Combination therapy has emerged as an efficacy strategy for treating complex diseases. Its potential to overcome drug resistance and minimize toxicity makes it highly desirable. However, the vast number of potential drug pairs presents a significant challenge, rendering exhaustive clinical testing impractical. In recent years, deep learning-based methods have emerged as promising tools for predicting synergistic drug combinations. This review aims to provide a comprehensive overview of applying diverse deep-learning architectures for drug combination prediction. This review commences by elucidating the quantitative measures employed to assess drug combination synergy. Subsequently, we delve into the various deep-learning methods currently employed for drug combination prediction. Finally, the review concludes by outlining the key challenges facing deep learning approaches and proposes potential challenges for future research.
{"title":"Deep learning for predicting synergistic drug combinations: State-of-the-arts and future directions","authors":"Yu Wang, Junjie Wang, Yun Liu","doi":"10.1002/ctd2.317","DOIUrl":"https://doi.org/10.1002/ctd2.317","url":null,"abstract":"<p>Combination therapy has emerged as an efficacy strategy for treating complex diseases. Its potential to overcome drug resistance and minimize toxicity makes it highly desirable. However, the vast number of potential drug pairs presents a significant challenge, rendering exhaustive clinical testing impractical. In recent years, deep learning-based methods have emerged as promising tools for predicting synergistic drug combinations. This review aims to provide a comprehensive overview of applying diverse deep-learning architectures for drug combination prediction. This review commences by elucidating the quantitative measures employed to assess drug combination synergy. Subsequently, we delve into the various deep-learning methods currently employed for drug combination prediction. Finally, the review concludes by outlining the key challenges facing deep learning approaches and proposes potential challenges for future research.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424893","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}
The incidence of end-stage renal disease (ESRD) is gradually increasing worldwide, with a 107% increase in the United States from 2000 to 2019.1 Compared to hemodialysis and peritoneal dialysis, kidney transplantation significantly reduces mortality rates and improves the quality of life for ESRD patients, making it the preferred form of renal replacement therapy. However, the glaring disparity between the demand for kidney donors and their availability persists. Consequently, we have to expand the criteria for using donor kidneys. However, such kidneys are often from older donors, those with hypertension, or those from patients who have undergone cardiopulmonary resuscitation. The short-term recovery and long-term prognosis of these donor kidneys face significant challenges. Among them, delayed graft function (DGF) is a common complication that affects prognosis.2 DGF is defined as the requirement for dialysis within the first week following transplantation and is indicative of significant acute tubular necrosis. IRI, which refers to damage caused when blood flow is restored to an ischemic organ, can lead to DGF, primary non-function and even loss of the transplanted kidney, significantly impacting early functional recovery and long-term survival of the transplant.3
In kidney transplantation, the warm and cold ischemic injuries to the transplanted kidney are unavoidable. Warm ischemia time is defined as the duration between the cessation of donor blood supply to an organ and the initiation of cold perfusion, while cold ischemia time refers to the period during which grafts are stored in a cold organ preservation solution.4 The mouse kidney transplantation with prolonged cold ischemia time is a suitable model, although it cannot fully replicate the clinical processes of human transplantation. Notably, human kidney grafts can withstand 24 h of cold ischemia, while mouse kidney grafts can tolerate a maximum of 10 h of cold ischemia, with varying degrees of maladaptive repair observed post-transplantation.5, 6
Regulatory T cells (Tregs) represent a subset of CD4+ T cells, which are categorized into three classes based on their origin and differentiation pathways. Among these, Tregs derived from immature T lymphocytes during thymic development, characterized by the CD4+ CD25+ Foxp3+ phenotype, are commonly utilized in research.7 The application of Tregs in the field of solid organ transplantation is particularly relevant to the goal of achieving tolerance, aiming to reduce or eliminate the need for immunosuppressive drugs while maintaining tissue repair and managing acute rejection responses. A key challenge in the clinical use of Tregs is how to effectively expand their numbers, whether by increasing the number of endogenous Tregs or through the direct infusion of exogenously expanded Tregs.
不过，除了 IL-2C 对 Tregs 的影响外，还需要进一步研究 IL-2C 对其他 T 细胞亚型的影响。虽然 IL-2C 在啮齿类动物身上显示出对寒冷 IRI 的保护作用，但如果应用于人类 DGF 病例，还需要进行更多的研究，以更好地了解啮齿类动物和人类之间的免疫学差异和风险。例如，检测临床样本中Tregs的细胞水平以及IL-2C对人类Treg细胞的影响，可以深入了解它们在移植功能中的作用。最终，移植后急性和慢性免疫排斥反应是决定移植肾预后的关键因素。因此，IL-2C对免疫排斥反应的影响也是决定其临床转化价值的关键因素，值得进一步探讨。作者声明无利益冲突。
{"title":"The therapeutic potential of interleukin-2/anti-interleukin-2 antibody complex in cold storage-associated kidney transplantation","authors":"Yao Xia, Jiefu Zhu","doi":"10.1002/ctd2.302","DOIUrl":"https://doi.org/10.1002/ctd2.302","url":null,"abstract":"<p>The incidence of end-stage renal disease (ESRD) is gradually increasing worldwide, with a 107% increase in the United States from 2000 to 2019.<span><sup>1</sup></span> Compared to hemodialysis and peritoneal dialysis, kidney transplantation significantly reduces mortality rates and improves the quality of life for ESRD patients, making it the preferred form of renal replacement therapy. However, the glaring disparity between the demand for kidney donors and their availability persists. Consequently, we have to expand the criteria for using donor kidneys. However, such kidneys are often from older donors, those with hypertension, or those from patients who have undergone cardiopulmonary resuscitation. The short-term recovery and long-term prognosis of these donor kidneys face significant challenges. Among them, delayed graft function (DGF) is a common complication that affects prognosis.<span><sup>2</sup></span> DGF is defined as the requirement for dialysis within the first week following transplantation and is indicative of significant acute tubular necrosis. IRI, which refers to damage caused when blood flow is restored to an ischemic organ, can lead to DGF, primary non-function and even loss of the transplanted kidney, significantly impacting early functional recovery and long-term survival of the transplant.<span><sup>3</sup></span></p><p>In kidney transplantation, the warm and cold ischemic injuries to the transplanted kidney are unavoidable. Warm ischemia time is defined as the duration between the cessation of donor blood supply to an organ and the initiation of cold perfusion, while cold ischemia time refers to the period during which grafts are stored in a cold organ preservation solution.<span><sup>4</sup></span> The mouse kidney transplantation with prolonged cold ischemia time is a suitable model, although it cannot fully replicate the clinical processes of human transplantation. Notably, human kidney grafts can withstand 24 h of cold ischemia, while mouse kidney grafts can tolerate a maximum of 10 h of cold ischemia, with varying degrees of maladaptive repair observed post-transplantation.<span><sup>5, 6</sup></span></p><p>Regulatory T cells (Tregs) represent a subset of CD4+ T cells, which are categorized into three classes based on their origin and differentiation pathways. Among these, Tregs derived from immature T lymphocytes during thymic development, characterized by the CD4+ CD25+ Foxp3+ phenotype, are commonly utilized in research.<span><sup>7</sup></span> The application of Tregs in the field of solid organ transplantation is particularly relevant to the goal of achieving tolerance, aiming to reduce or eliminate the need for immunosuppressive drugs while maintaining tissue repair and managing acute rejection responses. A key challenge in the clinical use of Tregs is how to effectively expand their numbers, whether by increasing the number of endogenous Tregs or through the direct infusion of exogenously expanded Tregs.<s","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424984","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}
Wenjie Bao, Qihua Fu, Xiaoqing Zhang, Xi Mo, Tingting Yu
Background
Molecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high-quality development of the discipline requires careful consideration by relevant management and professionals.
Methods
This study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.
Results
This study highlights the importance of molecular diagnostic technology in providing information and decision-making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross-discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.
Conclusions
Molecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.
{"title":"The clinical application and laboratory management of molecular genetic diagnosis in children's hospital","authors":"Wenjie Bao, Qihua Fu, Xiaoqing Zhang, Xi Mo, Tingting Yu","doi":"10.1002/ctd2.315","DOIUrl":"https://doi.org/10.1002/ctd2.315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Molecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high-quality development of the discipline requires careful consideration by relevant management and professionals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study highlights the importance of molecular diagnostic technology in providing information and decision-making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross-discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Molecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424983","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}
The creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies.
Methods
Using payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data.
Results
Of the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling $3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were $25 772 (standard deviation: $58 197) and $2761 (interquartile range: $322‒$15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from $588 054 in 2016 to $967 802 in 2019. The JBCS2022 chairperson and vice-chairperson received $246 936 (fourth highest) and $216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds.
Conclusion
This study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.
{"title":"Pharmaceutical company payments to Japanese breast cancer practice guideline authors","authors":"Anju Murayama, Kenichi Higuchi, Keerthana R. Byreddy, Kugo Hinari, Yuki Senoo","doi":"10.1002/ctd2.304","DOIUrl":"https://doi.org/10.1002/ctd2.304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling $3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were $25 772 (standard deviation: $58 197) and $2761 (interquartile range: $322‒$15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from $588 054 in 2016 to $967 802 in 2019. The JBCS2022 chairperson and vice-chairperson received $246 936 (fourth highest) and $216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326509","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}
The Hippo/Yap signalling pathway is known to be a conserved pathway that controls organ size by promoting tissue regeneration, however, the mechanism is not fully understood. Emerging experimental research has characterized various roles by which the Hippo mechanism promotes the regenerative capacity of distinct mouse organs such as the intestine, heart and the liver, nevertheless, attempts for therapeutic applications require additional efforts to avoid potential adverse effects. The junctional protein associated with coronary artery disease (JCAD) has been proposed as a new potential therapeutic target in medical conditions, mainly cardiovascular disease. Recently, it has been demonstrated that JCAD negatively regulates Hippo signalling, leading to the activation of YAP (yes-associated protein), the transcriptional effector of the pathway.1 Zhang and colleagues report novel results of JCAD in regulating liver regeneration in mice subjected to partial hepatectomy (PH) to model patients undergone liver resection or transplanted with small-for-size graft.2 Using both global JCAD knockout (JCAD-KO) and conditional JCAD knockout mice, they found decreased expression of genes involved in the cell cycle and impaired DNA replication. Moreover, JCAD deficiency in hepatocytes causes prolongation of the cell cycle due to G2/M transition blockage. When they overexpressed or replenished JCAD in JCAD KO primary hepatocytes, they were able to reverse cell cycle duration, which was abolished by administering the YAP inhibitor, verteporfin. The paper demonstrates that JCAD promotes cycle-dependent hepatocellular regeneration. The dramatic progress being made in the field makes the idea of expanding these findings more tempting. The proposed role of JCAD in liver regeneration opens new avenues for determining potential targets required for therapeutic approaches based on modulation of the cell-cycle machinery.
Previous works of the Hippo/YAP1 pathway have delineated numerous associations of this pathway with human diseases with a wide array of cellular functions.3 An interesting finding is learned from the result that JCAD competed with LATS2 for WWC1 interaction, causing inhibition of LATS2 and YAP activation, and enhanced expression of cell cycle regulatory genes. The mechanistic insights on how cell cycle gene expression integrates with each step of controlling regeneration in the liver will need to be investigated from broader aspects including the development of novel experimental tools required for both the prevention and improvement of different pathologies, with special emphasis on regeneration, transplantation and bioengineering. Sophisticated cell cycle manipulation approaches together with the understanding of how specific genomic regions or configurations respond to cell cycle modulation may precisely control cell fate.
{"title":"Novel roles of the junctional protein associated with coronary artery disease in regulating Hippo-YAP signalling axis to improve liver regenerative potential","authors":"Eltyeb Abdelwahid","doi":"10.1002/ctd2.306","DOIUrl":"https://doi.org/10.1002/ctd2.306","url":null,"abstract":"<p>The Hippo/Yap signalling pathway is known to be a conserved pathway that controls organ size by promoting tissue regeneration, however, the mechanism is not fully understood. Emerging experimental research has characterized various roles by which the Hippo mechanism promotes the regenerative capacity of distinct mouse organs such as the intestine, heart and the liver, nevertheless, attempts for therapeutic applications require additional efforts to avoid potential adverse effects. The junctional protein associated with coronary artery disease (JCAD) has been proposed as a new potential therapeutic target in medical conditions, mainly cardiovascular disease. Recently, it has been demonstrated that JCAD negatively regulates Hippo signalling, leading to the activation of YAP (yes-associated protein), the transcriptional effector of the pathway.<span><sup>1</sup></span> Zhang and colleagues report novel results of JCAD in regulating liver regeneration in mice subjected to partial hepatectomy (PH) to model patients undergone liver resection or transplanted with small-for-size graft.<span><sup>2</sup></span> Using both global JCAD knockout (JCAD-KO) and conditional JCAD knockout mice, they found decreased expression of genes involved in the cell cycle and impaired DNA replication. Moreover, JCAD deficiency in hepatocytes causes prolongation of the cell cycle due to G2/M transition blockage. When they overexpressed or replenished JCAD in JCAD KO primary hepatocytes, they were able to reverse cell cycle duration, which was abolished by administering the YAP inhibitor, verteporfin. The paper demonstrates that JCAD promotes cycle-dependent hepatocellular regeneration. The dramatic progress being made in the field makes the idea of expanding these findings more tempting. The proposed role of JCAD in liver regeneration opens new avenues for determining potential targets required for therapeutic approaches based on modulation of the cell-cycle machinery.</p><p>Previous works of the Hippo/YAP1 pathway have delineated numerous associations of this pathway with human diseases with a wide array of cellular functions.<span><sup>3</sup></span> An interesting finding is learned from the result that JCAD competed with LATS2 for WWC1 interaction, causing inhibition of LATS2 and YAP activation, and enhanced expression of cell cycle regulatory genes. The mechanistic insights on how cell cycle gene expression integrates with each step of controlling regeneration in the liver will need to be investigated from broader aspects including the development of novel experimental tools required for both the prevention and improvement of different pathologies, with special emphasis on regeneration, transplantation and bioengineering. Sophisticated cell cycle manipulation approaches together with the understanding of how specific genomic regions or configurations respond to cell cycle modulation may precisely control cell fate.</p><p>Interestingly, JCAD expression is mainly loca","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329373","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}
Cancer therapeutic development is the most challenging domain in cancer. Cell-based cancer therapeutics come up with promising effectiveness. This approach was also cell-modified for better targeting efficiency development. Cell engineering-based cancer therapeutic is a cutting-edge method in cancer therapy. Due to complications of this process, cost and post-treatment side effects, this phenomenon came into the question mark. In this scenario, extracellular vesicle (EVs) research introduces a cell-free cancer therapeutic approach. In the therapeutic aspect most used EVs, come from stem cells, plants, and engineered cells. Among several EVs populations, Exosomes are the most used worldwide cell-free therapeutic tool for ageing cancer. The most interesting facts about exosomes are the biocompatible, non-immunoreactive, cross-biological barrier, and non-toxic (depending on the parental cell's nature). In this article, we are exploring modified exosomes (biological or chemical) that create a remarkable outcome in cancer therapeutic development compared to engineered cell-based therapeutics. Hope, in the future, modified exosomes become an effective, affordable, and specific cancer-targeting precision medicine.
{"title":"Engineered cell versus modified exosomes in cancer therapy","authors":"Rajib Dhar, Arikketh Devi","doi":"10.1002/ctd2.320","DOIUrl":"https://doi.org/10.1002/ctd2.320","url":null,"abstract":"<p>Cancer therapeutic development is the most challenging domain in cancer. Cell-based cancer therapeutics come up with promising effectiveness. This approach was also cell-modified for better targeting efficiency development. Cell engineering-based cancer therapeutic is a cutting-edge method in cancer therapy. Due to complications of this process, cost and post-treatment side effects, this phenomenon came into the question mark. In this scenario, extracellular vesicle (EVs) research introduces a cell-free cancer therapeutic approach. In the therapeutic aspect most used EVs, come from stem cells, plants, and engineered cells. Among several EVs populations, Exosomes are the most used worldwide cell-free therapeutic tool for ageing cancer. The most interesting facts about exosomes are the biocompatible, non-immunoreactive, cross-biological barrier, and non-toxic (depending on the parental cell's nature). In this article, we are exploring modified exosomes (biological or chemical) that create a remarkable outcome in cancer therapeutic development compared to engineered cell-based therapeutics. Hope, in the future, modified exosomes become an effective, affordable, and specific cancer-targeting precision medicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315445","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}
Intervertebral disc (IVD) degeneration is a common phenomenon that affects patients with increasing prevalence with increasing age. Both conservative treatments, such as the use of pain medication or physical therapy, and surgical treatments, such as fusion or disc replacement therapies, are offered to patients. Both non-invasive and invasive treatments have been shown to improve pain and quality of life for patients. This review explores the role of regenerative medicine techniques as a promising therapeutic intervention that can be used before or in combination with conservative therapy and surgery to enhance the treatment process in patients with IVD degeneration or disc pathology. Currently, there are four major modules of regenerative medicine: genetic therapy, platelet-rich plasma therapy, stem cell transplantation and tissue engineering. Several research studies have shown promising outcomes of stem cell transplantation and tissue engineering when combined with either surgical or conservative treatment, resulting in improved pain outcomes. The additional benefit of regenerative medicine techniques, specifically stem cell transplantation, is the potential for treating the root pathology of degeneration. Regenerative medicine techniques also have the potential to either halt or reverse degeneration as opposed to current standards of care for managing symptoms. There is a plethora of current research highlighting the benefits of regenerative medicine techniques; however, there remains clinical concerns and ethical concerns regarding the use of regenerative therapy techniques such as stem cell transplantation in the context of IVD degeneration.
{"title":"Intervertebral disc degeneration and regenerative medicine","authors":"Mariam Farag, Rogina Rezk, Hunter Hutchinson, Alina Zankevich, Brandon Lucke-Wold","doi":"10.1002/ctd2.289","DOIUrl":"https://doi.org/10.1002/ctd2.289","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is a common phenomenon that affects patients with increasing prevalence with increasing age. Both conservative treatments, such as the use of pain medication or physical therapy, and surgical treatments, such as fusion or disc replacement therapies, are offered to patients. Both non-invasive and invasive treatments have been shown to improve pain and quality of life for patients. This review explores the role of regenerative medicine techniques as a promising therapeutic intervention that can be used before or in combination with conservative therapy and surgery to enhance the treatment process in patients with IVD degeneration or disc pathology. Currently, there are four major modules of regenerative medicine: genetic therapy, platelet-rich plasma therapy, stem cell transplantation and tissue engineering. Several research studies have shown promising outcomes of stem cell transplantation and tissue engineering when combined with either surgical or conservative treatment, resulting in improved pain outcomes. The additional benefit of regenerative medicine techniques, specifically stem cell transplantation, is the potential for treating the root pathology of degeneration. Regenerative medicine techniques also have the potential to either halt or reverse degeneration as opposed to current standards of care for managing symptoms. There is a plethora of current research highlighting the benefits of regenerative medicine techniques; however, there remains clinical concerns and ethical concerns regarding the use of regenerative therapy techniques such as stem cell transplantation in the context of IVD degeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264658","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}
Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, play crucial roles in cellular communication and disease processes. Among these, exosomes are particularly significant for diagnosing, and cancer (which remains a leading cause of death worldwide). Exosomes offer cutting-edge approaches in cancer nanomedicine, cancer biomarkers investigation (diagnosis and prognosis), and therapeutic. Exosomes are found in several body fluids (Blood, plasma, serum, urine, saliva, sweat, CSF, tear). It transforms the liquid biopsy method with more specificity. Exosome-based sensor (electrochemical and aptamer-based) developers were more effective and sensitive for cancer scanning. Therapeutic prospect stem cell-derived exosomes, and plant-derived exosomes become more promising. Due to its non-toxicity (depending on the source), non-immunogenic, biocompatibility and ability to cross biological membranes. Exosomes are an exciting nano-drug transporter with specificity. Current time-modified exosomes support to development of effective, efficient, and cost-effective nanomedicine against cancer. Advanced nanotechnology and exosome combining (single exosome profiling, exosome barcoding)transform cancer theranostics approaches. Exosomes introduce a new horizon of cancer nanomedicine.
{"title":"The prospective trajectory of exosomes-based cancer nanomedicine","authors":"Divya Mirgh, Swarup Sonar, Sidhanti Nyahatkar, Ketki Kalele, Manab Deb Adhikari","doi":"10.1002/ctd2.318","DOIUrl":"https://doi.org/10.1002/ctd2.318","url":null,"abstract":"<p>Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, play crucial roles in cellular communication and disease processes. Among these, exosomes are particularly significant for diagnosing, and cancer (which remains a leading cause of death worldwide). Exosomes offer cutting-edge approaches in cancer nanomedicine, cancer biomarkers investigation (diagnosis and prognosis), and therapeutic. Exosomes are found in several body fluids (Blood, plasma, serum, urine, saliva, sweat, CSF, tear). It transforms the liquid biopsy method with more specificity. Exosome-based sensor (electrochemical and aptamer-based) developers were more effective and sensitive for cancer scanning. Therapeutic prospect stem cell-derived exosomes, and plant-derived exosomes become more promising. Due to its non-toxicity (depending on the source), non-immunogenic, biocompatibility and ability to cross biological membranes. Exosomes are an exciting nano-drug transporter with specificity. Current time-modified exosomes support to development of effective, efficient, and cost-effective nanomedicine against cancer. Advanced nanotechnology and exosome combining (single exosome profiling, exosome barcoding)transform cancer theranostics approaches. Exosomes introduce a new horizon of cancer nanomedicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251317","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}
Meningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non-specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle-based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.
{"title":"Potential diagnostic and distinguishing roles of microneedle-based biosensors in bacterial and aseptic meningitis","authors":"Hamid Sadeghi, Nematollah Gheibi, Masoumeh Aslanimehr, Saeideh Gholamzadeh Khoei, Milad Badri","doi":"10.1002/ctd2.297","DOIUrl":"https://doi.org/10.1002/ctd2.297","url":null,"abstract":"<p>Meningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non-specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle-based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251290","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}
Shruti Kolli, Robert Medina, Chloe DeYoung, Brandon Lucke-Wold
Background
The use of cervical collars in the management of acute cervical spine injuries has been part of standard practice in the trauma setting for decades, aimed at preventing secondary injuries.
Objectives
To review the recent evidence challenging the routine use of cervical collars, addressing the limited scientific support, associated risks, and guidelines for their use.
Methods
A comprehensive literature review was conducted, analyzing recent studies and guidelines from authoritative bodies such as the American Association for Neurological Surgeons and the Congress of Neurological Surgeons. The review focused on the efficacy, risks, and recommendations regarding cervical collar use in acute cervical spine injuries.
Results
Recent evidence questions the routine use of cervical collars, highlighting limited scientific support and several associated risks, including pressure ulcers and decreased venous return. Cervical collars may also be contraindicated in individuals with abnormal spinal structures, such as those with Ankylosing Spondylitis. The efficacy of cervical collars is debated, particularly concerning undiagnosed spinal fractures, where delayed diagnosis can result in permanent injuries. Despite these risks, cervical collars may be beneficial in low-resource areas and when used effectively with early clearance post-injury. Current guidelines recommend immobilizing patients suspected of cervical spine injury but stress the importance of proper evaluation of the need for immobilization. Recent guidelines advocate for spinal motion restriction over traditional immobilization, emphasizing the need for better risk assessment and implementation strategies.
Conclusions/Clinical Importance
Re-evaluating the routine use of cervical collars is crucial due to potential risks and limited supporting evidence, with a focus on individualized assessment and adherence to updated guidelines favoring spinal motion restriction.
{"title":"Cervical collar use in spinal cord injury management","authors":"Shruti Kolli, Robert Medina, Chloe DeYoung, Brandon Lucke-Wold","doi":"10.1002/ctd2.316","DOIUrl":"https://doi.org/10.1002/ctd2.316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The use of cervical collars in the management of acute cervical spine injuries has been part of standard practice in the trauma setting for decades, aimed at preventing secondary injuries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To review the recent evidence challenging the routine use of cervical collars, addressing the limited scientific support, associated risks, and guidelines for their use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted, analyzing recent studies and guidelines from authoritative bodies such as the American Association for Neurological Surgeons and the Congress of Neurological Surgeons. The review focused on the efficacy, risks, and recommendations regarding cervical collar use in acute cervical spine injuries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recent evidence questions the routine use of cervical collars, highlighting limited scientific support and several associated risks, including pressure ulcers and decreased venous return. Cervical collars may also be contraindicated in individuals with abnormal spinal structures, such as those with Ankylosing Spondylitis. The efficacy of cervical collars is debated, particularly concerning undiagnosed spinal fractures, where delayed diagnosis can result in permanent injuries. Despite these risks, cervical collars may be beneficial in low-resource areas and when used effectively with early clearance post-injury. Current guidelines recommend immobilizing patients suspected of cervical spine injury but stress the importance of proper evaluation of the need for immobilization. Recent guidelines advocate for spinal motion restriction over traditional immobilization, emphasizing the need for better risk assessment and implementation strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions/Clinical Importance</h3>\u0000 \u0000 <p>Re-evaluating the routine use of cervical collars is crucial due to potential risks and limited supporting evidence, with a focus on individualized assessment and adherence to updated guidelines favoring spinal motion restriction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245849","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}
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