Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 11, 2025

Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction, is a major cause of secondary hypertension with significant cardiovascular complications. Current treatments mainly focus on symptom management rather than addressing underlying mechanisms. This study aims to discover novel therapeutic targets for PA using integrated bioinformatics and experimental validation approaches. We employed systematic approach combining: gene identification through transcriptome-wide association studies (TWAS); causal inference summary data-based Mendelian randomization (SMR) two-sample (MR) analyses; additional analyses included phenome-wide analysis, enrichment protein-protein interaction (PPI) networks, drug repurposing, molecular docking clinical aldosterone-producing adenomas (APAs) tissue. Through screening prioritization, we identified 163 PA-associated genes, which seven emerged as potential targets: CEP104, HIP1, TONSL, ZNF100, SHMT1, two long non-coding RNAs (AC006369.2 MRPL23-AS1). SHMT1 was the most promising target, showing significantly elevated expression in APAs compared adjacent non-tumorous tissues. Drug repurposing analysis four SHMT1-targeting compounds (Mimosine, Pemetrexed, Leucovorin, Irinotecan), supported studies. The integration multiple methods successfully hyperaldosteronism. particular, represents candidate future development. These findings provide new opportunities developing causative PA, though further warranted.

Язык: Английский

---

Systematic characterization of zinc in a series of breast cancer cell lines reveals significant changes in zinc homeostasis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

An optimal amount of labile zinc (Zn 2+ ) is essential for proliferation human cells, where Zn levels that are too high or low cause cell cycle exit. Tumors the breast have been characterized by total . Given role in cells and elevation cancer tumors, we examined concentration across a panel 5 lines, compared to normal MCF10A line. We found three lines (MDA-MB-231, MDA-MB-157, SK-Br-3) showed elevated cytosol, while T-47D significantly lower , MCF7 no change cells. There was as measured ICP-MS, but did observe difference ability accumulate when media elevated. Therefore, how each line affected increases decreases media. striking differences, MCF7) robust at concentrations killed MCF10A, T-47D, SK-Br-3 also discovered 4 demonstrate compromised increased death suggesting these may be addicted Overall, our study suggests significant differences homeostasis regulation different types with consequences both viability.

Язык: Английский

---

Impact of High-Temperature Stress on Maize Seed Setting: Cellular and Molecular Insights of Thermotolerance

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1283 - 1283

Опубликована: Фев. 2, 2025

Global warming poses a significant threat to crop production and food security, with maize (Zay mays L.) particularly vulnerable high-temperature stress (HTS). This review explores the detrimental impacts of elevated temperatures on development across various growth stages, analyzed within source–sink framework, particular focus seed setting yield reduction. It provides broad analysis cellular molecular responses HTS, highlighting key roles plant hormone abscisic acid (ABA) signaling, calcium chloroplast, DNA damage repair (DDR) system in maize. HTS disrupts ABA signaling pathways, impairing stomatal regulation reducing water-use efficiency, while orchestrates by activating heat shock proteins other protective mechanisms. Chloroplasts, as central photosynthesis, are sensitive often exhibiting photosystem II chlorophyll degradation. Recent studies also highlight significance DDR system, genes like ZmRAD51C playing crucial maintaining genomic stability during reproductive organ development. under conditions emerges factor contributing reduced set, although precise mechanisms remain be fully elucidated. Furthermore, examines cutting-edge genetic improvement strategies, aimed at developing thermotolerant cultivars. These recent research advances underscore need for further investigation into basis thermotolerance open door future advancements breeding crops.

Язык: Английский

---

Unraveling diversity by isolating peptide sequences specific to distinct taxonomic groups

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Abstract The identification of succinct, universal fingerprints that enable the characterization individual taxonomies can reveal insights into trait development and have widespread applications in pathogen diagnostics, human healthcare, ecology biomes. Here, we investigated existence peptide k-mer sequences are exclusively present a specific taxonomy absent every other taxonomic level, termed quasi-primes. By analyzing proteomes across 24,073 species, identified quasi-prime peptides to superkingdoms, kingdoms, phyla, uncovering their distributions functional relevance. These exhibit remarkable sequence uniqueness at six- seven-amino- acid lengths, offering evolutionary divergence lineage-specific adaptations. Moreover, show loci more prone harboring pathogenic variants, underscoring significance. This study introduces quasi-primes offers contributions proteomic diversity, pathways, adaptations tree life, while emphasizing potential impact on health disease.

Язык: Английский

---

Bacterial DNA methylases as novel molecular and synthetic biology tools: recent developments

Applied Microbiology and Biotechnology, Год журнала: 2025, Номер 109(1)

Опубликована: Март 6, 2025

Bacterial DNA methylases are a diverse group of enzymes which have been pivotal in the development technologies with applications including genetic engineering, bacteriology, biotechnology and agriculture. This review describes bacterial methylase types, main for targeted methylation or demethylation recent roles these molecular synthetic biology. can be exocyclic endocyclic exist as orphan part restriction-modifications (R-M) systems. As group, they display rich diversity sequence-specificity. Additional targeting involve using fusion proteins combining DNA-binding protein (DNBP) such zinc-finger (ZF), transcription activator-like effector (TALE) CRISPR/dCas9. contributed significantly to creation novel assembly techniques, improvement transformation crop plant engineering. Future studies define characteristics more potential identify new tools value biology widespread applications. KEY POINTS: • used direct specific sequences target has applied improve increase efficiency Site-selective alter gene expression phenotype.

Язык: Английский

---

Assessment of Heterozygosity in European Local and Cosmopolitan Pig Populations

Agriculture, Год журнала: 2025, Номер 15(7), С. 761 - 761

Опубликована: Апрель 1, 2025

Researchers focused on assessing differences in gene diversity within and between populations, whether cosmopolitan or local. However, the identification of patterns variation non-random heterozygous genomic stretches, known as Heterozygosity-Rich regions (HRRs), has not yet been determined European local pig breeds. A total 23 breeds (20 3 cosmopolitan) were assessed compared terms heterozygosity-rich regions. The with highest number HRRs Large White, Lithuanian Old type, Landrace, followed by Native, Mora Romagnola, Duroc. lowest Alentejana, Iberian, Majorcan Black. No shared HRR islands found all breeds, but enrichment analysis performed most common revealed several biologically important genes that cluster together play significant roles, primarily related to immune system. Permutation indicated some serve true reservoirs genetic diversity, displaying distinct unique characteristics heterozygosity. This study suggests importance investigating heterozygosity develop a comprehensive picture regardless production system, country origin, population size.

Язык: Английский

---

Molecular Functions and Potential Utilization of Zinc Finger Proteins in Protozoan Parasites

Опубликована: Апрель 10, 2025

Zinc finger proteins (ZFP) are metalloproteins whose zinc atom interacts with side chains of specific histidines and cysteines the motif, generating functional three dimensional structures. A good number these from different species similar while others divergent in structure function. Existing literature on structural features, functions their potential to be targeted for drug development or used as molecular tools parasitic protozoa was explored. Evidence reviewed articles revealed that, just like other eukaryotes, function various parasite cellular processes such as: transcription, RNA editing, mRNA processing & export and, turn-over among others. Some them had same features homologues eukaryotes including hosts. However, there were which studies aiming at replacing reported positive results some parasites Giardia lamblia, Trichomonas vaginalis Leishmania donovani though this is promising, off- target challenge that can cause effects, must solved before wide application achieved. Successful engineering use genome editing also Plasmodium falciparum. Since nucleases a powerful research medical tool, repurposing ZFPs useful therapy discovery. For succeed, more knowledge how regulated needed.

Язык: Английский

---

Rational design of a dual-bacterial system for synchronous removal of antibiotics and Pb(Ⅱ)/Cd(Ⅱ) from water

Journal of Hazardous Materials, Год журнала: 2024, Номер 485, С. 136773 - 136773

Опубликована: Дек. 4, 2024

Язык: Английский

---