Drug screening for ischemic stroke using larvae and adult zebrafish model: a review.

Ischemic stroke (IS) is the most recorded case of stroke that is caused by decreased blood flow to the brain. Nowadays, therapeutical agents for IS are limited and they have not shown maximum clinical results. Therefore, the exploration of new candidates for IS treatment continues to be done.

FBP1 controls liver cancer evolution from senescent MASH hepatocytes.

Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH). While increasing HCC risk, MASH triggers p53-dependent hepatocyte senescence, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear.

A novel therapeutic strategy for leukopenia: Miltefosine activates the Ras/MEK/ERK pathway to promote neutrophil differentiation.

Leukopenia, marked by diminished white blood cell (WBC) counts, presents significant challenges in the management of hematological malignancies and immunocompromised patients. This study evaluated the therapeutic potential of miltefosine (MFS), a phospholipid analogue, for treating leukopenia. In vitro studies using HL60 and NB4 cells revealed that MFS effectively promoted neutrophil differentiation and function, evidenced by the upregulation of surface markers CD11b, CD11c, CD14, and CD15, as well as enhanced bactericidal activity assessed through the NBT reduction assay.

Bioanalysis of protein-unbound prednisolone in serum using equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry.

Introduction: High-dose systemic prednisolone is the cornerstone treatment of many autoimmune- and inflammatory diseases. Since prednisolone shows non-linear protein binding at higher serum concentrations, quantification of the unbound prednisolone concentration is important to understand prednisolone pharmacokinetics. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify protein-unbound prednisolone in serum.

Attenuating Atherosclerosis through Inhibition of the NF-B/NLRP3/IL-1 Pathway-Mediated Pyroptosis in Vascular Smooth Muscle Cells (VSMCs).

Objective: We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway.

Methods And Results: Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 mol/L Res.

External Validation of the Population Pharmacokinetic Models of Amisulpride and Remedial Strategies for Delayed or Missed Doses.

Objective: This study aimed to evaluate the predictive performance of published amisulpride population pharmacokinetic (PopPK) models in schizophrenia patients with an external data set and establish remedial dosing regimens for nonadherent amisulpride-treated patients.

Methods: A systematic search was conducted on PubMed, Embase, and Web of Science to identify PopPK models for evaluation. The evaluation process involved analyzing 390 serum concentration samples obtained from 361 Chinese adult inpatients diagnosed with schizophrenia.

Unveiling the Mechanisms and Therapeutic Effects of Xiaoyao Sanjie Decoction in Triple-Negative Breast Cancer: A Network Pharmacology and Experimental Validation Approach.

Purpose: Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women's health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.

Computed Tomography Scan and Clinical-based Complete Response Prediction in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Machine Learning Approach.

Background: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy (nCRT), followed by total mesorectal excision. Examining the response to treatment is one of the most important factors in the follow-up of patients; therefore, in this study, radiomics patterns derived from pretreatment computed tomography images in rectal cancer and its relationship with treatment response measurement criteria have been investigated.

Methods: Fifty patients with rectal adenocarcinoma who were candidates for nCRT and surgery were included.

Phytochemical characterization and anti-arthritic potential of green-synthesized CuO nanoparticles derived from the root extract.

Introduction: Rheumatoid arthritis is an autoimmune disease that mainly causes joint damage. The patient experiences loss of appetite, pain, fever, and fatigue. The present study was designed to phytochemically characterize and evaluate the anti-arthritic activity of green-synthesized copper oxide (CuO) nanoparticles (NPs) using the hydroalcoholic extract of roots in an adjuvant-induced arthritic rat model.

Pharmacokinetic/pharma-codynamic study of pralurbactam (FL058) combined with meropenem in a neutropenic murine thigh infection model.

Introduction: Pralurbactam (FL058) is a novel β-lactamase inhibitor with good inhibitory activity on class A, C, and D β-lactamases. This study aimed to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of pralurbactam/meropenem in a neutropenic murine thigh infection model.

Methods: After 2-h infection, neutropenic mice was treated with meropenem every 2 h alone or in combination with pralurbactam at different dosing frequencies for 24 h, and the colony count in the thighs was determined before and after treatment.

Ezetimibe/Atorvastatin, a Treatment for Hyperlipidemia, Inhibits Supraspinatus Fatty Infiltration and Improves Bone-Tendon Interface Healing in a Rotator Cuff Tear Rat Model.

Background: Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair.

Purpose: To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model.

Study Design: Controlled laboratory study.

Injectable Fibrocartilage-Forming Cores Enhance Bone-Tendon Healing in a Rat Rotator Cuff Model.

Background: After surgical repair of rotator cuff (RC) tears, the torn tendon heals unsatisfactorily to the greater tuberosity owing to limited regeneration of the bone-tendon (BT) insertion. This situation motivates the need for new interventions to enhance BT healing in the RC repair site.

Purpose: To develop injectable fibrocartilage-forming cores by tethering fibroblast growth factor 18 (FGF18) on acellular fibrocartilage matrix microparticles (AFM-MPs) and evaluate their efficacy on BT healing.

Patient-derived response estimates from zero-passage organoids of luminal breast cancer.

Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.

A Smart Semi-Implantable Device Integrating Microchannel-Enhanced Sampling and Multiplex Biochemical Testing for Deep Wound Monitoring and Pathogen Identification.

Monitoring deep wounds is challenging but necessary for high-quality medical treatment. Current methodologies for deep wound monitoring are typically limited to indirect clinical symptoms or costly non-real-time imaging diagnosis. Herein, a smart system is proposed that enables in situ monitoring of deep wounds' status through a semi-implantable device composed of 2 seamlessly connected functional components: 1) the well-designed, microchannel-structured sampling needles that efficiently and conveniently collect samples from deep wound anatomical locations, and 2) the multiplex biochemical testing compartment that facilitates the immediate and persistent detection of multiple biochemical indicators based on a color image processing software accessible to a conventional smartphone.

Proteolysis targeting chimera (PROTAC)-driven antibody internalization of oncogenic cell surface receptors.

Antibody-drug conjugates (ADCs) are increasingly used in clinic for multiple indications and may improve upon the activity of parental antibodies by delivering cytotoxic payloads into target cells. This activity is predicated upon internalization to release the cytotoxic payloads intracellularly. Since binding of ADCs to their cell surface targets does not guarantee their internalization, we hypothesize that proteolysis targeting chimeras (PROTACs) could improve the activity of ADCs through forced internalization.

Clinical predictors of 3-month isoniazid rifapentine (3HP)-related adverse drug reactions (ADR) during tuberculosis preventive therapy (PAnDoRA-3HP study): an observational study protocol.

Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs.

Synergistic Eradication of Fibrosarcoma With Acquired Ifosfamide Resistance Using Methionine Restriction Combined With Ifosfamide in Nude-mouse Models.

Background/aim: Ifosfamide is used clinically with doxorubicin as first-line chemotherapy for soft-tissue sarcoma. However, ifosfamide efficacy for soft-tissue sarcoma is limited due to frequent occurence of ifosfamide resistance and thus more effective therapy is needed. The present study aimed to determine the synergy of recombinant methioninase (rMETase) plus ifosfamide against HT1080 human fibrosarcoma cells in vitro.

Preclinical Assessment of Safety and Efficacy of Deferoxamine (DFO)-pretreated Feline Adipose Mesenchymal Stem Cells.

Background/aim: This study aimed to investigate the safety and efficacy of deferoxamine (DFO) pretreated feline adipose tissue derived mesenchymal stem cells (fATMSCs) for the treatment of inflammatory disorders.

Materials And Methods: fATMSCs were isolated from feline adipose tissue and characterized using flow cytometry for surface marker expression and differentiation assays for adipogenic, osteogenic, and chondrogenic lineages. Different concentrations of DFO were used to evaluate its impact on fATMSC activity.

The Combination of Tumor-targeting A1-R Plus the Autophagy-inhibitor Chloroquine Synergistically Eradicates HT1080 Fibrosarcoma Cells and .

Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model.

Canine Stem Cell-derived Exosomes for Lung Inflammation: Efficacy of Intratracheal Intravenous Administration in an Acute Lung Injury Mouse Model.

Background/aim: Acute lung injury (ALI) is an important pathological process in acute respiratory distress syndrome; however, feasible and effective treatment strategies for ALI are limited. Recent studies have suggested that stem cell-derived exosomes can ameliorate ALI; however, there remains no consensus on the protocols used, including the route of administration. This study aimed to identify the appropriate route of administration of canine stem cell-derived exosomes (cSC-Exos) in ALI.

Orofacial pain models induce impairment in spatial learning and working memory in rodents: A systematic review and meta-analysis.

Orofacial pain is one of the most common causes of chronic pain leading to physical and cognitive disability. Several clinical and pre-clinical studies suggest that chronic pain results in cognitive impairment. However, there is a lack of meta-analyses examining the effects of orofacial pain models on behavioral learning and memory in rodents.

Illudin S inhibits p53-Mdm2 interaction for anticancer efficacy in colorectal cancer.

The impairment of the p53 pathway was once regarded as inadequately druggable due to the specificity of the p53 structure, its flat surface lacking an ideal drug-binding site, and the difficulty in reinstating p53 function. However, renewed interest in p53-based therapies has emerged, with promising approaches targeting p53 and ongoing clinical trials investigating p53-based treatments across various cancers. Despite significant progress in p53-targeted therapies, challenges persist in identifying effective therapeutic targets within the p53 pathway.

Xiaohuafuning tang intervenes liver-depression-and-spleen-deficiency syndrome chronic-atrophic-gastritis by reshaping amino acid metabolism through gut Microbiota.

Background: Xiaohua Funing Tang (XHFND) is a decoction formula of traditional Chinese medicine (TCM) and possesses the potential to manage chronic atrophic gastritis (CAG) with liver depression and spleen deficiency (LDSD), but the mechanisms were still unclear.

Purpose: Our aim is to reveal the overall synergistic mechanisms of XHFND against CAG with LDSD.

Methods: Based on a CAG rat model with LDSD, this study combined metabolomics, gut microbiota, and network pharmacology techniques to demonstrate the XHFND mechanisms with multiple components and targets.