Hahnwinters4628

Neuropathic pain is caused by a lesion or a functional impairment of the sensory nervous system and allodynia is one of the frequently observed symptoms in neuropathic pain. Allodynia represents abnormal pain due to a non-noxious stimulus that does not normally provoke pain. Cellular mechanisms underlying neuropathic pain remain mostly elusive, and partial pain relief can be achieved in a limited number of patients by antidepressants, anticonvulsants topical anesthetics, and others. Zonisamide (ZNS) is widely used as an anti-epileptic and anti-Parkinson's disease drug. A recent report shows that ZNS suppresses neuropathic pain associated with diabetes mellitus in a mouse model. We made a mouse model of neuropathic pain in the hindlimb by cutting the nerve at the intervertebral canal at lumbar level 4 (L4). At 28 days after nerve injury, ZNS ameliorated allodynic pain, and reduced the expression of inflammatory cytokines and the nerve injury-induced increase of Iba1-positive microglia in the spinal dorsal horn at L4. In BV2 microglial cells, ZNS reduced the number of lipopolysaccharide-induced amoeboid-shaped cells, representing activated microglia. These results suggest that ZNS is a potential therapeutic agent for neuropathic pain partly by suppressing microglia-mediated neuroinflammation.

The present study aimed to evaluate the impact of chronic smoking and high fat diet on the post-MI metabolic features and inflammation resolution.

Eight weeks old C57BL/6J mice were randomly divided into control(C), smoking(S), high-fat diet(H), and smoking plus high-fat diet(SH) groups for 16weeks. MI was induced by permanent coronary ligation. Cardiac function was assessed by echocardiography at 5days post-MI. The infarcted heart tissue was collected for the metabolic profile using metabolomics and quantification of pro-resolving mediators with immunoblotting.

Percentage of fractional shortening (FS%) and ejection fraction (EF%) were further reduced in SH than that in either S or H group (P<0.05). Myocardial metabolomics analysis indicated that 3, 6, and 11 disturbed metabolic pathways were considered as the most relevant pathway (Impact>0.1) in S, H, and SH groups, respectively. The common most relevant pathway among three groups was arachidonic acid metabolism. The levels of arachidonic acid and TXB2 were significantly higher, while the 5-LOX and HO-1 expression was significantly lower in SH group than that in either S or H group (P<0.05).

Smoking superimposed on high-fat diet could aggravate post-MI cardiac dysfunction and cause significant disturbance of metabolic pathways associated with inflammation, energy metabolism, as well as excessive oxidative stress. Smoking combined with high-fat diet could also magnify the post-MI inflammation and impair the resolution of inflammation in MI mice.

Smoking superimposed on high-fat diet could aggravate post-MI cardiac dysfunction and cause significant disturbance of metabolic pathways associated with inflammation, energy metabolism, as well as excessive oxidative stress. Smoking combined with high-fat diet could also magnify the post-MI inflammation and impair the resolution of inflammation in MI mice.Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT) drastically changed the care of patients with ischemic stroke due to large vessel occlusion. Nevertheless, despite revascularization, many patients do not achieve a good functional outcome. Moreover, not all patients with ischemic stroke are eligible for EVT. During ischemia, a cascade of ischemic and inflammatory changes lead to permanent damage. As such, adjunct therapies that can protect neurons during acute ischemic phase prior to revascularization have the potential of enhancing functional recovery. Donepezil, an acetylcholinesterase inhibitor, improves cognition and global function in patients with Alzheimer's and Vascular dementia via modulation of acetylcholine receptors and downstream inflammatory response. Preclinical studies demonstrated the potential neuroprotective effects of donepezil in ischemic stroke. However, only a handful of clinical studies investigated this drug's safety and efficacy in stroke patients. In this review, we summarize the current evidence for the utility, or lack thereof, donepezil in treating and rehabilitating patients with ischemic stroke.Islet beta-cell dysfunction is an important condition leading to the development of diabetes. Numerous studies have found that miRNA regulates islet β-cell function. In our previous research, the aberrant expression of miR-383 was revealed in type 2 diabetes mellitus (T2DM) serum. Herein, we aimed to assess the function and underlying mechanism of miR-383 in β-cells through in vitro and in vivo experiments. click here Using high glucose media, the β-cell injury was induced and transfected miR-383 overexpression vector to detect cell function in MIN6. Moreover, miR-383 overexpression lentivirus was administrated into high-fat induced diabetes mice to assess the in vivo effect. Results showed that overexpressing miR-383 reversed the cell apoptosis and oxidative stress, induced by high glucose which targets Toll-like receptors (TLR4) and Apolipoprotein C3 (ApoC3) genes. Furthermore, mechanistic studies demonstrated that miR-383 targeted the TLR4 and ApoC3 3' UTR consequently inhibiting TLR4 and ApoC3 expression in MIN6 cells. Besides, overexpression of miR-383 ameliorated hyperglycemia and pancreatic apoptosis in high-fat induced diabetic mice. Conclusively, miR-383 potentially alleviate pancreatic β-cell injury induced by high glucose and ameliorates high-fat induced diabetes by suppressing TLR4 and ApoC3 expression.

Postprandial lipemia is characterized by an increase in triglyceride-rich lipoproteins after fatty meals. MicroRNAs (miRs) play important roles in lipid and lipoprotein metabolism. The aim of this study was to determine relationship between levels of plasma miR expression and lipoprotein metabolism-related proteins in subjects with normal (NPR) and high postprandial response (HPR) in postprandial period.

The oral fat tolerance test was applied to 22 individuals with NPR and 22 with HPR.

Increased expressions of miR-122 and miR-33a and miR-122/30c ratio and decreased miR-30c expression were observed in fasting and postprandial period of HPR compared with NPR. ROC curve analysis showed that miR-122/30c ratio is a good biomarker for postprandial lipemia (AUC 0.97, p<0.001). Levels of TG, MTTP, and Apo B-48 and chylomicron (CM) particle size were significantly higher in HPR than in NPR (p<0.05). The miR-122/30c ratio at 2h was positively correlated with CM particle size, and with TG, MTTP and Apo B-48 levels at 4th hour.