FADD Activation in Hepatocellular Carcinoma Potentiates CD8+T Cell Responses and Sensitizes to Immune Checkpoint Inhibitors.

Turning immunologically "cold" tumors "hot" is required for effective immune checkpoint inhibitor (ICI) treatment in hepatocellular carcinoma (HCC). Here, we identified Fas-associated death domain (FADD) as a key molecule upregulated in HCC with dense tumor-infiltrating CD8+ T cells and better response to ICIs. CRISPR-mediated knockout of Fadd in murine HCC cells led to increased tumor weights in immunocompetent, but not immunodeficient, mice.

Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma.

Background: Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.

Objective: We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC).

Exploring the secrets of marine microorganisms: Unveiling secondary metabolites through metagenomics.

Marine microorganisms are increasingly recognized as primary producers of marine secondary metabolites, drawing growing research interest. Many of these organisms are unculturable, posing challenges for study. Metagenomic techniques enable research on these unculturable microorganisms, identifying various biosynthetic gene clusters (BGCs) related to marine microbial secondary metabolites, thereby unveiling their secrets.

PPP1R15A-expressing monocytic MDSCs promote immunosuppressive liver microenvironment in fibrosis-associated hepatocellular carcinoma.

Background & Aims: Recent studies demonstrated the importance of fibrosis in promoting an immunosuppressive liver microenvironment and thereby aggressive hepatocellular carcinoma (HCC) growth and resistance to immune checkpoint blockade (ICB), particularly via monocyte-to-monocytic myeloid-derived suppressor cell (M-MDSC) differentiation triggered by hepatic stellate cells (HSCs). We thus aimed to identify druggable targets in these immunosuppressive myeloid cells for HCC therapy.

Methods: M-MDSC signature genes were identified by integrated transcriptomic analysis of a human HSC-monocyte culture system and tumor-surrounding fibrotic livers of patients with HCC.

Myeloid-intrinsic cell cycle-related kinase drives immunosuppression to promote tumorigenesis.

Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20, also known as cell cycle-related kinase (CCRK), in hepatocellular carcinoma (HCC) correlates with reduced patient survival and low immunotherapy responsiveness. Beyond tumor-intrinsic oncogenicity, here we demonstrated that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC.

EVMP: enhancing machine learning models for synthetic promoter strength prediction by Extended Vision Mutant Priority framework.

Introduction: In metabolic engineering and synthetic biology applications, promoters with appropriate strengths are critical. However, it is time-consuming and laborious to annotate promoter strength by experiments. Nowadays, constructing mutation-based synthetic promoter libraries that span multiple orders of magnitude of promoter strength is receiving increasing attention.

Molecular identification and physiological functional analysis of NtNRT1.1B that mediated nitrate long-distance transport and improved plant growth when overexpressed in tobacco.

Although recent physiological studies demonstrate that flue-cured tobacco preferentially utilizes nitrate ( ) or ammonium nitrate (NHNO), and possesses both high- and low-affinity uptake systems for , little is known about the molecular component(s) responsible for acquisition and translocation in this crop. Here we provide experimental data showing that with a 1,785-bp coding sequence exhibited a function in mediating transport associated with tobacco growth on nutrition. Heterologous expression of in the uptake-defective yeast enabled a growth recovery of the mutant on 0.

Clinical significance of circulating tumor cell (CTC)-specific microRNA (miRNA) in breast cancer.

As a noninvasive method, circulating tumor cell (CTC) provides ideal liquid biopsy specimens for early cancer screening and diagnosis. CTCs detection in breast cancer is correlated with patient prognosis such as disease-free survival (DFS) and overall survival (OS). Besides, accumulating evidence supported that CTCs count may be indicator for chemotherapy response as well.

Development of Alkylated Hydrazides as Highly Potent and Selective Class I Histone Deacetylase Inhibitors with T cell Modulatory Properties.

Histone deacetylases (HDACs) are epigenetic regulators and additionally control the activity of non-histone substrates. We recently demonstrated that inhibition of HDAC8 overexpressed in various of cancers reduces hepatocellular carcinoma tumorigenicity in a T cell-dependent manner. Here, we present alkylated hydrazide-based class I HDAC inhibitors in which the -hexyl side chain attached to the hydrazide moiety shows HDAC8 selectivity .

Important Hormones Regulating Lipid Metabolism.

There is a wide variety of kinds of lipids, and complex structures which determine the diversity and complexity of their functions. With the basic characteristic of water insolubility, lipid molecules are independent of the genetic information composed by genes to proteins, which determine the particularity of lipids in the human body, with water as the basic environment and genes to proteins as the genetic system. In this review, we have summarized the current landscape on hormone regulation of lipid metabolism.

The mitotic regulator RCC2 promotes glucose metabolism through BACH1-dependent transcriptional upregulation of hexokinase II in glioma.

Weighted gene co-expression network analysis (WGCNA) identified a cell-cycle module that is associated with poor prognosis and aggressiveness of glioma. One of the core members, Regulator of chromatin condensation 2 (RCC2) is a component of the chromosome passenger complex. Accumulating evidence suggests that RCC2 plays a vital role in the mitotic process and that abnormal RCC2 expression is involved in cancer development.

IL-6: The Link Between Inflammation, Immunity and Breast Cancer.

Breast cancer is one of the leading causes of mortality in females. Over the past decades, intensive efforts have been made to uncover the pathogenesis of breast cancer. Interleukin-6 (IL-6) is a pleiotropic factor which has a vital role in host defense immunity and acute stress.

Genome-wide identification and expression analysis of genes in alfalfa () in response to cold stress.

Dehydration-responsive element-binding proteins (DREBs) belong to members of the AP2/ERF transcription factor superfamily, which has been reported to involve various abiotic-stress responses and tolerance in plants. However, research on the -family is still limited in alfalfa ( L.), a forage legume cultivated worldwide.

Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver.

Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure.

Sirtuin 7 super-enhancer drives epigenomic reprogramming in hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is a major cancer burden worldwide with increasing incidence in many developed countries. Super-enhancers (SEs) drive gene expressions required for cell type-specificity and tumor cell identity. However, their roles in HCC remain unclear because of data scarcity from primary tumors.

The significances and clinical implications of cholesterol components in human breast cancer.

Breast cancer is one the most common malignancies and leading cause of cancer-related mortality in women. Recent studies suggested that hypercholesterolemia may be the potential modifiable risk factors for breast cancer. Cholesterol was well-known for its strong association with cardiovascular disease for long.

The clinical efficacy and safety of anti-IgE therapy in recessive dystrophic epidermolysis bullosa.

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles.

A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma.

Insufficient T cell infiltration into noninflamed tumors, such as hepatocellular carcinoma (HCC), restricts the effectiveness of immune-checkpoint blockade (ICB) for a subset of patients. Epigenetic therapy provides further opportunities to rewire cancer-associated transcriptional programs, but whether and how selective epigenetic inhibition counteracts the immune-excluded phenotype remain incompletely defined. Here, we showed that pharmacological inhibition of histone deacetylase 8 (HDAC8), a histone H3 lysine 27 (H3K27)-specific isozyme overexpressed in a variety of human cancers, thwarts HCC tumorigenicity in a T cell-dependent manner.

An Update on the Potential of Mesenchymal Stem Cell Therapy for Cutaneous Diseases.

Mesenchymal stem or stromal cells (MSCs) are nonhematopoietic postnatal stem cells with self-renewal, multipotent differentiation, and potent immunomodulatory and anti-inflammatory capabilities, thus playing an important role in tissue repair and regeneration. Numerous clinical and preclinical studies have demonstrated the potential application of MSCs in the treatment of tissue inflammation and immune diseases, including inflammatory skin diseases. Therefore, understanding the biological and immunological characteristics of MSCs is important to standardize and optimize MSC-based regenerative therapy.

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p.

Emerging evidence suggests that long non-coding RNA (lncRNA) plays a critical role in human disease progression. Recently, a novel lncRNA ST8SIA6-AS1 was shown as an important driver in various cancer types. Nevertheless, its contribution to lung adenocarcinoma (LUAD) remains undocumented.

Aberrant expression of miR-16, B12 and CD272 in peripheral blood mononuclear cells from patients with active tuberculosis.

Tuberculosis (TB) immunity is affected by complex immune regulation processes, which involve various immune cells, immune molecules, and cytokines. Here, we evaluated the expression of B12, CD272 and miR-16 in peripheral blood mononuclear cells (PBMC) of patients with active pulmonary tuberculosis. The results showed that monocytes expressing CD272 or B12 were down-regulated in patients with tuberculosis.

Human haptoglobin contributes to breast cancer oncogenesis through glycolytic activity modulation.

Cellular metabolism reprogramming is a hallmark in cancers including breast cancer. Switching off the glycolytic energy in cancer has been indicated as one of the anti-cancer strategies. Aberrant haptoglobin () expression has been shown to cause metabolic dysfunction and implicated in different malignancies.

Epidemiological characteristics of dengue in mainland China from 1990 to 2019: A descriptive analysis.

In the past 30 years, dengue has undergone dramatic changes in China every year. This study explores the epidemiological trend of dengue in China during this period to identify high-risk seasons, regions, ages, susceptible populations, and provide information for dengue prevention and control activities.Dengue data from 1990 to 2019 were derived from the Public Health Science Data Center, Web of Science, China National Knowledge Infrastructure, PubMed, and Centers for Disease Control and Prevention of the corresponding province.