Diabetic cardiomyopathy, especially myocardial ischemia reperfusion (I/R) injury, is a major cause of morbidity and mortality in type 2 diabetic patients. The increasing of basal p38 MAP Kinase (p38 MAPK) activation is a major factor that aggravates cardiac death on diabetic cardiomyopathy. In addition, metformin also shows cardio-protective effects on myocardial ischemia/reperfusion injury. In this study, we investigated the effect of the combination between metformin and p38 MAPK inhibitor (SB203580) in diabetic rats subjected to I/R injury. H9c2 cells were induced into a hyperglycemic condition and treated with metformin, SB203580 or the combination of metformin and SB203580. In addition, cells in both the presence and absence of drug treatment were subjected to simulated ischemia/reperfusion injury. Cell viability and cellular reactive oxygen species (ROS) were determined. Moreover, the Goto-Kakizaki (GK) rats were treated with metformin, SB203580, and the combination of metformin and SB203580 for 4 weeks. Diabetic parameters and cardiac functions were assessed. Finally, rat hearts were induced ischemia/reperfusion injury for the purpose of infarct size analysis and determination of signal transduction. A high-glucose condition did not reduce cell viability but significantly increased ROS production and significantly decreased cell viability after induced sI/R. Treatment using drugs was shown to reduce ROS generation and cardiac cell death. The GK rats displayed diabetic phenotype by increasing diabetic parameters and these parameters were significantly decreased when treated with drugs. Treatment with metformin or SB203580 could significantly reduce the infarct size. Interestingly, the combination of metformin and SB203580 could enhance cardio-protective ability. Myocardial I/R injury significantly increased p38 MAPK phosphorylation, Bax/Bcl-2 ratio and caspase-3 level. Treatment with drugs significantly decreased the p38 MAPK phosphorylation, Bax/Bcl-2 ratio, caspase-3 level and increased Akt phosphorylation. In conclusion, using the combination of metformin and SB203580 shows positive cardio-protective effects on diabetic ischemic cardiomyopathy.

Excessive salt intake has been associated with the development of non-communicable diseases, including hypertension with several cardiovascular consequences. Although the detrimental effects of high salt on the skeleton have been reported, longitudinal assessment of calcium balance together with changes in bone microarchitecture and strength under salt loading has not been fully demonstrated. To address these unanswered issues, male Sprague–Dawley rats were fed normal salt diet (NSD; 0.8% NaCl) or high salt diet (HSD; 8% NaCl) for 5 months. Elevation of blood pressure, cardiac hypertrophy and glomerular deterioration were observed in HSD, thus validating the model. The balance studies were performed to monitor calcium input and output upon HSD challenge. The HSD-induced increase in calcium losses in urine and feces together with reduced fractional calcium absorption led to a decrease in calcium retention. With these calcium imbalances, we therefore examined microstructural changes of long bones of the hind limbs. Using the synchrotron radiation x-ray tomographic microscopy, we showed that trabecular structure of tibia and femur of HSD displayed a marked increase in porosity. Consistently, the volumetric micro-computed tomography also demonstrated a significant decrease in trabecular bone mineral density with expansion of endosteal perimeter in the tibia. Interestingly, bone histomorphometric analyses indicated that salt loading caused an increase in osteoclast number together with decreases in osteoblast number and osteoid volume. This uncoupling process of bone remodeling in HSD might underlie an accelerated bone loss and bone structural changes. In conclusion, long-term excessive salt consumption leads to impairment of skeletal mass and integrity possibly through negative calcium balance.

Chronic inflammatory conditions lead to the generation of excessive reactive oxygen species which can give rise to T cell hyporesponsiveness. Thus there has been an interest to target these mediators with nutrients which have anti-oxidant properties. Accordingly Moringa oleifera extract has been reported to have anti-inflammatory and anti-oxidant properties. We have now examined the effects of Moringa oleifera Lam. on the depressed human T-cell responses, (IL-2 and IL-2 mRNA production) and DNA damage (quantifying the oxidized derivative of deoxyguanosine, 8-OHdG) induced oxidative stress. T-cells treated with oxidative substances, uric acid, aluminum chloride, hydrogen peroxide, and ultraviolet irradiation showed marked reduction in IL-2 production, which was prevented by pre-treating the cells with Moringa extract. These effects correlated with its prevention of the down-regulation of IL2 gene expression and a reduction in the DNA damage caused by oxidative stress. Thus the ability of Moringa extract to reduce inflammation is likely to relate to its ability to prevent T-cell hyporesponsiveness experienced in inflammatory diseases, through an action at the pre-transcriptional level.

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Background: Skin rejuvenation plays a significant role in the esthetic medicine market. Microneedle patches have been developed for a wide range of applications based on the principles of transdermal drug delivery; however, clinical trials of microneedle patches for skin rejuvenation remain limited.Aims: This study was conducted to examine the efficacy of microneedle patches for improving nasolabial folds.Methods: A total of 23 Thai women completed this prospective clinical trial. The participants were treated according to a split-face design, with application of microneedle patch plus 1.8% hyaluronic acid solution to the right nasolabial fold and microneedle patch alone to the left nasolabial fold. The treatments were applied to the nasolabial fold for 8 weeks. The test areas were measured before treatment and at 2, 4, 8, 12, and 16 weeks after the use of the test product.Results: Combination treatment using the microneedle patch plus hyaluronic acid solution and use of the microneedle patch alone both significantly improved the Merz esthetic scales for nasolabial folds. Measurement of the nasolabial fold showed an improvement in the two groups, with no significant differences between the groups.No adverse effects were reported during the study period.Conclusions: Application of a microneedle patch with 1.8% hyaluronic acid solution or a microneedle patch alone were both effective treatments for improving facial wrinkles in the nasolabial folds.

Thalassemia causes anemia, ineffective erythropoiesis, bone loss and iron accumulation in several tissues, e.g., liver, bone and heart, the last of which leads to lethal cardiomyopathy and arrhythmia. Although exercise reportedly improves bone density in thalassemic mice, exercise performance is compromised and might pose risk of cardiovascular accident in thalassemic patients. Therefore, we sought to explore whether mild-intensity physical activity (MPA) with 30–50% of maximal oxygen consumption was sufficient to benefit the heart and bone. Herein, male hemizygous β-globin knockout (BKO) mice and wild-type littermates were subjected to voluntary wheel running 1 h/day, 5 days/week for 3 months (MPA group) or kept sedentary (SDN; control). As determined by atomic absorption spectroscopy, BKO-MPA mice had less iron accumulation in heart and bone tissues compared with BKO-SDN mice. Meanwhile, the circulating level of fibroblast growth factor-23—a factor known to reduce serum iron and intestinal calcium absorption—was increased early in young BKO-MPA mice. Nevertheless, MPA did not affect duodenal calcium transport or body calcium retention. Although MPA restored the aberrant bone calcium-phosphorus ratio to normal range, it did not change vertebral calcium content or femoral mechanical properties. Microstructural porosity in tibia of BKO-MPA mice remained unaltered as determined by synchrotron radiation X-ray tomographic microscopy. In conclusion, MPA prevents cardiac and bone iron accumulation, which is beneficial to thalassemic patients with limited physical fitness or deteriorated cardiac performance. However, in contrast to moderate-intensity exercise, MPA does not improve bone mechanical properties or reduce bone porosity.