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Targeting BCL-2 family proteins using BH3 mimetic drugs for cancer therapy: A systematic review of randomized clinical trials 使用 BH3 拟态药物靶向 BCL-2 家族蛋白治疗癌症:随机临床试验系统回顾
Medicine in Drug Discovery Pub Date : 2024-12-01 Epub Date: 2024-09-29 DOI: 10.1016/j.medidd.2024.100199
Fatimah Alharbi, Eyad Almanifi, Md. Ashrafuzzaman
{"title":"Targeting BCL-2 family proteins using BH3 mimetic drugs for cancer therapy: A systematic review of randomized clinical trials","authors":"Fatimah Alharbi,&nbsp;Eyad Almanifi,&nbsp;Md. Ashrafuzzaman","doi":"10.1016/j.medidd.2024.100199","DOIUrl":"10.1016/j.medidd.2024.100199","url":null,"abstract":"<div><div>Apoptosis plays a significant role in both carcinogenesis and cancer treatment. Apoptotic dysfunction may allow cancer cells to survive. Overexpression of anti-apoptotic B cell lymphoma-2 (BCL-2) family protein members is predicted to majorly contribute to apoptotic dysfunction. Therefore, targeting proteins in cancer has been of interest to scientists and drug developers. The most successful method to regulate apoptosis in cancer cells so far has been found in the development of BH3-mimetic drugs that may work towards downregulating anti-apoptotic BCL-2 protein functions. Clinical trials have dealt with a few molecules that mimic the function of BH3-only proteins and therefore inhibit their anti-apoptotic functions. Currently, this approach is one of the most promising and effective strategies for cancer treatment. Since the family has more than fifteen protein members, this review will focus on three members that have garnered interest as therapeutic targets: Bcl-2, Bcl-X<sub>L</sub>, and myeloid cell leukaemia 1 (Mcl-1), all are anti-apoptosis proteins. In addition, it covers the major functions of Bcl-2, Bcl-X<sub>L</sub>, and MCL-1, their implication in malignancy, as well as their pharmacologic inhibitors. The Food and Drug Administration has approved the first BH-3 mimetic, venetoclax, an oral Bcl-2 inhibitor shown to treat chronic lymphocytic leukemia. This systematic review of clinical trials investigates the efficacy and clinical relevance of BCL-2 family protein inhibitors in managing malignancies.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421142","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}
引用次数: 0
Coronavirus spike protein-based vaccines. Vaccine delivery systems 冠状病毒尖峰蛋白疫苗。疫苗输送系统
Medicine in Drug Discovery Pub Date : 2024-12-01 Epub Date: 2024-09-12 DOI: 10.1016/j.medidd.2024.100198
Akmal M. Asrorov , Mirzakamol S. Ayubov , Bin Tu , Mingjie Shi , Huiyuan Wang , Sharafitdin Mirzaakhmedov , Amit Kumar Nayak , Ibrokhim Y. Abdurakhmonov , Yongzhuo Huang
{"title":"Coronavirus spike protein-based vaccines. Vaccine delivery systems","authors":"Akmal M. Asrorov ,&nbsp;Mirzakamol S. Ayubov ,&nbsp;Bin Tu ,&nbsp;Mingjie Shi ,&nbsp;Huiyuan Wang ,&nbsp;Sharafitdin Mirzaakhmedov ,&nbsp;Amit Kumar Nayak ,&nbsp;Ibrokhim Y. Abdurakhmonov ,&nbsp;Yongzhuo Huang","doi":"10.1016/j.medidd.2024.100198","DOIUrl":"10.1016/j.medidd.2024.100198","url":null,"abstract":"<div><p>Spike protein has been established as one of the molecules playing a pivotal role in coronavirus infection. On its bases, several vaccines have been developed, passed preclinical and clinical stages, and reached medical practice at the early stages of the pandemic. It was found efficient enough to induce various types of immunoglobulins. However, the missense mutations made it necessary to develop new sequences with adjuvants to enhance the efficacy against a broad spectrum of SARS-CoV-2 and newly emerging variants. Some attempts were carried out to improve the vaccine efficiency by loading it into a delivery system, which caused a prolongation effect. In this paper, we reviewed data around spike protein-based vaccines in terms of their efficacy, which was analyzed based on enhanced quantities/titers of immunoglobulins/neutralizing antibodies. Our search on the PubMed database using ‘spike protein-based coronavirus vaccines’ keywords showed over 150 publications that were further filtered based on their relevance. Further, we added other relevant papers to support the expressed ideas. We compared the effects of various vaccines of different origins in clinical studies and animal experiments where relevant. The efficacy of adjuvants has been reviewed as a separate section. In several cases, we explained the significance of the spike protein trimeric structure. We also explained the essential role of mutation while developing protein vaccines. The contributions of adjuvants in inducing immune responses have been separated into one section. The outcomes of clinical studies were highlighted to prove their efficacies.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259009862400023X/pdfft?md5=1848354a80eb802b2c91988187479acd&pid=1-s2.0-S259009862400023X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240263","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}
引用次数: 0
Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy 受体酪氨酸激酶抑制剂的最新进展:前景广阔的癌症靶向治疗主力军
Medicine in Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-01 DOI: 10.1016/j.medidd.2024.100195
Rahul Kumar , Harsh Goel , Raghu Solanki , Laxminarayan Rawat , Saba Tabasum , Pranay Tanwar , Soumitro Pal , Akash Sabarwal
{"title":"Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy","authors":"Rahul Kumar ,&nbsp;Harsh Goel ,&nbsp;Raghu Solanki ,&nbsp;Laxminarayan Rawat ,&nbsp;Saba Tabasum ,&nbsp;Pranay Tanwar ,&nbsp;Soumitro Pal ,&nbsp;Akash Sabarwal","doi":"10.1016/j.medidd.2024.100195","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100195","url":null,"abstract":"<div><p>During the past two decades, significant advances have been made in the discovery and development of targeted inhibitors aimed at improving the survival rates of cancer patients. Among the multitude of potential therapeutic targets identified thus far, Receptor Tyrosine Kinases (RTKs) are of particular importance. Dysregulation of RTKs has been implicated in numerous human diseases, particularly cancer, where aberrant signaling pathways contribute to disease progression. RTKs have a profound impact on intra and intercellular communication, and they also facilitate post-translational modifications, notably phosphorylation, which intricately regulates a multitude of cellular processes. Prolonged phosphorylation or the disruption of kinase regulation may lead to significant alterations in cell signaling. The emergence of small molecule kinase inhibitors has revolutionized cancer therapy by offering a targeted and strategic approach that surpasses the efficacy of traditional chemotherapeutic drugs. Over the last two decades, a plethora of targeted inhibitors have been identified or engineered and have undergone clinical evaluation to enhance the survival rates of cancer patients. In this review, we have compared the expression of different RTKs, including Met, KDR/VEGFR2, EGFR, BRAF, BCR, and ALK across different cancer types in TCGA samples. Additionally, we have summarized the recent development of small molecule inhibitors and their potential in treating various malignancies. Lastly, we have discussed the mechanisms of acquired therapeutic resistance with a focus on kinase inhibitors in EGFR mutant and ALK-rearranged non-small cell lung cancer and BCR-ABL positive chronic myeloid leukemia.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000204/pdfft?md5=90e864d311e6f6cbf02a7d7750d65e67&pid=1-s2.0-S2590098624000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141541796","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}
引用次数: 0
Repurposing nitrofurantoin as a stimulant of fibroblast extracellular matrix repair for the treatment of emphysema 将硝基呋喃妥因重新用作治疗肺气肿的成纤维细胞细胞外基质修复刺激剂
Medicine in Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-06-22 DOI: 10.1016/j.medidd.2024.100194
Mathew N. Leslie , Zara Sheikh , Dikaia Xenaki , Brian G. Oliver , Paul M. Young , Daniela Traini , Hui Xin Ong
{"title":"Repurposing nitrofurantoin as a stimulant of fibroblast extracellular matrix repair for the treatment of emphysema","authors":"Mathew N. Leslie ,&nbsp;Zara Sheikh ,&nbsp;Dikaia Xenaki ,&nbsp;Brian G. Oliver ,&nbsp;Paul M. Young ,&nbsp;Daniela Traini ,&nbsp;Hui Xin Ong","doi":"10.1016/j.medidd.2024.100194","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100194","url":null,"abstract":"<div><p>Emphysema is a respiratory disease that causes the progressive loss of lung extracellular matrix (ECM) organisation, subsequently undermining lung integrity and reducing lung function. Fibroblasts must constantly repair damage to the lungs to preserve lung health, however, fibroblast ECM repair is reduced during emphysema, causing ECM damage to outweigh fibroblast ECM maintenance. Current treatments for emphysema fail to address the root causes of emphysematous progression, highlighting the need for novel methods of treating emphysema. Nitrofurantoin is a broad-spectrum antibiotic indicated for the treatment of urinary tract infections that also displays potential as a novel avenue of emphysema treatment. Nitrofurantoin is known to potentially cause fibrotic effects that could be repurposed to increase fibroblast repair and outweigh the progressive ECM damage of the emphysematous lung. Therefore, this study examined the effects of nitrofurantoin treatment on primary human lung fibroblasts derived from emphysema patients to determine if the drug holds potential as a novel treatment for emphysema. Nitrofurantoin was shown to stimulate migration and alter fibroblast morphology by increasing cell area and reducing roundness, suggesting that it could induce an ECM-repair primed phenotype in fibroblasts. Interestingly, nitrofurantoin treatment did not alter collagen-IV, perlecan, periostin or tenascin-C deposition, though fibronectin deposition was significantly upregulated at a higher dosage (20 μg/mL). This study highlighted the nitrofurantoin induced changes to fibroblast motility and morphology that facilitate ECM repair. Thus, nitrofurantoin induced pulmonary fibrosis could be caused by a change in cell phenotype that subsequently upregulates ECM repair, indicating its potential as a treatment for emphysema.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000198/pdfft?md5=e01ff09770a2b573a87f8957214ffc30&pid=1-s2.0-S2590098624000198-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478971","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}
引用次数: 0
The psychological distress associated with type 2 diabetes mellitus represents an unmet need for drug discovery 与 2 型糖尿病相关的心理困扰是药物研发中尚未满足的需求
Medicine in Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-08-07 DOI: 10.1016/j.medidd.2024.100196
S. Akshatha, Uday B. Nayak
{"title":"The psychological distress associated with type 2 diabetes mellitus represents an unmet need for drug discovery","authors":"S. Akshatha,&nbsp;Uday B. Nayak","doi":"10.1016/j.medidd.2024.100196","DOIUrl":"10.1016/j.medidd.2024.100196","url":null,"abstract":"<div><p>Non-adherence to antidiabetic medication remains the major factor contributing to poor clinical outcomes among patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the cross-sectional association between psychological distress and medication adherence in T2DM patients. Participants were 100 adults with T2DM from a teaching hospital in South India. Psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and the 8-item Morisky Medication Adherence Scale (MMAS-8) was used to assess medication adherence. This study demonstrated that a high proportion of patients (70 %) with T2DM experience psychological distress. Higher self-reported distress was the strongest independent predictor of medication non-adherence (β = −0.1145; P=0.0002). The study highlights that psychological distress in T2DM patients meets important drug discovery criteria such as unmet medical need, disease prevalence, and success probability. Understanding the biological mechanisms that underpin psychological distress would aid in the development of mechanism-based therapies. Better integration of medical and psychosocial treatments in general medical practice may be important to improve treatment adherence and reduce disparities in chronic disease care.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"23 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000216/pdfft?md5=84ca60766df327a2a797407c7cac8d77&pid=1-s2.0-S2590098624000216-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021477","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}
引用次数: 0
A complex molecular landscape to drug delivery concept for achieving precise therapy in psoriasis 从复杂分子图谱到给药概念,实现银屑病的精确治疗
Medicine in Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-03-08 DOI: 10.1016/j.medidd.2024.100183
Krishna Yadav , Kantrol Kumar Sahu , Sucheta , Renu Yadav , Wasim Raza , Sunita Minz , Manju Rawat Singh , Deependra Singh , Madhulika Pradhan
{"title":"A complex molecular landscape to drug delivery concept for achieving precise therapy in psoriasis","authors":"Krishna Yadav ,&nbsp;Kantrol Kumar Sahu ,&nbsp;Sucheta ,&nbsp;Renu Yadav ,&nbsp;Wasim Raza ,&nbsp;Sunita Minz ,&nbsp;Manju Rawat Singh ,&nbsp;Deependra Singh ,&nbsp;Madhulika Pradhan","doi":"10.1016/j.medidd.2024.100183","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100183","url":null,"abstract":"<div><p>Psoriasis is a chronic autoimmune disorder that has a major effect on the quality of life for millions of people throughout the world. The pathogenesis of psoriasis has revealed intricate molecular networks and signaling pathways, opening new avenues for precision medicine. Psoriasis treatments include topical therapy, phototherapy, systemic therapies, and biologics, but achieving optimal outcomes is difficult. Despite advancements in understanding the causes of psoriasis and the development of various treatments, optimizing therapeutic outcomes remains challenging. Managing psoriasis poses challenges in terms of drug delivery and evaluation models. Novel drug delivery systems capable of navigating complex skin barriers and delivering therapeutics precisely to target cells are crucial for advancing treatment options. This article provides an inclusive overview of psoriasis, highlighting recent discoveries and potential therapeutic targets. The article emphasizes the importance of combining different modalities, such as synthetic and herbal agents, with biologics to improve efficacy. Nanocarriers show promise for targeted drug delivery in psoriasis, as they can encapsulate antipsoriatic drugs, biologics, and gene therapies, providing enhanced stability, improved tissue penetration, and precise cellular targeting. These advancements in drug delivery systems have the potential to revolutionize psoriasis treatment by maximizing efficacy while minimizing side effects. The article also discusses the commercial outcomes in psoriasis formulations, including patents related to treatment and ongoing clinical trials, which provide valuable insights into the evolving landscape of psoriasis therapeutics. These insights contribute to the evolving field of psoriasis therapeutics and offer hope for improved outcomes for patients suffering from psoriasis.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000083/pdfft?md5=dc8eaee6cca333d71d3a446c45bd27aa&pid=1-s2.0-S2590098624000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140123196","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}
引用次数: 0
Experimental and computational characterization of p-Sulfocalix[4]arene mediated delivery system for morin hydrate 对磺基[4]炔介导的吗啉水合物输送系统的实验和计算表征
Medicine in Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-02-27 DOI: 10.1016/j.medidd.2024.100180
Sunaina Chaurasiya , Raghu Solanki , Mohd Athar , Ashok Kumar Jangid , Sunita Patel , Prakash C. Jha , Deep Pooja , Hitesh Kulhari
{"title":"Experimental and computational characterization of p-Sulfocalix[4]arene mediated delivery system for morin hydrate","authors":"Sunaina Chaurasiya ,&nbsp;Raghu Solanki ,&nbsp;Mohd Athar ,&nbsp;Ashok Kumar Jangid ,&nbsp;Sunita Patel ,&nbsp;Prakash C. Jha ,&nbsp;Deep Pooja ,&nbsp;Hitesh Kulhari","doi":"10.1016/j.medidd.2024.100180","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100180","url":null,"abstract":"<div><p>Calix[n]arene is a class of macrocyclic compounds and has been investigated to improve the physicochemical properties of water insoluble molecules. In this work, a complex of morin hydrate (MH) drug was prepared using p-sulfocalix[4]arene (SC[4]A) as complexing agent to increase its water solubility, dissolution rate and stability. Solvent evaporation methanol was used to prepare the inclusion complex (MH-SC[4]A) between pure MH and SC[4]A and analysed by FTIR, NMR, UV, DLS, TEM, and DSC techniques. Concentration-dependent solubility study showed 22 folds enhancement of MH at 8 mM concentration of SC[4]A. The <em>in vitro</em> anticancer efficacy of MH against A549 cells was increased after complex formation. AO/EtBr staining study showed the more apoptosis mediated anticancer activity than native MH. Molecular geometry, stabilizing interactions, release behaviour and full-unwinding pathway of the complex were characterized by the computed Potential of Mean Force (PMF) using extended umbrella sampling. The combined computational and experimental data confirmed that our designed MH-SC[4]A complex could be utilized as a promising drug delivery carrier for hydrophobic MH.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000058/pdfft?md5=673fcfeb90f34f8122e3a96ac47d884e&pid=1-s2.0-S2590098624000058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067369","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}
引用次数: 0
Erratum to “Potent anti-Toxoplasma gondii activity of 4-chlorophenylthioacetone-derived thiosemicarbazones: Involvement of CCR2 and CCR5 receptors and 5-lipoxygenase in the mode of action” [Med. Drug Discovery 18 (2023) 100157] 4-chlorophenylthioacetone-derived thiosemicarbazones 的强效抗弓形虫活性:CCR2 和 CCR5 受体及 5-脂氧合酶参与作用模式" [Med.
Medicine in Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-20 DOI: 10.1016/j.medidd.2024.100192
Rayane Aparecida Nonato Rabelo , Diego Rodney Rodrigues de Assis , Alexandre Almeida Oliveira , César Luís Nascimento Barbosa , Rafaela das Dores Pereira , Ricardo Wagner de Almeida Vitor , Wiliam César Bento Régis , Mauro Martins Teixeira , Heloísa Beraldo , Fabiana Simão Machado
{"title":"Erratum to “Potent anti-Toxoplasma gondii activity of 4-chlorophenylthioacetone-derived thiosemicarbazones: Involvement of CCR2 and CCR5 receptors and 5-lipoxygenase in the mode of action” [Med. Drug Discovery 18 (2023) 100157]","authors":"Rayane Aparecida Nonato Rabelo ,&nbsp;Diego Rodney Rodrigues de Assis ,&nbsp;Alexandre Almeida Oliveira ,&nbsp;César Luís Nascimento Barbosa ,&nbsp;Rafaela das Dores Pereira ,&nbsp;Ricardo Wagner de Almeida Vitor ,&nbsp;Wiliam César Bento Régis ,&nbsp;Mauro Martins Teixeira ,&nbsp;Heloísa Beraldo ,&nbsp;Fabiana Simão Machado","doi":"10.1016/j.medidd.2024.100192","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100192","url":null,"abstract":"","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000174/pdfft?md5=7f508b00f71d22603d13481fdba1b2b8&pid=1-s2.0-S2590098624000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141067733","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}
引用次数: 0
Treatment response and its predictors of immunosuppressive therapy in patients with severe or very severe aplastic anemia 重度或极重度再生障碍性贫血患者对免疫抑制疗法的治疗反应及其预测因素
Medicine in Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-02-27 DOI: 10.1016/j.medidd.2024.100181
Thanakrit Somprasertkul , Weerayaporn Trirattanapikul , Sittichai Khamsai , Verajit Chotmongkol , Kittisak Sawanyawisuth
{"title":"Treatment response and its predictors of immunosuppressive therapy in patients with severe or very severe aplastic anemia","authors":"Thanakrit Somprasertkul ,&nbsp;Weerayaporn Trirattanapikul ,&nbsp;Sittichai Khamsai ,&nbsp;Verajit Chotmongkol ,&nbsp;Kittisak Sawanyawisuth","doi":"10.1016/j.medidd.2024.100181","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100181","url":null,"abstract":"<div><p>Severe aplastic anemia (SAA) is a hematological condition with high morbidity and mortality. Treatment with immunosuppressive agents is alternative treatment if bone marrow transplant is not available. Several studies reported predictors of successful treatment in patients with SAA. However, the results are not consistent and not specific to anti-thymocyte globulin and cyclosporine. This study aimed to evaluate the predictor of response to treatment in this specific regimen. This study was a retrospective cohort study. The inclusion criteria were adult patients with SAA or very SAA who received this regimen. Clinical factors predictive of response to treatment were computed. There were 92 patients met the study criteria. Of those, 56 patients (60.87%) were in a group of response to treatment. There were nine factors in the predictive model for good response to treatment. Only body mass index was independently associated with response to treatment with an adjusted odds ratio of 1.31 (95% confidence interval of 1.04, 1.67). Age or hematological laboratory factors such as lymphocyte or neutrophil count were not significant. Low body mass index may be less likely to response to immunosuppressive treatment in patients with severe or very severe aplastic anemia.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259009862400006X/pdfft?md5=c7cc3102353ae4f94e197711f5758dd4&pid=1-s2.0-S259009862400006X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030220","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}
引用次数: 0
In vitro human colon microbiota culture model for drug research 用于药物研究的体外人体结肠微生物群培养模型
Medicine in Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-03-11 DOI: 10.1016/j.medidd.2024.100184
Tomoya Shintani , Daisuke Sasaki , Yasushi Matsuki , Akihiko Kondo
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