Isovitexin targets SIRT3 to prevent steroid-induced osteonecrosis of the femoral head by modulating mitophagy-mediated ferroptosis.

The death of osteoblasts induced by glucocorticoid (GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head (SIONFH). Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH. Isovitexin has demonstrated antioxidant properties, but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.

Epigenetic modulation of doxorubicin resistance and strategies for enhancing chemotherapeutic sensitivity.

With the rising global cancer burden, the dependency on chemotherapy also rises along with the complication of chemoresistance development. Studies on multi-drug resistant proteins provide a wide range of regulators, although the exact mechanism is not yet clearly understood. Epigenetic modifications play a vital role in the regulation of cellular processes and also in determining the efficacy of cancer therapy by modulating resistance development and tumor progression.

Role of miRNAs as epigenetic regulators of immune checkpoints in lung cancer immunity.

The advent of immunotherapy in cancer has provided new avenues in the treatment of many malignancies at various stages. Specifically, immune checkpoint inhibitors (ICIs) have transformed the field of lung cancer treatment. However, since some tumors can evade the immune system, not all patients respond properly.

Impact of Daily High Ergosterol Intake for 14 Weeks in Ovariectomized Rats on Cholesterol and Vitamin D Biosynthesis Pathways.

Postmenopausal women are at a higher risk of developing dyslipidemia and osteoporosis due to estrogen deficiency, necessitating regular vitamin D supplementation and the use of cholesterol inhibitors, respectively, to prevent these conditions. Despite current treatments, alternatives are needed to address both conditions simultaneously. Ergosterol, a precursor of vitamin D, is a fungal sterol converted to brassicasterol by 7-dehydrocholesterol reductase, a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D) into cholesterol.

Plasma membrane-coated nanoparticles and membrane vesicles to orchestrate multimodal antitumor immunity.

Background: A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit.

Dandelion extract suppresses the stem-like properties of triple-negative breast cancer cells by regulating CUEDC2/β-catenin/OCT4 signaling axis.

Ethnopharmacological Relevance: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, featuring a high proportion of cancer stem cells (CSCs) and the poorest clinical outcomes. Taraxacum mongolicum Hand. -Mazz.

Atovaquone and Selinexor as a Novel Combination Treatment Option in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia and is predominantly affecting older patients. It is a heterogenous disease, showing a broad spectrum of genomic alterations and mutations that influence the clinical outcome and treatment options. The expression of the signal transducer and activator of transcription 3 (STAT3) is often dysregulated in AML and its constitutive activation is associated with poor outcome.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat.

Introduction: Histone deacetylase inhibitors (HDACi) have shown promising preclinical activity in gastric cancer cells; unfortunately, however, these could not be confirmed in clinical trials. This highlights the need for the identification of underlying reasons, which may also provide the basis for possible combination therapies. Here, we delineated the effects of HDACi on components of EGFR signalling in gastric cancer cells.

Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.

Evaluating convalescent plasma therapy in severe COVID-19: a retrospective cohort study.

Introduction: Convalescent plasma (CP) therapy is a form of passive immunization which has been used as a treatment for coronavirus disease 2019 (COVID-19). This study aims to evaluate the efficacy and safety of CP therapy in patients with severe COVID-19.

Methodology: In this retrospective cohort study, 50 patients with severe COVID-19 treated with CP at Shahid Beheshti Hospital, Kashan, in 2019 were evaluated.

Role of ivermectin and colchicine in the treatment of COVID-19: a randomized controlled clinical trial.

Introduction: The objective of this study was to assess the effectiveness of ivermectin and colchicine as treatment options for coronavirus disease 2019 (COVID-19).

Methodology: A three-arm randomized controlled clinical trial was conducted in the Triage Clinic of the family medicine department at Ain Shams University Hospitals on participants who had been diagnosed with moderate COVID-19. Patients aged < 18 years or > 65 years, with any co-morbidities, pregnant or lactating females, and those with mild or severe COVID-19 confirmed cases were excluded.

Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Explainable vision transformer for automatic visual sleep staging on multimodal PSG signals.

Polysomnography (PSG) is crucial for diagnosing sleep disorders, but manual scoring of PSG is time-consuming and subjective, leading to high variability. While machine-learning models have improved PSG scoring, their clinical use is hindered by the 'black-box' nature. In this study, we present SleepXViT, an automatic sleep staging system using Vision Transformer (ViT) that provides intuitive, consistent explanations by mimicking human 'visual scoring'.

Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

Protective effect of Panax ginseng extract on cisplatin-induced AKI via downregulating cell death associated genes.

This study is designed to assess the effect of root extract of P. ginseng on kidney tissue injury attributed to cisplatin and its molecular mechanism involved in this process in the AKI rat model. Twenty-four male Wistar rats were randomly allocated into 4 experimental groups including: the control group, the cisplatin group, the extract 100 mg/kg group, and the extract 200 mg/kg group.

Pifithrin-μ sensitizes mTOR-activated liver cancer to sorafenib treatment.

TSC2, a suppressor of mTOR, is inactivated in up to 20% of HBV-associated liver cancer. This subtype of liver cancer is associated with aggressive behavior and early recurrence after hepatectomy. Being the first targeted regimen for advanced liver cancer, sorafenib has limited efficacy in HBV-positive patients.

Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD.

Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

Evaluation of an indirect Na1.7 inhibitor as adjunctive analgesic in burn-related neuropathic pain in a cat.

Burn-related neuropathic pain (BRNP) can arise following burn-induced nerve damage, affects approximately 6% of burned human patients and can result in chronic pain. Although widely studied in humans, data on BRNP or its treatment in animals is lacking. A 4-year-old domestic shorthair cat was presented with an infected, non-healing wound suspected to be a caustic burn.

Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study.

Background: B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.

Methods: Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining.

Automated scoring to assess RAD51-mediated homologous recombination in ovarian patient-derived tumor organoids.

PARP inhibitors (PARPi) have been shown to improve progression-free survival, particularly in homologous recombination deficient (HRD) ovarian cancers. Identifying patients eligible to PARPi is currently based on next-generation sequencing (NGS), but the persistence of genomic scars in tumors after restoration of HR or epigenetic changes can be a limitation. Functional assays could thus be used to improve this profiling and faithfully identify HRD tumors.

CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation.