MedCommPub Date : 2025-03-24DOI: 10.1002/mco2.70144
Yanqing Wu, Ting Li, Xingjun Jiang, Jianmin Ling, Zaihua Zhao, Jiahui Zhu, Chongyang Chen, Qian Liu, Xifei Yang, Xuefeng Shen, Rong Ma, Gang Li, Gongping Liu
{"title":"(−)-Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies","authors":"Yanqing Wu, Ting Li, Xingjun Jiang, Jianmin Ling, Zaihua Zhao, Jiahui Zhu, Chongyang Chen, Qian Liu, Xifei Yang, Xuefeng Shen, Rong Ma, Gang Li, Gongping Liu","doi":"10.1002/mco2.70144","DOIUrl":"https://doi.org/10.1002/mco2.70144","url":null,"abstract":"<p>In tauopathies, defects in autophagy-lysosomal protein degradation are thought to contribute to the abnormal accumulation of aggregated tau. Recent studies have shown that (−)-Epicatechin (Epi), a dietary flavonoid belonging to the flavan-3-ol subgroup, improves blood flow, modulates metabolic profiles, and prevents oxidative damage. However, less research has explored the effects of Epi on tauopathies. Here, we found that Epi rescued cognitive deficits in P301S tau transgenic mice, a model exhibiting characteristics of tauopathies like frontotemporal dementia and Alzheimer's disease, and attenuated tau pathology through autophagy activation. Proteomic and biochemical analyses revealed that P301S mice exhibit deficits in autophagosome formation via modulating mTOR, consequently inhibiting autophagy. Epi inhibited the mTOR signaling pathway to promote autophagosome formation, which is essential for the clearance of tau aggregation. By using chloroquine (CQ) to inhibit autophagy in vivo, we further confirmed that Epi induced tau degradation via the autophagy pathway. Lastly, Epi administration was also found to improve cognition by reversing spine decrease and neuron loss, as well as attenuating neuroinflammation. Our findings suggest that Epi promoted tau clearance by activating autophagy, indicating its potential as a promising therapeutic candidate for tauopathies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689976","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}
MedCommPub Date : 2025-03-24DOI: 10.1002/mco2.70146
Hong Lei, Aqu Alu, Jingyun Yang, Cai He, Jie Shi, Weiqi Hong, Dandan Peng, Yu Zhang, Jian Liu, Furong Qin, Xiya Huang, Chunjun Ye, Lijiao Pei, Xuemei He, Hong Yan, Guangwen Lu, Xiangrong Song, Xiawei Wei, Yuquan Wei
{"title":"Intranasal Inoculation of Cationic Crosslinked Carbon Dots-Adjuvanted Respiratory Syncytial Virus F Subunit Vaccine Elicits Mucosal and Systemic Humoral and Cellular Immunity","authors":"Hong Lei, Aqu Alu, Jingyun Yang, Cai He, Jie Shi, Weiqi Hong, Dandan Peng, Yu Zhang, Jian Liu, Furong Qin, Xiya Huang, Chunjun Ye, Lijiao Pei, Xuemei He, Hong Yan, Guangwen Lu, Xiangrong Song, Xiawei Wei, Yuquan Wei","doi":"10.1002/mco2.70146","DOIUrl":"https://doi.org/10.1002/mco2.70146","url":null,"abstract":"<p>Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract infections, especially in infants and the elderly. Developing an RSV vaccine that promotes a robust mucosal immune response is necessary to successfully prevent viral transmission and the development of severe disease. We previously reported that crosslinked carbon dots (CCD) may be an excellent adjuvant candidate for intranasal (IN) protein subunit vaccines. Considering the strong immunogenicity of RSV prefused F protein (preF), we prepared an IN RSV vaccine composed of the CCD adjuvant and the preF protein as antigen (CCD/preF) and evaluated the induced antigen-specific humoral and cellular immunity. We found that IN immunization with the CCD/preF vaccine elicited strong serum IgG responses and mucosal immunity, including secreted IgA antibodies, tissue-resident memory T (T<sub>RM</sub>) cells, and antigen-specific B cells, which lasted for at least 1 year. In addition, a combination of intramuscular and IN immunization with CCD/preF vaccine induced stronger systemic and mucosal immunity. Together, this study proved the high immunogenicity of the CCD/preF vaccines and supported the university of the mucosal CCD adjuvant, supporting further development of the CCD/preF vaccine in larger animal models and clinical studies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689877","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}
MedCommPub Date : 2025-03-24DOI: 10.1002/mco2.70133
Youmin Zhu, Yu Dai, Yuncai Tian
{"title":"The Peptide PROTAC Modality: A New Strategy for Drug Discovery","authors":"Youmin Zhu, Yu Dai, Yuncai Tian","doi":"10.1002/mco2.70133","DOIUrl":"https://doi.org/10.1002/mco2.70133","url":null,"abstract":"<p>In recent years, proteolysis targeting chimera (PROTAC) technology has made significant progress in the field of drug development. Traditional drugs mainly focus on inhibiting or activating specific proteins, while PROTAC technology provides new ideas for treating various diseases by inducing the degradation of target proteins. Especially for peptide PROTACs, due to their unique structural and functional characteristics, they have become a hot research topic. This review provides a detailed description of the key components, mechanisms, and design principles of peptide PROTACs, elaborates on their applications in skin-related diseases, oncology, and other potential therapeutic fields, analyzes their advantages and challenges, and looks forward to their future development prospects. The development of peptide PROTAC technology not only opens up new paths for drug research and development, but also provides new ideas for solving the resistance and safety issues faced by traditional small-molecule drugs. Compared with small-molecule PROTACs, peptide PROTACs have advantages such as multitargeting, biodegradability, low toxicity, and flexibility in structural design. With the deepening of research and the continuous maturity of technology, peptide PROTACs are expected to become one of the important strategies for future drug discovery, providing new hope for the treatment of more intractable diseases. Peptide PROTACs are ushering in a new era of precision medicine.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689967","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}
MedCommPub Date : 2025-03-22DOI: 10.1002/mco2.70113
Zhengyuan Liu, Junnan Xu, Xing Wang
{"title":"Bioactive hemostatic materials: a new strategy for promoting wound healing and tissue regeneration","authors":"Zhengyuan Liu, Junnan Xu, Xing Wang","doi":"10.1002/mco2.70113","DOIUrl":"https://doi.org/10.1002/mco2.70113","url":null,"abstract":"<p>Wound healing remains a critical global healthcare challenge, with an annual treatment cost exceeding $50 billion worldwide. Over the past decade, significant advances in wound care have focused on developing sophisticated biomaterials that promote tissue regeneration and prevent complications. Despite these developments, there remains a crucial need for multifunctional wound healing materials that can effectively address the complex, multiphase nature of wound repair while being cost effective and easily applicable in various clinical settings. This review systematically analyzes the latest developments in wound healing materials, examining their chemical composition, structural design, and therapeutic mechanisms. We comprehensively evaluate various bioactive components, including natural polymers, synthetic matrices, and hybrid composites, along with their different forms, such as hydrogels, powders, and smart dressings. Special attention is given to emerging strategies in material design that integrate multiple therapeutic functions, including sustained drug delivery, infection prevention, and tissue regeneration promotion. The insights provided in this review illuminate the path toward next-generation wound healing materials, highlighting opportunities for developing more effective therapeutic solutions that can significantly improve patient outcomes and reduce healthcare burden.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689420","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}
{"title":"Integrated Analysis of the Anoikis-Related Signature Identifies Rac Family Small GTPase 3 as a Novel Tumor-Promoter Gene in Hepatocellular Carcinoma","authors":"Dong Wu, Ze-Kun Liu, Ying Sun, Chu-Heng Gou, Run-Ze Shang, Meng Lu, Ren-Yu Zhang, Hao-Lin Wei, Can Li, Ying Shi, Cong Zhang, Yu-Tong Wang, Ding Wei, Zhi-Nan Chen, Huijie Bian","doi":"10.1002/mco2.70125","DOIUrl":"https://doi.org/10.1002/mco2.70125","url":null,"abstract":"<p>Anoikis resistance in hepatocellular carcinoma (HCC) cells boosts survival and metastasis. This study aimed to establish an anoikis-related genes (ARGs)-based model for predicting HCC patients’ outcomes and investigate the clinicopathological significance and function of crucial ARGs. The transcriptional expression patterns for HCC cohorts were compiled from TCGA, GEO and ICGC. Univariate and LASSO multivariate analyses were performed to screen for prognostic ARGs. Gain- and loss-of-function studies, RNA sequencing, and mass spectrometry were employed to elucidate the underlying mechanisms of ARGs in HCC. We established a five-gene ARGs risk model for HCC prognosis, with an AUC value of 0.812 for 1-year survival. Among the five genes, Rac family small GTPase 3 (RAC3) was upregulated in HCC relative to adjacent normal tissues and negatively correlated to overall survival and disease-free survival of patients with HCC. Silence of RAC3 in HCC cells resulted in an increased cell apoptosis and diminished cell proliferation and invasion. Mechanistically, we uncovered that RAC3 binding with SOX6 propelled the advancement of HCC cells through NNMT-mediated stimulation of the cAMP/MAPK/Rap1 signaling. In particular, EHop-016, a small molecule inhibitor targeting RAC3, significantly suppressed HCC progression.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689366","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}
{"title":"ATP11B Modulates Microglial Lipid Metabolism and Alleviates Alzheimer's Disease Pathology","authors":"Yuchen Zhang, Shibo Zhang, Xuyu Zhao, Peiru Wu, Yiwei Ying, Lingling Wu, Junyi Zhuang, Zixin Chen, Yufan Chao, Xin Dong, Robert Chunhua Zhao, Jiao Wang","doi":"10.1002/mco2.70139","DOIUrl":"https://doi.org/10.1002/mco2.70139","url":null,"abstract":"<p>Abnormal lipid metabolism in microglia leads to the formation of pathological lipid droplets (LDs), a phenomenon also observed in neurodegenerative diseases such as Alzheimer's disease (AD). The abnormal accumulation of LDs disrupts normal cellular function and exacerbates the pathological process of AD. ATP11B is a P4-ATPase and the expression of <i>Atp11b</i> changes in the brain of patients with AD and diseases of lipid metabolism. The present study aimed to explore the regulatory role of ATP11B in microglial lipid metabolism and assess the potential of ATP11B as a therapeutic target for AD. <i>Atp11b</i> deficiency caused excessive fatty acid uptake and activated the PPAR signaling pathway, resulting in abnormal synthesis of neutral lipids and mitochondrial energy metabolism in microglia. Further results showed that <i>Atp11b</i> deficiency led to the accumulation of pathological LDs in microglia and AD mice. Conversely, overexpression of <i>Atp11b</i> alleviated exploratory behavior impairment, learning and memory impairment, LD accumulation, beta-amyloid (Aβ) deposition, and inflammatory response in the brain of AD mice. These findings provide important clues for a better understanding of the pathogenesis of AD and for developing novel therapeutic strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689367","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}
MedCommPub Date : 2025-03-20DOI: 10.1002/mco2.70143
Yang Liu, Yaqian Han, Mei Feng, Ye Zhang, Kai Wang, Yuan Qu, Xuesong Chen, Jianghu Zhang, Jingwei Luo, Runye Wu, Ye-Xiong Li, Xiaodong Huang, Qiuyan Chen, Jingbo Wang, Junlin Yi
{"title":"Subsequent Survival and Loss of Lifetime for Patients With Progression-Free 24 Months After Treatment in Nasopharyngeal Carcinoma: A Comprehensive Nationwide Population-Based Analysis","authors":"Yang Liu, Yaqian Han, Mei Feng, Ye Zhang, Kai Wang, Yuan Qu, Xuesong Chen, Jianghu Zhang, Jingwei Luo, Runye Wu, Ye-Xiong Li, Xiaodong Huang, Qiuyan Chen, Jingbo Wang, Junlin Yi","doi":"10.1002/mco2.70143","DOIUrl":"10.1002/mco2.70143","url":null,"abstract":"<p>Currently, there is little evidence supporting the use of early endpoints to assess primary treatment outcomes in nasopharyngeal carcinoma (NPC). We aim to explore the relationship between 24-month progression-free survival (PFS24) and subsequent overall survival (sOS) as well as loss of lifetime (LoL) in NPC patients. sOS is defined as survival from the 24-month point or progression within 24 months leading to mortality. LoL represents the reduction in life expectancy due to NPC, compared to the general population matched by age, sex, and calendar year. The standardized mortality ratio (SMR) is defined as the ratio of observed mortality to expected mortality. The study included 6315 patients from nonendemic and endemic regions of China. Among them, 5301 patients (83.9%) achieved PFS24, with a 5-year sOS of 90.2% and an SMR of 1.0. Over a 10-year period following treatment, the mean LoL was only 0.01 months/year. For most subgroups, patients achieving PFS24 exhibited comparable sOS and LoL with the general population. However, patients failing to achieve PFS24 showed significantly worse outcomes, with 5-year sOS of 21.9%, SMR of 23.7, and LoL of 6.48 months/year. These notable outcome disparities highlight the importance of PFS24 in NPC risk stratification, patient monitoring, and study design.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672184","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}
MedCommPub Date : 2025-03-20DOI: 10.1002/mco2.70158
Ya Gao, Hai-Qian Nie, Hong-Min Liu, Xin-Hui Zhang, Li-Ying Ma
{"title":"Rational Design, Synthesis, and Biological Assessment of Potential Indole-Capped HDAC6 Inhibitors for Gastric Cancer Suppression","authors":"Ya Gao, Hai-Qian Nie, Hong-Min Liu, Xin-Hui Zhang, Li-Ying Ma","doi":"10.1002/mco2.70158","DOIUrl":"10.1002/mco2.70158","url":null,"abstract":"<p>Dear Editor,</p><p>Gastric cancer and gastroesophageal junction cancer have long been among the top killers in the cancer realm [<span>1</span>]. Moreover, East Asian countries such as China, Japan, and South Korea are known as high-incidence regions for gastric cancer on a global scale. As the limited availability of precision medicine drugs for gastric cancer at present, there is still a need for the development of small molecule compounds targeting novel targets. Accumulating evidence suggests a link between dysregulated histone deacetylase 6 (HDAC6) activity and numerous oncological disorders [<span>2, 3</span>]. HDAC6 is frequently overexpressed in various malignancies, including primary acute myeloid leukemia, gastric cancer, breast cancer, ovarian cancer, and colorectal cancer, and is strongly associated with unfavorable prognosis [<span>4</span>]. These findings underscore the pivotal role of HDAC6 as a prominent therapeutic target in the pathogenesis and progression of diverse tumor types.</p><p>To develop small molecule inhibitors targeting the HDAC6 enzyme, we relied on the in-house library compounds screening strategy and obtained a lead compound. We then optimized the structure of the lead compound <b>L9</b>. Among them, enzyme activity assays revealed compound <b>10n</b> exhibited excellent inhibitory effects on HDAC6 with an IC<sub>50</sub> value of 3.11 nM. Simultaneously, <b>10n</b> showed notable selectivity in inhibiting HDAC1, HDAC2, HDAC3, and HDAC8 compared to HDAC6, with selectivity ratios of 133.7-fold, 27.8-fold, 82.8-fold, and 622.22-fold, respectively. Ricolinostat (ACY-1215), one selective HDAC6 inhibitor in the clinical stage, exhibited IC<sub>50</sub> values of 50, 42, 60, 120, and 5.3 nM for HDAC1, 2, 3, 6, and 8, respectively. The selectivity ratios of HDAC1/6, 2/6, 3/6, and 8/6 are 9.4-fold, 7.9-fold, 11.3-fold, and 22.6-fold, respectively. Compound <b>10n</b> exhibits greater selectivity against HDAC1, HDAC2, HDAC3, and HDAC8 compared to HDAC6. This indicates that <b>10n</b> is a significantly selective HDAC6 inhibitor.</p><p><i>S</i>ilico docking study revealed that <b>10n</b> was capable of fitting into the substrate-binding pocket of HDAC6. Additionally, the C═O group was seen to form a hydrogen bond with a Zn<sup>2+</sup>-bound water molecule, with as O<b><sup>…</sup></b>H separation of 2.05 Å (Figure 1A). Furthermore, the N-benzylformamide-based linker portion nested in the hydrophobic tunnel and was sandwiched between P583 and P643, forming a clear π–π stacking interaction with P643 (Figure 1A). Additionally, BLI verified that <b>10n</b> exhibits a high affinity for HDAC6, with a Kd value of 330 ± 180 nM (Figure 1B).</p><p>Furthermore, <b>10n</b> exhibited enhanced cytotoxicity against MGC-803 and MKN-45 cells, with IC<sub>50</sub> values of 1.067 ± 0.312 and 2.704 ± 0.935 µM at 72 h. EdU incorporation assays and plate clone formation assays were conducted to evaluate the antiproliferative effects of <b>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672183","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}
{"title":"Mitigating Early Phosphatidylserine Exposure in a Tmem30a-Dependent Way Ameliorates Neuronal Damages After Ischemic Stroke","authors":"Chuanjie Wu, Jiaqi Guo, Yunxia Duan, Jiachen He, Shuaili Xu, Guiyou Liu, Chen Zhou, Yuchuan Ding, Xianjun Zhu, Xunming Ji, Di Wu","doi":"10.1002/mco2.70140","DOIUrl":"https://doi.org/10.1002/mco2.70140","url":null,"abstract":"<p>Phosphatidylserine (PS) exposes to the outer plasma membrane after a pathological insult (e.g., stroke) but not under normal conditions whereby PS remains within the inner plasma membrane. However, the reversibility and translational potential of PS exposure in damaged cells after stroke are still unknown. Here, we demonstrated that plasma Annexin V, which has a high affinity to membranes bearing PS, was increased in patients with salvage penumbra after endovascular therapy, and associated with early neurological improvement. Moreover, Annexin V treatment could decrease PS exposure and mitigate neurological impairments in transient ischemia/reperfusion mouse models, but not in permanent ischemia. Furthermore, we used a combination of cell, rodent, and nonhuman primate ischemia/reperfusion models and found that transmembrane protein 30A (Tmem30a) was increased in the ischemic penumbra after stroke and imperative for less PS exposure and better neurological functions. Mechanistically, mitigation of PS exposure mediated by Tmem30a/Annexin V connection led to decreased expression of apoptosis and necroptosis markers in neurons of penumbra. Overall, our findings reveal a previously unappreciated role of reducing PS exposure by Annexin V treatment in protecting the penumbra in a clinically relevant ischemia/reperfusion model. Tmem30a is essential for reducing PS exposure in the penumbra after ischemic stroke.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638781","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}
MedCommPub Date : 2025-03-18DOI: 10.1002/mco2.70142
Kaixi Liu, Lei Chen, Xinning Mi, Qian Wang, Yitong Li, Jingshu Hong, Xiaoxiao Wang, Yue Li, Yanan Song, Yi Yuan, Jie Wang, Dengyang Han, Taotao Liu, Ning Yang, Xiangyang Guo, Zhengqian Li
{"title":"Swimming Exercise Pretreatment Attenuates Postoperative Delirium-Like Behavior in Type 2 Diabetic Rats by Enhancing Mitochondrial Biogenesis Through Activation of SIRT2 Deacetylation","authors":"Kaixi Liu, Lei Chen, Xinning Mi, Qian Wang, Yitong Li, Jingshu Hong, Xiaoxiao Wang, Yue Li, Yanan Song, Yi Yuan, Jie Wang, Dengyang Han, Taotao Liu, Ning Yang, Xiangyang Guo, Zhengqian Li","doi":"10.1002/mco2.70142","DOIUrl":"https://doi.org/10.1002/mco2.70142","url":null,"abstract":"<p>Postoperative delirium (POD) is a common postsurgical complication that seriously affects patients' prognosis and imposes a heavy burden on families and society. Type 2 diabetes mellitus (T2DM) is a major risk factor for POD. The susceptibility mechanisms of POD in T2DM individuals and the role of exercise preconditioning remain unclear. Adult rats with and without T2DM were used to assess the promotive effect of diabetes on postoperative delirium-like behavior. The diabetic rats were also subjected to a swimming exercise program before surgery. The potential beneficial effect of exercise preconditioning on postoperative cognition was evaluated by examining neurobehavior, hippocampal neuroinflammation, mitochondrial morphology, and function in diabetic rats. Finally, underlying mechanisms were further analyzed by exploring the role of the sirtuin family in vivo and in vitro. We found that performing tibial fracture surgery resulted in delirium-like behavior and inhibited hippocampal mitochondrial biogenesis in diabetic rats but not in healthy rats. Preoperative swimming exercise was beneficial in attenuating delirium-like behavior, inhibiting neuroinflammation, and improving mitochondrial biogenesis and function. Preoperative swimming exercise achieved these positive effects by upregulating SIRT2-mediated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) deacetylation and activating mitochondrial biogenesis in T2DM rats.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638726","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}