A5053440938- RNA modifications and cancer
- Galectins and Cancer Biology
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- Hepatitis B Virus Studies
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Cancer, Lipids, and Metabolism
- Hepatitis C virus research
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- ATP Synthase and ATPases Research
- HIV Research and Treatment
- Bioactive Compounds in Plants
- Phagocytosis and Immune Regulation
- Lipid metabolism and biosynthesis
- Macrophage Migration Inhibitory Factor
Shandong University
2017-2024
Natural killer (NK) cells are enriched within the liver. Apart from conventional NK (cNK) cells, recent studies identified a liver-resident (LrNK) subset, which constitutes about half of hepatic and exhibits distinct developmental, phenotypic, functional features. However, it remains unclear whether how LrNK as well cNK participate in development hepatocellular carcinoma (HCC) individually. Here, we report that both significantly decreased HCC. The T-cell immunoglobulin mucin...
Resistance to PD-1 blockade in onco-immunotherapy greatly limits its clinical application. T cell immunoglobulin and mucin domain containing-3 (Tim-3), a promising immune checkpoint target, is cleaved by ADAM10/17 produce soluble form (sTim-3) humans, potentially becoming involved anti-PD-1 resistance. Herein, serum sTim-3 upregulation was observed non-small lung cancer (NSCLC) various digestive tumors. Notably, further upregulated non-responding patients undergoing therapy for NSCLC...
Abstract According to the latest evidence, microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8 + T cell‐mediated antitumor activity. However, direct target protein of UA and underlying mechanism remains unclear. Here, this research identifies ERK1/2 as specific crucial UA‐mediated cell activation. Even at low doses, markedly enhances persistence effector functions primary cytotoxic lymphocytes (CTLs) human chimeric antigen receptor (CAR)...
Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important role in processes leading to HCC. We previously identified the mammalian Zinc fingers homeoboxes 2 (ZHX2) gene as HCC-associated gene. In present study, we investigated whether oncogenic properties and, more specifically, HBx, involved ZHX2 silencing. Our data indicates...
Abstract Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated role of tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in progression NAFLD HCC. ZHX2 expression was significantly decreased tissues, especially with NAFLD–HCC. overexpression disturbed lipid homeostasis cultured HCC cells, inhibited deposition hepatocytes both vitro vivo. Moreover, uptake exogenous lipids through...
Sepsis is a life-threatening condition with limited therapeutic options, characterized as excessive systemic inflammation and multiple organ failure. Macrophages play critical roles in sepsis pathogenesis. Metabolism orchestrates homeostasis of macrophages. However, the precise mechanism macrophage metabolism during remains poorly elucidated. In this study, we identified key role zinc fingers homeoboxes (Zhx2), ubiquitous transcription factor, glycolysis by enhancing...
Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism signaling transduction. Here, we identified NAD central hub determine the homeostasis function of NK cells.NAD level was elevated activated cells. supplementation not only enhanced cytokine production cytotoxicity but also improved proliferation...
Abstract Covalently closed circular DNA (cccDNA) is the transcriptional template of hepatitis B virus (HBV), which interacts with both host and viral proteins to form minichromosome in nucleus resistant antiviral agents. Identification factors involved cccDNA regulation expected prove a new venue for HBV therapy. Recent evidence suggests involvement long noncoding RNAs (lncRNAs) mediating interaction various viruses, however, lncRNAs that targets represses transcription have not been fully...
Abstract Liver-resident natural killer cells, a unique lymphocyte subset in liver, develop locally and play multifaceted immunological roles. However, the mechanisms for maintenance of liver-resident cell homeostasis remain unclear. Here we show that early-life antibiotic treatment blunt functional maturation cells even at adulthood, which is dependent on durative microbiota dysbiosis. Mechanistically, significantly decreases butyrate level subsequently led to defective cell-extrinsic...
T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional exhausted cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using strategy combining virtual functional screening, we identified compound named ML-T7 that targets the FG-CC′ cleft of Tim-3, highly conserved binding site phosphatidylserine (PtdSer) carcinoembryonic antigen–related adhesion 1 (CEACAM1). enhanced survival antitumor activity primary...
Abstract Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin mucin domain-containing molecule 4 (TIM-4) promotes development progression cancer. However, role TIM-4 in mitochondria tumor cells remains completely unknown. In this study, we found that promoted growth by oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition OXPHOS reversed TIM-4-induced Notably, mitochondrial fusion via enhancing L-OPA1 protein...
T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in exhaustion. However, little known about the mechanisms regulate TIM-3 surface expression turnover. Here, we report human palmitoylated by palmitoyltransferase DHHC9 at residue cysteine 296 (Cys
BackgroundLiver cancer stem cells (CSCs) are critical determinants of HCC relapse and therapeutic resistance, but the mechanisms underlying maintenance CSCs poorly understood. We aimed to explore role tumor repressor Zinc-fingers homeoboxes 2 (ZHX2) in liver CSCs.MethodsCD133+ or EPCAM+ stem-like were sorted from tissues patients cell lines by flow cytometry. In addition, sorafenib-resistant cells, tumor-sphere forming side population (SP) respectively cultured isolated as hepatic CSCs. The...
Abstract Hepatocellular carcinoma (HCC) is one of the leading causes cancer‐related death worldwide. Lipogenesis has been considered as a critical player in HCC initiation and progression. However, underlying mechanism still not fully understood. Here, we identified zinc fingers homeoboxes 2 (ZHX2), an HCC‐associated tumor suppressor, important repressor de novo lipogenesis. Ectopic expression ZHX2 significantly inhibited lipogenesis cells decreased FASN, ACL, ACC1, SCD1. In accordance with...
Hyperlipidemia impairs anti-tumor immune responses and is closely associated with increased human cancer incidence mortality. However, the underlying mechanisms are not well understood. In present study, we show that natural killer (NK) cells isolated from high-fat-diet mice or treated oleic acid (OA) in vitro exhibit sustainable functional defects even after removal hyperlipidemic milieu. This accompanied by reduced chromatin accessibility promoter region of NK cell effector molecules....
Sorafenib resistance limits its survival benefit for treatment of hepatocellular carcinoma (HCC). Cholesterol metabolism is dysregulated in HCC, and role sorafenib HCC has not been fully elucidated. Aiming to elucidate this, vitro vivo resistant models were established. Sterol regulatory element binding transcription factor 2 (SREBF2), the key regulator cholesterol metabolism, was activated HepG2 Huh7 cells. Knockdown SREBF2 resensitized cells xenografts tumors sorafenib. Further study...
Glutamine is critical for tumor progression, and restriction of its availability emerging as a potential therapeutic strategy. The metabolic plasticity cells helps them adapting to glutamine restriction. However, the role cholesterol metabolism in this process relatively unexplored. Here, we reported that deprivation inhibited synthesis hepatocellular carcinoma (HCC). Reactivation enhanced glutamine-deprivation-induced cell death HCC cells, which partially duo augmented NADPH depletion lipid...
Abstract Inadequate β‐cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF‐α‐induced protein 8‐like 1 (Tipe1) plays a crucial role in multiple diseases, however, specific T2D pathogenesis remains largely unexplored. Herein, Tipe1 as key regulator T2D, contributing to maintenance β cell homeostasis is identified. The results show that β‐cell‐specific knockout (termed Ins2‐Tipe1BKO ) aggravated diabetic phenotypes db/db mice or with high‐fat...
Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts the controlled delivery of NK to enhance therapy tumors. Surface-functionalized HAp modified agonistic antibodies against NKG2D 4–1BB cytokines IL-2 IL-21 support survival dynamic activation. Thus, HAp-modified chitosan (CS)...
Mitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulators, such as PGC-1α MCJ, affect regeneration. Therefore, identification of modulators may pave the way for developing therapeutic strategies. Here, ZHX2 is identified a regulator during injury. both transcriptionally inhibits expression several electron transport chain genes decreases stability, leading reduction mass OXPHOS. Loss Zhx2 promotes recovery by increasing OXPHOS in mice with partial hepatectomy...