An integrative investigation of developmental toxicities induced by triphenyltin in a larval coral reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is widely distributed on coastlines, which makes coral reef fish a potential target of TPT pollution. However, the negative effects of TPT on coral reef fish remain poorly understood. Therefore, in the present study, the larval coral reef fish Amphiprion ocellaris was used to investigate the developmental toxicities of TPT at environmentally relevant concentrations (0, 1, 10 and 100 ng/L). After TPT exposure for 14 d, the cumulative mortality increased, and growth was suppressed. In addition, TPT exposure inhibited the development of melanophores and xanthophores and delayed white strip formation, which might be responsible for the disruption of the genes (erbb3b, mitfa, kit, xdh, tyr, oca2, itk and trim33) related to pigmentation. TPT exposure also attenuated ossification of head skeletal elements and the vertebral column and inhibited the expression of genes (bmp2, bmp4 and sp7) related to skeletal development. The observed developmental toxicities on growth, pigmentation and skeleton development might be associated with the disruption of thyroid hormones and the genes related to thyroid hormone regulation (tshß, thrα, thrß, tg, tpo, dio2, and ttr). In addition, TPT exposure interfered with locomotor and shoaling behavior, and the related genes dbh, avp and avpr1aa. Taken together, our results suggest that TPT pollution might threaten the development of one of the most iconic coral reef fish, which might produce disastrous consequences on the health of coral reef ecosystems.

Comprehensive analysis of treatment-related adverse events of immunotherapy in advanced gastric or gastroesophageal junction cancer: A meta-analysis of randomized controlled trials.

AIMS: Immune checkpoint inhibitors (ICIs) have been recognized as an effective treatment for advanced gastric or gastroesophageal junction cancer (AG/GEJC). However, the safety of ICIs in patients has not been established. We aimed to systematically assess the risk of all common treatment-related adverse events (TRAEs) in immunotherapy of AG/GEJC. METHODS: A systematic search of randomized controlled trials (RCTs) published until May 2022 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of nine RCTs, including 2918 patients, met the eligibility criteria. The pooled overall incidences of all grade TRAEs, grade 3 or higher TRAEs and treatment-related death were 54.5% (95% confidence interval [CI]: 48.7%-60.2%, I2=75.55%), 12.8% (95% CI: 10.2%-15.7%, I2=51.61%) and 0.11% (95% CI: 0.00%-0.51%, I2=1.63%). Subgroup analyses showed that CTLA-4 inhibitors had a higher risk of any type of TRAEs, when compared with PD-1 and PD-L1 inhibitors. Meta-regression showed significant correlation between all grade TRAEs and proportion of female. Fatigue and diarrhoea were involved in common TRAEs. CONCLUSIONS: Our study provides a comprehensive overview of ICIs-associated AEs in AG/GEJC. Immunotherapy did not have a significantly increased risk experiencing any type of TRAEs, and ICIs had a more manageable safety profile than chemotherapy. These findings provide important guidance to clinicians in counseling and management of patients with AG/GEJC.

Dietary inflammatory index, inflammation biomarkers and preeclampsia risk: a hospital-based case-control study.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.

Dietary and serum vitamin D and preeclampsia risk in Chinese pregnant women: a matched case-control study.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case-control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography-tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose-response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case-control study.

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Efficacy and safety of islet autotransplantation after total pancreatectomy in chronic pancreatitis: A systematic review and meta-analysis including 17 studies.

AIMS: Islet autotransplantation (IAT), in conjunction with total pancreatectomy (TP), is used to relieve pain in patients with chronic pancreatitis (CP), while reducing the incidence of brittle diabetes. We aimed to evaluate the efficacy and safety of IAT after TP (TPIAT) in this setting. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials since 1977. Data were extracted from published papers. Random-effects meta-analysis and meta-regression models were built to assess the outcomes and effect of different factors. Subgroup and sensitivity analyses were conducted to examine the between-study heterogeneity, which was assessed using Cochrane's Q and I2 statistic. RESULTS: A total of 17 studies, including 1024 patients, met the eligibility criteria. The median cohort size was 21 patients (range: 5-409). The pooled incidence rates of insulin independence, narcotic independence and mortality at last follow-up were 11.47 per 100 patient-years (95% CI: 6.79-21.60, I2=91.0%), 18.11 per 100 patient-years (95% CI: 5.29-62.04, I2=98.8%) and 2.88 per 100 patient-years (95% CI: 1.75-4.74, I2=46.8%), respectively. However, the heterogeneity level of our results was high, which was due to differences in research methods and definitions of outcomes between studies. Therefore, our results should be interpreted with caution. CONCLUSIONS: TPIAT can effectively relieve pain and reduce the risk of surgical diabetes with no increase in mortality or morbidity. Prospective, randomized, clinical trials are required to further evaluate selection of patients and the timing of TPIAT.

Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster.

The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene-gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w1118 compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.

Baicalein Exerts Beneficial Effects in d-Galactose-Induced Aging Rats Through Attenuation of Inflammation and Metabolic Dysfunction.

Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis Georgi. This study aimed to ascertain the effects and potential underlying mechanisms of baicalein in d-galactose (d-gal)-induced aging rat model by integration of behavior examination, biochemical detection, and 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Our findings suggest that baicalein significantly attenuated memory decline in d-gal-induced aging model, as manifested by increasing recognition index in novel object recognition test, shortening latency time, and increasing platform crossings in Morris water maze test. Baicalein significantly inhibited the releases of inflammatory mediators such as nitric oxide, interleukin-6, interleukin-1 beta, and tumor necrosis factor-α in d-gal-induced aging model. Metabolomic study revealed that 10 endogenous metabolites in cerebral cortex were considered as potential biomarkers of baicalein for its protective effect. Further metabolic pathway analysis showed that the metabolic alterations were associated with alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, inositol phosphate metabolism, and energy metabolism. These data indicate that baicalein improves learning and memory dysfunction in d-gal-induced aging rats. This might be achieved through attenuation of inflammation and metabolic dysfunction.

Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology.

Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

Glutathione S-transferase M1 polymorphism and esophageal cancer risk: An updated meta-analysis based on 37 studies.

AIM: To evaluate the relationship between glutathione S-transferase M1 (GSTM1) polymorphism and susceptibility to esophageal cancer (EC). METHODS: A comprehensive search of the United States National Library of Medicine PubMed database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC" (until November 1, 2014). The statistical analysis was performed using the SAS software (v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software (v.5.0; Oxford, England); crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC. RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this meta-analysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations (OR = 1.33, 95%CI: 1.12-1.57, P heterogeneity < 0.000001, and I (2) = 77.0%), particularly in the Asian population (OR = 1.53, 95%CI: 1.26-1.86, P heterogeneity < 0.000001, and I (2) = 77.0%), but not in the Caucasian population (OR = 1.02, 95%CI: 0.87-1.19, P heterogeneity = 0.97, and I (2) = 0%). CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations.

A Bioinformatic Approach for the Discovery of Antiaging Effects of Baicalein from Scutellaria baicalensis Georgi.

Aging is one of the most complicated phenomena and is the main risk factor for age-related diseases. Based on the public aging-related gene data, we propose a computational approach to predict the antiaging activities of compounds. This approach integrates network pharmacology and target fishing methods with the aim of identifying a potential antiaging compound from Scutellaria baicalensis Georgi. Utilizing this approach and subsequent experimental validation, it was found that baicalein at concentrations of 0.04, 0.2, and 1 mg/mL extended the mean, median, and maximum life spans in Drosophila melanogaster. Particularly, 0.2 mg/mL baicalein extends the mean and median life spans in male flies by 19.80% and 25.64%, respectively. Meanwhile, it was discovered that baicalein improved fertility in flies. Baicalein exerts antiaging effects likely through attenuating oxidative stress, including increases of CAT activity and GSH level and decrease of GSSG level.

[Baicalein prolongs the lifespan of Drosophila melanogaster through antioxidation activity].

In order to explore the anti-aging effect of baicalein, female Drosophila melanogaster as a model organism was used to study the effects of baicalein on natural aging model and aging models induced by hydrogen peroxide（H2O2） and paraquat. The bioinformatics approach was used to predict the possible target for the anti-aging activity of baicalein, and the target pathways were identified. The oxidative stress pathway was a focus in experiment. Baicalein at concentrations of 0.04 mg·m L-1 and 0.2 mg·m L-1 extended the mean and maximum lifespans in the natural aging model, and effectively reduced the damages of oxidative stress by H2O2 and paraquat. 31 senescence-related targets together with the oxidative stress pathway were modulated by baicalein. The experiments revealed that baicalein might delay aging process through attenuation of the oxidative stress response by decreasing the reactive oxygen species（ROS）, malondialdehyde（MDA） and oxidized glutathione（GSSG） in Drosophila melanogaster.