Mutations in fused-in-sarcoma (FUS) and TAR DNA binding protein-43 (TDP-43; TARDBP) are known to cause the severe adult-onset neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Proteinopathy caused by cellular stresses such as endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial stress and proteasomal stress and the formation of stress granules (SGs), cytoplasmic aggregates

Sorafenib resistance is a classic problem related to the treatment of advanced hepatocellular carcinoma (HCC). There is a recognized need to explore new drug resistance mechanisms and develop novel strategies to overcome the acquired resistance to sorafenib. Although one study has showed that the anti-epileptic drug valproic acid (VPA) could sensitize transforming growth factor-β (TGF-β)-induced sorafenib-resistant

Objective In sepsis, the protection of the vascular endothelium is essential and the maintenance of its function is critical to prevent further deterioration. High-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) is a bioactive lipid in plasma and its role in sepsis has not been extensively studied. This study aimed to investigate the effects of HDL-S1P on sepsis in cellular and animal

Asthma: A disease characterised by excessive and variable airway narrowing, and pathologies of inflammation and remodelling, particularly thickening of the airway smooth muscle (ASM). Treatment approaches dilate narrowed airways and reduce inflammation; however, remodelling seems largely neglected. This review considers the evolution of remodelling in asthma and whether conventional hypotheses that

Pulmonary fibrosis is characterised by excessive scarring in the lung which leads to compromised lung function, serious breathing problems and in some diseases, death. It includes several lung disorders with idiopathic pulmonary fibrosis (IPF) the most common and most severe. Pulmonary fibrosis is considered to be perpetuated by aberrant wound healing which leads to fibroblast accumulation, differentiation

Cardiac optical mapping utilises fluorescent dyes to directly image the electrical function of the heart at a high spatio-temporal resolution which far exceeds electrode techniques. It has therefore become an invaluable tool in cardiac electrophysiological research to map the propagation of heterogeneous electrical signals across the myocardium. In this review, we introduce the principles behind cardiac

Background Circular RNAs (circRNAs) play an important role in tumor development. The miRNA sponge is a common role played by circRNAs in various tumors, including breast cancer. Objective This study aimed to explore the role of circ-ZEB1 in the proliferation and apoptosis of triple negative breast cancer (TNBC) cells. Methods The expressions of several circRNAs which were predicted to be bound with

The discovery of a highly selective putative sigma-1 (σ1) receptor agonist, PRE-084, has revealed the numerous potential uses of this receptor subtype as a therapeutic target. While much work has been devoted to determining the role of σ1 receptors in normal and pathophysiological states in the nervous system, recent work suggests that σ1 receptors may be important for modulating functions of other

Osteosarcoma (OS) is a primary malignancy of bone with a tendency to metastasize early. An understanding of the pathways that regulate OS metastasis is required for the design of novel treatment approaches. Sperm-associated antigen 5 (SPAG5) is upregulated and functions as a potential tumor promoter in diverse human cancers, but has yet to be investigated in the OS. In the present study, results showed

Determining the sequence of DNA and RNA molecules has a huge impact on the understanding of cell biology and function. Recent advancements in next-generation short-read sequencing (NGS) technologies, drops in cost and a resolution down to the single-cell level shaped our current view on genome structure and function. Third-generation sequencing (TGS) methods further complete the knowledge about these

In this review, we describe key signaling pathways regulating potassium channels present in the inner mitochondrial membrane. The signaling cascades covered here include phosphorylation, redox reactions, modulation by calcium ions and nucleotides. The following types of potassium channels have been identified in the inner mitochondrial membrane of various tissues: ATP-sensitive, Ca2+-activated, voltage-gated

Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) family that contributes to tumor cell metastasis. Our previous data identified two splice variants of LOXL2 (i.e., LOXL2 Δ72 and Δ13) in esophageal squamous cell carcinoma (ESCC) cells that increased cell invasiveness and migration but had lower LOX activities than wild-type LOXL2 (LOXL2 WT). We generated a series of LOXL2 deletion

pH gradient reversal refers to intracellular alkalization and extracellular acidification commonly seen in malignant tumors. To meet their high anabolic demand, cancer cells rewire their glucose metabolism from oxidative phosphorylation to lactate fermentation, which results in the excessive generation of protons. To avoid lethal cytosolic acidification, lactate-fermenting cancer cells activate multiple

Hepatocellular carcinoma (HCC) is a fatal disease characterized by poor liver function with increasing morbidity and poor prognosis. Extracellular vesicles, released by different cells, have been associated with HCC development. Nevertheless, the mechanisms beyond extracellular vesicles in HCC remain uncharacterized. Therefore, the current study aimed to clarify the mechanism of pro-angiogenic microRNA-584-5p

NTCP (SLC10A1) has been well recognized as a basolateral (sinusoidal) Na+-bile acid co-transporter that mediates the hepatic uptake of bile acids. However, little is known about the effects of NTCP (SLC10A1) on hepatoblastoma (HB) and its underlying metabolic mechanisms. In this study, we found that NTCP (SLC10A1) expression was downregulated in HB cells and tissues, and it was demonstrated that NTCP

Neurological disorders are associated with increased oxidative stress. Reactive oxidants damage tissue and promote cell death, but it is apparent that oxidants can have more subtle effects on cell function through the modulation of redox-sensitive signalling pathways. Cells of the blood-brain barrier regulate the brain microenvironment but become dysfunctional during neurological disease. The blood-brain

Histone deacetylase inhibitors (HDACis) affect DNA repair pathways by modulating multiple cellular machineries, including chromatin state, DNA repair factor modification, and the cell cycle. These machineries can differentially affect DNA repair outcomes. With the aim to investigate the impacts of HDACis on DNA repair following CRISPR/Cas9 cleavage from the mixed actions, we used two pan-HDACis, trichostatin

Autophagy has been greatly implicated in injured endothelial cells during pulmonary arterial hypertension (PAH). β-arrestin1, a multifunctional cytoplasmic protein, has attracted considerable attention as an essential protective factor in PAH. However, its role in autophagy of injured pulmonary arterial endothelial cells (PAECs) remains to be determined. Here, we investigated the potential effects

Background/Aims Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling. Methods Male Sprague-Dawley

Genetically encoded biosensors are indispensable tools for visualizing the spatiotemporal dynamics of analytes or processes in living cells in vitro and in vivo. Their widespread adaptation has gone hand in hand with the development of sensors for new analytes or processes and improved functionality and robustness. In this review, we highlight some of the recent advances in genetically encoded biosensor

Objective Fraxetin, extracted from the bark of Fraxinus rhynchophylla, has been shown to exhibit antitumour and anti-inflammatory pharmacological properties. However, the mechanism underlying its anticancer activity towards colon adenocarcinoma (COAD) is not well understood. We aimed to determine the antitumour effect of fraxetin on COAD cell lines and elucidate its biochemical and molecular targets

Serotonin (5-HT) has traditional roles as a key neurotransmitter in the central nervous system and as a regulatory hormone controlling a broad range of physiological functions. Perhaps the most classically-defined functions of 5-HT are centrally in the control of mood, sleep and anxiety and peripherally in the modulation of gastrointestinal motility. A more recently appreciated role for 5-HT has emerged

Chronic Obstructive Pulmonary disease (COPD) involves airway inflammation and remodeling leading to small airways disease and emphysema, which results in irreversible airflow obstruction. During lung development, reciprocal interactions between the endoderm and mesoderm (epithelial-mesenchymal trophic unit (EMTU)) are essential for morphogenetic cues that direct cell proliferation, differentiation

Sex and gender differences affect all dimensions of human health ranging from the biological basis of disease to therapeutic access, choice and response. Genomics research has long ignored the role of sex differences as potential modulators and the concept is gaining more attention only recently. In the present review we summarize the current knowledge of the impact of sex differences on genomic and

Ovarian cancer (OC) is often diagnosed at an advanced stage because of the late onset of symptoms, and this together with the lack of effective treatments, has meant it is associated with a very high mortality. The aberrant expression of MicroRNA (miRNA) contributes to the initiation and development of human tumors including OC. Several miRNAs are secreted by tumor cells and can be identified in body

Expansion microscopy is a novel, fluorescence imaging technique, which allows three-dimensional nanoscale imaging of specimens on a conventional fluorescence microscope. This is achieved through an innovative sample treatment, which culminates in approximately 4.5-fold expansion of specimens in each dimension. This allows 70 nm lateral and 200 nm axial resolution. To further develop application of

Synaptic transmission is a complex process, dysregulation of which underlies several neurological conditions. Collapsin response mediator protein 2 (CRMP2) is a microtubule associated protein expressed ubiquitously in the central nervous system. Identified initially in the context of Semaphorin 3A (Collapsin) induced growth cone collapse, more recent findings revealed the involvement of CRMP2 in ion

Mycobacterium smegmatis MSMEG_0129 and Rv0164, its homologue in Mycobacterium tuberculosis, are single START-domain proteins essential for bacterial growth and survival, but their biochemical activities and biological roles remain undetermined. Here, we probed the possible functions of MSMEG_0129 and its underlying mechanisms by determining its cellular location, searching for its interaction partners

Population aging, as well as the handling of age-associated diseases, is a worldwide increasing concern. Among them, Alzheimer's disease stands out as the major cause of dementia culminating in full dependence on other people for basic functions. However, despite numerous efforts, in the last decades, there was no new approved therapeutic drug for the treatment of the disease. Calcium-activated potassium

Mitochondria exhibit high degree of heterogeneity within various tissues, including differences in terms of morphology, quantity, or function. Mitochondria can even vary among distinct sub-compartments of the same cell. Emerging evidence suggest that the molecular diversity of mitochondria can influence the identity and functionality of a given cell type. Human pathologies affecting mitochondria typically

This report aims to explore how LINC00691 regulates the proliferation and invasion of gastric cancer (GC). Clinical tissue and serum samples, as well as specimens in the Cancer Genome Atlas (TCGA) database, were used to analyse the expression of LINC00691 in GC. Our data indicated that the expression of LINC00691 in GC was significantly higher than that in healthy controls and was associated with clinicopathological

Single-molecule localisation microscopy (SMLM) gives access to biological information below the diffraction limit, allowing nanoscale cellular structures to be probed. The data output is unlike that of conventional microscopy images, instead consisting of an array of molecular coordinates. These represent a spatial point pattern that attempts to approximate, as closely as possible, the underlying positions

Cell adhesion molecule 4 (CADM4) is downregulated in many human cancers. However, CADM4 expression levels in human non-small cell lung cancer (NSCLC) tissues and its roles in NSCLC progression remain unknown. Our study aims to address these issues. We examined CADM4 levels in NSCLC tissues using real-time PCR and western blot. A549 and NCI-H1299 cells were then transfected with pcDNA3.1-CADM4 plasmid

OBJECTIVE To investigate circular RNA (circRNA) expression profile via microarray, and further assess the potential of candidate circRNAs as biomarkers in Alzheimer's disease (AD). METHODS CircRNA expression profile in cerebrospinal fluid from 8 AD patients and 8 control (Ctrl) subjects was assessed by microarray. Subsequently, 10 candidate circRNAs from microarray were validated by reverse transcription

Ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy. The proteasome-dependent and -independent

Single cell transcriptomics has emerged as a powerful method for dissecting cell type diversity and for understanding mechanisms of cell fate decisions. However, inclusion of temporal information remains challenging, since each cell can be measured only once by sequencing analysis. Here, we discuss recent progress and current efforts towards inclusion of temporal information in single cell transcriptomics

Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. Inflammasomes are large multimolecular complexes

Chronic inflammation enhances the detrimental role of dyslipidaemia during atherogenesis. Statins are among the most effective anti-atherosclerotic medications, being able to impact on both cardiovascular morbidity and mortality. Although these molecules have been first described as lipid-lowering medications, several lines of evidence suggest additional benefits through their "pleiotropic" anti-atherosclerotic

Diabetic kidney disease is growing exponentially. This review aims to discuss alternate therapeutic approaches beyond the glomerulocentric view and to consider a novel tubulocentric approach with focus on the primary cilia. Renin-angiotensin-aldosterone system blockade to decrease glomerular capillary pressure and prevent albuminuria has been the mainstay of treatment for diabetic and non-diabetic

G-protein-signaling modulator 2 (GPSM2) belongs to a protein family that regulates activation of G proteins and plays an important role in mitotic spindle orientation. However, the role of GPSM2 in lung adenocarcinoma (LUAD) is still unclear. In this study, it was found that GPSM2 correlates with clinicopathological features and patient's prognosis in LUAD. Knocking down GPSM2 promoted LUAD cell proliferation

Osteoporosis is a skeletal disorder, the pathogenic factors of which include the decreased ability of osteogenesis and enhanced osteolysis. Human-derived mesenchymal stem cells (hMSCs) possess the differential capacity to osteoblasts and chondrocytes, so the application of hMSCs in bone tissue is promising to be effective. A group of RNAs which lack of 5' and 3'ends called circular RNAs (circRNAs)

This report aims to explore how Bcl-xL, a Bcl-2 family protein, regulates PINK1/Parkin-dependent mitophagy. Compared with the Hela cells expressing Parkin alone, co-expression of Bcl-xL significantly inhibited CCCP (Carbonyl cyanide 3- chlorophenylhydrazone)-induced mitochondrial Parkin accumulation and mitophagy. Western blotting analysis illustrated that over-expressed Bcl-xL inhibited CCCP-induced

Cisplatin is one of the most widely used anticancer agents for patients with tongue squamous cell carcinoma (TSCC), but its efficacy is limited by chemoresistance. Accumulated evidence has demonstrated that reactive oxygen species (ROS) plays a critical role in multiple tumor chemotherapy resistance. In the present study, we aimed to investigate the role of ROS in cisplatin resistance of TSCC and explore

The emergence of the drugs targeting epigenetic alterations has brought an optimistic outlook for cancer patients and probably put an end into the devastating effects of the disease. Given to the prominent involvement of histone deacetylase (HDAC) enzymes in the formation of neoplastic nature of acute promyelocytic leukemia (APL), this study was aimed to evaluate the suppressive effect of pan-HDAC

Pancreatic cancer is a leading cause of cancer-related death worldwide. Cisplatin is an essential drug treating patients with BRCA1/2 or PALB2 mutations. Whether other genetic determinants of cisplatin sensitivity exist and their underlying mechanisms remain unclear. Immunohistochemistry was used to determine METTL14 expression in pancreatic cancer tissues and non-tumoural tissues. Cell proliferation

Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study,

Recent studies have shown that cardiac fibroblasts (CFs) can be transformed into induced cardiomyocytes (iCMs). This phenomenon represents a potential method for rescuing damaged myocardia after myocardial infarction. The mechanism underlying cardiac reprogramming regulation must be clarified to improve the induction efficiency of iCMs. In this study, we treated CFs with 5-aza for 24 h and added TGF-β

Autonomic nervous system dysregulation is involved in the pathophysiology of multiple cardiac arrhythmias, and therefore modulating sympathetic or parasympathetic input to the heart provides novel therapeutic options for arrhythmia management. Examples include decreasing intrinsic cardiac neuron communication, patterned vagal nerve stimulation, denervation, and blockade of post-ganglionic neurons.

The indulgent success of arsenic trioxide (ATO) in the induction of complete remission in acute promyelocytic leukemia (APL) patients has accommodated this agent into the therapeutic protocols. However, the intrusion of unfavorable side effects had put an unanswered question on the way of the application of this agent; whether the benefits of ATO may outweigh its drawbacks. In this study, we found

The activation of the β-adrenergic receptor (β-AR) regulates the human ether a-go-go-related gene (HERG) channel via protein kinase A (PKA), which in turn induces lethal arrhythmia in patients with long QT syndromes (LQTS). However, the role of A-kinase anchoring proteins (AKAPs) in PKA's regulation of the HERG channel and its molecular mechanism are not clear. Here, HEK293 cells were transfected with

BACKGROUND Long non-coding RNAs (lncRNAs) play important roles in regulation of gene expression and are involved in pathogenesis of different diseases including cancer. Recent studies suggested the lncRNA Colon cancer associated transcript-1 (CCAT1) to act as putative oncogene. In this study, to elucidate the role of this lncRNA in endometrial cancer, we examined its expression in normal endometrium

The human archease, hereafter named HArch, is identified as a key cofactor of the tRNA-splicing ligase complex, and a potential therapeutic target for treating nervous system injuries. However, little is known about the structural basis of HArch in tRNA maturation, mRNA splicing, and RNA repair. Here we report the crystal structures of HArch and its two mutants D51A and D178A with resolutions ranging

The role of microRNAs (miRNAs) in chronic kidney disease (CKD) is relatively well established, but much less is known about the role(s) of long noncoding RNAs (lncRNAs). Transforming growth factor β1 (TGF-β1) mediates inflammatory and fibrogenic signaling in CKD via the transcription factor Smad3; however, the extent of lncRNAs-based regulation of TGF-β1 signaling in CKD remains unknown. Herein, we