co-factor

Mutations in the human AAA-ATPase VPS4 isoform, VPS4A, cause severe neurodevelopmental defects and congenital dyserythropoietic anemia (CDA). VPS4 is a crucial component of the endosomal sorting complex required for transport (ESCRT) system, which drives membrane remodeling in numerous cellular processes, including receptor degradation, cell division, and neural pruning. Notably, while most organisms encode for a single VPS4 gene, human cells have 2 VPS4 paralogs, namely VPS4A and VPS4B, but the functional differences between these paralogs is mostly unknown...

Manganese is an important co-factor for numerous biological processes, including defense against reactive oxygen species. A common genetic variant in the manganese transporter SLC39A8 (p.Ala391Thr) has been associated with lower blood levels of manganese and with increases in markers of liver cell damage. Whether the variant confers an increased risk of liver disease is unclear. We tested the association of this variant with biochemical, imaging, and clinical hepatic traits and outcomes in large general population cohorts totaling up to one million individuals, including 991 cases with hepatocellular carcinoma (HCC) and 7,191 with cirrhosis...

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers...

PURPOSE: Complement dysregulation is a key component in the pathogenesis of age-related macular degeneration (AMD) and related diseases such as early-onset macular drusen (EOMD). Although genetic variants of complement factor H (CFH) are associated with AMD risk, the impact of CFH and factor H-like protein 1 (FHL-1) expression on local complement activity in human retinal pigment epithelium (RPE) remains unclear. METHODS: We identified a novel CFH variant in a family with EOMD and generated patient induced pluripotent stem cell (iPSC)-derived RPE cells...

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy...

Nano/microfluidic-based nucleic acid tests have been proposed as a rapid and reliable diagnostic technology. Two key steps for many of these tests are target nucleic acid (NA) immobilization followed by an enzymatic reaction on the captured NAs to detect the presence of a disease-associated sequence. NA capture within a geometrically confined volume is an attractive alternative to NA surface immobilization that eliminates the need for sample pre-treatment ( e.g. label-based methods such as lateral flow assays) or use of external actuators ( e...

Recently, metabolic associated steatotic liver disease (MASLD) became the leading cause of chronic liver disease worldwide and one of the most frequent causes of hepatocellular carcinoma (HCC). Nonetheless, in this epidemiological trend, viral hepatitis remains the major driver in hepatic carcinogenesis. Globally, hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma, with an overall attributable risk of approximately 40%, followed by hepatitis C virus (HCV), which accounts for 28-30% of cases, with significant geographic variations between the Eastern and Western world...

Despite recent advances in prevention, detection and treatment, oral squamous cell carcinoma (OSCC) remains a global health concern, strongly associated with environmental and lifestyle risk factors and infection with oncogenic viruses. Merkel Cell Polyomavirus (MCPyV), well known to be the causative agent of Merkel Cell Carcinoma (MCC) has been found in OSCC, suggesting its potential role as a co-factor in the development of oral cavity cancers. To improve our understanding about MCPyV in oral cavities, the detection and analysis of MCPyV DNA, transcripts and miRNA were performed on OSCCs and oral potentially malignant disorders (OPMDs)...

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is the leading risk factor of disability in the elderly. Harmonizing the metabolic actions of bone-making cells and bone resorbing cells to the mineralized matrix network is required to maintain bone mass homeostasis. The tricarboxylic acid (TCA) cycle in mitochondria is a crucial process for cellular energy production and redox homeostasis. The canonical actions of TCA cycle enzymes and intermediates are indispensable in oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis for osteogenic differentiation and osteoclast formation...

The Hippo pathway is an important regulator of organ growth and cell fate. The major mechanism by which Hippo is known to control transcription is by dictating the nucleo-cytoplasmic shuttling rate of Yorkie, a transcription co-activator, which promotes transcription with the DNA binding protein Scalloped. The nuclear biophysical behavior of Yorkie and Scalloped, and whether this is regulated by the Hippo pathway, remains unexplored. Using multiple live-imaging modalities on Drosophila tissues, we found that Scalloped interacts with DNA on a broad range of timescales, and enrichment of Scalloped at sites of active transcription is mediated by longer DNA dwell times...

(1) Background: Non-surgical endodontic treatment has been shown to be clinically successful; however, clinical long-term data are scarce. This practice-based retrospective clinical investigation evaluated endodontic outcomes over 40 years and identified relevant clinical co-factors. (2) Methods: Two experienced dental practitioners in two different private dental practices treated 174 patients with 245 teeth from 1969 to 1993. After root canal obturation, either a new direct restoration (amalgam, resin composite, or glass-ionomer cement) or the re-cementation of a pre-existing prosthetic restoration or renewal of prosthetic restoration followed...

DNA methylation is one of the most important epigenetic mark involved in many physiologic cellular processes and pathologies. During mitosis, the transmission of DNA methylation patterns from a mother to the daughter cells is ensured through the action of the Ubiquitin-like, containing PHD and RING domains, 1/DNA methyltransferase 1 (UHRF1/DNMT1) tandem. UHRF1 is involved in the silencing of many tumor suppressor genes (TSGs) via mechanisms that remain largely to be deciphered. The present study investigated the role and the regulation of UHRF1 poly-ubiquitination induced by thymoquinone, a natural anti-cancer drug, known to enhance or re-activate the expression of TSGs...

The overuse of chemical-based agricultural inputs has led to the degradation of soil with associated adverse effects on soil attributes and microbial population. This scenario leads to poor soil health and is reportedly on the rise globally. Additionally, chemical fertilizers pose serious risks to the ecosystem and human health. In this study, foliar sprays of biostimulant (AgroGain/LBS6) prepared from the cultivated, tropical red seaweed Kappaphycus alvarezii increased the phenotypic growth of Zea mays in terms of greater leaf area, total plant height, and shoot fresh and dry weights...

BACKGROUND: Vascular cognitive impairment (VCI) is a major cause of cognitive impairment in the elderly and a co-factor in the development and progression of most neurodegenerative diseases. With the continuing development of neuroimaging, multiple markers can be combined to provide richer biological information, but little is known about their diagnostic value in VCI. METHODS: A total of 83 subjects participated in our study, including 32 patients with vascular cognitive impairment with no dementia (VCIND), 21 patients with vascular dementia (VD), and 30 normal controls (NC)...

Endothelial dysfunction, underlying the vascular complications of, may result from uncoupling of endothelial nitric oxide synthase (eNOS) activity due to decreased levels of tetrahydrobiopterin (BH4), a critical co-factor for eNOS. Some clinical trials attempting to deliver exogenous BH4 as a potential therapeutic strategy in vascular disease states have failed due to oxidation of BH4 in the circulation. We sought to develop a means of protecting BH4 from oxidation while delivering it to dysfunctional endothelial cells...

Melanoma has the highest propensity among solid tumors to metastasize to the brain. Melanoma brain metastases (MBM) are a leading cause of death in melanoma and affect 40-60% of patients with late-stage disease. Therefore, uncovering the molecular mechanisms behind MBM is necessary to enhance therapeutic interventions. Vascular mimicry (VM) is a form of neovascularization linked to invasion, increased risk of metastasis, and poor prognosis in many tumor types, but its significance in MBM remains poorly understood...

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited...

[FeS] clusters are co-factors that are essential for life and are synthesized by dedicated multiprotein cellular machineries. In this review, we present the current scenario for the emergence and the diversification of the [FeS] cluster biosynthesis machineries. In addition to well-known NIF, ISC and SUF machineries, two alternative minimal systems, SMS, and MIS, were recently identified. Taxonomic distribution and phylogeny analyses indicate that SMS and MIS were present in the Last Universal Common Ancestor (LUCA), well before the increase of oxygen on Earth...

The three-dimensional structure of proteins determines their function in vital biological processes. Thus, when the structure is known, the molecular mechanism of protein function can be understood in more detail and obtained information utilized in biotechnological, diagnostics, and therapeutic applications. Over the past five years, machine learning (ML)-based modeling has pushed protein structure prediction to the next level with AlphaFold in the front line, predicting the structure for hundreds of millions of proteins...

Iron homeostasis is a critical process for living organisms because this metal is an essential co-factor for fundamental biochemical activities, like energy production and detoxification, albeit its excess quickly leads to cell intoxication. The protein Fur (ferric uptake regulator) controls iron homeostasis in bacteria by switching from its apo- to holo-form as a function of the cytoplasmic level of ferrous ions, thereby modulating gene expression. The Helicobacter pylori HpFur protein has the rare ability to operate as a transcriptional commutator; apo- and holo-HpFur function as two different repressors with distinct DNA binding recognition properties for specific sets of target genes...