Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PDMSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22-1.51) × 10(6)/kg, with an average of 1.35 × 10(6)/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU (P<0.01), and the C-peptide level was increased from 4.1 ±3.7 ng/mL to 5.6 ±3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

Congestive heart failure (CHF) remains the single most prevalent cause of mortality and morbidity; therefore, the identification of novel biomarkers is required for the diagnosis of CHF. The aim of the present study was to examine whether microRNA (miR)-423-5p is a novel biomarker for CHF, which was defined by the circulatory biomarker pro-brain natriuretic peptide (BNP). Samples of plasma from patients with CHF and healthy controls were collected and used for quantitative polymerase chain reaction analysis. In addition, the O-GlcNAc transferase (OGT) 3' untranslated region was cloned and used for a luciferase assay. The effects of the expression of miR-423-5p in cardiomyocytes were determined using western blotting and terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick-end labeling analyses. The results demonstrated that miR-423-5p was associated with CHF and the expression levels of proBNP; in addition, OGT was found to be a direct target of miR-423-5p. The expression of miR-423-5p significantly regulated the expression of OGT and its associated downstream targets and induced apoptosis in the cardiomyocytes. Therefore, the results of the present study indicated that miR-423-5p was involved in CHF via the direct targeting of OGT and the induction of apoptosis in cardiomyocytes.

BackgroundRecent studies have demonstrated that myocardial calpain triggers caspase-3 activation and myocardial apoptosis in models of sepsis, whereas the inhibition of calpain activity down-regulates myocardial caspase-3 activation and apoptosis. However, the mechanism underlying this pathological process is unclear. Therefore, in this study, our aim was to explore whether the Hsp90/Akt signaling pathway plays a role in the induction of myocardial calpain activity, caspase-3 activation and apoptosis in the septic mice.MethodsAdult male C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Next, myocardial caspase-3 activity and the levels of Hsp90/p-Akt (phospho-Akt) proteins were detected, and apoptotic cells were assessed by performing the TUNEL assay.ResultsIn the septic mice, there was an increase in myocardial calpain and caspase-3 activity in addition to an increase in the number of apoptotic cells; however, there was a time-dependent decrease in myocardial Hsp90/p-Akt protein levels. The administration of calpain inhibitors (calpain inhibitor-Ш or PD150606) prevented the LPS-induced degradation of myocardial Hsp90/p-Akt protein and its expression in cardiomyocytes in addition to inhibiting myocardial caspase-3 activation and apoptosis. The inhibition of Hsp90 by pretreatment with 17-AAG induced p-Akt degradation, and the inhibition of Akt activity by pretreatment with wortmannin resulted in caspase-3 activation in wildtype C57 murine heart tissues.ConclusionsMyocardial calpain induces myocardial caspase-3 activation and apoptosis in septic mice via the activation of the Hsp90/Akt pathway.

Metabolic syndrome is a medical disorder characterized by obesity, hyperglycemia, dyslipidemia, and hypertension. Thyroid hormone has been shown to affect many metabolic processes. This study was undertaken to explore the relationship between serum thyrotropin and components of metabolic syndrome in Chinese adolescents. Waist circumference (76.4 ± 10.7 versus 70.0 ± 10.6 cm, P = 0.006) and body mass index (23.90 ± 4.20 versus 21.51 ± 4.16 kg/m2, P = 0.011) were significantly greater among adolescents with subclinical hypothyroidism compared with euthyroid subjects. The risk of obesity in the subclinical hypothyroid group was 3.444 times that in the euthyroid group (odds ratio = 3.444, 95% confidence interval (CI): 1.570–7.553). Serum TSH was significantly positively correlated with waist circumference (β = 1.512, P = 0.019), TC (β = 0.160, P = 0.003), LDL-C (β = 0.032, P = 0.008), and TG (β = 0.095, P = 0.001). The TSH level in the metabolic syndrome group was significantly higher than that in nonmetabolic syndrome group (2.65 [2.28–3.80] versus 2.53 [1.92–3.45] mIU/L, P = 0.032). Serum TSH within the reference range was positively associated with TC (β = 0.173, P = 0.013), LDL-C (β = 0.031, P = 0.043), and TG (β = 0.132, P = 0.021). Increased serum TSH in adolescents may be a potential risk factor for metabolic syndrome.

Adiponectin may be used as a predictive biomarker of MetS, and shows a significant association with CVD risk factors in Chinese adolescents. Adiponectin gene polymorphisms are associated with serum adiponectin concentrations and the presence of MetS.