PPARα agonist ameliorates cholestatic liver injury by regulating hepatic macrophage homeostasis.

Inflammatory response plays an essential role in the pathogenesis of cholestatic liver injury. PPARα agonists have been shown to regulate bile acid homeostasis and hepatic inflammation. However, the immunoregulatory mechanisms through which PPARα agonists ameliorate cholestatic liver injury remain unclear.

Fibroblast Heterogeneity in Hepatocellular Carcinoma and Identification of Prognostic Markers Based on Single-cell Transcriptome Analysis.

Background: HCC is a malignant tumor with high morbidity and mortality. Fibroblasts play a key role in the tumor microenvironment (TME). However, the transcriptional regulatory mechanisms of fibroblasts remained unclear in HCC.

Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.

Recent studies have established the pivotal roles of patient-derived tumour organoids (PDTOs), innovative three-dimensional (3D) culture systems, in various biological and medical applications. PDTOs, as promising tools, have been established and extensively used for drug screening, prediction of immune response and assessment of immunotherapeutic effectiveness in various cancer types, including glioma, ovarian cancer and so on. The overarching goal is to facilitate the translation of new therapeutic modalities to guide personalised immunotherapy.

Glycyrrhizic acid alleviates concanavalin A-induced acute liver injury by regulating monocyte-derived macrophages.

Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive.

Identification of a novel first-generation HIV-1 circulating recombinant form (CRF152_DG) among people living with HIV in Karachi, Pakistan.

Unlabelled: The objective of this study was to characterize a novel circulating recombinant form of human immunodeficiency virus type 1 (HIV-1) among people living with HIV in Karachi, Pakistan. We conducted near-full-length genome (NFLG) sequencing on eight samples exhibiting D/G recombination signals in the gene region. We successfully obtained NFLG sequences (790-9,614; with reference to the HXB2 genome) from four of the eight samples and then conducted phylogenetic and recombination analyses on them.

Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.

Liver cancer (LC) poses a significant global health challenge due to its high incidence and poor prognosis. Current systemic treatment options, such as surgery, chemotherapy, radiofrequency ablation, and immunotherapy, have shown limited effectiveness for advanced LC patients. Moreover, owing to the heterogeneous nature of LC, it is crucial to uncover more in-depth pathogenic mechanisms and develop effective treatments to address the limitations of the existing therapeutic modalities.

Development of a promising PPAR signaling pathway-related prognostic prediction model for hepatocellular carcinoma.

The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status.

Distinct genetic clusters in HIV-1 CRF01_AE-infected patients induced variable degrees of CD4 T-cell loss.

Unlabelled: CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4 T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types.

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications.

RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs).

The spectrum of opportunistic infections and malignancies among women on antiretroviral therapy in Ethiopia.

AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; HR: hazard ratio; Mg/dl: milligram per deciliter; TB: tuberculosis; PCP: pneumocystis carinii pneumonia; ZJU: Zhejiang University.

Tryptophan metabolism in health and disease.

Tryptophan (Trp) metabolism primarily involves the kynurenine, 5-hydroxytryptamine, and indole pathways. A variety of bioactive compounds produced via Trp metabolism can regulate various physiological functions, including inflammation, metabolism, immune responses, and neurological function. Emerging evidence supports an intimate relationship between Trp metabolism disorder and diseases.

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.

The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression.

Effects of 3-HAA on HCC by Regulating the Heterogeneous Macrophages-A scRNA-Seq Analysis.

Kynurenine derivative 3-hydroxyanthranilic acid (3-HAA) is known to regulate the immune system and exhibit anti-inflammatory activity by inhibiting T-cell cytokine secretion and influencing macrophage activity. However, the definite role of 3-HAA in the immunomodulation of hepatocellular carcinoma (HCC) is largely unexplored. An orthotopic HCC model and treated with 3-HAA by intraperitoneal injection is developed.

Current understanding of the intratumoral microbiome in various tumors.

It is estimated that in the future, the number of new cancer cases worldwide will exceed the 19.3 million recorded in 2020, and the number of deaths will exceed 10 million. Cancer remains the leading cause of human mortality and lagging socioeconomic development.

New insights into iNKT cells and their roles in liver diseases.

Natural killer T cells (NKTs) are an important part of the immune system. Since their discovery in the 1990s, researchers have gained deeper insights into the physiology and functions of these cells in many liver diseases. NKT cells are divided into two subsets, type I and type II.

Multi-Omics Characterizes the Effects and Mechanisms of CD1d in Nonalcoholic Fatty Liver Disease Development.

Nonalcoholic fatty liver disease (NAFLD) is a class of metabolic-associated liver diseases. Aberrant lipid consumption plays an important role in NAFLD pathogenesis. It has been shown CD1d can bind to multiple different lysophospholipids and associated with NAFLD progression.

Prostaglandin E2 and Receptors: Insight Into Tumorigenesis, Tumor Progression, and Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common primary liver cancer with ∼750,000 annual incidence rates globally. PGE2, usually known as a pro-inflammatory cytokine, is over-expressed in various human malignancies including HCC. PGE2 binds to EP receptors in HCC cells to influence tumorigenesis or enhance tumor progression through multiple pathways such as EP1-PKC-MAPK, EP2-PKA-GSK3β, and EP4-PKA-CREB.

Regulatory mechanism of HIF-1α and its role in liver diseases: a narrative review.

Objective: To summarize the structure, regulatory mechanism, and target genes of hypoxia-inducible factor-1 alpha (HIF-1α) and to comprehensively expound its role in various chronic liver diseases, thus providing a new perspective on the treatment of various liver diseases.

Background: Liver disease, especially chronic liver disease, is a long-standing public health problem; the mortality rate due to end-stage cirrhosis and liver cancer is high worldwide and continues to grow. Moreover, there is a lack of effective targeted therapy for most liver diseases, such as fatty liver, alcoholic liver disease (ALD), and advanced liver cancer, for which drug treatment approaches are extremely limited.

Phosphoribosyl Pyrophosphate Amido Transferase: A New Prognostic Biomarker for Hepatocellular Carcinoma.

Background: PPAT (phosphoribosyl pyrophosphate amido transferase) catalyzes the first committed step of de novo purine biosynthesis and is a key regulatory point in the biosynthesis of nascent purine nucleotides. However, the clinical significance and biologic role of PPAT in hepatocellular carcinoma (HCC) remain unknown.

Methods: We compared the expression of PPAT in carcinomatous and precancerous hepatocellular carcinoma tissues by immunohistochemistry in 90 cases of HCC.

Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases.

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention.