Background Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. Methods A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. Results DCM rats exhibited abnormal blood glucose levels and lipid metabolism, cardiac inflammation and dysfunction. MSC infusion ameliorated metabolic abnormalities and preserved cardiac structure and function in DCM rats. Moreover, MSC infusion significantly increased the M2 phenotype macrophages and alleviated cardiac inflammation. Interestingly, this in vitro study revealed that the MSCs pretreated with a COX-2 inhibitor had little effect on M2 macrophage polarization, but this phenomenon could be reversed by adding prostaglandin E2 (PGE2). Conclusions Our results suggested that MSC infusions can protect against cardiac injury in DCM rats. The underlying mechanisms may include MSC-enhanced M2 macrophage polarization via the COX-2-PGE2 pathway.

The purpose of this study was to investigate the protective mechanism of leptin-mediated metabolic recovery against cerebral injury after ischemia and reperfusion. We determined the neurologic deficit score, extent of brain edema, and infarct volume after reperfusion. The histopathologic alterations and changes in glucose uptake in the brain were also observed. Moreover, the levels of lactate dehydrogenase (LDH), lactic acid, pyruvate, and ATP in brain tissue were detected. Leptin levels in serum were also detected. To further define leptin-induced neuroprotective signaling pathways, we examined the levels of phosphorylated Akt (p-Akt) in the brain and in cultured cells. After transient ischemia, leptin treatment markedly reduced the neurologic deficits, cerebral infarct volume, and brain edema. After leptin injection, ATP, leptin, and p-Akt levels were significantly increased, LDH levels and lactic acid/ pyruvate ratio were noticeably reduced, and histopathologic injuries were alleviated, which were all reversed by the PI 3 K inhibitor LY294002. These data show that leptin ameliorates cerebral ischemia/reperfusion injury by enhancing p-Akt, which in turn improves the supply of energy. The PI 3 K/Akt pathway was found to be the critical pathway for the mediation of leptin-induced neuroprotection, a finding that may prove to be useful in the treatment of ischemic stroke. Keywords: Akt pathway; cerebral ischemia; energy metabolism; leptin; neuroprotection; PI 3 K; reperfusion; stroke INTRODUCTION Acute ischemic stroke injuries to brain tissue are among the leading causes of death and long-term disability in humans and are instigated by a number of physiologic factors. These factors include the cessation of the glucose supply to challenged brain tissues that have high energy demands and the impediment of the delivery of oxygen, which is vital for cellular respiration. Journal of Cerebral BloodLeptin, a centrally acting hormone secreted by adipocytes, has significant biologic activity in the central nervous system and is known to inhibit food intake and stimulate energy expenditure.

Background: Diabetic cardiomyopathy (DCM) is a cardiac complication of long-term uncontrolled diabetes and is characterized by myocardial fibrosis and abnormal cardiac function. Mesenchymal stem cells (MSCs) are multipotent cells with immunoregulatory and secretory functions in diabetes and heart diseases. However, very few studies have focused on the effect and the underlying mechanism of MSCs on myocardial fibrosis in DCM. Therefore, we aimed to explore the therapeutic potential of MSCs in myocardial fibrosis and its underlying mechanism in vivo and in vitro. Methods: A DCM rat model was induced using a high-fat diet (HFD) combined with a low-dose streptozotocin (STZ) injection. After four infusions of MSCs, rat serum and heart tissues were collected, and the levels of blood glucose and lipid, cardiac structure, and function, and the degree of myocardial fibrosis including the expression levels of profibrotic factor and collagen were analyzed using biochemical methods, echocardiography, histopathology, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). We infused prostaglandin E2 (PGE2)-deficient MSCs to DCM rats in vivo and established a system mimicking diabetic myocardial fibrosis in vitro by inducing cardiac fibroblasts with high glucose (HG) and coculturing them with MSCs or PGE2-deficient MSCs to further explore the underlying mechanism of amelioration of myocardial fibrosis by MSCs.

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The association between cervical lymph node metastasis (LNM) and ultrasonographic features as well as BRAFV600E mutations in patients with papillary thyroid carcinoma (PTC) remained controversial. This study investigated the association between LNM and ultrasonographic features as well as BRAFV600E mutation in Chinese patients with PTC. A total of 280 patients with PTC in China were included in this study. 108 had cervical lymph node metastasis, while 172 had not. Younger age (<45years) and several ultrasonographic features were significantly associated with cervical LNM (Ps < 0.05). The BRAFV600E mutation was detected in 81.0% of patients with PTC (226/280). The status of BRAFV600E mutation was not associated with cervical LNM. However, Ct values by PCR and intensity of reactions by immunohistochemistry (IHC) for BRAFV600E expression had shown significant difference between group with and without LNM. Furthermore, an increased proportion of LNM was also found with the incremental intensity of IHC for BRAFV600E expression from weak to strong reaction after adjusted potential confounders. Further studies are required to verify this association and explore the intrinsic mechanism.

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Leptin is a multifunctional hormone produced by the ob gene and is secreted by adipocytes that regulate food intake and energy metabolism. Numerous studies demonstrated that leptin is a novel neuroprotective effector, however, the mechanisms are largely unknown. Herein, we demonstrate the protective activities of leptin after ischemic stroke and provide the first evidence for the involvement of the connexin 43 (Cx43) in leptin-mediated neuroprotection. We found that leptin treatment reduces the infarct volume, improves animal behavioral parameters, and inhibits the elevation of Cx43 expression in vivo. In vitro, leptin reverses ischemia-induced SY5Y and U87 cells Cx43 elevation, secreted glutamate levels in medium and SY5Y cell death, these roles could be abolished by leptin receptor blocker. Additionally, leptin administration upregulated the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. Moreover, ERK1/2 inhibitors pretreatment reversed the effects of leptin on Cx43 expression, glutamate levels and cell apoptosis. In conclusion, the present study demonstrated that leptin can reduce the Cx43 expression and cell death both in vivo and in vitro via ERK1/2 signaling pathway. This result provides a novel regulatory signaling pathway of the neuroprotective effects of leptin and may contribute to ischemic brain injury prevention and therapy.

Diagnosis of sepsis in critically ill patients is important to reduce morbidity and mortality. The present study was conducted to determine the role of serum leptin in the early diagnosis of sepsis and to establish a diagnostic model for sepsis. A retrospective study was conducted of 331 patients from an intensive care unit. All patients underwent consistent blood collection at 6:00 a.m. every morning after fasting. Serum leptin concentrations and additional markers of sepsis were compared between the sepsis group (n=128) and the non-sepsis group (n=203). Septic patients displayed significantly higher leptin serum concentrations compared with those of the non-sepsis group (mean concentration, 11.67 versus 4.824 mg/dl; P<0.001). The leptin levels in male patients were higher than those in female patients, particularly in the sepsis group. The accuracy of serum leptin levels in distinguishing septic patients from non-septic patients was 76%, and the area under the receiver operating characteristic (ROC) curve of serum leptin was ≤0.8. Additional markers of inflammation in the sepsis group were also significantly higher than those in the non-sepsis group. Positive correlations were identified between leptin and body temperature, heart rate and creatinine levels. Therefore, a prognostic model comprising a combination of leptin with temperature, platelet count, white blood cell count and heart rate was evaluated as an effective logistic regression model for the diagnosis of sepsis. The logistic regression output cut-off value was 0.46 and the area under the ROC curve was 0.953 (P<0.0001). It may be concluded that leptin is a valuable marker in the diagnosis of sepsis and the proposed prognostic model is an effective logistic regression model for the diagnosis of sepsis. The prognostic model is able to aid the differentiation of septic patients from non-septic patients.