Biochimica et Biophysica Acta. Molecular Basis of Disease

BACKGROUND: Metastasis is one of the main obstacles impeding the survival of nasopharyngeal carcinoma (NPC) patients, with the molecular mechanism underlying NPC metastasis still unclear. RESULTS: In this study, Cystatin A (CSTA) was found downregulated in NPC tissues with metastasis compared with those without metastasis. Shorter overall survival and distant metastasis-free survival were found in NPC patients with lower CSTA expression. Using functional assays, we found that CSTA prevented both the in vitro motility of NPC cells and their ability to metastasize in vivo...

Invasion and migration are significant challenges for treatment of oral squamous cell carcinomas (OSCCs). Tumor-associated macrophages (TAMs) interact with cancer cells and are involved in tumor progression. Our recent study demonstrated that melatonin inhibits OSCC invasion and migration; however, the mechanism by which melatonin influences crosstalk between TAMs and OSCCs is poorly understood. In this study, a co-culture system was established to explore the interactions between human monocytic cells (THP-1 cells) and human tongue squamous cell carcinoma cells (SCC-15 cells)...

Heart formation requires transcriptional regulators that underlie congenital anomalies and the fetal gene program activated during heart failure. Attributing the effects of congenital heart disease (CHD) missense variants to disruption of specific protein domains allows for a mechanistic understanding of CHDs and improved diagnostics. A combined chemical and genetic approach was employed to identify novel CHD drivers, consisting of chemical screening during pluripotent stem cell (PSC) differentiation, gene expression analyses of native tissues and primary cell culture models, and the in vitro study of damaging missense variants from CHD patients...

Bone marrow-derived mesenchymal stem cells (BMSCs) are considered promising materials for treating bone diseases such as osteoporosis (OP). This research explored the functions and molecular mechanism of ankyrin repeat domain 1 (ANKRD1) in BMSC osteogenesis. An OP model in mice was established by bilateral ovariectomy. Manipulation of ANKRD1 expression in BMSCs or femurs was achieved by lentivirus infection. Increased ANKRD1 expression was observed in BMSCs during osteogenic induction. Silencing of ANKRD1 impaired the osteogenesis of BMSCs, as shown by the decreased alkaline phosphatase (ALP) activity, osteogenic gene (Runx2, Col1a1, Bglap, and Spp1) expression, and mineralized formation...

Peroxiredoxin-3 (Prx-3), a thioredoxin-dependent peroxidase located exclusively in the mitochondrial matrix, catalyses peroxides/peroxinitrites. Altered levels of Prx-3 is associated with diabetic cardiomyopathy (DCM). However, molecular mechanisms of Prx-3 gene regulation remain partially understood. We undertook a systemic analysis of the Prx-3 gene to identify the key motifs and transcriptional regulatory molecules. Transfection of promoter-reporter constructs in the cultured cells identified -191/+20 bp domain as the core promoter region...

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Cell-free heme (CFH) is a product of hemoglobin, myoglobin and hemoprotein degradation, which is a hallmark of pathologies associated with extensive hemolysis and tissue damage. CHF and iron collectively induce cytokine storm, lung injury, respiratory distress and infection susceptibility in the lungs suggesting their key role in the progression of lung disease pathology. We have previously demonstrated that heme-mediated reactive oxygen species (ROS) induces platelet activation and ferroptosis. However, interaction of ferroptotic platelets and neutrophils, the mechanism of action and associated complications remain unclear...

Most gastrointestinal stromal tumors (GIST) harbor mutated receptor tyrosine kinase (RTK) KIT/PDGFRA, which provides an attractive therapeutic target. However, a majority of GISTs ultimately develop resistance to KIT/PDGFRA inhibitor imatinib, multiple therapeutic targets will be identified as a reasonable strategy in imatinib-resistant GISTs. Biological mechanisms of non-RTK activated CDC42 associated kinase 1 (ACK1) are still unclear, which has been found to be activated in GISTs. In the current report, ACK1 overexpression is demonstrated in GIST cell lines and biopsies...

The adipokine C1q Tumor Necrosis Factor 8 (CTRP8) is the least known member of the 15 CTRP proteins and a ligand of the relaxin receptor RXFP1. We previously demonstrated the ability of the CTRP8-RXFP1 interaction to promote motility, matrix invasion, and drug resistance. The lack of specific tools to detect CTRP8 protein severely limits our knowledge on CTRP8 biological functions in normal and tumor tissues. Here, we have generated and characterized the first specific antiserum to human CTRP8 which identified CTRP8 as a novel marker of tryptase+ mast cells (MCT ) in normal human tissues and in the prostate cancer (PC) microenvironment...

BACKGROUND: Neuronal loss is a vital pathological feature of temporal lobe epilepsy (TLE). However, the exact mechanism of neuronal loss in TLE is not fully understood. Pyroptosis, a novel form of programmed cell death (PCD), has been considered a contributor to the pathogenesis of TLE. However, recent studies have implicated extensive molecular crosstalk among pyroptosis, apoptosis, and necroptosis in various diseases, and they can be transformed to each other according to different contexts...

Normothermic machine perfusion (NMP) could provide a curative treatment to reduce biliary injury in donation after cardiac death (DCD) donor livers; however, the underlying mechanisms remain poorly understood. In a rat model, our study compared air-oxygenated NMP to hyperoxygenated NMP and found that air-oxygenated NMP improved DCD functional recovery. Here, we found that the charged multivesicular body protein 2B (CHMP2B) expression was substantially elevated in the intrahepatic biliary duct endothelium of the cold-preserved rat DCD liver after air-oxygenated NMP or in biliary endothelial cells under hypoxia/physoxia...

OBJECTIVES: Recent studies validated the expression of extraoral bitter taste receptors and established the importance of regulatory functions that are associated with various cellular biological processes of these receptors. However, the importance of bitter taste receptors' activity in neointimal hyperplasia has not yet been recognized. The bitter taste receptors activator amarogentin (AMA) is known to regulate a variety of cellular signals, including AMP-activated protein kinase (AMPK), STAT3, Akt, ERK, and p53, which are associated with neointimal hyperplasia...

BACKGROUND: Liver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl4 )-induced liver fibrosis and the underlying mechanism. MATERIALS AND METHODS: A liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed...

There is increasing evidence that the crosstalk between podocytes and glomerular endothelial cells (GECs) exacerbates the progression of diabetic kidney disease (DKD). Here, we investigated the underlying role of SUMO specific peptidase 6 (SENP6) in this crosstalk. In the diabetic mice, SENP6 was decreased in glomerular tissues and its knockdown further exacerbated glomerular filtration barrier injury. In the mouse podocyte cell line MPC5 cells, SENP6 overexpression reversed HG-induced podocyte loss by suppressing the activation of Notch1 signaling...

BACKGROUND: Astrocyte activation, which is polarized into classical neurotoxic A1, neuroprotective A2, A-pan, etc., is thought to be involved in the transition from acute to chronic post-thoracotomy pain. The C3aR receptor associated with astrocyte-neuron and -microglia interactions is necessary for A1 astrocytes polarization. This study aimed to determine whether C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 expression in a rat thoracotomy pain model. METHODS: A rat thoracotomy pain model was employed...

Tenascin C (TNC) is an extracellular matrix (ECM) protein and a potential biomarker affecting progression of different tumor types, such as pancreatic and lung cancer. Alternative splicing variants of TNC are known to have an impact on interaction partners like other ECM proteins or cell surface receptors, including epidermal growth factor receptor (EGFR), leading to numerous and sometimes opposite roles of TNC in tumor cell dissemination and proliferation. Only little is known about the impact of TNC on biologic characteristics of lung cancer, such as invasion and metastatic potential...

NF-κB-inducing kinase (NIK) is an essential upstream inducer of noncanonical NF-κB signaling and a critical regulator of immunity and inflammation. Our recent work has demonstrated that NIK regulates mitochondrial respiration and adaptive metabolic responses in cancer and innate immune cells. However, it is not clear whether NIK also has roles in regulating systemic metabolism. In this study, we demonstrate that NIK has local and systemic effects on developmental and metabolic processes. Our findings show that NIK-deficient mice exhibit reduced adiposity, as well as elevated energy expenditure both basally, and under the stress of a high-fat diet...

Among the numerous adhesion G protein-coupled receptors (GPCRs), adhesion G protein-coupled estrogen receptor F5 (ADGRF5) contains unique domains in the long N-terminal tail which can determine cell-cell and cell-matrix interaction as well as cell adhesion. Nevertheless, the biology of ADGRF5 is complex and still poorly explored. Accumulating evidence suggests that the ADGRF5 activity is fundamental in health and disease. For instance, ADGRF5 is essential in the proper function of lungs and kidney as well as the endocrine system, and its signification in vascularization and tumorigenesis has been demonstrated...

The SARS-CoV-2 induced coronavirus disease (COVID-19) has recently caused a pandemic. Patients with COVID-19 presented with a wide spectrum of symptoms for the disease, from entirely asymptomatic to full-blown pneumonia and multiorgan failures. More evidence emerged, showing the production of interferons (IFNs) in the severe cases were significantly lower than their milder counterparts, suggesting linkage of COVID-19 to impaired innate immunity. This review presents a brief overview of how coronaviruses evade innate immunity, based on the information from SARS-CoV and MERS-CoV...

Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase...