Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice.

OBJECTIVE: To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS). METHODS: The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively. RESULTS: LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups. CONCLUSION: HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.

Microplastics shape microbial interactions and affect the dissemination of antibiotic resistance genes in different full-scale wastewater treatment plants.

Wastewater treatment plants (WWTPs) pose a potential threat to the environment because of the accumulation of antibiotic resistance genes (ARGs) and microplastics (MPs). However, the interactions between ARGs and MPs, which have both indirect and direct effects on ARG dissemination in WWTPs, remain unclear. In this study, spatiotemporal variations in different types of MPs, ten ARGs (sul1, sul2, tetA, tetO, tetM, tetX, tetW, qnrS, ermB, and ermC), class 1 integron integrase (intI1) and transposon Tn916/1545 in three typical WWTPs were characterized. Sul1, tetO, and sul2 were the predominant ARGs in the targeted WWTPs, whereas the intI1 and transposon Tn916/1545 were positively correlated with most of the targeted ARGs. Saccharimonadales (4.15 %), Trichococcus (2.60 %), Nitrospira (1.96 %), Candidatus amarolinea (1.79 %), and SC-I-84 (belonging to phylum Proteobacteria) (1.78 %) were the dominant genera. Network and redundancy analyses showed that Trichococcus, Faecalibacterium, Arcobacter, and Prevotella copri were potential hosts of ARGs, whereas Candidatus campbellbacteria and Candidatus kaiserbacteria were negatively correlated with ARGs. The potential hosts of ARGs had a strong positive correlation with polyethylene terephthalate, silicone resin, and fluor rubber and a negative correlation with polyurethane. Candidatus campbellbacteria and Candidatus kaiserbacteria were positively correlated with polyurethane, whereas potential hosts of ARGs were positively correlated with polypropylene and fluor rubber. Structural equation modeling highlighted that intI1, transposon Tn916/1545 and microbial communities, particularly microbial diversity, dominated the dissemination of ARGs, whereas MPs had a significant positive correlation with microbial abundance. Our study deepens the understanding of the relationships between ARGs and MPs in WWTPs, which will be helpful in designing strategies for inhibiting ARG hosts in WWTPs.

Facial-onset sensory and motor neuronopathy with myasthenia gravis: A case report.

RATIONALE: Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG) is an antibody-mediated and complement-involved acquired autoimmune disorder of the post-synaptic neuromuscular junction. There have been few reports about if there is related between the 2. In this study, we present the case of a man who was diagnosed as FOSMN with MG in continuity. PATIENT CONCERNS: The patient chief complaints were right-side facial numbness and right-eyelid incomplete closure, followed by slurred speech and dysphagia, and the symptoms gradually progressed. The patient serum was positive for anti-AchR and anti-Titin antibodies. DIAGNOSES: The patient was diagnosed FOSMN with MG. INTERVENTIONS: The patient symptoms were relieved after pyridostigmine bromide and prednisolone treatment. OUTCOMES: Symptoms have improved. LESSONS: Facial-onset sensory and motor neuronopathy and MG have disparate clinical features. Therefore, we reported a rare case in which the 2 conditions concurrently existed. Immune dysfunction might be the pathogenesis of this association, while there is no definite evidence to support it, further studies are needed.

Effects of prenatal exposure to PM2.5 and its composition on cognitive and motor functions in children at 12 months of age: The Shanghai Birth Cohort Study.

BACKGROUND: Prenatal fine particulate matter (PM2.5) exposure has been linked to infant cognitive and motor functions, but the effects of PM2.5 chemical composition remain unclear. OBJECTIVES: We aimed to explore the associations of prenatal PM2.5 and its composition exposure with infant cognitive and motor functions. METHODS: We studied 2,435 mother-infant pairs in the Shanghai Birth Cohort Study. PM2.5 and its seven compositions [primary particles (black carbon, mineral dust and sea salts) and secondary particles (NH4+, NO3-, SO42- and organic matter)] during thethreetrimesters ofpregnancy were retrieved from the V4.CH.03 product developed by using a combined geoscience-statistical method. At the 12-month-old follow-up, infant cognitive and motor functions in five domains were assessed using the Ages and Stages Questionnaire (ASQ). We used multivariable linear regressions to estimate the effects of PM2.5 and its composition on the ASQ scores, for all infants and stratifying by sex and breastfeeding duration. RESULTS: PM2.5 exposure was negatively associated with gross motor, problem-solving and personal-social scores for all infants. PM2.5 compositions were inversely associated with ASQ scores in all five domains, and the effects of different compositions varied across domains. Specifically, all compositions except organic matter were correlated with lower problem-solving scores [e.g., ( [Formula: see text]  =  - 10.79, 95 % CI: -17.40, -4.18) ∼ ( [Formula: see text]  =  - 4.68, 95 % CI: -7.84, -1.53); for each 10 µg/m3 increase in PM2.5 compositions during the third trimester]. Primary and some secondary particles (organic matter, NO3-) were related to lower gross motor scores. Secondary particles were also inversely associated with communication (organic matter and NO3-), fine motor (NH4+, NO3-, SO42-) and personal-social (NH4+) scores. Additionally, boys and infants breastfed for < 6 months appeared to be more susceptible. CONCLUSIONS: We found negative associations of PM2.5 and its compositions with infant cognitive and motor functions over a range of domains, especially the problem-solving domain.

Systematic Evaluation of Randomized Clinical Trials of Huangqin Tang in Combination with Mesalazine for Ulcerative Colitis.

Objective: To systematically evaluate the efficacy and safety of Huangqin Tang (HQT) combined with mesalazine for the treatment of ulcerative colitis (UC). Methods: The China Knowledge Network, Wanfang Data, VIP, PubMed, SinoMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) of UC with HQT in Chinese and English. The search time was from the establishment of the database to October 2021. The included literature was evaluated for data extraction and risk of bias, efficacy and safety were evaluated using the RevMan5.3 software, and the quality of evidence was evaluated using GRADE. Results: Six studies with a total of 565 subjects were included, and a meta-analysis showed that HQT combined with mesalazine for UC significantly improved the cure rate (RR = 1.56, 95% CI [1.23, 1.98), P=0.0003) and overall efficacy rate (RR = 1.24, 95% CI [1.14, 1.35], P=0.00001), which significantly reduced the clinical symptom scores; however, all had high heterogeneity. HQT combined with mesalazine modulated the patients' serum IL-6, IL-10, IgA, and IgG levels. HQT combined with mesalazine for UC tended to reduce adverse effects; however, the difference was not statistically significant. All GRADE ratings of the quality of evidence were of low quality. Conclusions: HQT combined with mesalazine in the treatment of UC significantly improved the cure rate and overall treatment efficiency and regulated the expression levels of serum IL-6, IL-10, IgA, and IgG.

Effects of oral administration and intravenous injection of polygalacturonic acid on the immunomodulation and gut microbiota in UC mice.

This study aimed to compare the differences between oral administration and intravenous injection of polygalacturonic acid (PGA) in the regulation of immune and intestinal microflora in ulcerative colitis (UC) mice. PGA was administered orally or intravenously. PGA in the high-dose ig group was the most effective in treating UC by increasing colon length and downregulating disease activity index, histopathological score and proinflammatory cytokine levels. In spleen, the efficacy of PGA on restoring Th17/Treg balance in the high-dose iv group was better than that in the high-dose ig group, the opposite was observed in the lamina propria. The level of colonic IL-17A in the high-dose ig group was lower than that in the high-dose iv group, the opposite was observed for that of colonic IL-10. Western blot and immunohistochemistry analysis revealed that PGA in the high-dose ig group decreased the protein expression of RORγt, and increased that of FOXP3. Furthermore, PGA in the high-dose ig group was more effective than that in the high-dose iv group in improving the intestinal microflora structure. Our results suggest that in immune regulation, oral PGA is more effective in the lamina propria and gut microbiota while intravenous PGA is more effective in the spleen.

Urinary organophosphate metabolite concentrations and birth sizes among women conceiving through in vitro fertilization in Shanghai, China.

BACKGROUND: Few studies have examined the adverse birth sizes of preconception exposure to organophosphate pesticides (OPs) in women undergoing in vitro fertilization (IVF). OBJECTIVES: We investigated the relationship of preconception OP exposure with birth sizes among Chinese women undergoing IVF. METHODS: This study included 302 couples seeking infertility treatment in the China National Birth Cohort Study, from Shanghai, China, who gave birth to singleton infants between 2018 and 2021. Clinical data were collected from medical records. We measured the concentrations of six nonspecific dialkyl phosphates (DAP) metabolites of OPs [diethylthiophosphate (DETP), diethylphosphate (DEP), diethyldithiophosphate (DEDTP), dimethyldithiophosphate (DMTP), dimethylphosphate (DMP), and dimethyldithiophosphate (DMDTP)] in maternal urine. DMDTP and DEDTP were precluded from further analyses due to the low detection rates. Generalized linear models (GLMs) and weighted quantile sum (WQS) regression analyses were performed to examine the individual and joint effects of OP exposures on gestational age, birth weight, body length, and ponderal index. Odder ratio (OR) of preterm birth were estimated using logistic regression models. RESULTS: Women in the highest as compared with lowest quartile of DEP had shorter gestational age (ß = - 0.68; 95% CI = -1.24, -0.11). The association was modified by sex, with boys showing larger decreases in gestational age (ß = - 0.86; 95% CI = -1.60, -0.13). No associations were found between other DAP metabolites and birth sizes. Results from linear models with individual DAP metabolites were corroborated by the WQS regression where DEP had the largest contribution to the overall mixture effect on gestational age (weight = 0.70). Moreover, DEP concentration was associated with an elevated risk of preterm birth (OR = 1.35, 95% CI = 1.11, 2.25). CONCLUSION: Preconception DEP concentration was associated with shortened gestational age and increased risk of preterm birth, and the association was more pronounced among boys than girls.

Prenatal neonicotinoid insecticides Exposure, oxidative Stress, and birth outcomes.

BACKGROUND: An increasing number of studies have reported neonicotinoid insecticides (NEOs), the emerging alternatives to conventional insecticides, may increase oxidative stress and cause adverse health effects, but limited is known about the prenatal NEOs exposures and their impact on birth outcomes. OBJECTIVES: We investigated the levels of prenatal exposure to NEOs/metabolites, to assess their associations with birth outcomes, and investigate whether these associations could be mediated by oxidative stress using 8-OHdG as the biomarker. METHODS: We studied 296 mother-infant pairs recruited from Laizhou Wan Birth Cohort in 2010 - 2013. Two NEOs (IMI and ACE), three metabolites (6-CN, ND-ACE, and 2CTCA), and 8-OHdG were measured in maternal urine collected before delivery. Birth outcomes including birth weight, birth length, ponderal index (PI), head circumference, and gestational age, were acquired. We examined the associations between NEOs/metabolites and birth outcomes using multivariable linear regression. Mediation analysis was conducted to clarify the role of 8-OHdG on the association of NEOs/metabolites exposure and birth outcomes. RESULTS: Highest detection rate was observed for ACE (100.0%), followed by IMI (98.3%) and 6-CN (98.0%), suggesting the common exposure of pregnant women. The highest median concentration was observed for 6-CN with creatinine-adjusted median levels of 9.58 µg/g creatinine. A decrease in newborns' head circumference was observed with a 10-fold increase in IMI (ß = -1.83; 95% CI = -3.04, -0.62) and ACE (ß = -2.27; 95% CI = -3.56, -0.98). An increase in newborns' PI was observed with a 10-fold increase in IMI (ß = 0.40; 95% CI = 0.03, 0.75). Maternal 8-OHdG demonstrated 38.5-65.5% mediating effects in the negative association of IMI, ACE, 2-CTCA with head circumference. These associations might differ between boys and girls. CONCLUSIONS: Pregnant women were widely exposed to NEOs/metabolites in China. Results suggested the potential impacts of prenatal exposure to certain neonicotinoid insecticides on head circumference. Urinary 8-OHdG may partly mediate these associations.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Child Growth Trajectories in the First Two Years.

BACKGROUND: Pregnant women are ubiquitously exposed to per- and polyfluoroalkyl substances (PFAS). Prenatal exposure to PFAS has been associated with lower birth weight but also with excess adiposity and higher weight in childhood. These mixed findings warrant investigation of the relationship between PFAS and dynamic offspring growth. OBJECTIVES: To investigate the association between prenatal PFAS exposure and early-life growth trajectories during the first 2 y. METHODS: Pregnant women (n=3,426) were recruited from 2013 to 2016 from the Shanghai Birth Cohort (SBC) Study, and their children were followed up from birth to 2 y of age. Seven PFAS congeners were quantified in pregnant women's serum during the first trimester. Our study population was restricted to 1,350 children who had five repeated measurements for at least one anthropometric measure. Four anthropometric measures, including weight, length/height, weight-for-length, and head circumference, were evaluated at birth, 42 d, 6 months, 12 months, and 24 months, and standardized into z-scores using the World Health Organization reference. Trajectories of each measure were classified into five groups using group-based trajectory modeling. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for trajectory groups according to log2-transformed PFAS concentrations, and the moderate-stable group was selected as the reference group for all measures. RESULTS: Higher prenatal exposure to PFAS was associated with elevated odds for the low-rising weight-for-age z-score (WAZ) trajectory, and the high-rising length-for-age z-score (LAZ) trajectory. Meanwhile, PFAS levels were associated with decreased odds for the low-rising and high-rising weight-for-length z-score (WLZ) trajectories. In addition, the associations of PFAS with growth trajectory groups differed by sex, where males had greater odds for the low-rising and low-stable WAZ trajectories and for the high-stable and low-rising WLZ trajectories. In contrast, inverse associations were consistently observed with trajectories of the high-stable, low-stable, and low-rising head-circumference-for-age z-score (HCZ) in relation to most individual PFAS congeners. PFAS mixtures analysis further confirmed the above findings. DISCUSSION: Trajectory analysis approach provided insight into the complex associations between PFAS exposure and offspring growth. Future studies are warranted to confirm the present findings with trajectory modeling strategies and understand the clinical significance of these trajectory groups. https://doi.org/10.1289/EHP9875.

Associations between exposure to a mixture of phenols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016.

BACKGROUND: Humans are typically exposed to mixtures of environmental endocrine-disrupting chemicals simultaneously, but most studies have considered only a single chemical or a class of similar chemicals. OBJECTIVES: We examined the association of exposure to mixtures of 7 chemicals, including 2 phenols [bisphenol A (BPA) and bisphenol S (BPS)], 2 parabens [methylparaben (MeP) and propyl paraben (PrP)], and 3 phthalate metabolites [Mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), mono (carboxyoctyl) phthalate (MCOP)] with sex steroid hormones. METHODS: A total of 1179 children aged 6-19 years who had complete data on both 7 chemicals and sex steroid hormones of estradiol (E2), total testosterone (TT), and sex hormone-binding globulin (SHBG) were analyzed from the U.S. National Health and Nutrition Examination Survey 2013-2016. Free androgen index (FAI) calculated by TT/SHBG, and the ratio of TT to E2 (TT/E2) were also estimated. Puberty was defined if TT ≥ 50 ng/dL in boys, E2 ≥ 20 pg/mL in girls; otherwise prepuberty was defined. Linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were performed to estimate the associations of individual chemical or chemical mixtures with sex hormones. RESULTS: The linear regression showed that 2 phenols, 2 parabens, and 3 phthalate metabolites were generally negatively associated with E2, TT, FAI, and TT/E2, while positively with SHBG. Moreover, these associations were more pronounced among pubertal than prepubertal children. The aforementioned associations were confirmed when further applying WQS and BKMR, and the 3 phthalates metabolites were identified to be the most heavily weighing chemicals. CONCLUSIONS: Exposure to phenols, parabens, and phthalates, either individuals or as a mixture, was negatively associated with E2, TT, FAI and TT/E2, while positively with SHBG. Those associations were stronger among pubertal children.

Association of maternal exposure to perfluoroalkyl and polyfluroalkyl substances with infant growth from birth to 12 months: A prospective cohort study.

BACKGROUND: Although maternal perfluoroalkyl and polyfluroalkyl substances (PFASs) were associated with adverse birth outcomes, much less is known about their impact on infant growth during early infancy. OBJECTIVES: We investigated the association between maternal PFASs exposure and infant growth during the first 12 months of life. METHODS: Participating 2395 pregnancies were recruited from Shanghai Birth Cohort between 2013 and 2016. Ten PFASs were quantified from maternal plasma collected during early pregnancy (median, 15 gestational weeks). We measured infant length, weight, and head circumference at birth, 42 days, 6 months, and 12 months. Linear mixed regression model was used to estimate the associations between PFAS concentrations and repeated measurements of infant growth. Effect modification by infant sex was estimated. RESULTS: Elevated perfluoroheptanoic acid (PFHpA) concentration was negatively associated with infant length-for-age Z score (LAZ) (ß = -0.06, 95% confidence interval (CI): -0.11, -0.01) during the first year. Adverse associations were also observed for perfluorobutane sulfonate (PFBS) and weight-for-length Z score (WFL) (ß = -0.02, 95% CI: -0.04, -0.00) and BMI-for-age Z score (BAZ) (ß = -0.02, 95% CI: -0.04, -0.00). However, perfluorododecanoic acid (PFDoA) was positively associated with WFL (ß = 0.03, 95% CI: 0.00, 0.06) and BAZ (ß = 0.03, 95% CI: 0.00, 0.06). The adverse association of PFHpA and LAZ was more pronounced among males (ß = -0.06; 95% CI: -0.11, -0.00) than females (ß = 0.06; 95% CI: 0.01, 0.12). CONCLUSIONS: In our study, negative associations were found for maternal PFHpA exposure and infant LAZ, PFBS and WFL and BAZ. Meanwhile, maternal PFDoA exposure was positively related with WFL and BAZ. The adverse association of maternal PFHpA exposure and infant LAZ was more pronounced among males. The results should be interpreted with caution, further prospective cohort studies with longitudinal and detailed measures are warranted to confirm these findings.

Association between maternal serum concentration of perfluoroalkyl substances (PFASs) at delivery and acute infectious diseases in infancy.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent. OBJECTIVES: We investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood. METHODS: Participating 235 mother-infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively. RESULTS: The risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%-116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia. CONCLUSIONS: Exposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH. OBJECTIVES: To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH. METHODS: From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses. RESULTS: Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: -15.15, -1.97) and 5.87 (95%CI: -8.07, -3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (ß = 8.14, 95%CI: -15.39, -0.98). CONCLUSIONS: PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4.

Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation.

OBJECTIVE: To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α). METHODS: In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1ß and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot. RESULTS: In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1ß, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05). CONCLUSION: HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.

Atractylenolide­1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/c­kit signaling pathway.

Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in Sprague­Dawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide­1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow. Compared with the DGP group, atractylenolide­1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZ­induced group compared with the vehicle control group. Moreover, the STZ­induced group displayed downregulated expression levels of the DGP indicator KIT proto­oncogene, receptor tyrosine kinase (c­kit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stress­related markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide­1 significantly counteracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZ­induced DGP model rats. Further research indicated that atractylenolide­1 regulated oxidative stress reactions and improved gastric function by activating the SCF/c­kit signaling pathway. Collectively, the results of the present study suggested that atractylenolide­1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/c­kit signaling pathway, providing novel insights for the treatment of DGP.

Genetic study of a Chinese pedigree with early onset Parkinson's disease caused by novel compound heterozygous mutations in PARKIN gene.

Objective: To explore the genetic basis for a Chinese pedigree where two siblings were affected with early-onset Parkinson's disease (EOPD). Methods: Clinical examinations and genomic analyses were performed on five subjects belonging to two generations of a Han Chinese family. Target regions capture and high throughput sequencing were used to screen these genes associated with Parkinson's disease (PD), tremor, spinocerebellar ataxia, and dystonia. The multiplex ligation dependent probe amplification (MLPA) method was applied to detect rearrangements and large deletion in PARKIN exons. Results: Two family members were diagnosed with PD by clinical manifestations. Compound heterozygous mutations, consisting of a fragment deletion in exon 2 and 3 of the PARKIN gene, identified by MLPA in II-3, II-5. Individual exon2 deletion mutations were detected in II-1 while individual exon3 deletion mutations were detected in two thirds generations (III-5, III-6). The compound heterozygous mutations have co-segregated with the disease in the pedigree. Other mutations in some genes associated with PD, tremor, dystonia and other movement disorders were not detected. Conclusion: A novel compound heterozygous deletion mutations of the PARKIN gene were identified in a Chinese pedigree and might represent a cause of familial EOPD with autosomal dominant inheritance. Early-onset Parkinson's disease (PD) with PARKIN gene mutation has genetic and clinical heterogeneity.

LPS promotes the expression of PD-L1 in gastric cancer cells through NF-κB activation.

Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.

Hydrogen generation using a CuO/ZnO-ZrO2 nanocatalyst for autothermal reforming of methanol in a microchannel reactor.

In the present work, a microchannel reactor for autothermal reforming of methanol using a synthesized catalyst porous alumina support-CuO/ZnO mixed with ZrO2 sol washcoat has been developed and its fine structure and inner surface characterized. Experimentally, CuO/ZnO and alumina support with ZrO2 sol washcoat catalyst (catalyst slurries) nanoparticles is the catalytically active component of the microreactor. Catalyst slurries have been dried at 298 K for 5 h and then calcined at 623 K for 2 h to increase the surface area and specific pore structures of the washcoat catalyst. The surface area of BET N2 adsorption isotherms for the as-synthesized catalyst and catalyst/ZrO2 sol washcoat samples are 62 and 108 ± 2 m²g⁻¹, respectively. The intensities of Cu content from XRD and XPS data indicate that Al2O3 with Cu species to form CuAl2O4. The EXAFS data reveals that the Cu species in washcoat samples have Cu-O bonding with a bond distance of 1.88 ± 0.02 Å and the coordination number is 3.46 ± 0.05, respectively. Moreover, a hydrogen production rate of 2.16 L h⁻¹ is obtained and the corresponding methanol conversion is 98% at 543 K using the CuO/ZnO with ZrO2 sol washcoat catalyst.