Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility.

Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes.

V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.

Declines in lysosomal acidification and function with aging are observed in organisms ranging from yeast to humans. V-ATPases play a central role in organelle acidification, and V-ATPase activity is regulated by reversible disassembly in many different settings. Using the yeast Saccharomyces cerevisiae as a replicative aging model, we demonstrate that V-ATPases disassemble into their V and V subcomplexes in aging cells, with release of V subunit C (Vma5) from the lysosome-like vacuole into the cytosol.

Biological function and mechanism of NAT10 in cancer.

-acetyltransferase 10 (NAT10) is a nucleolar acetyltransferase with an acetylation catalytic function and can bind various protein and RNA molecules. As the N4-acetylcytidine (ac4C) "writer" enzyme, NAT10 is reportedly involved in a variety of physiological and pathological activities. Currently, the NAT10-related molecular mechanisms in various cancers are not fully understood.

The BEN domain protein LIN-14 coordinates neuromuscular positioning during epidermal maturation.

Development and function of an organism depend on coordinated inter-tissue interaction. How such interactions are maintained during tissue renewal and reorganization remains poorly understood. Here, we find that BEN domain transcription factor LIN-14 is required in epidermis for maintaining the position of motor neurons and muscles during developmental tissue reorganization.

Antibacterial Activity of Crude , , and Methanolic Extracts on serovar Manilae.

Background And Objective: Leptospirosis is a disease caused by pathogenic prevalent in tropical countries like the Philippines. Some studies have shown that the role of currently used antibiotics for leptospirosis is unclear since trials have found no significant benefit to patient outcomes compared to placebo. This signals the need for alternative therapies, such as herbal medicines, which may provide effective therapeutic regimens in treating this infection.

Rheumatic Heart Disease Burden in Africa and the Need to Build Robust Infrastructure.

Rheumatic heart disease (RHD) is an important public health problem in Africa. Mapping the epidemiology of RHD involves elucidating its geographic distribution, temporal trends, and demographic characteristics. The prevalence of RHD in Africa varies widely, with estimates ranging from 2.

Two-dimensional Health State Map to define metabolic health using separated static and dynamic homeostasis features: a proof-of-concept study.

Defining metabolic health is critical for the earlier reversing of metabolic dysfunction and disease, and fasting-based diagnosis may not adequately assess an individual's metabolic adaptivity under stress. We constructed a novel Health State Map (HSM) comprising a Health Phenotype Score (HPS) with fasting features alone and a Homeostatic Resilience Score (HRS) with five time-point features only ( = 30, 60, 90, 180, 240 min) following a standardized mixed macronutrient tolerance test (MMTT). Among 111 Chinese adults, when the same set of fasting and post-MMTT data as for the HSM was used, the mixed-score was highly correlated with the HPS.

Praziquantel activates a native cation current in .

Introduction: Praziquantel (PZQ), an anthelmintic drug discovered in the 1970s, is still used to treat schistosomiasis and various other infections caused by parasitic flatworms. PZQ causes a triad of phenotypic effects on schistosome worms - rapid depolarization, muscle contraction, and damage throughout the worm tegument. The molecular target mediating these effects has been intimated as a Ca-permeable ion channel, but native currents evoked by PZQ have not been reported in any schistosome cell type.

Molecular and Immunological Properties of a Chimeric Glycosyl Hydrolase 18 Based on Immunoinformatics Approaches: A Design of a New Anti- Vaccine.

Leishmaniasis is a chronic inflammatory zoonotic illness caused by protozoan flagellates belonging to the genus. Current data suggest that over 1 billion people worldwide are susceptible to infection, primarily in tropical and subtropical countries, where up to 2 million new cases are reported annually. Therefore, the development of a vaccine is crucial to combating this disease.

Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.

Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.

JARID1D-dependent androgen receptor and JunD signaling activation of osteoclast differentiation inhibits prostate cancer bone metastasis through demethylating H3K4.

Bone metastasis and skeletal-related complications are primary causes of mortality in advanced-stage prostate cancer (PCa). Epigenetic regulation, particularly histone modification, plays a key role in this process; however, the underlying mechanisms remain elusive. In mouse models, JARID1D was an important mediator of both visceral and bone metastases.

Revisiting the unobtrusive role of exogenous stem cells beyond neural circuits replacement in spinal cord injury repair.

Stem cell transplantation is a promising strategy to establish neural relays in situ for spinal cord injury (SCI) repair. Recent research has reported short-term survival of exogenous cells, irrespective of immunosuppressive drugs (ISD), results in similar function recovery, though the mechanisms remain unclear. This study aims to validate this short-term repair effect and the potential mechanisms in large animals.

Unveiling urinary extracellular vesicle mRNA signature for early diagnosis and prognosis of bladder cancer.

Bladder cancer (BC) ranks as one of the most prevalent cancers. Its early diagnosis is clinically essential but remains challenging due to the lack of reliable biomarkers. Extracellular vesicles (EVs) carry abundant biological cargoes from parental cells, rendering them as promising cancer biomarkers.

C-1 Substituted isoquinolines potentiate the antimycobacterial activity of rifampicin and ethambutol.

Introduction: The emergence of extensively drug-resistant strains of threatens decades of progress in the treatment of a disease which remains one of the leading infectious causes of death worldwide. The development of novel antimycobacterial compounds is therefore essential to reinforce the existing antitubercular drug discovery pipeline. There is also interest in new compounds which can synergize with existing antitubercular drugs and can be deployed as part of a combination therapy.

Mitochondrial cholesterol metabolism related gene model predicts prognosis and treatment response in hepatocellular carcinoma.

Background: The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC.

in enhancing the effect of defactinib on gastric cancer cells via the inhibition of FAK phosphorylation.

Background: Chromosome segregation 1 like () overexpression can promote proliferation and migration in cancer. In previous study, we found that CSE1L expression was higher in gastric cancer (GC) tissues compared to normal tissues. However, the biological function and molecular mechanism of CSE1L in GC remains unclear.

Mycobactin analogue interacting with siderophore efflux-pump protein: insights from molecular dynamics simulations and whole-cell assays.

Introduction: In response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species.

Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in .

Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation.

Unveiling the impacts of metformin on hepatocellular carcinoma: A bioinformatic exploration in cell lines.

The most common type of liver cancer is hepatocellular carcinoma (HCC), accounting for 75-85% of cases. Despite its associated side effects, sorafenib remains the standard treatment for HCC. Given the critical need to improve therapeutic efficacy while minimizing adverse effects, alternative drugs must be thoroughly investigated.

Dual sgRNA-directed knockout gene expression using CRISPR/Cas9 technology for editing gene in triple-negative breast cancer.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) offers a robust approach for genome manipulation, particularly in cancer therapy. Given its high expression in triple-negative breast cancer (TNBC), targeting with CRISPR/Cas9 holds promise as a therapeutic strategy. The aim of this study was to design specific single guide ribonucleic acid (sgRNA) for CRISPR/Cas9 to permanently knock out the gene, exploring its potential as a therapeutic approach in breast cancer while addressing potential off-target effects.

Exploring the anti-inflammatory and antiapoptotic properties of phloroglucinol on pancreatic cells in diabetic models: In silico and in vivo study.

Pancreatic cell damage in diabetes mellitus is closely linked to inflammation and apoptosis. This study aimed to investigate the protective effects of phloroglucinol on pancreatic cells in a streptozotocin-induced diabetic model by assessing its anti- inflammatory and anti-apoptotic mechanisms. Phloroglucinol ligand and the structures of Bax, Bcl-2, and caspase-3 proteins were sourced from the PubChem database.

Inhibition of B-cell activating factor activity using active compounds from in the mechanism of nephrotic syndrome improvement: A computational approach.

Nephrotic syndrome, a multifaceted medical condition characterized by significant proteinuria, has recently prompted a reorientation of research efforts toward B-cell-mediated mechanisms. This shift underscores the pivotal role played by B-cells in its pathogenesis. The aim of this study was to explore potential therapeutic pathways, with specific attention given to compounds found in , including withanolides, such as physalins, which constitute one of the five distinct withanolide subgroups identified in .

Senescence in neural cell lines: comparative insights from SH-SY5Y and ReNcell VM.

Senescence, a crucial yet paradoxical phenomenon in cellular biology, acts as a barrier against cancer progression while simultaneously promoting aging and age-related pathologies. This duality underlines the importance of precise monitoring of senescence response, especially with regard to the proposed use of drugs selectively removing senescent cells. In particular, little is known about the role of senescence in neurons and in neurodegenerative diseases.

Combined replacement of lnc-MEG3 and miR-155 elicit tumor suppression in multiple myeloma.

Aims: To investigate the biological impact of simultaneous overexpression of lncRNA MEG3 and miR-155, termed a "double hit," on multiple myeloma (MM) cells compared to individual biomarker substitution.

Materials And Methods: Human MM cells were transfected with MEG3-overexpressed plasmids and miR-155 mimics. Cell cytotoxicity, apoptosis, and gene expression were evaluated in transfected cells and clinical samples.

Laboratory investigation of METTL7A driving MSC osteogenic differentiation through YAP1 translation enhancement via eIF4F recruitment.

Aim: Effective control of mesenchymal stem cell (MSC) differentiation towards osteogenic lineages is fundamental for bone regeneration. This study elucidates the regulatory role of methyltransferase like 7A (METTL7A) in the osteogenic differentiation of MSCs.

Methodology: Alkaline phosphatase staining, Alizarin Red S staining, western blotting, and in vivo studies were conducted to determine the effects of METTL7A depletion or overexpression on the osteogenic differentiation of various types of MSCs.