Microneedle-based two-step transdermal delivery of Langerhans cell-targeting immunoliposomes induces a Th1-biased immune response.

Novel Coronavirus is affecting human's life globally and vaccines are one of the most effective ways to combat the epidemic. Transcutaneous immunization based on microneedle (MN) has attracted much attention because of its painlessness, rapidity, high efficiency and good compliance. In this study, CD11c monoclonal antibody-immunoliposomes (OVA@CD11c-ILP) actively targeting to Langerhans cells (LCs) were successfully prepared and were delivered by the microchannels of skin produced by MN to induce an immune response in vivo. OVA@CD11c-ILP could be targeted to LCs by conjugating CD11c monoclonal antibody to the surface of the ILP. OVA@CD11c-ILP promoted the maturation of dendritic cells (DCs) and the uptake and endocytosis of antigen by LCs. Moreover, OVA@CD11c-ILP immunization can significantly inhibit tumor growth and prolong overall survival. Furthermore, a higher antibody's titer ratio of IgG1/IgG2a indicated that the immune response stimulated by this immunization method was Th1-biased and the liposomes showed Th1-type adjuvant effect. In conclusion, the combination delivery system of immunoliposomes and microneedle can significantly improve the efficiency of antigen presentation and effectively activate cellular immune responses in the body, which is expected to be a promising transdermal immune strategy.

The association between meat consumption and the metabolic syndrome: a cross-sectional study and meta-analysis.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

Dexmedetomidine Relieves Neuropathic Pain in Rats With Chronic Constriction Injury via the Keap1-Nrf2 Pathway.

This study aimed to determine the role of dexmedetomidine (Dex) in neuropathic pain (NP) after chronic constriction injury (CCI) in a rat model as well as its underlying mechanism. First, a CCI rat model was established. After treatment with Dex, the severity of NP was ascertained by monitoring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different time points. Immunohistochemical analysis was performed to determine the levels of Keap1 and Nrf2 in the spinal cord. Furthermore, the levels of Keap1-Nrf2-HO-1 pathway molecules, apoptotic proteins, and antioxidant genes in the spinal cord or isolated primary microglia were determined using quantitative polymerase chain reaction and western blotting. The release of proinflammatory cytokines was detected via enzyme-linked immunosorbent assay. To evaluate Dex-treated CCI-induced NP via the Keap1-Nrf2-HO-1 pathway, the rats were intrathecally injected with lentivirus to upregulate or downregulate the expression of Keap1. We found that Dex inhibited pathological changes and alleviated sciatic nerve pain as well as repressed inflammation, apoptosis, and redox disorders of the spinal cord in CCI rats. Keap1 protein expression was substantially downregulated, whereas Nrf2 and HO-1 expressions were significantly upregulated in the spinal cord after Dex administration. Additionally, Keap1 overexpression counteracted Dex-mediated inhibition of NP. Keap1 overexpression led to a decrease in Nrf2 and HO-1 levels as well as PWT and PWL but led to an aggravation of inflammation and antioxidant disorders and increased apoptosis. Keap1 silencing alleviated NP in rats with CCI, as evidenced by an increase in PWT and PWL. Keap1 depletion resulted in the alleviation of inflammation and spinal cord tissue injury in CCI rats. Collectively, these findings suggest that Dex inhibits the Keap1-Nrf2-HO-1-related antioxidant response, inflammation, and apoptosis, thereby alleviating NP in CCI rats.

Green Tea Consumption May Be Associated with Cardiovascular Disease Risk and Nonalcoholic Fatty Liver Disease in Type 2 Diabetics: A Cross-Sectional Study in Southeast China.

Dietary factors play a crucial role in the management of type 2 diabetes mellitus (T2DM) by reducing cardiovascular disease (CVD) risk. Therefore, we aimed to examine the associations between habitual green tea consumption and risk factors of CVD among T2DM patients. A total of 1013 patients with T2DM were included in a community-based cross-sectional study. Data on dietary habits, including tea consumption, were collected using a food frequency questionnaire. A multivariable logistic regression model was used to analyze the associations. In men, as compared with nongreen tea drinkers, odds ratios (ORs) (95% confidence interval [CI]) of nonalcoholic fatty liver disease (NAFLD) were 2.06 (95% CI, 1.20-3.55) for those with green tea consumption of once per day and 2.45 (95% CI, 1.31-4.58) for more than or equal to twice per day (P-trend = .004); ORs (95% CI) of general obesity were 2.19 (95% CI, 1.02-4.68) and 2.70 (95% CI, 1.18-6.21), respectively (P-trend = .021); whereas no such association was found in women. Sensitivity analysis according to self-awareness of their T2DM status revealed that the positive association between green tea consumption and general obesity was not reliable. Higher intake of green tea was still positively associated with NAFLD, but it only persisted in participants aged ≥52 years or the lower dietary quality subgroup in further analyses. Our findings suggest that tea consumption was associated with an increased risk of NAFLD among male T2DM patients aged 52 years or older, and those with lower dietary quality, which needs to be confirmed in future prospective studies.

Dexmedetomidine relieves formaldehyde-induced pain in rats through both α2 adrenoceptor and imidazoline receptor.

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons. Acetycholine (Ach) and noradrenaline (NA) levels were determined by using ELISA method. The expressions of natural nitric oxide synthase (nNOS), protein kinase γ (PKCγ) and protease-activated receptor 2 (PAR2) were determined by using western blot. DEX treatment relieved formaldehyde-induced pain in rats in a dose-dependent manner. Furthermore, DEX showed little neuro-toxicity on the spinal cord neurons, even at the highest dosage used in our study. Ach level was significantly increased in Sham group compared with control group. DEX treatment decreased NA levels and increased Ach levels in the incubation medium of spinal cord sections. Western blot analysis showed that the expression of nNOS, PKCγ and PAR2 was significantly decreased in DEX group compared with Sham group, whereas these effects of DEX on nNOS, PKCγ and PAR2 were blocked by both yohimbine and idazoxan, indicating that the analgesic effect of DEX is mediated by both α2 adrenergic receptor and imidazoline receptor. Yohimbine and idazoxan treatment significantly enhanced pain scores compared to DEX group, and which antagonizes the effects DEX. In conclusion, our study demonstrated that DEX could inhibit formaldehyde-induced pain by inhibiting nNOS, PKCγ and PAR2 expression through α2 adrenergic receptor and imidazoline receptor.

Gene-gene interaction of GJB2, SOD2, and CAT on occupational noise-induced hearing loss in Chinese Han population.

The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.

Preliminary research on the expression, purification and function of the apoptotic fusion protein, Sival.

The objective of the present study was to investigate cloning, expression, and functions of the recombinant protein, Siva1. Siva1 gene was synthesized by RT-PCR from HCT116 cells. Plasmids were cleaved with the restriction endonuclease, BamH1/Sal1 and products were connected to pQE30, which underwent cleavage by BamH1/Sal1. The recombinant plasmid, pQE30-Siva1, was identified after digestion with restriction endonucleases followed by transformation into E. coli M15. Expression of Siva1 was induced by IPTG and identified by SDS- PAGE following purification with affinity chromatography. The results showed that size of Siva1 was 12 kDa, consistent with the molecular weight of the His-Siva1 fusion protein. Functional test demonstrated that Siva1 significantly inhibited the invasion and migration of HCT116 cells. It may thus find clinical application for control of cancers.

The effects of neuromuscular blockade on operating conditions during general anesthesia for spinal surgery.

BACKGROUND: Muscle relaxants are prescribed routinely for patients undergoing general anesthesia, but the requirement for paralysis in spinal surgery is unclear. This study compared the operating conditions of general anesthesia with and without a muscle relaxant on spinal surgery patients. METHODS: Eighty-six adults who underwent elective spinal surgery were randomly assigned to a relaxant group (group R) or a no-relaxant group (group NR). All patients were induced with intravenous midazolam (0.05 mg/kg), fentanyl (4 µg/kg), propofol (1.0 mg/kg), and succinylcholine (2 mg/kg) and then atracurium was used in group R but not in group NR. The operating conditions, including muscle tone, body movements, airway pressure, anesthetics consumption, eye-opening time, extubation time, and the Observer's Assessment of the Alertness/Sedation (OAA/S) score 20 minutes after the extubation were compared between the 2 groups. RESULTS: The operating conditions including muscle tone scales, body movements, and airway pressure did not differ between the 2 groups. Eye-opening time (9.35±2.34 vs. 11.02±2.50 min; P=0.002) and extubation time (13.95±3.41 vs. 16.72±3.67 min; P=0.001) were shorter in group NR than in group R. The BIS score at extubation (87.2±5.0 vs. 83.3±5.7; P=0.001) and the OAA/S score 20 minutes after extubation (5 [3 to 5] vs. 4 [3 to 5]; P=0.005) were significantly higher in group NR than in group R. Propofol consumption was higher in group NR than in group R (4206.10±415.80 vs. 3900.60±365.40 µg/kg, respectively; P=0.001). CONCLUSIONS: General anesthesia without muscle relaxant provides similar working conditions to those observed with muscle relaxant, and it is associated with earlier eye opening and extubation and higher level of consciousness on emergence from spinal surgery.

Gene-gene interaction of GJB2, SOD2, and CAT on occupational noise-induced hearing loss in Chinese Han population / 生物医学与环境科学（英文）

The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.