Inner Amino Acid Contacts Are Key Factors of Multistage Structural Rearrangements of DNA and Affect Substrate Specificity of Apurinic/Apyrimidinic Endonuclease APE1

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11474 - 11474

Published: July 14, 2023

Apurinic/apyrimidinic endonuclease 1 (APE1) is one of the most important enzymes in base excision repair. Studies on this enzyme have been conducted for a long time, but some aspects its activity remain poorly understood. One such question concerns mechanism damaged-nucleotide recognition by enzyme, and answer could shed light substrate specificity control all class. In present study, pulsed electron-electron double resonance (DEER, also known as PELDOR) spectroscopy pre-steady-state kinetic analysis along with wild-type (WT) APE1 from Danio rerio (zAPE1) or three mutants (carrying substitution N253G, A254G, E260A), we aimed to elucidate molecular events process damage recognition. The data revealed that zAPE1 mutant E260A has much higher toward DNA substrates containing 5,6-dihydro-2'-deoxyuridine (DHU), 2'-deoxyuridine (dU), alpha-2'-deoxyadenosine (αA), 1,N6-ethenoadenosine (εA). Examination conformational changes clearly multistep rearrangements during formation catalytic complex. These structural are directly associated capacity damaged enzyme-induced bending unwinding, which required eversion nucleotide duplex placement into active site enzyme. Taken together, results experimentally prove factors AP zAPE1.

Language: Английский

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Identification of lncRNAs associated with uterine corpus endometrial cancer prognosis based on the competing endogenous RNA network

International Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 20(12), P. 1600 - 1615

Published: Jan. 1, 2023

Uterine Corpus Endometrial Carcinoma (UCEC) is one of the major malignant tumors female reproductive system. However, there are limitations in currently available diagnostic approaches for UCEC. Long non-coding RNAs (lncRNAs) play important roles regulating biological processes as competitive endogenous RNA (ceRNA) tumors. To study potential lncRNAs non-invasive tumor markers, RNA-sequencing dataset UCEC patients from The Cancer Genome Atlas was used to identify differentially expressed genes. A lncRNA-miRNA-mRNA ceRNA network constructed by lncRNAs, miRNAs and miRNAs. Pathway enrichment functional analysis mRNAs provide direction future research demonstrating most affected pathways. Seven lncRNA biomarkers (C20orf56, LOC100144604, LOC100190940, LOC151534, LOC727677, FLJ35390, LOC158572) were validated quantitative real-time PCR. Notably, LOC100190940 LOC158572 identified novel molecules with unknown functions. Receiver operating characteristic (ROC) curve demonstrated that combined 7 had a high value area under (AUC) 0.941 (95% CI: 0.875-0.947). Our highlights panel UCEC, providing new insights into pathogenesis.

Language: Английский

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Harnessing Technology to Revolutionize Personalized Therapies for Metrorrhagia

Archives of Obstetrics and Gynaecology, Journal Year: 2024, Volume and Issue: 5(1), P. 40 - 47

Published: Jan. 1, 2024

Background: Metrorrhagia is defined as irregular uterine bleeding occurring between normal menstrual cycles. Unlike menstruation, metrorrhagia in frequency, duration, and volume. Understanding the etiology of requires reviewing hormonal regulation cycle. Purpose: This abstract provides an overview metrorrhagia, including epidemiology, etiology, diagnostic evaluation, management approaches, future directions. Main Body: has a variable prevalence depending on age underlying causes. Etiologies include dysfunction leading to anovulatory cycles, structural abnormalities like fibroids or polyps, systemic conditions affecting coagulation thyroid function, iatrogenic causes such intrauterine devices. Diagnostic evaluation aims elucidate cause through history, physical exam, laboratory studies, imaging pelvic ultrasound endometrial biopsy. Treatment targets using therapy regulate ovulation procedural interventions for unresponsive medical management. Traditional herbal medicines provide another historical approach managing though most lack standardization. Looking forward, advances genomics, biologics, artificial intelligence may enable more personalized, targeted therapies. Conclusion: arises from diverse etiologies encompassing hormonal, structural, systemic, Diagnosis hinges thorough direct appropriate treatment ranging medications surgery. Further research individualized therapies promises progress long-term

Language: Английский

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