Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice / 生理学报

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.

Inhibition effect of active fraction from clove on PI3K/Akt/mTOR signaling pathway to induce apoptosis of human colon cancer HCT116 cells / 中国中药杂志

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 μg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/β-actin after treatment of AFC(100 μg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 μg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.

Preparation of exosome-coated Bcl-2 siRNA and its inhibitory effect on the growth of pancreatic cancer cells / 药学学报

High expression of Bcl-2 is associated with the development of pancreatic cancer, and downregulation of Bcl-2 is an effective approach for the treatment of pancreatic malignancy. In the present study exosomes were isolated from the cultured medium of human embryonic kidney cells (HEK293) by ultracentrifugation and exosome-coated Bcl-2 siRNA (exosiBcl-2) was synthesized using electroporation. The results showed that the particle size of exosiBcl-2 was 67.3 ± 9.7 nm and the morphology of exosomes displayed a concave ring structure as determined by transmission electron microscopy (TEM). Western blot analysis indicated that exosomal proteins including CD9, CD81, CD63 and TSG101 were highly expressed. Confocal microscopy revealed that exosiBcl-2 was widely distributed in Miapaca-2 cells, and the transfection efficiency of exosiBcl-2 in Miapaca-2 was 77.2% as determined by flow cytometry. Treatment with exosiBcl-2 at a concentration of 100 nmol·L-1 resulted in an inhibitory effect on the growth of Miapaca-2 cells with an inhibition rate of 63%. ExosiBcl-2 treatment can downregulate Bcl-2 and upregulate Bax protein. This study provides evidence that exosiBcl-2 is able to inhibit the growth of pancreatic cancer cells and the nanoparticles have potential to be developed as a novel anticancer agent.

Allergic reactions to antivenom in a patient bitten twice by the same snake within a month: A rare case report and literature review / 中华创伤杂志(英文版)

Antivenom is the most effective method currently available for the treatment of poisonous snake bite. Allergic reactions to antivenom have been reported in the past. Here we shared a case of allergic reactions to antivenom in an old male patient who was bitten twice by the same snake (probably same one) at the same biting site within a month whereas the patient did not show any allergic disorder in the first bitten. Envenomations twice in a short period time by the same kind of snake are very rare. Physician should be alert to the occurrence of allergic reactions in treating this type of patients with antivenom. The skin allergy test has a certain value in predicting the allergic response before the second use of antivenom. Desensitization may reduce the incidence of allergic reactions, but this is insufficient. Rather than non-IgE-mediated immediate hypersensitivity, patients receiving the second treatment of antivenom may develop IgE-mediated immediate hypersensitivity. Once happened, the antivenom treatment should be stopped promptly and anti-allergy treatment should be given immediately.

Expression profiles of miRNA-182 and Clock mRNA in the pineal gland of neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes of miRNA expression in the pineal gland of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible roles of miRNA in the pathogenesis of circadian rhythm disturbance after HIBD.</p><p><b>METHODS</b>Seven-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: HIBD and sham-operated. HIBD was induced according to the Rice-Vannucci method. The pineal glands were obtained 24 hours after the HIBD event. The expression profiles of miRNAs were determined using GeneChip technigue and quantitative real-time PCR (RT-PCR). Then the miRNA which was highly expressed was selected. The expression levels of the chosen miRNA were detected in different tissues (lungs, intestines, stomach, kidneys, cerebral cortex, pineal gland). RT-PCR analysis was performed to measure the expression profiles of the chosen miRNA and the targeted gene Clock mRNA in the pineal gland at 0, 24, 48 and 72 hours after HIBD.</p><p><b>RESULTS</b>miRNA-182 that met the criteria was selected by GeneChip and RT-PCR. miRNA-182 was highly expressed in the pineal gland. Compared with the sham-operated group, the expression of miRNA-182 was significantly up-regulated in the pineal gland at 24 and 48 hours after HIBD (P<0.05). Compared with the sham-operated group, Clock mRNA expression in the HIBD group increased at 0 hour after HIBD, decreased at 48 hours after HIBD and increased at 72 hours after HIBD (P<0.05).</p><p><b>CONCLUSIONS</b>miRNA-182 may be involved in the pathogenesis of circadian rhythm disturbance after HIBD.</p>

Effects of fructopyrano-(1 → 4)-glucopyranose extracted from Radix Isatidis on tumor growth and immune function in tumor-bearing mice / 中国药学杂志

OBJECTIVE: To study the effects of fructopyrano-(1 → 4)-glucopyranose (FG) extracted from Radix Isatidis on the tumor growth and immune activity in tumor-bearing mice. METHODS: The antitumor activity of FG in vivo was observed by implanted H22 and S180 mouse models. The effect of FG on immune function in tumor-bearing mice was investigated by using phagocytosis test, T plymphocyte proliferation test, and Elisa for determining the expression levels of TNF-α, IL-2, IL-6, and IL-12. RESULTS: At dosages of 50, 100 and 200 mg · kg-1, the inhibition rates of FG were 23.60%, 36.76% and 49.26% for S180, 22.61%, 36.52%, and 46.95% for H22, respectively. FG increased the spleen index and chest gland index, improved the phagocytosis function of the macrophage and enhance the T lymphocytes proliferation, and increased the expression levels of TNF-α, IL-2, IL-6, and IL-12. CONCLUSION: FG exhibits significant anti-tumor effect in vivo and the mechanism may be related to enhancing immune function. Copyright 2012 by the Chinese Pharmaceutical Association.

Study on the comparison of high risk behaviors related to AIDS between heterosexual and homosexual men among men who have had sex with men / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the risk sexual behaviors related to AIDS between heterosexual and homosexual men who have had sex with men.</p><p><b>METHODS</b>Target sampling, anonymous questionnaires were adopted to compare sexual behaviors between the two groups.</p><p><b>RESULTS</b>The total amount of sex partners with same-sex was 13.8 on average among heterosexual men including 3.8 with male partners in the past 6 months. Numbers of male partners who had oral sex with was 10.5 and anal sex was 12.4 which were both less than with same sex. Among heterosexual men, the total number of female partners was 4.9 on average but number of female partners in the past 6 months was 1.7 which were both more than that among the homosexuals who were all in marriage status. The rate of condom use was 68.8% (lower than that among homosexual men), among heterosexual men when having sex with men. The rate of condom use among heterosexual men during last anal intercourse was 91.3% with male partners or 63.7% with females. Both figures were higher than that among the homosexuals. The rates of condom use among the two groups were 91.3% and 71.0% respectively during the last anal intercourse with men which were higher than the corresponding rate of condom use during the last oral sex. The rate of heterosexual men who ever had engaged in group sex was 9.9% in the previous year and the incidence of bleeding was 16.7% during sexual intercourse. 11.4% of them reported ever having had sex with partners from other areas in the last year and 4.2% had experienced same-sex harassment before 16 years of age. 4.6% had paid for male-male sex. All these figures were lower than that of the homosexuals.</p><p><b>CONCLUSION</b>The characteristics of high risk sexual behaviors related to AIDS showed much difference in the two groups which called for attention among these groups of MSM.</p>

Effects of benazepril on renal function and kidney expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in diabetic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Excessive deposition of extracellular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was undertaken to investigate the activity of matrix metalloproteinase-2 (MMP-2), the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in kidney tissues of diabetic rats, and to explore the degradative pathway of type IV collagen (IV-C) and the renal protective effects of ACE inhibition-benazepril.</p><p><b>METHODS</b>Twenty-four healthy male Wistar rats were divided randomly into normal control group (NC group), untreated diabetes mellitus group (DM group), and diabetes mellitus group treated with benazepril (DL group). The rat model of diabetes mellitus was induced by intraperitoneal injection of streptozocin (60 mg/kg). After the establishment of DM model, benazepril (10 mg.kg(-1).d(-1)) was given to the DL group for 12 weeks, and the same volume of water was given to the other two groups. At the end of 12 weeks, renal function was evaluated with 24-hour urinary protein (Upro), clearance of creatinine (Ccr), and blood urea nitrogen (BUN). MMP-2 activity was determined by gelatin zymography. The levels of MMP-2, TIMP-2 and collagen IV (IV-C) protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-2 and TIMP-2 was measured by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The levels of BUN, Upro and Ccr in the DM group were higher than those in the NC group. In the DM group, the mRNA, enzymatic activity and proteins of MMP-2 decreased, but the expressions of IV-C and TIMP-2 increased. All diabetes-associated changes in renal function and MMP/TIMP were attenuated after benazepril treatment with reduced IV-C accumulation.</p><p><b>CONCLUSIONS</b>The changes of MMP-2 and TIMP-2 expressions in kidney tissues of diabetes rats may contribute to the occurrence and progression of diabetic nephropathy. Benazepril could exert protective effects on diabetic nephropathy, owing to the upregulation of MMP-2 and downregulation of TIMP-2 expressions, which further inhibits the excessive deposition of extracellular matrix in the glomerulus.</p>

Prospective study on the gastro-pulmonary infection route of ventilator-associated pneumonia / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the role of gastro-pulmonary infection route in the development of ventilator-associated pneumonia (VAP), so as to improve the management of VAP.</p><p><b>METHODS</b>Forty-three patients who received mechanical ventilation (MV) were enrolled in the study. Intra-gastric contents were labeled with (99)mTc-DTPA. Randomized two-period crossover trial was employed to determine the radioactive level in the oropharyngeal and bronchial secretion when patients were in supine or semi-reclining position. Gastric juice, oropharyngeal secretion and tracheal lavage fluid were collected for bacterial culture every other day. Bronchoalveolar lavage fluid (BALF) was harvested from those suspected of VAP for quantitative bacterial culture. Infrequent-restriction site amplification (IRS-PCR) was employed in the identification of the identity of the bacteria from intra-gastric colonization with those causing VAP. The sIgA content in the BALF was determined.</p><p><b>RESULTS</b>The gastroesophageal regurgitation rate was higher (89.7%) with lower aspiration rate (28.5%) in patients receiving MV. Moreover, the aspiration rate and the radioactivity of deep tracheal aspirates in patients in supine position were significantly higher than those in semi-reclining position (P < 0.01). There was high homology of the bacteria isolated from intra-gastric colonization with that causing VAP (55.8%). The sIgA content in BALF in VAP patients was evidently lower than that in non-VAP patients (P < 0.01).</p><p><b>CONCLUSION</b>Regurgitation and aspiration of stomach contents are very common in patients receiving MV. Intra-gastric colonized bacteria might be one of the important origins causing VAP. The lowering of sIgA in BALF in patients with MV could be a risk factor for VAP.</p>

Relationship between Renal Nitric Oxide and Glomerular Hyper filtration in Experimental Diabetic Rats / 实用儿科临床杂志

Objective To explore the mobile changes of nitric oxide(NO) and the relationship between nitric oxide and glomerular hyperfiltration in experimental diabetic rats.Methods Experimental diabetes mellitus(DM) was induced in rats with streptozotocin(STZ).The levels of NO and NOS in renal tissue homogenate were assayed after establishment of diabetesat the 4 th,8 th,12 th week.At the same time, renal morphology in diabetic rats was examined by light microscope and image of computer.Results The contents of NO and NOS in renal homegenates were evidently increased at 4 th week,and decreased gradually from 8 th week(P