Pub Date : 2024-11-21DOI: 10.62958/j.cjap.2024.034
Ruchi Tiwari
There are several biological, genetic, and environmental variables that contribute to lung cancer, which is one of the main causes of cancer-related death globally. In addition to exposure to radon gas, air pollution, and occupational dangers like asbestos, smoking is a major risk factor because it releases carcinogens like nitrosamines and polycyclic aromatic hydrocarbons (PAHs) into the lungs. The risk of developing lung cancer is also influenced by genetic predispositions, such as variations in genes like EGFR, KRAS, and TP53. Additionally, new research emphasises how epigenetic changes, such as DNA methylation and histone acetylation, affect the expression of genes connected to the development of cancer. In determining risk and spotting early indicators of lung cancer, biomarkers have become important instruments. Cell-free DNA (cfDNA), circulating tumour cells (CTCs), and certain microRNAs (miRNAs) in blood are non-invasive biomarkers that indicate tumour heterogeneity and load. Molecular indicators include anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, and programmed death-ligand 1 (PD-L1) expression have proved very important in tailoring the therapy of lung cancer. Inflammatory indicators such as interleukins and C-reactive protein (CRP) are also linked to the prognosis of lung cancer. Finding and confirming these biomarkers is essential for improving early detection, tracking the course of the disease, and directing focused treatments. As research progresses, combining molecular, genetic, and environmental insights might improve lung cancer care, prevention, and early diagnosis, thereby lowering the disease's worldwide burden.
肺癌是全球癌症相关死亡的主要原因之一,有多种生物、遗传和环境变量可导致肺癌。除了暴露于氡气、空气污染和石棉等职业危险之外,吸烟也是一个主要的风险因素,因为吸烟会向肺部释放亚硝胺和多环芳烃等致癌物质。罹患肺癌的风险还受到遗传倾向的影响,如表皮生长因子受体、KRAS 和 TP53 等基因的变异。此外,新的研究还强调了表观遗传变化(如 DNA 甲基化和组蛋白乙酰化)如何影响与癌症发展相关的基因表达。在确定肺癌风险和发现肺癌早期指标方面,生物标志物已成为重要工具。血液中的无细胞DNA(cfDNA)、循环肿瘤细胞(CTCs)和某些微RNAs(miRNAs)是非侵入性生物标志物,可显示肿瘤的异质性和负荷。分子指标包括无性淋巴瘤激酶(ALK)重排、表皮生长因子受体(EGFR)突变和程序性死亡配体 1(PD-L1)表达,这些指标已被证明对肺癌的定制治疗非常重要。白细胞介素和C反应蛋白(CRP)等炎症指标也与肺癌的预后有关。找到并确认这些生物标志物对于改善早期检测、跟踪病程和指导有针对性的治疗至关重要。随着研究的不断深入,将分子、遗传和环境方面的知识结合起来,可能会改善肺癌的护理、预防和早期诊断,从而降低该疾病给全世界带来的负担。
{"title":"Breakthrough Biomarkers in Lung Cancer: Pioneering Early Detection and Precision Treatment Strategies.","authors":"Ruchi Tiwari","doi":"10.62958/j.cjap.2024.034","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.034","url":null,"abstract":"<p><p>There are several biological, genetic, and environmental variables that contribute to lung cancer, which is one of the main causes of cancer-related death globally. In addition to exposure to radon gas, air pollution, and occupational dangers like asbestos, smoking is a major risk factor because it releases carcinogens like nitrosamines and polycyclic aromatic hydrocarbons (PAHs) into the lungs. The risk of developing lung cancer is also influenced by genetic predispositions, such as variations in genes like EGFR, KRAS, and TP53. Additionally, new research emphasises how epigenetic changes, such as DNA methylation and histone acetylation, affect the expression of genes connected to the development of cancer. In determining risk and spotting early indicators of lung cancer, biomarkers have become important instruments. Cell-free DNA (cfDNA), circulating tumour cells (CTCs), and certain microRNAs (miRNAs) in blood are non-invasive biomarkers that indicate tumour heterogeneity and load. Molecular indicators include anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, and programmed death-ligand 1 (PD-L1) expression have proved very important in tailoring the therapy of lung cancer. Inflammatory indicators such as interleukins and C-reactive protein (CRP) are also linked to the prognosis of lung cancer. Finding and confirming these biomarkers is essential for improving early detection, tracking the course of the disease, and directing focused treatments. As research progresses, combining molecular, genetic, and environmental insights might improve lung cancer care, prevention, and early diagnosis, thereby lowering the disease's worldwide burden.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240034"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682259","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}
Pub Date : 2024-11-04DOI: 10.62958/j.cjap.2024.033
D Benito Johnson, Gurinderdeep Singh, Deeksha Sharma, Venkatesan Natarajan, Knv Chenchu Lakshmi, Ram C Dhakar, Sadhana R Shahi, Suresh Velayutham, Ruchi Tiwari
The physicochemical properties of the physiological makeup and the chemical componentof the system make this challenging throughout strenuous procedure. The current review concentrated on in silico modelling of drug disposition, involving absorption process, distribution process, and excretion process and includes thorough knowledge of various database expeditions, the development of a pharmacophore model, molecular docking studies, homology modelling supported sequence similarity and quantitative structure-activity relationships (QSAR)/ quantitative structure-property relationships (QSPR) evaluation along with all information about drug movement and related computational tools for understanding potential chemical and pathophysiological changes. The primary development in ADMET modeling in current times has been the clarification of the function and effective modeling of various transporters. In ADMET modelling, there is still work to be done on including the impact of these transporters into existing models. The present state of modelling different elements of drug disposal at the systemic level will then be discussed, along with recent developments in modelling a wide range of active transporters and their effects on drug pharmacokinetic profiles. A more thorough knowledge of the underlying processes governing different aspects of drug disposition should also lead to an increase in mechanism-based modelling methods that are simple to grasp and put into practice. These developments will hasten the transition of model construction from computational to experimental scientists.
{"title":"Exploring Computational Advancements in ADME: Essential Insights for Drug Disposition.","authors":"D Benito Johnson, Gurinderdeep Singh, Deeksha Sharma, Venkatesan Natarajan, Knv Chenchu Lakshmi, Ram C Dhakar, Sadhana R Shahi, Suresh Velayutham, Ruchi Tiwari","doi":"10.62958/j.cjap.2024.033","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.033","url":null,"abstract":"<p><p>The physicochemical properties of the physiological makeup and the chemical componentof the system make this challenging throughout strenuous procedure. The current review concentrated on in silico modelling of drug disposition, involving absorption process, distribution process, and excretion process and includes thorough knowledge of various database expeditions, the development of a pharmacophore model, molecular docking studies, homology modelling supported sequence similarity and quantitative structure-activity relationships (QSAR)/ quantitative structure-property relationships (QSPR) evaluation along with all information about drug movement and related computational tools for understanding potential chemical and pathophysiological changes. The primary development in ADMET modeling in current times has been the clarification of the function and effective modeling of various transporters. In ADMET modelling, there is still work to be done on including the impact of these transporters into existing models. The present state of modelling different elements of drug disposal at the systemic level will then be discussed, along with recent developments in modelling a wide range of active transporters and their effects on drug pharmacokinetic profiles. A more thorough knowledge of the underlying processes governing different aspects of drug disposition should also lead to an increase in mechanism-based modelling methods that are simple to grasp and put into practice. These developments will hasten the transition of model construction from computational to experimental scientists.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240033"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576986","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}
Pub Date : 2024-10-29DOI: 10.62958/j.cjap.2024.032
Stuti Dwivedi, Praveencumar R, T Sivakumar, Mahesh Kumar Posa, Ram C Dhakar, Ruchi Tiwari
In this review article we will highlight the evidences that how oncogenes are formed due to the physical genetic variations in proto-oncogenes and tumor suppressor genes and various planned immunotherapies which will include- The immune checkpoint inhibitor-opposing antibodies, adoptive cell treatments, and biologic modifiers (cytokines and vaccines). We will make an effort to provide guidance and potential fixes for these issues, along with pertinent sources for foundational research. For suitable studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. One type of gene known as an oncogene-a cellular gene that becomes dysfunctional owing to mutation and overexpression-is the cause of cancer. Certain oncogenes seem to inhibit the homeostatic mechanism by limiting the single cell lineage of leukemia stem cells. According to the clonal theory of oncogenes, tumors are thought to begin in a single cell, Moreover, the growth of tumors is closely linked to the prevention of apoptosis, or programmed cell death. These activities of oncogene can be minimized by some immunological therapies.
在这篇综述文章中,我们将重点介绍原癌基因和抑癌基因的物理遗传变异如何形成癌基因的证据,以及各种计划中的免疫疗法,其中包括:免疫检查点抑制剂对抗抗体、收养细胞疗法和生物调节剂(细胞因子和疫苗)。我们将努力为这些问题提供指导和潜在的解决方案,并提供基础研究的相关资料来源。对于合适的研究,我们从 PubMed、EMBASE 和 Google Scholar 等各种数据库来源进行了文献检索。有一种基因被称为癌基因--由于突变和过度表达而功能失调的细胞基因--是导致癌症的原因。某些癌基因似乎通过限制白血病干细胞的单细胞系来抑制平衡机制。此外,肿瘤的生长与细胞凋亡或程序性细胞死亡的阻止密切相关。一些免疫疗法可以最大限度地减少癌基因的这些活动。
{"title":"Oncogenetics: Unraveling the Genetic Underpinnings of Cancer for Improved Immunotherapeutic Outcomes.","authors":"Stuti Dwivedi, Praveencumar R, T Sivakumar, Mahesh Kumar Posa, Ram C Dhakar, Ruchi Tiwari","doi":"10.62958/j.cjap.2024.032","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.032","url":null,"abstract":"<p><p>In this review article we will highlight the evidences that how oncogenes are formed due to the physical genetic variations in proto-oncogenes and tumor suppressor genes and various planned immunotherapies which will include- The immune checkpoint inhibitor-opposing antibodies, adoptive cell treatments, and biologic modifiers (cytokines and vaccines). We will make an effort to provide guidance and potential fixes for these issues, along with pertinent sources for foundational research. For suitable studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. One type of gene known as an oncogene-a cellular gene that becomes dysfunctional owing to mutation and overexpression-is the cause of cancer. Certain oncogenes seem to inhibit the homeostatic mechanism by limiting the single cell lineage of leukemia stem cells. According to the clonal theory of oncogenes, tumors are thought to begin in a single cell, Moreover, the growth of tumors is closely linked to the prevention of apoptosis, or programmed cell death. These activities of oncogene can be minimized by some immunological therapies.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240032"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523156","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}
There have been several non-invasive administrations that have emerged recently to replace conventional needle injections. With its minimal rejection rate, remarkable ease of administration, and remarkable patient comfort and perseverance, the transdermal drug delivery system (TDDS) is the most attractive of them all. The skincare industry, which includes cosmetics, may also find use for TDDS in addition to the pharmaceutical industry. As this strategy mainly entails local drug administration, it can prevent untargeted drug delivery to tissues not intended for the treatment and buildup of localized drug concentrations. Transdermal delivery is hampered by a number of physicochemical characteristics of the skin, which have led to a great deal of research into ways to get over these barriers. The majority of transdermal medicines that have proved effective do so by using smaller lipophilic compounds, which have a molecular weight of a few 100 Daltons. Transferosomes have proven to be an effective method for transdermal distribution of a range of therapies, including hydrophilic actives, bigger molecules, peptides, proteins, and nucleic acids, in order to get around the medications' size and lipophilicity limits. Because of their flexible form and increased surface hydrophilicity, transferosomes are essential for the delivery of medicines and other solutes through and into the skin by exploiting hydration gradients a source of energy. As a result, the medication is released into the skin layers under regulated conditions and has improved overall penetration. In this section we outline the development of transferosomes from liposomes and solid lipid nanoparticles, as well as their subsequent advancements as commercially available dosage forms, physical-chemical characteristics, and cutaneous kinetics.
{"title":"Recent Innovations and Future Perspectives in Transferosomes for Transdermal Drug Delivery in Therapeutic and Pharmacological Applications.","authors":"SanjayKumar Patel, Ismail Y, Satendra Singh, Sanjesh Rathi, Shreya Shakya, Sachin S Patil, Shrinivas Bumrela, Priya Chhotulal Jain, Priyanka Goswami, Shubham Singh","doi":"10.62958/j.cjap.2024.031","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.031","url":null,"abstract":"<p><p>There have been several non-invasive administrations that have emerged recently to replace conventional needle injections. With its minimal rejection rate, remarkable ease of administration, and remarkable patient comfort and perseverance, the transdermal drug delivery system (TDDS) is the most attractive of them all. The skincare industry, which includes cosmetics, may also find use for TDDS in addition to the pharmaceutical industry. As this strategy mainly entails local drug administration, it can prevent untargeted drug delivery to tissues not intended for the treatment and buildup of localized drug concentrations. Transdermal delivery is hampered by a number of physicochemical characteristics of the skin, which have led to a great deal of research into ways to get over these barriers. The majority of transdermal medicines that have proved effective do so by using smaller lipophilic compounds, which have a molecular weight of a few 100 Daltons. Transferosomes have proven to be an effective method for transdermal distribution of a range of therapies, including hydrophilic actives, bigger molecules, peptides, proteins, and nucleic acids, in order to get around the medications' size and lipophilicity limits. Because of their flexible form and increased surface hydrophilicity, transferosomes are essential for the delivery of medicines and other solutes through and into the skin by exploiting hydration gradients a source of energy. As a result, the medication is released into the skin layers under regulated conditions and has improved overall penetration. In this section we outline the development of transferosomes from liposomes and solid lipid nanoparticles, as well as their subsequent advancements as commercially available dosage forms, physical-chemical characteristics, and cutaneous kinetics.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240031"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509341","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}
The current study examined the antipsychotic properties of ethanolic extracts of Crinum asiaticum (EECA) and Crinum defixum (EECD). The effects of the extracts on rodents' ketamine-induced hyperactivity, amphetamine-induced stereotypy, forced swim test, conditioned avoidance response, and catalepsy were assessed. According to the findings, EECA and EECD both significantly outperformed typical antipsychotic medications in antipsychotic-like behaviours across a variety of behavioural paradigms. The extracts exhibited a 50-75% reduction in ketamine-induced hyperactivity, indicating a possible impact on glutamatergic signalling. Additionally, they greatly reduced amphetamine-induced stereotypy, suggesting a potential antagonistic interaction with the dopamine D2 receptor. Similar to haloperidol, EECD at 400 mg/kg dramatically decreased avoidance behaviour in the conditioned avoidance response test. Though less so than with haloperidol, both extracts caused catalepsy in rodents. The reversal of ketamine's effect in the forced swim test suggests that it may be effective in preventing psychosis's negative symptoms. Given that oxidative stress is a contributing factor to psychotic disorders, the antipsychotic effect of these extracts may be associated with their anti-inflammatory and antioxidant characteristics. These results bolster the long-standing usage of Crinum species in the treatment of mental illnesses and imply that they could be rich sources of new antipsychotic chemicals. To determine the active ingredients, clarify the mechanisms of action, and assess the safety and effectiveness of clinical trials, more study is necessary.
{"title":"Antipsychotic Activity of Ethanolic Extracts of Crinum asiaticum and Crinum defixum in Animal Models.","authors":"Parthasarathi Mishra, Aswini Kumar Senapati, Sudhansu Ranjan Swain, Sujit Dash, Suchismita Kar","doi":"10.62958/j.cjap.2024.030","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.030","url":null,"abstract":"<p><p>The current study examined the antipsychotic properties of ethanolic extracts of Crinum asiaticum (EECA) and Crinum defixum (EECD). The effects of the extracts on rodents' ketamine-induced hyperactivity, amphetamine-induced stereotypy, forced swim test, conditioned avoidance response, and catalepsy were assessed. According to the findings, EECA and EECD both significantly outperformed typical antipsychotic medications in antipsychotic-like behaviours across a variety of behavioural paradigms. The extracts exhibited a 50-75% reduction in ketamine-induced hyperactivity, indicating a possible impact on glutamatergic signalling. Additionally, they greatly reduced amphetamine-induced stereotypy, suggesting a potential antagonistic interaction with the dopamine D2 receptor. Similar to haloperidol, EECD at 400 mg/kg dramatically decreased avoidance behaviour in the conditioned avoidance response test. Though less so than with haloperidol, both extracts caused catalepsy in rodents. The reversal of ketamine's effect in the forced swim test suggests that it may be effective in preventing psychosis's negative symptoms. Given that oxidative stress is a contributing factor to psychotic disorders, the antipsychotic effect of these extracts may be associated with their anti-inflammatory and antioxidant characteristics. These results bolster the long-standing usage of Crinum species in the treatment of mental illnesses and imply that they could be rich sources of new antipsychotic chemicals. To determine the active ingredients, clarify the mechanisms of action, and assess the safety and effectiveness of clinical trials, more study is necessary.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240030"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476256","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}
Pub Date : 2024-10-10DOI: 10.62958/j.cjap.2024.029
Bhoomi D Patel, Shailesh P Suthar, Arman M Mansuri, Vishvash D Joshi
The Abbreviated New Drug Application (ANDA) is used for the regulatory submission of generic drugs, which are pharmaceutical equivalents to brand-name drugs and distributed without patent protection. Different countries have their own regulatory requirements for the approval of generic drugs, enforced by authorities such as the CDSCO in India, EDQM in Europe, and USFDA in the United States. This review aims to compare the regulatory processes and requirements for generic drug approval in India, Europe, and the US, highlighting key differences and challenges. The involvement of regulatory authorities in the drug development process is crucial for expediting approval and addressing queries, helping to minimize delays. The Common Technical Document (CTD) format is employed across regions to harmonize submission requirements. This study underscores the differences in dossier submission for generics across the three regions, illustrating India's position in the global generic drug approval landscape. By comparing approval requirements, this work provides insight into the hurdles India must overcome to streamline its approval process. The ANDA allows generic manufacturers to submit bioequivalence studies, using the original innovator's safety and efficacy data. However, obtaining approval simultaneously from multiple regulatory authorities remains a challenging task. Careful review of regulatory documents by skilled personnel can reduce regulatory queries, ultimately accelerating the market launch of generic drugs. This review provides a comprehensive overview of the generic drug approval process, emphasizing the need for harmonization and improved efficiency in India's regulatory framework.
{"title":"A Comparative Analysis of Generic Drug Assessment and Regulatory Approval in the USA, Europe and India.","authors":"Bhoomi D Patel, Shailesh P Suthar, Arman M Mansuri, Vishvash D Joshi","doi":"10.62958/j.cjap.2024.029","DOIUrl":"10.62958/j.cjap.2024.029","url":null,"abstract":"<p><p>The Abbreviated New Drug Application (ANDA) is used for the regulatory submission of generic drugs, which are pharmaceutical equivalents to brand-name drugs and distributed without patent protection. Different countries have their own regulatory requirements for the approval of generic drugs, enforced by authorities such as the CDSCO in India, EDQM in Europe, and USFDA in the United States. This review aims to compare the regulatory processes and requirements for generic drug approval in India, Europe, and the US, highlighting key differences and challenges. The involvement of regulatory authorities in the drug development process is crucial for expediting approval and addressing queries, helping to minimize delays. The Common Technical Document (CTD) format is employed across regions to harmonize submission requirements. This study underscores the differences in dossier submission for generics across the three regions, illustrating India's position in the global generic drug approval landscape. By comparing approval requirements, this work provides insight into the hurdles India must overcome to streamline its approval process. The ANDA allows generic manufacturers to submit bioequivalence studies, using the original innovator's safety and efficacy data. However, obtaining approval simultaneously from multiple regulatory authorities remains a challenging task. Careful review of regulatory documents by skilled personnel can reduce regulatory queries, ultimately accelerating the market launch of generic drugs. This review provides a comprehensive overview of the generic drug approval process, emphasizing the need for harmonization and improved efficiency in India's regulatory framework.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240029"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393780","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}
Pub Date : 2024-10-09DOI: 10.62958/j.cjap.2024.028
Pranshul Sethi, Ronald Darwin C, Ramakrishna Borra, Shahin Vahora, Ankur Vashi, Rajesh Kumar Mukherjee, Belide Pavani, Gaurav Tiwari
Abnormal hyperphosphorylation and microtubule-associated protein tau aggregation development in the brain are characteristics of neurodegenerative diseases referred to as tauopathies, which include Alzheimer's disease (AD). The current review summarizes the complex relationships that exist between oxidative stress and tau illness, with particular attention to the roles played by the tau protein, reactive oxygen species and their consequences, and tau phosphorylation and oxidative stress. Two key elements of detrimental cycle that are critical in neurodegenerative tauopathies are tau hyperphosphorylation and oxidative stress. When tau and microtubules are not connected properly, microtubule instability, issues with microtubule transport, and ultimately neuronal death result. While the causes of the more prevalent sporadic late-onset variants and the connections between tau hyperphosphorylation and neurodegeneration remain largely unknown, mutations in the microtubule-associated protein tau (MAPT) gene have been identified in familial cases of early-onset tauopathies. Another detrimental feature of tauopathies is oxidative stress, but the exact role it plays in the development of the disease is unclear. The source of reactive oxygen species (ROS), which lead to oxidative stress within neural tissue, remains an unresolved topic. Although mitochondria have historically been thought to be a primary source of oxidative stress, microglial cells have recently been discovered to create reactive oxygen species in tauopathies. In conclusion, enhancing our comprehension of the impact of oxidative stress on various diseases could facilitate the identification of new disease markers and lead to the formulation of treatment strategies aimed at halting, reversing, or mitigating disease progression.
大脑中异常的高磷酸化和微管相关蛋白tau聚集是神经退行性疾病的特征,这些疾病被称为tau病,其中包括阿尔茨海默病(AD)。本综述总结了氧化应激与 tau 病之间存在的复杂关系,尤其关注 tau 蛋白、活性氧及其后果以及 tau 磷酸化和氧化应激所发挥的作用。在神经退行性 tau 病中,tau 过度磷酸化和氧化应激是有害循环的两个关键因素。当 tau 和微管不能正常连接时,就会导致微管不稳定、微管运输问题,最终导致神经元死亡。虽然更常见的散发性晚发型变异病的病因以及 tau 过度磷酸化与神经退行性变之间的联系在很大程度上仍然未知,但在家族性早发型 tau 病例中发现了微管相关蛋白 tau(MAPT)基因的突变。氧化应激是陶陶病的另一个有害特征,但氧化应激在疾病发展中的确切作用尚不清楚。导致神经组织内氧化应激的活性氧(ROS)的来源仍是一个悬而未决的课题。虽然线粒体历来被认为是氧化应激的主要来源,但最近发现小胶质细胞也会在陶陶病中产生活性氧。总之,提高我们对氧化应激对各种疾病的影响的认识有助于确定新的疾病标志物,并制定旨在阻止、逆转或减轻疾病进展的治疗策略。
{"title":"Mechanistic Insights into Tau Protein-Mediated Regulation of Oxidative Stress.","authors":"Pranshul Sethi, Ronald Darwin C, Ramakrishna Borra, Shahin Vahora, Ankur Vashi, Rajesh Kumar Mukherjee, Belide Pavani, Gaurav Tiwari","doi":"10.62958/j.cjap.2024.028","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.028","url":null,"abstract":"<p><p>Abnormal hyperphosphorylation and microtubule-associated protein tau aggregation development in the brain are characteristics of neurodegenerative diseases referred to as tauopathies, which include Alzheimer's disease (AD). The current review summarizes the complex relationships that exist between oxidative stress and tau illness, with particular attention to the roles played by the tau protein, reactive oxygen species and their consequences, and tau phosphorylation and oxidative stress. Two key elements of detrimental cycle that are critical in neurodegenerative tauopathies are tau hyperphosphorylation and oxidative stress. When tau and microtubules are not connected properly, microtubule instability, issues with microtubule transport, and ultimately neuronal death result. While the causes of the more prevalent sporadic late-onset variants and the connections between tau hyperphosphorylation and neurodegeneration remain largely unknown, mutations in the microtubule-associated protein tau (MAPT) gene have been identified in familial cases of early-onset tauopathies. Another detrimental feature of tauopathies is oxidative stress, but the exact role it plays in the development of the disease is unclear. The source of reactive oxygen species (ROS), which lead to oxidative stress within neural tissue, remains an unresolved topic. Although mitochondria have historically been thought to be a primary source of oxidative stress, microglial cells have recently been discovered to create reactive oxygen species in tauopathies. In conclusion, enhancing our comprehension of the impact of oxidative stress on various diseases could facilitate the identification of new disease markers and lead to the formulation of treatment strategies aimed at halting, reversing, or mitigating disease progression.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240028"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393781","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}
Pub Date : 2024-09-29DOI: 10.62958/j.cjap.2024.027
Baddela Nagaiah, S Nirmala
Objective: Bosutinib (BST) is a Biopharmaceutics Classification System Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST lead to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggest that the absolute bioavailability of BST is about 14-34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid-based drug delivery systems such as solid lipid nanoparticles (SLNs) can be used.
Methods: SLNs are submicron colloidal carriers having a size range of 50-1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. BST can be conveniently loaded into SLNs to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of BST suspension (SUS).
Results: An in vitro cytotoxicity study was done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method through ATCC cell lines; the percent inhibition was more in SLN when compared with SUS. The pharmacokinetics of BST-SLNs after oral administration in male Wistar rats was studied. The bioavailability of BST was increased by 2.28 fold when compared with that of a BST SUS.
Conclusion: The results are indicative of SLNs as suitable lipid-based carrier system for improving the oral bioavailability of BST.
{"title":"In Vitro Cytotoxicity and Pharmacokinetic Study for Bosutinib Solid Lipid Nanoparticles.","authors":"Baddela Nagaiah, S Nirmala","doi":"10.62958/j.cjap.2024.027","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.027","url":null,"abstract":"<p><strong>Objective: </strong>Bosutinib (BST) is a Biopharmaceutics Classification System Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST lead to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggest that the absolute bioavailability of BST is about 14-34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid-based drug delivery systems such as solid lipid nanoparticles (SLNs) can be used.</p><p><strong>Methods: </strong>SLNs are submicron colloidal carriers having a size range of 50-1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. BST can be conveniently loaded into SLNs to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of BST suspension (SUS).</p><p><strong>Results: </strong>An in vitro cytotoxicity study was done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method through ATCC cell lines; the percent inhibition was more in SLN when compared with SUS. The pharmacokinetics of BST-SLNs after oral administration in male Wistar rats was studied. The bioavailability of BST was increased by 2.28 fold when compared with that of a BST SUS.</p><p><strong>Conclusion: </strong>The results are indicative of SLNs as suitable lipid-based carrier system for improving the oral bioavailability of BST.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240027"},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355435","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}
Introduction: Incorporating rare and threatened healing plants from Traditional Chinese Medicine (TCM) into modern medicine is a hopeful way to expand treatment choices and encourage the long-term use of plant resources. These plants have been used in Traditional Chinese Medicine for a long time. They have powerful healing properties, including the ability to reduce inflammation and fight cancer. They also protect nerves and the heart.
Method: A thorough study of all the scientific studies, clinical trials, ethnobotanical surveys, and conservation reports that were found were all looked at in relation to rare and threatened medical plants used in TCM. We looked through databases like PubMed, Scopus, and Web of Science for relevant pieces. Studies published in peer-reviewed journals, reports from reputable conservation organisations, and written down traditional knowledge were all considered to be relevant.
Results: Key results show that plants like Dendrobium, Panax notoginseng, Taxus chinensis, and Cistanche deserticola can be used as medicines and that there are good ways to protect them. Some of the conservation methods that have been named are agroforestry, community-based management, current breeding techniques, and sustainable gathering. Collaboration in research, clinical trials, personalised medicine, regulatory harmonisation, and public education programs are all part of the integration with modern medicine. These programs try to solve problems like scientific proof, protection, and cultural integration.
Conclusion: When rare and threatened medical plants from Traditional Chinese Medicine (TCM) are used in modern medicine, it can improve health and help protect wildlife. Using both old information and new science discoveries together can lead to new treatments and long-term uses for these plant materials. Large-scale clinical studies, new ways of growing plants, and looking into how TCM herbs and regular drugs can work together should be the main topics of future study. For global healthcare to improve and for these important plant resources to be used in the long term, academics, healthcare workers, lawmakers, and local communities must work together.
导言:将传统中医学中稀有和濒危的治疗植物融入现代医学,是扩大治疗选择和鼓励长期使用植物资源的一种充满希望的方式。这些植物在传统中医中的应用由来已久。它们具有强大的治疗功效,包括消炎和抗癌。它们还能保护神经和心脏:我们对所有科学研究、临床试验、民族植物学调查和保护报告进行了全面研究,这些研究都与中医药中使用的珍稀濒危药用植物有关。我们通过 PubMed、Scopus 和 Web of Science 等数据库查找相关资料。在同行评议期刊上发表的研究报告、知名保护组织的报告以及写下来的传统知识都被认为是相关的:主要结果表明,铁皮石斛、三七、紫杉和肉苁蓉等植物可作为药物使用,而且有保护它们的好方法。其中一些保护方法包括农林业、社区管理、当前的育种技术和可持续采集。研究合作、临床试验、个性化医疗、监管协调和公众教育计划都是与现代医学结合的一部分。这些计划试图解决科学论证、保护和文化融合等问题:当传统中医药中的珍稀和濒危药用植物被用于现代医学时,可以改善健康状况,并有助于保护野生动物。同时利用旧信息和新科学发现,可以为这些植物材料带来新的治疗方法和长期用途。大规模临床研究、种植植物的新方法,以及研究中草药和常规药物如何共同发挥作用,应该是未来研究的主要课题。要想改善全球医疗保健状况,使这些重要的植物资源得到长期利用,学术界、医疗工作者、立法者和当地社区必须共同努力。
{"title":"Unveiling the Therapeutic Potential and Conservation Strategies for Rare and Endangered Medicinal Plants in Traditional Chinese Medicine: A Comprehensive Review.","authors":"Sonali Rastogi, Ritu Verma, Rajapandi Raju, Venkateshan Narayanan, Pooja Anand Mundada, Rakhee Maheshwari, Yuvraj Pandhare, Ruchi Tiwari","doi":"10.62958/j.cjap.2024.024","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.024","url":null,"abstract":"<p><strong>Introduction: </strong>Incorporating rare and threatened healing plants from Traditional Chinese Medicine (TCM) into modern medicine is a hopeful way to expand treatment choices and encourage the long-term use of plant resources. These plants have been used in Traditional Chinese Medicine for a long time. They have powerful healing properties, including the ability to reduce inflammation and fight cancer. They also protect nerves and the heart.</p><p><strong>Method: </strong>A thorough study of all the scientific studies, clinical trials, ethnobotanical surveys, and conservation reports that were found were all looked at in relation to rare and threatened medical plants used in TCM. We looked through databases like PubMed, Scopus, and Web of Science for relevant pieces. Studies published in peer-reviewed journals, reports from reputable conservation organisations, and written down traditional knowledge were all considered to be relevant.</p><p><strong>Results: </strong>Key results show that plants like Dendrobium, Panax notoginseng, Taxus chinensis, and Cistanche deserticola can be used as medicines and that there are good ways to protect them. Some of the conservation methods that have been named are agroforestry, community-based management, current breeding techniques, and sustainable gathering. Collaboration in research, clinical trials, personalised medicine, regulatory harmonisation, and public education programs are all part of the integration with modern medicine. These programs try to solve problems like scientific proof, protection, and cultural integration.</p><p><strong>Conclusion: </strong>When rare and threatened medical plants from Traditional Chinese Medicine (TCM) are used in modern medicine, it can improve health and help protect wildlife. Using both old information and new science discoveries together can lead to new treatments and long-term uses for these plant materials. Large-scale clinical studies, new ways of growing plants, and looking into how TCM herbs and regular drugs can work together should be the main topics of future study. For global healthcare to improve and for these important plant resources to be used in the long term, academics, healthcare workers, lawmakers, and local communities must work together.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240024"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156155","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}
Pub Date : 2024-08-30DOI: 10.62958/j.cjap.2024.025
Nandhini J, B Anandhi, Soumya Stuti Patnaik, Rahul Lotan Shirole, Navinraj Dudhnath Mourya, Nahida Siddiqui, Jithin Mathew, V R Ravikkumar, E Karthikeyan
The main issue with Hypertension therapy is quick commencement of effect. The creation of suitable dose forms may help address the issue of medications having a delayed beginning of effect. Oral Antihypertensive medication treatment is best suited for and has seen a rise in popularity with fast-disintegrating tablets. In terms of patient compliance, quick start of action, precise dosage, strong chemical stability, ease of self-administration, and compactness, they are superior to other traditional methods. As a popular hypertension medication, Propranolol HCl is a strong candidate for development into Fast Dissolving Tablets (FDTs). Because to first pass metabolism, it has a limited bioavailability. Therefore, the primary goal of the research was to create Propranolol HCl fast-dissolving tablets in order to increase the drug's bioavailability and dissolution rate. Microcrystalline cellulose used to make fast-dissolving Propranolol HCl tablets, together with varying concentrations of super disintegrates such as Chia Seed mucilage and sodium starch glycolate. Each batch was made by compressing it directly. Three formulation variables were combined, and the combined impact was examined using a 23 Full Factorial design. Here, the disintegration time is examined as a dependent parameter and the concentrations of chia seed mucilage, Sodium Starch Glycolate, and Microcrystalline Cellulose were considered as independent variables, X1, X2, and X3, respectively. The program Design Expert is used to depict the data.
{"title":"Design and Development of Propranolol HCl Fast Dissolving Tablets by Using Isolated Mucilage of Salvia Hispanica for the Treatment of Hypertension by Using DoE tools.","authors":"Nandhini J, B Anandhi, Soumya Stuti Patnaik, Rahul Lotan Shirole, Navinraj Dudhnath Mourya, Nahida Siddiqui, Jithin Mathew, V R Ravikkumar, E Karthikeyan","doi":"10.62958/j.cjap.2024.025","DOIUrl":"https://doi.org/10.62958/j.cjap.2024.025","url":null,"abstract":"<p><p>The main issue with Hypertension therapy is quick commencement of effect. The creation of suitable dose forms may help address the issue of medications having a delayed beginning of effect. Oral Antihypertensive medication treatment is best suited for and has seen a rise in popularity with fast-disintegrating tablets. In terms of patient compliance, quick start of action, precise dosage, strong chemical stability, ease of self-administration, and compactness, they are superior to other traditional methods. As a popular hypertension medication, Propranolol HCl is a strong candidate for development into Fast Dissolving Tablets (FDTs). Because to first pass metabolism, it has a limited bioavailability. Therefore, the primary goal of the research was to create Propranolol HCl fast-dissolving tablets in order to increase the drug's bioavailability and dissolution rate. Microcrystalline cellulose used to make fast-dissolving Propranolol HCl tablets, together with varying concentrations of super disintegrates such as Chia Seed mucilage and sodium starch glycolate. Each batch was made by compressing it directly. Three formulation variables were combined, and the combined impact was examined using a 23 Full Factorial design. Here, the disintegration time is examined as a dependent parameter and the concentrations of chia seed mucilage, Sodium Starch Glycolate, and Microcrystalline Cellulose were considered as independent variables, X1, X2, and X3, respectively. The program Design Expert is used to depict the data.</p>","PeriodicalId":23985,"journal":{"name":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","volume":"40 ","pages":"e20240025"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112757","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}