Cdk1

Among women, breast carcinoma is one of the most complex cancers, with one of the highest death rates worldwide. There have been significant improvements in treatment methods, but its early detection still remains an issue to be resolved. This study explores the multifaceted function of hyaluronan-mediated motility receptor (HMMR) in breast cancer progression. HMMR's association with key cell cycle regulators (AURKA, TPX2, and CDK1) underscores its pivotal role in cancer initiation and advancement. HMMR's involvement in microtubule assembly and cellular interactions, both extracellularly and intracellularly, provides critical insights into its contribution to cancer cell processes...

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis...

Sixteen novel 2-aminobenzothiazole compounds with different amines or substituted piperazine moieties were designed, synthesized, and tested using various methods. Potential interactions were assessed by docking new compounds in the adenosine triphosphate (ATP) binding domain of the PI3Kγ enzyme (PDB code: 7JWE) by nucleophilic substitution or solvent-free/neat fusion for docked compound synthesis. Final 2-aminobenzothiazole compounds were characterized by direct probe gas chromatography-mass spectrometry (GC-MS), proton (1 H-NMR), carbon-13 (13 C-NMR), and attenuated total reflectance-infrared Fourier transform infrared (ATR FT-IR)...

Picornaviridae represent a large family of single-stranded positive RNA viruses of which different members can infect both humans and animals. These include the enteroviruses (e.g., poliovirus, coxsackievirus, and rhinoviruses) as well as the cardioviruses (e.g., encephalomyocarditis virus (EMCV)). Picornaviruses have evolved to interact with, use, and/or evade cellular host systems to create the optimal environment for replication and spreading. It is known that viruses modify kinase activity during infection, but a proteome-wide overview of the (de)regulation of cellular kinases during picornavirus infection is lacking...

Hepatocellular carcinoma (HCC) stands as a leading cause of mortality, and despite recent advancements in the overall survival rates, the prognosis remains dismal. Prunetin 4-O-glucoside (Prunetrin or PUR), an active compound derived from Prunus sp., was explored for its impact on HepG2 and Huh7 cells. The cytotoxicity assessment revealed a notable reduction in cell viability in both cell lines, while exhibiting non-toxicity towards HaCaT cells. Colony formation studies underscored PUR's inhibitory effect on cell proliferation, dose-dependently...

Meiosis is a complex variant of the mitotic cell cycle, and as such relies on many of the same proteins involved in mitotis, but utilizes these in novel ways. As in mitosis, Cdk1 and its cyclin partners, Cyclin A, B and B3 are required at multiple steps in meiosis. Here we study the effect of stabilized forms of the three mitotic cyclins to study the consequences of failure to degrade the cyclins in meiosis. We find that stabilized Cyclin B3 promotes ectopic microtubule polymerization throughout the egg, dependent on APC/C activity and apparently due to the consequent destruction of Cyclin A and Cyclin B...

With the evidence emerging that abnormal expression of long noncoding RNAs (lncRNAs) are involved in onset of Parkinson's disease (PD), the role of NR_030777 contributing to this disease is of great interest. We recently found that a novel lncRNA "NR_030777" demonstrates protective effects on PQ-induced neurodegeneration. However, the underlying molecular mechanisms of NR_030777 in the regulation of mitochondrial fission and mitophagy involved in PQ-induced neuronal damage remain to be explored. NR_030777 brain conditional overexpressing mice as well as in vitro primary neuronal cells from cerebral cortex and Neuro2a cells were adopted...

Abscission is the final step of cytokinesis which allows the physical separation of sister cells through the scission of the cellular membrane. This deformation is driven by ESCRT-III proteins which can bind membranes and form dynamic helices. A crucial step in abscission is the recruitment of ESCRT-III proteins at the right time and place. Alix is one of the best characterized proteins that recruits ESCRT-III proteins from yeast to mammals. However, recent studies in vivo revealed that pathways acting independently or redundantly with Alix are also required at abscission sites in different cellular contexts...

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis...

This study aims to investigate the induction effect of LncRNA-CIR6 on MSC differentiation into cardiogenic cells in vitro and in vivo. In addition to pretreatment with Ro-3306 (a CDK1 inhibitor), LncRNA-CIR6 was transfected into BMSCs and hUCMSCs using jetPRIME. LncRNA-CIR6 was further transfected into the hearts of C57BL/6 mice via 100 μL of AAV9-cTnT-LncRNA-CIR6-ZsGreen intravenous injection. After three weeks of transfection followed by AMI surgery, hUCMSCs (5 × 105 /100 μL) were injected intravenously one week later...

Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of HMGB1 and HMGB2 silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected...

BACKGROUND: Environmental factors serve as one of the important pathogenic factors for gliomas. Yet people focus only on the effect of electromagnetic radiation on its pathogenicity, while metals in the environment are neglected. This study aimed to investigate the relationship between metal ion stimulation and the clinical characteristics and immune status of GM patients. METHODS: Firstly, mRNA expression profiles of GM patients and normal subjects were obtained from Chinese GM Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) to identify differentially expressed metal ion stimulation-related genes(DEMISGs)...

BACKGROUND: Resistance to targeted therapies represents a significant hurdle to successfully treating hepatocellular carcinoma (HCC). While epigenetic abnormalities are critical determinants of HCC relapse and therapeutic resistance, the underlying mechanisms are poorly understood. We aimed to address whether and how dysregulated epigenetic regulators have regulatory and functional communications in establishing and maintaining drug resistance. METHODS: HCC-resistant cells were characterized by CCK-8, IncuCyte Live-Cell analysis, flow cytometry and wound-healing assays...

Nematode infections are common in both humans and livestock, with major adverse planetary health and economic impacts. Wuchereria bancrofti is a parasitic nematode that causes lymphatic filariasis, a neglected tropical disease that can lead to severe disability and deformity worldwide. For the long-term survival of the bancroftian parasites in the host, a complex immune invasion strategy is involved through immunomodulation. Therefore, immunomodulation can serve as a site of research and innovation for molecular targets...

Cyclin-dependent kinase 1 (Cdk1) complexed with cyclin B phosphorylates multiple sites on hundreds of proteins during mitosis. However, it is not fully understood how multi-site mitotic phosphorylation by cyclin B-Cdk1 controls the structures and functions of individual substrates. Here we develop an easy-to-use protocol to express recombinant vertebrate cyclin B and Cdk1 in insect cells from a single baculovirus vector and to purify their complexes with excellent homogeneity. A series of in-vitro assays demonstrate that the recombinant cyclin B-Cdk1 can efficiently and specifically phosphorylate the SP and TP motifs in substrates...

Background Adenoid cystic carcinoma (ACC) poses clinical challenges with its unique histology and potential for perineural invasion, recurrence, and distant metastases. Recent genomic advancements have unveiled key genetic alterations in ACC, offering insights into its pathogenesis. Aim This study aims to unravel the intricate molecular landscape of ACC through a comprehensive analysis of gene expression patterns. By integrating data from multiple microarray datasets, the study explores differentially expressed genes (DEGs), their functional enrichment, protein-protein interactions (PPI), hub genes, microRNA (miRNA) involvement, transcription factors, and potential drug-gene interactions...

BACKGROUND: Liver cancer, one of the most common types of cancer worldwide, accounts for millions of cases annually. With its multi-target and wide-ranging therapeutic effects, traditional Chinese medicine has emerged as a potential approach for treating various tumors. Codonopsis pilosula, a traditional herb, is known for its anti-inflammatory and antioxidant properties. In this study, we investigated the potential molecular mechanisms of Codonopsis pilosula in regulating the inhibition of CDK1 and the modulation of PDK1/β-catenin, which are involved in hepatocellular carcinoma growth and metastasis...

OBJECTIVE: Synovial Sarcoma (SS), a highly malignant mesenchymal neoplasm, typically carries a grim prognosis for patients presenting with high-grade or metastatic disease. Although Anlotinib, a new agent for treating soft tissue sarcomas, holds promise, its underlying mechanism remains incompletely understood. This investigation aims to delineate Anlotinib's anticancer effectiveness and potential mechanistic underpinnings in patients suffering from advanced, refractory SS. MATERIALS AND METHODS: Employing microarray assay, we examined the potential downstream targets of Anlotinib in SS therapy...

BACKGROUND AND PURPOSE: Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification. METHODS: Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer...

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid ( 1 ), together with isocupressic acid ( 2 ), 3,4-dimethoxycinnamoyl alcohol ( 3 ) and deoxypodophyllotoxin ( 4 ). The chemical structures of 1-4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC50 of 3...