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Chen Liu

Publications and source records attributed to Chen Liu.

At least 19 recordsLinked to original sources
PubMed2026

TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sjögren's syndrome.

OBJECTIVES: This study aims to determine the role of acid‑sensitive nonspecific cation channels transmembrane protein 176A (TMEM176A) and TMEM176B in autoimmune diseases, with a focus on primary Sjögren's Syndrome (pSS). METHODS: We examined the expression patterns of TMEM176A and TMEM176B across tissues and cells utilizing bulk RNA-seq and scRNA-seq datasets. Immunophenotyping analysis was performed by flow cytometry to compare CD62L expression between TMEM176B⁺ and TMEM176B⁻ monocytes. The proportion of TMEM176B+ cells in monocytes was interrogated in both pSS patients and healthy controls. Clinical correlations of TMEM176B with anti‑SSB antibody and complement C4 levels were also evaluated. RESULTS: TMEM176A and TMEM176B showed conserved co‑expression and were significantly upregulated in autoimmune diseases. TMEM176B⁺ monocytes displayed higher CD62L positivity rate than TMEM176B- monocytes. In pSS patients, the proportion of TMEM176B⁺ monocytes was elevated in total monocytes, classical monocytes (cMo) and intermediate monocytes (iMo). The proportion of TMEM176B+ monocytes positively correlated with anti‑SSB levels, while several TMEM176B-associated monocyte subset markers inversely correlated with C4. CONCLUSION: TMEM176A and TMEM176B are highly correlated. TMEM176B expression in monocytes is linked to pSS and may serve as a novel auxiliary diagnostic biomarker.

Humans↗
PubMed2026

FMRP promotes gastric cancer progression via m6A-dependent stabilization of DVL2 and activation of the Wnt/PCP-JNK pathway.

BACKGROUND: N6-methyladenosine (m6A) modification has emerged as a critical regulator in gastric cancer progression. Fragile X messenger ribonucleoprotein 1 (FMRP), an RNA-binding protein with tumorigenic potential, remains poorly characterized in gastric cancer. METHODS: FMRP expression in gastric cancer was assessed through bioinformatic analyses and tissue microarray-based immunohistochemistry. Its biological functions were examined through loss-of-function experiments in vitro and in vivo. Mechanistic investigations, including RNA interaction, m6A site mutation, and RNA stability analyses, were performed to identify downstream targets and pathways regulated by FMRP. RESULTS: Bioinformatic analyses and tissue microarray-based immunohistochemistry showed that FMRP was significantly upregulated in gastric cancer tissues. FMRP depletion suppressed tumor growth and metastasis. Subsequently, Dishevelled segment polarity protein 2 (DVL2) was identified as a candidate downstream target of FMRP. DVL2 was also significantly upregulated in gastric cancer tissues, and its expression positively correlated with FMRP expression. Mechanistically, FMRP bound to DVL2 mRNA and enhanced its stability in an m6A-dependent manner. Among the candidate sites tested, mutation of 1271A attenuated FMRP-mediated regulation of DVL2 reporter activity, supporting the involvement of this site. Functionally, FMRP promoted activation of the noncanonical Wnt/planar cell polarity (PCP) signaling pathway and enhanced the proliferative, migratory, and invasive capacities of gastric cancer cells via DVL2. CONCLUSIONS: These results define FMRP as an oncogenic driver in gastric cancer that operates via the DVL2/Wnt/PCP axis. Targeting this pathway may provide a potential therapeutic strategy for gastric cancer.

Stomach Neoplasms↗
PubMed2026

Characterization of age-related changes in the gut microbiome and metabolome of Kunming dogs and their associations with police performance.

BACKGROUND: Gut microbiota plays a pivotal role in regulating the host's central nervous system (CNS) activity and behavior. However, its influence on the police performance of Kunming dogs and the underlying mechanisms remain largely unexplored. This study was the first to apply multi-omics technologies to investigate the dynamic variations in gut microbiota and their metabolic profiles across different ages of Kunming dogs. Furthermore, we systematically examined the associations between these microbial alterations and police performance metrics, providing a theoretical foundation for enhancing the working capabilities of Kunming dogs through targeted modulation of intestinal microecology. RESULTS: The study showed that puppies, young dogs and adult dogs had significantly better police performance than elderly dogs, with young dogs exhibiting the highest scores. Analysis of 16S rRNA sequencing demonstrated that gut microbial diversity and stability were highest during the young dog stage, gradually declining with age. Metagenomic analysis revealed that the abundance of Lactobacillus acidophilus, Lactobacillus johnsonii, Limosilactobacillus reuteri, Ligilactobacillus animalis and Muribaculum gordoncarteri were strongly correlated with police performance. The results of metagenome-assembled genomes (MAGs) indicated that the above species have functional genes involved in GABAergic and glutamatergic synapse pathways. Furthermore, metabolomic analysis showed that differential metabolites were enriched in the neuroactive ligand-receptor interaction pathway, in which GABA (γ-aminobutyric acid), histamine and tyramine metabolites were positively correlated with the above species and police performance. CONCLUSION: The species L. acidophilus, L. johnsonii, L. reuteri, L. animalis, and M. gordoncarteri, which were enriched in the gut of puppies and young Kunming dogs, may potentially influence the nervous system through the production of neurotransmitters and neuromodulators, suggesting a possible association with police performance. Video Abstract.

Animals↗
PubMed2026

Cross-kingdom genomic variation in chicken gut microbiomes: insights from China's diverse local breeds.

BACKGROUND: The gut microbiome possesses substantial genetic diversity that supports microbial adaptation, but the genomic variation patterns across its prokaryotic and viral populations remain incompletely characterized. RESULTS: Through integrated metagenomic and metatranscriptomic analysis of ten indigenous chicken breeds from China, we recovered 1527 representative prokaryotic MAGs, 37,555 representative DNA viral contigs, and 1867 representative RNA viral contigs (primarily comprising Bacillota/Bacteroidota, Uroviricota, and Lenarviricota/Pisuviricota, respectively). By integrating complementary short-read and long-read metagenomics with metatranscriptomics, we identified structural variants (SVs) and single-nucleotide variants (SNVs) in these cross-kingdom genomes. Positive SV-SNV density correlations occurred consistently across all microbial groups, indicating coordinated mutational processes. DNA viruses exhibited the highest variant prevalence (86.9% SNVs, 47.7% SVs), with temperate phages accumulating significantly more variants than virulent phages. Functionally, prokaryotic variants accumulated in carbohydrate metabolism and amino acid metabolism, while viral variants demonstrated broad metabolic hijacking. Horizontal gene transfer (HGT) was characterized by a strong virus-associated signature (69.40% of 536 events) and marked by an asymmetric pattern, with phage-to-bacteria (P-to-B) flow alone constituting 37.50% of all events. Random forest analysis revealed a strong bidirectional predictive relationship between SV and SNV densities across prokaryotic, DNA viral, and RNA viral populations, suggesting coupled genomic instability. Niche breadth emerged as a major driver of SNVs across kingdoms and was positively correlated with variant density. In prokaryotes, HGT events significantly shaped variant patterns. For viruses, genomic GC content was an important factor and consistently showed a negative correlation with SNV density in both DNA and RNA viruses. CONCLUSIONS: These findings demonstrate that coordinated mutational processes and kingdom-specific intrinsic factors drive genomic variation, with viruses serving as key genetic exchange vectors in chicken gut ecosystems. Video Abstract.

Animals↗
PubMed2024

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Graft vs Host Disease↗
PubMed2023

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

Bacteroides ovatus↗
PubMed2007

3D architectures of iron molybdate: phase selective synthesis, growth mechanism, and magnetic properties.

Monoclinic and orthorhombic Fe(2)(MoO(4))(3) microsized particles with complex 3D architectures have been selectively prepared by a template-free hydrothermal process. The pH value, reaction time, temperature, and molybdenian source have crucial influence on the phase formation, shape evolution, and microstructures. Monoclinic Fe(2)(MoO(4))(3) particles obtained at pH 1 and pH 1.65 display ferromagnetic ordering at 10.4 K and 10.5 K, respectively, and the ferromagnetic component is determined to be 0.0458 mu(B) and 0.0349 mu(B) per Fe-ion at 10 K, respectively. For orthorhombic beta-Fe(2)(MoO(4))(3), antiferromagnetic ordering was observed about 12 K. At higher temperatures, beta-Fe(2)(MoO(4))(3) began to follow the Curie-Weiss law with theta=-70 K. Such 3D architectures of monoclinic and orthorhombic beta-Fe(2)(MoO(4))(3) microparticles with unique shapes and structural characteristics may find applications as catalysts and as well as in other fields.

Crystallization↗
PubMed2007

Hepatocellular carcinoma arising from ectopic liver tissue in the pancreas.

Liver tissue ectopia is a well-documented phenomenon. Rarely, hepatocellular carcinoma arises from the ectopic liver tissue. In this paper, we report a case of a primary, well-differentiated hepatocellular carcinoma arising from ectopic liver tissue in the pancreas. The patient is a 58-year-old Hispanic man with no history of underlying liver diseases or chronic pancreatic diseases. Patient presented with a several days history of abdominal pain with radiation to his right upper quadrant. Imaging study revealed a 3.7 x 3.3-cm mass in the distal pancreas. No other lesions were identified. Preoperative fine needle aspiration revealed blood and atypical hepatocytes. The patient underwent distal pancreatectomy and splenectomy for suspected neuroendocrine tumor. Gross examination revealed a well-circumscribed 3.3-cm, beige-tan, pseudolobulated tumor with focal areas of hyperpigmentation. A microscopic examination revealed hepatoid cells arranged in a trabecular pattern with focal bile pigment. Immunohistochemistry study showed that the tumor cells were reactive with hepatocyte antigen (Hep par 1), alpha-1 antitrypsin, but negative for synaptophysin and chromogranin. Immunostain for polyclonal carcinoembryonic antigen showed a typical bile canalicular pattern. These results support that this tumor in the pancreas is hepatocellular carcinoma, most likely arising from ectopic liver tissue within the pancreas.

Carcinoma, Hepatocellular↗
PubMed2006

Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus.

PURPOSE: A dual-regulated adenovirus variant CNHK500, in which human telomerase reverse transcriptase promoter drove the adenovirus 5 (Ad5) E1a gene and hypoxia-response promoter controlled the E1b gene, was engineered. This virus has broad anticancer spectrum and higher specificity compared with mono-regulated adenovirus CNHK300. The objective of the current study is to show its antitumor selectivity and therapeutic potential. EXPERIMENTAL DESIGN: The antitumor specificity of human telomerase reverse transcriptase and hypoxia response promoters was evaluated in a panel of tumor and normal cells. Under the control of these promoters, the tumor-selective expression of E1a and E1b genes was evaluated. Further in vitro antitumor specificity and potency of this virus were characterized by viral replication and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, hepatocellular carcinoma xenografts were established to evaluate CNHK500 antitumor efficacy in vivo by different routes of virus administration and different dosages. RESULTS: Human telomerase reverse transcriptase and hypoxia response promoters were activated in a tumor-selective manner or under hypoxia treatment in a broad panel of cells. Selective adenoviral early gene expression, efficient viral replication, and oncolysis were observed in all tested cancer cells with more attenuated replication capacity in normal cells. Significant regression of hepatocellular carcinoma xenografts and prolonged survival were observed by either i.t. or i.v. administration. CONCLUSIONS: CNHK500 greatly reduced side effects in normal cells via dual control of adenoviral essential genes while still preserving potent antitumor efficacy on broad-spectrum cancer cells in vitro and in vivo. It can be used as a powerful therapeutic agent not only for liver cancers but also for other solid tumors.

Adenoviridae↗
PubMed2006

Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: An association between nonalcoholic fatty liver disease (NAFLD) and the insulin resistance (IR) syndrome exists. Familial clustering of IR may support a genetic predisposition to NAFLD or cryptogenic cirrhosis (CC). METHODS: Patients with NAFLD (n = 20) and healthy controls (n = 20) matched for age, sex, and body mass index with at least 4 living relatives and 2 generations of lineage participated in a familial aggregation study. A medical history was obtained from each subject and confirmed with first-degree family members. RESULTS: NAFLD patients were more likely to have cirrhosis (odds ratio [OR] = 12.0), cardiac disease (OR, 3.0), hyperlipidemia (OR, 12.1), diabetes mellitus (DM) (OR, 9.1), renal stones (OR, 4.1), and arthritis (OR, 6.1). IR (P = .042) (the primary dependent variable) and DM (P = .013) were noted in their first-degree relatives. A trend for familial clustering of NAFLD or CC (P = .059) with a maternal linkage for disease expression also may exist. Cholelithiasis (P = .047), presumed NAFLD and/or CC (P = .049), and a trend toward IR (P = .07) were noted in the mothers, but not the fathers, of patients with NAFLD. An increased risk of DM (OR, 4.2; 95% confidence interval, 1.26-18.7; P = .013), IR (OR, 2.86; 95% confidence interval, 1.02-9.38; P = .042), and smoking (OR, 3.41; 95% confidence interval, 1.43-9.07; P = .003) was observed in first-degree relatives of NAFLD patients. No significant survival difference was observed between family cohorts. CONCLUSIONS: Familial clustering and a potential maternal linkage for IR support a genetic predisposition for NAFLD. Alternatively, the presence of suppressor genes modifying the expression of IR in paternal lineage warrants further investigation.

Adult↗
PubMed2006

An effective cancer vaccine modality: lentiviral modification of dendritic cells expressing multiple cancer-specific antigens.

Viral modification of dendritic cells (DCs) may deliver a "danger signal" critical to the hypo-reactive DCs in cancer patients. Using three highly differentially expressed hepatoma tumor-associated antigens (TAAs): stem cell antigen-2 (Sca-2), glycoprotein 38 (GP38) and cellular retinoic acid binding protein 1 (RABP1), we explored the therapeutic potential of the DCs modified with lentiviral vectors (LVs). Preventive and therapeutic injection of the LV-TAA-DC vaccine into tumor-bearing mice elicited a strong anti-tumor response and extended survival, which was associated with tumor-specific interferon-gamma and cytotoxic T cell responses. In vivo elimination of the LV-TAA-DCs by a co-expressed thymidine kinase suicide gene abrogated the therapeutic effect. The modification of DCs with LVs encoding multiple TAAs offers a great opportunity in cancer immunotherapy.

Animals↗
PubMed2006

Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.

Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) of interferon-gamma (IFN-gamma) may be useful because of the possibility that it will yield IFN-gamma-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a human TERT promoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or human IFN-gamma gene to generate novel immune gene-viral therapeutic systems, CNHK300-mIFN-gamma and CNHK300-hIFN-gamma, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-gamma induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.

Adenoviridae↗
PubMed2006

Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation.

Cyclosporine is an immunosuppressive agent widely used in the management of liver transplant recipients. Cyclosporine has been shown to have antiviral activities against HIV, herpes simplex, and vaccinia viruses. The aim of this study was to determine the effect of Cyclosporine in viral clearance in the liver transplant recipients during therapy with combination of interferon and ribavirin, and to determine the anti-viral potential of Cyclosporine in vitro. Immunosuppression consisted of either Cyclosporine or Tacrolimus-based therapy. Both groups received therapy with interferon and ribavirin for 48 weeks when evidence of progressive histologic disease was determined. We found that subjects on Cyclosporine-based immunosuppression (n = 56) had a higher sustained virological response of 46% compared to 27% in the patients on Tacrolimus-based therapy (n = 59, P = 0.03). In vitro studies were performed to evaluate the antiviral effect of Cyclosporine in the replicon system. These studies showed that Cyclosporine inhibits hepatitis C viral replication in a dose-dependent manner. Combination of Cyclosporine with interferon showed additive effect, and its function is independent of interferon signaling pathways. In conclusion, Cyclosporine may offer an advantage to Tacrolimus in those patients undergoing interferon-based therapy and should be studied in a prospective randomized trial.

Adult↗
PubMed2006

Hepatitis C virus: virology and experimental systems.

Over the past several years, significant progress has been made toward the understanding of hepatitis C virus, especially the development of in vitro cell culture models. The scientific community now has the tools to gain a better understanding of the virus, which should translate into better clinical therapeutic modalities. Many new drugs are currently being evaluated, and a few are already undergoing clinica trials. This article focuses on the current advances in hepatitis C virus virology.

Animals↗
PubMed2006

Enhancing the bioavailability of cyclosporine a using solid dispersion containing polyoxyethylene (40) stearate.

Solid dispersion containing polyoxyethylene (40) stearate and cyclosporine A was prepared by solvent-melt method and characterized using differential scanning calorimetry, powder X-ray diffraction, and Infrared Fourier Transform Spectroscopy (FTIR). Dissolution of the drug from solid dispersion was dramatically enhanced compared to that from the drug powder alone and physical mixture. In vivo oral bioavailability of cyclosporine A from the solid dispersion in Wistar rats was comparable to that from a commercial product, Sandimmun Neoral (P>0.05). The formulation is stable up to six months under 30 degrees C/RH60% and one year at 25 degrees C/RH 60% when packed in aluminum-polyethylene laminated bags.

Animals↗