Current protein & peptide science最新文献

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A Valuable Target for Therapy: The Metalloproteinase ADAM10.
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-02-10 DOI: 10.2174/0113892037348066250117070824
Siddhant Tripathi, Yashika Sharma, Dileep Kumar
{"title":"A Valuable Target for Therapy: The Metalloproteinase ADAM10.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0113892037348066250117070824","DOIUrl":"https://doi.org/10.2174/0113892037348066250117070824","url":null,"abstract":"<p><p>A special kind of posttranslational process known as proteolytic cleavage controls the half-lives and functions of several extracellular and intracellular proteins. The metalloproteinase ADAM10 has attracted attention because it cleaves a growing amount of protein substrates close to the extracellular membrane leaflet. The process known as \"ectodomain shedding\" controls the turnover of certain transmembrane proteins that are essential for receptor signaling and cell adhesion. It may trigger nuclear transport, intramembrane proteolysis, and cytoplasmic domain signaling. Additional human illnesses linked to ADAM10 include cancer, immune system malfunction, and neurodegeneration. The difficulty in targeting proteases for medicinal reasons stems from the many substrates that these enzymes, particularly ADAM10, have. It is usually necessary to precisely identify the therapeutic beneficial window of use since blocking or accelerating a particular protease activity is linked with undesirable side effects. More knowledge of the regulatory pathways governing ADAM10 expression, subcellular localization, and activity will probably lead to the identification of viable therapeutic targets, enabling more targeted and precise manipulation of the enzyme's proteolytic activity.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413671","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
Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases.
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-02-10 DOI: 10.2174/0113892037350729241129054701
Xuefeng Zhang, Yujie Chen, Yuan Tan, Tong Pan, Guanghong Wei
{"title":"Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases.","authors":"Xuefeng Zhang, Yujie Chen, Yuan Tan, Tong Pan, Guanghong Wei","doi":"10.2174/0113892037350729241129054701","DOIUrl":"https://doi.org/10.2174/0113892037350729241129054701","url":null,"abstract":"<p><p>The misfolding and aggregation of amyloid proteins are closely associated with a range of neurodegenerative diseases. Liquid-liquid phase separation (LLPS) can initiate the aggregation of proteins, indicating that LLPS may serve as an alternative pathway for the pathological aggregation of amyloid proteins. The co-occurrence of two or more amyloid pathologies has been observed in extensive pathophysiological studies and is linked to faster disease progression. The co- LLPS (also known as co-condensation) and co-aggregation of different disease-related proteins have been proposed as a potential molecular mechanism for combined neuropathology. Here, we reviewed the current state of knowledge regarding the co-aggregation and co-condensation of various amyloid proteins, including Aβ, tau, α-synuclein, TDP-43, FUS, and hnRNPA/B protein family, C9orf72 dipeptide repeats and prion protein. We briefly introduced the epidemiological correlation among different neurodegenerative diseases and specifically presented recent experimental findings about co-aggregation and co-condensation of two different amyloid proteins. Additionally, we discussed computational studies focusing on the molecular interactions between amyloid proteins to offer mechanistic insights into the co-LLPS and co-aggregation processes. This review provides an overview of the synergistic interactions between different disease-related proteins, which is helpful for understanding the mechanisms of combined neuropathology and developing targeted therapeutic strategies.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413674","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
The Impact of Thermal and pH Variations on the Structure of Cathepsin D in the Hepatopancreas of Japanese Clam (Ruditapes philippinarum).
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-30 DOI: 10.2174/0113892037244173241206055736
Cadena-Cadena Francisco, Ezquerra-Brauer Josafat Marina, Cinco-Moroyoqui Francisco Javier, López-Zavala Alonso Alexis, Santacruz-Ortega Hisila Del Carmen, Rivero-Espejel Ignacio Alfredo, Rouzaud-Sández Ofelia, Cárdenas-López José Luis
{"title":"The Impact of Thermal and pH Variations on the Structure of Cathepsin D in the Hepatopancreas of Japanese Clam (Ruditapes philippinarum).","authors":"Cadena-Cadena Francisco, Ezquerra-Brauer Josafat Marina, Cinco-Moroyoqui Francisco Javier, López-Zavala Alonso Alexis, Santacruz-Ortega Hisila Del Carmen, Rivero-Espejel Ignacio Alfredo, Rouzaud-Sández Ofelia, Cárdenas-López José Luis","doi":"10.2174/0113892037244173241206055736","DOIUrl":"https://doi.org/10.2174/0113892037244173241206055736","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin D is a lysosomal enzyme that plays a critical role in the process of protein catabolism. In marine organisms, research has primarily concentrated on the identification of the enzyme. However, in crustaceans and molluscs, it is known to have digestive functions, as it is the sole enzyme responsible for protein degradation at extremely acidic pH in the hepatopancreas. In the Japanese clam (Ruditapes philippinarum), cathepsin D was purified and partially characterised by the hepatopancreas.</p><p><strong>Methods: </strong>To evaluate changes in secondary structure, circular dichroism (CD) was employed under a range of 5-70°C and pH of 1-7.5. Following dissection, the enzyme was purified from the hepatopancreas by ultrafiltration and affinity chromatography. SDS-PAGE was used to verify the sample purity, and gel filtration was used to determine the molecular weight.. CD spectra were obtained at a concentration of 0.125 mg/mL, expressed as mean ellipticity per residue.</p><p><strong>Results: </strong>The purified cathepsin D demonstrated a specific activity of 5,553 ± 220 U/mg and a molecular weight of 36.5 kDa. The enzyme demonstrated optimal activity within a temperature range of 45-50°C and a pH range of 3-3.5. CD analyses demonstrated alterations in the secondary structure at elevated temperatures and pH fluctuations, which were correlated with a reduction in enzyme activity.</p><p><strong>Conclusion: </strong>cathepsin D from R. philippinarum exhibited high thermostability up to 50°C and activity at pH 2-4. Its stability and characteristics are comparable to those of other species, which opens avenues in biotechnology for protein hydrolysis and peptide production.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122216","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
Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures.
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-28 DOI: 10.2174/0113892037336137250102104842
Komal Gupta, Tohfa Siddiqui, Vikram Sharma
{"title":"Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures.","authors":"Komal Gupta, Tohfa Siddiqui, Vikram Sharma","doi":"10.2174/0113892037336137250102104842","DOIUrl":"https://doi.org/10.2174/0113892037336137250102104842","url":null,"abstract":"<p><p>In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes. In pharmaceuticals, gene therapy holds immense potential for addressing genetic disorders, offering a personalized approach to medicine. Immunotherapy, on the other hand, harnesses the body's immune system to combat diseases, including tumors, by enhancing immune responses or directly targeting malignant cells. RNA-based therapeutics have gained prominence due to their ability to modulate gene expression, offering targeted and precise interventions for a wide range of diseases. Cell-based therapies involve the transplantation or manipulation of cells to restore or enhance their function, offering innovative solutions for diseases such as neurodegenerative disorders and cardiovascular diseases. Furthermore, targeted tumor therapies have revolutionized tumor cure by specifically targeting molecular alterations driving tumor growth and minimizing damage to healthy cells. Overall, these novel therapeutic approaches represent a paradigm shift in medicine, offering tailored and precise interventions with the potential to significantly improve patient outcomes and quality of life.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058334","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
Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-27 DOI: 10.2174/0113892037338028241230092414
Shikha Rani, Minkal Tuteja
{"title":"Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.","authors":"Shikha Rani, Minkal Tuteja","doi":"10.2174/0113892037338028241230092414","DOIUrl":"https://doi.org/10.2174/0113892037338028241230092414","url":null,"abstract":"<p><p>The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051908","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
The Role of Sirtuins in Diabetic Nephropathy: A Comprehensive Review.
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-21 DOI: 10.2174/0113892037340795241202044932
Pranay Wal, Tarannum Tarannum, Lalji Baldaniya, Kiranjeet Kaur, Priyanka Singh, Namra Aziz, Komal Singh, Amin Gasmi
{"title":"The Role of Sirtuins in Diabetic Nephropathy: A Comprehensive Review.","authors":"Pranay Wal, Tarannum Tarannum, Lalji Baldaniya, Kiranjeet Kaur, Priyanka Singh, Namra Aziz, Komal Singh, Amin Gasmi","doi":"10.2174/0113892037340795241202044932","DOIUrl":"https://doi.org/10.2174/0113892037340795241202044932","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy is characterized by elevated oxidative stress and chronic inflammation in the kidneys. A class of proteins called sirtuins is well-known to be important for a number of cellular functions, such as metabolism, stress tolerance, and ageing. Among them, SIRT1 is associated with the progression of diabetic nephropathy, a dangerous kidney-related consequence of diabetes mellitus. Thus, this study aims to examine the function and pathways of sirtuin that are responsible for the progression of this disease.</p><p><strong>Methods: </strong>Publications considered from the standard databases like PUBMED-MEDLINE, Google Scholar, and Scopus using standard keywords, \"Sirtuin,\" Signalling pathway\", and \"Diabetic Nephropathy\" well described the actual knowledge on the scientific literature indicating patient susceptibility to kidney disease that is influenced by sirtuin-1 gene variants.</p><p><strong>Results: </strong>The research results imply that sirtuins offer enormous promise as cutting-edge therapeutic targets for kidney disease prevention and management. Renal fibrosis, metabolic disorders, renal impairment, and a possible regulation mechanism all probably entail blocking inflammation through various signalling pathways.</p><p><strong>Conclusion: </strong>A comprehensive understanding of the fundamental pathophysiological pathways targeting sirtuin is essential as a diagnostic tool. For the treatment of diabetic nephropathy, researchers are developing therapeutic techniques to target biological roles and functions of different types of sirtuin, processes, and signalling pathways.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022609","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
The Expression Characteristics and Interrelationships of FNDC5 and Pyroptosis-Associated Molecules in the Peripheral Blood of Patients with Coronary Heart Disease. 冠心病患者外周血FNDC5及焦解热相关分子的表达特征及相互关系
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-10 DOI: 10.2174/0113892037338952241113104224
Yujia Pan, Hangjun Ou, Danan Liu
{"title":"The Expression Characteristics and Interrelationships of FNDC5 and Pyroptosis-Associated Molecules in the Peripheral Blood of Patients with Coronary Heart Disease.","authors":"Yujia Pan, Hangjun Ou, Danan Liu","doi":"10.2174/0113892037338952241113104224","DOIUrl":"https://doi.org/10.2174/0113892037338952241113104224","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to investigate the expression characteristics and interrelationships of FNDC5 and pyroptosis-associated molecules in peripheral blood mononuclear cells of patients with coronary heart disease (CHD).</p><p><strong>Methods: </strong>Patients were divided into stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI) groups based on different clinical symptoms. According to the Gensini score, they were then divided into mild, moderate, and severe lesion groups. The control (NC) group was also set. ELISA assay was employed to detect the levels of Irisin, IL-1β, and IL-18, and the levels of pyroptosis-associated molecules, NF-κB p50, NF-κB p65, and FNDC5 were detected and compared by qRT-PCR and Western blot (WB). Logistic regression and Spearman's partial correlation analysis were used to analyze the pathogenic factors of CHD and explore the interrelationships between FNDC5 and the molecules.</p><p><strong>Results: </strong>IL-1β and IL-18 of CHD patients were increased, while the Irisin was decreased. With the aggravation of symptoms and severity of coronary artery stenosis, the former increased, and the Irisin gradually decreased (P<0.05). About qRT-PCR and WB: With the aggravation of symptoms, the levels of pyroptosis-associated molecules and other indicators were increased, and FNDC5 was decreased (P<0.05). NLRP3, Caspase-1, and NF-κB p50 protein were positively correlated with the incidence of CHD, and FNDC5 was also negatively correlated with that of CHD. Spearman's Partial Correlation Analysis: Even when common risk factors for CHD were taken into account, FNDC5 and NLRP3 were still found to be negatively connected.</p><p><strong>Conclusion: </strong>The decreased expression level of FNDC5 and the increased level of pyroptosis-associated molecules may be related to CHD.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983087","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
Advances in Migraine Treatment: A Comprehensive Clinical Review. 偏头痛治疗进展:综合临床综述。
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-10 DOI: 10.2174/0113892037329429241123095325
Rapuru Rushendran, Chitra Vellapandian
{"title":"Advances in Migraine Treatment: A Comprehensive Clinical Review.","authors":"Rapuru Rushendran, Chitra Vellapandian","doi":"10.2174/0113892037329429241123095325","DOIUrl":"https://doi.org/10.2174/0113892037329429241123095325","url":null,"abstract":"<p><p>Migraine is a neurological disease that, while not inherently causing \"chronic headaches,\" can evolve into a chronic condition over time including major symptoms such as nausea, and light, sound, and allodynia, particularly in cases of frequent episodic migraine or due to factors such as medication overuse or inadequate management. This condition's complex pathophysiology makes treatment difficult. Genetics, trigeminovascular system activation, and cortical spreading depression are involved. Epidemiological research estimates that one in seven persons worldwide are affected, mostly women. Migraine prevalence has increased dramatically in recent decades; however, it varies by demographic and location. This review covers pharmaceutical and non-pharmacological migraine therapy methods and their future. Second-generation triptans have reduced side effects and administration issues, however, Zolmitriptan and Sumatriptan still treat migraines. Monoclonal antibodies that target calcitonin gene-related peptides may prevent migraines; however, their accessibility and safety are problems. Antiepileptics, beta-blockers, and neuromodulation devices are also available. Wearable technology offers customized monitoring and intervention. Precision medicine and gene-based medicines provide hope for tailored migraine treatments, but access, privacy, and informed consent raises ethical concerns. Stakeholder engagement must promote patient autonomy and well-being, responsible implementation, and equal access to novel therapies. A holistic and multidisciplinary approach is needed to manage migraines, taking into consideration present and future therapy developments and new challenges. Research, collaboration, and ethics can improve migraine outcomes and quality of life.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983083","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
An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells In Vitro and In Vivo. 一种抗癌生物活性肽联合奥沙利铂在体外和体内抑制胃癌细胞。
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-08 DOI: 10.2174/0113892037350632241205040150
Xian Li, Lihua Kang, Wenyan Han, Xiulan Su
{"title":"An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Xian Li, Lihua Kang, Wenyan Han, Xiulan Su","doi":"10.2174/0113892037350632241205040150","DOIUrl":"https://doi.org/10.2174/0113892037350632241205040150","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated.</p><p><strong>Methods: </strong>The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR.</p><p><strong>Results: </strong>The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice.</p><p><strong>Conclusion: </strong>ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946116","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
In-vitro, In-silico Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines. 体外,计算机研究揭示了从Lonar Soda湖分离的放线菌发酵代谢产物对HeLa癌细胞的潜在细胞毒活性。
IF 1.9 4区 生物学
Current protein & peptide science Pub Date : 2025-01-08 DOI: 10.2174/0113892037334392241216074545
Pradip Bawane, Santosh Yele
{"title":"<i>In-vitro, In-silico</i> Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.","authors":"Pradip Bawane, Santosh Yele","doi":"10.2174/0113892037334392241216074545","DOIUrl":"https://doi.org/10.2174/0113892037334392241216074545","url":null,"abstract":"<p><strong>Background: </strong>Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.</p><p><strong>Aim: </strong>To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing <i>in-vitro</i> and <i>in-silico</i> methods.</p><p><strong>Objectives: </strong>Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.</p><p><strong>Materials and methods: </strong>The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).</p><p><strong>Results: </strong>Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC50 values were 82.9 μg/ml (LLSD-5), 162.3 μg/ml (LLSD-7), and 20.15 μg/ml (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.</p><p><strong>Conclusion: </strong>The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both <i>in-vitro</i> and <i>in-silico</i> analyses support the potential of these metabolites as anticancer agents.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946114","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
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