GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Background: Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported.

Methods: GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3β and GSK3α).

Metabolic modulation of CtBP dimeric status impacts the repression of DNA damage repair genes and the platinum sensitivity of ovarian cancer.

Platinum drug-based chemotherapy plays a dominant role in OC (ovarian cancer) treatment. The expression of DNA damage repair (DDR) genes is critical in distinguishing drug-sensitive and drug-refractory patients, as well as in the development of drug resistance in long-term treated patients. CtBP is a highly expressed oncogene in OC and was found to repress DDR genes expression in our previous study.

Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.

Glycogen synthase kinase-3 (GSK3) is a highly evolutionarily conserved serine/threonine protein kinase first identified as an enzyme that regulates glycogen synthase (GS) in response to insulin stimulation, which involves GSK3 regulation of glucose metabolism and energy homeostasis. Both isoforms of GSK3, GSK3α, and GSK3β, have been implicated in many biological and pathophysiological processes. The various functions of GSK3 are indicated by its widespread distribution in multiple cell types and tissues.

Nuclear HKII-P-p53 (Ser15) Interaction is a Prognostic Biomarker for Chemoresponsiveness and Glycolytic Regulation in Epithelial Ovarian Cancer.

In epithelial ovarian cancer (EOC), carboplatin/cisplatin-induced chemoresistance is a major hurdle to successful treatment. Aerobic glycolysis is a common characteristic of cancer. However, the role of glycolytic metabolism in chemoresistance and its impact on clinical outcomes in EOC are not clear.

From impossible to possible: the lessons from the control of recent COVID-19 outbreaks in China.

The COVID-19 pandemic has catastrophically impacted the world. Before the success in vaccination, this virus shows no sign of stop spreading. Nearly all the countries have implemented stringent approaches to slow down the transmission of the virus, but the virus still caused over 2 million deaths and the number is increasing.

Applications of the CRISPR-Cas system for infectious disease diagnostics.

Introduction: Rapid and accurate diagnostic approaches are essential for impeding the spread of infectious diseases. This review aims to summarize current progress of clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems in the applications for diagnostics of infectious diseases including the ongoing COVID-19 epidemic.

Areas Covered: In this review, we discuss class 2 CRISPR-Cas biosensing systems-based diagnostics in various emerging and reemerging infectious diseases, CRISPR-Cas systems have created a new era for early diagnostics of infectious diseases, especially with the discovery of the collateral cleavage activity of Cas12 and Cas13.

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer.

Background: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood.

Methods: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019.

Nuclear localization of Desmoplakin and its involvement in telomere maintenance.

The interaction between genomic DNA and protein fundamentally determines the activity and the function of DNA elements. Capturing the protein complex and identifying the proteins associated with a specific DNA locus is difficult. Herein, we employed CRISPR, the well-known gene-targeting tool in combination with the proximity-dependent labeling tool BioID to capture a specific genome locus associated proteins and to uncover the novel functions of these proteins.

Non-classical estrogen signaling in ovarian cancer improves chemo-sensitivity and patients outcome.

Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers, especially the epithelial ovarian cancer (EOC) which shows defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown. : We analyzed the estrogen receptor α (ERα) binding profile in EOC cell lines and investigated its association with genome instability, HRR deficiency and sensitivity to chemotherapy using extensive public datasets and / experiments.

Applications of Protein Fragment Complementation Assays for Analyzing Biomolecular Interactions and Biochemical Networks in Living Cells.

Protein-protein interactions (PPIs) are indispensable for the dynamic assembly of multiprotein complexes that are central players of nearly all of the intracellular biological processes, such as signaling pathways, metabolic pathways, formation of intracellular organelles, establishment of cytoplasmic skeletons, etc. Numerous approaches have been invented to study PPIs both in vivo and in vitro, including the protein-fragment complementation assay (PCA), which is a widely applied technology to study PPIs and biomolecular interactions. PCA is a technology based on the expression of the bait and prey proteins in fusion with two complementary reporter protein fragments, respectively, that will reassemble when in close proximity.

RETRACTED: PP2ACα deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling.

Metastasis is the process through which the primary cancer cells spread beyond the primary tumor and disseminate to other organs. Most cancer patients die of metastatic disease. EMT is proposed to be the initial event associated with cancer metastasis and how it occurred is still a mystery.

BioID: A Proximity-Dependent Labeling Approach in Proteomics Study.

Biological activities are mainly executed by proteins and in most of the occasions these activities are accomplished by protein complexes or through protein-protein interactions (PPI). So it is critical to reveal how the protein complexes are organized and demonstrate the PPIs involved in the biological processes. In addition to the traditional biochemical approaches, proximity-dependent labeling (PDL) has recently been proposed to identify the interacting partners of a given protein.

Immunogenomic Analyses of Advanced Serous Ovarian Cancer Reveal Immune Score is a Strong Prognostic Factor and an Indicator of Chemosensitivity.

Ovarian cancer is one of the first human cancers for which immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required. From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score.

Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4.

Glucose and Glutamine are two essential ingredients for cell growth. However, it remains open for investigation whether there is a general mechanism that coordinates the consumption of glucose and glutamine in cancer cells. Glutamine is mainly metabolized through the glutaminolysis pathway and our previous report indicated that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway.

Integrated Analysis Reveals Tubal- and Ovarian-Originated Serous Ovarian Cancer and Predicts Differential Therapeutic Responses.

The relative importance of fallopian tube (FT) compared with ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. A collection of transcriptome data of 80 FTs, 89 OSEs, and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors.

Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy.

Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis.

Genome-wide methylome and chromatin interactome identify abnormal enhancer to be risk factor of breast cancer.

Enhancer is critical cis regulatory elements in gene expression. To understand whether and how the aberrant enhancer activation may contribute to cancer risk, the differentially methylated enhancers (eDMRs) in normal and malignant breast tissues were identified and analyzed. By incorporating genome-wide chromatin interaction, integrated analysis of eDMRs and target gene expression identified 1,272 enhancer-promoter pairs.

Proximity Labeling of Interacting Proteins: Application of BioID as a Discovery Tool.

Proteins perform biochemical functions by forming complexes, or protein-protein interactions (PPIs). Many different approaches such as phage display, yeast hybridization, etc. were developed to illustrate the PPIs, and disclose the composition and organization of protein complexes.

Distinct mutation accumulation rates among tissues determine the variation in cancer risk.

Cancer is believed to be a result of accumulated mutations. However, this concept has not been fully confirmed owing to the impossibility of tracking down the ancestral somatic cell. We sought to verify the concept by exploring the correlation between cancer risk and mutation accumulation among different tissues.

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

Objective: This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy.

Methods: 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells.

Wnt/β-Catenin Mediates AICAR Effect to Increase GATA3 Expression and Inhibit Adipogenesis.

A better understanding of the mechanism and manipulation of the tightly regulated cellular differentiation process of adipogenesis may contribute to a reduction in obesity and diabetes. Multiple transcription factors and signaling pathways are involved in the regulation of adipogenesis. Here, we report that the AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) can activate AMPK in preadipocytes and thus increase the expression of GATA3, an anti-adipogenic factor.

Phase II multi-center clinical study on using S-1 to treat advanced breast cancer after resistance to anthracycline and taxane drugs in Chinese patients.

Background: Treatment for metastatic breast cancer (MBC) in patients who have relapsed from anthracycline and taxane is difficult. S-1, an oral 5-FU derivative, has demonstrated a potential antitumor effect in patients with MBC. Thus, we evaluated the efficacy and safety of S-1 as second-line chemotherapy MBC patients in a phase II trial.