410,086 results match your criteria: "Department of Clinical Pharmacology & Pharmacometrics[Affiliation]"

This research article presents a thorough and all-encompassing examination of predictive models utilized in the estimation of viscosity for ionic liquid solutions. The study focuses on crucial input parameters, namely the type of cation, the type of anion, the temperature (measured in Kelvin), and the concentration of the ionic liquid (expressed in mol%). This study assesses three influential machine learning algorithms that are based on the Decision Tree methodology.

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With breakthroughs in Natural Language Processing and Artificial Intelligence (AI), the usage of Large Language Models (LLMs) in academic research has increased tremendously. Models such as Generative Pre-trained Transformer (GPT) are used by researchers in literature review, abstract screening, and manuscript drafting. However, these models also present the attendant challenge of providing ethically questionable scientific information.

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This study investigates the potential treatment of breast cancer utilizing Gentiana robusta King ex Hook. f. (QJ) through an integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulation.

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Ensuring everyone enjoys healthy lifestyles and well-being at all ages, Progress has been made in increasing access to clean water and sanitation facilities and reducing the spread of epidemics and diseases. The synthesis of nano-particles (NPs) by using microalgae is a new nanobiotechnology due to the use of the biomolecular (corona) of microalgae as a capping and reducing agent for NP creation. This investigation explores the capacity of a distinct indigenous microalgal strain to synthesize silver nano-particles (AgNPs), as well as its effectiveness against multi-drug resistant (MDR) bacteria and its ability to degrade Azo dye (Methyl Red) in wastewater.

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Fast and sensitive multivalent spatial pattern-recognition for circular RNA detection.

Nat Commun

December 2024

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, China.

While circular RNAs (circRNAs) exhibit lower abundance compared to corresponding linear RNAs, they demonstrate potent biological functions. Nevertheless, challenges arise from the low concentration and distinctive structural features of circRNAs, rendering existing methods operationally intricate and less sensitive. Here, we engineer an intelligent tetrahedral DNA framework (TDF) possessing precise spatial pattern-recognition properties with exceptional sensing speed and sensitivity for circRNAs.

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The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention.

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Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

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Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

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Concurrent optoacoustic tomography and magnetic resonance imaging of resting-state functional connectivity in the mouse brain.

Nat Commun

December 2024

Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Resting-state functional connectivity (rsFC) has been essential to elucidate the intricacy of brain organization, further revealing clinical biomarkers of neurological disorders. Although functional magnetic resonance imaging (fMRI) remains a cornerstone in the field of rsFC recordings, its interpretation is often hindered by the convoluted physiological origin of the blood-oxygen-level-dependent (BOLD) contrast affected by multiple factors. Here, we capitalize on the unique concurrent multiparametric hemodynamic recordings of a hybrid magnetic resonance optoacoustic tomography platform to comprehensively characterize rsFC in female mice.

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METTL14 Mediates m6A methylation to improve osteogenesis under oxidative stress condition.

Redox Rep

December 2025

Department of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.

Objectives: Bone remodeling imbalance contributes to osteoporosis. Though current medications enhance osteoblast involvement in bone formation, the underlying pathways remain unclear. This study was aimed to explore the pathways involved in bone formation by osteoblasts, we investigate the protective role of glycolysis and N6-methyladenosine methylation (m6A) against oxidative stress-induced impairment of osteogenesis in MC3T3-E1 cells.

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Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

Nat Commun

December 2024

Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, SE1 9RT, UK.

The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages.

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Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).

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Antimicrobial susceptibility testing (AST) in the veterinary sector by broth microdilution is mainly based on commercially available microtitre plates with specific panels. A critical review of commercially available microtitre panels identified AST panels that fulfil the requirements for obtaining reliable AST results by covering the necessary antimicrobial concentrations for both clinical breakpoints as well as quality control (QC) ranges for approved QC strains. However, there are AST panels in which these prerequisites are only in part fulfilled, and some AST panels that do not fulfil the aforementioned criteria at all.

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Since the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, there has been a surge in scientific research to find a permanent cure for the disease. The main challenge in effective drug discovery is the continuously mutating nature of the SARS-CoV-2 virus. Thus, we have used the I-TASSER modeling to predict the structure of the SARS-CoV-2 viral envelope protein followed by combinatorial computational assessment to predict its putative potential small molecule inhibitors.

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Despite the variety of proposed solutions, anastomotic leakage is still a critical complication after colorectal surgery, which causes increased clinical mortality and morbidity. By enhancing microcirculation in the colonic mucosa, the use of Iloprost (Ilo) has shown promising results for the healing of anastomosis. The purpose of this study is to examine the performance of Ilo-impregnated Polycaprolactone:Gelatin electrospun membranes (PCL/Gel/Ilo) on anastomosis repair and intra-abdominal adhesion behavior in the Rat colon.

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Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

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The treatment of multiple sclerosis (MS) has undergone significant changes since the first disease-modifying therapy (DMT) drug was introduced. Currently, 19 original DMT drugs are registered in the European Union. The choice of optimal therapy is becoming increasingly challenging in the absence of reliable biomarkers on the basis of which disease progression and prognosis can be determined.

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Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.

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The two most clinically important members of the flavivirus genus, Zika virus (ZIKV) and dengue virus (DENV) pose a significant public health challenge. They cause a range of diseases in humans, from hemorrhagic to neurological manifestations, leading to economic and social burden worldwide. Nevertheless, there are no approved antiviral drugs to treat these infections.

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Bacterial biofilms represent a formidable challenge in the treatment of chronic wounds, largely because of their resistance to conventional antibiotics. The emergence of multidrug-resistant (MDR) bacterial strains exacerbates this issue, necessitating a shift towards exploring alternative therapeutic approaches. In response to this urgent need, there has been a surge in research efforts aimed at identifying effective non-antibiotic treatments.

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Cancers have become the second leading cause of death worldwide, following cardiovascular diseases.Traditional anti- cancer strategies, including radiotherapy chemotherapy, surgery, and targeted therapies, have been widely used but are often reassessed due to their significant side effects and relatively low cure rate. Recently, the development of novel formulations for anti-tumor drugs has gained considerable attention, marking a pivotal step forward in cancer treatment advancements.

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Background And Objectives: The study aimed to investigate the epidemiology and clinical therapy of candidemia in burn patients hospitalized in Velayat Hospital, Rasht, Iran.

Materials And Methods: The blood samples of suspected patients were cultured and PCR-sequencing was performed. Antifungal susceptibility testing was done by the CLSI M27-A4 document.

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Objectives: This study investigated the impact of hypoxic preconditioning on the survival and oxidative stress tolerance of nestin-expressing hair follicle stem cells (hHFSCs) and SH-SY5Y neuroblastoma cells, two crucial cell types for central nervous system therapies. The study also examined the relative expression of three key genes, HIF1α, BDNF, and VEGF following hypoxic preconditioning.

Materials And Methods: hHFSCs were isolated from human hair follicles, characterized, and subjected to hypoxia for up to 72 hours.

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Metformin improves infection by strengthening macrophage antimicrobial functions.

Front Immunol

December 2024

Centre of Molecular Inflammation Research, Department of Molecular and Clinical Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Introduction: The incidence and prevalence of infections with non-tuberculous mycobacteria such as (Mav) are increasing. Prolonged drug regimens, inherent antibiotic resistance, and low cure rates underscore the need for improved treatment, which may be achieved by combining standard chemotherapy with drugs targeting the host immune system. Here, we examined if the diabetes type 2 drug metformin could improve Mav-infection.

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CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights from spatial whole transcriptomic analysis.

Front Immunol

December 2024

Department of Thoracic and Cardiovascular Surgery, Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: We investigated the effects of C-reactive protein (CRP) deposition on the vessel walls in abdominal aortic aneurysm (AAA) by analyzing spatially resolved changes in gene expression. Our aim was to elucidate the pathways that contribute to disease progression.

Methods: AAA specimens from surgically resected formalin-fixed paraffin-embedded tissues were categorized into the AAA-high CRP [serum CRP ≥ 0.

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