Kaempferol Remodels Liver Monocyte Populations and Treats Hepatic Fibrosis in Mice by Modulating Intestinal Flora and Metabolic Reprogramming.

Changes in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods.

EFNA5 suppresses cell proliferation and tumor metastasis in hepatoma via epithelial-to-mesenchymal transition.

Background: EphrinA5 belongs to a subclass of ephrin ligands. Abnormal signal transduction of EFNA5 shows a relationship to the development of various tumors. In this study, we explored the level of EFNA5 in hepatoma cells and the influence of up regulation of EFNA5 expression level on the proliferation, invasion, and migration of HepG2 and LM3 cells.

Oroxylin A suppresses breast cancer-induced osteoclastogenesis and osteolysis as a natural RON inhibitor.

Background: Malignant breast cancer cells trigger the over-activation of osteoclast precursor cells, leading to bone loss and severe pain. Targeted inhibition of osteoclast differentiation has emerged as an important strategy for treating bone syndromes induced by breast cancer.

Purpose: The objective is to discover natural osteoclast inhibitor to treat osteoclastogenesis and bone destruction induced by breast cancer, and clarify the specific mechanisms.

Erianin serves as an NFATc1 inhibitor to prevent breast cancer-induced osteoclastogenesis and bone destruction.

Introduction: Breast cancer-related bone metastasis can lead to skeletal-related events (SREs), which decrease patient quality of life. Inhibition of osteoclastogenesis is a key treatment for SREs; however, the availability of clinical drugs remains limited, and all existing ones disrupt physiological bone formation, while exhibiting no effect on patient survival time.

Objectives: This study aimed to identify a novel osteoclast inhibitor for the treatment of breast cancer-induced SREs.

Immune-Cell-Based Therapy for COVID-19: Current Status.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. The interplay between innate and adaptive immune responses plays a crucial role in managing COVID-19. Cell therapy has recently emerged as a promising strategy to modulate the immune system, offering immense potential for the treatment of COVID-19 due to its customizability and regenerative capabilities.

Flot2 deficiency facilitates B cell-mediated inflammatory responses and endotoxic shock.

Sepsis is a life-threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin-induced septic mice.

Polyphyllin VII protects from breast cancer-induced osteolysis by suppressing osteoclastogenesis via c-Fos/NFATc1 signaling.

Bone is a preferred metastatic site of advanced breast cancer and the 5-year overall survival rate of breast cancer patients with bone metastasis is only 22.8%. Targeted inhibition of osteoclasts can treat skeletal-related events (SREs) in breast cancer patients.

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC.

For hepatocellular carcinoma (HCC) patients, we attempted to establish a new oxidative stress (OS)-related prognostic model for predicting prognosis, exploring immune microenvironment, and predicting the immunotherapy response. Significantly differently expressed oxidative stress-related genes (DEOSGs) between normal and HCC samples from the Cancer Genome Atlas (TCGA) were screened, and then based on weighted gene coexpression network analysis (WGCNA), HCC-related hub genes were discovered. Based on the least absolute shrinkage and selection operator (LASSO) and cox regression analysis, a prognostic model was developed.

A stratification model of hepatocellular carcinoma based on expression profiles of cells in the tumor microenvironment.

Background: A malignancy of the liver, hepatocellular carcinoma (HCC) is among the most common and second-leading causes of cancer-related deaths worldwide. A reliable prognosis model for guidance in choosing HCC therapies has yet to be established.

Methods: A consensus clustering approach was used to determine the number of immune clusters in the Cancer Genome Atlas and Liver Cancer-RIKEN, JP (LIRI_JP) datasets.

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer.

Objective: The aims of this study were to examine the prognostic value of SHP-1 in breast cancer, its roles in the regulation of breast cancer cell growth and metastasis, and the underlying mechanisms.

Methods: Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan-Meier and multivariate Cox regression analyses. RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas.

LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines.

EFNA4 promotes cell proliferation and tumor metastasis in hepatocellular carcinoma through a PIK3R2/GSK3β/β-catenin positive feedback loop.

Rapid tumor progression, metastasis, and diagnosis in advanced stages of disease are the main reasons for the short survival time and high mortality rate of patients with hepatocellular carcinoma (HCC). Ephrin A4 (EFNA4), the ligand of the EPH family, participates in the development of blood vessels and epithelium by regulating cell migration and rejection. In our study, based on bioinformatics analyses, we found that EFNA4 was highly expressed and led to poor prognosis in patients with HCC.

FOXC2 is a prognostic biomarker and contributes to the growth and invasion of human hepatocellular carcinoma.

Background: Forkhead box C2 (FOXC2) is a crucial factor involving in various cancers. However, its functions in hepatocellular carcinoma (HCC) is unknown. Here, we explored the role of FOXC2 in the progression of HCC and its potential mechanisms.

Knockout of NCOA5 impairs proliferation and migration of hepatocellular carcinoma cells by suppressing epithelial-to-mesenchymal transition.

Nuclear receptor coactivator 5 (NCOA5) plays important roles in the development of a variety of malignancies. However, the underlying mechanisms remain obscure. In this study, we successfully generated the NCOA5 knockout hepatocellular carcinoma (HCC) cells by CRISPR/Cas9 - mediated genome editing and found that knockout of NCOA5 inhibited the proliferation and tumor microsphere formation of HCC cells significantly.

FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients.

Background: Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure.

Methods: Here, we investigated the role of FOXA1 in the development of HCC by applying gene function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing outcomes with those of clinical HCC samples.

Results: Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was identified as a FOXA1 target gene.

A single non-synonymous NCOA5 variation in type 2 diabetic patients with hepatocellular carcinoma impairs the function of NCOA5 in cell cycle regulation.

Type 2 Diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). We have previously described that haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) is a genetic defect linking glucose intolerance to HCC. Here we report identification and characterization of a single nucleotide variation (T445A) in NCOA5, causing an amino acid Thr to Ala substitution, in adjacent non-tumorous liver tissues derived from patients with concurrent HCC and T2D.

Overexpression of TIP30 inhibits the growth and invasion of glioma cells.

Glioma is an aggressive malignancy with limited effective treatment and poor prognosis. Therefore, the identification of novel prognostic markers and effective therapeutic targets is important for the treatment of human glioma. TIP30 is a tumor suppressor involved in the regulation of numerous cellular processes, including tumor cell growth, metastasis, and angiogenesis in various human cancers.

Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma.

Although protein kinase D (PKD) has been shown to contribute to invasion and metastasis in several types of cancer, the role of PKD in the epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) has remained unclear. We found that PKD2 is up-regulated in HCC and is correlated with the metastasis of HCC. PKD2 positively regulated TNF-α-induced EMT and metastasis of HCC.

High expression of Sirt7 served as a predictor of adverse outcome in breast cancer.

Objective: Sirt7, as one of the seven Sirtuin family members, which plays distinct roles in cancer progression, is bringing emerging attention due to its oncogenic characteristic. The expression of Sirt7 in breast cancer remained unclear, and the aim of this study was to elucidate its role in breast cancer.

Methods: A total of 188 cases included in this study were immunohistochemically evaluated for Sirt7, and western blot assay was used to assess its expression in breast cell lines as well as 36 breast cancer tissues and 36 paired non-cancerous tissues.

TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma.

Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in the progression of human carcinomas. We found that TIP30, a tumor suppressor protein, translocated into the nucleus of human lung adenocarcinoma cells following EGF treatment, and the selective inhibitors of EGFR signaling pathways blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30 negatively regulated EGF-dependent transcriptional activation of CCND1 through a HDAC1-dependent mechanism.

The true role of mRECIST guideline: does it really estimate viable tumor or merely improve accuracy in hepatocellular carcinoma response evaluation?

Purpose: Modified Response Evaluation Criteria In Solid Tumors (mRECIST), developed by the American Association for the Study of Liver Diseases (AASLD) criteria measure changes in arterialized hepatocellular carcinoma (HCC) and aim at providing a common framework for the design of clinical trials. It still isn't determined whether mRECIST can be applied in routine clinical practice and whether mRECIST could estimate viable tumor correctly.

Methods: We retrospectively analyzed data from patients subjected to transcatheter arterial chemoembolization (TACE) as initial treatment for advanced HCC in our institution.

NCOA5 haploinsufficiency results in glucose intolerance and subsequent hepatocellular carcinoma.

Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers.