERK/ERK, pJNK/JNK, pJNK/JNK, and pSTAT3/STAT3 were evaluated by ELISA. Additionally, cardiac mirR-21 and miR-26a were assessed. A combined administration of DOX/Trz disrupted redox and Ca2+ homeostasis in cardiac tissue induced myocardial fibrosis and myofibril loss and triggered cardiac DNA damage and apoptosis. This cardiotoxicity was accompanied by decreased NRG-1 mRNA expression, HER2 protein expression, and suppressed AKT and ERK phosphorylation, while triggering JNK phosphorylation. Histological and ultra-structural examination of cardiac specimens revealed features typical of cardiac tissue injury. Moreover, a significant decline in cardiac function was observed through biochemical testing of serum cardiac markers and echocardiography. In contrast, the intraperitoneal administration of MSCs-derived exosomes alleviated cardiac injury in both protective and curative protocols; however, superior effects were observed in the protective protocol. The results of the current study indicate the ability of MSCs-derived exosomes to protect from and attenuate DOX/Trz-induced cardiotoxicity. The NRG-1/HER2, MAPK, PI3K/AKT, PJNK/JNK, and PSTAT/STAT signaling pathways play roles in mediating these effects.

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway.Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin).Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR.Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.

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 thatthe oxidative stress induced by fluoxetine administration in rats could be reduced by vitamin D supplementation.

Background Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells. Objective We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG). Methods Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined. Results Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V. Conclusion VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.

Up to 70% of thrombotic patients with no identifiable risk factors were termed idiopathic. Now, molecular diagnostics combined with existing laboratory techniques allow accurate classification of at least half of patients with inherited thrombotic disorders. However, the previously studied genetic variants explain only a fraction of all thromboembolic events, so the aim of the present study was to expand the genetic prevalence determination to include also more extensive thrombophilic gene polymorphisms in patients with DVT compared to healthy subjects in Egyptian population. This study was conducted on 75 patients with DVT and 45 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient’s history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. Both groups were assessed for thrombophilic gene polymorphisms using multiplex polymerase chain reaction and reverse-hybridization technique through CVD strip assay. It was found that FV Leiden G1691A (P=0.001), Factor V H1299R (P=0.02), MTHFR A1298C (P=0.02), β-fibrinogen−455 G/A (P=0.01), PAI-1 4G/5G (P=0.03) and ACE (P=0.03) polymorphisms were all significantly associated with an increased risk of DVT. Our data are of extreme importance in clinical practice for introducing the extended CVD panel into routine molecular diagnostic tests to allow management of thrombotic patients and screening, thromboprophylaxis and genetic counselling for high-risk individuals.

Zinc oxide nanoparticles (ZnO-NPs) are used in many industries and medications, increasing the exposure to ZnO-NPs that may have harmful side effects. So, we studied the hepatotoxic effect of ZnO-NPs and explored the role of vitamin E in the reduction of their toxic effects. Forty male albino rats, divided into four groups (10 rats per group) were included in the study; control group, ZnO-NPs intoxicated group, vitamin E control group and vitamin E protected ZnO-NPs intoxicated group. ZnO-NPs were given in a dose of 400 mg / kg body weight for seven days. Vitamin E was given in a dose of 100 mg / kg body weight for four weeks. Our results showed that ZnO-NPs induced liver damage indicated by significant increase of serum ALT and AST and significant decrease of serum albumin and total protein levels. Moreover, ZnO-NPs induced oxidative stress in the liver suggested by significant elevation of malondialdehyde level and significant reduction of reduced glutathione level, glutathione peroxidase activity and glutathione peroxidase-1 expression in liver homogenate. Furthermore, ZnO-NPs caused significant increase in the serum pro-inflammatory biomarker, tumor necrosis factor alpha (TNF- α). On the other hand, vitamin E alleviated the liver damage, oxidative stress and the elevated serum TNF- α induced by ZnO-NPs.

Background Transfusion Transmitted virus (TTV) is a novel single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-G type. Clinical significance of TTV infection was analyzed in Egyptian hepatocellular carcinoma (HCC) patients. The present study attempted to clarify these issues in Egypt, particularly in Qaluobia governorate, a country known for its high endemicity of liver disease and hepatotropic viruses. Methods TTV are determined in the serum of 60 samples obtained from HCC and liver cirrhosis (LC) patients and 30 healthy individuals. TTV DNA is amplified by nested-PCR with TTV-specific mixed primers derived from the conserved open reading frame 1 (ORF1) region followed by digestion with restriction enzyme. Using the enzymes HaeIII, DraI, EcoRI and PstI, we are able to distinguish between the four TTV genotypes. Results The positive rate of TTV detection was 46.7%, 40% and 36.7% among HCC, LC patients and healthy individuals respectively. The more prevalence genotype was detected in the positive serum samples was genotype 1 (35.7%) in HCC patients, (50%) in LC and (63.3%) in healthy individuals, Genotype 5 (21.4%), (25.5%) and (18.2%) in HCC, LC and healthy individuals respectively. Discussion This study indicates that TTV is commonly present in adult patients with HCC and LC as well as healthy individuals. The most prevalence TTV genotype is genotype 1. It seems that the infection neither contribute to the severity of liver disease no to the causation of HCC.