Molecular Biology Reports最新文献_第9页

Integrating phenotypic and molecular profiling for selection of promising advanced breeding lines for blast resistance in rice (Oryza sativa L.).

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-02-01 DOI: 10.1007/s11033-025-10279-8

Anil Kumar Gangireddy, Muga D Sreevalli, Sreelakshmi Chintala, Madhusudhan Puchakayala, Lavanya Kumari Padherla, Girish Kumar Killada, Bhanu Prakash Vulusala, Reddyyamini Bommisetty, Bhargava Kotte, Lakshminarayana R Vemireddy

{"title":"Integrating phenotypic and molecular profiling for selection of promising advanced breeding lines for blast resistance in rice (Oryza sativa L.).","authors":"Anil Kumar Gangireddy, Muga D Sreevalli, Sreelakshmi Chintala, Madhusudhan Puchakayala, Lavanya Kumari Padherla, Girish Kumar Killada, Bhanu Prakash Vulusala, Reddyyamini Bommisetty, Bhargava Kotte, Lakshminarayana R Vemireddy","doi":"10.1007/s11033-025-10279-8","DOIUrl":"https://doi.org/10.1007/s11033-025-10279-8","url":null,"abstract":"Background: Rice is susceptible to several major and minor diseases, with blast disease caused by Magnaporthe oryzae being a significant constraint, leading to substantial economic losses worldwide. Exploiting genetic resistance in cultivars is a preferred strategy for managing this disease, offering an alternative to chemical control.Methods and results: The objective of this study was to identify advanced breeding lines (ABLs) with blast resistance, superior yield, and good grain quality using Marker-Assisted Selection (MAS). Leaf blast resistance screening revealed that 25 ABLs exhibited moderate resistance. Molecular analysis with 10 polymorphic markers linked to blast resistance genes (Pi1, Pi2, Pi9, Pi37, Pi38, Pi39, Pi54, Pita, Pitp, and Piz5) identified the highest number of positive alleles (8) in MTU1061, IR36, and SVGP-26. Additionally, seven ABLs (SVGP-1, SVGP-14, SVGP-23, SVGP-37, SVGP-38, SVGP-39, and SVGP-48) showed co-segregation of markers with blast resistance. Genetic diversity analysis revealed significant variability among the genotypes, indicating diverse genetic backgrounds. Based on their yield performance, quality traits, and resistance to blast, five parents (NLR 34449, NLR 40024, MTU 1061, MTU 3626, and IR 36) and five ABLs (SVGP-13, SVGP-16, SVGP-40, SVGP-47, and SVGP-32) were selected for further yield trials.Conclusion: The study identified high-yielding, blast-resistant lines with good grain quality and diverse genetic backgrounds as promising donor sources for improving blast resistance in rice breeding programs. These findings enhance the genetic base for developing resistant rice cultivars with improved agronomic traits.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"184"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075266","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 silico analysis of non-conventional gene targets for genetic interventions to enhance fatty acid production: a review.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-31 DOI: 10.1007/s11033-025-10308-6

Neha Sawant, Sudeshna Chandra, Deepti Appukuttan, Harinder Singh

{"title":"In silico analysis of non-conventional gene targets for genetic interventions to enhance fatty acid production: a review.","authors":"Neha Sawant, Sudeshna Chandra, Deepti Appukuttan, Harinder Singh","doi":"10.1007/s11033-025-10308-6","DOIUrl":"https://doi.org/10.1007/s11033-025-10308-6","url":null,"abstract":"Since the 1990s, fatty acids (FA) have drawn significant industrial attention due to their diverse applications creating a demand for biological systems capable of producing high FA titers. While various strategies have been explored to achieve this, many of the conventional approaches rely on extensive genetic manipulations, which often result in strain instability, thus limiting its potential to yield better FA titers. Moreover, stresses such as pH, osmotic, and oxidative imbalances generated during FA production aggravate these challenges, further limiting FA titers. Under stress conditions, the cellular system responds by regulating stress-response proteins to bring about homeostasis. Recent findings suggest that transmembrane proteins, regulators of two-component systems, and cytoplasmic regulators can be strategically leveraged to address the problems related to stress-induced strain instability. Thus, non-conventional genetic targets, like chaperones (e.g., heat shock proteins) and DNA-binding transcriptional regulators (e.g., RcdA), which are not directly involved in FA metabolism, represent promising candidates to enhance strain stability and FA yields. Tools like Opt-Box and Weighted Gene Co-expression Network Analysis (WGCNA) serve as excellent platforms for understanding the cross-talk between these regulators and downstream enzymes. This review emphasizes the need for a shift towards identifying novel genetic targets by employing advanced in silico analysis and explains several molecular techniques that can aid in strain construction. Lastly, it discusses certain non-conventional gene targets that can help to overcome strain instability arising due to various stresses generated during/due to FA production.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"182"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066587","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

Upregulation of the MAP2K4 gene triggers endothelial-mesenchymal transition in COVID-19.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-31 DOI: 10.1007/s11033-025-10289-6

Esra Yilmaz, Dilek Yilmaz, Can Gokay Yildiz, Ercan Cacan

{"title":"Upregulation of the MAP2K4 gene triggers endothelial-mesenchymal transition in COVID-19.","authors":"Esra Yilmaz, Dilek Yilmaz, Can Gokay Yildiz, Ercan Cacan","doi":"10.1007/s11033-025-10289-6","DOIUrl":"https://doi.org/10.1007/s11033-025-10289-6","url":null,"abstract":"Background: SARS-CoV-2 infection is marked by an excessive inflammatory response, leading to elevated production of pro-inflammatory cytokines through activation of intracellular pathways like mitogen-activated protein kinase (MAPK). Viruses can use the MAPK signaling pathway to their advantage, but the relationship of this pathway to the severe SARS-CoV-2 period has not been fully elucidated. MAP2K4 is involved in the MAPK signaling pathway and affects cellular processes such as cell-cell junction, cell proliferation, differentiation and apoptosis.Methods and results: In this study, we sought to determine the associated biomarkers that are involved in the MAP2K4 pathway and elucidate its possible roles in terms of some clinical features associated with COVID-19. We evaluated the expressions of MAP2K4, SNAI1, SLUG, ZEB1 and E-Cadherin. For this purpose, we prospectively recruited 66 individuals, 39 of whom were women and had a mean age of 65 years. The results revealed that MAP2K4 upregulation increased SNAI1 gene expression level whereas E- Cadherin level was decreased in SARS-CoV-2 positive participants. In addition, negative correlations were determined with PLT, Lymphocyte and CKMB and E- Cadherin levels in positive participants. We also observed a negative correlation between the MAP2K4 and AST, and a positive correlation between SLUG and BUN, ZEB1 and CK.Conclusions: We conclude that SARS-CoV-2 infection triggers fibrosis by increasing MAP2K4 regulation. Additionally, this is the first study to demonstrate the possible contribution of MAP2K4 in influencing COVID-19 clinical features, which may be relevant for identifying COVID-19 positive participants with severe complications.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"180"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066658","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

Non-coding RNAs in the pathogenesis of Alzheimer's disease: β-amyloid aggregation, Tau phosphorylation and neuroinflammation.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-31 DOI: 10.1007/s11033-025-10284-x

Irma A Jiménez-Ramírez, Enrique Castaño

{"title":"Non-coding RNAs in the pathogenesis of Alzheimer's disease: β-amyloid aggregation, Tau phosphorylation and neuroinflammation.","authors":"Irma A Jiménez-Ramírez, Enrique Castaño","doi":"10.1007/s11033-025-10284-x","DOIUrl":"https://doi.org/10.1007/s11033-025-10284-x","url":null,"abstract":"Alzheimer's disease is a progressive neurodegenerative disorder primarily affecting individuals aged 65 and older, characterized by cognitive decline and diminished quality of life. The molecular hallmarks of AD include extracellular β-amyloid plaques, intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and chronic neuroinflammation. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as potential therapeutic targets due to their regulatory roles in AD pathogenesis. For example, miR-124 has been shown to modulate Aβ levels, while lncRNAs such as BACE1-AS regulate the expression of BACE1, a crucial enzyme in Aβ production. Transcriptomic studies of AD patients have revealed dysregulation of ncRNA expression, further supporting their involvement in disease progression. This review examines the regulatory functions of ncRNAs in AD, focusing on their impact on Aβ, tau hyperphosphorylation, and neuroinflammation. Additionally, we discuss the emerging role of ncRNAs in liquid-liquid phase separation and the formation of protein aggregates, key processes contributing to AD pathology.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"183"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075267","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

Therapeutical potential of natural products in treatment of pancreatic cancer: a review.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-31 DOI: 10.1007/s11033-025-10287-8

Sanjeev Kumar Sahu, Pranav Kumar Prabhakar, Manish Vyas

{"title":"Therapeutical potential of natural products in treatment of pancreatic cancer: a review.","authors":"Sanjeev Kumar Sahu, Pranav Kumar Prabhakar, Manish Vyas","doi":"10.1007/s11033-025-10287-8","DOIUrl":"https://doi.org/10.1007/s11033-025-10287-8","url":null,"abstract":"Pancreatic cancer remains as global health challenge, ranking as the seventh leading cause of cancer-related deaths worldwide with high mortality rates and a low five-year survival rate. Despite advancements in conventional therapies, including surgery, chemotherapy, and radiation, the overall survival rates for pancreatic cancer patients have shown minimal improvement. Consequently, there is an urgent need for alternative therapeutic strategies. The search for effective treatments has increasingly turned towards natural products, which offer a diverse array of bioactive compounds with potential anticancer properties. All the natural products, derived from plants, marine organisms, and microorganisms, have emerged as promising candidates in cancer treatment. The review explores the potential role of various natural compounds such as polyphenols, alkaloids, terpenoids, and flavonoids in pancreatic cancer management. With over 60% of cancer medications in clinical trials having natural origins, the review underscores the importance of exploring these compounds for their chemopreventive potential. It covers the epidemiological, molecular pathways influenced by these natural products (such as apoptosis, cell cycle regulation and signaling pathways) and therapeutic aspects aims to contribute to the ongoing efforts in understanding and addressing the complexities of pancreatic cancer. Overall, this review highlights the urgency of developing novel therapeutic strategies and incorporating natural compounds into current treatment modalities to improve outcomes for pancreatic cancer patients.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"179"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066656","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

Molecular detection of Wolbachia sp. and Cytoplasmic incompatibility factors (CifA/B) in wild caught mosquitoes in Côte d'Ivoire.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-31 DOI: 10.1007/s11033-025-10280-1

Raymond Karlhis Yao, Michel Kiréopori Gomgnimbou, Ibrahima Zanakoungo Coulibaly, Christiane You Essoh, Issouf Traoré, Miriam Félicité Amara, Berenger Aristide Ako, Abdoulaye Diabate, Etienne Bilgo

{"title":"Molecular detection of Wolbachia sp. and Cytoplasmic incompatibility factors (CifA/B) in wild caught mosquitoes in Côte d'Ivoire.","authors":"Raymond Karlhis Yao, Michel Kiréopori Gomgnimbou, Ibrahima Zanakoungo Coulibaly, Christiane You Essoh, Issouf Traoré, Miriam Félicité Amara, Berenger Aristide Ako, Abdoulaye Diabate, Etienne Bilgo","doi":"10.1007/s11033-025-10280-1","DOIUrl":"https://doi.org/10.1007/s11033-025-10280-1","url":null,"abstract":"Background: Wolbachia is an endosymbiont bacterium known to stimulate host immunity against arboviruses and protozoa. Côte d'Ivoire is in a malaria-endemic region, and has experienced several dengue epidemics in recent decades as well. In order to help reduce the transmission of pathogens by mosquito vectors, we studied the prevalence of Wolbachia and the distribution of Cytoplasmic incompatibility factors (Cif) genes in different mosquito species caught in the wild in Cote d'Ivoire.Methods and results: Mosquitoes of the genera Anopheles, Aedes, Culex, Eretmapodites and Mansonia were captured in five cities. Mosquitoes were collected at larval stage in breeding sites and adults were captured using BG sentinel traps. The mosquitoes were identified morphologically and Wolbachia and Cif were screened using qPCR targeting the 16s rRNA gene and the CifA, B genes. A total of 518 mosquito samples belonging to 15 species and 4 genera were examined. 60% of the species were infected with Wolbachia. The three medically important mosquito species Aedes aegypti, Anopheles gambiae s.l. and Culex quinquefasciatus had a prevalence of 12.84%, 13.46% and 72.64% respectively. The Wolbachia strains infecting the different mosquito species of the genus Culex encoded 98.46% for the CifA gene and 77.69% for the CifB gene.Conclusion: The presence of Wolbachia and CifA, B genes in mosquitoes of different species in Côte d'Ivoire offer a promising opportunity to reduce the competence of mosquito vectors. Characterization of Wolbachia strains and cytoplasmic incompatibility factors will provide a better understanding of these endosymbionts, enabling the development of vector control strategies.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"181"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066589","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

Distribution analysis of RAB11A and RAB11B, small GTP-binding proteins, in mice.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-30 DOI: 10.1007/s11033-025-10282-z

Yumi Tsuneura, Tohru Matsuki, Shima Eda, Nanako Hamada, Akihiro Harada, Koh-Ichi Nagata, Atsuo Nakayama

{"title":"Distribution analysis of RAB11A and RAB11B, small GTP-binding proteins, in mice.","authors":"Yumi Tsuneura, Tohru Matsuki, Shima Eda, Nanako Hamada, Akihiro Harada, Koh-Ichi Nagata, Atsuo Nakayama","doi":"10.1007/s11033-025-10282-z","DOIUrl":"https://doi.org/10.1007/s11033-025-10282-z","url":null,"abstract":"Background: RAB11 is a small GTP-binding protein that regulates intracellular trafficking of recycling endosomes and is thereby involved in several neural functions. Highly similar RAB11 isoforms are encoded by RAB11A and RAB11B genes, and their pathogenic variants are associated with similar neurodevelopmental disorders, suggesting that RAB11A and RAB11B play similar and important roles in brain development. However, the detailed distribution patterns of these isoforms in various organs, including the brain, remain undetermined.Methods and results: We generated an antibody against RAB11A and analyzed the distribution of RAB11A and RAB11B in mice. RAB11A was highly expressed in the ovary and the uterus but less abundant in the brain, whereas RAB11B was abundant in the brain, the testis, the ovary, and the uterus. In the developing cortex, RAB11A was enriched in the apical endfeet of apical radial glial cells, whereas RAB11B was abundantly expressed in postmigratory neurons of the cortical plate. In the adult mouse brain, RAB11A and RAB11B were similarly expressed in most neurons, with weak RAB11A signals also observed in the neuropil. In cultured neurons, RAB11A and RAB11B showed only partial co-localization and differential distribution in both soma and neurites. Notably, RAB11A appeared to be more abundant at presynapses than RAB11B.Conclusions: RAB11A and RAB11B exhibit distinct and characteristic distributions in the brain and other organs, suggesting they play different roles throughout the body. In particular, our results suggest they make distinct contributions to cortical development and regulation of the synaptic vesicle cycle.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"178"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066580","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 synergistic effects of citicoline and silymarin on liver injury and thyroid hormone disturbances in γ-irradiated rats.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-30 DOI: 10.1007/s11033-025-10255-2

Nahed Abdel-Aziz, Azza El-Bahkery, Ehab A Ibrahim

{"title":"The synergistic effects of citicoline and silymarin on liver injury and thyroid hormone disturbances in γ-irradiated rats.","authors":"Nahed Abdel-Aziz, Azza El-Bahkery, Ehab A Ibrahim","doi":"10.1007/s11033-025-10255-2","DOIUrl":"https://doi.org/10.1007/s11033-025-10255-2","url":null,"abstract":"Background: Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats.Methods and results: The rats were exposed to γ-radiation (7 Gy) and treated with citicoline (300 mg/kg/day) and/or silymarin (50 mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure.Conclusions: Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"176"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066643","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

Protein kinase C iota (PKCι) and pVHL are both needed for lysosomal degradation of α5 integrin in renal carcinoma cells.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-30 DOI: 10.1007/s11033-025-10272-1

Alissa F Schurr, Chandni S Dave, Prachi J Shah, Jennifer L Meth, Alexandria S Jaramillo, Kelly Bartley, Alan R Schoenfeld

{"title":"Protein kinase C iota (PKCι) and pVHL are both needed for lysosomal degradation of α5 integrin in renal carcinoma cells.","authors":"Alissa F Schurr, Chandni S Dave, Prachi J Shah, Jennifer L Meth, Alexandria S Jaramillo, Kelly Bartley, Alan R Schoenfeld","doi":"10.1007/s11033-025-10272-1","DOIUrl":"10.1007/s11033-025-10272-1","url":null,"abstract":"Background: von Hippel-Lindau (VHL) hereditary cancer syndrome is caused by mutations in the VHL tumor suppressor gene and is characterized by a predisposition to form various types of tumors, including renal cell carcinomas, hemangioblastomas, and pheochromocytomas. The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-α) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).Methods and results: To better understand the relationship between pVHL and aPKC, the PKC iota (PKCι) isoform of aPKC was knocked out in renal carcinoma cells, both pVHL-negative and those with replaced pVHL. Cellular properties associated with pVHL function were assayed. Knockout of PKCι in pVHL-expressing cells led to greater downregulation of HIF-α than seen with pVHL alone, suggesting that the presence of PKCι opposes complete regulation of HIF-α by pVHL. In contrast, absence of either pVHL or PKCι disrupted tight junction formation and led to upregulated levels of α5 integrin, both of which were phenocopied by lysosomal inhibition. LAMP1 (lysosome associated membrane protein 1), a marker for lysosomes, showed dysregulated localization and altered electrophoretic gel migration in the absence of pVHL. While the upregulated α5 integrin seen in the absence of either pVHL or PKCι loss was associated with increased cell adhesion, loss of pVHL caused increased cell motility whereas loss of PKCι decreased motility.Conclusions: These data are consistent with a known role of PKCι in endocytosis of α5 integrin and suggest a subsequent novel role of pVHL in targeting a pool of endocytosed α5 integrin for lysosomal degradation.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"177"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds.

IF 2.6 4区生物学

Molecular Biology Reports Pub Date : 2025-01-30 DOI: 10.1007/s11033-025-10270-3

Negin Arami, Amineh Sadat Tajani, Maryam Hashemi, Tahoura Rezaei, Razieh Ghodsi, Vahid Soheili, Bibi Sedigheh Fazly Bazzaz

{"title":"Targeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds.","authors":"Negin Arami, Amineh Sadat Tajani, Maryam Hashemi, Tahoura Rezaei, Razieh Ghodsi, Vahid Soheili, Bibi Sedigheh Fazly Bazzaz","doi":"10.1007/s11033-025-10270-3","DOIUrl":"https://doi.org/10.1007/s11033-025-10270-3","url":null,"abstract":"Background: Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system. Pqs circuit specificity in P. aeruginosa made this system an attractive target for antipseudomonal therapy. The current study focuses on novel chalcone derivatives that attenuate P. aeruginosa's pathogenicity by inhibiting the QS system. Chalcones are included in the flavonoid class of phenolic compounds. This family forms one of the greatest groups of bioactive natural products.Method: The chalcone derivatives's potential activity against the QS system was evaluated through biofilm inhibition, decreased virulence factors production, and gene expression.Results: Among all the tested compounds, 5H and NMe2 chalcone derivatives reduced biofilm formation by 60.9% and 78.9%, respectively, and virulence factors production, including pyocyanin (decreased by 5H 30.9% and NMe2 30.7%) and pyoverdine (decreased by 5H 47.1% and NMe2 56.9%) and the QS gene expression (LasR, RhlR, and PqsR) more effectively than other derivatives.Conclusion: These chalcone compounds can be used as a supplement besides antimicrobial chemotherapy to attenuate pseudomonas pathogenicity.","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"175"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066640","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