Pub Date : 2025-06-01Epub Date: 2025-03-22DOI: 10.1016/j.medidd.2025.100206
Hui Sin Lim , Christopher J. Serpell , Satoshi Ogawa , Yong Yu Hu , Eng Hwa Wong
Animal-derived products, such as organs, secretions, and mucus, have been part and parcel of traditional medicine and are often overlooked in the modern healthcare system. Nevertheless, researchers have begun to explore the untapped potential of bioactive compounds from marine organisms, reptiles, amphibians, and insects, thus offering innovative solutions for wound care. This review delved into the medicinal properties of animal-based bioactive compounds in wound healing based on in vitro and in vivo studies. A comparative analysis of the empirical evidence was performed to determine the benefits and limitations of animal-derived bioactive compounds. In summary, the literature suggests that animal-derived products could regulate biological pathways involved in inflammation and tissue regeneration. Clinical trials are underway to affirm the feasibility and safety of these compounds for human health applications.
{"title":"From Fins to Furs: Unlocking the Therapeutic Potential of Animal-derived Bioactives for Wound Care","authors":"Hui Sin Lim , Christopher J. Serpell , Satoshi Ogawa , Yong Yu Hu , Eng Hwa Wong","doi":"10.1016/j.medidd.2025.100206","DOIUrl":"10.1016/j.medidd.2025.100206","url":null,"abstract":"<div><div>Animal-derived products, such as organs, secretions, and mucus, have been part and parcel of traditional medicine and are often overlooked in the modern healthcare system. Nevertheless, researchers have begun to explore the untapped potential of bioactive compounds from marine organisms, reptiles, amphibians, and insects, thus offering innovative solutions for wound care. This review delved into the medicinal properties of animal-based bioactive compounds in wound healing based on in vitro and in vivo studies. A comparative analysis of the empirical evidence was performed to determine the benefits and limitations of animal-derived bioactive compounds. In summary, the literature suggests that animal-derived products could regulate biological pathways involved in inflammation and tissue regeneration. Clinical trials are underway to affirm the feasibility and safety of these compounds for human health applications.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"26 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820675","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}
Status epilepticus is an emergency condition with a high mortality rate. However, there is currently limited data on the timing of antiepileptic drugs (AED) and mortality, particularly generalized convulsive status epilepticus. This study aims to evaluate if early AED treatment is associated with mortality in patients with generalized convulsive status epilepticus. This was a retrospective cohort study, which enrolled patients 18 years or over who had been diagnosed with generalized convulsive status epilepticus and had discharge status. Eligible patients were selected from the database of University Hospital. Predictors for mortality were analyzed by logistic regression analysis. A total of 77 patients met the study criteria; of those 27 patients (35.06 %) died. There were seven factors included in the stepwise multivariable logistic regression analysis. Among those, only five factors were retained in the predictive model for mortality: These included the time from seizure onset to benzodiazepine treatment, the time from the seizure onset to the first AED, number of AEDs, AED withdrawal, and Status Epilepticus Severity Score (STESS). Of those, only the time from seizure onset to benzodiazepine treatment and the STESS were independently associated with mortality with adjusted odds ratios of 1.03 (95 % confidence interval of 1.01, 1.06) and 1.54 (95 % confidence interval of 1.08, 2.22), respectively. Sensitivity of time from seizure onset to benzodiazepine treatment of five minutes or more had a sensitivity of 100 %. Early treatment with benzodiazepine, that is within five minutes after the occurrence of status epilepticus may lower mortality rate in adult patients with generalized convulsive status epilepticus.
{"title":"Timing of benzodiazepine treatment and mortality in adult patients with generalized convulsive status epilepticus","authors":"Au Auvichayapat , Verajit Chotmongkol , Kittisak Sawanyawisuth , Somsak Tiamkao","doi":"10.1016/j.medidd.2025.100209","DOIUrl":"10.1016/j.medidd.2025.100209","url":null,"abstract":"<div><div>Status epilepticus is an emergency condition with a high mortality rate. However, there is currently limited data on the timing of antiepileptic drugs (AED) and mortality, particularly generalized convulsive status epilepticus. This study aims to evaluate if early AED treatment is associated with mortality in patients with generalized convulsive status epilepticus. This was a retrospective cohort study, which enrolled patients 18 years or over who had been diagnosed with generalized convulsive status epilepticus and had discharge status. Eligible patients were selected from the database of University Hospital. Predictors for mortality were analyzed by logistic regression analysis. A total of 77 patients met the study criteria; of those 27 patients (35.06 %) died. There were seven factors included in the stepwise multivariable logistic regression analysis. Among those, only five factors were retained in the predictive model for mortality: These included the time from seizure onset to benzodiazepine treatment, the time from the seizure onset to the first AED, number of AEDs, AED withdrawal, and Status Epilepticus Severity Score (STESS). Of those, only the time from seizure onset to benzodiazepine treatment and the STESS were independently associated with mortality with adjusted odds ratios of 1.03 (95 % confidence interval of 1.01, 1.06) and 1.54 (95 % confidence interval of 1.08, 2.22), respectively. Sensitivity of time from seizure onset to benzodiazepine treatment of five minutes or more had a sensitivity of 100 %. Early treatment with benzodiazepine, that is within five minutes after the occurrence of status epilepticus may lower mortality rate in adult patients with generalized convulsive status epilepticus.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"26 ","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090222","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}
Recent advances in targeted drug delivery system (DDS) have generated high expectations for the treatment of various diseases. The main advantages of DDS are precise and efficient drug delivery, increased concentration and effectiveness of drugs at the site of action, minimal systemic distribution of harmful drugs, and reduced side effects. The choice of DDS often depends on the specific disease being treated, with common options including liposomes, nanoparticles, microspheres, and various biomaterials such as cell lines and microbial components.
DDS is most prominent in cancer therapy, where challenges such as limited access to tumor tissues and drug-inactivating environments complicate treatment. However, in recent decades, the emergence of antibiotic resistance and the therapeutic difficulties associated with chronic and intracellular bacterial infections have made infectious diseases a key focus for DDS development. Initial DDS approaches for bacterial infections were based on nano-derivatives. During more advanced stages of research, even the bacteria themselves became vehicles for DDS focused on microbial infections. All aspects of the bacteria- cell lysates, envelopes, derived vesicles, spores, and so forth-have been evaluated as DDS. This form of DDS does not only promote the immediate treatment of an infection but also expedites recovery times through immunological manipulation. Despite these advancements, there remains a lack of cohesive data regarding bacterial DDS in the treatment of infectious diseases. Therefore, this review aims to provide an overview of the various types of bacterial DDS, their applications, advancements, and the challenges they face.
靶向给药系统（targeted drug delivery system， DDS）近年来的进展使人们对多种疾病的治疗产生了很高的期望。DDS的主要优点是给药精确和高效，增加作用部位药物的浓度和有效性，减少有害药物的全身分布，减少副作用。DDS的选择通常取决于所治疗的特定疾病，常见的选择包括脂质体、纳米颗粒、微球和各种生物材料，如细胞系和微生物成分。DDS在癌症治疗中最为突出，在癌症治疗中，诸如限制进入肿瘤组织和药物失活环境等挑战使治疗复杂化。然而，近几十年来，抗生素耐药性的出现以及与慢性和细胞内细菌感染相关的治疗困难使传染病成为DDS发展的关键焦点。最初用于细菌感染的DDS方法是基于纳米衍生物的。在更高级的研究阶段，甚至细菌本身也成为专注于微生物感染的DDS的载体。细菌的所有方面——细胞裂解物、包膜、衍生囊泡、孢子等等——都被评估为DDS。这种形式的DDS不仅促进感染的立即治疗，而且通过免疫操作加快恢复时间。尽管取得了这些进展，但仍然缺乏关于细菌DDS治疗传染病的一致数据。因此，本文就不同类型的细菌DDS及其应用、进展和面临的挑战进行综述。
{"title":"Bacterial-based drug delivery systems: A new way to combat infectious disease","authors":"Parastoo TabibzadehTehrani , Mina Nazari , Pedram Rastgoo , Niloofar Seyed Bolouri , Reyhaneh HeydariKarsaf , Abtin Hadiani , Zeinab Mohsenipour","doi":"10.1016/j.medidd.2025.100205","DOIUrl":"10.1016/j.medidd.2025.100205","url":null,"abstract":"<div><div>Recent advances in targeted drug delivery system (DDS) have generated high expectations for the treatment of various diseases. The main advantages of DDS are precise and efficient drug delivery, increased concentration and effectiveness of drugs at the site of action, minimal systemic distribution of harmful drugs, and reduced side effects. The choice of DDS often depends on the specific disease being treated, with common options including liposomes, nanoparticles, microspheres, and various biomaterials such as cell lines and microbial components.</div><div>DDS is most prominent in cancer therapy, where challenges such as limited access to tumor tissues and drug-inactivating environments complicate treatment. However, in recent decades, the emergence of antibiotic resistance and the therapeutic difficulties associated with chronic and intracellular bacterial infections have made infectious diseases a key focus for DDS development. Initial DDS approaches for bacterial infections were based on nano-derivatives. During more advanced stages of research, even the bacteria themselves became vehicles for DDS focused on microbial infections. All aspects of the bacteria- cell lysates, envelopes, derived vesicles, spores, and so forth-have been evaluated as DDS. This form of DDS does not only promote the immediate treatment of an infection but also expedites recovery times through immunological manipulation. Despite these advancements, there remains a lack of cohesive data regarding bacterial DDS in the treatment of infectious diseases. Therefore, this review aims to provide an overview of the various types of bacterial DDS, their applications, advancements, and the challenges they face.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"26 ","pages":"Article 100205"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681976","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}
Pub Date : 2025-06-01Epub Date: 2025-04-04DOI: 10.1016/j.medidd.2025.100207
Letícia de Oliveira Souza Bratti , Bruno Fonseca Nunes , Daphany Marah Gorges , Emerita Quintina de Andrade Moura , Ana Carolina Rabello de Moraes , Fabíola Branco Filippin-Monteiro
Objective
This study aimed to investigate the impact of bariatric surgery on vitamin D metabolism and associated micronutrient deficiencies in individuals with obesity, emphasizing the prevalence of vitamin D deficiency in patients with severe obesity—a persistent concern after significant weight loss.
Methods
A comprehensive analysis of serum levels of 25(OH)D, parathyroid hormone (PTH), and calcium was conducted in patients with obesity before and after bariatric surgery, with a six-month follow-up. Medication usage was examined, and outcomes between different surgical techniques were compared.
Results
Notable metabolic improvements, linked to reduced BMI and diminished medication reliance post-surgery, were observed. Sleeve gastrectomy (SG) demonstrated potential advantages in preventing micronutrient deficiencies. Many patients had preoperative vitamin D deficiency and elevated PTH levels. Correlation analysis revealed that among those with preoperative PTH levels exceeding 70 pg/mL, higher PTH levels were associated with lower weight loss after six months. No significant correlation was found for vitamin D.
Conclusion
This study underscores the importance of critically assessing bone health in bariatric surgery candidates, emphasizing the need for meticulous preoperative evaluation and postoperative monitoring, particularly in cases of secondary hyperparathyroidism. These considerations are pivotal for optimizing the long-term well-being of bariatric surgery patients.
{"title":"Impact of bariatric surgery on vitamin D metabolism and micronutrient deficiencies in severe obesity","authors":"Letícia de Oliveira Souza Bratti , Bruno Fonseca Nunes , Daphany Marah Gorges , Emerita Quintina de Andrade Moura , Ana Carolina Rabello de Moraes , Fabíola Branco Filippin-Monteiro","doi":"10.1016/j.medidd.2025.100207","DOIUrl":"10.1016/j.medidd.2025.100207","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the impact of bariatric surgery on vitamin D metabolism and associated micronutrient deficiencies in individuals with obesity, emphasizing the prevalence of vitamin D deficiency in patients with severe obesity—a persistent concern after significant weight loss.</div></div><div><h3>Methods</h3><div>A comprehensive analysis of serum levels of 25(OH)D, parathyroid hormone (PTH), and calcium was conducted in patients with obesity before and after bariatric surgery, with a six-month follow-up. Medication usage was examined, and outcomes between different surgical techniques were compared.</div></div><div><h3>Results</h3><div>Notable metabolic improvements, linked to reduced BMI and diminished medication reliance post-surgery, were observed. Sleeve gastrectomy (SG) demonstrated potential advantages in preventing micronutrient deficiencies. Many patients had preoperative vitamin D deficiency and elevated PTH levels. Correlation analysis revealed that among those with preoperative PTH levels exceeding 70 pg/mL, higher PTH levels were associated with lower weight loss after six months. No significant correlation was found for vitamin D.</div></div><div><h3>Conclusion</h3><div>This study underscores the importance of critically assessing bone health in bariatric surgery candidates, emphasizing the need for meticulous preoperative evaluation and postoperative monitoring, particularly in cases of secondary hyperparathyroidism. These considerations are pivotal for optimizing the long-term well-being of bariatric surgery patients.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"26 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799703","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}
Breast cancer is one of the primary reasons for cancer-related death all around the world, and drug resistance poses a big challenge in its effective treatment. This review gives a detailed explanation regarding the complex mechanisms causing drug resistance in breast cancer, that are of two types one being intrinsic, and the other being acquired resistance. An elaborate discussion regarding hormone receptor-mediated resistance, including progesterone receptor and estrogen receptor pathways, is provided, emphasizing alterations in signaling cascades and epigenetic modifications. Similarly, the role of human epidermal growth factor receptor 2-positive breast cancer in developing resistance through mutations, receptor crosstalk, and downstream signaling disruptions is thoroughly examined. To combat multidrug resistance in breast cancer, several therapeutic strategies have been explored. This review discusses how nanotherapeutics show promise in managing drug efflux alongside enhancing drug targeting capabilities. The article discusses combination therapy strategies because they aim to combat resistance through multiple simultaneous target pathways. The application of phytochemicals represents a new approach for managing drug resistance through their natural bioactive compounds, which demonstrate anti-cancer capabilities. Understanding these molecular mechanisms and novel therapeutic interventions is essential for enhancing breast cancer outcomes and developing more effective strategies to combat resistance.
{"title":"Understanding drug resistance in breast cancer: Mechanisms and emerging therapeutic strategies","authors":"Shreastha Gautam , Rashmi Maurya , Akash Vikal , Preeti Patel , Shubham Thakur , Amandeep Singh , Ghanshyam Das Gupta , Balak Das Kurmi","doi":"10.1016/j.medidd.2025.100210","DOIUrl":"10.1016/j.medidd.2025.100210","url":null,"abstract":"<div><div>Breast cancer is one of the primary reasons for cancer-related death all around the world, and drug resistance poses a big challenge in its effective treatment. This review gives a detailed explanation regarding the complex mechanisms causing drug resistance in breast cancer, that are of two types one being intrinsic, and the other being acquired resistance. An elaborate discussion regarding hormone receptor-mediated resistance, including progesterone receptor and estrogen receptor pathways, is provided, emphasizing alterations in signaling cascades and epigenetic modifications. Similarly, the role of human epidermal growth factor receptor 2-positive breast cancer in developing resistance through mutations, receptor crosstalk, and downstream signaling disruptions is thoroughly examined. To combat multidrug resistance in breast cancer, several therapeutic strategies have been explored. This review discusses how nanotherapeutics show promise in managing drug efflux alongside enhancing drug targeting capabilities. The article discusses combination therapy strategies because they aim to combat resistance through multiple simultaneous target pathways. The application of phytochemicals represents a new approach for managing drug resistance through their natural bioactive compounds, which demonstrate anti-cancer capabilities. Understanding these molecular mechanisms and novel therapeutic interventions is essential for enhancing breast cancer outcomes and developing more effective strategies to combat resistance.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"26 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124717","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}
Nanoparticles have emerged as a promising tool in the field of drug delivery, offering targeted and controlled release of therapeutic agents. However, the increasing use of nanoparticles has raised concerns about their potential toxicity and adverse effects on human health and the environment. This review article provides a comprehensive overview of the recent approaches in nanotoxicity assessment for drug delivery applications, highlighting the challenges and future prospects in this rapidly evolving field. The article explores into the cellular and molecular mechanisms underlying nanoparticle toxicity, including oxidative stress, inflammation, genotoxicity, and neurotoxicity. The importance of nanoparticle characterization and the role of physicochemical properties, such as size, shape, surface chemistry, and composition, in determining their toxicological profile are emphasized. The article also discusses the current trends in nanotoxicity assessment, focusing on advanced in vitro and in vivo models, high-throughput screening techniques, and the use of alternative animal models, such as zebrafish and C. elegans. The regulatory landscape surrounding nanotoxicology is explored, emphasizing the need for standardized testing protocols and risk assessment frameworks. Furthermore, the article highlights the importance of a multidisciplinary approach, integrating expertise from fields such as material science, toxicology, and pharmacology, to address the complexities of nanotoxicity assessment. By providing a critical analysis of the current state of nanotoxicity research and identifying key knowledge gaps, this review article aims to guide future research efforts and contribute to the development of safer and more effective nanoparticle-based drug delivery systems.
{"title":"Recent approaches in nanotoxicity assessment for drug delivery applications: Challenges and prospects","authors":"Jithin Thomas , Vinay Kumar , Neha Sharma , Nayomi John , Mridul Umesh , Lohith Kumar Dasarahally Huligowda , Komalpreet Kaur , Divya Utreja","doi":"10.1016/j.medidd.2025.100204","DOIUrl":"10.1016/j.medidd.2025.100204","url":null,"abstract":"<div><div>Nanoparticles have emerged as a promising tool in the field of drug delivery, offering targeted and controlled release of therapeutic agents. However, the increasing use of nanoparticles has raised concerns about their potential toxicity and adverse effects on human health and the environment. This review article provides a comprehensive overview of the recent approaches in nanotoxicity assessment for drug delivery applications, highlighting the challenges and future prospects in this rapidly evolving field. The article explores into the cellular and molecular mechanisms underlying nanoparticle toxicity, including oxidative stress, inflammation, genotoxicity, and neurotoxicity. The importance of nanoparticle characterization and the role of physicochemical properties, such as size, shape, surface chemistry, and composition, in determining their toxicological profile are emphasized. The article also discusses the current trends in nanotoxicity assessment, focusing on advanced in vitro and in vivo models, high-throughput screening techniques, and the use of alternative animal models, such as zebrafish and <em>C. elegans</em>. The regulatory landscape surrounding nanotoxicology is explored, emphasizing the need for standardized testing protocols and risk assessment frameworks. Furthermore, the article highlights the importance of a multidisciplinary approach, integrating expertise from fields such as material science, toxicology, and pharmacology, to address the complexities of nanotoxicity assessment. By providing a critical analysis of the current state of nanotoxicity research and identifying key knowledge gaps, this review article aims to guide future research efforts and contribute to the development of safer and more effective nanoparticle-based drug delivery systems.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"25 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444941","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}
Pub Date : 2024-12-01Epub Date: 2024-08-22DOI: 10.1016/j.medidd.2024.100197
Girish B S Pharm.D, Nikitha B S Pharm.D, Roopa K Pharm.D, Meghana C S Pharm.D, Srinivasan R M.Pharm, PhD
GPCRs are a class of membrane proteins that are essential to signal transduction, and this is a vital process in many different physiologies. The significant mortality rate and widespread occurrence of stroke highlight the need to accelerate the research to develop viable treatment agents. A promising prospect for the development of new treatment approaches is the increasing comprehension of the pathophysiology of stroke and the crucial roles played by GPCRs. Because of the blood clot, the glial cells’ vascular supply is abruptly cut off, which sets off a series of events that include inflammation and neuronal damage and ultimately lead to cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator and urokinase, have been discovered as potential neuroprotective medicines; however, their use is restricted because of the modest therapeutic window. Accepting that GPCRs are the pertinent factors in ischemic stroke, we explore the potential medicinal promise of GPCR-targeted treatments and the shortcomings that ought to be resolved in order to translate these discoveries to clinical cases.
{"title":"Unlocking the therapeutic capabilities of GPCR in the treatment of ischemic stroke: A translational literature","authors":"Girish B S Pharm.D, Nikitha B S Pharm.D, Roopa K Pharm.D, Meghana C S Pharm.D, Srinivasan R M.Pharm, PhD","doi":"10.1016/j.medidd.2024.100197","DOIUrl":"10.1016/j.medidd.2024.100197","url":null,"abstract":"<div><p>GPCRs are a class of membrane proteins that are essential to signal transduction, and this is a vital process in many different physiologies. The significant mortality rate and widespread occurrence of stroke highlight the need to accelerate the research to develop viable treatment agents. A promising prospect for the development of new treatment approaches is the increasing comprehension of the pathophysiology of stroke and the crucial roles played by GPCRs. Because of the blood clot, the glial cells’ vascular supply is abruptly cut off, which sets off a series of events that include inflammation and neuronal damage and ultimately lead to cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator and urokinase, have been discovered as potential neuroprotective medicines; however, their use is restricted because of the modest therapeutic window. Accepting that GPCRs are the pertinent factors in ischemic stroke, we explore the potential medicinal promise of GPCR-targeted treatments and the shortcomings that ought to be resolved in order to translate these discoveries to clinical cases.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000228/pdfft?md5=7ea1babb292d6f267fc89fefc770927a&pid=1-s2.0-S2590098624000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083841","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}
Pub Date : 2024-12-01Epub Date: 2024-09-27DOI: 10.1016/j.medidd.2024.100200
Hui-juan Zhang , Kai-xuan Lin , Li-dan Fu , Francis Chanda , Abdallah Iddy Chaurembo , Jian-yuan Huang , Yun-jing Xu , Chi Shu , Ke Yang , Na Xing , Wei-bo Dai , Han-bin Lin
Dragon’s blood (Resina Draconis) is the red resin of Dracaena spp, which has a variety of biological activities and pharmacological effects, including anti-thrombotic, anti-inflammatory, anti-bacterial, analgesic, anti-oxidant, anti-tumor, and immunosuppressive. In China, the main source of dragon’s blood is Dranaena Cochinchinensis (Lour.) S.C.Chen. A wide array of studies have speculated that the dragon’s blood derived from Dranaena Cochinchinensis (Lour.) S.C.Chen possesses cardiovascular protective effects. It has been reported that Chinese dragon’s blood can potentially alleviate and treat conditions such as coronary heart disease, myocardial infarction, and myocardial ischemia–reperfusion through its anti-inflammatory and antioxidant properties, which have not been systematically stated in previous reviews. Moreover, the precise underlying pharmacological mechanisms through which the Chinese dragon’s blood exhibits cardioprotective effects are not fully understood. Therefore, this article discusses the pharmacological action and biomolecular mechanism of dragon’s blood from Dranaena Cochinchinensis (Lour.) S.C.Chen and how it prevents and protects against cardiovascular diseases. The review article concludes with prospects for further application of dragon’s blood in respect to cardiovascular diseases.
{"title":"Pharmacological effects of dragon’s blood from Dranaena cochinchinensis (Lour.) S.C. Chen and its application in cardiovascular diseases","authors":"Hui-juan Zhang , Kai-xuan Lin , Li-dan Fu , Francis Chanda , Abdallah Iddy Chaurembo , Jian-yuan Huang , Yun-jing Xu , Chi Shu , Ke Yang , Na Xing , Wei-bo Dai , Han-bin Lin","doi":"10.1016/j.medidd.2024.100200","DOIUrl":"10.1016/j.medidd.2024.100200","url":null,"abstract":"<div><div>Dragon’s blood (<em>Resina Draconis</em>) is the red resin of <em>Dracaena</em> spp, which has a variety of biological activities and pharmacological effects, including anti-thrombotic, anti-inflammatory, anti-bacterial, analgesic, anti-oxidant, anti-tumor, and immunosuppressive. In China, the main source of dragon’s blood is <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen. A wide array of studies have speculated that the dragon’s blood derived from <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen possesses cardiovascular protective effects. It has been reported that Chinese dragon’s blood can potentially alleviate and treat conditions such as coronary heart disease, myocardial infarction, and myocardial ischemia–reperfusion through its anti-inflammatory and antioxidant properties, which have not been systematically stated in previous reviews. Moreover, the precise underlying pharmacological mechanisms through which the Chinese dragon’s blood exhibits cardioprotective effects are not fully understood. Therefore, this article discusses the pharmacological action and biomolecular mechanism of dragon’s blood from <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen and how it prevents and protects against cardiovascular diseases. The review article concludes with prospects for further application of dragon’s blood in respect to cardiovascular diseases.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421143","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}
Pub Date : 2024-12-01Epub Date: 2024-10-10DOI: 10.1016/j.medidd.2024.100202
Sanjida Mir , Ryan J. Keenan , Romke Bron , Cameron J. Nowell , Catriona McLean , Leah C. Beauchamp , Laura J. Vella , Brian Dean , Daniel Hoyer , Laura H. Jacobson
Hypocretin (Hcrtr, HCRTR) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of Hcrtr1/HCRTR1 and Hcrtr2/HCRTR2 mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of Hcrtr1 mRNA was in the locus coeruleus (LC) whereas Hcrtr2 mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both HCRTR1 and HCRTR2 mRNA, whereas the mouse predominantly expressed Hcrtr2 mRNA. The noradrenergic neurons of the human LC showed high signals for both HCRTR1 (71.7%) and HCRTR2 (81.5%) mRNA. Expression of HCRTR2 mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected.
{"title":"The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain","authors":"Sanjida Mir , Ryan J. Keenan , Romke Bron , Cameron J. Nowell , Catriona McLean , Leah C. Beauchamp , Laura J. Vella , Brian Dean , Daniel Hoyer , Laura H. Jacobson","doi":"10.1016/j.medidd.2024.100202","DOIUrl":"10.1016/j.medidd.2024.100202","url":null,"abstract":"<div><div>Hypocretin (<em>Hcrtr, HCRTR</em>) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of <em>Hcrtr1/HCRTR1</em> and <em>Hcrtr2/HCRTR2</em> mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of <em>Hcrtr1</em> mRNA was in the locus coeruleus (LC) whereas <em>Hcrtr2</em> mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both <em>HCRTR1</em> and <em>HCRTR2</em> mRNA, whereas the mouse predominantly expressed <em>Hcrtr2</em> mRNA. The noradrenergic neurons of the human LC showed high signals for both <em>HCRTR1</em> (71.7%) and <em>HCRTR2</em> (81.5%) mRNA. Expression of <em>HCRTR2</em> mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554117","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}
Pub Date : 2024-12-01Epub Date: 2024-10-10DOI: 10.1016/j.medidd.2024.100201
Wenqin Xie , Jinglin Lai , Hongmin Cai , H. Eric Xu , Wanchao Yin
G protein-coupled receptors (GPCRs) constitute a diverse and extensive array of cell surface receptors, rendering them essential targets for drugs aimed at various human diseases. Responding to a range of extracellular or intracellular cues, GPCRs regulate cellular signaling through downstream transducers such as heterotrimer G proteins, GPCR kinases (GRKs), and arrestins. The wealth of 3D structures available for GPCRs and their signaling complexes significantly enhances our understanding of GPCR biology and expedites the development of structure-based drug discovery methods aimed at GPCR signaling. While the structural exploration of GPCR-G protein complexes has advanced, recent years have seen substantial breakthroughs in unraveling the mechanism behind arrestin-mediated GPCR signaling. This review aims to explore emerging insights into arrestin activation and its interaction with GPCRs, shedding light on the various ways GPCRs engage with arrestins both conservatively and diversely. Additionally, we summarize recent endeavors focused on designing functionally selective (’biased’) ligands targeting GPCRs, with desired effects on/off arrestin signaling. Our goal with this review is to spotlight studies investigating the structural aspects of GPCR activation and arrestin-binding modes, with a specific emphasis on arrestin-mediated GPCR signaling.
{"title":"Structural features of arrestin-mediated GPCR signaling","authors":"Wenqin Xie , Jinglin Lai , Hongmin Cai , H. Eric Xu , Wanchao Yin","doi":"10.1016/j.medidd.2024.100201","DOIUrl":"10.1016/j.medidd.2024.100201","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) constitute a diverse and extensive array of cell surface receptors, rendering them essential targets for drugs aimed at various human diseases. Responding to a range of extracellular or intracellular cues, GPCRs regulate cellular signaling through downstream transducers such as heterotrimer G proteins, GPCR kinases (GRKs), and arrestins. The wealth of 3D structures available for GPCRs and their signaling complexes significantly enhances our understanding of GPCR biology and expedites the development of structure-based drug discovery methods aimed at GPCR signaling. While the structural exploration of GPCR-G protein complexes has advanced, recent years have seen substantial breakthroughs in unraveling the mechanism behind arrestin-mediated GPCR signaling. This review aims to explore emerging insights into arrestin activation and its interaction with GPCRs, shedding light on the various ways GPCRs engage with arrestins both conservatively and diversely. Additionally, we summarize recent endeavors focused on designing functionally selective (’biased’) ligands targeting GPCRs, with desired effects on/off arrestin signaling. Our goal with this review is to spotlight studies investigating the structural aspects of GPCR activation and arrestin-binding modes, with a specific emphasis on arrestin-mediated GPCR signaling.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445054","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号