Macro-based collagen quantification and segmentation in picrosirius red-stained heart sections using light microscopy.

Picrosirius red staining constitutes an important and broadly used tool to visualize collagen and fibrosis in various tissues. Although multiple qualitative and quantitative analysis methods to evaluate fibrosis are available, many require specialized devices and software or lack objectivity and scalability. Here, we aimed to develop a versatile and powerful "" macro in the FIJI image processing software capable of automated, robust, and quick collagen quantification in cardiac tissue from light micrographs.

Mechanistic Insights of the LEMD2 p.L13R Mutation and Its Role in Cardiomyopathy.

Background: Nuclear envelope proteins play an important role in the pathogenesis of hereditary cardiomyopathies. Recently, a new form of arrhythmic cardiomyopathy caused by a homozygous mutation (p.L13R) in the inner nuclear membrane protein LEMD2 was discovered.

Hypertriglyceridemic waist phenotype and risk of chronic kidney disease in community-dwelling adults aged 60 years and older in Tianjin, China: a 7-year cohort study.

Background: The hypertriglyceridemic waist (HTGW) phenotype has been proposed to be related to the occurrence and progression of chronic kidney disease (CKD). The ageing trend of the Chinese population continues to intensify, and elderly individuals are at high risk of CKD. The purpose of this study was to investigate the cross-sectional and longitudinal associations between the HTGW phenotype and the risk of CKD by following community-dwelling adults aged 60 years and older in Tianjin, China, for 7 years.

FBW7 Mediates Senescence and Pulmonary Fibrosis through Telomere Uncapping.

Tissue stem cells undergo premature senescence under stress, promoting age-related diseases; however, the associated mechanisms remain unclear. Here, we report that in response to radiation, oxidative stress, or bleomycin, the E3 ubiquitin ligase FBW7 mediates cell senescence and tissue fibrosis through telomere uncapping. FBW7 binding to telomere protection protein 1 (TPP1) facilitates TPP1 multisite polyubiquitination and accelerates degradation, triggering telomere uncapping and DNA damage response.

Sestrin1 exerts a cytoprotective role against oxygen-glucose deprivation/reoxygenation-induced neuronal injury by potentiating Nrf2 activation via the modulation of Keap1.

Sestrin1 (Sesn1) acts as a stress-inducible protein that performs a remarkable cytoprotective function upon diverse cellular stresses. However, whether Sesn1 exerts a cytoprotective role in neurons following cerebral ischemia/reperfusion injury is unknown. The goal of this work was to evaluate the role of Sesn1 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury in vitro.

Generation of two patient-derived iPSC lines from siblings (LIBUCi001-A and LIBUCi002-A) and a genetically modified iPSC line (JMUi001-A-1) to mimic dilated cardiomyopathy with ataxia (DCMA) caused by a homozygous DNAJC19 mutation.

Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from mutations in DNAJC19. Two patient-derived dermal fibroblast cell lines of siblings with the same homozygous splice acceptor site mutation in DNAJC19 (NM_145261.4):c.

Plasma triglyceride levels and central obesity predict the development of kidney injury in Chinese community older adults.

Despite the achievement of blood glucose, blood pressure targets, the risk for kidney injury remains high among older adults. This observational retrospective study investigated whether high TG or high WC contribute to this high residual risk for kidney injury. A total of 843 elderly from Dongli Community, Tianjin, China, we selected 666 individuals with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.

Characterization of a Unique Form of Arrhythmic Cardiomyopathy Caused by Recessive Mutation in LEMD2.

Nuclear envelope proteins have been shown to play an important role in the pathogenesis of inherited dilated cardiomyopathy. Here, we present a remarkable cardiac phenotype caused by a homozygous mutation in patients of the Hutterite population with juvenile cataract. Mutation carriers develop arrhythmic cardiomyopathy with mild impairment of left ventricular systolic function but severe ventricular arrhythmias leading to sudden cardiac death.

TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence.

Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis.

Telomerase Deficiency Causes Alveolar Stem Cell Senescence-associated Low-grade Inflammation in Lungs.

Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear. In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype. Deficiency in TERC or TERT causes a remarkable elevation in various proinflammatory cytokines, including IL-1, IL-6, CXCL15 (human IL-8 homolog), IL-10, TNF-α, and monocyte chemotactic protein 1 (chemokine ligand 2 (CCL2)); decrease in TGF-β1 and TGFβRI receptor in the lungs; and spillover of IL-6 and CXCL15 into the bronchoalveolar lavage fluids.

Stressed SIRT7: facing a crossroad of senescence and immortality.

SIRT7 with coenzyme NAD catalyzes protein de-acetylation. In stress response, SIRT7 regulates protein folding in mitochondria with unknown mechanisms. Decreases in SIRT7 entrain hematopoietic stem cell senescence, but increasing SIRT7 causes elevation of hematopoietic stem cell regenerative function.

Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex.

Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase maintenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To investigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid [3 + 1] form-one human telomeric intra-molecular G-quadruplex.

Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1.

Mechanistic investigations have shown that, upon agonist activation, hydroxy-carboxylic acid receptor-1(HCA1) couples to a Gi protein and inhibits adenylate cyclase activity, leading to inhibition of liberation of free fatty acid. However, the underlying molecular mechanisms for HCA1 signaling remain largely unknown. Using CHO-K1 cells stably expressing HCA1, and L6 cells, which endogenously express rat HCA1 receptors, we found that activation of ERK1/2 by HCA1 was rapid, peaking at 5 min, and was significantly blocked by pertussis toxin.

Consideration of dual characters of exosomes in the tumour immune response.

Efforts to get a strong and sustained anti-tumour immune response induced by a tumour specific antigen have failed, but sipuleucel-T has been approved by the US Food and Drug Administration (FDA). We noticed that exosomes secreted by tumour cells or immune cells may be crucially involved in the tumour immune response, whereas others have had inconsistent findings on exosome involvement. Based on immune network theory, we summarise research advances of exosomes and speculate that in the tumour immune response exosomes follow the immune response curve hypothesis.

Adenylate kinase 2 (AK2) promotes cell proliferation in insect development.

Background: Adenylate kinase 2 (AK2) is a phosphotransferase that catalyzes the reversible reaction 2ADP(GDP) ↔ ATP(GTP) + AMP and influences cellular energy homeostasis. However, the role of AK2 in regulating cell proliferation remains unclear because AK2 has been reported to be involved in either cell proliferation or cell apoptosis in different cell types of various organisms.

Results: This study reports AK2 promotion of cell proliferation using the lepidopteran insect Helicoverpa armigera and its epidermal cell line HaEpi as models.

Radiosensitization by inhibiting complex I activity in human hepatoma HepG2 cells to X-ray radiation.

The purpose of this study is to investigate the influence of mitochondrial respiratory chain complex I inhibition on the radiosensitivity of HepG2 cells. The complex I inhibitor rotenone was used to inhibit complex I activity on HepG2 cells before X-ray irradiation. The cytotoxicity of rotenone was analyzed by MTT assay at various doses.