Critical Reviews in Eukaryotic Gene Expression最新文献

Abnormal levels of homocysteine (Hcy) and potassium are associated with poor prognosis of patients with ischemic stroke. Nonetheless, the roles Hcy and potassium in the prognosis of patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT) with recombinant tissue-type plasminogen activator (rt-PA) are still unknown. Therefore, the purpose of this study is to investigate the association between the levels of Hcy and potassium and clinical prognosis in AIS patients receiving IVT with rt-PA. AIS patients receiving IVT with rt-PA were enrolled in this study. AIS patients were divided into early neurological deterioration (END) and no END group according to the National Institutes of Health Stroke Scale (NIHSS) scores. Moreover, patients were divided into favorable outcome and poor outcome according to the modified Rankin Scale (mRS) scores. Multivariate logistic regression analysis was applied for detecting the risk factors. Four-hundred-twenty-six patients with AIS IVT with rt-PA were recruited: 24 patients showed END within 24 h. One-hundred-fifty-seven patients showed poor outcome. Multivariate analysis showed that higher levels of Hcy level (P < 0.001) and lower levels of potassium level (P < 0.01) were more frequently in patients with END and poor outcomes in AIS patients with IVT at the three-month visit. Taken together, the high Hcy and low potassium levels may be the potential biomarker for AIS patients receiving IVT with rt-PA.

Uterine corpus endometrial carcinoma (UCEC) is a prevalent malignancy within the female reproductive system, with a rising global incidence. Although thyroid hormone receptor interacting protein 13 (TRIP13) has been implicated in various tumor etiologies and progressions, its role in UCEC remains poorly characterized. This study aimed to delineate TRIP13's expression profile in UCEC by analyzing transcriptome data from multiple databases. We investigated genomic alterations and epigenetic modifications of the TRIP13 gene using the cBioPortal tool. The prognostic value of TRIP13 was assessed via Kaplan-Meier survival analysis and Cox regression modeling. Additionally, we examined TRIP13's impact on immunotherapy responsiveness and chemotherapy sensitivity through immunological and pharmacological analyses. The expression of TRIP13 in both normal endometrial and cancer cell lines was evaluated using quantitative real-time polymerase chain reaction (qPCR). Our findings reveal that TRIP13 expression in UCEC tumor samples is significantly higher than in normal tissues and increases with tumor grade and stage progression. High TRIP13 expression is significantly associated with poor prognosis in UCEC patients, establishing it as an independent prognostic biomarker. TRIP13 shows a positive correlation with immunosuppressive cell infiltration and a negative correlation with immune-activating cell infiltration, suggesting a potential role in tumor immune evasion. Further analysis identified TRIP13 as a potential biomarker for predicting immunotherapy response. Moreover, TRIP13 expression is significantly associated with sensitivity to certain chemotherapeutic agents, indicating its potential as a therapeutic target. qPCR experiments confirmed the overexpression of TRIP13 in endometrial cancer cell lines. The role of TRIP13 in modulating the tumor immune microenvironment, as well as its predictive value for immunotherapy and chemotherapy responses, underscores its importance in developing personalized treatment strategies for UCEC. These findings provide novel molecular targets and therapeutic insights for a precision medicine approach to UCEC.

The uridine diphosphate-glycosyltransferase (UGT) family catalyses the glucuronidation of the glycosyl group of a nucleotide sugar to an acceptor compound (substrate), it serves as controlling reaction for bioactivity, storage and decrease toxicity of different compounds in living organisms. UGT71B8 belongs to 71B family of UGTs and its donor sugars are UDP glucose, UDP galactose and UDP 5S glucose, respectively. The current study was designed to induce site-directed mutagenesis (SDM) to investigate the activity in UGT71B8 enzyme. During first step, in silico conformational change through 3D structure model was drawn and it was found that all the amino acids of mutation site were found in allowed region. The relative surface accessibility (RSA) and absolute surface accessibility (ASA) of UGT71B8 were found as 0.042-0.037 and 7.424, respectively, which shows that UGT71B8 T138M remains stable after SDM. This prediction model thus led to the efficacious mutation of UGT71B8 enzyme. Mass spectrometric analysis of UGT71B8T138M showed reduced activity with its substrate UDP glucose and kaempherol as acceptor molecule. Moreover, no new substrate activity of UGT71B8 was found. This data would direct future endeavors to engineer more glycosyltransferases of plants to augment its activity with different substrates and provide a basis for more exploration of UGT71B8 as an active compound for potential anti-cancer therapeutics.

Long non-coding RNAs (lncRNAs) are intensively involved in the pathogenesis of multiple myeloma (MM). The purpose of this study was to investigate the potentials of DUBR in MM. Gene expression was determined using RT-qPCR and western blot. The release of ROS, MDA, ferrous iron, and GSH was detected with corresponding assays. Cell behavior was detected using CCK-8, colony formation, transwell, and PI staining assays. The binding sites between miR-17-3p and DUBR/TFRC was verified firmed by RIP, RNA pull-down, as well as luciferase assays. We found that low levels of DUBR predicted poor prognosis of MM patients. However, overexpressed DUBR enhanced the chemosensitivity of MM cells to bortezomib (BTZ), as well as promoted the ferroptosis of MM cells. DUBR sponged miR-17-3p to upregulate TFRC. However, TFRC knockdown abrogated the effects of overexpressed DUBR and promoted the aggressiveness of MM cells. In summary, DUBR promotes the chemosensitivity of MM cells to BTZ via regulating miR-17-3p/TFRC axis. Therefore, targeting DUBR may be a potential target for MM.