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New Advancements in Prognostic Biomarkers for Upper Tract Urothelial Carcinoma.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-07 DOI: 10.2174/0109298673339558250123110322
Xiaotong Shi, Guodong Zhu

As research on upper tract urothelial carcinoma (UTUC) has deepened, the value of biomarkers in the prognostic evaluation of UTUC has been gradually highlighted. As a high-grade epithelial tumor derived from the renal pelvis or ureter, UTUC has a significant prognostic challenge to patients, given its high invasiveness and recurrence rate for the formation of post-operative bladder cancer. To better predict the recurrence and metastasis risk of UTUC, this article provides a comprehensive review of hematologic, urologic, genetic, and histologic biomarker studies on the prognostic assessment of UTUC. This study covers a broad range of different kinds of biomarkers, asshown in the graphical abstract. By systematically analyzing these biomarkers, we will have a better understanding of the biological features of UTUC, which will provide more comprehensive and accurate information for its prognostic assessment. This will not only help clinicians develop more precise treatment strategies, but also provide patients with more personalized rehabilitation recommendations.

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引用次数: 0
The Role and Molecular Mechanism of Icaritin in the Treatment of Alzheimer's Disease.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-07 DOI: 10.2174/0109298673354454250124074057
Chong-Bo Zheng, Li-Zhen Wu, Wan-Ying Song, Liang Luo, Jia-Ting Cai, Zhi-Hua Huang, Ke-Qiang Tian

Alzheimer's disease (AD), a degenerative disease of the central nervous system, affects approximately 70 million individuals worldwide. As the number of elderly in the population increases, the prevalence and incidence of AD are increasing annually. Although the drugs are currently used to alleviate certain cognitive symptoms, their overall therapeutic efficacy remains unclear. Consequently, there is significant societal demand for safe and effective therapeutic options. Icaritin (ICT), a bioactive compound derived from Epimedium brevicornu Maxim, has anti-apoptotic, antioxidant, anti-neuroinflammatory, anti-aging, and neuroprotective properties. In recent years, it has garnered significant interest because of its potential preventative and therapeutic effects in the context of AD. In this review, we analyze the therapeutic effects of ICT on AD, namely the inhibition of neuroinflammation, effects against oxidative stress and apoptosis, and promotion of cellular autophagy. The aim of this review was to provide a general reference for the research and development of new drugs, in particular ICT, for the prevention and treatment of AD.

{"title":"The Role and Molecular Mechanism of Icaritin in the Treatment of Alzheimer's Disease.","authors":"Chong-Bo Zheng, Li-Zhen Wu, Wan-Ying Song, Liang Luo, Jia-Ting Cai, Zhi-Hua Huang, Ke-Qiang Tian","doi":"10.2174/0109298673354454250124074057","DOIUrl":"https://doi.org/10.2174/0109298673354454250124074057","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a degenerative disease of the central nervous system, affects approximately 70 million individuals worldwide. As the number of elderly in the population increases, the prevalence and incidence of AD are increasing annually. Although the drugs are currently used to alleviate certain cognitive symptoms, their overall therapeutic efficacy remains unclear. Consequently, there is significant societal demand for safe and effective therapeutic options. Icaritin (ICT), a bioactive compound derived from Epimedium brevicornu Maxim, has anti-apoptotic, antioxidant, anti-neuroinflammatory, anti-aging, and neuroprotective properties. In recent years, it has garnered significant interest because of its potential preventative and therapeutic effects in the context of AD. In this review, we analyze the therapeutic effects of ICT on AD, namely the inhibition of neuroinflammation, effects against oxidative stress and apoptosis, and promotion of cellular autophagy. The aim of this review was to provide a general reference for the research and development of new drugs, in particular ICT, for the prevention and treatment of AD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-07 DOI: 10.2174/0109298673361923250101072831
Saurav Kumar Mishra, Anshuman Chandra, Namrata Mitra, Nikita Krishna, Nagendra Singh, Shopnil Akash, Yousef A Bin Jardan, Mohammed Bourhia, John J Georrge

Aim: This study aimed to screen the potential phytochemicals derived from Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the host-- pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular dynamics approach.

Background: The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing infection cases. Drugs and vaccines for smallpox are being used to contain it. However, no specific drugs or vaccines are available to combat this infection.

Methods: The TMPK and D9 decapping enzymes were retrieved from the MPXV virus UK strain in FASTA format. Due to the unavailability of an experimentally determined structure, the 3D structure was modelled via SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from Asparagus racemosus using a maestro module. The potential inhibitors were examined via QSAR analysis. Additionally, through MD simulation 250ns, the stability was analyzed, and the MM-GBSA was employed to calculate the binding affinities.

Results: The molecular investigation revealed asparoside-C (PubChem ID: 158598) and asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via the ADME and QSAR analyses. Moreover, the simulation study of over 250ns revealed strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MMGBSA exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK and the D9 decapping enzyme according to their respective scores.

Conclusion: The docking, QSAR, and simulation investigation revealed dual-target inhibitors activity of phytochemicals from Asparagus racemosus towards the MPXV via targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.

{"title":"Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus.","authors":"Saurav Kumar Mishra, Anshuman Chandra, Namrata Mitra, Nikita Krishna, Nagendra Singh, Shopnil Akash, Yousef A Bin Jardan, Mohammed Bourhia, John J Georrge","doi":"10.2174/0109298673361923250101072831","DOIUrl":"10.2174/0109298673361923250101072831","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to screen the potential phytochemicals derived from Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the host-- pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular dynamics approach.</p><p><strong>Background: </strong>The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing infection cases. Drugs and vaccines for smallpox are being used to contain it. However, no specific drugs or vaccines are available to combat this infection.</p><p><strong>Methods: </strong>The TMPK and D9 decapping enzymes were retrieved from the MPXV virus UK strain in FASTA format. Due to the unavailability of an experimentally determined structure, the 3D structure was modelled via SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from Asparagus racemosus using a maestro module. The potential inhibitors were examined via QSAR analysis. Additionally, through MD simulation 250ns, the stability was analyzed, and the MM-GBSA was employed to calculate the binding affinities.</p><p><strong>Results: </strong>The molecular investigation revealed asparoside-C (PubChem ID: 158598) and asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via the ADME and QSAR analyses. Moreover, the simulation study of over 250ns revealed strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MMGBSA exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK and the D9 decapping enzyme according to their respective scores.</p><p><strong>Conclusion: </strong>The docking, QSAR, and simulation investigation revealed dual-target inhibitors activity of phytochemicals from Asparagus racemosus towards the MPXV via targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Scoping Review of Rho Kinase Inhibitors and their Role in Glaucoma Treatment.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-07 DOI: 10.2174/0109298673366619250113103213
Menglong Hao, Yalong Dang, Fang Lei

Objective: The purpose of this scoping review is to provide researchers with a comprehensive knowledge map and identify existing knowledge gaps.

Introduction: Glaucoma is the leading cause of irreversible blindness worldwide. ROCK inhibitors are a novel class of intraocular pressure-lowering drugs that specifically target trabecular meshwork cells. Current research on ROCK inhibitors is dispersed across multiple directions, and their precise mechanisms of action in glaucoma treatment remain incompletely understood. For these reasons, we sought to integrate the existing evidence using a scoping review approach.

Methods: Relevant articles published between 2014 and 2024 were identified and screened using keywords in the PubMed and Embase databases. Articles were analyzed based on the inclusion and exclusion criteria.

Results: The collected studies were categorized into three main themes: intraocular pressure reduction, neuroprotection, and anti-fibrosis. A total of 23 articles were included in the review. We found that studies related to intraocular pressure reduction accounted for the majority (approximately 74%), while research on neuroprotection and anti-fibrosis was relatively limited (approximately 14% each). Furthermore, among the 23 included articles, only one was a systematic review or meta-analysis.

Conclusion: ROCK inhibitors directly act on the trabecular meshwork to lower IOP and have potential neuroprotective and anti-fibrotic effects. However, these potential effects require further clinical trials to validate their efficacy in humans. In the future, more systematic reviews and meta-analyses are also needed to integrate and summarize the current primary research findings.

{"title":"A Scoping Review of Rho Kinase Inhibitors and their Role in Glaucoma Treatment.","authors":"Menglong Hao, Yalong Dang, Fang Lei","doi":"10.2174/0109298673366619250113103213","DOIUrl":"https://doi.org/10.2174/0109298673366619250113103213","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this scoping review is to provide researchers with a comprehensive knowledge map and identify existing knowledge gaps.</p><p><strong>Introduction: </strong>Glaucoma is the leading cause of irreversible blindness worldwide. ROCK inhibitors are a novel class of intraocular pressure-lowering drugs that specifically target trabecular meshwork cells. Current research on ROCK inhibitors is dispersed across multiple directions, and their precise mechanisms of action in glaucoma treatment remain incompletely understood. For these reasons, we sought to integrate the existing evidence using a scoping review approach.</p><p><strong>Methods: </strong>Relevant articles published between 2014 and 2024 were identified and screened using keywords in the PubMed and Embase databases. Articles were analyzed based on the inclusion and exclusion criteria.</p><p><strong>Results: </strong>The collected studies were categorized into three main themes: intraocular pressure reduction, neuroprotection, and anti-fibrosis. A total of 23 articles were included in the review. We found that studies related to intraocular pressure reduction accounted for the majority (approximately 74%), while research on neuroprotection and anti-fibrosis was relatively limited (approximately 14% each). Furthermore, among the 23 included articles, only one was a systematic review or meta-analysis.</p><p><strong>Conclusion: </strong>ROCK inhibitors directly act on the trabecular meshwork to lower IOP and have potential neuroprotective and anti-fibrotic effects. However, these potential effects require further clinical trials to validate their efficacy in humans. In the future, more systematic reviews and meta-analyses are also needed to integrate and summarize the current primary research findings.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher Selective Targeting of Telomeric Multimeric G-quadruplex by Natural Product Berberine.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-06 DOI: 10.2174/0109298673345414241202094409
Jixin Chen, Yi He, Yang Xu, Muhammad Umer, Naureen Anwar, Shiya Wei, Wenbin Liu, Zhangqian Wang, Chao Gao

Introduction: G-quadruplexes (G4s) are non-classical high-level structures that are formed by DNA/RNA sequences and have been a promising target for developing antitumor drugs. However, it is still a challenge to find a ligand that binds to a particular G4 with selectivity. Telomeric multimeric G4s are more accessible for screening for specific ligands due to their higher-order structure compared with telomeric monomeric G4s.

Methods: In this study, the natural product berberine was found to exhibit a higher selectivity for telomeric multimeric G4 in comparison with other G4s. The mechanism of interaction between telomeric G4s and berberine was further investigated by fluorescence spectra measurements, job plot analysis, and UV titrations. We found that there are three binding sites for berberine on telomeric dimeric G-quadruplex Tel45, which are located at the 5' and 3' terminal G-quartet surfaces and the pocket between the two quadruplex units of Tel45. It was worth noting that the berberine preferred to interact within the interfacial cavity between two G4 units.

Results: Moreover, via dynamic light scattering (DLS) and native polyacrylamide gel electrophoresis (Native-PAGE) assays, it was found that the particle size of the telomeric multimeric G4s conformation was significantly increased by the addition of berberine. In contrast, the particle sizes of Tel21 did not change significantly after the addition of berberine. An immunofluorescence assay indicated that berberine induced the formation of endogenous telomeric G4 structures along with the related telomeric DNA damage response.

Conclusion: This study provides a hypothetical basis for the development of natural products targeting telomeric G4 as antitumor drugs.

{"title":"Higher Selective Targeting of Telomeric Multimeric G-quadruplex by Natural Product Berberine.","authors":"Jixin Chen, Yi He, Yang Xu, Muhammad Umer, Naureen Anwar, Shiya Wei, Wenbin Liu, Zhangqian Wang, Chao Gao","doi":"10.2174/0109298673345414241202094409","DOIUrl":"https://doi.org/10.2174/0109298673345414241202094409","url":null,"abstract":"<p><strong>Introduction: </strong>G-quadruplexes (G4s) are non-classical high-level structures that are formed by DNA/RNA sequences and have been a promising target for developing antitumor drugs. However, it is still a challenge to find a ligand that binds to a particular G4 with selectivity. Telomeric multimeric G4s are more accessible for screening for specific ligands due to their higher-order structure compared with telomeric monomeric G4s.</p><p><strong>Methods: </strong>In this study, the natural product berberine was found to exhibit a higher selectivity for telomeric multimeric G4 in comparison with other G4s. The mechanism of interaction between telomeric G4s and berberine was further investigated by fluorescence spectra measurements, job plot analysis, and UV titrations. We found that there are three binding sites for berberine on telomeric dimeric G-quadruplex Tel45, which are located at the 5' and 3' terminal G-quartet surfaces and the pocket between the two quadruplex units of Tel45. It was worth noting that the berberine preferred to interact within the interfacial cavity between two G4 units.</p><p><strong>Results: </strong>Moreover, via dynamic light scattering (DLS) and native polyacrylamide gel electrophoresis (Native-PAGE) assays, it was found that the particle size of the telomeric multimeric G4s conformation was significantly increased by the addition of berberine. In contrast, the particle sizes of Tel21 did not change significantly after the addition of berberine. An immunofluorescence assay indicated that berberine induced the formation of endogenous telomeric G4 structures along with the related telomeric DNA damage response.</p><p><strong>Conclusion: </strong>This study provides a hypothetical basis for the development of natural products targeting telomeric G4 as antitumor drugs.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrative Multi-omics Analysis and Mendelian Randomization Reveal Potential Therapeutic Targets and their Stratification in Lung Squamous Cell Carcinoma.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-06 DOI: 10.2174/0109298673334210241228062116
Youpeng Chen, Enzhong Li, Zhenglin Chang, Yifei Xie, Xiaoyi Chen, Junquan Sun, Xuntao Lai, Zhangkai J Cheng, Baoqing Sun

Background: Lung Squamous Cell Carcinoma (LUSC), a major subtype of non-small cell lung cancer, presents significant treatment challenges due to limited targeted therapy options. This study aims to identify novel therapeutic targets to improve therapeutic strategies for LUSC.

Methods: By employing bulk RNA sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), survival analysis, and Mendelian Randomization (MR), we pinpointed genes with prognostic relevance to LUSC. These genes were further scrutinized for their therapeutic potential through LASSO regression, Protein-Protein Interaction (PPI) network analysis, and immune infiltration assessments. To delve into the roles and cell-specific expressions of these genes within the LUSC microenvironment, pathway enrichment analysis, single-cell RNA sequencing (scRNA-seq), and pseudotime analysis were conducted.

Results: Our integrative approach identified 23 prognostically significant therapeutic targets, categorized into tier-one, tier-two, and tier-three genes based on their potential therapeutic relevance. Functional enrichment analyses highlighted the significant role of these genes in immune response regulation, particularly in T-cell receptor signaling and the complement system. scRNA-seq analysis revealed cell-type-specific expression patterns and pseudotime analysis provided insights into cellular heterogeneity and developmental trajectories in LUSC.

Conclusions: In this study, we identified 3 tier-one genes (MCM6, C4B, CTC-463A16.1), 7 tier-two genes (C4A, HLA-DRB9, LIMS2, LINC00654, MYO7B, SIGLEC5, TIE1), and 13 tier-three genes (AC007743.1, AC147651.4, ALDH2, BTN3A2, BTNL9, CCR1, GIPC3, HLA-DQB1, ICAM5, LIMD1, PM20D1, RP11-302L19.3, RP11-768F21.1).

{"title":"Integrative Multi-omics Analysis and Mendelian Randomization Reveal Potential Therapeutic Targets and their Stratification in Lung Squamous Cell Carcinoma.","authors":"Youpeng Chen, Enzhong Li, Zhenglin Chang, Yifei Xie, Xiaoyi Chen, Junquan Sun, Xuntao Lai, Zhangkai J Cheng, Baoqing Sun","doi":"10.2174/0109298673334210241228062116","DOIUrl":"https://doi.org/10.2174/0109298673334210241228062116","url":null,"abstract":"<p><strong>Background: </strong>Lung Squamous Cell Carcinoma (LUSC), a major subtype of non-small cell lung cancer, presents significant treatment challenges due to limited targeted therapy options. This study aims to identify novel therapeutic targets to improve therapeutic strategies for LUSC.</p><p><strong>Methods: </strong>By employing bulk RNA sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), survival analysis, and Mendelian Randomization (MR), we pinpointed genes with prognostic relevance to LUSC. These genes were further scrutinized for their therapeutic potential through LASSO regression, Protein-Protein Interaction (PPI) network analysis, and immune infiltration assessments. To delve into the roles and cell-specific expressions of these genes within the LUSC microenvironment, pathway enrichment analysis, single-cell RNA sequencing (scRNA-seq), and pseudotime analysis were conducted.</p><p><strong>Results: </strong>Our integrative approach identified 23 prognostically significant therapeutic targets, categorized into tier-one, tier-two, and tier-three genes based on their potential therapeutic relevance. Functional enrichment analyses highlighted the significant role of these genes in immune response regulation, particularly in T-cell receptor signaling and the complement system. scRNA-seq analysis revealed cell-type-specific expression patterns and pseudotime analysis provided insights into cellular heterogeneity and developmental trajectories in LUSC.</p><p><strong>Conclusions: </strong>In this study, we identified 3 tier-one genes (MCM6, C4B, CTC-463A16.1), 7 tier-two genes (C4A, HLA-DRB9, LIMS2, LINC00654, MYO7B, SIGLEC5, TIE1), and 13 tier-three genes (AC007743.1, AC147651.4, ALDH2, BTN3A2, BTNL9, CCR1, GIPC3, HLA-DQB1, ICAM5, LIMD1, PM20D1, RP11-302L19.3, RP11-768F21.1).</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Construction of a Subcutaneous Fat Transplantation Model Infected with Mycobacterium.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-04 DOI: 10.2174/0109298673345671250114235930
Wuliang Diao, Yang Hu, Xiangyu Chen, Weidong Li, Julius K S K Kpegah, Xuan Chen, Mingzhu Wang, Jianda Zhou, Ping Li

Introduction: Fat grafting procedures for body contouring and cosmetic reconstruction have received widespread attention.

Method: In recent years, there has been an increase in post-fat grafting infections caused by Mycobacterium abscessus (MA), and there is a lack of representative and standardized murine models of infection; therefore, there has been limited research on the treatment of post-fat grafting MA infections. To overcome this challenge, we constructed an MA infection model after fat grafting.

Result: By evaluating skin charge, dermatopathology, and inflammatory markers, we found that the fat graft + 1 × 109 CFU/mL bacterial suspension infection group had significant inflammatory symptoms and elevated inflammatory factors on postoperative day 10.

Conclusion: The model construction process was simple and reproducible, which paves the way for further studies on the impact of MA pathogenesis and the efficacy of new treatments.

{"title":"Construction of a Subcutaneous Fat Transplantation Model Infected with Mycobacterium.","authors":"Wuliang Diao, Yang Hu, Xiangyu Chen, Weidong Li, Julius K S K Kpegah, Xuan Chen, Mingzhu Wang, Jianda Zhou, Ping Li","doi":"10.2174/0109298673345671250114235930","DOIUrl":"https://doi.org/10.2174/0109298673345671250114235930","url":null,"abstract":"<p><strong>Introduction: </strong>Fat grafting procedures for body contouring and cosmetic reconstruction have received widespread attention.</p><p><strong>Method: </strong>In recent years, there has been an increase in post-fat grafting infections caused by Mycobacterium abscessus (MA), and there is a lack of representative and standardized murine models of infection; therefore, there has been limited research on the treatment of post-fat grafting MA infections. To overcome this challenge, we constructed an MA infection model after fat grafting.</p><p><strong>Result: </strong>By evaluating skin charge, dermatopathology, and inflammatory markers, we found that the fat graft + 1 × 109 CFU/mL bacterial suspension infection group had significant inflammatory symptoms and elevated inflammatory factors on postoperative day 10.</p><p><strong>Conclusion: </strong>The model construction process was simple and reproducible, which paves the way for further studies on the impact of MA pathogenesis and the efficacy of new treatments.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of Shiga Toxin 2 for E. coli O157 Control: An In-Silico Study on Natural and Synthetic Compounds.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-04 DOI: 10.2174/0109298673363373250118144235
Ashiq Ali, Isra Noor, Maleeha Shaukat, Warda Waheed, Kaynaat Akbar, Ziyi Ji, Zhongjing Su

Introduction/objectives: Escherichia coli strains are known to cause various gastrointestinal disorders, with Shiga toxin 2, a potent cytotoxin, being a key virulence factor contributing to disease severity. Targeting Shiga toxin 2 presents a promising approach for therapeutic intervention in controlling E. coli O157 infections. This study aims to explore natural and synthetic inhibitors as potential therapeutic agents against Shiga toxin 2 through in-silico molecular docking and drug-likeness predictions.

Methods: An in-silico molecular docking study was conducted using AutoDock Vina and Chimera to assess the binding affinity of various natural and synthetic inhibitors against Shiga toxin 2. The selected inhibitors were evaluated for their drug-likeness based on adsorption, distribution, metabolism, and excretion (ADME) properties, applying Lipinski's rule of five and the Boiled-Egg technique to predict their suitability as potential drugs in biological systems.

Results: During the screening process, luteolin, a natural flavonoid, exhibited the highest binding affinity to Shiga toxin 2, with a notable negative binding energy of -8.7 kcal/- mol, indicating strong interaction potential.

Conclusion: The findings suggest that luteolin holds promise as a lead molecule for further development as a therapeutic agent against E. coli infections, warranting additional studies to validate its efficacy and safety.

{"title":"Inhibition of Shiga Toxin 2 for E. coli O157 Control: An In-Silico Study on Natural and Synthetic Compounds.","authors":"Ashiq Ali, Isra Noor, Maleeha Shaukat, Warda Waheed, Kaynaat Akbar, Ziyi Ji, Zhongjing Su","doi":"10.2174/0109298673363373250118144235","DOIUrl":"https://doi.org/10.2174/0109298673363373250118144235","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>Escherichia coli strains are known to cause various gastrointestinal disorders, with Shiga toxin 2, a potent cytotoxin, being a key virulence factor contributing to disease severity. Targeting Shiga toxin 2 presents a promising approach for therapeutic intervention in controlling E. coli O157 infections. This study aims to explore natural and synthetic inhibitors as potential therapeutic agents against Shiga toxin 2 through in-silico molecular docking and drug-likeness predictions.</p><p><strong>Methods: </strong>An in-silico molecular docking study was conducted using AutoDock Vina and Chimera to assess the binding affinity of various natural and synthetic inhibitors against Shiga toxin 2. The selected inhibitors were evaluated for their drug-likeness based on adsorption, distribution, metabolism, and excretion (ADME) properties, applying Lipinski's rule of five and the Boiled-Egg technique to predict their suitability as potential drugs in biological systems.</p><p><strong>Results: </strong>During the screening process, luteolin, a natural flavonoid, exhibited the highest binding affinity to Shiga toxin 2, with a notable negative binding energy of -8.7 kcal/- mol, indicating strong interaction potential.</p><p><strong>Conclusion: </strong>The findings suggest that luteolin holds promise as a lead molecule for further development as a therapeutic agent against E. coli infections, warranting additional studies to validate its efficacy and safety.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthesis, Anticancer Activity, and Mitochondria-targeted Bioimaging Applications of Novel Fluorescent Calix [4]arenes-benzimidazole Derivatives.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-31 DOI: 10.2174/0109298673356048241120182243
Beyza Solmaz, Alev Oguz, Mehmet Oguz, Bahadir Ozturk, Mustafa Yilmaz

Background: Calix[n]arenes have attracted great attention due to their biocompatibility and superior stability. When the necessary functional groups are attached to these compounds, they may have the potential to target tumor tissues. Benzimidazoles were among the anticancer drugs discovered in recent years.

Aim: The aim of this study was to design and synthesise a series of calix[4]arenes-benzimidazole. For comparison purposes, a benzimidazole derivative was synthesized by attaching it to the diester. Present the anticancer effects of these compounds by performing cell proliferation, apoptosis and cell imaging studies in cancer cell lines.

Methods: Some of the obtained compounds were synthesized by methods in literature studies, and the rest were synthesized by modifying previous methods. As a result, a total of 3 new fluorescent calix[4]arene-benzimidazole derivatives were synthesized. MTT was used for cell proliferation, and Annexin V was used for apoptosis studies. For Confocal imaging studies, cells were treated with DAPI and MitoTracker dyes.

Results: Four designed calix[4]arene-benzimidazole were successfully synthesized and structurally confirmed by NMR, and IR spectroscopy. Anticancer study of four synthesized substances was performed. Bio-imaging studies were performed using Confocal Microscopy for these three successfully synthesized fluorescent compounds.

Conclusion: CB5-a and CB5-b were found to be the most effective against HT-29 cells and CB5-c against HELA cells in the MTT test. Apoptosis analyses also proved that these compounds inhibited the proliferation of cancer cells. As a comparison substance, the synthesized CB5-R proven to be less cytotoxic than the fluorescent compounds by the MTT method, and we can say that the cationic compound bound to the calix[4]arene is more effective than the molecule bound to the diester.

{"title":"Synthesis, Anticancer Activity, and Mitochondria-targeted Bioimaging Applications of Novel Fluorescent Calix [4]arenes-benzimidazole Derivatives.","authors":"Beyza Solmaz, Alev Oguz, Mehmet Oguz, Bahadir Ozturk, Mustafa Yilmaz","doi":"10.2174/0109298673356048241120182243","DOIUrl":"https://doi.org/10.2174/0109298673356048241120182243","url":null,"abstract":"<p><strong>Background: </strong>Calix[n]arenes have attracted great attention due to their biocompatibility and superior stability. When the necessary functional groups are attached to these compounds, they may have the potential to target tumor tissues. Benzimidazoles were among the anticancer drugs discovered in recent years.</p><p><strong>Aim: </strong>The aim of this study was to design and synthesise a series of calix[4]arenes-benzimidazole. For comparison purposes, a benzimidazole derivative was synthesized by attaching it to the diester. Present the anticancer effects of these compounds by performing cell proliferation, apoptosis and cell imaging studies in cancer cell lines.</p><p><strong>Methods: </strong>Some of the obtained compounds were synthesized by methods in literature studies, and the rest were synthesized by modifying previous methods. As a result, a total of 3 new fluorescent calix[4]arene-benzimidazole derivatives were synthesized. MTT was used for cell proliferation, and Annexin V was used for apoptosis studies. For Confocal imaging studies, cells were treated with DAPI and MitoTracker dyes.</p><p><strong>Results: </strong>Four designed calix[4]arene-benzimidazole were successfully synthesized and structurally confirmed by NMR, and IR spectroscopy. Anticancer study of four synthesized substances was performed. Bio-imaging studies were performed using Confocal Microscopy for these three successfully synthesized fluorescent compounds.</p><p><strong>Conclusion: </strong>CB5-a and CB5-b were found to be the most effective against HT-29 cells and CB5-c against HELA cells in the MTT test. Apoptosis analyses also proved that these compounds inhibited the proliferation of cancer cells. As a comparison substance, the synthesized CB5-R proven to be less cytotoxic than the fluorescent compounds by the MTT method, and we can say that the cationic compound bound to the calix[4]arene is more effective than the molecule bound to the diester.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid Biochemistry and its Role in Human Diseases.
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-30 DOI: 10.2174/0109298673351452241220071215
Amine Nehaoua, Amin Gasmi, Asma Gasmi Benahmed, Sadaf Noor, Geir Bjørklund

Lipids play a variety of roles in living systems. They are a source of extremely high energy and a part of almost all signaling and biological processes. Despite the liver being the hub of lipid metabolism, lipid metabolism occurs across the human body. Any perturbation in the lipid metabolism or lipid storage systems can lead to diseases or disorders that can hamper the normal functioning of the human body. Lipids have been explored for their role in cancers. The intake of saturated fatty acids has been found to increase the metastasis and growth of cancerous cells. The role of lipids has also been studied in brain diseases. In Tay-Sachs disease, the inability to metabolize GM2 ganglioside alters normal nerve cell functioning. Similarly, lipids also play critical roles in Parkinson's and Alzheimer's disease. Moreover, atherosclerosis is a leading cause of cardiovascular diseases and brain stroke. Dyslipidemia or excess fatty acids is a leading cause of non-alcoholic fatty liver disease, insulin resistance, and diabetes mellitus. Dyslipidemia also leads to jaundice, which, in turn, can seriously damage the kidneys. This review focuses on the various human diseases occurring because of lipid metabolism.

{"title":"Lipid Biochemistry and its Role in Human Diseases.","authors":"Amine Nehaoua, Amin Gasmi, Asma Gasmi Benahmed, Sadaf Noor, Geir Bjørklund","doi":"10.2174/0109298673351452241220071215","DOIUrl":"https://doi.org/10.2174/0109298673351452241220071215","url":null,"abstract":"<p><p>Lipids play a variety of roles in living systems. They are a source of extremely high energy and a part of almost all signaling and biological processes. Despite the liver being the hub of lipid metabolism, lipid metabolism occurs across the human body. Any perturbation in the lipid metabolism or lipid storage systems can lead to diseases or disorders that can hamper the normal functioning of the human body. Lipids have been explored for their role in cancers. The intake of saturated fatty acids has been found to increase the metastasis and growth of cancerous cells. The role of lipids has also been studied in brain diseases. In Tay-Sachs disease, the inability to metabolize GM2 ganglioside alters normal nerve cell functioning. Similarly, lipids also play critical roles in Parkinson's and Alzheimer's disease. Moreover, atherosclerosis is a leading cause of cardiovascular diseases and brain stroke. Dyslipidemia or excess fatty acids is a leading cause of non-alcoholic fatty liver disease, insulin resistance, and diabetes mellitus. Dyslipidemia also leads to jaundice, which, in turn, can seriously damage the kidneys. This review focuses on the various human diseases occurring because of lipid metabolism.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Current medicinal chemistry
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