Publications by authors named "Simin Wen"

Background: Sarcopenia severely affects the physical health of the elderly. Currently, there is no specific drug available for sarcopenia. This study aims to identify pathogenic proteins and druggable targets for sarcopenia through Mendelian randomization (MR)-based analytical framework.

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As the elite force of our immune system, T cells play a determining role in the effectiveness of cancer immunotherapy. However, the clever tumor cells construct a strong immunosuppressive tumor microenvironment (TME) fortress to resist the attack of T cells. Herein, a magnesium peroxide (MP)-based biomimetic nanoigniter loaded with doxorubicin (DOX) and metformin (MET) is rationally designed (D/M-MP@LM) to awake T cell-mediated cancer immunotherapy via comprehensively destroying the strong TME fortress.

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Background: Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality.

Methods: Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure.

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Exploring the mechanisms underlying abnormal glycemic traits is important for deciphering type 2 diabetes and characterizing novel drug targets. This study aimed to decipher the causal associations of circulating proteins with fasting glucose (FG), 2-h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) using large-scale proteome-wide Mendelian randomization (MR) analyses. Genetic data on plasma proteomes were obtained from 10 proteomic genome-wide association studies.

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Background: The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations.

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Hypoxia is a pervasive feature of solid tumors, which significantly limits the therapeutic effect of photodynamic therapy (PDT) and further influences the immunotherapy efficiency in breast cancer. However, the transient alleviation of tumor hypoxia fails to address the underlying issue of increased oxygen consumption, resulting from the rapid proliferation of tumor cells. At present, studies have found that the reduction of the oxygen consumption rate (OCR) by cytochrome C oxidase (COX) inhibition that induced oxidative phosphorylation (OXHPOS) suppression was able to solve the proposed problem.

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Objectives: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework.

Methods: Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA.

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Article Synopsis
  • A genetic change called rs12252-C influences how a protein, called IFITM3, works and is linked to severe flu in Chinese people.
  • Scientists created special mice to study this change and found that these mice had stronger immune responses after getting a flu vaccine compared to normal mice.
  • The study showed that the change helps the IFITM3 protein to stay in a better position in cells, which helps immune cells work better and fight off the flu.
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Background: The influenza viruses pose a threat to human health and medical services, and vaccination is an important way to prevent infection. However, the effectiveness of influenza vaccines is affected by various aspects. This study aimed to explore factors related to the immune response to influenza vaccines.

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Influenza is a global public health problem for its detrimental impact on human health. Annual vaccination is the most effective prevention of influenza infection. Identifying host genetic factors associated with the responsiveness to influenza vaccines can provide clues for developing more effective influenza vaccines.

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Currently, the clinical factors affecting immune responses to influenza vaccines have not been systematically explored. The mechanism of low responsiveness to influenza vaccination (LRIV) is complicated and not thoroughly elucidated. Thus, we integrate our in-house genome-wide association studies (GWAS) analysis result of LRIV (N = 111, Ncase [Low Responders] = 34, Ncontrol [Responders] = 77) with the GWAS summary of 10 blood-based biomarkers (sample size ranging from 62 076-108 794) deposited in BioBank Japan (BBJ) to comprehensively explore the shared genetics between LRIV and blood-based biomarkers to investigate the causal relationships between blood-based biomarkers and LRIV by Mendelian randomization (MR).

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The annual death associated with seasonal influenza is 290,000-650,000 globally, which can be effectively reduced by influenza vaccination. However, the protective hemagglutination inhibition (HAI) antibody response to influenza vaccine is affected by many factors, among which single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can alter the antigen-presenting function of the HLA molecule, thus influencing the process of antibody mounting against vaccine antigen. Healthy subjects of the Han nationality were recruited and received seasonal trivalent influenza vaccine.

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Objective: The purpose of this project is to make sequential and indepth observation of the variations of retinal microvascular, microstructure, and inflammatory mediators at the early stage of diabetic retinopathy (DR) in streptozotocin-induced diabetes mellitus (DM) rats.

Methods: DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin (STZ). The fluorescein fundus angiography, hematoxylin and eosin staining, periodic acid-Schiff staining, fluorescence imaging techniques, quantitative real-time PCR, and vascular endothelial growth factor- (VEGF-) A ELISA were performed on the 8 day, at the 4 week, 6 week, 8 week, and 10 week after DM induction, respectively.

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Although previous studies have proposed leptin plays an important role in energy metabolism as well as in immune response, the effects of leptin-related genes on influenza vaccine-induced immune response remain unexplored. In this study, we aimed to investigate the potential association of leptin gene (), leptin receptor gene (), and peroxisome proliferator activated receptor gamma gene () polymorphisms with humoral immune response to influenza vaccine. Based on the seroconversion to influenza vaccine, 227 low-responders and 365 responders were selected in this study, and 11 candidate single nucleotide polymorphisms (SNPs) were genotyped using the MassARRAY technology platform.

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Background: Annual vaccination is the most effective prevention of influenza infection. Up to now, a series of studies have demonstrated the role of genetic variants in regulating the antibody response to influenza vaccine. However, among the Chinese population, the relationship between genetic factors and the responsiveness to influenza vaccination has not been clarified through genome-wide association study (GWAS).

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Annual vaccination is the best prevention of influenza. However, the immunogenicity of influenza vaccines varies among different populations. It is important to fully identify the factors that may affect the immunogenicity of the vaccines to provide best protection for vaccine recipients.

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The increasing misgivings of environmental pollution derived from antibiotic residues make it imperative to explore a bifunctional platform for synchronous monitoring and removal of antibiotics. Herein, zeolite imidazolate framework-8 (ZIF-8) is anchored on two-dimensional (2D) amino-functionalized Al-metal organic framework (NH-MIL-53(Al)) nanoplates to construct a dual metal-organic frameworks smart platform (ZIF-8/NH-MIL-53(Al)) for simultaneous capture and fluorescence sensing of tetracyclines (TCs). ZIF-8 nanoparticles anchored on 2D nanoplates having a smaller size and a larger specific surface area boost the adsorption capabilities (561, 533, 526 and 578 mg g for doxycycline (DOX), tetracycline (TET), oxytetracycline (OTC) and chlortetracycline (CTC), respectively).

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Preoperational hemogram parameters have been reported to be associated with the prognosis of several types of cancers. This study aimed to investigate the prognostic value of hematological parameters in gastric cancer in a Chinese population. A total of 870 gastric cancer patients who underwent radical tumorectomy were recruited from January 2008 to December 2012.

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Objectives: To investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis B surface antigen (HBsAg)(+)/hepatitis B e antigen (HBeAg)(-).

Design: Nested case-control study.

Setting: Changchun, China.

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Infants born to HBV carrier mothers are persistently at a higher risk for HBV infection. We investigated the association between HLA SNPs and low responsiveness to HBV vaccination, and the differences of immune response in carriers of risk genotypes who received different doses of the vaccination. 1040 infants from the prevention of mother-to-infant transmission of HBV cohort were included.

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Background: Recent studies have unraveled mutations which have led to changes in the original conformation of functional proteins targeted by frontline drugs against Mycobacterium tuberculosis. These mutations are likely responsible for the emergence of drug-resistant strains of M. tuberculosis.

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Gastric cancer (GC) is one of the most prominent global cancer-related health threats. Genes play a key role in the precise mechanisms of gastric cancer. SNPs in mi-RNAs could affect mRNA expression and then affect the risk and prognosis of GC.

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18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA.

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Article Synopsis
  • EMT is important for tumor metastasis and involves changes in gene expression due to epigenetic modifications, specifically the tri-methylation of histone H3 lysine 4 (H3K4me3).* -
  • In prostate cancer cells, TGF-Beta1 triggers increased H3K4me3 and RbBP5 binding near the Snail gene, and knocking down RbBP5 reduces Snail expression and EMT.* -
  • The study connects SMAD2/3 signaling to Snail transcription through H3K4me3 modification, suggesting that RbBP5 and WRAD could be potential targets for prostate cancer treatment.*
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