Impact of fine particulate matter on liver injury: evidence from human, mice and cells.

BACKGROUND: A recently discovered risk factor for chronic liver disease is ambient fine particulate matter (PM2.5). Our research aims to elucidate the effects of PM2.5 on liver injury and the potential molecular mechanisms. METHODS AND RESULTS: A population-based longitudinal study involving 102,918 participants from 15 Chinese cities, using linear mixed-effect models, found that abnormal alterations in liver function were significantly associated with long-term exposure to PM2.5. The serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, direct bilirubin, and triglyceride increased by 2.05%, 2.04%, 0.58%, 2.99%, and 1.46% with each 10 µg/m3 increase in PM2.5. In contrast, the serum levels of total protein, albumin, and prealbumin decreased by 0.27%, 0.48%, and 2.42%, respectively. Mice underwent chronic inhalation exposure to PM2.5 experienced hepatic inflammation, steatosis and fibrosis. In vitro experiments found that hepatocytes experienced an inflammatory response and lipid metabolic dysregulation due to PM2.5, which also activated hepatic stellate cells. The down-regulation and mis-localization of polarity protein Par3 mediated PM2.5-induced liver injury. CONCLUSIONS: PM2.5 exposure induced liver injury, mainly characterized by steatosis and fibrosis. The down-regulation and mis-localization of Par3 were important mechanisms of liver injury induced by PM2.5.

Effect of high-intensity interval training on cardiorespiratory in children and adolescents with overweight or obesity: a meta-analysis of randomized controlled trials.

Objective: This meta-analysis aimed to examine the effect of high-intensity interval training on cardiorespiratory fitness in children and adolescents with overweight or obesity, and to explore the optimal dose of high-intensity interval training to improve cardiorespiratory fitness in children and adolescents with overweight or obesity. Methods: Randomized controlled trials on the effects of HIIT on cardiorespiratory fitness in children and adolescents with overweight or obesity were retrieved from six electronic databases, including PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. The quality assessment of the included studies was conducted following the revised quality evaluation method based on the PRISMA principles. Keywords for literature search mainly include high-intensity interval, cardiorespiratory fitness, overweight, obese, children, and adolescent, etc. Results: (1) A total of 18 studies, comprising 581 participants (288 in the intervention group and 293 in the control group), were included and all of them were of moderate to high quality. (2) HIIT had a positive effect on the cardiorespiratory fitness levels of in children and adolescents with overweight or obesity (SMD = 0.91; 95% CI: 0.66, 1.15; p < 0.00001). (3) The improvement in cardiorespiratory fitness was more significant when the HIIT intervention lasted for more than 10 weeks (SMD = 1.04; 95% CI: 0.74, 1.34; p < 0.00001), was conducted 3 times per week, with 2 to 8 sets per session (SMD = 1.13; 95% CI: 0.71, 1.55; p < 0.00001), and maintained a ratio of approximately 1:1 between exercise and rest intervals (SMD = 1.11; 95% CI: 0.73, 1.50; p < 0.00001). Conclusion and recommendations: (1) Long-term HIIT can improve cardiorespiratory fitness in children and adolescents with overweight or obesity. (2) To achieve significant improvements in cardiorespiratory fitness in a short period, children and adolescents with overweight or obesity can engage in HIIT programs lasting for more than 10 weeks, conducted 3 times per week, with 2 to 8 sets per session, and a ratio of approximately 1:1 between exercise and rest intervals. Systematic Review Registration: Identifier: INPLASY202350033.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Src Family Kinases in Hepatocellular Carcinoma.

BACKGROUND: Src family kinases (SFKs) belong to the non-receptor protein tyrosine kinase family and are generally dysregulated in a variety of tumors. This study aimed to thoroughly investigate the mutation status, expression level, prognostic value and relationship with immune infiltration of SFKs in hepatocellular carcinoma (HCC). METHODS: TIMER2.0, UALCAN, cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter were used to analyze the differential expression, genetic alteration, prognostic value and immune cell infiltration of SFKs in HCC patients. Furthermore, we used quantitative real-time PCR (qPCR) and western blot (WB) analysis to measure SFKs mRNA and protein expression in matching specimens of normal tissue and HCC. We analyzed the biological effects of FYN in Huh7 cells and subcutaneous xenograft tumor model. We also studied the biological effects of SRC on Huh7 cells. RESULTS: The mRNA expression levels of LYN, SRC and SRM were elevated in HCC tissues, whereas FYN was reduced. Approximately 10% genetic alterations rate of SFKs was observed in HCC. The mRNA levels of BLK, BRK, FRK, FYN, LCK, LYN, SRC, SRM and YES were correlated with clinical cancer stage. Elevated FYN mRNA levels in HCC were positively correlated with overall survival (OS), whereas SRC was negatively correlated with OS. All SFKs members in HCC were significantly associated with at least half of the six immune-infiltrating cells, including B cells, macrophages, dendritic cells, neutrophils, CD4+ T cells and CD8+ T cells. Furthermore, we confirmed that the protein expression level of FYN was decreased in patients with HCC and in a human hepatoma cell line. Overexpression of FYN suppressed Huh7 cell proliferation, migration, invasion, and tumorigenesis in xenograft nude mice. Knockdown of SRC inhibited Huh7 cell proliferation, migration and invasion. CONCLUSIONS: Dysregulated FYN and SRC expression in HCC is associated with poor prognosis and may be used as novel prognostic biomarkers in patients with HCC.

Immunoglobulin superfamily 9 (IGSF9) is trans-activated by p53, inhibits breast cancer metastasis via FAK.

Metastasis of breast cancer represents the major reason for its poor prognosis, leading to high mortality. In breast cancer, a tumor suppressor gene TP53 is commonly mutated. TP53 mutation leads to an altered expression of various genes, an event that is associated with aggressive tumor and is a strong independent marker for survival. In this study, we identified a novel p53 target gene, immunoglobulin superfamily 9 (IGSF9). IGSF9 is generally down-regulated in breast cancer tissues. Loss of IGSF9 is associated with frequent metastasis and poor prognosis of breast cancer patients. Wild-type p53, but not R175H mutant, trans-activates the transcription of IGSF9 via binding to its promoter (-137 to -131 bp), inhibits epithelial-mesenchymal transition (EMT), consequently the inhibition of breast cancer cells migration and invasion. IGSF9 interacts with focal adhesion kinase (FAK) and inhibits FAK/AKT signaling activity. PND1186, FAK inhibitor, inhibits breast cancer metastasis induced by IGSF9 knockdown in vitro and in vivo. Taken together, IGSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. IGSF9 could serve as a prognostic marker and potential therapeutic target for breast cancer.

Acupuncture therapy for radiotherapy-induced adverse effect: A systematic review and network meta-analysis.

Objective: To evaluate the efficacy of different acupuncture therapies for radiotherapy-induced adverse effects (RIAEs) and find out the optimal scheme. Methods: Eligible randomized controlled trials (RCTs) were collected from inception to June 2020 from 9 bibliographic databases. The risk of bias evaluation of the analyzed literature was carried out using the Cochrane risk-of-bias tool. Network meta-analysis was mainly performed using STATA 14.2 and OpenBUGS 3.2.3 by figuring out the network diagrams, league figures, and SUCRA values. Results: A total of 41 studies with 3,011 participants reported data suitable for network meta-analysis. There was a low to moderate risk of bias in twenty of the articles. ST36 was the most widely prescribed acupoint. Based on network meta-analysis, four outcome indicators were described, namely, acupuncture + medication ranked first in treating radiation enteritis, moxibustion + medication ranked first in preventing radiotherapy-induced leukopenia, acupuncture + medication ranked first in preventing radioactive oral mucositis, and acupuncture ranked first in improving the stimulated salivary flow rate of radioactive xerostomia. Conclusion: The findings of the network meta-analysis manifested that acupuncture therapy combined with medication has superiority in most RIAEs, both reducing incidence and relieving symptoms. However, high-quality studies are still needed to provide conclusive evidence. Systematic review registration: https://inplasy.com/inplasy-2020-7-0054/, identifier: INPLASY202070054.

H2AFZ Is a Prognostic Biomarker Correlated to TP53 Mutation and Immune Infiltration in Hepatocellular Carcinoma.

H2A family member Z (H2AFZ) is a highly conserved gene encoding H2A.Z.1, an isoform of histone variant H2A.Z, and is implicated in cancer. In this study, we report that overexpression of H2AFZ is associated with tumor malignancy and poor prognosis in HCC patients. Functional network analysis suggested that H2AFZ mainly regulates cell cycle signaling and DNA replication via pathways involving several cancer-related kinases and transcription factor E2F1. Further studies revealed that H2AFZ overexpression is regulated by TP53 mutation and led to an attenuation of rapid proliferation phenotype and aggressive behavior in HCC cells. Moreover, we found that H2AFZ was related to immune infiltrations and was co-expressed with immune checkpoint genes, including CD274 (PD-L1), CTLA-4, HAVCR2 (TIM3), LAG3, PDCD1 (PD-1), and TIGIT (VSIG9) in HCC, indicating that H2AFZ-overexpressed HCC patients may be sensitive to immune checkpoint blockades (ICBs). Integrated analysis suggested that H2AFZhigh/TP53mut patients had the shortest OS and PFS time, but most likely to respond to ICBs. These findings indicate that the H2AFZ possesses potential value as a novel prognostic indicator for HCC patients and is correlated with immune infiltration in HCC, laying a foundation for future study of HCC investigation and intervention.

Acupuncture therapy for radiotherapy-induced adverse effects: a protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Radiotherapy is the cornerstone in cancer treatment, and its adverse effects have been recognized widely nowadays. In response, effective and nontoxic therapies are in demand for patients affected by radiotherapy-induced adverse effects (RIAE). As a multitude of clinical studies have suggested that acupuncture therapies seem to be potential in treating RIAE, this study aims to make a systematic review and Bayesian network meta-analysis (NMA) to evaluate effectiveness and safety of different acupuncture treatments. METHODS: A full-scale search will be performed in the following databases from inception to June, 2020: PubMed/Medline, Cochrane library, Web of Science, Ebsco, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database and China Biology Medicine disc (CBM). Randomized controlled trials meeting the eligible criteria based on PICOS elements will be included. The primary outcome is the response rate of RIAE or the incidence of RIAE. The secondary outcome is the incidence of adverse events directly related to acupuncture. Cochrane risk-of-bias tool (ROB 2.0) will be employed to evaluate the quality of chosen literatures. Stata, Addis and OpenBUGS will be performed to manage data. DISCUSSION: The results can provide a relatively objective evidence to assess effectiveness and safety of acupuncture therapies for each RIAE, which may be rewarding as a guiding proposal for researchers concerning RIAE. TRIAL REGISTRATION: This study has been registered at INPLASY (https://inplasy.com/) with a registration ID INPLASY202070054.

Acupuncture therapy for preventing the nausea and vomiting following high emetic risk chemotherapy: A protocol for systematic review and Bayesian Network meta-analysis.

BACKGROUND: Nausea and vomiting are the most common complications after chemotherapy, which cannot be completely controlled even with commonly prescribed antiemetic drugs, particularly in patients receiving highly emetogenic chemotherapy Acupuncture therapy is an effective replacement method for chemotherapy-induced nausea and vomiting (CINV), which effectiveness and safety have been observed by many clinicians. However, different acupuncture treatments have various effectiveness. Based on enough clinical researches, the study aims to uses Bayesian network meta-analysis (NMA) to evaluate the effectiveness of different acupuncture therapies used for preventing CINV. METHODS: Authors will search PubMed/Medline, Cochrane library, Web of Science, Ebsco, Ovid/Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine from setup time to July 2020. All randomized control trails meet the standard will be included. Quality evaluation of included studies will be implemented with Cochrane risk-of-bias tool. STATA 14.0 will be used to perform pairwise meta-analysis. Addis 1.16.8 (University Medical Center Groningen (UMCG), Groningen, NL) and OpenBUGS 3.2.3 (Medical Research Council (MRC), London, UK) will be used to conduct NMA. RESULTS: The results of this review will generate a comprehensive review of current evidence and be published on a peer-reviewed journal. CONCLUSION: The result of this systematic review and Bayesian NMA may offer better options for patients in relieving CINV.Systematic review registration number: INPLASY202070070.

Exosomes isolated from CAPS1­overexpressing colorectal cancer cells promote cell migration.

Calcium­dependent activator protein for secretion 1 (CAPS1) has been reported to promote metastasis in colorectal cancer (CRC), however, the underlying mechanisms have not yet been elucidated. The present study revealed that exosomes derived from CAPS1­overexpressing CRC cells could enhance the migration of normal colonic epithelial FHC cells. GW4869, an inhibitor of exosomes, could attenuate the migration of FHC cells. Furthermore, liquid chromatography­mass spectrometry (LC­MS) and bioinformatics analysis demonstrated that overexpression of CAPS1 could alter the expression pattern of exosomal proteins involved in cell migration. Bone morphogenetic protein 4, which may serve vital roles in the process of CAPS1­induced cell migration, was downregulated in the exosomes. In summary, the present results demonstrated that CAPS1 promotes cell migration by regulating exosomes. Inhibiting the secretion of exosomes may be helpful for the treatment of patients with metastatic CRC.