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Assessment of combined antiviral drug treatment against selected α-, β-, and γ-herpesviruses.

Human herpesvirus infections cover a wide range of pathogenic outcomes and challenging situations in the medical field. All herpesviral α-, β-, and γ-subfamilies comprise representatives with a huge clinical impact on human health. The basic and translational research efforts are strongly directed towards the improved molecular understanding of infections and development of novel antiviral test systems and preventive measures. We utilized cell culture-based quantitative models for the assessment of antiviral prototype drugs against human and animal pathogenic herpesviruses. Our analysis focuse

miR-155 Directly Targets MARCH7 and Modulates Viability and Invasive Phenotypes in Breast Cancer Cells.

miR-155 is an oncogenic microRNA implicated in breast cancer, but its downstream post-transcriptional targets remain incompletely defined. This study tested membrane-associated RING-CH 7 (MARCH7) as a direct miR-155 target and examined associated molecular and cellular phenotypes in MCF-7 and MDA-MB-231 breast cancer cells. Basal miR-155 expression was assessed in MCF-10A, MCF-7, and MDA-MB-231 cells. MCF-7 cells were analyzed by MTT, RT-qPCR, Western blotting, bioinformatic prediction, dual-luciferase reporter assays, and MARCH7 knockdown; MDA-MB-231 cells were additionally evaluated by MTT,

Investigation of the Effects of Silymarin on Ovarian Ischemia Reperfusion via Nrf-2/HO-1/NQO1, Ki-67 and Wnt Signaling Pathways.

Ovarian ischemia is a pathological condition that usually occurs due to ovarian torsion, resulting in the interruption of blood supply to the ovaries and oxygen deficiency. Silymarin (SLM) is a flavonoid complex of plant origin with pharmacological properties such as antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we investigated the effects of SLM through different pathways in rats subjected to experimental ovarian ischemia/reperfusion (I/R). Female Wistar rats were divided into five groups: Control, SLM (50 mg/kg), I/R, I/R + SLM25 (25 mg/kg), and I/R + SLM50 (50 mg

18β-Glycyrrhetinic acid inhibits the proliferation and metastasis of gastric cancer by inhibiting the TCTP/AKT/P53 signaling pathway.

18β-Glycyrrhetinic acid (18β-GA) has a therapeutic effect on gastric cancer (GC), but its mechanism of action is still unclear. We analyzed the effects of 18β-GA on the proliferation, migration and invasion of GC cells using CCK technology, colony formation assay, wound healing assay and Transwell assay. BALB/c nude mice were used to establish subcutaneous transplantation models, orthotopic transplantation models and tail vein Liver metastasis models, and GC proliferation and metastasis models were constructed using zebrafish. After continuous treatment with 18β-GA, the inhibitory effect of dr

Sex-Dependent Variations in Gene Expression in Corneal Endothelial Cells Among Healthy Individuals and Patients With Fuchs Endothelial Corneal Dystrophy.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) displays a higher incidence in females than in males, yet the underlying mechanism remains unclear. This study aimed to elucidate sex-dependent differential gene expressions in corneal endothelial cells (CECs) from healthy non-FECD individuals and from patients with FECD. METHODS: RNA-Seq data from CECs of non-FECD subjects (3 males, 4 females) and FECD subjects (5 males, 5 females) were analyzed to identify differentially expressed genes (DEGs) between the sexes. We used heatmaps and principal component analysis for expression pattern visua

Neuroprotective effects of SGLT2 inhibitors empagliflozin and dapagliflozin on Aβ1-42-induced neurotoxicity and neuroinflammation in cellular models of Alzheimer's disease.

BackgroundAlzheimer's disease (AD) is a chronic brain degenerative disease that leads to dementia.ObjectiveThe aim of the present study is to investigate the neuroprotective impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) (empagliflozin and dapagliflozin) on tau phosphorylation, oxidative stress, and neuroinflammation.MethodsWe used MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, annexin-V-FITC kit, and DCFH-DA (dichloro-dihydro-fluorescein diacetate) to respectively evaluate the effect of the SGLT2i (empagliflozin and dapagliflozin) on amyloid-β (Aβ)1-4

CDK11 Promotes Paclitaxel Resistance in Cervical Cancer by Regulating LATS1-Mediated Hippo Signaling Pathway Through Phosphorylation of NF2.

Paclitaxel (PTX) is a first-line chemotherapeutic agent for cervical cancer, but resistance remains a major clinical challenge. This study investigates the role of cyclin-dependent kinase 11 (CDK11) in mediating PTX resistance and explores its underlying molecular mechanisms. Cell viability, proliferation, and apoptosis were measured using CCK8, EdU staining, colony formation, and flow cytometry, respectively. The transcriptional activity of YAP/TEAD was assessed using a dual luciferase reporter gene assay, and LATS1 ubiquitination level was assessed using an IP assay. The binding relationship

Systematic review of novel target therapies and clinical trials in chordoma.

INTRODUCTION: Chordoma represents a central nervous system tumor with an incidence of 8.4 per 10 million individuals in the U.S. Current treatment options include surgical resection and radiotherapy. Despite recent studies demonstrating significant improvement in molecular understanding of disease, treatment options remain limited. OBJECTIVES: To evaluate a database of high-throughput drug screening in conjunction with a systematic literature review of potential novel target sites. METHODS: A systematic review using terms "chordoma" AND "targeted therapy" OR "clinical trial" yielded 4560 art

Depleting CBR1 increases chemosensitivity by reducing stemness and quiescence traits in non-small cell lung cancer.

Carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily, is implicated in tumor progression and treatment resistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. This study examined CBR1 expression in NSCLC tissues and cell lines, using gene interference and pharmacological inhibition to assess its impact on stemness, chemosensitivity, and quiescence, and to explore underlying mechanisms. Our findings indicate that CBR1 expression is elevated in NSCLC tissues and cell lines, and further increases in the presence of cisplat

MicroRNA-221: A Context-Dependent Mediator in Human Diseases-Highlights from Molecular Mechanisms to Clinical Translation.

MicroRNA-221 (miR-221), a conserved small non-coding RNA, acts as a pivotal modulator of biological processes across multiple organ systems, the dysregulation of which is closely linked to the pathogenesis of various human diseases. This review systematically summarizes its multifaceted roles in cancer, cardiovascular diseases (CVDs), neurological disorders, digestive system diseases, respiratory conditions, and adipose-endocrine dysfunction. In cancer, miR-221 exerts context-dependent oncogenic/tumor-suppressive effects by targeting phosphatase and tensin homolog (PTEN), cyclin-dependent kina

FOXG1 Improves Cognitive Function in Alzheimer's Disease by Promoting Endogenous Neurogenesis.

Strategies aimed at enhancing the capacity of neural stem cells (NSCs) to generate multipotential, proliferative, and migratory cell populations capable of efficient neuronal differentiation are crucial for structural repair following neurodegenerative damage. The role of Forkhead-box gene 1 (FOXG1) in pattern formation, cell proliferation, and specification has been established. However, its involvement in Alzheimer's disease (AD) remains largely unknown. Here, we investigated the association between Foxg1 gene variants and AD-like behavioral deficits, amyloid-β (Aβ) aggregate formation, as w

α-Mangostin from the mangosteen (Garcinia mangostana) fruit for prostate cancer.

Xanthones from the mangosteen are a collection of bioactive compounds derived from the Garcinia mangostana L. The fruit of the mangosteen has been widely studied for its medicinal properties with multiple reports describing its anticancer properties. Despite recent advancements in treatment of prostate cancer, therapeutic resistance driven by the AR-V7 splice variant remains a significant challenge. This review elucidates the ability of mangosteen xanthones to exhibit anti-proliferative and apoptotic activity in prostate cancer models. Mechanistic studies reveal that α-mangostin, the most abun

Palliative care use and end-of-life care quality in HR+/HER2- metastatic breast cancer.

PURPOSE: Metastatic breast cancer (MBC) is incurable, despite therapeutic advances, especially in hormone receptor positive (HR+) and human epidermal growth factor-2 negative (HER2-) disease. Specialist palliative care (SPC) is recommended to alleviate distress and reduce overly aggressive end-of-life (EoL) care. This study determined rates of SPC, hospice utilization, and aggressive EoL care in patients with HR+/HER2- MBC. METHODS: A retrospective review was performed of patients with treatment naïve HR+/HER2- MBC treated with endocrine therapy and/or cyclin-dependent kinase 4 and 6 inhibito

Clinically proven natural products against breast cancer, with mechanistic insights.

BackgroundBreast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14% of all female cancer-related deaths worldwide. This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.MethodologyRequired data for this review article was retrieved employing several readily obtainable search databases, including Web of Science® (Thomson Reuters, USA), PubMed® (U.S. National Library of Medicine, USA), and SciVerse Scopus® (Elsevier Properties S.A., USA), takin

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… First off, it might inhibit the synthesis of cyclins, which would hinder the cell cycle phases from progressing as intended. Moreover, cell cycle suppressors like p21 and p27, which stop the cell cycle by blocking cyclin-dependent kinases (CDKs), can be upregulated by PI3K inhibition. … They intricately control cell cycle advancement by acting on essential proteins like cyclin E1, cyclins, and cyclin-dependent kinase increases, causing cell cycle halt at critical checkpoints including G1/M and G2/M transitions in MCF-7 human breast cancer cells [ 111 ]. …

Tetrandrine induces cell cycle arrest in cutaneous melanoma cells by inhibiting IL-6/CDC42 signaling.

BACKGROUND: Cutaneous melanoma (CM) is a skin melanocytes-derived malignant tumor accounting for most of the death in skin cancers. The clinical drug for CM is limited or with poor efficacy. Tetrandrine is a natural alkaloid with diverse pharmacological effects including anti-cancer. This study investigated the anti-cancer potential and mechanisms of tetrandrine in CM, which might provide more therapeutic options for CM. METHODS: The effects of tetrandrine on CM cell proliferation were evaluated via CCK8 and colony formation assay. The cell cycle analysis was conducted by flow cytometry. qRT-

Gilteritinib suppresses prostate cancer cell proliferation and migration and induces ER stress-mediated non-autophagic cytoplasmic vacuolization cell death.

Prostate cancer (PCa) is a leading malignancy among men and lacks effective treatment, particularly for metastatic stages. Metastasis contributes significantly to cancer morbidity and mortality. Gilteritinib showed anticancer activity against lung and colorectal cancer but has not been thoroughly investigated for its potential in PCa therapy. This study evaluated the anticancer effects of gilteritinib on PCa cell lines (PC3 and DU145) by assessing cytotoxicity, cell proliferation, colony formation, and migration. Mechanistic studies were conducted to determine its impact on the cell cycle, epi

Probenecid and Eugenol Mitigate Testosterone Induced Benign Prostatic Hyperplasia by Targeting Uric Acid-Induced Inflammation and Pro-Survival Pathways.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent condition among aging males, significantly impacting their quality of life. Emerging evidence links elevated uric acid (UA) levels to prostatic inflammation and hyperplasia, potentially through oxidative stress and activation of proliferative pathways. However, the role of UA in BPH pathogenesis remains poorly defined. The study aims to investigate the potential protective effects of a natural phenolic compound, eugenol, and/or probenecid against testosterone-BPH in rats, along with the possible underlying mechanisms. METHODS: BPH

Comparative Study of Conventional, Grinding, and Microwave-Assisted Synthesis of Aminopyrazolones and Diaminopyrazoles: Exploring the Antitumor Activity, Dual CDK-2/CA IX Inhibition Potential, and Apoptosis Induction.

Embracing drug design approaches including ring variation, substituent variation, and bioisosteric modifications, aminopyrazolones 2-7 and diaminopyrazoles 9-14 were synthesized as dual potent CDK-2 and CA IX inhibitors for the first time. The eco-friendly preparation of the target analogs was performed by three procedures: conventional, grinding, and microwave-assisted methods. The synthesized congeners were estimated for their antitumor effect against breast MCF-7, hepatocellular HepG2, and colon HCT-116 cells where the aminopyrazolones 4 and 7 presented significant cytotoxicity against the

Design, synthesis, biological and computational evaluation of novel S/N-glycerolyl and peptide-conjugated [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potent CDK2 inhibitors for anticancer therapy.

Targeting Cyclin-Dependent Kinase 2 (CDK2) remains a critical strategy in anticancer drug discovery. This study unveils a highly promising series of novel [1,2,4]triazolo[1,5-a]pyrimidine (TP) derivatives, achieved through innovative S/N-glycerolylation and peptide conjugation strategies. We report the rational design, efficient multi-step synthesis (yields up to 85 %), and comprehensive biological and computational evaluation. Notably, peptide conjugate 14c emerged as an exceptionally potent and selective lead, exhibiting outstanding anticancer activity against MCF-7 (IC50 = 0.7 μM), HCT-116

The novel selective HDAC1 inhibitor ZJH-1 exhibits potent antitumor activity in castration-resistant prostate cancer, potentially involving HSP90AA1.

Histone deacetylase (HDAC) inhibitors are being explored as a therapeutic approach for prostate cancer (PCa), particularly castration-resistant variants with limited treatment options. In this study, we designed and synthesized ZJH-1, a novel hydroxamate-based HDAC1-selective inhibitor, and systematically evaluated its anti-tumor efficacy and molecular mechanisms. Biochemical and affinity analyses showed ZJH-1 possesses the highest HDAC1 selectivity among isoforms, associated with H3 hyperacetylation at Lys9/27 in PCa cells. ZJH-1 demonstrated cytotoxic effects (IC50 = 65 nM in PC3 cells and 3