The physiological effects of resveratrol and its potential application in high altitude medicine

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.

Preventive effects of Bifidobacterium lactis Probio-M8 on ovalbumin-induced food allergy in mice

Food allergy is a significant public health concern globally.Certain probiotics have been found to enhance food allergy by regulating immune-microbe interactions in animal models and patients.However,the effects of Bifidobacterium lactis Probio-M8 on food allergy have not been thoroughly investigated.The present study examined the anti-allergic properties of Probio-M8,particularly in relation to immune response and gut microbiota composition.Results demonstrate that oral administration of Probio-M8 effectively mitigated the allergy symptoms triggered by ovalbumin(OVA)by ameliorating the morphological damage in the jejunum,reducing OVA-specific IgE and histamine levels in the serum,and suppressing Th2 cytokines(interleukin(IL)4 and IL-13)while increasing Th1 cytokines(interferon(IFN)γ)and regulatory T(Treg)cytokines(IL-10 and transforming growth factor(TGF)β1)in the culture supernatants of splenic cells.Furthermore,Probio-M8 effectively altered the diversity and composition of gut microbiota,particularly the relative abundances of Akkermansia_muciniphila in OVA-induced mice.Compared to the OVA group,the Probio-M8 group showed a decrease in the relative abundance of Akkermansia_muciniphila.In conclusion,Probio-M8 demonstrates the potential to alleviate food allergy by regulating the Th1/Th2 response and modulating gut microbiota,thereby offering a novel therapeutic strategy for patients with food allergy.

Isolation and Characterization of an Algicidal Bacterium Indigenous to Lake Taihu with a Red Pigment able to Lyse Microcystis aeruginosa

Objective To isolate and characterize indigenous algicidal bacteria and their algae-lysing compounds active against Microcystis aeruginosa, strains TH1, TH2, and FACHB 905. Methods The bacteria were identified using the Biolog automated microbial identification system and 16S rDNA sequence analysis. The algae-lysing compounds were isolated and purified by silica gel column chromatography and reverse-phase high performance liquid chromatography. Their structures were confirmed by Nuclear Magnetic Resonance （NMR） and Fourier Transform infrared （FT-IR） spectroscopy. Algae-lysing activity was observed using microscopy. Results The algae-lysing bacterium LTH-2 isolated from Lake Taihu was identified as Serratia marcescens. Strain LTH-2 secreted a red pigment identified as prodigiosin （C20H25N30）, which showed strong lytic activity with algal strains M. aeruginoso TH1, TH2, and FACHB 905 in a concentration-dependent manner. The 50% inhibitory concentration （ICs0） of prodigiosin with the algal strains was 4.8 （±0.4）×10^-2 μg/mL, 8.9 （±1.1）×10^-2μg/mL, and 1.7 （±0.1）×10^-1 μg/mL in 24 h, respectively. Conclusion The bacterium LTH-2 and its pigment related to damage of cell membranes. The bacterium for regulating blooms of harmful M. aeruginosa. had strong Microcystis-lysing activity probably LTH-2 and its red pigment are potentially useful

miR-93-5p Transferred by Exosomes Promotes the Proliferation of Esophageal Cancer Cells via Intercellular Communication by Targeting PTEN

Objective To investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells,exerted through exosomes.Methods The expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting.Results Upregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1.Conclusion Our study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.

Prevalence of Overweight and Obesity among Students Aged 7-22 Years in Jiangsu Province,China

Objective To report the prevalence and trend of overweight and obesity among students aged 7-22 years in Jiangsu, 2010 to 2013. Methods This cross-sectional study was carried out as part of students physical fitness and health survey in Jiangsu province. A total of 255,581 subjects （50.03% males and 49.97% females） enrolled in 82 school and 10 universities in Jiangsu. Weights and heights were obtained for each subject and its body mass index （BMI） was calculated using the Chinese Working Group on Obesity in China （CWGO）. Results Anthropometric measurement including bodyweight, height, BMI and bust were significantly different between males in urban compared to females living rural areas （P〈0.001）. The total prevalence of overweight and obesity was 12.4% and 5.7%. Males had a significantly higher rate than in female＇s student. The prevalence of overweight and obesity by age groups was （14.5%, 10.3%） at age 7-11 years, （11.2%, 6.8%） at age 12-14 years, （11.7%, 3.1%） at age 15-17 years, and （11.4%, 2.3%） at age 18-22 years. By regions; the highest prevalence of overweight obesity reported in Taizhou （10.0%, 14.2%）, Xuzhou （9.4%, 12.5%）, and Nanjing （9.2%, 15.6%）, respectively. Conclusion The finding declares that overweight and obesity are important health problems among students in Jiangsu Province. Early intervention programme are needed to address this problems.

Protective Effect of Wheat Peptides Against Small Intestinal Damage Induced by Non-Steroidal Anti-Inflammatory Drugs in Rats

Non-steroidal anti-inflammatory drugs（NSAIDs） were able to produce tissue damage and oxidative stress in animal models of small intestinal damage. In this study, the putative protective effect of wheat peptides was evaluated in a NSAID-induced small intestinal damage model in rats, different doses of wheat peptides or distilled water were administered daily by intragastric administration for 30 d until small intestinal damage was caused. Before sacrificing, NSAIDs（aspirin and indomethacin） or physiological saline were infused into the digestive tract twice. Wheat peptides administration reduced edema and small intestinal damage, and significantly decreased the level of tumor necrosis factor（TNF）-α in mucous membrane of small intestine. Oxidative stress was significantly increased after NSAID infusion and was reduced by wheat peptides. Wheat peptides increased glutathione peroxidase（GSH-Px） activity in mucous membrane of small intestine. μ-Opioid receptor mRNA expression decreased more significantly in wheat peptides treated rats than in the model control group. Overall, the results suggest that non-steroidal anti-inflammatory drugs induced small intestinal damage in rats and wheat peptides administration may be an effective tool for protecting small intestinal tissue against NSAID-induced small intestinal damage and oxidative stress.

Detection of CYP2E1,a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population

Objective Cytochrome P450 2E1 （CYP2E1） is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis （SCGE）. Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.

Pulmonary Toxicity in Rats Caused by Exposure to Intratracheal Instillation of SiO2 Nanoparticles

Objective The effect of the silica nanoparticles（SNs） on lungs injury in rats was investigated to evaluate the toxicity and possible mechanisms for SNs.Methods Male Wistar rats were instilled intratracheally with 1 mL of saline containing 6.25,12.5,and 25.0 mg of SNs or 25.0 mg of microscale SiO_2 particles suspensions for 30 d,were then sacrificed.Histopathological and ultrastructural change in lungs,and chemical components in the urine excretions were investigated by light microscope,TEM and EDS.MDA,NO and hydroxyproline（Hyp） in lung homogenates were quantified by spectrophotometry.Contents of TNF-α,TGF-β1,IL-1β,and MMP-2 in lung tissue were determined by immunohistochemistry staining.Results There is massive excretion of Si substance in urine.The SNs lead pulmonary lesions of rise in lung/body coefficients,lung inflammation,damaged alveoli,granuloma nodules formation,and collagen metabolized perturbation,and lung tissue damage is milder than those of microscale SiO_2 particles.The SNs also cause increase lipid peroxidation and high expression of cytokines.Conclusion The SNs result into pulmonary fibrosis by means of increase lipid peroxidation and high expression of cytokines.Milder effect of the SNs on pulmonary fibrosis comparing to microscale SiO_2 particles is contributed to its elimination from urine due to their ultrafine particle size.

Organoids revealed:morphological analysis of the profound next generation in-vitro model with artificial intelligence

In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.

Poly(ADP-ribosyl)ation of Apoptosis Antagonizing Transcription Factor Involved in Hydroquinone-Induced DNA Damage Response

The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.

Application of zebrafish in the study of the gut microbiome

Zebrafish(D anio rerio)have attracted much attention over the past decade as a reliable model for gut microbiome research.Owing to their low cost,strong genetic and development coherence,efficient preparation of germ-f ree(GF)larvae,availability in high-t hroughput chemical screening,and fitness for intravital imaging in vivo,zebrafish have been extensively used to investigate microbiome-h ost interactions and evaluate the toxicity of environmental pollutants.In this review,the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm-b looded animal models are first summarized.Then,the roles of zebrafish gut microbiome on host development,metabolic pathways,gut-b rain axis,and immune disorders and responses are addressed.Furthermore,their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed.We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification,resistance against bacterial infection,and disease prevention and cure.Overall,the zebrafish model promises a brighter future for gut microbiome research.

Influence of luteolin on the apoptosis of esophageal cancer Eca109 cells and its mechanism of action

The present study was conducted to verify the influence of luteolin on apoptosis of Eca109 cells and to further investigate the possible mechanisms underlying its effect on apoptosis.The cells were exposed to different concentrations of luteolin(0,40,80,120,160,200,240M)for 24,48,and 72 h respectively.The influence of luteolin on proliferation of Eca109 cells was detected using MTT assay.Eca109 cells were then treated with luteolin(0,40,160,240M)for 24 h.The effect of luteolin on cell cycle progression and apoptosis was assayed by using flow cytometry(FCM).Expression of caspase9 and caspase3 mRNA and protein was analyzed by real-time PCR and Western blot respectively.The results showed that luteolin could inhibit the proliferation of Eca109 cells at all concentrations in a time-dependent manner and the relative inhibition rate showed an inverted U-shaped association with the concentration of luteolin.Further,the cell cycle was arrested in the S phase following treatment with luteolin.Apoptosis analysis indicated that luteolin could induce the apoptosis of Eca109 cells across the three concentration groups,which exhibited a trend of first promotional and then inhibitory with the increases in luteolin concentration.The effect of luteolin on the mRNA and protein expression of caspase 9 and caspase3 first manifested as promotion,then inhibition.Therefore,luteolin may serve a role in promoting cell apoptosis by inducing Eca109 cell apoptosis that involves the expression of caspase3,caspase9 mRNA and protein.This study provides theoretical basis for further study and clinical application of luteolin.The specific mechanism has not yet been clarified and the other activation pathways inducing apoptosis need to be further studied.

The Short-term Effects of Temperature on Infectious Diarrhea among Children under 5 Years Old in Jiangsu,China:A Time-series Study(2015-2019)

The association between meteorological factors and infectious diarrhea has been widely studied in many countries.However,investigation among children under 5 years old in Jiangsu,China remains quite limited.Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu,China from 2015 to 2019 were collected.The lag-effects up to 21 days of daily maximum temperature(Tmax)on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model(DLNM)approach.The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors,and the burden of disease mainly occurred among children aged 0-2 years old.Moreover,when the reference value was set at 16.7°C,Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province,which was increased remarkably in cold weather with the highest risk at 8℃.The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities.The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18(95% CI:1.09,1.29).Suzhou which had the highest number of diarrhea cases(15830 cases),had a maximum RR of 1.04(95%CI:1.03,1.05)on lag 15 days.Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu,which reminds us that in cold seasons,more preventive strategies and measures should be done to prevent infectious diarrhea.

Inverse relations between Helicobacter pylori infection and risk of esophageal precancerous lesions in drinkers and peanut consumption

BACKGROUND Helicobacter pylori(H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma(ESCC) remains a topic of much debate.AIM To evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODS Two hundred patients with esophageal precancerous lesions(EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTS A total of 47(23.5%) EPL cases and 58(29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio(OR) = 0.32, 95% confidence interval(95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection(OR = 0.39, 95%CI: 0.20-0.74).CONCLUSION Our study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.

Milled flaxseed-added diets ameliorated hepatic inflammation by reducing gene expression of TLR4/NF-κB pathway and altered gut microbiota in STZ-induced type 1 diabetic mice

Flaxseed has displayed the potential beneficial as functional foods.However,most studies focused on effects of flaxseed extracts or ingredients in flaxseed.Besides,few studies showed that flaxseed extracts contributed to anti-type 1 diabetes(T1D),yet the underlying mechanism is still unknown.In the present study,16.7% of milled flaxseed(MF)-added diet was given to diabetic mice induced by streptozocin for 6 weeks.The results showed that MF feeding 1)slightly decreased blood glucose levels and improved the ability of glucose tolerance by oral glucose tolerance test,2)decreased liver tumor necrosis factor-αlevels and increased liver glycogen levels with significance via down-regulating TLR4/NF-κB pathways,3)and significantly altered some beneficial bacteria in gut microbiota.In conclusion,the present study showed that milled flaxseed showed the potential on anti-T1D through anti-inflammation via TLR4/NF-κB and altering the gut microbiota in STZ-induced diabetic mice.

Impact of Enterprise Ownership and Size on Registered Hematotoxicity in Benzene-exposed Workers

Benzene is a classified as ahuman carcinogen that can cause myelodysplastic syndrome and acute myelogenousleukemia;.This compound is also a potent toxin suppressing the bone marrow.Accordingly,benzene causes serious hematological adverse effects,such as pancytopenia and aplastic

LncRNA LUCAT1 Activation Mediated by theDown-regulation of DNMT1 Is Involved inCell Apoptosis Induced by PM2.5

Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than

Dietary Restriction Reduces Blood Lipids and Ameliorates Liver Function of Mice with Hyperlipidemia

Dietary restriction（DR） can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet（HFD）（34% of energy）, then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group（P〈0.05 or P〈0.01）, so did alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, lactate dehydrogenase（LDH） levels and the ratio of LDL-C/HDL-C in the DR50% group（P〈0.05 or P〈0.01）. Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1（SIRT1） in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma（PPARγ） in adipose（P〈0.05 or P〈0.01）. The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.

Effects of long-term exposure to TDCPP in zebrafish( Danio rerio )–Alternations of hormone balance and gene transcriptions along hypothalamus-pituitary axes

Background : TDCPP is one of the major chemical of organophosphate flame retardants(OPFRs) that has been detected ubiquitously in both the environment and biota. Previously we observed that it influenced the concentrations of sex and thyroid hormones in a sex-dependent pattern, leading to reproductive impairments after short-term exposure in zebrafish. Here we investigate the consequences of longerterm exposure to TDCPP on the hypothalamic-pituitary-gonad(HPG), hypothalamicpituitary-i nterrenal(HPI), and hypothalamic-pituitary-thyroid(HPT) axes of zebrafish( Danio rerio).Methods : A 120-day exposure test to 0.005, 0.05 and 0.5 mg/L TDCPP was initiated with fertilized eggs. Sex steroid hormones in the treated fishes were measured and transcriptional changes were analyzed.Results : In female fish, exposure to TDCPP resulted in increases in plasma cortisol,follicle stimulating hormone(FSH), luteinizing hormone(LH), 17β-estradiol(E2), cortisol, thyroxine(T4), and triiodothyronine(T3). Transcription of most target genes along HPG, HPI and HPT axes were increased by the exposure. While in male fish the exposure led to decreases in cortisol, FSH, LH, T4, T3, testosterone(T), and 11-ketotestosterone(11-KT). Transcription of genes along HPG, HPI and HPT axes,especially steroidogenic genes, were inhibited in male zebrafish. While, E2/T or E2/11-KT ratio was increased in both female and females. The sex-dependent changes in hormones might be due to differential responses to TDCPP induced stresses. An increase in cortisol level coincided with increases in E2 and THs in female fish, while in males decreases in cortisol as well as T, 11-KT and THs were observed. Long-term exposure to TDCPP at very low(μg/L) concentrations could disrupt hormone balances in a sex dependent way.Conclusion : This study revealed that TDCPP could affect endocrine axes – HPG, HPI and HPT – in zebrafish, and impair zebrafish development.

Association between Polymorphisms of MALAT1 and Blood Lead Levels in Lead-exposed Workers

Lead,a heavy metal,which is nonessential but may be harmful to the human body,has been widely used to manufacture many products for use in the modern world.Lead-acid batteries have the advantages of low price,high safety,and advanced technology.