SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer.

It is well known that activation of oncogenic K-ras alone is insufficient to drive tumor development and that additional factors are needed for full malignant transformation, but the metabolic pathways and regulatory mechanisms that facilitate K-ras-driven cancer development remain to be characterized. Here we show that SQLE, a key enzyme in cholesterol synthesis, is upregulated in K-ras-driven cancer and its high expression is correlated with poor clinical outcome. K-ras regulates SQLE expression in a biphasic manner through reactive oxygen species and MYC signaling.

Integrating transcriptomic and polygenic risk scores to enhance predictive accuracy for ischemic stroke subtypes.

Ischemic stroke (IS), characterized by complex etiological diversity, is a significant global health challenge. Recent advancements in genome-wide association studies (GWAS) and transcriptomic profiling offer promising avenues for enhanced risk prediction and understanding of disease mechanisms. GWAS summary statistics from the GIGASTROKE Consortium and genetic and phenotypic data from the UK Biobank (UKB) were used.

DAA treatment for HCV reduce risk of hepatocellular carcinoma: a 10-years follow-up study based on Chinese patients with hepatitis C.

The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022.

Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

Background: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels.

Methods: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels.

Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data.

Background: Most existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model.

Associations of socioeconomic status with infectious diseases mediated by lifestyle, environmental pollution and chronic comorbidities: a comprehensive evaluation based on UK Biobank.

Background: Socioeconomic status (SES) inequity was recognized as a driver of some certain infectious diseases. However, few studies evaluated the association between SES and the burden of overall infections, and even fewer identified preventable mediators. This study aimed to assess the association between SES and overall infectious diseases burden, and the potential roles of factors including lifestyle, environmental pollution, chronic disease history.

Genetic mutations in NF-κB pathway genes were associated with the protection from hepatitis C virus infection among Chinese Han population.

Host genetic polymorphism is one of major unalterable major factors for HCV infection. NF-κB proteins play multiple roles in immune response and involve in HCV infection and progression. This study was conducted to explore the relationship between single nucleotide polymorphisms (SNPs) in NF-κB pathway and the susceptibility as well as resolution of HCV infection.

Metabolic reprogramming and redox adaptation in sorafenib-resistant leukemia cells: detected by untargeted metabolomics and stable isotope tracing analysis.

Background: Internal tandem duplications (ITD) within the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3) represent a poor prognostic indicator in acute myeloid leukemia (AML). Therapeutic benefits of tyrosine kinase inhibitors, such as sorafenib, are limited due to the emergence of drug resistance. While investigations have been conducted to improve the understanding of the molecular mechanisms underlying the resistance to this FLT3 inhibitor, a profile of cell functioning at the metabolite level and crosstalk between metabolic pathways has yet to be created.

Correction to: Association of CXCR2 genotype variations with HCV clearance in a Chinese population.

Unfortunately, the funding statement was published with error in original publication and is corrected here.

Association of CXCR2 genotype variations with HCV clearance in a Chinese population.

Chemokines are known to play a vital role in guiding and regulating the immune response to viral infections. The chemokine CXC subfamily is a major subfamily in the chemokine family. Outcomes of hepatitis C virus (HCV) infection, as well as the response to treatment, depend on virus and host factors.

The association of CCL3 and CCL4 polymorphisms with HCV clearance in Chinese Han population.

Aim: To explore the association of CCL3 (rs1063340) and CCL4 (rs1049807) polymorphisms with hepatitis C virus (HCV) clearance and sustained virologic response (SVR).

Methods: Two populations were enrolled in the current study; one was a general population including 1585 untreated individuals, with HCV infection and the other was a treatment population comprising 353 HCV-infected patients treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). Two single nucleotide polymorphisms (SNPs) were genotyped, and the relationship between HCV clearance and treatment outcome was analysed.

Genetic variants in chemokine CC subfamily genes influence hepatitis C virus viral clearance.

Chemokine genes may influence both hepatitis C virus (HCV) spontaneous clearance in acute infection and treatment response in chronic infection. We conducted this study to evaluate whether the genetic variants in several CC family genes influence HCV spontaneous clearance and treatment response. The current research genotyped eight SNPs, including CCR1 rs3733096, rs13096371, CCR5 rs746492, rs1800874, CCL3 rs1130371, CCL5 rs3817656, CCL8 rs1133763, CCL14 rs854625, to explore their associations with HCV spontaneous clearance and response to treatment in two populations.

Polymorphisms of chemokine receptor genes and clearance of hepatitis C virus infection in Chinese population.

Background: Chemokine genes play an essential role in both spontaneous clearance in acute infection and therapy of HCV. We investigated whether several CXC family-related genes associated with HCV spontaneous clearance and response to treatment.

Methods: The current study genotyped four SNPs, respectively are CXCR6 rs2234358, CXCL12 rs1801157, CXCL9 rs10336, rs3733236 to assess their associations with HCV spontaneous clearance and response to treatment in a two stage study (668 chronic and 400 resolvers in discovery group, meanwhile 333 chronic and 199 resolver in replication group), and a treatment cohort of HCV with 282 patients.

Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type 1 Infection.

Background: gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in gene in HCV treatment outcomes.

Methods: We genotyped four SNPs from the candidate genes ( and ) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV).