The AAA-ATPase NVL2 associates with an RNA helicase MTR4 and the nuclear RNA exosome in the course of ribosome biogenesis. In our proteomic screen, we had identified a ribosome biogenesis factor WDR74 as a MTR4-interacting partner, whose dissociation is stimulated by the ATP hydrolysis of NVL2. In this study, we report the identification of splicing factor 30 (SPF30), another MTR4-interacting protein

Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), or glutaric aciduria type II (GAII), is a group of clinically heterogeneous disorders caused by mutations in electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) – the two enzymes responsible for the re-oxidation of enzyme-bound flavin adenine dinucleotide (FADH2) via electron transfer to the respiratory chain at the

Toxoplasma gondii is an obligate intracellular protozoan parasite that can cause serious public health problems. The development of a safe and effective vaccine against T. gondii is urgently needed to prevent and control the spread of toxoplasmosis. The aim of this study was to evaluate the immune responses induced by a pcGRA14 + pcROP13 vaccine cocktail in BALB/c mice. All groups were immunized intramuscularly

Background and aims Cluster of differentiation 36 (CD36) is a key scavenger receptor in the control of macrophage uptake of oxidised low-density lipoproteins (oxLDL). CD36 expression levels are not down regulated by intracellular cholesterol but are upregulated by oxidised low density lipoprotein (oxLDL) leading to the formation of lipid loaded foam cells, a major constituent of atherosclerotic plaques

Diabetic Endotheliopathy is widely regarded as a principal contributor to cardiovascular disease pathogenesis in individuals with Diabetes mellitus. The endothelium, the innermost lining of blood vessels, consists of an extensive monolayer of endothelial cells. Previously regarded as an interface, the endothelium is now accepted as an organ system with critical roles in vascular health; its dysfunction

Beyond its well-known canonical function as a tumor suppressor, p53 is also involved in numerous cellular processes through altered transcription under both normal and pathological conditions. The functional diversity of p53 outputs is complex and dependent on cell context. However, the underlying mechanisms responsible for this diversity remain largely unclear. The emerging evidence of p53 mutations

Oncogenic KRAS is one of the most common drivers of human cancer. Despite intense research, no effective therapy to directly inhibit oncogenic KRAS has yet been approved and KRAS mutant tumors remain associated with a poor prognosis. This short review discusses the current knowledge of the redox regulation of RAS and examines the newest findings on cysteine 118 (C118) as a potential novel target for

The Kank (kidney or KN motif and ankyrin repeat domain-containing) family of proteins has been described as essential for crosstalk between actin and microtubules. Kank1, 2, 3 and 4 arose by gene duplication and diversification and share conserved structural domains. KANK proteins are localised mainly to the plasma membrane in focal adhesions, indirectly affecting RhoA and Rac1 thus regulating actin

Cells have developed a unique set of molecular mechanisms that allows them to probe mechanical properties of the surrounding environment. These systems are based on deformable primary mechanosensors coupled to tension transmitting proteins and enzymes generating biochemical signals. This modular setup enables to transform a mechanical load into more versatile biochemical information. Src kinase appears

Nitric Oxide is a very well known gaseous second messenger molecule and vasorelaxant agent involved in a variety of signaling in the body such as neurotransmission, ion channel modulation, and inflammation modulation. However, it’s reversible covalent attachment to thiol groups of cysteine residues under nitrosative stress leading to aberrant protein S-nitrosylation (PSNO) has been reported in several

Agonist-mediated exocytosis of Weibel-Palade bodies underpins the endothelium’s ability to respond to injury or infection. Much of this important response is mediated by the major constituent of Weibel-Palade bodies: the ultra-large glycoprotein von Willebrand factor. Upon regulated WPB exocytosis, von Willebrand factor multimers unfurl into long, platelet-catching ‘strings’ which instigate the pro-haemostatic

The Major Histocompatibility Complex (MHC) on the short arm of chromosome 6 is associated with more diseases than any other region of the genome; it encodes the antigen-presenting Human Leukocyte Antigen (HLA) proteins and is one of the key immunogenetic regions of the genome. Accurate genome inference and interpretation of MHC association signals have traditionally been hampered by the region’s uniquely

Fibrotic diseases account for more than 8 million deaths worldwide annually. Reactive oxygen species (ROS) has been shown to activate pyroptosis and promote the production of interleukin (IL)-1β and IL-18, leading to fibrosis development. However, the role of dual oxidase 1 (DUOX1)-induced ROS production and pyroptosis in cardiac fibrosis remains largely unknown. Activin A was used to induce ROS and

Abnormal intraglandular stromal-epithelial interactions have been known as a main key contributing factor for development of Benign Prostatic Hyperplasia (BPH). However, the underlying mechanism for the dysregulated intercellular communication remains unclear. In this study we compared the proteomic profiles of hyperplastic tissue with adjacent normal tissue of BPH and identified Rab27B small GTPase

Cancers are characterized by several dramatic biological changes. Among the many post-transcriptional regulatory mechanisms, microRNAs are known as fine-tune regulators for their transcript silencing ability. Competing endogenous RNAs (ceRNAs) are transcripts that share microRNA binding elements and can compete for them, thus regulating each other indirectly. ceRNA networks interconnect the regulatory

Acute myocardial infarction (AMI) is the most common type of ischemic heart diseases with a high mortality rate. Although recent advances in medical cares and therapies have increased the patient’s outcomes, but, still there is no real and effective therapeutic modality for AMI. Hence, development of novel therapeutic strategies is under focus of investigations. MSCs-based therapy has been proposed

Nonlinear microscopy is a technique that utilizes nonlinear interactions between light and matter to image fluorescence and scattering phenomena in biological tissues. Very high peak intensities from focused short pulsed lasers are required for nonlinear excitation due to the extremely low probability of the simultaneous arrival of multiple photons of lower energy to excite fluorophores or interact

Even though subclasses of macrophage have distinct roles during progression of infectious diseases, it remains poorly understood whether there is a subset-specific difference in drug responses. Here, we report that ABCG2 was expressed specifically in M2-like macrophages and that it controlled their efflux activities. Abcg2 expression is markedly induced during polarization of PMA-primed macrophages

Cullin 4B (CUL4B), encoding a scaffold protein in Cullin RING ubiquitin-ligase complexes (CRL4B), is overexpressed and serves as an oncogene in various solid tumors. However, the roles and the underlying mechanisms of CUL4B in renal cell carcinoma (RCC) are still unknown. In this study, we demonstrated that CUL4B was significantly upregulated in RCC cells and clinical specimens, and its overexpression

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of TIPE/TNFAIP8 family, has been involved in the development and progression of various human cancers. We hypothesized that TNFAIP8 promotes prostate cancer (PCa) progression via regulation of oxidative phosphorylation (OXPHOS) and glycolysis. Ectopic expression of TNFAIP8 increased PCa cell proliferation/migration/spheroid formation by

Eukaryotic cells perform a range of complex processes, some essential for life, others specific to cell type, all of which are governed by post-translational modifications of proteins. Among the repertoire of dynamic protein modifications, ubiquitination is arguably the most arcane and profound due to its complexity. Ubiquitin conjugation consists of three main steps, the last of which involves a multitude

Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by the accumulation of lipids and inflammatory debris in large arteries, high morbidity, and AS-related disease mortality. AS is a complex process, involving endothelial cell dysfunction and inflammation, smooth muscle cell proliferation, and macrophage activation. However, the currently available therapies for AS are not

Galectin-3 is a beta-galactoside-binding mammalian lectin and part of the 15 member galectin family that are evolutionarily highly conserved. It is the only chimeric protein with a C‐terminal carbohydrate recognition domain (CRD) linked to a proline, glycine, and tyrosine rich additional N‐terminal domain. Galectin-3 binds several cell surface glycoproteins via its CRD domain as well as undergoing

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Although many effective therapies exist, a substantial portion of patients remain unprotected by current measures. Recent advances in the understanding of the underpinning cause of CVD, atherosclerosis, have demonstrated the important causative role of inflammation in disease progression. Monocytes are important protagonists of

Enhancing the functions of mesenchymal stem cells (MSCs) is considered a potential approach for promoting tissue regeneration. In this study, we investigated the effects of Matrix Metalloproteinase-1 (MMP-1) on bone marrow mesenchymal stem cells (BMSCs) and its mechanism. Our results showed that knockdown of MMP-1 impeded scratch closure, attenuated proliferation, inhibited ALP activity, ALP denser

Primary cilia are microtubule-based sensory cell organelles that are vital for tissue and organ development. They act as an antenna, receiving and transducing signals, enabling communication between cells. Defects in ciliogenesis result in severe genetic disorders collectively termed ciliopathies. In recent years, the importance of the direct and indirect involvement of actin regulators in ciliogenesis

Mevalonate pathway is a highly conserved pathway that produces isoprenoids and cholesterol, and it is often increased in cancer cells. Cholesterol, upstream metabolites including isoprenoids and cholesterol derivatives such as oxysterols modulate cell proliferation, motility, stemness and drug resistance. Moreover, when produced by cancer cells or immune infiltrating cells, they modulate the activity

Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in muscles and autonomic ganglia and regulate cytokine and neurotransmitter release in the brain and non-excitable cells. The α7 nAChRs localized in the outer membrane of mitochondria regulate cytochrome c release stimulated by apoptosis-inducing agents. However, the mechanisms through which nAChRs influence mitochondrial

Oxidative stress is an important feature of asthma pathophysiology that is not currently targeted by any of our frontline treatments. Reactive oxygen species, generated during times of heightened oxidative stress, can damage cellular lipids causing the production of oxidation specific epitopes (OSE). OSEs are elevated in chronic inflammatory diseases and promoting their clearance by the body, through

During the orthodontic tooth movement, cells in periodontal ligament could differentiate into osteoblasts to synthesize alveolar bone as well as affect the proliferation, migration and differentiation of mesenchymal stem cells, which also contribute to bone remodeling. However, the mechanism is still largely elusive. Here, we evaluated the expression of CREB at the tension site of mouse periodontal

The introduction of immune checkpoint inhibitors (ICI) has ushered in a new, golden age for cancer immunotherapy. However, their clinical success remains limited in several solid cancer types because of the low intrinsic immunogenicity of tumors and the development of immune escape mechanisms. Cancer stem cells (CSC), a small population of cancer cells that are responsible for tumor onset, metastatic

Oxidative stress is one of the main mechanisms involved in the pathophysiology of vascular diseases. Among others, oxidative stress promotes endothelial dysfunction, and accelerated ageing and remodelling of vasculature. Lately, NADPH oxidases have been demonstrated to be involved in cardiovascular diseases. NADPH oxidase 5 has emerged as a new player in oxidative stress-mediated endothelial alterations

Venous thrombosis is a life-threatening condition with high morbidity and mortality. Abnormal functioning of different cells in the blood is an integral part of its pathogenesis. In this review, we describe the contribution of bone marrow-derived cells to the development of this debilitating disease. We present both epidemiological and clinical data demonstrating involvement of various cell types in

The nuclear pore protein NUP62 localizes to spindle poles in mitosis and plays a role in maintaining centrosome homeostasis. In this study, we found that NUP62-depleted cells exhibited a defective spindle assembly checkpoint (SAC) and that depletion of NUP62 caused a slight decrease in MAD2 protein levels after nocodazole treatment. However, depletion of NUP62 did not cause a failure in kinetochore

The cell’s resistance to cell death by adhesion loss to extracellular matrix (anoikis), contributes to tumor progression and metastasis. Various adhesion molecules are involved in the anoikis resistance, including the syndecan-4 (SDC4), a heparan sulfate proteoglycan (HSPG) present on the cell surface. Changes in the expression of SDC4 have been observed in tumor and transformed cells, indicating its

Gestational diabetes (GDM) affects about 20 % of pregnancies globally. Defective insulin receptor (IR) signaling has been found in the placenta from patients with GDM, but the underly mechanism is still unclear. In the present study, the mRNA and protein levels of IR-α, insulin receptor substrate 1(IRS-1) and inulin like growth factor 1 receptor (IGF1R) were detected in the placenta tissue samples

Tumor necrosis factor-related apoptotic induction ligand can induce cell apoptosis in various tumor cells. However, many cancer cells are resistant to tumor necrosis factor-related apoptotic induction ligand. Therefore, overcoming the tumor necrosis factor-related apoptotic induction ligand resistance makes it possible for tumor necrosis factor-related apoptotic induction ligand-based anti-cancer therapies

Ras Guanine Exchange Factor (RasGEF) domain family member 1b is encoded by a Toll-like receptor (TLR)-inducible gene expressed in macrophages, but transcriptional mechanisms that govern its expression are still unknown. Here, we have functionally characterized the 5′ flanking Rasgef1b sequence and analyzed its transcriptional activation. We have identified that the inflammation-responsive promoter

Objective The purpose of this study was to establish and validate a nomogram to predict the prognosis in patients with non-small cell lung cancer (NSCLC) from multiple perspectives. Results A total of 98,640 eligible patients were randomly divided into a training set (n = 69,048) and a validation set (n = 29,592). The baseline characteristics of the two sets were similar. We used clinical data from

A number of solid tumors are treated with radiation therapy (RT) as a curative modality. At the same time, for certain types of cancers the applicable doses of RT are not high enough to result in a successful eradication of cancer cells. This is often caused by limited pharmacological tools and strategies to selectively sensitize tumors to RT while simultaneously sparing normal tissues from RT. We

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality rates. In spite of numerous advancements have been made in therapeutic methods, the prognosis of HNSCC patients remains poor. Therefore, investigation of crucial genes during HNSCC tumorigenesis which could be exploited as biomarkers and therapeutic targets is greatly needed. In this study, original

Activating foreign genes in bovine skeletal muscle is necessary in the study of the role of related genes in skeletal muscle development and the effects on skeletal muscle formation, especially in the study of transgenic cattle. At this time, a skeletal muscle-specific promoter should be selected to initiate a functional foreign gene. Here, calpain3 (CAPN3) was found to be highly expressed in skeletal

Human caseinolytic peptidase B protein homolog (CLPB), also known as suppressor of potassium transport defect 3 (SKD3), is a broadly-expressed member of the family of ATPases associated with diverse cellular activities (AAA+). Mutations in the human CLPB gene cause 3-methylglutaconic aciduria type VII. CLPB is upregulated in acute myeloid leukemia (AML), where it contributes to anti-cancer drug resistance

Epidermal growth factor receptor is a cancer driver whose nuclear localization has been associated with the progression of prostate cancer to the castration-resistant phenotype. Previous reports indicated a functional interaction between this receptor and the protein Annexin A1, which has also been associated with aggressive tumors. The molecular pathogenesis of castration-resistant prostate cancer

Identifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid

Objective To investigate the role of hsa_circ_0008934 in osteosarcoma and the molecular mechanism involved in the regulation of the occurrence and development of osteosarcoma Methods Differentially expressed circRNAs in the osteosarcoma cell lines SaOS2 and MG63 and in the normal human osteoblast cell line hFOB1.19 were identified via next-generation RNA sequencing. The expression and circular morphology

The extracellular matrix is an integral component of the vasculature, contributing to both developmental processes and structural and functional homeostasis. We describe here the types of extracellular matrices that occur in different blood vessel types, ranging from capillaries to veins, venules and arteries, and focus on the endothelial basement membranes and the laminin family of proteins. We summarize

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