Protein and Peptide Letters最新文献

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Improving Acid-Base Pair Concentration in Wash/Elution Buffer Eliminates Elution Peak-Shouldering in Cation Exchange Chromatography. 提高洗涤/洗脱缓冲液中酸碱对浓度,消除阳离子交换色谱中洗脱峰肩现象。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-10-03 DOI: 10.2174/0109298665394172250926073117
Fei Huang, Na Liu
{"title":"Improving Acid-Base Pair Concentration in Wash/Elution Buffer Eliminates Elution Peak-Shouldering in Cation Exchange Chromatography.","authors":"Fei Huang, Na Liu","doi":"10.2174/0109298665394172250926073117","DOIUrl":"https://doi.org/10.2174/0109298665394172250926073117","url":null,"abstract":"<p><strong>Introduction: </strong>Peak-shouldering elution behavior was a common and unexpected result in bind-and-elute mode Cation Exchange Chromatography (CEX), which may be due to the pH transition during the elution step and the aggregation tendency of target proteins.</p><p><strong>Methods: </strong>Improving the concentration of acid-base pairs in the wash buffers or elution buffers without changing pH or conductivity effectively resolved the peak-shouldering issue in CEX.</p><p><strong>Results: </strong>In the case of molecule A, the shoulder peak was eliminated in the CEX run by increasing the NaAc-HAc concentration from 50 mM to 100 mM in the elution buffer or from 50 mM to 75 mM in the wash buffer. Higher NaAc-HAc concentrations affect the pH transition in the early stages of the elution step, which may explain the elimination of the shoulder peak. A similar result was observed for molecule B, where increasing the Tris-HCl concentration in the elution buffer from 50 mM to 80 mM also removed the shoulder peak during elution.</p><p><strong>Discussion: </strong>The successful elimination of peak-shouldering behavior by increasing acid-base pair concentrations highlights the critical role of buffer capacity in modulating pH transitions during CEX. While this strategy offers a simple and effective solution, further investigation is needed to assess its applicability across diverse protein types and buffer systems.</p><p><strong>Conclusion: </strong>These results demonstrate that increasing the concentration of acid-base pairs in the elution buffer or wash buffer of CEX using NaAc-HAc or Tris-HCl buffers is an effective strategy for eliminating the shoulder-peak.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PLEKHG7 Expression: A Biomarker for Prognosis and Targeted Therapy in Diffuse Large B-cell Lymphoma. PLEKHG7表达:弥漫性大b细胞淋巴瘤预后和靶向治疗的生物标志物
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-10-03 DOI: 10.2174/0109298665398122250929045705
Guizhen Lyu, Dongbing Li
{"title":"PLEKHG7 Expression: A Biomarker for Prognosis and Targeted Therapy in Diffuse Large B-cell Lymphoma.","authors":"Guizhen Lyu, Dongbing Li","doi":"10.2174/0109298665398122250929045705","DOIUrl":"https://doi.org/10.2174/0109298665398122250929045705","url":null,"abstract":"<p><strong>Introduction: </strong>Pleckstrin homology and RhoGEF domain-containing G7 (PLEKHG7) is a largely uncharacterized gene whose role in diffuse large B-cell lymphoma (DLBCL) remains unexplored. Thus, we aimed to profile PLEKHG7 expression, assess its prognostic value, and explore therapeutic implications.</p><p><strong>Methods: </strong>RNA-seq data from TCGA-DLBCL (n=48) and GTEx normal tissues were analyzed via UCSC XENA. Differential expression was tested using the Wilcoxon rank-sum test and FDR correction. Prognostic significance was evaluated by Kaplan-Meier and multivariate Cox regression (nomogram). Gene set enrichment analysis (GSEA) mapped PLEKHG7-associated pathways. Drug sensitivity correlations were extracted from RNAactDrug. qRT-PCR validated expression in DLBCL cell lines (OCI-Ly3, SU-DHL-4) versus normal B lymphocytes (GM12878).</p><p><strong>Results: </strong>PLEKHG7 was markedly up-regulated in DLBCL tissues (P < 0.001) and cell lines versus normal controls (AUC = 0.739). High PLEKHG7 expression predicted inferior overall survival (HR = 8.88; 95% CI: 1.09-72.27; P = 0.041) and remained an independent prognostic factor (HR = 10.109; P = 0.033). GSEA linked PLEKHG7 to ribosome, oxidative phosphorylation, proteasome, cytokine-cytokine receptor interaction, spliceosome, and ECM-receptor pathways. Elevated PLEKHG7 negatively correlated with sensitivity to idelalisib, omipalisib, belinostat, methotrexate, and dacinostat.</p><p><strong>Discussion: </strong>The study's limitations include reliance on bioinformatics data and the lack of functional validation. Further research is needed to elucidate the molecular mechanisms underlying PLEKHG7's role in DLBCL and validate its clinical utility.</p><p><strong>Conclusion: </strong>PLEKHG7 is significantly overexpressed in DLBCL and independently predicts poor prognosis. Its association with key oncogenic pathways and drug resistance underscores its potential as both a prognostic biomarker and a therapeutic target, warranting further functional validation.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cloning, Expression, Purification, and Characterization of Superoxide Dismutase from the Soil Metagenome. 土壤宏基因组超氧化物歧化酶的克隆、表达、纯化和鉴定。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-10-03 DOI: 10.2174/0109298665415743250926072254
Nancy, Sudarshan Singh Lakhawat, Rajender Kumar, Pushpender Kumar Sharma
{"title":"Cloning, Expression, Purification, and Characterization of Superoxide Dismutase from the Soil Metagenome.","authors":"Nancy, Sudarshan Singh Lakhawat, Rajender Kumar, Pushpender Kumar Sharma","doi":"10.2174/0109298665415743250926072254","DOIUrl":"https://doi.org/10.2174/0109298665415743250926072254","url":null,"abstract":"<p><strong>Introduction: </strong>Superoxide Dismutases (SODs) are enzymes that catalyze the conversion of toxic free radicals generated during stress conditions into nontoxic forms. Thus, the enzyme superoxide dismutase contributes to the adaptation and survival of microorganisms across a variety of environmental conditions, making it an indispensable enzyme during the response to stress. In this study, we embarked upon investigating and characterizing a Superoxide Dismutase (SOD) from DNA extracted directly from garden soil, where the average temperature ranges from 4°C- 45°C.</p><p><strong>Materials and methods: </strong>Metagenomic DNA was extracted by employing a kit. The gene was amplified using PCR. The amplified PCR product was gel eluted and ligated into the pGEMT-easy vector and subcloned into an expression vector. The protein was purified using Ni-NTA chromatography and characterized using biophysical, biochemical, and computational approaches.</p><p><strong>Results: </strong>The recombinant SOD was expressed and purified; the purified protein exhibited activity and stability over a broad pH and temperature range, with optimal activity observed at 40°C and pH 8, respectively. The enzyme remains completely stable at 40°C for 3 h. However, in contrast, it loses 50% of its activity when incubated at 50°C and 60°C for 3 h. The biophysical investigation revealed stable confirmation of the secondary structure of the protein, as evident from circular dichroism and intrinsic Tryptophan (Trp) fluorescence studies. In silico sequence and structural analysis revealed a close similarity of the SOD reported in this study to the Mn SOD of multi- Bacillus species. Molecular simulation dynamics experiments revealed the all-over conformational stability of protein structures at varying pH, indicating broad pH functioning of the enzyme.</p><p><strong>Discussion: </strong>The study provides a comprehensive analysis of the structure and function of a superoxide dismutase enzyme derived from a soil metagenome. A Mn2+ binding site identified in the study offers an opportunity to further facilitate engineering and design of mutant SOD.</p><p><strong>Conclusion: </strong>The enzyme exhibits distinct attributes that hold significant industrial relevance. Owing to the wide functionality of SOD at different pH and temperature, it can be tailored for its potential industrial applications, which include its therapeutic potential, thus opening new avenues for enhanced antioxidant therapies and novel biocatalyst designing.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Preliminary Study on the Antibacterial Activity of the Secretion of the Levantine Water Frog, Pelophylax bedriagae (Camerano, 1882) (Anura:Ranidae). 黎凡特水蛙Pelophylax bedriagae (Camerano, 1882)分泌物抑菌活性的初步研究(无尾目:蛙科)。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-10-02 DOI: 10.2174/0109298665385364250917100034
Nazlı Atçi, Ebru Tanriverdio, Dinçer Ayaz
{"title":"A Preliminary Study on the Antibacterial Activity of the Secretion of the Levantine Water Frog, Pelophylax bedriagae (Camerano, 1882) (Anura:Ranidae).","authors":"Nazlı Atçi, Ebru Tanriverdio, Dinçer Ayaz","doi":"10.2174/0109298665385364250917100034","DOIUrl":"https://doi.org/10.2174/0109298665385364250917100034","url":null,"abstract":"<p><strong>Introduction: </strong>The skin of amphibians performs some vital roles, such as camouflage, ion and water transport, and gas exchange. Additionally, it plays a significant role in the immune system by preventing pathogen invasion. The secretions produced by the granular glands in the skin possess antimicrobial properties, which help prevent harmful microorganisms from entering the animal's body. The study aims to determine the total protein amounts in the secretion of Pelophylax bedriagae (Levant water frog) distributed in Türkiye and to reveal whether it has antimicrobial properties. In this context, it is a pioneering study on antimicrobial peptides in the skin secretion of Pelophylax.</p><p><strong>Method: </strong>Field research was carried out at İzmir, Türkiye's Homeros Valley. Because AMPs are species-specific, not sex-specific peptides, both male and female adults were used, regardless of sex. The average weight of the animals used in the experiment was 21 grams. Granular glands were stimulated using a specialized device, and the secretions were collected for analysis. The collected secretions were lyophilized after centrifugation. Then, the total protein amount in the secretion was determined by Bicinchoninic Acid (BCA). The antibacterial activities of the skin secretions against Escherichia coli and Staphylococcus aureus were assessed using a plate well diffusion assay. The peptide profiles in the skin secretions were determined using the Tricine-SDS-- PAGE electrophoresis method.</p><p><strong>Results: </strong>The plate well diffusion assay demonstrated that the skin secretions created a 21 mm inhibition zone against E. coli and a 20 mm inhibition zone against S. aureus. The results of the Tricine-SDS-PAGE electrophoresis revealed the presence of peptides with five different molecular weights, including one smaller than 5 kDa. As a result of the analysis, it was determined that P. bedriagae secretion exhibits antimicrobial properties, and many proteins with different molecular masses were identified in the skin secretion.</p><p><strong>Discussion: </strong>There are no skin secretion studies on P. bedriage in the literature. However, activity studies were also conducted on the skin secretion of another Pelophylax species, P. ridibundus. The study examined the antibacterial activities of the skin secretion against some gram-positive and gram-negative bacteria using a plate well diffusion assay. Their study showed that E. coli formed a 21 mm zone and S. aureus formed a 24 mm zone.</p><p><strong>Conclusion: </strong>This study is preliminary, and in future studies, AMPs in skin secretions can be isolated by chromatographic methods, such as HPLC, and peptides can be sequenced and identified in detail.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effective Plant-Derived Proteins and Peptides in Leukemia Treatment. 有效的植物源性蛋白和多肽治疗白血病。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-09-10 DOI: 10.2174/0109298665395842250814085828
Zahra Moghaddasi, Azam Bolhassani, Elnaz Agi
{"title":"Effective Plant-Derived Proteins and Peptides in Leukemia Treatment.","authors":"Zahra Moghaddasi, Azam Bolhassani, Elnaz Agi","doi":"10.2174/0109298665395842250814085828","DOIUrl":"https://doi.org/10.2174/0109298665395842250814085828","url":null,"abstract":"<p><p>Leukemia is one of the most prevalent malignancies worldwide that causes the unusual evolution of hematopoietic stem cells. The type of leukemia determines the optimal treatment plan and the patient's survival. However, finding safer and more effective medications and developing novel therapeutic strategies are still the most challenging research topics. Nowadays, over half of the medications used to treat cancer are derived from natural ingredients. Medicinal plants are a reliable natural source of anti-leukemic medications. Plant-derived biologically active compounds, including secondary metabolites, have long been considered extremely valuable for treating various human illnesses. However, the limitations of secondary metabolites have led scientists to seek alternative biologically active compounds. Plant-derived proteins and peptides have recently been explored as potential treatments for various human ailments, showing anti-microbial, anti-oxidant, anti-HIV, anti-cancer, ribosome-inactivating, and neuromodulatory properties. Until now, no review article has documented the biologically active proteins and peptides against leukemia. This review article explores the therapeutic properties of plant-derived proteins and peptides against leukemia.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of the Cardioprotective Potential of Syzygium aromaticum in High-Glucose and Trimethylamine-N-Oxide-Induced In-Vitro Diabetic Cardiomyopathy. 芳香合欢对高糖和三甲胺- n-氧化物诱导的体外糖尿病性心肌病的心脏保护潜力评价。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-09-10 DOI: 10.2174/0109298665390952250814224511
Shivani Singhal, Jatin Gupta, Prem Prakash Kushwaha, Vibha Rani
{"title":"Evaluation of the Cardioprotective Potential of Syzygium aromaticum in High-Glucose and Trimethylamine-N-Oxide-Induced In-Vitro Diabetic Cardiomyopathy.","authors":"Shivani Singhal, Jatin Gupta, Prem Prakash Kushwaha, Vibha Rani","doi":"10.2174/0109298665390952250814224511","DOIUrl":"https://doi.org/10.2174/0109298665390952250814224511","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic hyperglycemia is often associated with elevated levels of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite that was recently identified as a risk factor for cardiovascular diseases. The combined presence of hyperglycemia and TMAO can aggravate cardiac dysfunction in diabetic patients. This study aimed to evaluate the protective effects of the methanolic extract of Syzygium aromaticum against the toxic effects induced by TMAO and hyperglycemia in cultured rat cardiomyocytes.</p><p><strong>Methods: </strong>Rat cardiomyocytes, H9C2 were exposed to high glucose and TMAO, individually and in combination to simulate diabetic and dysbiotic stress conditions. Cells were treated with optimized doses of Syzygium aromaticum extract under dual-stress conditions. Cellular and nuclear morphology were assessed microscopically. Oxidative stress markers were evaluated. Proteomic profiling using liquid chromatography-mass spectrometry (LC-MS) was conducted to identify differentially expressed proteins. Crucial targets were identified and functionally annotated using integrated bioinformatics tools and databases. Expression of the critical transcription factor Yin- Yang-1 (YY1) was analysed using quantitative PCR (qPCR).</p><p><strong>Results: </strong>Dual exposure to TMAO and hyperglycemia resulted in greater morphological and oxidative damage compared to exposure to either individual stressor alone. Treatment with Syzygium aromaticum extract significantly reduced cellular and nuclear damage as well as oxidative stress under dual-stress conditions. Proteomic analysis revealed several differentially expressed proteins, with YY1 identified as a key regulatory factor. qPCR confirmed the suppression of YY1 expression by Syzygium aromaticum treatment.</p><p><strong>Discussion: </strong>Our findings suggest that Syzygium aromaticum mitigates cardiomyocyte injury caused by metabolic and microbial stress. Its protective effect may be mediated through antioxidant activity and transcriptional regulation, particularly via the downregulation of YY1, a key player in cardiac stress responses.</p><p><strong>Conclusion: </strong>Syzygium aromaticum exhibits multifaceted cardioprotective and prebiotic potential by mitigating TMAO and hyperglycemia-induced toxicity, highlighting its therapeutic promise in managing gut dysbiosis linked to diabetic cardiomyopathy.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Essential Role of Non-Conserved α4-His178 in Stabilizing the α4-α5 Hairpin and Biotoxicity of the Cry4Aa Mosquitocidal Protein. 非保守α4- his178在Cry4Aa杀蚊蛋白α4-α5发夹稳定及生物毒性中的重要作用
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-09-05 DOI: 10.2174/0109298665393672250715000125
Chompounoot Imtong, Walairat Bourchookarn, Apichai Bourchookarn, Somsri Sakdee, Hui-Chun Li, Chanan Angsuthanasombat
{"title":"Essential Role of Non-Conserved α4-His178 in Stabilizing the α4-α5 Hairpin and Biotoxicity of the Cry4Aa Mosquitocidal Protein.","authors":"Chompounoot Imtong, Walairat Bourchookarn, Apichai Bourchookarn, Somsri Sakdee, Hui-Chun Li, Chanan Angsuthanasombat","doi":"10.2174/0109298665393672250715000125","DOIUrl":"https://doi.org/10.2174/0109298665393672250715000125","url":null,"abstract":"<p><strong>Background: </strong>Bacillus thuringiensis Cry toxins are well known for their insecticidal properties, primarily through the formation of ion-leakage pores via α4-α5 hairpins. His178 in helix 4 of the Cry4Aa mosquito-active toxin has been suggested to play a crucial role in its biotoxicity.</p><p><strong>Objective: </strong>This study aimed to investigate the functional importance of Cry4Aa-His178 through experimental and computational analyses.</p><p><strong>Methods: </strong>Ten His178-substituted Cry4Aa mutants (H178D, H178E, H178K, H178R, H178G, H178F, H178Y, H178S, H178C, and H178Q) were generated via site-directed mutagenesis and expressed in Escherichia coli. Toxin solubility was assessed in carbonate buffer (pH 10.0), and biotoxicity was tested against Aedes aegypti larvae. Trypsin-treated toxins were evaluated using fluorescent dye-release assays. Ion channel formation was studied in planar lipid bilayers (PLBs), and structural analysis was performed via MD simulations and sequence alignments with known Cry toxins.</p><p><strong>Results: </strong>All His178-substituted mutants were overexpressed as 130-kDa protoxin inclusions at levels comparable to the wild-type (WT). Replacing His178 with nonpolar or bulky polar residues reduced Cry4Aa biotoxicity to less than 10%, while substitutions with small, moderately polar, or negatively charged residues retained 50-85% activity, consistent with their in vitro solubility. Selected bioactive mutants, H178C and H178D, retained membrane-perturbing ability, like trypsin- activated WT, while the bioinactive H178Y mutant exhibited decreased membrane permeability. All tested mutants, including WT, induced cation-selective channels in PLBs with ~130-pS conductance. Sequence-structure analysis indicated that Cry4Aa-His178 likely forms a hydrogen bond with His217, a conserved His residue in helix 5.</p><p><strong>Discussion: </strong>Specific physicochemical properties of residue 178 are critical for optimal larvicidal activity, making it a promising target for engineering more potent mosquito-control toxins.</p><p><strong>Conclusion: </strong>His178 in Cry4Aa-α4 potentially forms a stabilizing hydrogen bond with α5-His217, which maintains the structural integrity of the α4-α5 hairpin. This structural stability is essential for efficient membrane insertion and optimal larvicidal activity.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mevalonate Metabolic Reprogramming Drives Cisplatin Resistance in Bladder Cancer: Mechanisms and Therapeutic Targeting. 甲羟丙酸代谢重编程驱动膀胱癌顺铂耐药:机制和治疗靶向。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-09-03 DOI: 10.2174/0109298665403178250806111943
Qixiang Fang, Chengyu You, Xi Xiao, Yang Liu, Weiguang Yang, Qingchao Li, Liangliang Qing, Zhilong Dong
{"title":"Mevalonate Metabolic Reprogramming Drives Cisplatin Resistance in Bladder Cancer: Mechanisms and Therapeutic Targeting.","authors":"Qixiang Fang, Chengyu You, Xi Xiao, Yang Liu, Weiguang Yang, Qingchao Li, Liangliang Qing, Zhilong Dong","doi":"10.2174/0109298665403178250806111943","DOIUrl":"https://doi.org/10.2174/0109298665403178250806111943","url":null,"abstract":"<p><strong>Introduction: </strong>Dysregulation of mevalonate metabolism is a hallmark of tumorigenesis and therapy resistance across malignancies, though its role in bladder cancer remains unclear. This study aimed to elucidate its impact on prognosis and cisplatin chemosensitivity in bladder cancer.</p><p><strong>Methods: </strong>Transcriptomic data and clinical information of bladder cancer patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Non-negative matrix factorization (NMF) was used to cluster mevalonate metabolism-related genes into distinct metabolic subtypes (C1 and C2). Associations between mevalonate metabolism, clinical characteristics, immune infiltration, and cisplatin resistance were analyzed using Gene Set Variation Analysis (GSVA), Kaplan-Meier survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), and in vitro experiments.</p><p><strong>Results: </strong>NMF clustering classified bladder cancer patients into two metabolic subtypes (C1/C2). The C1, characterized by higher mevalonate metabolism (MVAscore), was associated with a poorer prognosis, shorter overall survival (OS), and higher T-stage and pathological grades. Immune analysis showed lower immune cell infiltration in C1. Immune infiltration analysis revealed significantly lower immune infiltration levels in the C1. Further analysis revealed a positive correlation between mevalonate metabolism and platinum resistance, with a notable increase in mevalonate metabolism observed in cisplatin-resistant bladder cancer cells. In vitro, simvastatin inhibited the proliferation of bladder cancer cells and enhanced their sensitivity to cisplatin.</p><p><strong>Discussion: </strong>Mevalonate metabolism drives BCa heterogeneity and chemoresistance while suppressing anti-tumor immunity. Its dysregulation serves as both a prognostic biomarker and a target for therapeutic intervention.</p><p><strong>Conclusion: </strong>Mevalonate metabolism contributes to cisplatin resistance in bladder cancer and represents a potential therapeutic target. Simvastatin targeting this pathway enhances the efficacy of cisplatin, providing a novel personalized chemotherapy strategy.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders. 精确酶:神经退行性疾病的靶向药物发现。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-09-01 DOI: 10.2174/0109298665391103250825102319
Sampriti Paul, Prashant Tiwari, Sonal Dubey
{"title":"Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.","authors":"Sampriti Paul, Prashant Tiwari, Sonal Dubey","doi":"10.2174/0109298665391103250825102319","DOIUrl":"https://doi.org/10.2174/0109298665391103250825102319","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.</p><p><strong>Methods: </strong>A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.</p><p><strong>Results: </strong>Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.</p><p><strong>Discussion: </strong>Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.</p><p><strong>Conclusion: </strong>Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of Anti-cancer Potential of Abelmoschus esculentus (Okra). 秋葵的抗癌潜力评价。
IF 1.1 4区 生物学
Protein and Peptide Letters Pub Date : 2025-08-21 DOI: 10.2174/0109298665365981250801110725
Maanniya Gakhar, Lovepreet Singh, Sanjeev Routh, Arunika Mukhopadhaya, Desh Deepak Singh
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