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Shikonin a potent phytotherapeutic: a comprehensive review on metabolic reprogramming to overcome drug resistance in cancer.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-29 DOI: 10.1007/s11033-025-10459-6
Stuti Biswal, Sanjeeb Kumar Sahoo, Bijesh K Biswal
{"title":"Shikonin a potent phytotherapeutic: a comprehensive review on metabolic reprogramming to overcome drug resistance in cancer.","authors":"Stuti Biswal, Sanjeeb Kumar Sahoo, Bijesh K Biswal","doi":"10.1007/s11033-025-10459-6","DOIUrl":"https://doi.org/10.1007/s11033-025-10459-6","url":null,"abstract":"<p><p>Drug resistance remains a major challenge in cancer therapy, often leading to treatment failure. Metabolic reprogramming, a hallmark of cancer, plays a pivotal role in drug resistance. Phytocompounds, particularly shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, have garnered significant interest as potential alternatives for cancer prevention and treatment. This review focuses on the anticancer properties of shikonin, particularly its ability to modulate metabolic reprogramming and overcome drug resistance. This review, based on extensive searches in databases like PubMed, Web of Science, Google Scholar, and Scopus, highlights shikonin's potential as a therapeutic agent. Shikonin exhibits a wide range of anticancer activities, including induction of apoptosis, autophagy, necroptosis, inhibition of angiogenesis, invasion, and migration, as well as disruption of the cell cycle and promotion of DNA damage. It targets altered cancer cell metabolism to inhibit proliferation and reverse drug resistance, making it a promising candidate for therapeutic development. Preliminary clinical trials suggest that shikonin can enhance the efficacy of established chemotherapeutic agents, immunotherapies, and radiation through additive and synergistic interactions. Despite its promise, further research is needed to elucidate the precise mechanisms underlying shikonin's metabolic reprogramming effects in cancer. A comprehensive understanding could pave the way for its integration into standard oncological treatments. With its capacity to act on multiple cancer pathways and enhance conventional treatments, shikonin stands out as a viable candidate for combating drug-resistant cancers and advancing clinical oncology.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"347"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743353","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
Comparative transcriptome analysis of Isatis indigotica under different precipitation conditions.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-29 DOI: 10.1007/s11033-025-10451-0
Wenlong Zhao, Ziqi Wei, Honggang Chen, Jinbao Zhang, Haijing Duan, Ling Jin
{"title":"Comparative transcriptome analysis of Isatis indigotica under different precipitation conditions.","authors":"Wenlong Zhao, Ziqi Wei, Honggang Chen, Jinbao Zhang, Haijing Duan, Ling Jin","doi":"10.1007/s11033-025-10451-0","DOIUrl":"https://doi.org/10.1007/s11033-025-10451-0","url":null,"abstract":"<p><strong>Background: </strong>Plant adaptation to environmental stress is crucial for improving crop resilience and productivity. The growth and yield of Isatis indigotica are significantly affected by water conditions. In this study, high-throughput transcriptome sequencing was performed on leaf samples from Isatis indigotica after different treatments: normal precipitation (CK), 40% rainfall reduction (R1), 80% rainfall reduction (R2), 40% rainfall enhancement (I1) and 80% rainfall enhancement (I2).</p><p><strong>Results: </strong>Under 80% rainfall augmentation (I2), the malondialdehyde (MDA) content of Isatis indigotica leaves was the lowest, and the proline (pro) and catalase (CAT) activities were the highest. These findings indicate that normal precipitation conditions do not meet the optimal water requirements for the growth of Isatis indigotica and that appropriate irrigation can be used to improve the accumulation and quality of medicinal substances from this species. Transcriptome analysis of Isatis indigotica leaves compared with those in the control group (CK) revealed 896, 2551, 1294, and 3082 differentially expressed genes in the reduced rainfall reduction groups (R1, R2) and increased rainfall groups (I1, 12), respectively. The number of differentially expressed genes (DEGs) gradually increased with increasing rainfall and decreased after rainfall reduction. The GO enrichment results revealed that the DEGs were significantly enriched in functions such as cellular processes, metabolic processes, stimulus response, cell structure, and catalytic and binding activities. KEGG analysis revealed that metabolic pathways such as glutathione metabolism, phenylpropanoid biosynthesis, and plant hormone signaling were significantly enriched, with the greatest number of enriched genes. This study revealed 32 antioxidant system-related genes, 49 phenylpropanoid biosynthesis-related genes, and 49 plant hormone signaling pathway-related genes among the significantly enriched pathways.</p><p><strong>Conclusions: </strong>This study provides new insights into the regulation of Isatis indigotica leaves in response to different water contents at the molecular level. The findings also provide a reference for optimizing the field management of Isatis indigotica and improving the quality and yield of medicinal materials.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"348"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743349","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 comprehensive review of eucalyptol: synthesis, metabolism, and therapeutic applications in disease treatment.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-28 DOI: 10.1007/s11033-025-10461-y
Bin Yao, Bin He, Jiahua Peng, Xin Song, Rui Zhao, Yu Sun, Yanfang Zhang
{"title":"The comprehensive review of eucalyptol: synthesis, metabolism, and therapeutic applications in disease treatment.","authors":"Bin Yao, Bin He, Jiahua Peng, Xin Song, Rui Zhao, Yu Sun, Yanfang Zhang","doi":"10.1007/s11033-025-10461-y","DOIUrl":"https://doi.org/10.1007/s11033-025-10461-y","url":null,"abstract":"<p><strong>Background: </strong>Eucalyptol (1,8-cineole), a naturally occurring monoterpenoid compound, is ubiquitously distributed across plant, animal, and microbial organisms. This bioactive molecule demonstrates significant therapeutic potential for various neurological and respiratory disorders, including cancer, epilepsy, and tracheitis, attributable to its potent antioxidant, anti-inflammatory, and antimicrobial properties.</p><p><strong>Scope and thrust: </strong>The present review systematically examines the biosynthetic pathways and metabolic routes of eucalyptol, while elucidating its molecular mechanisms underlying microbial inhibition. We comprehensively summarize its principal therapeutic pathways in major disease interventions, with particular emphasis on its multi-target pharmacological actions. Furthermore, this analysis addresses potential toxicological concerns associated with eucalyptol application and discusses emerging strategies utilizing biological agents for active enhancement.</p><p><strong>Conclusion and significance: </strong>This comprehensive evaluation not only enhances our understanding of eucalyptol's therapeutic mechanisms but also provides critical insights for its development as a promising phytopharmaceutical agent in clinical practice.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"346"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735992","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
Genome-wide identification and transcriptional expression profiles of the transcription factor WRKY in Gentiana macrophylla.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-27 DOI: 10.1007/s11033-025-10452-z
Xiaohui Gu, Lipan Zhou, Yang Pu, Fan Jiang, Li Yang, Tianyi Zhang, Tao Zhou, Xumei Wang
{"title":"Genome-wide identification and transcriptional expression profiles of the transcription factor WRKY in Gentiana macrophylla.","authors":"Xiaohui Gu, Lipan Zhou, Yang Pu, Fan Jiang, Li Yang, Tianyi Zhang, Tao Zhou, Xumei Wang","doi":"10.1007/s11033-025-10452-z","DOIUrl":"10.1007/s11033-025-10452-z","url":null,"abstract":"<p><p>Gentiana macrophylla Pall., a valuable Chinese traditional medicinal herb, exhibits notable anti-inflammatory and analgesic effects. The WRKY transcription factor plays a pivotal role in regulating development and stress responses. Although the WRKY family extensively characterized in diverse plant species, a comprehensive analysis of this gene family in G. macrophylla remains unexplored. In this study, we systematically identified 84 WRKY genes (GmWRKYs) from the G. macrophylla genome and classified them into three primary clades based on phylogenetic analysis. Further characterization of motif architectures, gene structures, chromosomal distributions, and syntenic relationships revealed conserved evolutionary patterns within this gene family. Notably, both phylogenetic evidence and whole-genome duplication (WGD) event analyses suggested that GmWRKYs originated from a common ancestor and underwent expansion through lineage-specific WGDs. RNA-seq and qRT-PCR analysis revealed that GmWRKYs had different expression patterns in different tissues of G. macrophylla. Weighted gene co-expression network analysis (WGCNA) further identified significant co-expression relationships between GmWRKYs and key genes involved in iridoid biosynthesis. Our results provide a potential theoretical basis for future investigation on the role of WRKY genes in the biosynthesis of iridoid in G. macrophylla.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"344"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720556","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
Identification of c-Jun phosphorylation as a crucial mediator of complement activation in renal ischemia-reperfusion injury revealed by phosphoproteomics and functional validation.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-27 DOI: 10.1007/s11033-025-10414-5
Yufeng Zhao, Yirui Cao, Ying Su, Juntao Chen, Xuanchuan Wang, Peipei Ding, Weiguo Hu, Tongyu Zhu, Chao Hu
{"title":"Identification of c-Jun phosphorylation as a crucial mediator of complement activation in renal ischemia-reperfusion injury revealed by phosphoproteomics and functional validation.","authors":"Yufeng Zhao, Yirui Cao, Ying Su, Juntao Chen, Xuanchuan Wang, Peipei Ding, Weiguo Hu, Tongyu Zhu, Chao Hu","doi":"10.1007/s11033-025-10414-5","DOIUrl":"10.1007/s11033-025-10414-5","url":null,"abstract":"<p><strong>Background: </strong>Ischemia reperfusion injury (IRI) is an unavoidable condition that primarily affects graft function in renal transplantation. Blockage of complement activation by complement receptor immunoglobulin/ factor H (CRIg/FH), a novel complement inhibitor, shows great potency to ameliorate renal IRI. Sublytic membrane attack complex (MAC) disrupts cellular functions via the activation of different protein kinases and phosphorylation of critical signal transduction factors. We aimed to investigate whether complement activation triggered shift in phosphorylation status in IRI.</p><p><strong>Methods and results: </strong>We performed a LC-MS/MS-based quantitative phosphoproteomic analysis of CRIg/FH-IRI, PBS-IRI and Sham mice, depicting a thorough protein phosphorylation profile. C3d and MAC staining were conducted to study the complement activation status. In vitro model mimicking complement mediated IRI tubular injury was achieved by applying normal human serum (NHS) to TCMK cells. By hierarchical clustering, we observed that CRIg/FH treatment reversed the hyperphosphorylation status triggered by IRI. Differentially expressed phosphoproteins (DEPs) were associated with focal adhesion, integrin activation, actin cytoskeleton organization and cell junction. We identified c-Jun as the most differentially phosphorylated transcriptional factor regulated by complement activation, the S63 phosphorylation of which was verified both in vitro and in vivo and screened for its downstream targets. JNK inhibitor reduced the phosphorylation of c-Jun and attenuated accumulation of the C3d on the tubular epithelial cells.</p><p><strong>Conclusion: </strong>We proposed a crucial role of c-Jun phosphorylation in complement activation induced by renal IRI by combining phosphoproteomic approaches and protein validation, which hopefully could provide novel insights into the pathological mechanisms of IRI.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"345"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720560","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
MALAT1 SNP (rs619586) shows a protective effect against type 1 diabetes mellitus, while the miR-146a SNP (rs57095329) is linked to an increased risk of developing the disease.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-26 DOI: 10.1007/s11033-025-10404-7
Soha M Hamdy, Heba A Ibrahim, Omayma O Abdelaleem, Olfat G Shaker, Sherin K Hussein, Sara M A K Massoud, Ola N Sayed
{"title":"MALAT1 SNP (rs619586) shows a protective effect against type 1 diabetes mellitus, while the miR-146a SNP (rs57095329) is linked to an increased risk of developing the disease.","authors":"Soha M Hamdy, Heba A Ibrahim, Omayma O Abdelaleem, Olfat G Shaker, Sherin K Hussein, Sara M A K Massoud, Ola N Sayed","doi":"10.1007/s11033-025-10404-7","DOIUrl":"https://doi.org/10.1007/s11033-025-10404-7","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes mellitus (T1DM), one of the most distinct and intricate metabolic diseases, is characterized by the death of pancreatic β-cells, which leads to a lack of insulin secretion and, ultimately, hyperglycemia. The condition is more common in children and adolescents. Long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. They are essential to the control of several vital physiological processes. Many diseases have been linked to genetic variations in LncRNAs and miRNAs, though, their significance in type 1 diabetes mellitus (T1DM) is yet underappreciated.</p><p><strong>Methods: </strong>Ninety-two Egyptian children diagnosed with T1DM as well as 92 healthy age- and sex-matched subjects were incorporated in the current research. Real-time polymerase chain reaction (RT-PCR) was used to assess rs619586 and rs57095329 in the study subjects.</p><p><strong>Results: </strong>The GG and AG genotypes and the G allele of MALAT1 (rs619586) were associated with a significant decrease in the risk of T1DM.Also, the AG and GG genotypes as well as the G allele of miR-146a (rs57095329) were associated with a significant increase in the risk of T1DM (p > 0.05, each).</p><p><strong>Conclusion: </strong>For the first time, our investigation had shown the connection between MALAT1 (rs619586) and miRNA-146a (rs57095329) polymorphisms and the risk of development of T1DM in Egyptians.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"340"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730364","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
Utilization of TEP miRNAs in tumor proliferation, diagnostic evaluation, therapeutic intervention, and prognostic assessment.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-26 DOI: 10.1007/s11033-025-10433-2
Yuhan Wang, Ling Jiang, Jie Wang, Yuanshuai Huang, Ya Dong
{"title":"Utilization of TEP miRNAs in tumor proliferation, diagnostic evaluation, therapeutic intervention, and prognostic assessment.","authors":"Yuhan Wang, Ling Jiang, Jie Wang, Yuanshuai Huang, Ya Dong","doi":"10.1007/s11033-025-10433-2","DOIUrl":"https://doi.org/10.1007/s11033-025-10433-2","url":null,"abstract":"<p><p>According to the most recent 2022 statistics, China accounts for 4.82 million cancer patients, leading globally in prevalence. Early detection and intervention remain the most effective strategies for tumor prevention, treatment, and mortality reduction. There is an urgent need to enhance capabilities in cancer diagnosis and prevention. This study examines the association between tumor-educated platelet (TEP) microRNAs (miRNAs) and malignancies, as well as the role of TEP miRNAs in common cancers. TEP miRNAs offer significant advantages over tissue biopsies, conventional tumor biomarkers, and circulating miRNAs, including simplified sampling procedures, efficient monitoring, and longitudinal assessment of therapeutic dynamics. These advantages are instrumental in advancing tumor screening, diagnosis, treatment, and monitoring.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"343"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720618","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
Assessment of HJV and SMN1 gene expression levels in infertile men: laboratory and bioinformatic approaches.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-26 DOI: 10.1007/s11033-025-10407-4
Sasan Bouk, Kheirollah Yari, Parimah Pournaghi, Kamran Mansouri, Bijan Soleymani
{"title":"Assessment of HJV and SMN1 gene expression levels in infertile men: laboratory and bioinformatic approaches.","authors":"Sasan Bouk, Kheirollah Yari, Parimah Pournaghi, Kamran Mansouri, Bijan Soleymani","doi":"10.1007/s11033-025-10407-4","DOIUrl":"https://doi.org/10.1007/s11033-025-10407-4","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Infertility is a complex condition, with one of its key factors being the regulation of spermatogenesis, a process involving several critical genes. Previous in-silico studies have predicted a potential link between the HJV and SMN1 genes and spermatogenesis. This study aims to investigate the relationship between HJV and SMN1 gene expression in both blood and semen samples, and their association with male infertility, specifically azoospermia and oligospermia, through laboratory analysis. Furthermore, bioinformatic analyses were conducted to gain novel insights into these genes and, where applicable, to confirm their role in male infertility.</p><p><strong>Methods and results: </strong>The expression levels of HJV and SMN1 genes were analyzed using Real-Time PCR to compare differences between healthy and infertile groups. Additionally, to gain novel insights into the role of these genes in male infertility, we analyzed validated online datasets using R Studio with various packages, including Limma. Regarding the blood samples, the HJV gene mRNA was almost absent and the SMN1 gene expression level showed a significant decrease in infertile patients compared to healthy men. In the case of semen samples, real-time analysis showed a decreased expression of both genes in the samples of infertile patients. The in-silico analysis on the existing datasets showed the agreement of some data with the data of the present analysis.</p><p><strong>Conclusion: </strong>The significant differences in HJV and SMN1 gene expression observed in the semen samples of healthy and infertile men suggest a potential connection between these genes and defects in the spermatogenesis process in these patients. While some datasets supported these findings, others did not show a significant relationship.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"341"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720611","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
Characterization and molecular dynamics simulation of Lk2 lipase expressed in Pichia pastoris.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-26 DOI: 10.1007/s11033-025-10440-3
Annisa Ananda, Leyla Novita Brigiyanti, Made Puspasari Widhiastuty, Titin Haryati, Suharti, Ilma Fauziah Ma'ruf, Akhmaloka
{"title":"Characterization and molecular dynamics simulation of Lk2 lipase expressed in Pichia pastoris.","authors":"Annisa Ananda, Leyla Novita Brigiyanti, Made Puspasari Widhiastuty, Titin Haryati, Suharti, Ilma Fauziah Ma'ruf, Akhmaloka","doi":"10.1007/s11033-025-10440-3","DOIUrl":"https://doi.org/10.1007/s11033-025-10440-3","url":null,"abstract":"<p><strong>Background: </strong>Lipase is a versatile enzyme that serves as a biocatalyst in various industries. lk2 was successfully isolated from household waste compost through a metagenomic approach.</p><p><strong>Materials and methods: </strong>lk2 from plasmid pPICZαA- lk2 was integrated into chromosomes of Pichia. pastoris GS115 using the electroporation method. Lk2 was expressed on Pichia. pastoris by methanol induction. The enzyme was purified through Ion Metal Affinity Chromatography Ni-NTA. The purified enzyme was characterized based on hydrolytic activity and in silico analysis.</p><p><strong>Results: </strong>Lk2 was successfully expressed as an extracellular protein in Pichia pastoris. The cell-free supernatant exhibited hydrolysis activity to para-nitro phenyl laurate. The purified protein showed 15 times activity compared to cell-free supernatant and the size at around 35 kDa following gel electrophoresis. The enzyme showed optimum activity at 60<sup>o</sup>C and pH 8. Lk2 preferred para nitro phenyl laurate as substrate. The enzyme's preference for medium-long carbon chains was corroborated by in silico analysis, which revealed favorable interactions between the enzyme and substrate, including affinity binding energy and optimal orientation of catalytic pocket to the substrate. Furthermore, the radius of gyration analysis of the Lk2 showed that the best structural compactness of Lk2 was at 60<sup>o</sup>C. This is in line with the optimal temperature of Lk2 activity. In addition, docking analysis found important substrate binding residues, including Tyr30, Ser85, Leu121, Leu163, Leu166, Leu 233, and Leu254 beside Ser85, Asp231, and His253 as triad catalytic.</p><p><strong>Conclusion: </strong>Lk2 belongs to a thermotolerant and alkaline lipase, prefers a medium-length carbon chain as substrate and is confirmed by in silico analysis. Several amino acid residues were probed to be important for substrate binding residues. The data give valuable information to develop the possibility of Lk2 as an industry's enzyme.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"342"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720615","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 mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-03-26 DOI: 10.1007/s11033-025-10463-w
Nisha Ali, Usman Sayeed, Syed Monowar Alam Shahid, Salman Akhtar, Mohammad Kalim Ahmad Khan
{"title":"Molecular mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.","authors":"Nisha Ali, Usman Sayeed, Syed Monowar Alam Shahid, Salman Akhtar, Mohammad Kalim Ahmad Khan","doi":"10.1007/s11033-025-10463-w","DOIUrl":"https://doi.org/10.1007/s11033-025-10463-w","url":null,"abstract":"<p><p>Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD), are significant global health challenges, owing to their profound impact on cognitive, motor, and behavioral functions. The etiology and progression of these disorders are influenced by a complex interplay of environmental factors and genetic predispositions with specific genetic markers, such as mutations in the APOE and HTT genes, which play pivotal roles. Current therapeutic interventions predominantly focus on symptom management; however, emerging strategies, including gene therapies, anti-amyloid agents, and neuroprotective approaches, are designed to directly target the underlying disease mechanisms. Advances in biomarker discovery and imaging methodologies have emerged as essential tools for early diagnosis and monitoring of therapeutic efficacy in these disorders. In the context of AD, cerebrospinal fluid (CSF) amyloid-beta (Aβ) and tau levels, along with positron emission tomography (PET) imaging, are well-established biomarkers. Similarly, CSF alpha-synuclein and dopamine transporter (DAT) imaging have been employed as diagnostic tools for PD. Moreover, emerging biomarkers, such as blood-based tau and the Aβ42/40 ratio for AD, as well as the neurofilament light chain (NfL) for ALS and PD, hold promise for enhancing early diagnostic accuracy and facilitating the longitudinal assessment of disease progression. This study comprehensively examined the molecular mechanisms underlying these neurodegenerative disorders, focusing on amyloid-beta plaque deposition and tau protein aggregation in AD, alpha-synuclein misfolding in PD, and aberrant protein aggregation in ALS and HD, thereby contributing to a deeper understanding of the pathophysiological basis of these disorders.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"337"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730370","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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