Graphical abstract

Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started after 6 weeks from induction of diabetes and continued for the next 4 weeks. Blood samples were collected for assessment of glucose, insulin, and cardiac enzymes. Hearts were removed and used for isolated heart studies, and gene expression of: myocyte enhancer factor-2 (), peroxisome proliferator-activated receptor gamma coactivator1-alpha (), nuclear factor kappa B () and autophagic markers: light chain 3 () and beclin by real-time reverse transcription-polymerase chain reaction. The cardiac mitochondrial protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by ELISA and western blot technique, respectively. Treated groups showed significant improvement in left ventricular function associated with improvement in the cardiac injury and myopathic markers compared to the non treated diabetic group. was down-regulated while cardiolipin,, and beclin were up-regulated in all treated groups. These data suggest that the cardioprotective effects of MSCs, exendin-4 or pioglitazone based on their ability to improve mitochondrial functions through targeting inflammatory and autophagy signaling. The co- administration of pioglitazone or exendin-4 with MSCs showed significant superior improvement compared with MSCs alone, indicating the ability to use them in supporting cardioprotective effects of MSCs.

Endometrial fibrosis is the presence of intrauterine adhesions (IUAs) after any uterine surgery or curettage and it results in infertility and recurrent pregnancy loss. We evaluated the role of human mesenchymal stem cells (hMSCs) as a therapeutic agent of endometrial fibrosis. We also compared the effect of MSCs with the effect of estrogen and neupogen either each alone or as a combined therapy with MSCs. This experimental study was performed on 84 albino rats which were divided into seven groups (n=12 rats/group) as follows, group1: normal control rats, group 2: induced fibrosis, group 3: induced fibrosis that received oral estrogen, group 4: induced fibrosis that received hMSCs, group 5: induced fibrosis that received hMSCs and estrogen, group 6: induced fibrosis that received neupogen, and group 7: induced fibrosis that received hMSCs and neupogen. The extent of fibrosis, vascularization, and inflammation were evaluated by; qRT-PCR for interleukin 1 (IL-1), interleukin 6 (IL-6), TNF, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and RUNX; ELISA for connective tissue growth factor (CTGF); Western blotting for collagen-I; immunohistochemistry examination for VEGF and RUNX-2; and histopathological assessment. In therapeutic groups either by hMSCs alone or combined with estrogen or neupogen; fibrosis and inflammation (IL-1, IL-6, TNF, TGF-β, RUNX, CTGF, and collagen-I) were significantly decreased but vascularization (VEGF) was significantly increased (P<0.05) compared with induced fibrosis group. The most significant result was obtained in fibrosis that received combined therapy of hMSCs and neupogen (P=0.000). Stem cells and neupogen are a highly effective alternative regenerative agents in endometrial fibrosis.

Behcet's disease is a chronic, multisystem, inflammatory disease of unknown etiology. Oral ulcers, genital ulcers, cutaneous lesions, and ocular and articular involvement are the prominent features of the disease. The aim of the study was to assess expression of microRNA-146a and its gene polymorphism in Egyptian Behcet's disease (BD) patients and to evaluate their possible relation with clinical manifestations and activity. This is a case-control study, included 47 BD Egyptian patients, recruited from the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University Hospitals, and 50 healthy controls. BD activity was assessed using the BD Current Activity Score. Quantitative expressions of serum microRNA-146a and microRNA-146a rs2910164 SNP genotyping were performed by real-time polymerase chain reaction (RT-PCR). P values < 0.05 were considered statistically significant. Serum microRNA-146a expression was significantly higher in BD patients than in controls (7. 27 ± 4.11, 1.13 ± .37) (P < 0.001). There was a significant association between microRNA-146a expression and eye activity (P = 0.033) and vascular activity (P = 0.041). miRNA-146a rs2910164 genotyping revealed that the frequency of CC genotype was higher in controls (12 vs 8.5%) and the frequency of GG genotype of rs2910164 was higher in the BD patients (59.6 vs 24%) (P = 0.138). MicroRNA-146a expression in Egyptian BD patients is significantly higher than that in controls; there is significant association between microRNA-146a expression and eye and vascular activity of BD. The frequency of CC genotype of rs2910164 was decreased; frequency of GG genotype of rs2910164 was increased in BD patients as compared to controls, suggesting that GG genotype of rs2910164 confers susceptibility to BD while CC genotype has a protective role against BD development.

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