DDX41 dissolves G-quadruplexes to maintain erythroid genome integrity and prevent cGAS-mediated cell death.

Deleterious germline variants constitute the most common inherited predisposition disorder linked to myeloid neoplasms (MNs). The role of DDX41 in hematopoiesis and how its germline and somatic mutations contribute to MNs remain unclear. Here we show that DDX41 is essential for erythropoiesis but dispensable for the development of other hematopoietic lineages.

Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube.

The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important to their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the fallopian tube that molecularly, functionally, and architecturally resembles the organ. Global label-free proteomics, innovative assays capturing physiological functions of the fallopian tube (i.

Pleckstrin-2 Mediates the Activation of AKT in Prostate Cancer and Is Repressed by Androgen Receptor.

Phosphoinositide 3-kinase (PI3K)-AKT and androgen receptor (AR) pathways are commonly activated in prostate cancers. Their reciprocal regulation makes advanced prostate cancers difficult to treat. The current study shows that pleckstrin-2 (PLEK2), a proto-oncoprotein involved in the activation and stabilization of AKT, connects these two pathways.

A 3D in vitro assay to study combined immune cell infiltration and cytotoxicity.

Immune cell-mediated killing of cancer cells in a solid tumor is prefaced by a multi-step infiltration cascade of invasion, directed migration, and cytotoxic activities. In particular, immune cells must invade and migrate through a series of different extracellular matrix (ECM) boundaries and domains before reaching and killing their target tumor cells. These infiltration events are a central challenge to the clinical success of CAR T cells against solid tumors.

mDia formins form hetero-oligomers and cooperatively maintain murine hematopoiesis.

mDia formin proteins regulate the dynamics and organization of the cytoskeleton through their linear actin nucleation and polymerization activities. We previously showed that mDia1 deficiency leads to aberrant innate immune activation and induces myelodysplasia in a mouse model, and mDia2 regulates enucleation and cytokinesis of erythroblasts and the engraftment of hematopoietic stem and progenitor cells (HSPCs). However, whether and how mDia formins interplay and regulate hematopoiesis under physiological and stress conditions remains unknown.

Precision-engineered biomimetics: the human fallopian tube.

Unlabelled: The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models to study its pathophysiology. The state-of-the-art organoid model has been compared to two-dimensional tissue sections and molecularly assessed providing only cursory analyses of the model's accuracy.

Metformin induces mitochondrial fission and reduces energy metabolism by targeting respiratory chain complex I in hepatic stellate cells to reverse liver fibrosis.

The activation and proliferation of hepatic stellate cells (HSCs) are critical processes for the treatment of liver fibrosis. It is necessary to identify effective drugs for the treatment of liver fibrosis and elucidate their mechanisms of action. Metformin can inhibit HSCs; however, no systematic studies demonstrating the effects of metformin on mitochondria in HSCs have been reported.

Chromatin reconstruction during mouse terminal erythropoiesis.

Mammalian terminal erythropoiesis involves chromatin and nuclear condensation followed by enucleation. Late-stage erythroblasts undergo caspase-mediated nuclear opening that is important for nuclear condensation through partial histone release. It remains unknown the dynamic changes of three-dimensional (3D) genomic organization during terminal erythropoiesis.

Clonal hematopoiesis and bone marrow inflammation.

Clonal hematopoiesis (CH) occurs in hematopoietic stem cells with increased risks of progressing to hematologic malignancies. CH mutations are predominantly found in aged populations and correlate with an increased incidence of cardiovascular and other diseases. Increased lines of evidence demonstrate that CH mutations are closely related to the inflammatory bone marrow microenvironment.

Targeted lipidomics analysis of lysine 179 acetylation of ACSF2 in rat hepatic stellate cells.

Activation of hepatic stellate cells (HSCs) is generally recognized as a central driver of liver fibrosis. Metabolism of fatty acids (FA) plays a critical role in the activation of HSCs. Proteomics analysis on lysine acetylation of proteins in activated HSCs in our previous study indicated that acetylation of the lysine residues on ACSF2 is one of the most significantly upregulated sites in activated-HSCs and K179 is its important acetylation site.

Bone marrow-confined IL-6 signaling mediates the progression of myelodysplastic syndromes to acute myeloid leukemia.

Myelodysplastic syndromes (MDS) are age-related myeloid neoplasms with increased risk of progression to acute myeloid leukemia (AML). The mechanisms of transformation of MDS to AML are poorly understood, especially in relation to the aging microenvironment. We previously established an mDia1/miR-146a double knockout (DKO) mouse model phenocopying MDS.

Proteome remodeling and organelle clearance in mammalian terminal erythropoiesis.

Purpose Of Review: The differentiation from colony forming unit-erythroid (CFU-E) cells to mature enucleated red blood cells is named terminal erythropoiesis in mammals. Apart from enucleation, several unique features during these developmental stages include proteome remodeling and organelle clearance that are important to achieve hemoglobin enrichment. Here, we review the recent advances in the understanding of novel regulatory mechanisms in these processes, focusing on the master regulators that link these major events during terminal erythropoiesis.

Mitigation of liver fibrosis via hepatic stellate cells mitochondrial apoptosis induced by metformin.

Liver fibrosis, a disease characterized by the excessive accumulation of extracellular matrix originating from activated hepatic stellate cells (HSCs), is a common pathological response to chronic liver injury resulting from a variety of insults. However, drugs that effectively block the activation of HSCs have still not been adequately investigated. This study demonstrates that metformin decreased the number of activated-HSCs through induction of apoptosis, but did not impact numbers of hepatocytes.

RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis.

Most cancer deaths are due to the colonization of tumor cells in distant organs. More evidence indicates that overexpression of RACGAP1 plays a critical role in cancer metastasis. However, the underlying mechanism still remains poorly understood.

Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission.

Long non-coding RNAs (lncRNAs) are emerging as key molecules in various cancers, yet their potential roles in the pathogenesis of breast cancer are not fully understood. Herein, using microarray analysis, we revealed that the lncRNA RACGAP1P, the pseudogene of Rac GTPase activating protein 1 (RACGAP1), was up-regulated in breast cancer tissues. Its high expression was confirmed in 25 pairs of breast cancer tissues and 8 breast cell lines by qRT-PCR.

BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy.

Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans.

SETDB1 induces epithelial‑mesenchymal transition in breast carcinoma by directly binding with Snail promoter.

SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 methyltransferase that is highly expressed in various tumor types, including breast cancer. However, how SETDB1 functions in breast cancer is unclear. In the present study, proliferation, migration and invasion assays were performed to explore the role of SETDB1 in breast cancer cells.

Erythropoietin-producing hepatocellular A6 overexpression is a novel biomarker of poor prognosis in patients with breast cancer.

Erythropoietin-producing hepatocellular A6 (EphA6) is a member of the Eph receptor tyrosine kinase family, which has been implicated in tumorigenesis. However, little is known about the expression and function of EphA6 in breast cancer. The aim of the present study was to investigate the expression of EphA6 and the possible association between EphA6 and clinicopathological characteristics in breast cancer.

HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma.

Hepatocellular carcinoma-related protein 1 (HCRP1), also known as human vacuolar protein sorting 37 homologue A (hVps37A), has not been detected or is significantly downregulated in hepatocellular carcinoma (HCC) tissues. However, information on the regulatory mechanisms of HCRP1 in HCC remains unclear. Here we found that the downregulation of HCRP1 in HepG2 cells (with low invasion capacity) significantly enhanced migration and invasion, whereas HCRP1 upregulation in SMMC-7721 cells (with high invasion capacity) generated the opposite result.

MicroRNA-320a inhibits breast cancer metastasis by targeting metadherin.

Dysregulated microRNAs play important pathological roles in carcinogenesis that are yet to be fully elucidated. This study was performed to investigate the biological functions of microRNA-320a (miR-320a) in breast cancer and the underlying mechanisms. Function analyses for cell proliferation, cell cycle, and cell invasion/migration, were conducted after miR-320a silencing and overexpression.

Decreased HCRP1 promotes breast cancer metastasis by enhancing EGFR phosphorylation.

Previous study showed that hepatocellular carcinoma related protein 1 (HCRP1) is decreased in breast cancer. HCRP1 expression is inversely related to epithelial growth factor receptor (EGFR) in breast cancer tissues, and patients with breast cancer expressing lower HCRP1 tended to suffer a shorter life expectancy. However, the detailed biological functions of HCRP1 in breast cancer as well as the interaction between HCRP1 and EGFR remain unexplored.