Pub Date : 2023-01-01Epub Date: 2023-05-12DOI: 10.26502/fjppr.070
Huawei Zhang, Jane J Border, Xing Fang, Yedan Liu, Chengyun Tang, Wenjun Gao, Shaoxun Wang, Seung Min Shin, Ya Guo, Chao Zhang, Ezekiel Gonzalez-Fernandez, Hongwei Yu, Peng Sun, Richard J Roman, Fan Fan
Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in Dusp5 KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from Dusp5 KO rats. Dusp5 KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in Dusp5 KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in Dusp5 KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models.
{"title":"Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5.","authors":"Huawei Zhang, Jane J Border, Xing Fang, Yedan Liu, Chengyun Tang, Wenjun Gao, Shaoxun Wang, Seung Min Shin, Ya Guo, Chao Zhang, Ezekiel Gonzalez-Fernandez, Hongwei Yu, Peng Sun, Richard J Roman, Fan Fan","doi":"10.26502/fjppr.070","DOIUrl":"10.26502/fjppr.070","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in <i>Dusp5</i> KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from <i>Dusp5</i> KO rats. <i>Dusp5</i> KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in <i>Dusp5</i> KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in <i>Dusp5</i> KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models.</p>","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"7 2","pages":"49-61"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Jalgaonkar, R. Tripathi, Nishtha Khatri, Rachana Patankar, S. Gajbhiye, Mohsin Sayyed, A. Shankar
{"title":"Analgesic, Anti-inflammatory, and Antioxidant potential of S-adenosyl L-Methionine on Nitroglycerine induced Migraine in mice Models","authors":"S. Jalgaonkar, R. Tripathi, Nishtha Khatri, Rachana Patankar, S. Gajbhiye, Mohsin Sayyed, A. Shankar","doi":"10.26502/fjppr.067","DOIUrl":"https://doi.org/10.26502/fjppr.067","url":null,"abstract":"","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69347625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vonoprazan-Based versus Esomeprazole-Based Triple Therapy for Helicobacter Pylori: A Randomized Trial","authors":"Yasser A. Abdelghani, Mahmoud M. Moussa","doi":"10.26502/fjppr.078","DOIUrl":"https://doi.org/10.26502/fjppr.078","url":null,"abstract":"","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69347905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Zhong, Tamara Glazer, Meghana Kshirsagar, Richard Johnston, Rahul Dodhia, Allen Kim, Divya Michael, Santiago Salcido, Sameer Nair-Desai, Thomas C. Tsai, Stefanie Friedhoff, William B Weeks, Juan M. Lavista
Introduction: In early 2021, effective SARS-CoV-2 (COVID-19) vaccines became available in the United States; by mid-April 2021, vaccine availability outstripped demand, daily vaccination rates peaked, and COVID-19 vaccines were found highly effective in adult populations. Accurate estimates of the number of vaccine-preventable deaths had higher vaccination rates been attained could have helped local policymakers and possibly persuaded more to get vaccinated.
{"title":"Estimating Vaccine-Preventable COVID-19 Deaths Among Adults Under Counterfactual Vaccination Scenarios in The United States: A Modeling Study Using Observational Data","authors":"Ming Zhong, Tamara Glazer, Meghana Kshirsagar, Richard Johnston, Rahul Dodhia, Allen Kim, Divya Michael, Santiago Salcido, Sameer Nair-Desai, Thomas C. Tsai, Stefanie Friedhoff, William B Weeks, Juan M. Lavista","doi":"10.26502/fjppr.079","DOIUrl":"https://doi.org/10.26502/fjppr.079","url":null,"abstract":"Introduction: In early 2021, effective SARS-CoV-2 (COVID-19) vaccines became available in the United States; by mid-April 2021, vaccine availability outstripped demand, daily vaccination rates peaked, and COVID-19 vaccines were found highly effective in adult populations. Accurate estimates of the number of vaccine-preventable deaths had higher vaccination rates been attained could have helped local policymakers and possibly persuaded more to get vaccinated.","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"137 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135446756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Supramolecular chemistry is a captivating and interdisciplinary field that explores the interactions between molecules to form complex and functional assemblies through non-covalent forces. This review paper presents an in-depth exploration of the fundamental concepts, supramolecular assemblies and structures, applications in nanotechnology and biology, as well as challenges and future perspectives in supramolecular chemistry. The paper begins by elucidating the fundamental principles of supramolecular chemistry, emphasizing the significance of weak, non-covalent interactions such as hydrogen bonding, van der Waals forces, and π-π interactions. Molecular recognition, self-assembly, and host-guest interactions are highlighted as key concepts shaping the field. Subsequently, the review delves into various supramolecular assemblies and structures, showcasing the diversity of nanoscale architectures that arise from self-assembly processes. From nanotubes and nanofibers to metal-organic frameworks and dynamic supramolecular systems, each structure's properties and potential applications are explored. The application of supramolecular chemistry in nanotechnology and biology is a central focus of the paper. It covers the design of supramolecular materials for drug delivery, nanoelectronics, nanosensors, and biomimetic systems. Additionally, the integration of supramolecular approaches in biology, including molecular recognition, enzyme mimics, and bioimaging, is discussed in detail. Furthermore, the challenges faced by supramolecular chemistry, such as predictability, stability, and scalability, are addressed. The paper also looks into the future perspectives of the field, envisioning adaptive materials, supramolecular machines, and data-driven design as exciting prospects. Overall, this comprehensive review offers a thorough understanding of the captivating world of supramolecular chemistry and its potential to revolutionize various scientific and technological domains. Through interdisciplinary efforts and a focus on sustainability, supramolecular chemistry holds promise for addressing real-world challenges and shaping a future defined by innovative materials and transformative applications.
{"title":"Supramolecular Chemistry: Unveiling the Fascinating World of Non-Covalent Interactions and Complex Assemblies","authors":"Shreya Talreja, Shashank Tiwari","doi":"10.26502/fjppr.075","DOIUrl":"https://doi.org/10.26502/fjppr.075","url":null,"abstract":"Supramolecular chemistry is a captivating and interdisciplinary field that explores the interactions between molecules to form complex and functional assemblies through non-covalent forces. This review paper presents an in-depth exploration of the fundamental concepts, supramolecular assemblies and structures, applications in nanotechnology and biology, as well as challenges and future perspectives in supramolecular chemistry. The paper begins by elucidating the fundamental principles of supramolecular chemistry, emphasizing the significance of weak, non-covalent interactions such as hydrogen bonding, van der Waals forces, and π-π interactions. Molecular recognition, self-assembly, and host-guest interactions are highlighted as key concepts shaping the field. Subsequently, the review delves into various supramolecular assemblies and structures, showcasing the diversity of nanoscale architectures that arise from self-assembly processes. From nanotubes and nanofibers to metal-organic frameworks and dynamic supramolecular systems, each structure's properties and potential applications are explored. The application of supramolecular chemistry in nanotechnology and biology is a central focus of the paper. It covers the design of supramolecular materials for drug delivery, nanoelectronics, nanosensors, and biomimetic systems. Additionally, the integration of supramolecular approaches in biology, including molecular recognition, enzyme mimics, and bioimaging, is discussed in detail. Furthermore, the challenges faced by supramolecular chemistry, such as predictability, stability, and scalability, are addressed. The paper also looks into the future perspectives of the field, envisioning adaptive materials, supramolecular machines, and data-driven design as exciting prospects. Overall, this comprehensive review offers a thorough understanding of the captivating world of supramolecular chemistry and its potential to revolutionize various scientific and technological domains. Through interdisciplinary efforts and a focus on sustainability, supramolecular chemistry holds promise for addressing real-world challenges and shaping a future defined by innovative materials and transformative applications.","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136138934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Therapeutic targeting of MYC directly has proven difficult, prompting indirect strategies using a synthetic lethal drug. Here, we characterize one such drug dimethylfasudil (diMF), a rho-associated protein kinase (ROCK) inhibitor. But this diMF activity is not linked to the synthetic lethal interaction with MYC. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as Centromere Protein F (CENP-F), failed to localize at kinetochores in early mitosis, confirming a deficit in centromere assembly. This, presumably, contributed to the development of anomalies in chromosome segregation in cells treated with diMF. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the central spindlin complex, and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.
{"title":"Characterization of Mitotic Phenotypes Associated with a MYC Synthetic Lethal Compound","authors":"Qiong Shi","doi":"10.26502/fjppr.082","DOIUrl":"https://doi.org/10.26502/fjppr.082","url":null,"abstract":"Therapeutic targeting of MYC directly has proven difficult, prompting indirect strategies using a synthetic lethal drug. Here, we characterize one such drug dimethylfasudil (diMF), a rho-associated protein kinase (ROCK) inhibitor. But this diMF activity is not linked to the synthetic lethal interaction with MYC. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as Centromere Protein F (CENP-F), failed to localize at kinetochores in early mitosis, confirming a deficit in centromere assembly. This, presumably, contributed to the development of anomalies in chromosome segregation in cells treated with diMF. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the central spindlin complex, and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135843645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Leonard, Ballo Mahamadou, Soudré Albert, T. Basile, Bah Sekou, B. Balé
{"title":"Effects of Fruits of Aqueous Extract of Sarcocephalus Latifolius B. on Gentamicin-Induced Nephrotoxicity in Rats","authors":"D. Leonard, Ballo Mahamadou, Soudré Albert, T. Basile, Bah Sekou, B. Balé","doi":"10.26502/fjppr.066","DOIUrl":"https://doi.org/10.26502/fjppr.066","url":null,"abstract":"","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69347620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pablo Borque, Juan Carlos Galán, Beatriz Romero, Francesca Gioia, Rosa Escudero, Pilar Martín-Dávila Santiago Moreno, Jesús Fortún
Background: Human herpesviruses (HHV)-6 and HHV-7 are ubiquitous viruses with a global seroprevalence of around 90%, but their pathogenic significance remains unclear.
{"title":"Clinical Significance of Human Herpesvirus 6 and 7 Infection in a Tertiary Hospital: a Case-Control Study","authors":"Pablo Borque, Juan Carlos Galán, Beatriz Romero, Francesca Gioia, Rosa Escudero, Pilar Martín-Dávila Santiago Moreno, Jesús Fortún","doi":"10.26502/fjppr.080","DOIUrl":"https://doi.org/10.26502/fjppr.080","url":null,"abstract":"Background: Human herpesviruses (HHV)-6 and HHV-7 are ubiquitous viruses with a global seroprevalence of around 90%, but their pathogenic significance remains unclear.","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"155 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135843647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanyuan Chen, Philip Hei Li, Cheng Zhang, Ning Wang, Yibin Feng, Che-Shing Lau
{"title":"A Framework on Developing an Integrative Medicine Clinical Practice Guideline (CPG) for Systemic Lupus erythematosus (SLE) with Comorbidities Management in Hong Kong","authors":"Yuanyuan Chen, Philip Hei Li, Cheng Zhang, Ning Wang, Yibin Feng, Che-Shing Lau","doi":"10.26502/fjppr.085","DOIUrl":"https://doi.org/10.26502/fjppr.085","url":null,"abstract":"","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134883193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}