MedComm最新文献

{"title":"Targeting intracellular cancer proteins with tumor-microenvironment-responsive bispecific nanobody-PROTACs for enhanced therapeutic efficacy","authors":"Changping Deng,&nbsp;Jiacheng Ma,&nbsp;Yuping Liu,&nbsp;Xikui Tong,&nbsp;Lei Wang,&nbsp;Jiayi Dong,&nbsp;Ping Shi,&nbsp;Meiyan Wang,&nbsp;Wenyun Zheng,&nbsp;Xingyuan Ma","doi":"10.1002/mco2.70068","DOIUrl":"10.1002/mco2.70068","url":null,"abstract":"<p>Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity. In this study, we engineered BumPeD, a novel bispecific nanobody-targeted PROTACs-like platform, by fusing two nanobodies with a Furin protease cleavage site (RVRR) and a degron sequence (ALAPYIP or KIGLGRQKPPKATK), enabling the tumor microenvironment to direct the degradation of intracellular proteins. We utilized KN035 and Nb4A to target PD-L1 (programmed death ligand 1) on the cell surface and intracellular Survivin, respectively. In vitro experiments showed that BumPeD triggers Survivin degradation via the ubiquitin-proteasome pathway, inducing tumor apoptosis and suppressing bladder tumor cell proliferation and migration. In vivo experiments further confirmed BumPeD's robust anti-tumor efficacy, underscoring its potential as a precise protein degradation strategy for cancer therapy. Our platform provides a systematic approach to developing effective and practical protein degraders, offering a targeted theoretical basis and experimental support for the development of novel degradative drugs, as well as new directions for cancer therapy.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018693","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":"Circulating tumor DNA analysis for prediction of prognosis and molecular insights in patients with resectable gastric cancer: results from a prospective study","authors":"Zheng Liu,&nbsp;Zhongyi Shi,&nbsp;Wenchao Jiang,&nbsp;Zhenbin Shen,&nbsp;Weidong Chen,&nbsp;Kuntang Shen,&nbsp;Yihong Sun,&nbsp;Zhaoqing Tang,&nbsp;Xuefei Wang","doi":"10.1002/mco2.70065","DOIUrl":"10.1002/mco2.70065","url":null,"abstract":"<p>This study aimed to evaluate the prognostic value of plasma circulating tumor DNA (ctDNA) level in patients with resectable gastric cancer (GC). A total of 59 patients were prospectively enrolled, with their ctDNA detected and paired tumor tissue collected at various peri-operative time points. Patients with higher 1-month post-operative ctDNA levels demonstrated shorter overall survival status (hazard ratio [HR] = 5.30, <i>p</i> = 0.0022) and a higher risk of recurrence (HR = 3.85, <i>p</i> = 0.011). The model combining ctDNA with conventional serum tumor markers for GC, including carcinoembryonic antigen, carbohydrate antigen 19-9, and CA72-4, shows high predictive effectiveness for GC prognosis with an area under the curve of 0.940 (<i>p</i> = 0.002), which is higher than net ctDNA and other models without ctDNA. Patients with lower ctDNA levels were more likely to have positive stromal programmed cell death ligand 1 expression (<i>p</i> = 0.046). Additionally, DCAF4L2 mutation was identified as the crucial gene mutation in ctDNA suggesting poor prognosis of patients with GC. Overall, this study highlights that post-operative ctDNA can serve as an effective biomarker for prognostic prediction and recurrence surveillance in resectable GC.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019114","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":"A novel allosteric driver mutation of β-glucuronidase promotes head and neck squamous cell carcinoma progression through STT3B-mediated PD-L1 N-glycosylation","authors":"Zhonglong Liu,&nbsp;Xiaoyan Meng,&nbsp;Xiao Tang,&nbsp;Jian Zhang,&nbsp;Zhiyuan Zhang,&nbsp;Yue He","doi":"10.1002/mco2.70062","DOIUrl":"10.1002/mco2.70062","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) develops and advances because of the accumulation of somatic mutations located in orthosteric and allosteric areas. However, the biological effects of allosteric driver mutations during tumorigenesis are mostly unknown. Here, we mapped somatic mutations generated from 10 tumor-normal matched HNSCC samples into allosteric sites to prioritize the mutated allosteric proteins via whole-exome sequencing and AlloDriver, identifying the specific mutation H351Q in β-glucuronidase (GUSB), a lysosomal enzyme, as a novel allosteric driver mutation, which considerably encouraged HNSCC progression both in vitro and in vivo. Mechanistically, the allosteric mutation of H351Q remarkably attenuated protein trafficking from the endoplasmic reticulum (ER) to lysosomes, leading to ER retention, in which GUSB-H351Q facilitated the aberrant N-glycosylation of PD-L1 through increasing protein stability and mRNA transcripts of the STT3 oligosaccharyltransferase complex catalytic subunit B, an oligosaccharyltransferase complex. Moreover, GUSB-H351Q reshaped a more immunosuppressive microenvironment featuring increased infiltration of exhausted CD8⁺ T cells and remodeled tumor metabolism, characterized by increased activity of the purine metabolism pathways and pyruvic acid accumulation. This study provides a mechanism-driven approach to overcoming HNSCC progression and immune evasion and identifies novel druggable targets based on the presence of GUSB allosteric driver mutation.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019041","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":"Estimating myocardial fibrosis in aortic stenosis using the serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio","authors":"Svante Gersch,&nbsp;Philipp Bengel,&nbsp;Niels B. Paul,&nbsp;Susana Ravassa,&nbsp;Stephan von Haehling,&nbsp;Andreas Fischer,&nbsp;Elisabeth M. Zeisberg,&nbsp;Miriam Puls,&nbsp;Gerd Hasenfuß,&nbsp;Moritz Schnelle","doi":"10.1002/mco2.70069","DOIUrl":"10.1002/mco2.70069","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Aortic stenosis (AS) is the most prevalent valvular disorder in the western world imposing significant morbidity and mortality. Progressive AS primarily affects the left ventricle, leading to adaptations of the myocardium, resulting in cardiac hypertrophy and myocardial fibrosis (MF). We and others recently demonstrated a link between the amount of MF and impaired outcomes following aortic valve replacement in patients with severe AS,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; highlighting its clinical relevance. Although cardiac biopsy remains the gold standard for MF quantification, this method is complex, invasive, and may be associated with severe complications. Thus, easier ways of determining MF levels are direly needed.&lt;/p&gt;&lt;p&gt;Different peptides of collagen metabolism have recently been suggested as serum biomarkers for MF and/or associated risk prediction in patients with heart failure (HF).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For instance, low serum levels of procollagen type I C-terminal propeptide (PICP), formed during the extracellular conversion of procollagen type I into mature fibril-forming collagen type I, were shown to be linked to reduced risk of cardiovascular death or HF-associated hospitalization in HF patients with reduced ejection fraction (EF). Levels of the amino-terminal propeptide of procollagen type III (PIIINP), formed during the conversion of procollagen type III into mature collagen type III, correlated with the collagen type III volume fraction in HF patients with ischemic heart disease or idiopathic dilated cardiomyopathy.&lt;/p&gt;&lt;p&gt;The level of MF is not only a matter of quantity, that is, collagen deposition, but also quality as reflected by the degree of myocardial collagen cross-linking. This can be indirectly assessed by the serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP1), a negative index of myocardial collagen cross-linking, and can be used for HF-associated hospitalization risk prediction in hypertensive HF.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Investigations on serum biomarker identification for MF assessment in AS patients with different hemodynamic subtypes have not yet been performed. Thus, our study was designed to evaluate the association of PICP, PIIINP, and CITP:MMP1 with histological MF (measured as collagen volume fraction) in cardiac biopsies, obtained during transcatheter aortic valve replacement (TAVR), in our well-defined cohort of patients with severe AS.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Biomarkers were measured in serum samples from 95 AS patients prior to TAVR. This study focused on the four different hemodynamic AS subtypes: (I) normal EF and high transvalvular pressure gradient (NEF-HG AS), (II) low/reduced EF and high gradient (LEF-HG AS), (III) low/reduced EF and low gradient referred to as classical low-flow low-gradient AS (classical LF-LG AS), and (IV) paradoxical low-flow low-gradient despite normal EF (PLF-LG AS). Details regarding hemodynamics (Table S1) and a","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019096","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":"Vascular endothelial cell injury: causes, molecular mechanisms, and treatments","authors":"Tian Xia,&nbsp;Jiachi Yu,&nbsp;Meng Du,&nbsp;Ximeng Chen,&nbsp;Chengbin Wang,&nbsp;Ruibing Li","doi":"10.1002/mco2.70057","DOIUrl":"https://doi.org/10.1002/mco2.70057","url":null,"abstract":"<p>Vascular endothelial cells form a single layer of flat cells that line the inner surface of blood vessels, extending from large vessels to the microvasculature of various organs. These cells are crucial metabolic and endocrine components of the body, playing vital roles in maintaining circulatory stability, regulating vascular tone, and preventing coagulation and thrombosis. Endothelial cell injury is regarded as a pivotal initiating factor in the pathogenesis of various diseases, triggered by multiple factors, including infection, inflammation, and hemodynamic changes, which significantly compromise vascular integrity and function. This review examines the causes, underlying molecular mechanisms, and potential therapeutic approaches for endothelial cell injury, focusing specifically on endothelial damage in cardiac ischemia/reperfusion (I/R) injury, sepsis, and diabetes. It delves into the intricate signaling pathways involved in endothelial cell injury, emphasizing the roles of oxidative stress, mitochondrial dysfunction, inflammatory mediators, and barrier damage. Current treatment strategies—ranging from pharmacological interventions to regenerative approaches and lifestyle modifications—face ongoing challenges and limitations. Overall, this review highlights the importance of understanding endothelial cell injury within the context of various diseases and the necessity for innovative therapeutic methods to improve patient outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143115645","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":"Novel vaccine strategies to induce respiratory mucosal immunity: advances and implications","authors":"Ming Zhou,&nbsp;Haiqin Xiao,&nbsp;Xinyi Yang,&nbsp;Tong Cheng,&nbsp;Lunzhi Yuan,&nbsp;Ningshao Xia","doi":"10.1002/mco2.70056","DOIUrl":"10.1002/mco2.70056","url":null,"abstract":"<p>Rapid advances in vaccine technology are becoming increasingly important in tackling global health crises caused by respiratory virus infections. While traditional vaccines, primarily administered by intramuscular injection, have proven effective, they often fail to provide the broad upper respiratory tract mucosal immunity, which is urgently needed for first-line control of respiratory viral infections. Furthermore, traditional intramuscular vaccines may not adequately address the immune escape of emerging virus variants. In contrast, respiratory mucosal vaccines developed using the body's mucosal immune response mechanism can simultaneously establish both systemic and mucosal immunity. This dual action effectively allows the respiratory mucosal immune system to function as the first line of defense, preventing infections at the entry points. This review highlights the efficacy of respiratory mucosal vaccines, including innovative delivery methods such as nasal and oral formulations, in enhancing local and systemic immune barriers. Notably, respiratory mucosal vaccines offer potential advantages in protecting against emerging virus variants and maintaining long-term and multidimensional immune memory in the upper respiratory tract. In addition, a combination of intramuscular and respiratory mucosal delivery of vaccines largely improves their coverage and effectiveness, providing valuable insights for future vaccine development and public inoculation strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017740","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":"A novel innate immunity-mediated senescence mechanism regulated by cGAS–STING–IRF3–pRB","authors":"Linbin Zhou,&nbsp;Jiahui Li,&nbsp;Wai Kit Chu","doi":"10.1002/mco2.70072","DOIUrl":"10.1002/mco2.70072","url":null,"abstract":"&lt;p&gt;In a study recently published in &lt;i&gt;Science Advances&lt;/i&gt;, Wu et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; demonstrated that the retinoblastoma protein (pRB) engages the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) cascade via interacting with interferon regulatory factor 3 (IRF3) to initiate senescence in hepatic stellate cells, which hampers liver fibrosis. These intriguing findings are important for developing novel therapeutic strategies for inducing senescence via manipulating the cGAS–STING–IRF3–pRB cascade.&lt;/p&gt;&lt;p&gt;The cyclic cGAS–STING pathway functions as an innate immune defense primed by cytosolic DNA. Upon sensing cytosolic DNA, cGAS–STING recruits and activates the inhibitor of NF-κB kinase (IKK) and TANK-binding kinase 1 (TBK1). The activated IKK and TBK1 activate nuclear factor kappa-B (NF-κB) and IRF3, respectively, which, in turn, enter the nucleus and induce the expression of multiple cytokines.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Hitherto, the cGAS–STING signaling has been demonstrated to play crucial roles in various biological processes, ranging from autophagy and cellular condensation to cell death.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Deregulation of the cGAS–STING cascade frequently results in autoimmune, infectious and degenerative diseases, and cancers.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; A crucial role of the cGAS–STING cascade in driving senescence has recently emerged,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; yet the underlying mechanisms of cGAS–STING-induced senescence need more investigations.&lt;/p&gt;&lt;p&gt;pRB functions as a negative regulator of the cell cycle by controlling the G1 to S phase transition, where pRB is inactivated via cyclin-dependent kinases (CDK)-mediated hyperphosphorylation, allowing E2F to release from the pRB–E2F complex.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; E2F can then induce the expression of genes required for the G1 to S phase transition.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; As such, pRB has long been viewed as one of the central regulators of senescence, a cellular state with irreversible cell cycle arrests. Recent findings from Wu and colleagues demonstrated that pRB is involved in the cGAS–STING-induced senescence under DNA damage conditions, where phosphorylated IRF3 outcompetes CDK4/6 in interacting with pRB to maintain pRB in a hypophosphorylation state, which promotes pRB–E2F binding and hampers E2F-induced gene expression (Figure 1).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Wu and colleagues observed cGAS–STING signaling activation and senescence after DNA damage induction in various cells. IRF3 ablation suppressed the DNA damage-induced senescence in these cells. Furthermore, a marked decrease in pRB phosphorylation levels was observed in DNA damage-induced senescent cells, while IRF3 ablation reversed it. Conversely, in IRF3-ablated cells, reintroducing IRF3 restored pRB hypophosphorylation under DNA damage-induced senescence. Importantly, pRB was further identified as a prominent IRF3-binding protein. Notably, among the components of the cGAS–STING signal","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 2","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019080","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":"The crosstalk between senescence, tumor, and immunity: molecular mechanism and therapeutic opportunities","authors":"Zehua Wang,&nbsp;Chen Chen,&nbsp;Jiaoyu Ai,&nbsp;Yaping Gao,&nbsp;Lei Wang,&nbsp;Shurui Xia,&nbsp;Yongxu Jia,&nbsp;Yanru Qin","doi":"10.1002/mco2.70048","DOIUrl":"10.1002/mco2.70048","url":null,"abstract":"<p>Cellular senescence is characterized by a stable cell cycle arrest and a hypersecretory, proinflammatory phenotype in response to various stress stimuli. Traditionally, this state has been viewed as a tumor-suppressing mechanism that prevents the proliferation of damaged cells while activating the immune response for their clearance. However, senescence is increasingly recognized as a contributing factor to tumor progression. This dual role necessitates a careful evaluation of the beneficial and detrimental aspects of senescence within the tumor microenvironment (TME). Specifically, senescent cells display a unique senescence-associated secretory phenotype that releases a diverse array of soluble factors affecting the TME. Furthermore, the impact of senescence on tumor–immune interaction is complex and often underappreciated. Senescent immune cells create an immunosuppressive TME favoring tumor progression. In contrast, senescent tumor cells could promote a transition from immune evasion to clearance. Given these intricate dynamics, therapies targeting senescence hold promise for advancing antitumor strategies. This review aims to summarize the dual effects of senescence on tumor progression, explore its influence on tumor–immune interactions, and discuss potential therapeutic strategies, alongside challenges and future directions. Understanding how senescence regulates antitumor immunity, along with new therapeutic interventions, is essential for managing tumor cell senescence and remodeling the immune microenvironment.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985895","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":"Connection between oral health and chronic diseases","authors":"Di Fu,&nbsp;Xingyue Shu,&nbsp;Ge Zhou,&nbsp;Mengzhen Ji,&nbsp;Ga Liao,&nbsp;Ling Zou","doi":"10.1002/mco2.70052","DOIUrl":"10.1002/mco2.70052","url":null,"abstract":"<p>Chronic diseases have emerged as a paramount global health burden, accounting for 74% of global mortality and causing substantial economic losses. The oral cavity serves as a critical indicator of overall health and is inextricably linked to chronic disorders. Neglecting oral health can exacerbate localized pathologies and accelerate the progression of chronic conditions, whereas effective management has the potential to reduce their incidence and mortality. Nevertheless, limited resources and lack of awareness often impede timely dental intervention, delaying optimal therapeutic measures. This review provides a comprehensive analysis of the impact of prevalent chronic diseases—such as diabetes mellitus, rheumatoid arthritis, cardiovascular disorders, and chronic respiratory diseases—on oral health, along with an exploration of how changes in oral health affect these chronic conditions through both deterioration and intervention mechanisms. Additionally, novel insights into the underlying pathophysiological mechanisms governing these relationships are presented. By synthesizing these advancements, this review aims to illuminate the complex interrelationship between oral health and chronic diseases while emphasizing the urgent need for greater collaboration between dental practitioners and general healthcare providers to improve overall health outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985891","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":"Ginsenoside Rk2 alleviates hepatic ischemia/reperfusion injury by enhancing AKT membrane translocation and activation","authors":"Hong Shen,&nbsp;Jiajun Fu,&nbsp;Jiayue Liu,&nbsp;Toujun Zou,&nbsp;Kun Wang,&nbsp;Xiao-Jing Zhang,&nbsp;Jian-Bo Wan","doi":"10.1002/mco2.70047","DOIUrl":"10.1002/mco2.70047","url":null,"abstract":"<p>Hepatic ischemia–reperfusion injury (IRI) poses a significant threat to clinical outcomes and graft survival during hemorrhagic shock, hepatic resection, and liver transplantation. Current pharmacological interventions for hepatic IRI are inadequate. In this study, we identified ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin, as a promising agent against hepatic IRI through high-throughput screening. The pharmacological effects and molecular mechanisms of Rk2 on hepatic IRI were further evaluated and elucidated in vitro and in vivo. Rk2 significantly reduced inflammation and apoptosis caused by oxygen-glucose deprivation and reperfusion in hepatocytes and dose dependently protected against hepatic I/R-induced liver injury in mice. Integrated approaches, including network pharmacology, molecular docking, transcriptome analysis, and isothermal titration calorimetry, along with experimental validation, indicated that Rk2 protects against hepatic IRI by targeting and activating the AKT (RAC serine/threonine protein kinase) signaling pathway. Pharmacological inhibition of AKT pathway or knockdown of AKT1 effectively diminished protective effects of Rk2. Rk2 directly binds to AKT1, facilitating its translocation from the cytoplasm to plasma membrane. This process markedly enhanced AKT interaction with PDPK1, promoting the activation of AKT1 and its downstream signaling. Our findings demonstrate that Rk2 protects against hepatic IRI by activating AKT signaling through direct binding to AKT1 and facilitating its membrane translocation.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985893","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}