NLRP3 inhibition attenuates the allergic rhinitis symptoms in a mouse model.

BACKGROUND: Recent human and animal studies have demonstrated that Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is closely involved in the development of allergic diseases. OBJECTIVE: To identify the mechanism underlying the activation of NLRP3 inflammasome signaling pathway in an ovalbumin (OVA)-induced allergic rhinitis (AR) mice model and to validate the effect of a specific inhibitor of the NLRP3, MCC950. METHODS: Mice were divided into three groups and each group consisted of ten mice (saline group, the negative control group; OVA group, the OVA-induced AR model group; and OVA+MCC group, treated with 10 mg/kg MCC950). MCC950 was administered intraperitoneally every second day. Multiple parameters of AR, including NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 were evaluated by using ELISA, RT-qPCR, histopathology, and immunohistochemistry. RESULTS: The mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 were upregulated in the OVA group compared with those of the saline group. MCC950 significantly inhibited the mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 in nasal tissue. Further, AR symptoms and eosinophil count were normalized after MCC950 treatment. However, OVA-specific IgE was not restored in the OVA+MCC group. CONCLUSION: NLRP3 inflammasome signaling pathway may be an alternative pathway to induce AR symptoms in OVA-induced AR model. MCC950 is a specific inhibitor of NLRP3 cascade, which attenuates AR symptoms regardless of IgE.

The heterophilicic epitopes in conserved HA regions of human and avian influenza viruses can produce antibodies that bound to kidney tissue.

Influenza virus infection can cause kidney damage. However, the link between influenza infection and disease is still unclear. The purpose of this study was to analyze the relationship between heterophilic epitopes on H5N1 hemagglutinin (HA) and disease. The monoclonal antibody (mAb) against H5N1 was prepared, mAbs binding to human kidney tissue were screened, and the reactivities of mAbs with five different subtypes of influenza virus were detected. Design and synthesize the peptides according to the common amino acid sequence of these antigens, and analyze the distribution of the epitope on the crystal structure of HA. Immunological methods were used to detect whether the heterophilic epitopes could induce the production of antibodies that cross-react with kidney tissue. The results showed that H5-30 mA b binding to human kidney tissue recognized the heterophilic epitope 191-LVLWGIHHP-199 on the head of HA. The key amino acid were V192, L193, W194 and I196, which were highly conserved in human and avian influenza virus HA. The heterophilic epitope could induce mice to produce different mAbs binding to kidney tissue. Such heterophilic antibodies were also detected in the serum of the patients. It can provide materials for the mechanism of renal diseases caused by influenza virus infection.

Comparative Study of the Efficacy of Autologous Tooth Bone Powder and Inorganic Bovine Bone Powder on the Repair of Jaw Defects.

Context: The main pathological features of jaw cysts are bone defects. Obtaining autologous bone for transplantation repair has been associated with postoperative complications, and the amount of bone that dentist can collect is limited. Studies have found that autologous tooth bone powder is safe and has good bone-formation ability and stability. Objective: The study intended to examine the efficacy of implantation of autologous tooth bone powder and inorganic bovine bone powder, after marsupialization and second-stage curettage for large jaw cysts that dentist can't directly remove by surgery in clinical practice. Design: The research team designed a prospective randomized controlled trial. Setting: The study took place in the Head and Neck Surgery Department at Chongqing University Cancer Hospital in Chongqing, China. Participants: Participants were 60 patients at the hospital between 2016 and 2018 who had mandibular cysts that surgical operation couldn't directly remove by surgery in clinical practice. Intervention: At 4 months after curettage, the research team randomly divided participants into three groups: (1) an intervention group who received implants of autologous tooth bone powder into the bone defects, (2) a positive control group who received implants of inorganic bovine bone powder, and (3) a negative control group who received no implants of any material. Outcome Measures: The research team performed: (1) periodontal probing at a fixed anatomical point for the intervention and both control groups postintervention at one day and 4 months after surgery and recorded the changes in probing depth and (2) computed tomography (CT) scans at baseline one day before and postintervention at 4 months after the implantation to determine changes in the bone mineral density and compared them among the three groups. Results: The change in the height of the intervention group's fixed anatomical point postintervention at 4 months after surgery was significantly smaller than that of the positive control group (P < .05). In the CT scan analysis, the differences between the intervention and negative control groups and between the positive and negative control groups were statistically significant (P < .05); however, the difference between the intervention and positive control groups wasn't significant (P > .05). Conclusions: Autologous tooth bone powder and inorganic bovine bone powder can effectively repair bone defects caused by large jaw cysts and that the repaired effect may be better than that of spontaneous osteogenesis. The autologous tooth bone powder was associated with lower levels of bone loss than those seen with use of inorganic bovine bone powder.

[Simultaneous determination of four anthraquinones in Polygonum multiflorum by QAMS].

A simple, specific and selective quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of anthraquinones and anthraquinone glycosides in Polygonum multiflorum was developed. Four main anthraquinones and its glycosides, emodin, emodin-8-O-ß-D-glucoside, physcion and physcion-8-O-ß-D-glucoside were selected as analytes to evaluate the quality of P. multiflorum. Emodin was used as the internal standard, and the relative correction factors(RCFs) between emodin and the other three anthraquinones were calculated. Comparison of the contents of the four components in 30 batches of P. multiflorum from different regions and 12 batches decoction pieces from different manufacturers by QAMS and external standard method(ESM) showed that there was no significant difference between QAMS and ESM for quantification of the four main components by using relative error results, and the QAMS method was accurate and reliable, and had a good repeatability. In addition, compared with the results calculated by the difference method between total anthraquinone and free anthraquinone in the content determination of P. multiflorum in Chinese Pharmacopoeia, the results of direct determination combined anthraquinone by QAMS were very close to that by measured the external standard method. Therefore, simultaneous quantification of four main anthraquinones by using QAMS is suitable to evaluate the quality of P. multiflorum. Then the optimized assay method of the combined anthraquinone contents showed simple and feasible, which could be replaced and improved the quantification method of the combined anthraquinone in the current Chinese Pharmacopeia.

Hymenobacter metallilatus sp. nov., isolated from abandoned lead-zinc ore.

An aerobic, non-motile, Gram-stain-negative, red-to-pinkish and rod-shaped bacterium, designated 9PBR-2T, was isolated from an abandoned lead-zinc ore sample collected from Meizhou, Guangdong Province, PR China. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain 9PBR-2T belongs to the genus Hymenobacter and was most closely related to Hymenobacter rigui KCTC 12533T (98.0 %), Hymenobacter swuensis KCTC 32018T (97.8 %) and Hymenobacter perfusus LMG 26000T (97.6 %). The calculated average nucleotide identity values based on whole genome sequences between strain 9PBR-2T and closely related type strains ranged from 81.3 to 84.1 %. Correspondingly, the digital DNA-DNA hybridization values ranged from 25.5 to 28.1 %. The major fatty acids of strain 9PBR-2T were iso-C15:0, anteiso-C15:0, C16:1ω5c, summed feature 3 (C16:1ω6c and/or C16:1ω7c) and summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B). It contained menaquinone 7 (MK-7) as the major isoprenoid quinone and phosphatidylethanolamine as the major polar lipid. The genomic DNA G+C content based on whole genome sequence was 59.8 mol%. Characterization based on phylogenetic, chemotaxonomic and phenotypic analyses clearly indicated that strain 9PBR-2T represents a novel species of the genus Hymenobacter, for which the name Hymenobactermetallilatus sp. nov. is proposed. The type strain is 9PBR-2T (=GDMCC 1.1492T=JCM 32699T).

[Establishment of extraction method for Gardeniae Fructus extract and its application in evaluating different Gardeniae Fructus decoction pieces].

In this experiment,the gradation analysis method was used to evaluate the quality of different pieces of Gardeniae Fructus through the extraction rate difference and the difference analysis of the main components in the extract. In this experiment cold-dip and hot-dip methods were used to compare the yield of Gardeniae Fructus extract and the content of chemical constituents with water,25%,50%,75% and 95% ethanol fractions. By weighted calculation,the optimal extraction method of Gardeniae Fructus was determined,and this was verified by practical application. RESULTS:: showed that for the water-soluble extract,cold dip method was better than the hot dip method; and for alcohol-soluble extract,75% ethanol under cold dip method was best. The verification results showed that water-soluble extracts under cold dip methods could be used to significantly distinguish the raw Gardeniae Fructus( GF) and processed( stir-baked) GF( GFP) collected from the market. Meanwhile,this method could be also used to distinguish the same batch of GF,GFP and carbonized GF( GFC) with significant differences,respectively( P<0. 05). Ethanol-soluble extract can be used to clearly distinguish GFP and GFC pieces in the same batch( P<0. 05). The results of content determination showed that the variation coefficient of components in GF processed products was higher than that in extracts,and the content of hydroxygeniposide was the most significant component between GF and its processed products. It is suggested that the method of water-soluble extract of GF and the determination of the content of gardoside should be combined together to evaluate the quality of GF and its heat processed products.

Application of self-retaining bidirectional barbed absorbable suture in retroperito- neoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and feasibility of self-retaining bidirectional barbed absorbable suture application in retroperitoneoscopic partial nephrectomy. MATERIALS AND METHODS: From Sep 2011 and Aug 2012, 76 cases of retroperitoneoscopic partial nephrectomy were performed at our hospital. The patients were divided into two groups: self-retaining barbed suture (SRBS) group (n = 36) and non-SRBS group (n = 40). There was no significant difference in age, sex, tumor size and location between the two groups. Clinical data and outcomes were analyzed retrospectively. RESULTS: All 76 cases of retroperitoneoscopic partial nephrectomy were successfully performed, without conversion to open surgery or serious intraoperative complications. In the SRBS group, the suture time, warm ischemia time and operation blood loss were significantly shorter than that of non-SRBS group (p < 0.01), and operation time and hospital stay were shorter than that of non-SRBS group (p < 0.05). CONCLUSIONS: The application of self-retaining bidirectional barbed absorbable suture in retroperitoneoscopic partial nephrectomy could shorten suture time and warm ischemia time, with good safety and feasibility, worthy of being used in clinic.

[Effective Components of three kinds of shen-supplementing Chinese medicine on self-renewal and neuron-like differentiation of NSCs in AD mouse embryos: an experimental research].

OBJECTIVE: To observe the regulatory effects of psoralen, oleanolic acid, and stilbene glucoside, three active components of psoralea fruit, glossy privet fruit and tuber fleeceflower root respectively, on Aß25-35induced self-renewal and neuron-like differentiation of neural stem cells (NSCs). METHODS: Embryonic NSCs werein vitro isolated and cultured from Kunming mice of 14-day pregnancy, and randomly divided into the control group, the Aß25-35 group, the Aß25-35 +psoralen group, the Aß25-35 +oleanolic acid group, and the Aß25-35 + stilbene glucoside group. The intervention concentration of Aß25-35 was 25 µmol/L, and the intervention concentration of three active components of Chinese medicine was 10(-7)mol/L. The effect of three active components of Chinese medicine on the proliferation of NSCs was observed by counting method. The protein expression of Tubulin was observed by Western blot and immunofluorescence. The ratio of Tubulin+/DAPI was caculated. Results Compared with the control group, the sperical morphology of NSCs was destroyed in the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin /DAPI all decreased (P <0.01, P <0.05). Compared with the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin + /DAPI all increased in the three Chinese medicine treated groups (P <0. 01, P <0. 05). CONCLUSIONS: 25 µmol/L Aß25-35 could inhibit self-renewal and neuron-like differentiating of NSCs. But psoralen, oleanolic acid, and stilbene glucoside could promote self-renewal of NSCs and neuron-like differentiation.

EtOS2K as a C1 Source: Solvent- and Temperature-Controlled Selective Synthesis of Quinoline-2-thione and Quinoline-2-one Derivatives.

Herein, we disclosed a highly chemoselective synthesis of quinoline-2-one and quinoline-2-thione derivatives using EtOS2K as the C1 source. Quinoline-2-one derivatives were synthesized selectively with NaCl as a catalyst in the solvent DMSO/H2O, while quinoline-2-thione derivatives were produced without the need for any catalyst in an environmentally friendly solvent EtOH/H2O. The reaction conditions were mild and had good functional group tolerance.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model.

BACKGROUND: Interleukin (IL) 17A, a key cytokine of T(H)17 cells, is a well-known proinflammatory cytokine. Despite the important role of T(H)17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. OBJECTIVE: To investigate the role of IL-17A in the allergic response in AR. METHODS: Wild-type BALB/c and IL-17A-deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. RESULTS: IL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A-deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A-deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow-derived mast cells from IL-17A-deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A-deficient mice. CONCLUSION: These results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of T(H)2 cytokine.

[Investigation of health status of workers exposed to low concentration cadmium in a zinc powder factory].

OBJECTIVE: To explore the health status of workers exposed to Cd at low concentration. METHODS: One hundred eighteen workers of zinc powder finishing and 34 staffs were served as the exposure group and control group, respectively. The physical examination, blood cadmium, urinary cadmium, blood lead, urinary 32-microglobin, urine creatine, chest film, pulmonary function , pure tone teat and were detected for all subjects. RESULTS: Twelve air samples from 6 monitoring points in workshop were detected, the air Cd concentrations were 0.002-0.015 mg/m³, which were under the national limit of occupational exposure. In exposure group, the rates of exceeding standards of blood Cd and urinary Cd were 65.25% and 38.16%, respectively, the rate of exceeding standards of urinary Cd for two times was 27.12%, the rate of exceeding standard of urine Cd for two times plus the positive urinary 32-microglobin was 2.54 %. In control group, the rates of exceeding national standard of blood Cd was 26.47 %, but the values of urinary Cd were normal. In exposure group, the rate of exceeding standards of urinary Cd increased with the service length. Smoking could enhance the rates of exceeding standards of blood Cd and urinary Cd. CONCLUSION: In zinc powder finishing, the low-concentration cadmium exposure could cause the occupational cadmium poisoning, the comprehensive protection measures can reduce the occupational cadmium poisoning. It is suggested that the limits of occupational exposure to cadmium should be declined.

[Analysis of urine cadmium and blood cadmium of workers before and after the cadmium dust control].

OBJECTIVE: To analyze the urinary cadmium, blood cadmium and urinary beta2-MG of workers in a zinc powder processing plant before and after the cadmium dust control, and to explore the effects of dust control on the prevention and treatment of cadmium hazards. METHODS: The on-site occupational hazard survey was used to investigate the changes of urine cadmium, blood cadmium and beta3-MG of 84 workers exposed to cadmium before and after the treatment by self-control analysis for evaluating the effects of dust control measures in a zinc powder processing plant. RESULTS: After treatment of the cadmium dust, the geometric mean of zinc dust in the workplace significantly decreased from 3.38 mg/m3 to 2.22 mg/m3 (P < 0.01). The geometric mean concentration of blood cadmium [(2.19 +/- 1.19) microg/L] and urine cadmium [(1.96 +/- 0.74) microg/g Cr] before treatment were significantly higher than those of one year [(1.63 +/- 0.83) microg/L] and [(1.25 +/- 0.83) microg/g Cr] and two years [(1.36 +/- 0.95) microg/L] and [(0.94 +/- 0.72) microg/g Cr] after the cadmium dust control (P < 0.01), respectively. The positive correlations analysis between urine cadmium and blood cadmium concentration of one and two years before and after the cadmium dust treatment implied that there was significant difference (r = 0.466, P < 0.01). CONCLUSION: Dust treatment could reduce the impact of low concentration cadmium on the urine cadmium and blood cadmium concentrations of the workers exposed to cadmium, and effectively prevent the cadmium poisoning.

Discovery of Mycothiogranaticins from Streptomyces vietnamensis GIMV4.0001 and the Regulatory Effect of Mycothiol on the Granaticin Biosynthesis.

Granaticins are benzoisochromanequinone polyketides with remarkable antibacterial and anticancer activities. Three sulfur-containing granaticin congeners, mycothiogranaticins A (1), B (2) and granaticin MA (3) were discovered from a granaticin-producing strain of Streptomyces vietnamensis GIMV4.0001. Two of them were structurally determined with mycothiol or N-acetylcysteine moieties and found to be bio-actively reluctant. Disruption of the mshA gene (SVTN_RS20640) that encodes the D-inositol-3-phosphate glycosyltransferase crucial for mycothiol biosynthesis, fully abolished the production of mycothiogranaticins. The result substantiated that the newly discovered mycothiogranaticins are consequences of the combination of the granaticin and mycothiol biosynthetic pathways. The overall granaticin production of the ΔmshA mutant strain was unexpectedly decreased by at least more than 50%, while similar production level of granaticins to that of the wild type strain was observed in an mycothiol-S transferase gene (SVTN_RS22215) disruptant Δmst. These results indicated that the mycothiol deficiency was responsible for the decreased production of granaticins. Mycothiol may positively regulate the biosynthesis of granaticin possibly by maintaining the cellular redox balance. To the best of our knowledge, this is the first report that mycothiol can not only be a direct building block of polyketides but also play a regulatory role in the polyketide biosynthesis.

Prediction of acute renal allograft rejection by combined HLA-G 14-bp insertion/deletion genotype analysis and detection of kidney injury molecule-1 and osteopontin in the peripheral blood.

INTRODUCTION: Acute renal rejection usually fails to be diagnosed before the increase in the serum creatinine levels, and the resultant damage to the renal tissues occur in varying degrees. We hypothesized that the combined detection of human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion genotypes and kidney injury molecule-1 (KIM-1) and osteopontin (OPN) levels in serum might facilitate the prediction of acute renal allograft rejections in kidney transplant recipients. METHODS: HLA-G 14-bp insertion/deletion genotypes and the serum KIM-1 and OPN levels of 77 kidney transplant recipients were determined and compared before operation and on days 1, 4, and 7 after the operation (32 in acute rejection [AR] group and 45 in stable allograft function [STA] group). These 3 indicators were combined to establish a model for the early prediction of AR. RESULTS: The KIM-1 levels in the serum of patients were significantly higher in the AR group than in the STA group. The area under the receiver operator characteristics (ROC) curve (AUC) of KIM-1 for the prediction of rejection was maximized on the1st day after operation, with a sensitivity of 84.4% and a specificity of 86.7%. The OPN levels in the serum of patients were significantly higher in the AR group than in the STA group only before operation and on the 7th day after operation. The AUC of OPN for the prediction of rejection was maximized on 7th day after operation, with a sensitivity of 68.8% and a specificity of 88.9%. The HLA-G + 14-bp allele frequency was also significantly higher in the AR group than in the STA group. The results of these three indicators were converted into a qualitative method. If any two of the three indicators show as positive, it was diagnosed as acute rejection, and it has the highest ability to predict acute rejection with a sensitivity and specificity of 84.38% and 91.11%, respectively. CONCLUSIONS: The HLA-G 14-bp insertion/deletion genotype and KIM-1 and OPN levels in the patients' serum were significantly different between the AR and STA groups. The power of predicting acute renal allograft rejection could be improved by combined these three biomarkers.

Human Rhinovirus Infection Enhances the Th2 Environment in Allergic and Non-allergic Patients with Chronic Rhinosinusitis.

OBJECTIVES: This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). METHODS: Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. RESULTS: The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). CONCLUSION: This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

The different role of YKL-40 in glioblastoma is a function of MGMT promoter methylation status.

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

Antiallergic Effect of Hizikia fusiformis in an Ovalbumin-Induced Allergic Rhinitis Mouse Model.

OBJECTIVES: The extract of Hizikia fusiformis is known to exhibit anticancer, antiatopic and antioxidant activities. We aimed to investigate the extract of H. fusiformis on allergic rhinitis inflammation in a mouse model. METHODS: The 4-week-old BALB/c mice were randomly assigned into four groups: group A, control group (n=9); group B, allergic rhinitis group (n=10); group C (n=10) received 300 mg/kg of H. fusiformis during nasal challenging period; group D (n=10) received 600 mg/kg of H. fusiformis during general sensitization period and 300 mg/kg of H. fusiformis during nasal challenging period. Allergic inflammation was made with ovalbumin (OVA) and alum then challenged intranasally with OVA. H. fusiformis was intraperitoneally administered 3 hours before the OVA administration. Allergic symptom score and the levels of immunoglobulin G1 (IgG1), IgG2a, OVA-specific IgE antibodies, levels of cytokines in the nasal mucosa and in spleen cell culture supernatant, such as tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-13, and IL-10 were assessed. The percentage of regulatory T cell was analyzed by flow cytometry. Eosinophilic infiltration and goblet cell hyperplasia were also evaluated. RESULTS: H. fusiformis administered groups C and D showed significant inhibitory effects on nasal symptoms, IL-13 mRNA expression and eosinophil infiltration/goblet cell hyperplasia in the nasal tissue; OVA-specific IgE production in serum (P<0.05). In group D, H. fusiformis treatment downregulated IL-4, IL-5, IL-13, TNF-α, and IL-10 cytokine expression in splenocyte culture as well as significantly decreased IgG2a, IgG1 levels in serum compared with group B (P<0.05). However, the expressions of IL-5, interferon-γ and forkhead box P3 mRNA did not change in groups C and D. CONCLUSION: H. fusiformis could induce antiallergic inflammation by suppressing the T-helper type 2 cytokine production (IL-13) locally and systemically, OVA-specific IgE formation, goblet cell hyperplasia, and eosinophilic infiltration in a mouse model of allergic rhinitis. Thus, H. fusiformis could be considered as a potential therapeutic agent in treating allergic rhinitis.

[Analysis on acupoint selection rules of acupuncture for Alzheimer's disease based on complex network].

OBJECTIVE: To explore the acupoint selection rules of acupuncture for Alzheimer's disease (AD) in modern clinical practice by complex network technology. METHODS: The relevant articles of clinical trials were retrieved from CNKI published before December 2017. Using Microsoft Excel 2010, the database was established. Using Gephi 0.8.2 software, the complex network mode was built and its topological structure was analyzed. RESULTS: Finally, 81 articles were eligible and 114 acupoint prescriptions were extracted. The constructed complex network of acupoint prescriptions for AD was characteristics as small world effect and scale-free property, the crucial acupoints included Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Yintang (GV 29), Shenmen (HT 7), Shenting (GV 24), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3). In acupoint combination, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Sanyinjiao (SP 6) were the most common, and the combination of the distal and nearby points was predominant. Using k-core for acupoint optimization, 29 core acupoints were screened and they were mostly located on the governor vessel and the head and neck, with the highest use frequency. 82.76% of acupoints were specific acupoints and the influential points were dominant. Using community structure partition, these acupoints were classified into two groups, i.e. deficiency syndrome and excess syndrome. CONCLUSION: The selection of local acupoints is the first choice in acupuncture treatment for AD. The combination of distal and nearby points is the most common and the special points are the core. In clinical practice, the great consideration is provided on mind regulation, integration of disease and symptoms, the mutual treatment of the primary and the secondary as well as the deficiency and the excess.

[Effect of electroacupuncture on neurological deficit and activity of TLR2/NF-κB signaling in ce-rebral ischemia /reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neurological behavior and activity of Toll-like receptor 2 / nuclear factor kappa B (TLR2/NF-κB) signaling of the ischemic cerebral area in cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its mechanisms underlying improvement of CIRI. METHODS: A total of 120 male SD rats were randomly divided into blank control, sham operation, model, EA and EA＋NF-κB inhibitor (Pyrrolidine Dithiocarbamate Hydrochloride, PDTC, EA＋PDTC) groups which were further divided into 3, 7, 14 and 28 d subgroups (n＝6 in each subgroup). The CIRI model was established by occlusion of the middle cerebral artery for 90 min, followed by reperfusion. EA (1－20 Hz, 6 V) was applied to "Shuigou" (GV26), "Neiguan" (PC6), "Sanyinjiao" (SP6) and "Weizhong" (BL40) for 30 min, once a day for 28 days. For rats of the EA＋PDTC group, PDTC solution (120 mg/kg) was intraperitoneally injected on the 3rd day after successful modeling and before EA intervention. The neurological deficit severity (Zea Longa score) was assessed 3, 7, 14 and 28 days after modeling. The expression levels of TLR2, Interleukin-1 receptor-associated kinase (IRAK) and NF-κB mRNAs in the ischemic penumbra region of brain tissue were detected by real-time fluorescence quantitative PCR. RESULTS: Following modeling, the neurological deficit scores were significantly increased from the 3rd day on after CIRI (P<0.05), the expression levels of TLR2 mRNA on day 3, 7, 14 and 28, and IRAK mRNA on day 3 and 7, as well as NF-κB mRNA on day 3, 7 and 14 were significantly up-regulated in the model group relevant to the blank control group (P<0.05). After EA intervention, the neurological deficit scores were significantly decreased in the EA group on day 3, 7 and 28 and in the EA＋PDTC group on day 3, 7, 14 and 28 in comparison with those of the model group (P<0.05). In addition, the expression levels of TLR2 mRNA and NF-κB mRNA on day 3, 7 and 14 in the EA group, and on day 3, 7, 14 and 28 in the EA＋PDTC group, IRAK mRNA on day 3 in the EA and EA＋PDTC group were significantly down-regulated (P<0.05), but those of IRAK mRNA on day 14 and 28 in the EA group were significantly up-regulated in comparison with those of the model group (P<0.05). The effect of the EA＋PDTC was obviously superior to that of simple EA in down-regulating the expression of TLR2 (on day 28), and IRAK (on day 3, 14, 28), and NF-κB (on day 3, 7 and 14) (all P<0.05). CONCLUSION: EA stimulation can improve the symptoms of neurological deficits in CIRI rats, which may be related to its effect in suppressing the expression of TLR2, NF-κB and IRAK mRNAs of the ischemic cerebral tissue, i．e., down-regulating the activity of TLR2/NF-κB signaling.