Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice / 西安交通大学学报(医学版)

【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.

Knock-down of ROCK2 gene improves cognitive function and reduces neuronal apoptosis in AD mice by promoting mitochondrial fusion and inhibiting its division / 细胞与分子免疫学杂志

Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice / 国际口腔科学杂志·英文版

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Molecular guidance cues in the development of visual pathway

70%-80% of our sensory input comes from vision. Light hit the retina at the back of our eyes and the visual information is relayed into the dorsal lateral geniculate nuclei (dLGN) and primary visual cortex (V1) thereafter, constituting the image-forming visual circuit. Molecular cues are one of the key factors to guide the wiring and refinement of the image-forming visual circuit during pre- and post-embryonic stages. Distinct molecular cues are involved in different developmental stages and nucleus, suggesting diverse guidance mechanisms. In this review, we summarize molecular guidance cues throughout the image-forming visual circuit, including chiasm determination, eye-specific segregation and refinement in the dLGN, and at last the reciprocal connections between the dLGN and V1.

Effect of Propofol Target-controlled Infusion on Extubation Time of Patients with ENT Surgery under the Narcotrend Classification Guidance / 中国药房

OBJECTIVE:To explore the effect of propofol target-controlled infusion on extubation time in patients with ENT surgery under Narcotrend classification guidance. METHODS:52 patients with endotracheal intubation intravenous anesthesia and minimally invasive ENT surgery received target-controlled infusion for anesthesia induction and anesthesia. NI value, plasma concentration of propofol(cm),mean arterial pressure(MAP),pulse oxygen saturation(SpO2)before anesthesia and different time points in recovery period,the correlation of NI with propofol cm of all patients were recorded,and NI with propofol cm and time when extubation was omalysed. RESULTS:There were no significant differences in SpO2 before anesthesia and different time points in recovery period(P>0.05);MAP was significantly higher than before anesthesia at T3,MAP was significantly lower than before anesthesia at T0-T1,propofol cm was T0>T1>T2>T3>T4>T5,NI was significantly lower than before anesthesia at T0-T3, and T00.05). NI when extubation was(86.17±5.29),propofol cm was(0.96±0.31)μg/ml,and average extubation time was (8.26 ± 2.93) min. When extubation,NI showed negative correlation with propofol cm(r=-0.812);and decreased with the prolong of extubation time (r=-0.792);the predictive rates of NI and propofol cm's prediction awareness change in recovery period were 0.93 and 0.86. There were no obvious adverse reactions during treatment. CONCLUSIONS:Propofol target-controlled infusion under Narcotrend classification guidance can accurately predict the awareness change from no response to stimuli to shouting and opening eyes,has a high reference value on extubation time.

Two cases of neck region Kimura's disease / 临床耳鼻咽喉头颈外科杂志

Kimura's disease is a rare, benign, slow-growing chronic inflammatory swelling with a predilection for the head and neck region and is almost always with peripheral blood eosinophilia and elevated serum IgE levels. It is endemic in Asian males and rare in Western people. Surgical excision of the lesion is the first line therapy. Drug and radiation therapy have to be considered for the refractory lesions.

Liver resection for patients with hepatocellular carcinoma and portal hypertension / 中国癌症杂志

Background and purpose: The proportion of hepatocellular carcinoma (HCC) patients with cirrhosis and portal hypertension (PHT) is high. PHT may increase the risk of hemorrhage and liver failure. The aim of this study was to evaluate the safety and efifcacy of liver resection (LR) for patients with HCC and PHT. Methods:From 2006 to 2010, a total of 564 HCC patients with Child-Pugh A liver function and with (78) or without PHT (486) were retrospective analyzed. Complications after surgry, 30 and 90-day mortality, overall survival (OS), and recurrence rates were compared between the two groups. Propensity score analysis was also conducted to reduce confounding bias between the groups. Moreover, subgroup analysis based on tumor stage and the range of resection was carried out. Results:The complications after surgry, 30 and 90-day mortality of patients with PHT were signiifcantly higher than those without PHT, before and after propensity analysis (P0.05). Conclusion: PHT is not the contraindication of LR for patients with HCC. Those with early stage HCC and who underwent minor hepatectomy are the best candidates to LR therapy.

Expression, Purification of Recombinant Flounder MRF4 Protein in Escherichia coli and Analysis of Its Polyclonal Antibodies / 生物化学与生物物理进展

MRF4 is one of muscle regulatory factors and plays critical roles during skeletal muscle development. The muscle development is important for the fish growth which is an important economic factor for the fish culture. To analyze the function of MRF4 in fish, the founder MRF4 antibody was prepared. The flounder MRF4 was cloned, ligated into prokaryotic expression vector pET-30b and expressed in strain E. coli BL21 (DE3). The recombinant flounder MRF4 fusion protein was soluble and purified with cobalt IMAC resins. To prepare MRF4 polyclonal antibodies, rabbits were immunized with the soluble protein and the increasing level of antibodies was determined by Western blot. Also, the endogenous flounder MRF4 was recognized by the anti-serum. The result further proved the existence of the anti-MRF4 antibody in the anti-serum, which will be useful for studies on the function of flounder MRF4.