The checkmark association between gamma glutamyl-transpeptidase and body mass index in a large Chinese population.

BACKGROUND: Obesity has long been regarded as a risk factor for abnormal liver function, although the quantitative relationship between them is not clear. This study aimed to investigate the relationship between body mass index (BMI) and gamma-glutamyl transpeptidase (GGT) in different gender populations. METHODS: The cross-sectional study included 221,934 people aged over 18 years and under 90 years who underwent physical examinations at Yijishan Hospital in Wuhu City from 2011 to 2016. t-test and Chi-square test were used to compare the differences in demographic characteristics and biochemical indexes between men and women. Linear regression model and smooth curve method were used to investigate the relationship between BMI and GGT. RESULTS: The smooth curve shows a checkmark association between GGT and BMI. After adjusting for confounders, the cut-off BMI for the whole population was 19.5 kg/m2. When BMI was less than 19.5 kg/m2, GGT levels decreased with increasing BMI, and when BMI was greater than 19.5 kg/m2, GGT levels increased with increasing BMI. After gender stratification, there was a checkmark association between male and female GGT levels and BMI, but the trend of male GGT levels changing with BMI was more obvious than that of females. CONCLUSIONS: Our investigation demonstrated that the GGT level in obese Chinese people is significantly higher than that in non-obese people living in Wuhu City. BMI level can be considered as an early warning index for diseases related to liver function injury in the clinic, although the influence of gender difference should be specifically considered.

Malinzi, a traditional medicinal plants: Comprehensive review of botany, medical application, chemical composition, and pharmacology.

Malinzi is the dry ripe seed of Iris Lactea Pall. var. chinensis (Fisch.) Koidz and is a tradtional medicinal plant with significant development and utilization value. A total of 31 compounds from Malinzi have been reported, including flavonoids, quinones, oligostilbenes, and other constituents. Modern pharmacological studies have shown that Malinzi has good activities in anti-tumor, radio-sensitization, boost immunity, anti-oxidation, anti-fertility, and glucolipid metabolism. In this paper, by reviewing the domestic and foreign research literatures of Malinzi and summarizing its traditional uses, chemical constituents, and pharmacological activities, it is expected to provide theoretical reference for the subsequent in-depth research and application of Malinzi.

Dyslipidemia and hyperuricemia: a cross-sectional study of residents in Wuhu, China.

BACKGROUND: While dyslipidemia has been recognized as a potential risk factor for hyperuricemia, there is currently a dearth of large-scale data specifically focused on studying the relationship between these two conditions. To address this gap, the present study analyzed a dataset of 298,891 physical examination records to investigate in greater detail the clinical classification and compositional relationship between hyperuricemia and dyslipidemia. METHODS: For this investigation, a cross-sectional research design was utilized to analyze physical examination data that was gathered from Yijishan Hospital in Wuhu, China between 2011 and 2016. Logistic regression was employed to examine the association between hyperuricemia and dyslipidemia. Furthermore, the association between hyperuricemia and dyslipidemia was evaluated based on the clinical classifications of dyslipidemia and its components. RESULTS: A total of 298,891 participants from China (124,886 [41.8%] females) were included in the study, with an age range of 18 to 90 years (mean [SD]: 47.76 [13.54] years). In multivariate analysis, the odds of hyperuricemia was 1.878 times higher in patients with dyslipidemia compared to those without dyslipidemia (95% confidence interval [CI]: 1.835-1.922). In the clinical classification of dyslipidemia, individuals with hypertriglyceridemia and mixed hyperlipidemia had 1.753 times (95% CI: 1.706-1.802) and 1.925 times (95% CI: 1.870-1.982) higher odds of hyperuricemia, respectively, compared to those without dyslipidemia. Among the components of dyslipidemia, the odds ratios for hyperuricemia in individuals in the fourth quartile compared to those in the first quartile were 3.744 (95% CI: 3.636-3.918) for triglycerides, 1.518 (95% CI: 1.471-1.565) for total cholesterol, and 1.775 (95% CI: 1.718 - 1.833) for non-high-density lipoprotein cholesterol. CONCLUSIONS: Dyslipidemia has been independently linked with hyperuricemia. Moreover, the elevation of triglycerides or total cholesterol levels, including conditions such as hypertriglyceridemia and mixed hyperlipidemia, have been observed to have a positive association with the development of hyperuricemia.

Risk factors of venous thromboembolism for liver tumors: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a significant complication in liver tumors patients, and understanding the associated risk factors is essential for effective risk assessment, prevention, and management strategies. This systematic review and meta-analysis aimed to identify key risk factors and their clinical implications for VTE in liver tumors patients. METHODS: A comprehensive search of multiple databases was conducted to identify relevant studies. Eligible studies were selected, and odds ratios (ORs) and 95% confidence intervals (CIs) were extracted and synthesized for meta-analysis. RESULTS: A total of 11 studies involving 73,652 liver tumors patients and 2049 VTE cases were included. The analysis identified several significant risk factors for VTE in liver tumors patients. Age (≥65 years), male gender, high BMI, diabetes, hepatitis B and C infections, elevated D-dimer and AST levels, reduced albumin levels, and MELD score were all associated with increased VTE risk. CONCLUSION: This systematic review and meta-analysis revealed several key risk factors for VTE in liver tumors patients, these findings highlight the importance of risk assessment, prevention, and management strategies in this high-risk population. Further research with larger sample sizes and standardized methods is needed to strengthen the existing evidence and validate these findings.

Clinical development and informatics analysis of natural and semi-synthetic flavonoid drugs: A critical review.

BACKGROUND: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. AIM OF REVIEW: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. KEY SCIENTIFIC CONCEPTS OF REVIEW: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

Comprehensive survey of target prediction web servers for Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) is characterized by multi-components, multiple targets, and complex mechanisms of action and therefore has significant advantages in treating diseases. However, the clinical application of TCM prescriptions is limited due to the difficulty in elucidating the effective substances and the lack of current scientific evidence on the mechanisms of action. In recent years, the development of network pharmacology based on drug systems research has provided a new approach for understanding the complex systems represented by TCM. The determination of drug targets is the core of TCM network pharmacology research. Over the past years, many web tools for drug targets with various features have been developed to facilitate target prediction, significantly promoting drug discovery. Therefore, this review introduces the widely used web tools for compound-target interaction prediction databases and web resources in TCM pharmacology research, and it compares and analyzes each web tool based on their basic properties, including the underlying theory, algorithms, datasets, and search results. Finally, we present the remaining challenges for the promising future of compound-target interaction prediction in TCM pharmacology research. This work may guide researchers in choosing web tools for target prediction and may also help develop more TCM tools based on these existing resources.

Impact of carotid hemodynamics on carotid plaque location: Age difference.

PURPOSE: This study was aimed to investigate the influence of carotid hemodynamics in common carotid artery (CCA) and internal carotid artery (ICA) on carotid plaque location. METHODS: A total of 4444 participants from Anhui Maanshan People's Hospital were selected from December 2013 to December 2018. Doppler ultrasound was used to measure the location of carotid plaque. Patients were divided into four groups according to plaque location: LEFT, RIGHT, BOTH, and NONE. Multiple logistic regression and smooth curve were applied to determine the relationship of carotid plaque location and hemodynamic indexes. RESULTS: Compared with the NONE group, the ratio of artery systolic and diastolic blood flow velocity in right internal carotid (RICA S/D) was a risk factor for LEFT group (OR=1.548) after adjustment; artery systolic and diastolic blood flow velocity ratio of left common carotid artery (LCCA S/D) was a risk factor for RIGHT group (OR=1.250); resistance index of right internal carotid (RICA RI) was a protective factor for BOTH group (OR=0.097), while LCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.201, OR=1.457). Compared with the RIGHT group, artery systolic and diastolic blood flow velocity ratio of right common carotid (RCCA S/D) was the risk factor for the LEFT group (OR=1.463), LCCA S/D and RICA S/D were the risk factors for BOTH group (OR=1.706, OR=2.111). After age stratification, resistance index of right common carotid artery (RCCA RI) and resistance index of left internal carotid artery (LICA RI) were protective factors for BOTH group (OR=0.046, OR=0.042) in group younger than 52. RCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.557, OR=1.843). Resistance index of left common carotid artery (LCCA RI) was a protective factor in the LEFT group compared with the RIGHT group (OR=0.476). In group older than 52, RICA S/D was a risk factor for LEFT group (OR=1.388). LCCA S/D was a risk factor for RIGHT group (OR=1.575). LCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.348, OR=1.311). RICA S/D and RCCA S/D were protective factors in the LEFT group compared with the RIGHT group (OR=0.567, OR=0.680).

Gender-based relationship between serum creatinine and carotid plaque stability: A cross-sectional study in China.

OBJECTIVE: Carotid plaque instability is a risk factor for ischemic stroke, and changes in serum creatinine are associated with carotid plaque. However, the relationship between serum creatinine and carotid plaque stability is not well explained. This study aimed to interpret this relationship for clinical treatment of carotid plaque. METHODS: A total of 4363 subjects aged 29-86 from December 2013 to December 2018 were included in this study. The stability of carotid plaque was determined based on ultrasound echoes and divided into two groups: carotid plaque stable group and carotid plaque unstable group. The relationship between serum creatinine and carotid plaque stability was determined using curve fitting methods as well as logistic regression. RESULTS: After age stratification, there was an inverted U-shaped curve between the stability of right carotid plaque and serum creatinine in males, When serum creatinine levels were less than 84 µmol/L, the probability of carotid plaque instability gradually increased, and the carotid plaque became stable when creatinine levels were greater than 84 µmol/L. The relationship between left carotid female plaque stability and serum creatinine showed a U-shaped curve. When serum creatinine levels were less than 80 µmol/L, the carotid plaque stability stabilized, and the probability increased when creatitine levels were more than 80 µmol/L, as the carotid plaque instability rose. CONCLUSION: There was an inverted U-shaped relationship between the stability of carotid plaque in the right carotid artery and serum creatinine in males, and a U-shaped relationship between the stability of carotid plaque in the left carotid artery and serum creatinine in females.

The V-shaped curve relationship between fasting plasma glucose and human serum albumin in a large health checkup population in China.

BACKGROUND: This study aimed to investigate the relationship between fasting plasma glucose (FPG) and human serum albumin (HSA) in a large health checkup population in China. METHODS: In this cross-sectional health checkup study, we enrolled a population of 284,635 subjects from Wuhu between 2011 and 2016. All participants completed the physical examination, blood biochemical examination, and blood routine examination. RESULTS: The prevalence of diabetes in men and women was 6.11% and 2.98%, respectively. The average level of HSA and FPG was significantly higher in men than in women (48.44 ± 3.25 vs. 47.14 ± 3.22, P < 0.0001; 5.50 ± 1.26 vs. 5.26 ± 0.94, P < 0.0001). There were significant differences in blood biochemistry and blood routine values by gender. After adjusting for confounding factors, the results showed that FPG and HSA were a V-shaped curve, and the threshold value of HSA was 40.7 mmol/L. FPG and HSA still showed a V-shaped curve after stratification by gender and age. In the male group, FPG decreased with HSA when HSA<42.3 mmol/L, and increased when HSA ≥ 42.3 mmol/L. In the female group, FPG decreased with HSA when HSA<35.7 mmol/L, and increased when HSA ≥ 35.7 mmol/L. In the age<65 group, FPG decreased with HSA when HSA<37.5 mmol/L, and increased when HSA ≥ 37.5 mmol/L. In the age ≥ 65 group, FPG decreased with HSA when HSA<43.2 mmol/L, and increased when HSA ≥ 43.2 mmol/L. CONCLUSIONS: A V-shape relationship exists between fasting plasma glucose and human serum albumin among the Chinese health checkup population studied.

Propofol Regulates HIF-1 α Effect of Expression of Targeted SIRT1 Signal pathway on Kidney Renal Clear Cell Carcinoma.

The objective of this study was to investigate the effect of propofol on kidney renal clear cell carcinoma (KIRC) by regulating hypoxia-inducible factor-1α (HIF-1α) expression and silencing signal regulatory factor 1 (SIRT1) signal pathway. In this regard, human KIRC cell line RCC4 was added into 0, 5 and 10 µ G/ml propofol treatment and was divided into a control group (CG), low dose group (LG) and high dose group (HG). CCK8 was used to detect the proliferative ability of the three groups of cells, ELISA was used to detect the level of inflammatory factors in the cells, Western blot was used to detect the protein expression, qPCR was used to detect the related mRNA expression level, and Transwell method was used to detect the invasive ability of the cells in vitro. The experimental results showed that propofol decreased the proliferation and invasion ability of KIRC cells, up-regulated the expression of TGF- ß 1, IL-6, TNF- α, HIF-1 α, Fas, bax and FasL, and down-regulated the expression of SIRT1 in a dose-dependent manner. It was concluded that propofol can inhibit the SIRT1 signal pathway by up-regulating the level of HIF-1α in KIRC, which can significantly decrease the proliferation and invasion ability of KIRC cells, induce apoptosis and increase the release of intracellular inflammatory factors.

A novel aptamer-G-quadruplex/hemin self-assembling color system: rapid visual diagnosis of invasive fungal infections.

BACKGROUND: The clinical symptoms of invasive fungal infections (IFI) are nonspecific, and early clinical diagnosis is challenging, resulting in high mortality rates. This study reports the development of a novel aptamer-G-quadruplex/hemin self-assembling color system (AGSCS) based on (1 → 3)-ß-D-glucans' detection for rapid, specific and visual diagnosis of IFI. METHODS: We screened high affinity and specificity ssDNA aptamers binding to (1 → 3)-ß-D-glucans, the main components of cell wall from Candida albicans via Systematic Evolution of Ligands by EXponential enrichment. Next, a comparison of diagnostic efficiency of AGSCS and the (1 → 3)-ß-D-glucans assay ("G test") with regard to predicting IFI in 198 clinical serum samples was done. RESULTS: Water-soluble (1 → 3)-ß-D-glucans were successfully isolated from C. albicans ATCC 10,231 strain, and these low degree of polymerization glucans (< 1.7 kD) were targeted for aptamer screening with the complementary sequences of G-quadruplex. Six high affinity single stranded DNA aptamers (A1, A2, A3, A4, A5 and A6) were found. The linear detection range for (1 → 3)-ß-D-glucans stretched from 1.6 pg/mL to 400 pg/mL on a microplate reader, and the detection limit was 3.125 pg/mL using naked eye observation. Using a microplate reader, the sensitivity and specificity of AGSCS for the diagnosis of IFI were 92.68% and 89.65%, respectively, which was higher than that of the G test. CONCLUSION: This newly developed visual diagnostic method for detecting IFI showed promising results and is expected to be developed as a point-of-care testing kit to enable quick and cost effective diagnosis of IFI in the future.

Vitex rotundifolia L. f. and Vitex trifolia L.: A review on their traditional medicine, phytochemistry, pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex rotundifolia L. f. and Vitex trifolia L. belong to the genus Vitex, and Vitex rotundifolia L. f. evolved from Vitex trifolia L. Both are essential ethnic medicinal plants with a long history, commonly used to treat headaches, fever, diarrhea, hair loss, wound recovery, and other diseases. AIM OF THE REVIEW: The research status of Vitex trifolia L. and its relative species Vitex rotundifolia L. f. were reviewed from the aspects of traditional medicinal use, phytochemistry, and pharmacological activities, to provide a reference for the further development and utilization of Vitex rotundifolia L. f. and Vitex trifolia L. MATERIALS AND METHODS: In this paper, a comprehensive search of published literature was conducted through various books and online databases to obtain relevant information on Vitex rotundifolia L. f. and Vitex trifolia L. The search terms "(Vitex rotundifolia) OR (Vitex trifolia) OR (Fructus viticis)" were entered in PubMed, Web of Science, China national knowledge infrastructure (CNKI), Wanfang Data, Baidu Scholar, respectively. In addition to setting the year threshold of "2018-2022" on Baidu Scholar, other databases searched all fields and found 889, 283, 1263, 1023, and 147 articles, respectively. Among them, review, repetition, overlapping data, and other reasons were excluded, and finally, a total of 164 articles were included in the review study. RESULTS: A total of 369 compounds have been identified, including 159 terpenoids, 51 flavonoids, 83 phenylpropanoids, and 76 other compounds. Pharmacological studies have shown that Vitex rotundifolia L. f. and Vitex trifolia L. have a variety of pharmacological activities, such as anti-tumor, analgesic, antipyretic, anti-inflammatory, antioxidant, antibacterial, and estrogen-like activity. Modern clinical use for treating cold headaches, diarrhea dysentery, irregular menstruation, and other diseases. CONCLUSIONS: As traditional medicinal plants, Vitex rotundifolia L. f. and Vitex trifolia L. have wealthy chemical constituents and extensive pharmacological activities and are widely used in clinical practice from traditional to modern times. However, the research on the pharmacological activities of Vitex rotundifolia L. f. and Vitex trifolia L. is not in-depth, and the potential active components still need to be explored.

The mutation rate of rpoB gene showed an upward trend with the increase of MIRU10, MIRU39 and QUB4156 repetitive number.

BACKGROUND: Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) is a frequently used typing method for identifying the Beijing genotype of Mycobacterium tuberculosis (Mtb), which is easily transformed into rifampicin (RIF) resistance. The RIF resistance of Mtb is considered to be highly related with the mutation of rpoB gene. Therefore, this study aimed to analyze the relationship between the repetitive number of MIRU loci and the mutation of rpoB gene. METHODS: An open-source whole-genome sequencing data of Mtb was used to detect the mutation of rpoB gene and the repetitive number of MIRU loci by bioinformatics methods. Cochran-Armitage analysis was performed to analyze the trend of the rpoB gene mutation rate and the repetitive number of MIRU loci. RESULTS: Among 357 rifampicin-resistant tuberculosis (RR-TB), 304 strains with mutated rpoB genes were detected, and 6 of 67 rifampicin susceptible strains were detected mutations. The rpoB gene mutational rate showed an upward trend with the increase of MIRU10, MIRU39, QUB4156 and MIRU16 repetitive number, but only the repetitive number of MIRU10, MRIU39 and QUB4156 were risk factors for rpoB gene mutation. The Hunter-Gaston discriminatory index (HGDI) of MIRU10 (0.65) and QUB4156 (0.62) was high in the overall sample, while MIRU39 (0.39) and MIRU16 (0.43) showed a moderate discriminatory Power. CONCLUSION: The mutation rate of rpoB gene increases with the addition of repetitive numbers of MIRU10, QUB4156 and MIRU39 loci.

Age and sex trend differences in hemoglobin levels in China: a cross-sectional study.

BACKGROUND: Both age and gender are the influence factors of hemoglobin concentration. However, the changing trend of hemoglobin levels between males and females with age remains unclear. This study aimed to explore their changing characteristics in different genders. METHODS: A cross-sectional study was conducted in Physical Examination Center of the First Affiliated Hospital of Wannan Medical College in Wuhu, China from 2014 to 2016. The generalized linear model was applied to explore the relationship between age, gender and hemoglobin levels. RESULTS: Among the 303,084 participants, the mean age for females and males was 46.9 ± 13.4(15-98) and 48.1 ± 13.7(14-98) years old, respectively. Generalized smoothing splines showed that hemoglobin levels increased up to age 25 and then decreased in men; in women the levels increased up until age 20, and then decreased, with slight increase again (ß = 0.244, P < 0.01). After dividing all participants into hyperglycemia and normal groups, only the normal female group showed a significant upward trend (ß = 0.257, P < 0.01) between ages 50-59. CONCLUSIONS: Hemoglobin concentration changes with age and the curve is different in males and females. The slightly upward trend of female hemoglobin in the age range of 50-59 years old should be considered in developing the reference range of hemoglobin making.

Discovery of natural polyphenols from the wild vegetable Suaeda salsa L. with potential cardioprotective functions.

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1-14), eight phenolic acids (15-22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27-29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1-5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3-5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.

A bibliometric and visualization-based analysis of temozolomide research hotspots and frontier evolution.

The literature related to TMZ research in the Web of Science (WOS) database was analyzed using bibliometrics and visualization by Citespace and VOSviewer.The publication status (number of publications, institutions, and frequency of citations), collaborations, and research focus was analyzed to clarify the current situation of TMZ research. And the recent research on TMZ provides a detailed summary. Based on objective data analysis, this study provides a complete analysis portraying the progression of historical milestones in TMZ development and future research directions from various TMZ research domains.

Association between the Triglyceride-Glucose Index and the Risk of Large Artery Atherosclerotic Stroke.

The aim of this study is to evaluate the value of the triglyceride-glucose (TyG) index and the risk of large artery atherosclerotic (LAA) stroke. Information on general demographic and clinical characteristics, magnetic resonance angiography (MRA) examination, and blood biochemical index determination were obtained. Based on age stratification, three models to evaluate the odds ratio (OR) and the 95% confidence interval (95% CI) were employed to determine the correlation between the TyG index and the risk of LAA stroke. The most effective TyG index threshold in predicting a high risk of LAA stroke was identified using receiver operating characteristic (ROC) curve analysis. Logistic regression verified the association between the risk of LAA stroke and the TyG index. Both with and without age stratification, logistic regression analysis showed that the TyG index was a significant predictor of the occurrence of LAA stroke (P < 0.05). The maximum Youden index for determining a high risk of LAA stroke was found at a TyG index of 4.60. The area under the ROC curve was 0.69 (95% CI: 0.646-0.742, P < 0.05), sensitivity was 78.0%, and specificity was 63.4%. An elevated TyG index was remarkably associated with a high risk of LAA stroke.

Rural environment reduces allergic inflammation by modulating the gut microbiota.

Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.

Inhibition of miR-495-3p ameliorated sevoflurane induced damage through BDNF/ERK/CREB signaling pathways in HT22 cells.

OBJECTIVE: Sevoflurane is used in anesthesia for surgery including in organ transplantation. We investigated the role of a non-coding single-stranded microRNA, miR-495-3p, in the sevoflurane-induced neurotoxicity using a mouse hippocampal neuronal cell line (HT22). METHODS: The levels of miR-495-3p in sevoflurane-exposed mice and HT22 cells were determined via RT-qPCR. The role of miR-495-3p on cell viability and apoptosis were determined by CCK-8 and flow cytometric assay, respectively. Western blotting was explored to measure levels of Bax, Bcl-2, active caspase 3, BDNF, p-ERK/ERK and p-CREB/CREB in HT22 cells. ELISA assay was used to examine the levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in cells. Dual luciferase reporter assay was used to explore the interaction of miR-495-3p and BDNF. RESULTS: The level of miR-495-3p was increased sevoflurane-exposed mice and in sevoflurane-treated HT22 cells. Downregulation of miR-495-3p inhibited sevoflurane-induced apoptosis and promoted cell proliferation by upregulating the proteins of Bcl-2 and downregulating the expressions of Bax and active caspase-3 in HT22 cells. In addition, inhibition of miR-495-3p alleviated sevoflurane-induced oxidative injuries in HT22 cells via decline of ROS and upregulation of SOD and GPX. MiR-495-3p can inhibit the ERK/CREB pathway by targeting BDNF. CONCLUSION: Downregulation of miR-495-3p can decrease oxidative status in HT22 cells and alleviate sevoflurane-induced cytotoxicity through stimulating the BDNF/ERK/CREB pathway.