Multifunctional nanoparticles and collagenase dual loaded thermosensitive hydrogel system for enhanced tumor-penetration, reversed immune suppression and photodynamic-immunotherapy.

Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells.

Drug repurposing for Alzheimer's disease and other neurodegenerative disorders.

Repurposed drugs provide a rich source of potential therapies for Alzheimer's disease (AD) and other neurodegenerative disorders (NDD). Repurposed drugs have information from non-clinical studies, phase 1 dosing, and safety and tolerability data collected with the original indication. Computational approaches, "omic" studies, drug databases, and electronic medical records help identify candidate therapies.

Guggulsterone ameliorates psoriasis by inhibiting keratinocyte proliferation and inflammation through induction of miR-17 directly targeting JAK1 and STAT3.

The pathogenesis of psoriasis involves hyperproliferation of epidermal keratinocytes and abnormal interactions between activated keratinocytes and infiltrating immune cells. Emerging evidence has shown that keratinocytes play essential roles in both the initiation and maintenance of psoriasis, suggesting that exposing keratinocytes to agents with antiproliferative and anti-inflammatory effects may be effective for psoriasis treatment. Guggulsterone (GS), a plant sterol derived from the gum resin of Commiphora wightii, possesses a variety of pharmacological activities.

Artificial intelligence machine learning based evaluation of elevated left ventricular end-diastolic pressure: a Cleveland Clinic cohort study.

Background: Left ventricular end-diastolic pressure (LVEDP) is a key indicator of cardiac health. The gold-standard method of measuring LVEDP is invasive intra-cardiac catheterization. Echocardiography is used for non-invasive estimation of left ventricular (LV) filling pressures; however, correlation with invasive LVEDP is variable.

A structurally informed human protein-protein interactome reveals proteome-wide perturbations caused by disease mutations.

To assist the translation of genetic findings to disease pathobiology and therapeutics discovery, we present an ensemble deep learning framework, termed PIONEER (Protein-protein InteractiOn iNtErfacE pRediction), that predicts protein-binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms to generate comprehensive structurally informed protein interactomes. We demonstrate that PIONEER outperforms existing state-of-the-art methods and experimentally validate its predictions. We show that disease-associated mutations are enriched in PIONEER-predicted protein-protein interfaces and explore their impact on disease prognosis and drug responses.

infections in a patient following high supracondylar osteotomy to treat osteoarthritis: a case report.

() is a coagulase-negative staphylococcus that is commonly found in animal pathogens. rarely causes infections in clinical practice due to its low pathogenic ability and opportunistic pathogen, which results in few relevant clinical reports. In this paper, the authors primarily report a patient infected with after a high supracondylar osteotomy and the was identified by the means of the next-generation sequencing technology.

γ-aminobutyric acid receptor B signaling drives glioblastoma in females in an immune-dependent manner.

Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying sex specific immune-cancer interactions are poorly understood. Here, we identify the neurotransmitter γ-aminobutyric acid (GABA) as a driver of GBM-promoting immune response in females.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

Background: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated.

Methods: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6.

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Introduction: New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Methods: We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024.

Artificial intelligence and open science in discovery of disease-modifying medicines for Alzheimer's disease.

The high failure rate of clinical trials in Alzheimer's disease (AD) and AD-related dementia (ADRD) is due to a lack of understanding of the pathophysiology of disease, and this deficit may be addressed by applying artificial intelligence (AI) to "big data" to rapidly and effectively expand therapeutic development efforts. Recent accelerations in computing power and availability of big data, including electronic health records and multi-omics profiles, have converged to provide opportunities for scientific discovery and treatment development. Here, we review the potential utility of applying AI approaches to big data for discovery of disease-modifying medicines for AD/ADRD.

Preparation and Improvement of Physicochemical and Functional Properties of Dietary Fiber from Corn Cob Fermented by .

Corn cobs were fermented with to produce soluble dietary fiber (SDF) of high quality and excellent food safety. In this work, the fermentation process was optimized by single-factor test and response surface methodology (RSM). The optimal fermentation conditions were determined to be a material-liquid ratio of 1:30, an inoculum concentration of 11%, a temperature of 32°C, a time of 6 days, and a shaking speed of 200 r/min.

CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.

Lung cancer is the leading cause of cancer-related death worldwide. KRAS mutations are the most common oncogenic alterations found in lung cancer. Unfortunately, treating KRAS-mutant lung adenocarcinoma (ADC) remains a major oncotherapeutic challenge.

Alzheimer's disease drug development pipeline: 2023.

Introduction: Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Methods: We searched ClinicalTrials.gov for all current Phase 1, 2 and 3 clinical trials for AD and mild cognitive impairment (MCI) attributed to AD.

GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity.

The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor.

Structurally-informed human interactome reveals proteome-wide perturbations by disease mutations.

Human genome sequencing studies have identified numerous loci associated with complex diseases. However, translating human genetic and genomic findings to disease pathobiology and therapeutic discovery remains a major challenge at multiscale interactome network levels. Here, we present a deep-learning-based ensemble framework, termed PIONEER (rotein-protein nteractin itrfac pediction), that accurately predicts protein binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms, generating comprehensive structurally-informed protein interactomes.

Interpretable deep learning translation of GWAS and multi-omics findings to identify pathobiology and drug repurposing in Alzheimer's disease.

Translating human genetic findings (genome-wide association studies [GWAS]) to pathobiology and therapeutic discovery remains a major challenge for Alzheimer's disease (AD). We present a network topology-based deep learning framework to identify disease-associated genes (NETTAG). We leverage non-coding GWAS loci effects on quantitative trait loci, enhancers and CpG islands, promoter regions, open chromatin, and promoter flanking regions under the protein-protein interactome.

The Alzheimer's Cell Atlas (TACA): A single-cell molecular map for translational therapeutics accelerator in Alzheimer's disease.

Introduction: Recent advances in generating massive single-cell/nucleus transcriptomic data have shown great potential for facilitating the identification of cell type-specific Alzheimer's disease (AD) pathobiology and drug-target discovery for therapeutic development.

Methods: We developed The Alzheimer's Cell Atlas (TACA) by compiling an AD brain cell atlas consisting of over 1.1 million cells/nuclei across 26 data sets, covering major brain regions (hippocampus, cerebellum, prefrontal cortex, and so on) and cell types (astrocyte, microglia, neuron, oligodendrocytes, and so on).

Transcriptomics-based network medicine approach identifies metformin as a repurposable drug for atrial fibrillation.

Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. This study demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug targets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF.

A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.

Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients.

A comprehensive SARS-CoV-2-human protein-protein interactome network identifies pathobiology and host-targeting therapies for COVID-19.

Physical interactions between viral and host proteins are responsible for almost all aspects of the viral life cycle and the host's immune response. Studying viral-host protein-protein interactions is thus crucial for identifying strategies for treatment and prevention of viral infection. Here, we use high-throughput yeast two-hybrid and affinity purification followed by mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of both binary and co-complex interactions.

Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.

We developed an endophenotype disease module-based methodology for Alzheimer's disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier. Based on retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio = 0.