Discovery medicine最新文献

{"title":"Construction of a Multi-View Deep Learning Model for the Severity Classification of Acute Pancreatitis.","authors":"Kailai Xiang, Dong Shang","doi":"10.24976/Discov.Med.202537192.7","DOIUrl":"https://doi.org/10.24976/Discov.Med.202537192.7","url":null,"abstract":"<p><strong>Background: </strong>Acute pancreatitis (AP) is a prevalent pathological condition of abdomen characterized by sudden onset, high incidence and complex progression. Timely assessment of AP severity is crucial for informing intervention decisions so as to delay deterioration and reduce mortality rates. Existing AP-related scoring systems can only assess current condition of patients and utilize only a single type of clinical data, which is of great limitation. Therefore, it is imperative to establish more accurate and data-compatible methods for predicting the severity of AP. The artificial intelligence (AI) algorithm based on artificial neural network (ANN) allow for the adaptive feature extraction for objective task through its internal complex network, instead of the hand-crafted methods commonly used in traditional machine learning (ML) algorithms. In this study, we delve into the final severity classification prediction of newly admitted AP patients, using deep learning (DL) algorithm to develop multi-view models, incorporated with patients' demographic information, vital signs, AP-related laboratory indexes and admission computed tomography (CT) images.</p><p><strong>Methods: </strong>The pancreatitis database in the platform of Clinical Data Research Center of Acute Abdominal Surgery at the First Affiliated Hospital of Dalian Medical University was used to gather AP cases. Deep neural network (DNN) and convolutional neural network (CNN) were utilized to construct models. The DNN prediction models with clinical data as input, the CNN prediction models with admission CT as input, and the multi-view models combining the two inputs were respectively established to predict the severity of AP.</p><p><strong>Results: </strong>DL models for AP severity classification based on clinical indexes, imaging data and merged data were constructed. The multi-view model based on merged data offered more accurate prediction of the final severity classification of AP, with an overall accuracy rate of 80.26% (95% confidence interval (CI): 79.58%-80.94%). The constituent accuracy rates for mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis were 91.69% (95% CI: 87.80%-95.57%), 64.90% (95% CI: 58.85%-70.95%), and 75.56% (95% CI: 68.58%-82.53%), respectively.</p><p><strong>Conclusion: </strong>The multi-view models using clinical indexes and imaging data as input outperform single-view models in AP severity prediction.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"37 192","pages":"73-92"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Application of a Big Data Machine Learning Analysis Model for Osteoporotic Fracture Risk Assessment Built on Multicenter Clinical Data in Qingdao City.","authors":"Bing Li, Yanru Yang, Feng Shen, Yuelei Wang, Ting Wang, Xiaxia Chen, Chun Lu","doi":"10.24976/Discov.Med.202537192.5","DOIUrl":"https://doi.org/10.24976/Discov.Med.202537192.5","url":null,"abstract":"<p><strong>Background: </strong>Osteoporotic fractures (OPF) pose a public health issue, imposing significant burdens on families and societies worldwide. Currently, there is a lack of comprehensive and validated risk assessment models for OPF. This study aims to develop a model to assess and predict the risk of OPF in Qingdao City, China.</p><p><strong>Methods: </strong>From January 2021 to January 2023, we recruited 84 osteoporotic patients diagnosed with fractures from Qingdao University Affiliated Hospital, Qingdao Municipal Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, and Qingdao Central Hospital as the experimental group. In addition, 112 osteoporotic patients without fractures were recruited as the control group. In this study, we employed seven machine learning models, namely Adaboost, random forest (RF), K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Naive Bayes (NB), and Gradient Boosting Decision Trees (GBDT), to analyze the risk factors influencing the occurrence of OPF. Next, we plotted receiver operating characteristic (ROC), Precision-Recall (PR), and calibration curves to evaluate the predictive values of the different risk assessment models for OPF.</p><p><strong>Results: </strong>Among the seven models built based on the training set data, the Adaboost model showed area under the curve (AUC), sensitivity, and specificity values close to 1, indicating the best classification performance. In the test set, the AUC values for the RF, SVM, LR, KNN, NB, AdaBoost, and GBDT models were 0.936, 0.905, 0.88, 0.93, 0.862, 0.939, and 0.859, respectively (<i>p</i> < 0.001). All sensitivity and specificity values for these models were higher than 0.8, with sensitivity and specificity values of the Adaboost model closest to 1. Additionally, six models had an area under the Precision-Recall curve (prAUC) values higher than 0.9, except KNN at 0.284 (<i>p</i> < 0.001). The calibration curves of the seven models did not significantly deviate from the ideal curve, indicating acceptable discriminative ability and predictive performance of the predictive model. All results showed that trabecular bone score (TBS) was the most important variable affecting the model, followed by osteocalcin (OST) and hunchback.</p><p><strong>Conclusions: </strong>Given the various clinical data from patients with OPF, we assessed and demonstrated the good predictive performance of our risk predictive models. This model will enable us to take timely intervention measures to reduce the incidence of OPF and improve patient prognosis.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"37 192","pages":"55-63"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated Amphetamine Exposure Blunted Angiotensin II-Induced Responses Mediated by AT₁ Receptors.","authors":"Brenda Solange Casarsa, Victoria Belén Occhieppo, María Josefina Piermarini, Osvaldo Martín Basmadjian, Gustavo Baiardi, Claudia Bregonzio","doi":"10.24976/Discov.Med.202537192.9","DOIUrl":"https://doi.org/10.24976/Discov.Med.202537192.9","url":null,"abstract":"<p><strong>Background: </strong>Angiotensin II, is critical in regulating the sympathetic and neuroendocrine systems through angiotensin II type 1 receptors (AT₁-R). Angiotensin II intracerebral administration increases water and sodium intake, as well as renal sodium excretion. Previously, our group has shown that AT₁-R is involved in behavioral and neurochemical sensitization induced by amphetamine. We aimed to assess the physiological output, behavioral, and neurochemical responses to intracerebral angiotensin II administration, via the AT₁-R, twenty-one days after amphetamine administration.</p><p><strong>Material and methods: </strong>Male Wistar rats received daily vehicle or AT₁-R antagonist (oral) for 10 days, and amphetamine or saline intraperitoneal (i.p.) from day 6 to 10. On day 25 they were implanted with an intracerebral cannula. On day 32, the animals received intracerebral angiotensin II. First group: the animals were tested in a free choice paradigm for 2% NaCl and water intake, and sacrificed for neuronal activity assessment via c-Fos immunohistochemistry. Second group: urine samples were collected for electrolyte determination. Third group: the animals were tested in the plus maze or the hole board for anxiety and working memory evaluation, respectively, and sacrificed for c-Fos immunohistochemistry.</p><p><strong>Results: </strong>Amphetamine exposure blunted the increase in sodium intake (<i>p</i> = 0.0022), and potentiated the natriuretic (<i>p</i> = 0.0043) and kaliuretic effect (<i>p</i> = 0.0002) induced by angiotensin II. Moreover, amphetamine exposure prevented the expression of the anxiogenic effect (drug effect <i>p</i> < 0.0001) and the memory deficit (<i>p</i> = 0.1314) induced by cerebral angiotensin II administration. Amph decreased c-Fos immunoreactivity in nucleus tractus solitarii (NTS) <i>p</i> = 0.0037; paraventricular nucleus (PVN) <i>p</i> = 0.0047; Central amygdala (CeA) <i>p</i> = 0.0008; Basolateral amygdala (BLA) <i>p</i> = 0.0018; increased in hippocampus region CA1 <i>p</i> = 0.0043; CA3 <i>p</i> = 0.026; and dentate gyrus (DG) <i>p</i> = 0.0057. The blockade of AT₁-R prevented these alterations (sodium intake <i>p</i> = 0.0421 natriuresis <i>p</i> = 0.019; kaliuresis <i>p</i> = 0.196; working memory (<i>p</i> < 0.0001); but no the anxiogenic response to angiotensin II (drug effect <i>p</i> < 0.0001); as well as the c-Fos changes (NTS <i>p</i> = 0.0052; PVN <i>p</i> = 0.029; CeA <i>p</i> = 0.0002; BLA <i>p</i> = 0.0021; CA1 <i>p</i> = 0.0026; CA3 <i>p</i> = 0.022; and DG <i>p</i> = 0.0016).</p><p><strong>Conclusion: </strong>Most of the long-lasting AT₁-R altered responses to brain angiotensin II administration induced by repeated amphetamine exposure could be prevented by AT₁-R blockade.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"37 192","pages":"103-116"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Risk Factors Associated with Organic Erectile Dysfunction in Patients with Type 2 Diabetes Mellitus and Erectile Dysfunction.","authors":"Mingming Lu, Dawei Ni, Wei Wu, Chi Xu, Yanbin Zhang","doi":"10.24976/Discov.Med.202537192.12","DOIUrl":"https://doi.org/10.24976/Discov.Med.202537192.12","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is a common metabolic disorder, and diabetic erectile dysfunction (DMED) is one of its common complications. The differentiation of the types of erectile dysfunction (ED) is fundamental to treatment, yet there is a lack of simple and efficacious tools for this purpose in clinical practice. In this study, we endeavor to predict ED types using commonly available clinical data from diabetic patients, aiming to develop and assess a risk prediction model for organic erectile dysfunction in individuals with type 2 diabetes.</p><p><strong>Methods: </strong>The study was a retrospective analysis. Data were obtained from the hospital's internal medical record system. We selected and analyzed the clinical data of 250 patients with type 2 diabetes. Lasso regression was used for risk factor selection, and the selected variables were included in a multivariate logistic regression analysis to establish the risk prediction model. Internal validation was performed using the bootstrap method, and the discrimination, calibration, and clinical effectiveness of the model were evaluated using the C-index, calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>Among the 250 patients, 168 (67.2%) were diagnosed with organic ED. The risk factors included in the logistic regression analysis were the duration of diabetes, low-density lipoprotein cholesterol (LDL-C), red blood cell distribution width (RDW), intima-media thickness of the carotid artery, diabetic retinopathy, diabetic nephropathy, and peripheral neuropathy. The C-index was 0.827 (95% confidence interval (CI) = 0.772-0.882). The distribution curve of the predicted values and the calibration curve of the model were well fitted. The decision curve analysis (DCA) suggested that using the model could be clinically beneficial when the threshold probability was between 28% and 100%.</p><p><strong>Conclusion: </strong>By combining the duration of diabetes, carotid artery intima-media thickness, diabetic retinopathy, diabetic nephropathy, peripheral neuropathy, RDW, and LDL-C, this study preliminarily establishes a risk prediction model for organic ED in patients with type 2 diabetes mellitus. The model demonstrates good predictive performance.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"37 192","pages":"141-151"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting LncRNA <i>ADAMTS9-AS1</i> is a Promising Therapeutic Strategy to Inhibit the Progression of Bladder Cancer.","authors":"Zhu Yu, Gongxiang Tan, Chunyan Yu, Yamei Chen, Huijie Zheng, Wenfang Xu, Mingzhu Yu","doi":"10.24976/Discov.Med.202436191.226","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436191.226","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is a malignant tumor that begins in the cells of the bladder, characterized by poor cell differentiation and strong invasion capacity, with a high incidence rate. Identifying key molecules that enhance BC cells' cisplatin sensitivity can help improve the clinical efficacy of BC treatment. Hence, this study aimed to determine the expression level of long non-coding RNA (lncRNA) ADAM Metallopeptidase with Thrombospondin Type 1 Motif 9 Antisense RNA 1 (<i>ADAMTS9-AS1</i>) in BC and explore its related mechanism underlying the amplification of cisplatin sensitivity.</p><p><strong>Methods: </strong>Cancer tissues and para-cancerous tissues of 10 BC patients treated in The 908th Hospital of Joint Logistic Support Force of PLA were collected retrospectively and analyzed for the expression of the lncRNA <i>ADAMTS9-AS1</i> and fused in sarcoma (<i>FUS</i>) in this tissue. Normal bladder epithelial cell line SV-HUC1, and BC cell lines such as T24, J82, 5637, KU-19-19, and EJ were cultured for <i>in vitro</i> experimentation. Then, the expression levels of <i>ADAMTS9-AS1</i>, <i>FUS</i> mRNA, and FUS protein were detected by means of reverse-transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry. pcDNA3.1 vector, pcDNA3.1-ADAMTS9-AS1, or pcDNA3.1-ADAMTS9-AS1 and <i>FUS</i> overexpression plasmid was transfected into the cultured T24 and 5637 cells. A series of tests were performed to detect cell proliferation, migration capacity, apoptosis, and cisplatin half-effective concentration (IC50) values of BC cells using Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound healing assay, flow cytometry, and gradient cisplatin culturation.</p><p><strong>Results: </strong>Compared with SV-HUC1 cell line and adjacent normal tissues, <i>ADAMTS9-AS1</i> levels were significantly decreased in T24, J82, 5637, KU-19-19, EJ cell lines, and BC tissues, while <i>FUS</i> mRNA and protein expression levels were up-regulated (<i>p</i> < 0.05). After transfection with pcDNA3.1-ADAMTS9-AS1, the colony number, cell viability, wound healing ratio, and cisplatin IC50 value, were remarkably reduced (<i>p</i> < 0.05), but apoptosis ratio, cleaved-caspase3 and cleaved-poly-ADP-ribose polymerases (<i>PARP</i>) expressions were increased (<i>p</i> < 0.05). <i>ADAMTS9-AS1</i> was found to directly target <i>FUS</i>, and overexpression of <i>FUS</i> reversed <i>ADAMTS9-AS1</i> effects on BC cells.</p><p><strong>Conclusions: </strong><i>ASAMTS9-AS1</i> can inhibit the proliferation and migration, and promote apoptosis and cisplatin sensitivity of BC cells through regulating <i>FUS</i>, thus providing a theoretical basis for <i>ADAMTS9-AS1</i> as a potential therapeutic target in BC treatment.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2454-2464"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Interleukin-17A Regulation of Mesenchymal Stroma/Stem Cell Osteogenic Differentiation.","authors":"Juan F Santibanez","doi":"10.24976/Discov.Med.202436191.216","DOIUrl":"10.24976/Discov.Med.202436191.216","url":null,"abstract":"<p><p>The immune and musculoskeletal systems closely interplay in bone repair and regeneration. After bone injury, the body produces high levels of cytokines and signaling molecules to balance bone formation and resorption. Interleukin (IL)-17A, a cytokine expressed early in the inflammatory process, profoundly influences osteoprogenitor cell fate, thereby contributing to bone homeostasis. In addition, mesenchymal stromal/stem cells (MSCs) can differentiate into osteoblasts, contributing to bone repair and regeneration. Although IL-17A can influence MSCs to become early osteoprogenitor cells, it also can inhibit bone formation. However, the reasons for these dual roles are not yet fully understood. This review overviews IL-17A signaling and the mechanisms that govern MSCs' osteogenic differentiation and summarizes relevant data from the literature on IL-17A's pro- and anti-osteogenic roles.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2343-2355"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Cortaderia selloana</i> or the Disregarded Impact of Worldwide Expanding Plant Invasions on Human Health.","authors":"María Lucas, Alberto Gandarillas","doi":"10.24976/Discov.Med.202436191.228","DOIUrl":"10.24976/Discov.Med.202436191.228","url":null,"abstract":"<p><p>Invasive alien plant species (IAPS) are well known to disrupt biodiversity, natural ecosystems, and infrastructures, resulting in a significant worldwide economic cost. However, the impact of IAPS on human health has been generally disregarded, despite a significant potential risk. Currently, due to new evidence and the concept of <i>One Health</i>, this concern is gaining strength. The spread of invasive plants at a global scale can profoundly affect human health through pollen and toxin production. Allergic respiratory diseases caused by pollen are likely the primary risks posed by IAPS. Because of the frequent invasion of populated areas and their different pollination period throughout the year, IAPS might further contribute to the current striking increase in allergies. Respiratory allergies significantly affect the quality of life of patients, along with associated economic impacts. In this study, we focus on a paradigmatic IAPS that is invading considerable areas of the globe, <i>Cortaderia selloana</i> (Pampas grass), to illustrate the increasing and widely disregarded human health risk posed by IAPS. Our aim is to raise awareness of the IAPS concern among the medical community and health policymakers, suggesting rapid action to address associated concerns.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2468-2474"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Control of Parasitic Diseases through Local Narratives: Lessons from Thailand and Laos.","authors":"Francesco Branda, Krishna Prasad Acharya, Sarita Phuyal, Giancarlo Ceccarelli","doi":"10.24976/Discov.Med.202436191.227","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436191.227","url":null,"abstract":"<p><p>In recent decades, technological advancements and scientific progress have significantly improved disease control strategies. However, the exclusive focus on these aspects often overlooks the crucial role of social and cultural factors. Local narratives, reflecting community traditions and beliefs, offer valuable insights that can influence the success of public health interventions. Case studies, such as fascioliasis control in Thailand and <i>Schistosoma mekongi</i> infection in Laos, demonstrate the importance of integrating local stories into health programs. These examples highlight the effectiveness of a holistic approach that considers biological, ecological, social, and cultural dynamics, aligned with the \"One Health\" framework. Incorporating local knowledge into disease control interventions is essential for sustainability and long-term success.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2465-2467"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncommon but Significant: Onset, Characteristics and Management of Vasculitis and Connective Tissue Diseases Induced by Immunomodulators during Cancer Treatment.","authors":"Caterina Gagliano, Roberta Foti, Elisa Visalli, Edoardo Dammino, Antonino Maniaci, Riccardo Foti, Dalila Incognito, Rosario Foti, Marco Zeppieri","doi":"10.24976/Discov.Med.202436191.215","DOIUrl":"10.24976/Discov.Med.202436191.215","url":null,"abstract":"<p><p>The introduction of immunomodulators as adjuvant therapies in cancer treatment has represented a significant advancement in oncology, improving therapeutic response and patient survival. Emerging targets and molecules could provide new therapeutic opportunities for cancer patients. However, these agents can induce immunological side effects, including vasculitis and connective tissue diseases, which, while uncommon, present significant clinical challenges. This review analyzes the prevalence, clinical characteristics, therapeutic strategies, and management difficulties of vasculitis and connective tissue disorders triggered by immunomodulators in the context of cancer treatment. Although rare, these conditions significantly impact patients, demanding thorough management. Common rheumatological immune-related adverse events include inflammatory arthritis, Sjogren's disease, systemic lupus erythematosus, and systemic sclerosis, all of which require prompt recognition and appropriate intervention. Treatment frequently includes corticosteroids and immunosuppressive drugs, with new alternatives currently accessible. Efficient coordination between oncologists and rheumatologists enhances patient outcomes, highlighting the necessity for organized multidisciplinary strategies. Future research initiatives emphasize the identification of biomarkers for early diagnosis and the development of preventive methods to reduce immune-related adverse events in cancer therapy.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2333-2342"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Perspective for Improving COPD: Ginsenoside Rg3 Links SIRT1 to Inhibit Mitochondrial Autophagy.","authors":"Yuanyuan Wang, Nianzhi Zhang, Feng Liu, Jing Zhou, Gang Teng, He Huang","doi":"10.24976/Discov.Med.202436191.220","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436191.220","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic obstructive pulmonary disease (COPD) is a prevalent yet manageable respiratory condition. However, treatments presently used normally have side effects and cannot cure COPD, making it urgent to explore effective medications. The ginsenoside Rg3 (Rg3) has been shown to have anti-inflammatory and anti-tumor properties and can improve COPD. The primary objectives of this investigation were to explore the impact of Rg3 on COPD and delve into the associated mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; models exposed human bronchial epithelial cells (BEAS-2B) to cigarette smoke extract (CSE), and &lt;i&gt;in vivo&lt;/i&gt; models induced COPD in mice through chronic inhalation of cigarette smoke (CS). Sirtuin 1 (SIRT1) expression was regulated via cell transfection or mice infection with recombinant lentiviruses. &lt;i&gt;SIRT1&lt;/i&gt; mRNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and SIRT protein levels were assessed by western blot or enzyme-linked immunosorbent assays (ELISA). Mitophagy was evaluated by light chain 3 (LC3) II/I and phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) levels, and apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Lung function was measured with the Buxco system, and inflammation was assessed via interleukin 6 (IL-6) and keratinocyte-derived cytokine (KC) levels in bronchial alveolar lavage fluid. Lung morphological impairments were determined through Hematoxylin and Eosin (H&E) staining and mean linear intercept (MLI) measurement.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In BEAS-2B cells, CSE treatment caused a decrease in SIRT1 expression (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) and an increase in LC3 II/I (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) and PINK1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), which were all reversed by Rg3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), with 20 μM Rg3 performing the best and being used subsequently. CSE increased apoptosis of BEAS-2B cells (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), which was reversed by Rg3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Upregulated SIRT1 further decreased levels of LC3 II/I (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), PINK1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), and cell apoptosis (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) for CSE- and Rg3-treated cells, whereas downregulated SIRT1 reversely increased levels of LC3 II/I (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), PINK1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), and cell apoptosis (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). The establishment of COPD caused a decrease in SIRT1 mRNA (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), SIRT1 protein (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), and lung functions (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) whereas IL-6 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), KC (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), lung impairment, and MLI (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) were increased; all of these effects were reversed by Rg3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Moreover, the Rg3-induced reversion was furthered by SIRT1 upregulation (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and was disrupted by SIRT1 downregulation (&lt;i&gt;p&lt;/i&gt; &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Rg3, through activation of SIRT1, suppresses mitophagy and apoptosis, ameliorates COPD, and improve","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 191","pages":"2386-2398"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901323","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}