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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.

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Background: Medications to prevent the development of NSAID-induced gastric ulcers have a large range of unpleasant side effects. Recent efforts have been focused on determining safer alternative nontoxic and natural forms of anti-ulcer treatments. Methods: Twenty-four male rats were divided into 4 groups: 1: control group that received no treatment; 2: the indomethacin-treated group that received 20 mg/kg of indomethacin for 2 days to induce the development of gastric ulcers; 3: quercetin-treated group that in addition to the indomethacin treatment, received 50 mg/kg of quercetin 6 hours after and then daily for 14 days and; 4: the melatonin-treated group which received 20 mg/kg of melatonin 6 hours after each indomethacin treatment and then daily for 14 days. All drugs were administered orally. The following parameters were assessed in each group: mean ulcer index of gastric tissue, gastric acid volume and pH, oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH), inflammatory markers: PGE-2, TNF-α, and IL-10, nitric oxide (NO) levels and the relative gene expression of BAX, BCL-2 and COX-2 by real time PCR. Results: Our findings revealed that the indomethacin-treated group had a significantly increased (p< 0.05) ulcer index, gastric acid volume, and elevated levels of stress, inflammatory, and apoptotic markers compared to controls. In the groups that received quercetin or melatonin, these factors were all significantly decreased (p< 0.05). Between quercetin and melatonin, there was no significant difference in their gastroprotective effect. Conclusions: Both quercetin and melatonin had protective antioxidant, anti-inflammatory and antiapoptotic activity against indomethacin-induced gastric ulcers.

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Background: Hypoxia is a common feature in several respiratory diseases. It is known to impair force generation and increases fatigability of respiratory and peripheral skeletal muscles. The precise mechanisms involved in hypoxia-induced impairment in contractile performance are incompletely understood, but oxidative and nitrosative stress could be at play. Little is known about the effects of hypoxia on the contractility of aged muscles. Aim: To investigate the effect of aging on the contractility of unfatigued diaphragm under hypoxic conditions. And to ask whether there is an age-specific difference in oxidative damage that could partially account for the differential response of the contractility of the diaphragm to hypoxia with age. Materials and Methods: This experimental work was conducted on 2 groups of albino rats. Group I was the young adult rats (aged 8mo n=10). Group II was the old one (aged 24mo,n=10). Rat diaphragm muscle strips from each group were studied in vitro while aerated with 95% O 2-5% CO 2 (hyperoxia ,n=10) or 95% N 2-5% CO 2 (hypoxia,n=10). Results: The contractility was significantly decreased in old rats when compared with young rats specially under hypoxic conditions. On the other hand the markers of oxidative stress; MDA and nitrotyrosine were significantly higher in old rats than adults. Conclusion: There is an age-specific difference in oxidative damage that could partially account for the differential response of the contractility of the unfatigued diaphragm to hypoxia with age.