摘要：
Recent studies have shown that autophagy is involved in peripheral nervous system disease. However, the role of autophagy in the pathogenesis of experimental autoimmune neuritis (EAN) remains unclear. Therefore, EAN was induced by a subcutaneous injection into both hind footpads of synthetic neuritogenic P2(57-81) peptide in male Lewis rats. The clinical evaluation was completed using a 10-point scale method. The histological alteration of sciatic nerves was analyzed by hematoxylin and eosin and luxol fast blue staining. The ultrastructure of sciatic nerves was analyzed by transmission electron microscopy. Expressions of beclin-1 and microtubule-associated protein light chain-3 (LC3) and p62/SQSTM1 were determined by western blot. 3-Methyladenine, the inhibitor of autophagy, was used in this research. Results showed that the clinical scores were significantly increased from day 6 to day 16 after immunization compared with the control group. Compared with the control group, the number of inflammatory cells and the histological score of sciatic nerves were significantly increased, expressions of beclin-1 and LC3-II and the ratio of LC3-II/LC3-I in the sciatic nerve were significantly increased, and the expression of p62 was significantly decreased in the EAN model group. Considerable double-membrane autophagosomes in axons and myelin sheaths of sciatic nerves were observed and the number of autophagosomes in axons and myelin sheaths of sciatic nerves in the EAN model group was obviously increased compared with the control group. 3-Methyladenine ameliorated the neurologic severity of EAN. Our results suggest that autophagy activity in nerve tissue of EAN rats is increased, which may be associated with the pathogenesis of EAN.
摘要：
Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1 beta (IL-1 beta) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.
摘要：
The present study aimed to investigate the effect of hydrogen sulfide (H2S) on kidney injury induced by urinary-derived sepsis. Rabbits were randomly divided into control, sham, sepsis, NaHS 2.8 mumol/kg and NaHS 8.4 mumol/kg groups, with six rabbits in each group. Upper urinary tract obstruction and acute infection was induced to establish the sepsis model. Blood was collected to carry out a white blood cell (WBC) count, and creatinine (Cr) and blood urea nitrogen (BUN) analysis. Morphological changes were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). Cystathionine-gamma-lyase (CSE) activity was measured by the spectrophotometric methylene blue method and the blood H2S concentration was measured by deproteinization. WBC, Cr and BUN levels were significantly elevated in the sepsis group compared with those in the control group (P<0.05). Following treatment with NaHS, the WBC, Cr and BUN levels were significantly decreased in the NaHS groups compared with those in the sepsis group (P<0.05). The pathological features of kidney injury were also alleviated by NaHS. In the sepsis group, the levels of TNF-alpha, IL-10 and NF-kappaB were significantly increased compared with those in the control group (P<0.05). In the NaHS groups, the TNF-alpha and NF-kappaB levels were significantly reduced whereas the IL-10 level was significantly increased compared with the respective levels in the sepsis group (P<0.05). The H2S concentration was significantly decreased in the sepsis group and this reduction was attenuated in the NaHS groups (P<0.05). Furthermore, the NaHS 8.4 mumol/kg dose revealed a more potent effect than the NaHS 2.8 mumol/kg dose. Thus, exogenous H2S reduced kidney injury from urinary-derived sepsis by decreasing the levels of NF-kappaB and TNF-alpha, and increasing the level of IL-10.
摘要：
Aims: The objective of this study was to investigate the role of plasma and platelet microRNAs in the occurrence of ischemic stroke in patients with diabetes mellitus. Methods: miR-223, miR-146a, miR-495, and miR-107 expression in the plasma and platelets, blood glucose concentration, and platelet activation rate were measured in patients with diabetes mellitus and ischemic stroke, diabetes mellitus only, ischemic stroke only, and healthy controls. Platelet activity was measured by flow cytometric measurement of P-selectin expression, while miRNA was measured by real-time PCR. Results: The expressions of platelet and plasma miR-223 and miR-146a were significantly downregulated in patients with ischemic stroke and diabetes mellitus or diabetes mellitus only, but not in patients with ischemic stroke only compared to healthy controls. The expressions of platelet and plasma miR-495 and miR-107 showed no significant differences among these four groups. The expression of platelet miR-223 and miR-146a significantly correlated with plasma miR-223 and miR-146a levels, blood glucose concentration, and platelet activation rate. Conclusions: Hyperglycemia may downregulate the expressions of miR-223 and miR-146a, leading to subsequent platelet activation in patients with diabetes mellitus. Low platelet and plasma miR-223 and miR-146a expression is a risk factor for ischemic stroke in Chinese diabetes mellitus patients. (c) 2014 Elsevier Inc. All rights reserved.
期刊：
International Journal of Clinical and Experimental Pathology,2014年7(2):709-715 ISSN：1936-2625
通讯作者：
Ren, Jihao
作者机构：
[Xie, Shumin; Ren, Jihao; Hu, Bing; Liu, Wei; Ren, Hongmiao; Chen, Xing; Yin, Tuanfang] Cent S Univ, Dept Otolaryngol Head & Neck Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China.;[Xiang, Yuyan] Univ South China, Dept Human Anat, Hengyang, Peoples R China.;[Rao, Xingwang] Wenzhou Med Univ, Dept Otolaryngol Head & Neck Surg, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China.
通讯机构：
[Ren, Jihao] C;Cent S Univ, Dept Otolaryngol Head & Neck Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China.
关键词：
Cholesteatoma;IL-6;STAT3
摘要：
Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma.
摘要：
The aim of the present study was to determine the efficacy of ulinastatin (UTI) for the treatment of sepsis and to investigate the associated molecular mechanisms. Twenty-four male rabbits were randomly divided into 4 groups, the normal, sham, sepsis model and UTI groups, each containing 6 rabbits. Serum levels of interleukin (IL)-10 and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay (ELISA). Liver, kidney and lung tissues were stained with hematoxylin and eosin (H&E) 36 h after sacrifice and morphological changes were observed under an optical microscope. The expression levels of IL-10 and TNF-alpha proteins in rabbit kidney tissue in each group were determined by immunohistochemical detection and western blot analysis. ELISA results indicated that, compared with the sepsis model, IL-10 levels were significantly higher in the UTI treatment group (183.91 +/- 11.521 pg/ml) at 36 h (P=0.000), while serum TNF-alpha concentration decreased significantly in the UTI treatment group (31.637 +/- 2.770 pg/ml; P=0.000). Results of western blot analysis were consistent with the immunohistochemistry, indicating that UTI upregulates IL-10 and downregulates TNF-alpha levels. In the current study, UTI was demonstrated to effectively treat urinary sepsis and alleviate the inflammatory response in tissues. These effects were mediated by the upregulation of IL-10 and downregulation of TNF-alpha levels.
