Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis.

Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Studies on the mechanism of energy metabolism via AMPK/PGC-1α signaling pathway induced by compatibility of Ligusticum chuanxiong Hort and Gastrodia.

AMP-activated protein kinase (AMPK) regulates overall energy consumption and energy intake through cytokines. Ligusticum striatum DC (CX) combined with Gastrodia elata Blume (TM) has been used for migraine treatment for millennia. When used alone in clinical practice, CX causes symptoms of thirst, irritability, and yellow urine and has influenced the levels of cytokines such as AMP that activate the AMPK pathway of energy metabolism. However, relationships between this compatibility prescription, integral biological energy metabolism, and the AMPK pathway remain unclear. Studies were performed by treating normal rats with physiological saline, CX extract, CX coupled TM extract, and TM extracts separately for 4 weeks. Food intake, water intake, urine output, stool output, and body weight were monitored once a week by the metabolic cage method. Values of FBG, BUN, TP, TC and TG in blood samples were detected approaching the whole blood automatic detector from 1 to 4 weeks. Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cAMP, and cGMP activity were determined by the enzyme-linked immunosorbent assay (ELISA); the biological samples that were obtained at 1, 2, 3, and 4 weeks after drug administration were tested by GC-TOF-MS. Then real-time PCR and Western Blot were applied to detect changes in expression of some substances involved in energy metabolism. The results demonstrated that administering CX alone increased energy input, mobility, and respiratory exchange ratio, accelerated energy consumption, and caused inflammatory infiltration in the liver. CX coupled with TM led to lower energy metabolism and liver damage in comparison with CX used alone. Moreover, CX-treated rats harbored higher levels of differential metabolites (including pyrophosphate, oxaloacetic acid, and galactinol). Glycerophospholipid metabolism and the citrate cycle are closely related to the differential metabolites above. In addition, CX-induced unbalanced energy metabolism depends on cAMP activation mediated by the AMPK/PGC-1α pathway in rats. Our findings suggest that CX-induced energy metabolism imbalance was corrected after coupling with TM by mediating the AMPK/PGC-1α pathway.

[Contamination level and population exposure assessment of chloropropanol esters in edible vegetable oil in Shandong Province from 2016 to 2020].

OBJECTIVE: To investigate the contamination of 2-chloropropanol esters and 3-chloropropanol esters in commercial edible vegetable oils in Shandong Province, and to assess the dietary 3-chloropropanol esters exposure and the health risk of intaking 3-chloropropanol esters. METHODS: From 2016 to 2020, 406 individually packaged edible vegetable oils were collected from stores and farmers' markets in 16 prefecture-level cities in Shandong Province. According to the 2016 National Food Contamination and Harmful Factors Risk Monitoring Manual, using gas chromatography-triple quadrupole tandem mass spectrometry detection, isotope internal standard method for quantification, laboratory determination of 2-chloropropanol ester and 3-chloropropanol in vegetable oil ester content. Combined with population weight, oil consumption and monitoring data, the point assessment method was used to evaluate the exposure of residents in Shandong Province to 3-chloropropanol esters. RESULTS: The detection rate of 3-chloropropanol ester was 92.4%(375/406), the concentration range was<limit of detection(LOD)-18.4 mg/kg, the median was 0.470 mg/kg, the average was 0.833 mg/kg, and the maximum value was 18.4 mg/kg in rice oil; the detection rate of 2-chloropropanol ester was 88.7%(360/406), the concentration range was <LOD-8.46 mg/kg, the median value was 0.204 mg/kg, the average value was 0.432 mg/kg, and the maximum value was 8.46 mg/kg in rice oil. The average exposure of each age group was less than the tolerable daily intake, and the high-end exposure of the children(2-6 years old) and adolescents(7-10 years old) group was greater than the tolerable daily intake. CONCLUSION: The contamination of chloropropanol esters of edible vegetable oil in Shandong Province from 2016 to 2020 is widespread, and the highest detection value appears in rice oil. Children(2-6 years old) and adolescents(7-10 years old) in high-risk situations ingest 3-chloropropanol esters present health risks.

EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers.

BACKGROUND: A critical and challenging process in immunotherapy is to identify cancer patients who could benefit from immune checkpoint inhibitors (ICIs). Exploration of predictive biomarkers could help to maximize the clinical benefits. Eph receptors have been shown to play essential roles in tumor immunity. However, the association between EPH gene mutation and ICI response is lacking. METHODS: Clinical data and whole-exome sequencing (WES) data from published studies were collected and consolidated as a discovery cohort to analyze the association between EPH gene mutation and efficacy of ICI therapy. Another independent cohort from Memorial Sloan Kettering Cancer Center (MSKCC) was adopted to validate our findings. The Cancer Genome Atlas (TCGA) cohort was used to perform anti-tumor immunity and pathway enrichment analysis. RESULTS: Among fourteen EPH genes, EPHA7-mutant (EPHA7-MUT) was enriched in patients responding to ICI therapy (FDR adjusted P < 0.05). In the discovery cohort (n = 386), significant differences were detected between EPHA7-MUT and EPHA7-wildtype (EPHA7-WT) patients regarding objective response rate (ORR, 52.6% vs 29.1%, FDR adjusted P = 0.0357) and durable clinical benefit (DCB, 70.3% vs 42.7%, FDR adjusted P = 0.0200). In the validation cohort (n = 1144), significant overall survival advantage was observed in EPHA7-MUT patients (HR = 0.62 [95% confidence interval, 0.39 to 0.97], multivariable adjusted P = 0.0367), which was independent of tumor mutational burden (TMB) and copy number alteration (CNA). Notably, EPHA7-MUT patients without ICI therapy had significantly worse overall survival in TCGA cohort (HR = 1.33 [95% confidence interval, 1.06 to 1.67], multivariable adjusted P = 0.0139). Further gene set enrichment analysis revealed enhanced anti-tumor immunity in EPHA7-MUT tumor. CONCLUSIONS: EPHA7-MUT successfully predicted better clinical outcomes in ICI-treated patients across multiple cancer types, indicating that EPHA7-MUT could serve as a potential predictive biomarker for immune checkpoint inhibitors.

Association between cigarette smoking and colorectal cancer sidedness: A multi-center big-data platform-based analysis.

BACKGROUND: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. METHODS: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. RESULTS: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. CONCLUSIONS: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

Meta-analysis of genotype and phenotype studies to confirm the predictive role of the RNF213 p.R4810K variant for moyamoya disease.

BACKGROUND AND PURPOSE: The aim of this meta-analysis study was to assess the predictive effects of RNF213 p.R4810K on phenotype in moyamoya disease (MMD). METHODS: Electronic databases (e.g., Pubmed and EMBASE) were searched, and relevant articles published up to August 2020 were retrieved. Review Manager 5.3 and Stata 12.0 were used for all statistical analyses. Pooled odds ratios, with 95% confidence intervals, and three comparison models were evaluated to analyze the association between RNF213 pR4810K variant and clinical characteristics of MMD patients using a fixed-effects model. RESULTS: A total of 2798 patients with MMD were selected and the effects of the heterozygous or homozygous RNF213 p.R4810K variant on 18 clinical features were identified. There were more patients aged <15 years in the GA and AA groups (AA vs GA: p = 0.009; AA vs GG: p = 0.003; GA vs GG: p = 0.001). Among homozygous patients, the majority experienced MMD onset before the age of 4 years (AA vs. GA: p < 0.00001; AA vs GG: p < 0.00001). The frequency of infarctions and transient ischemic attack was significantly higher in homozygotes and heterozygotes，respectively. However, the frequency of intracerebral/intraventricular hemorrhage was lower in patients with the GA than the GG genotype. More MMD patients with AA and GA genotypes had a family history of the disease (p = 0.003, p < 0.00001, respectively). Posterior cerebral artery involvement was more common in patients with the GA genotype (p < 0.00001). CONCLUSION: The homozygous or heterozygous RNF213 variant may be an efficient biomarker with which to classify different clinical phenotypes of MMD.

Association of Genetic Variants With Moyamoya Disease in 13 000 Individuals: A Meta-Analysis.

Background and Purpose- A growing body of evidence indicates genetic components play critical roles in moyamoya disease (MMD). Firm conclusions from studies of this disease have been stymied by small sample sizes and a lack of replicative results. This meta-analysis was conducted to determine whether these genetic polymorphisms are associated with MMD. Methods- PubMed, Google Scholar, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify potentially relevant studies published until January 2020. The Review Manager 5.2 and Stata 15.0 software programs were used to perform the statistical analysis. Heterogeneity was assessed using the Cochran Q test and quantified using the I2 test. Results- Four thousand seven hundred eleven MMD cases and 8704 controls in 24 studies were included, evaluating 7 polymorphisms in 6 genes. The fixed-effect odds ratios (95% CI) in allelic model of MMP-2 rs243865 were 0.60 (0.41-0.88) (P=0.008). In the country-based subgroup analysis, the fixed-effect odds ratios (95% CI) of RNF213 rs112735431 in allelic model were China, 39.74 (26.63-59.31), Japan, 74.65 (42.79-130.24) and Korea, 50.04 (28.83-86.88; all P<0.00001). In the sensitivity analysis, the fixed-effect odds ratios (95% CI) of allelic and dominant models were the RNF213 rs148731719 variant, 2.17 (1.36-3.48; P=0.001), 2.20 (1.35-3.61; P=0.002), the TIMP-2 rs8179090 variant, 0.33 (0.25-0.43; P<0.00001), 0.88 (0.65-1.21; P=0.440) and the MMP-3 rs3025058 variant, 0.61 (0.47-0.79; P=0.0002), 0.55 (0.41-0.75; P=0.0001), respectively. Conclusions- RNF213 rs112735431 and rs148731719 were positively, and TIMP-2 rs8179090, MMP-2 rs243865, and MMP-3 rs3025058 were inversely associated with MMD using multiple pathophysiologic pathways. Studies in larger population should be conducted to clarify whether and how these variants are associated with MMD.

Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis.

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03-1.83) and homozygous model (OR=1.54, 95% CI=1.15-2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18-2.42; homozygous: OR=1.99, 95% CI=1.38-2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02-1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.

Association of MTHFR gene polymorphisms with pancreatic cancer: meta-analysis of 17 case-control studies.

BACKGROUND: Pancreatic cancer (PC) is a seriously malignant tumor with a low 5-year survival rate. The relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and PC has been reported by several studies. However, the results were controversial. Thus, we conducted a meta-analysis to summarize available data on MTHFR gene and PC. METHODS: We searched PubMed, Embase, Web of Science, Wanfang, CNKI databases prior to July 2019. Data were analyzed by RevMan 5.3 and STATA 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the association. Subgroup analysis, sensitivity analysis and assessment of publication bias were performed in this study. RESULTS: Ten articles with 17 reports (10 for C677T, 7 for A1298C) were eligible for inclusion in the meta-analysis (1864 cases and 3165 controls for C677T, and 1488 cases and 1946 controls for A1298C). Our meta-analysis detected that C677T was associated with PC for three genetic models (allele model: OR = 1.24, 95% CI: 1.00-1.53, P = 0.047; recessive model: OR = 1.39, 95% CI: 1.04-1.86, P = 0.027; homozygous model: OR = 1.60, 95% CI: 1.04-2.45, P = 0.034). In the stratified analyses according to ethnicity, source of controls and genotyping method, significant association was observed in genotyping method subgroup. For the A1298C polymorphism, no significant association was observed either in overall analysis or in subgroup analysis under all genetic models. CONCLUSIONS: MTHFR gene C677T rather than A1298C polymorphism may be associated with PC. Larger sample size studies should be performed to find the association between MTHFR gene and PC.

RNF213 p.R4810K Polymorphism and the Risk of Moyamoya Disease, Intracranial Major Artery Stenosis/Occlusion, and Quasi-Moyamoya Disease: A Meta-Analysis.

BACKGROUND: Accumulating studies have reported that there is an association between the Ring finger protein 213 (RNF213) p.R4810K (rs112735431, c.14576G>A) single nucleotide polymorphism and the predisposition of moyamoya disease (MMD), intracranial major artery stenosis/occlusion (ICASO), quasi-moyamoya disease (quasi-MMD), and other vascular diseases. However, to this day, analyses about this association have remained scarce in the literature. We attempted to conduct a meta-analysis to systematically summarize and clarify the issue. METHODS: Electronic databases dated up to January 2018 were searched, retrieved, and used. Revman 5.2 software and STATA version 12.0 were used for statistical analysis. The association between RNF213 p.R4810K and MMD, ICASO, and quasi-MMD were assessed by odds ratios and 95% confidence intervals using fixed effects models. Between-study heterogeneity was evaluated by I-squared (I2) statistics and sensitivity analysis was performed by omitting 1 study at a time. A funnel plot and Begg's test were used to assess the potential publication bias. RESULTS: The outcomes showed a statistically significant association between RNF213 p.R4810K and MMD, ICASO, and quasi-MMD, especially in the dominant model. Apart from the first 2 diseases, no significant association was identified under the recessive, the homozygote, and the heterozygote models in ICASO. CONCLUSIONS: RNF213 p.R4810K was associated with MMD, ICASO, and quasi-MMD in different genetic models. Subgroup analysis indicated highly significantly higher risk in the Japanese patients. However, further well-designed studies with larger sample size and comprehensive data are needed to confirm our findings and provide a profound conclusion.

A Meta-Analysis of the Association between Microrna-196A2 and Risk of Ischemic Stroke and Coronary Artery Disease in Asian Population.

OBJECT: Single nucleotide polymorphisms (SNPs) of small non-coding RNAs (sncRNAs) that affect the sncRNA function and target gene expression to mediate the risk of certain diseases. The association between the miR-196a2 rs11614913 and ischemic stroke (IS) and coronary artery disease (CAD) is still conflicting and inconclusive. This meta-analysis aimed at analysing studies which have been done so far to get a more precise assessment of the association between the mutation and these two diseases. METHODS: Electronic databases dated up to April 2018 were searched, retrieved and used. Revman 5.2 software and STATA version 12.0 were used for statistical analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to identify any potential associations. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. RESULTS: The overall meta-analysis results showed that miR-196a2 rs11614913 T > C polymorphism was significantly associated with CAD risk in certain genetic models, as well as in subgroup analysis (CC versus TT, OR = .43, 95%CI = .39-.47, P < .00001). However, no significant association was detected between the miR-196a2 rs11614913 T > C and IS risk in all genetic models. CONCLUSIONS: Our study suggests that miR-196a2 rs11614913 T > C may contribute to CAD susceptibility but further well-designed studies with larger sample size and comprehensive data are needed to confirm our findings and provide a profound conclusion.

Nitrogen Addition and Heterotroph Exclusion Affected Plant Species Diversity-Biomass Relationship by Affecting Plant Functional Traits.

(1) Background: Heterotrophs can affect plant biomass and alter species diversity-productivity relationships. However, these studies were conducted in systems with a low nitrogen (N) availability, and it is unclear how heterotroph removal affects the relationship between plant species diversity and productivity in different N habitats. (2) Methods: Three typical understory herbaceous plants were selected to assemble the plant species diversity (three plant species richness levels (1, 2, and 3) and seven plant species compositions), and the control, insecticide, fungicide, and all removal treatments were performed at each plant species diversity level in systems with or without N addition treatments. (3) Results: In systems without N addition, the insecticide treatment increased the plant aboveground biomass, total biomass, and leaf area, while the fungicide treatment reduced the plant belowground biomass, root length, and root tip number; the presence of Bidens pilosa increased the plant aboveground biomass. Similarly, the presence of Bletilla striata increased the plant belowground biomass and root diameter under each heterotroph removal treatment. In systems with N addition, all removal treatments reduced the plant belowground biomass and increased the plant leaf area; the presence of B. pilosa significantly increased the plant aboveground biomass, total biomass, and root length under each heterotroph removal treatment. The presence of B. striata significantly increased the plant belowground biomass and leaf area under insecticide and fungicide treatments. (4) Conclusions: Heterotroph removal alters the plant species diversity-biomass relationship by affecting the plant functional traits in systems with different N availabilities. The impact of biodiversity at different trophic levels on ecosystem functioning should be considered under the background of global change.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Heavy metals in meat products from Shandong, China and risk assessment.

In this study 13 heavy metals were analysed in representative livestock meat, poultry meat, livestock offal and poultry offal samples (20 per category) from marketplaces and retail stores in 16 cities in Shandong province, China. The investigated heavy metals were Cu, Cr, V, Ni, As, Se, Sn, Cd, Pb, Sb, Mn, Ba and Hg. Results revealed mean levels of total heavy metals in meat and offal of 1.56 mg/kg and 39.8 mg/kg, respectively. Cu, Cr, Mn, Ni, Se, Ba and Pb were found in all samples (100%), followed by Hg (95.0%), V (91.3%), Sn (73.8%), Cd (51.3%), As (21.3%) and Sb (11.3%). Hazard Quotient (HQ) and Hazard Index (HI) values showed that high meat intake can cause potential health risks. Thus, continuous monitoring of health risks and trends of heavy metals in meat products is needed, both for food safety and consumer's health.

Decoction regulating phytochemicals' micromorphology changes and anti-inflammation activity enhancements originated from herb medicine supermolecules.

BACKGROUND: Mahuang Fuzi decoction (MGF) is composed of three herb medicines that has been clinically used to treat inflammatory diseases for a long history. At present, more and more active phytochemicals' aggregations have been found during the thermodynamic process of herb medicine decoction, and revealing the clinical efficacy of herb medicine through supramolecular strategies is the focus of current research. However, it is not clear whether decoction induced supermolecules' morphological changes to modify activity. METHODS: Dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) were used to analyze the micromorphology of MGF, MGF SA (MGF supermolecules), and MIX (physical mixture of MGF single decoction). The interaction and thermodynamic parameters of single herbs in a decoction were investigated by Isothermal titration calorimetry (ITC). The phytochemicals were systematically analyzed by ultra high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). Under the safe dose on RAW264.7 cells, NO, IL-6 and TNF-α were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA) method. NF-κB p65 translocation from the cytoplasm into the nucleus was examined using the immunofluorescence assay and the western blot, respectively. Furthermore, Metabolomics was used to discover potential biomarkers and the associated metabolic pathways of MGF SA treatment. RESULTS: There were nanoscale aggregations in MGF, and the micromorphology of the extracted MGF SA consisted of uniform particles; while the MIX micromorphology had no uniformity. ITC showed that the interaction MH-GC and FZ-GC were a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly. Though the micromorphology between MGF, MGF SA, and MIX was obviously different, UHPLC-Q-Orbitrap HRMS results displayed that the main phytochemicals of MGF and MIX had nearly the same components. Interestingly, MGF and MGF SA could significantly inhibit the production of NO, and had better inhibition effect on the expression of nuclear protein NF-κB p65 than MIX, among which MGF SA had the best effect. Further investigation indicated that the perturbance of metabolic profiling in RAW264.7 inflammatory cells was obviously reversed by MGF SA. CONCLUSIONS: The decoction enriched the key active phytochemicals and regulated the formation of homogeneous nanoparticles in MGF SA. The supermolecules in MGF SA significantly enhanced its anti-inflammatory activity, primarily affecting the NF-κB signaling pathway and the biosynthesis and metabolism of arginine in RAW264.7 inflammatory cells. Current study displayed that co-decocting herbal medicine were beneficial to the treatment of diseases than the mixture of the single herbs' extraction.

Per- and polyfluoroalkyl substances (PFASs) in bivalve molluscs from Shandong Province, China: Occurrence, distribution, and implications for human consumption.

We examined the occurrence and levels of 19 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in 7 species of marine bivalve molluscs collected from four coastal cities of Shandong Province, China. Perfluorooctanoic acid (PFOA) was the most prevalent component, accounting for 68.1 % of total PFASs. The total PFASs in bivalve molluscs ranged from 0.86 to 6.55 ng/g wet weight, with the highest concentration found in Meretrix meretrix L. The concentration of total PFASs in bivalve molluscs showed the following trend: clams > scallops > oysters > mussels. Estimation on the human intake of PFASs from consumption of bivalve molluscs resulted in hazard ratios (HR) ranging from 0.12 to 6.40. Five of the seven species had HR >1, indicating high exposure risks associated with PFASs. Therefore, the occurrence of PFASs in marine biota is particularly concerning and further investigations on the sources of PFASs in Shandong are warranted.

Self-assembly variation of glycyrrhetinic acid epimers: Assembly mechanism and antibacterial efficacy between 18 α-GA and 18 ß-GA.

Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 ß-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 ß-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a "head-to-head" manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials.

Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds.

ABSTRACT: The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

Intra-articular delivery system of methotrexate for rheumatoid arthritis therapy: An in-suit thermosensitive comprehensive gel of polysaccharide from Aconitum carmichaelii Debx.

The polysaccharides (FP) extracted from the lateral roots of Aconitum carmichaelii Debx. (Fuzi) are natural compounds, which have effective therapy for rheumatoid arthritis (RA). Methotrexate (MTX) is the first-line drug for RA, but its application is greatly limited to the toxicity in liver and kidney and drug resistance. In this study, an attempt is made to apply oxidized FP (OFP) as a polymer carrier based on intra-articular delivery system loaded MTX. The FP could be modified and used as comprehensive gel carriers with biocompatibility and degradability for therapy of RA. Firstly, OFP-chitosan-poloxamer 407 in situ gel (OFP-CS-F407-MTX gel) was prepared by natural non-toxic cross-linking agents. Physicochemical characterization was performed by using 1H NMR and FTIR spectroscopic techniques to assess the successful functionalization of OFP. TGA, SEM and rheological experiment of OFP-CS-F407-MTX gel were investigated. Notably, we loaded MTX into OFP-CS-F407-MTX gel which had remarkable therapeutic efficacy and biosafety for RA. Therefore, OFP-CS-F407-MTX in situ gel delivery system can potentially reduce systemic toxicity and irritation of oral administration of MTX but hold a controlled release of drug for a long period of time.