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Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models...
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RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18...
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Prior studies examined Acidocin 4356’s antibacterial and antivirulence effects against Pseudomonas aeruginosa, including cell membrane penetration abilities. Building on prior research, an in-vitro co-culture of human cells was established to evaluate the selectivity of Acidocin (ACD) by concurrently cultivating human cells and bacterial pathogens....
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Silencers, the yin to enhancers’ yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers...
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Tuberculosis (TB) remains a major global threat, with 10 million new cases and 1.5 million deaths each year. In multidrug-resistant tuberculosis (MDR-TB), resistance is most commonly observed against isoniazid (INH) and rifampicin (RIF), the two frontline drugs. Isoniazid resistance is predominantly linked to mutations in the InhA gene, which encod...
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Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial c...
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Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18trunc mutations are oncogenic and that Z18 plays an evolutionarily conserv...
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Background Recent genome‐wide association studies (GWAS) of Alzheimer’s disease (AD) have identified approximately 70 genetic loci linked to the disorder. The pivotal challenge in the post‐GWAS era is dissecting the underlying causal variants and effector genes, a crucial step for effective therapeutic development. Most of these variants reside in...
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Aureobasidium melanogenum is a black yeast-like fungus that occurs frequently both in nature and in domestic environments. It is becoming increasingly important as an opportunistic pathogen. Nevertheless, its effect on human cells has not yet been studied. In this study, we investigated the effect of A. melanogenum cells and extracellular vesicles...
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SADS-CoV, a recently identified Rhinolophus bat coronavirus HKU2-associated swine coronavirus, is a malignant pathogen that causes acute diarrhea, severe diarrhea, and weight loss in infected piglets. The virus was first detected in Guangdong Province, China, in 2017 and has since been observed in Jiangxi, Fujian, and Guangxi Provinces. In 2023, th...
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Background Accumulation of misfolded a‐synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α‐synuclein from dopaminergic neurons could i...
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By virtue of their ability to bind different growth factors, morphogens and extracellular matrix proteins, heparan sulfate proteoglycans (HSPGs) play a determinant role in cancer cell differentiation and migration. Despite a strong conceptual basis and promising preclinical results, clinical trials have failed to demonstrate any significant advanta...
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The spirochete Borrelia burgdorferi causes Lyme disease. In some patients, an excessive, dysregulated proinflammatory immune response can develop in joints leading to persistent arthritis. In such patients, persistence of antigenic B. burgdorferi peptidoglycan (PG Bb ) fragments within joint tissues may contribute to the immunopatho-genesis, even a...
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Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally a...
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Recent advances in the clinical development of oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs) and small interfering RNAs, have attracted attention as promising therapeutic modalities for genetic and intractable diseases. These oligonucleotide therapeutics exert their efficacy by binding to target RNAs present within cells;...
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Chronic wounds are a major health problem, affecting millions of people worldwide. Resistance to treatment is frequently observed, requiring an extension of the wound healing time, and improper care can lead to more problems in patients. Smart wound dressings that provide a controlled drug release can significantly improve the healing process. In t...
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Pre-mRNA splicing, carried out in the nucleus by a large ribonucleoprotein machine known as the spliceosome, is functionally and physically coupled to the mRNA surveillance pathway in the cytoplasm called nonsense mediated mRNA decay (NMD). The NMD pathway monitors for premature translation termination signals, which can result from alternative spl...
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In an era of escalating environmental challenges, converting organic residues into high-value bioactive compounds provides a sustainable way to reduce waste and enhance resource efficiency. This study explores the potential of the circular bioeconomy through the valorization of agricultural byproducts, with a focus on the antioxidant properties of...
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Background/Objectives: The aim was to study the possibilities of biomedical application of gadolinium oxide nanoparticles (Gd2O3 NPs) synthesized under industrial conditions, and evaluate their physicochemical properties, redox activity, biological activity, and safety using different human cell lines. Methods: The powder of Gd2O3 NPs was obtained...
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The cellular stress response (CSR) is a conserved mechanism that protects cells from environmental and physiological stressors. The heat shock response (HSR), a critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic stress caused by elevated temperatures. We hypothesized that while the canonical HSR pathways are conser...
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Heterozygosity for loss-of‐function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis re...
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The development of fluorescence-based methods for bioassays and medical diagnostics requires the design and synthesis of specific markers to target biological microobjects. However, biomolecular recognition in real cellular systems is not always as selective as desired. A new concept for creating fluorescent biomolecular probes, utilizing a fluorog...
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Antimicrobial resistance in methicillin-resistant Staphylococcus aureus (MRSA) is a major global health challenge. This study reports the design and synthesis of novel phenyltriazole derivatives as potential anti-MRSA agents. The new scaffold replaces the thiazole core with a 1,2,3-triazole ring, enhancing antimicrobial efficacy and physicochemical...
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In recent years, in vitro skin sensitization assays have been recommended as animal-free alternatives for the safety assessment of cosmetics and topical drugs, and these methods have been adopted in OECD test guidelines. However, existing assays remain complex and costly. To address this, we recently developed a more efficient, cost-effective, and...
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Sucralose, a commonly nonnutritive sweetener used in daily products of habitual diet, is related to impairing the gut microbiome by disrupting inflammatory response, promoting weight gain by increasing adipose tissue and promoting chronic inflammatory processes. Considering the impact of sucralose in the development of metabolic diseases, in this w...
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The safety of titanium dioxide (TiO2), widely used in foods and personal care products, has been of ongoing concern. Significant toxicity of TiO2 has been reported, suggesting a risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO2 product to which humans could be exposed on DNA methylation, a primary epi...
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The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as tiamulin, leads to the appearance of residues in edible animal tissues. The...
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All great apes differ karyotypically from humans due to the fusion of chromosomes 2a and 2b, resulting in human chromosome 2. Yet, the structure, function, and evolutionary history of the genomic regions associated with this fusion remain poorly understood. Here, we analyze finished telomere-to-telomere chromosomes in great apes and macaques to sho...
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Motivation The difficulties in producing cell-free translation systems from different cell types limit the ability to study regulatory mechanisms that depend on different biological contexts. Developing systems tailored to diverse cell types would be instrumental in investigating cell-type-specific translational control, co- and post-translational...
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. The development of antiviral drugs for COVID-19 has been hampered by the requirement of a biosafety level 3 (BSL3) laboratory for experiments related to SARS-CoV-2, and by the lack of easy and precise methods for quantification of infection. Here, we de...
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Background: To explore the tropism and replication proficiency of specific human adenoviruses, namely HAdV-7 and HAdV-3, across a spectrum of human cell lines, and to elucidate the relationship between viral infection and the levels of hDSG2 and hCD46 receptor expression. Methods: We employed a variety of human cell lines originating from diverse t...
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The current study aimed to synthesize nitrogen-doped quantum dots (NQDs) and to study their effect on germination and drought tolerance of two rice cultivars (Sakha Super 300 and Sakha 108) at seedling stage. Microwave-assisted carbonization of glucose in presence of ammonia was followed to obtain NQDs that were characterized by spectral analysis,...
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These authors contributed equally to this work. Abstract: Accurate normalization in miRNA studies requires the use of appropriate endogenous controls, which can vary significantly depending on cell types, treatments, and physiological or pathological conditions. This study aimed to identify suitable endogenous miRNA controls for neural progenitor c...
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Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in...
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The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage speci...
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Various DNA damage checkpoint control mechanisms in eukaryotic cells help maintain genomic integrity. Among these, NBS1, a key component of the MRE11-RAD50-NBS1 (MRN) complex, is an essential protein involved in the DNA damage response (DDR). In this study, we discovered that DNA damage-binding protein 1 (DDB1) interacts with NBS1. DDB1 is a DDR se...
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Background Relapsed head and neck squamous cell carcinoma (HNSCC) unrelated to HPV infection carries a poor prognosis. Novel approaches are needed to improve the clinical outcome and prolong survival in this patient population which has poor long-term responses to immune checkpoint blockade. This study evaluated the chemokine receptors CXCR1 and CX...
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Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutat...
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Alkylphenols are byproducts of anthropogenic activities that widely contaminate waters, soils and air; among them, the most represented are 4-nonylphenol (4-NP) and 4-octylphenol (4-OP). These compounds tend to bioaccumulate in animal and plant tissues and also represent a risk to human health. Indeed, humans are constantly exposed to alkylphenols...
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Background Helicobacter pylori is a persistent pathogen in the human stomach. However, the proposed transmission route via the oral cavity is not understood and under intense debate. While dozens of studies have shown by PCR that H. pylori DNA is frequently present in the oral cavity, data on the growth and characterization of viable H. pylori from...
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The present work aims to study the cytotoxic effect of the methanolic extract of leaves and oil of three olive cultivars: Manzanillo, Picual and Koronieki. Against six cancer cell lines, namely MCF-7 and MDA (breast cancer), HepG2 (liver cancer), PC3 (prostate cancer), Caco-2 (colon cancer), and A549 (lung cancer) using the MTT method. The results...
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Staphylococcus aureus is a human pathogen responsible for a variety of diseases, from skin, soft tissue, and lung infections to severe cases such as meningitis, infective endocarditis, and bacteremia. The high level of antibiotic resistance in these pathogens, exemplified by methicillin-resistant Staphylococcus aureus (MRSA), necessitates the devel...
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Endocrine-disrupting chemicals (EDCs), found in various cosmetic products, interfere with the normal functioning of the endocrine system, impacting hormone regulation and posing risks to human health. Common cosmetic EDCs, such as ultraviolet (UV) filters, parabens, and triclosan, can enter the human body through different routes, including skin ab...
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Regulation of endoplasmic reticulum (ER) homeostasis plays a critical role in maintaining cell survival. When ER stress occurs, a network of three pathways called the unfolded protein response (UPR) is activated to reestablish homeostasis. While it is known that there is cross-talk between these pathways, how this complex network is regulated is no...
Preprint
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Cultured pluripotent stem cells are unique in being the only fully diploid immortal human cell lines. However, during continued culture they can acquire significant chromosome abnormalities. Chromosome 12 trisomy is the most common whole-chromosome abnormality found during culture of human induced pluripotent stem cells (iPSCs). The conventional pa...
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Several studies highlight the identification of some enzymes with additional abilities, especially those involved in metabolic pathways and/or host defence processes, classified as multitasking proteins. In this context, we report the characterization of melleatin (17.5-kDa), a multitasking enzyme isolated from Armillaria mellea fruiting bodies. Me...
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Agunmu (ground herbal medicine) is a form of West African traditional medicine consisting of a cocktail of herbs. The goal of this study is to evaluate a formulation of Agunmu made from M. indica, A. repens, E. chlorantha, A. boonei, and B. ferruginea, sold in the open market and commonly used for the treatment of malaria by the locals, for its ant...
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Elemental sulfur, commonly known for its wide range of biological activities, has a long history of use in protecting all garden and vegetable crops from a range of pests and diseases, including powdery mildew, ascochyta blight, clubroot, plant mites, oidium, anthracnose, and scab. In the present study, a quick and environmentally friendly approach...
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Background Since ancient times many traditional medicine systems around the world have been using different parts of Annona muricata L. (AM), to treat cancer. Indeed, numerous in vitro and in vivo studies also have shown anticancer properties of different solvent extracts of different parts of AM. Even the same part of the plant has shown different...
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Human essential proteins (HEPs) are indispensable for individual viability and development. However, experimental methods to identify HEPs are often costly, time consuming and labor intensive. In addition, existing computational methods predict HEPs only at the cell line level, but HEPs vary across living human, cell line and animal models. Here we...
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The interaction of transcription factors (TFs) with DNA precisely regulates gene transcription. In mammalian cells, thousands of TFs often interact with DNA cis‐regulatory elements in a combinatorial manner rather than act alone. The identification of cooperativity between TFs can help to explore the mechanism of transcriptional regulation. However...
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Nanotechnology offers a novel strategy for enhancing the susceptibility of pathogens resistant to traditional antibiotics. Another effective strategy is combination therapy, where multiple agents are used together to improve treatment efficacy. In this study, both nanoparticle-based formulation and combinatorial therapy were utilized to develop a p...
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Purpose For optimization of respiratory drug delivery, the selection of suitable in vitro cell models plays an important role in predicting the efficacy and safety of (bio)pharmaceutics and pharmaceutical formulations. Therefore, an in-depth comparison of different primary and permanent in vitro cellular airway models was performed with a focus on...
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Non-essential metals are extremely toxic to living organisms, posing significant health risks, particularly in developing nations where they are a major contributor to illness and death. Although their toxicity is widely acknowledged, the mechanisms by which they are regulated within human cells remain incompletely understood. Specifically, the rol...
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The Hippo signaling pathway plays a key role in tumorigenesis in different cancer types. We investigated the role of the Hippo "effector" YAP1 on the tumor immune microenvironment (TIME) of urothelial carcinoma of bladder (UCB) and evaluated the efficacy of immunotherapy in the context of YAP1 signaling. We performed numerous in vitro and in vivo e...
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L-arginine: glycine amidinotransferase (AGAT) gained academic interest as the rate-limiting enzyme in creatine biosynthesis and its role in the regulation of creatine homeostasis. Of clinical relevance is the diagnosis of patients with AGAT deficiency but also the potential role of AGAT as therapeutic target for the treatment of another creatine de...
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Microtubules play essential roles in diverse cellular processes and are important pharmacological targets for treating human disease. Here, we sought to identify cellular factors that modulate the sensitivity of cells to antimicrotubule drugs. We conducted a genome-wide CRISPR/Cas9-based functional genetics screen in human cells treated with the mi...
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N 6-Methyladenosine (6mA) is an epigenetic mark in eukaryotes regulating development, stress response and tumor progression. METTL4 has been reported as a 6mA methyltransferase induced by hypoxia. The detection and annotation of 6mA signals in mammalian cells have been hampered by the techniques and analytical methods developed so far. Here we deve...