IP6K1 rewires LKB1 signaling to mediate hyperglycemic endothelial senescence.

Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.

GraphkmerDTA: integrating local sequence patterns and topological information for drug-target binding affinity prediction and applications in multi-target anti-Alzheimer's drug discovery.

Identifying drug-target binding affinity (DTA) plays a critical role in early-stage drug discovery. Despite the availability of various existing methods, there are still two limitations. Firstly, sequence-based methods often extract features from fixed length protein sequences, requiring truncation or padding, which can result in information loss or the introduction of unwanted noise.

Preclinical evaluation of the potential PARP-imaging probe [carbonyl-C]DPQ.

Background: Poly (ADP-ribose) polymerase (PARP) enzymes are crucial for the repair of DNA single-strand breaks and have become key therapeutic targets in homologous recombination-deficient cancers, including prostate cancer. To enable non-invasive monitoring of PARP-1 expression, several PARP-1-targeting positron emission tomography (PET) tracers have been developed. Here, we aimed to preclinically investigate [carbonyl-C]DPQ as an alternative PARP-1 PET tracer as it features a strongly distinct chemotype compared to the frontrunners [F]FluorThanatrace and [F]PARPi.

Harmonized technical standard test methods for quality evaluation of medical fluorescence endoscopic imaging systems.

Fluorescence endoscopy technology utilizes a light source of a specific wavelength to excite the fluorescence signals of biological tissues. This capability is extremely valuable for the early detection and precise diagnosis of pathological changes. Identifying a suitable experimental approach and metric for objectively and quantitatively assessing the imaging quality of fluorescence endoscopy is imperative to enhance the image evaluation criteria of fluorescence imaging technology.

Targeting BMP-1 enhances anti-tumoral effects of doxorubicin in metastatic mammary cancer: common and distinct features of TGF-β inhibition.

Purpose: Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process.

Molecular Epidemiology and Clinical Aspects of Dermatophytosis in Guiyang, Southwest China (2017-2023): A Single-Institution Retrospective Study.

Epidemiological studies combining taxonomic and clinical data have been limited globally, particularly Guiyang, the most under-developed economic provincial capital city in southwestern China. A retrospective analysis was performed of dermatophyte epidemiology involving all culture-positive cases received between May 2017 and May 2023 at the Affiliated Hospital of Guizhou Medical University. Phylogenetic analysis was conducted on 391 dermatophyte isolates collected from patients using the rDNA internal transcribed spacer sequences.

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies.

Purpose: This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies.

Methods: Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024.

Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 3: solid cancers and vascular abnormalities.

This study discusses disseminated intravascular coagulation (DIC) associated with solid cancers and various vascular abnormalities, both of which generally exhibit chronic DIC patterns. Solid cancers are among the most significant underlying diseases that induce DIC. However, the severity, bleeding tendency, and progression of DIC vary considerably depending on the type and stage of the cancer, making generalization difficult.

Amyotrophic Lateral Sclerosis and Parkinson's Disease: Brain Tissue Transcriptome Analysis Reveals Interactions.

This study utilises amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) human brain samples from the GEO database and employs differential expression gene (DEG) analysis to identify genes that are pivotal in both neurodegenerative diseases. Through in depth GO and KEGG enrichment analyses, we elucidated the biological functions and potential pathways associated with these DEGs. Furthermore, by constructing protein‒protein interaction networks, we highlight the significance of shared DEGs in both cellular physiology and disease contexts.

Sustained treatment-free remission in two chronic myeloid leukemia patients after asciminib discontinuation: a report of two cases.

Selected chronic myeloid leukemia (CML) patients may discontinue their tyrosine kinase inihibitor (TKI) in an attempt to achieve sustained treatment-free remission (TFR), which mitigates therapy-related side effects and limits treatment costs. TFR has been extensively studied following the discontinuation of adenosine triphosphate (ATP) - competitive TKI. However, there is minimal data concerning TFR after the discontinuation of the novel TKI asciminib.

Coptisine inhibits esophageal carcinoma growth by modulating pyroptosis via inhibition of HGF/c-Met signaling.

Esophageal carcinoma is a highly prevalent malignancy worldwide. The present study aimed to investigate the mechanism by which the natural compound coptisine affects pyroptosis in esophageal squamous cell carcinoma (ESCC). The expression of c-Met in ESCC patients was assessed by immunohistochemical analysis of tissue microarrays.

Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.

Purpose: Geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD), has limited treatment options. This study introduces a novel mouse model featuring an expanding GA patch that can be used to test mechanisms and therapeutics.

Methods: C57Bl/6J male mice (n = 96) aged 9-10 weeks received an intraperitoneal (IP) injection of 20 mg/kg sodium iodate (NaIO3).

Sox10 is required for systemic initiation of bone mineralization.

Heterozygous variants in SOX10 cause congenital syndromes affecting pigmentation, digestion, hearing, and neural development, primarily attributable to failed differentiation or loss of non-skeletal neural crest derivatives. We report here an additional novel requirement for Sox10 in bone mineralization. Neither crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production.

Fluoride-Induced Autophagy and Apoptosis in the Mouse Ovary: Genomic Insights into IL-17 Signaling and Gut Microbiota Dysbiosis.

Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice.

Uncovering Antiviral Potential of Cistus ladanifer Extracts Against HSV-1 and SARS-CoV-2 by In Vitro and In Silico Analysis.

Infectious diseases remain a major global health concern. Cistus ladanifer, a plant commonly employed in Moroccan traditional medicine, has been identified as a potential antiviral candidate. This study aimed to evaluate the antiviral activity of C.

The coronavirus nsp14 exoribonuclease interface with the cofactor nsp10 is essential for efficient virus replication and enzymatic activity.

Coronaviruses (CoVs) encode non-structural proteins (nsp's) 1-16, which assemble to form replication-transcription complexes that function in viral RNA synthesis. All CoVs encode a proofreading 3'-5' exoribonuclease in non-structural protein 14 (nsp14-ExoN) that mediates proofreading and high-fidelity replication and is critical for other roles in replication and pathogenesis. The enzymatic activity of nsp14-ExoN is enhanced in the presence of the cofactor nsp10.

Computational Analysis of Missense Mutations: Insight into Protein Structure and Interaction Dynamics.

is implicated in a range of conditions, including autism spectrum disorder, intellectual disability, seizures, autosomal recessive nonsyndromic intellectual disability, heterotaxy, and ciliary dysfunction. In order to understand the molecular mechanisms underlying these conditions, we focused on the structural and dynamic activity consequences of mutations within this gene. In this study, whole exome sequencing identified the c.

2'-Fucosyllactose inhibits human norovirus replication in human intestinal enteroids.

Unlabelled: Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals.

Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.

The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).

Tracking clonal and plasmid transmission in colistin- and carbapenem-resistant .

The surveillance of mobile genetic elements facilitating the spread of antimicrobial resistance genes has been challenging. Here, we tracked both clonal and plasmid transmission in colistin- and carbapenem-resistant using short- and long-read sequencing technologies. We observed three clonal transmissions, all containing Incompatibility group (Inc) L plasmids and New Delhi metallo-beta-lactamase , although not co-located on the same plasmid.

A murine model of induced myocarditis and cardiac dysfunction.

Unlabelled: is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of infection. Despite the importance of as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of associated cardiomyopathy.

Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy.

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction B (n, alpha) Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, "AB-type" Lactosome nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely -Carborane (Carb) or 1,2-dihexyl--Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the "molecular glue" effect.

Trying to Kill a Killer; Impressive Killing of Patient Derived Glioblastoma Cultures Using NK-92 Natural Killer Cells Reveals Both Sensitive and Highly Resistant Glioblastoma Cells.

The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of 5:1 and 1:1. This enabled direct comparison of the degree of glioblastoma cell loss across a broader range of glioblastoma cultures.

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.