Military Medical Research最新文献

{"title":"D-mannose alleviates intervertebral disc degeneration through glutamine metabolism.","authors":"Zheng-Lin Dong, Xin Jiao, Zeng-Guang Wang, Kai Yuan, Yi-Qi Yang, Yao Wang, Yun-Tao Li, Tian-Chang Wang, Tian-You Kan, Jian Wang, Hai-Rong Tao","doi":"10.1186/s40779-024-00529-4","DOIUrl":"10.1186/s40779-024-00529-4","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored.</p><p><strong>Methods: </strong>The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.</p><p><strong>Results: </strong>In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.</p><p><strong>Conclusions: </strong>In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IV","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"28"},"PeriodicalIF":21.1,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain","authors":"Qu Xing, Antonio Cibelli, Greta Luyuan Yang, Preeti Dohare, Qing-Hua Li, Eliana Scemes, Fang-Xia Guan, David C. Spray","doi":"10.1186/s40779-024-00525-8","DOIUrl":"https://doi.org/10.1186/s40779-024-00525-8","url":null,"abstract":"The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca2+ responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of β-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG. The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammato","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-terminal pro-brain natriuretic peptide – a significant biomarker of disease development and adverse prognosis in patients with exertional heat stroke","authors":"Long Feng, Jian-Yuan Yin, Yao-Hong Liu, Pei Zhang, Ya-Li Zhao, Qing Song, Ping Ping, Shi-Hui Fu","doi":"10.1186/s40779-024-00531-w","DOIUrl":"https://doi.org/10.1186/s40779-024-00531-w","url":null,"abstract":"<p>Dear Editor,</p><p>The most serious heat related injury is exertional heat stroke (EHS). EHS occurs when healthy individuals perform physical activity in a hot and humid environment [1]. A disrupted balance between heat production and dissipation in the human body results in excessive body heat storage in cases. It occurs frequently in the military population because of work characteristics such as the requirements to perform essential duties under prolonged heat stress, the need to achieve mission objectives during deployment operations, or the opportunities for training and selection for elite units [2]. The pathophysiology of EHS is complex, which often results in thermoregulation failure, hemodynamic disturbance, and endotoxin release<i>,</i> and further causes multiple organ failure, probably increasing myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Rhabdomyolysis caused by EHS often results from mechanical and metabolic injury to the striated muscle fibers accompanied with the release of muscle contents into the circulation [3]. Liu et al. [4] also found that NT-proBNP levels were significantly higher in dead group than those in survival group in the EHS related study. There are scarce literature assessing biochemical biomarkers including myocardial enzymes and NT-proBNP in patients with EHS all around the world. Our hospital is located in Sanya, Hainan Province of China, in the tropics with long-term high temperature and humidity exposure and receives patients with EHS every year because of long exposure to field work, marathon running, and so on. The aim of the present study was to analyze whether myocardial enzymes and NT-proBNP levels were associated with the disease and the prognosis in order to provide scientific reference for identifying and managing these patients with EHS.</p><p>A total of 45 participants with EHS and 45 participants without EHS were admitted to Hainan Hospital of Chinese PLA General Hospital. All participants in the present study had ejection fraction > 50%, without reduced ejection fraction. Samples of venous blood were routinely collected by venipuncture and delivered to our biochemistry department. Red blood cell counts (RBC), white blood cell counts (WBC), and levels of albumin, total bilirubin (TB), NT-proBNP, lactate dehydrogenase (LDH), myoglobin (Mb), creatine kinase (CK), creatine kinase-MB (CK-MB), high-sensitivity cardiac troponin T (hs-cTnT), and uric acid (UA) in serum were monitored by qualified technicians without the knowledge of clinical data when the patients’ first arrival to our hospital. From June 1, 2013 to July 1, 2022, all participants were followed up for a median period of 749 (455, 1148) d.</p><p>The whole cohort had a median age of 24 (21, 30) years with males accounting for 90.0%. Participants with EHS had lower diastolic blood pressure, RBC and albumin levels, and higher WBC, TB, NT-proBNP, LDH, Mb, CK, CK-MB, hs-cTnT levels and mortality, co","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"246 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction","authors":"Ting Gong, You-Tan Liu, Jie Fan","doi":"10.1186/s40779-024-00527-6","DOIUrl":"https://doi.org/10.1186/s40779-024-00527-6","url":null,"abstract":"Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"88 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?","authors":"Lioba Huelsboemer, Leonard Knoedler, Alejandro Kochen, Catherine T. Yu, Helia Hosseini, Katharina S. Hollmann, Ashley E. Choi, Viola A. Stögner, Samuel Knoedler, Henry C. Hsia, Bohdan Pomahac, Martin Kauke-Navarro","doi":"10.1186/s40779-024-00528-5","DOIUrl":"https://doi.org/10.1186/s40779-024-00528-5","url":null,"abstract":"Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"18 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis","authors":"Kai-Wei Jia, Ren-Qi Yao, Yi-Wen Fan, Ding-Ji Zhang, Ye Zhou, Min-Jun Wang, Li-Yuan Zhang, Yue Dong, Zhi-Xuan Li, Su-Yuan Wang, Mu Wang, Yun-Hui Li, Lu-Xin Zhang, Ting Lei, Liang-Chen Gui, Shan Lu, Ying-Yun Yang, Si-Xian Wang, Yi-Zhi Yu, Yong-Ming Yao, Jin Hou","doi":"10.1186/s40779-024-00524-9","DOIUrl":"https://doi.org/10.1186/s40779-024-00524-9","url":null,"abstract":"Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep−/−. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"80 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy","authors":"De-Chao Feng, Wei-Zhen Zhu, Jie Wang, Deng-Xiong Li, Xu Shi, Qiao Xiong, Jia You, Ping Han, Shi Qiu, Qiang Wei, Lu Yang","doi":"10.1186/s40779-024-00526-7","DOIUrl":"https://doi.org/10.1186/s40779-024-00526-7","url":null,"abstract":"In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"20 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.","authors":"Mi Zhou, Yang-Wu-Yue Liu, Yu-Hang He, Jing-Yu Zhang, Hao Guo, Hao Wang, Jia-Kui Ren, Yi-Xun Su, Teng Yang, Jia-Bo Li, Wen-Hui He, Peng-Jiao Ma, Man-Tian Mi, Shuang-Shuang Dai","doi":"10.1186/s40779-024-00523-w","DOIUrl":"10.1186/s40779-024-00523-w","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.</p><p><strong>Methods: </strong>Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice.</p><p><strong>Results: </strong>We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1^high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1^high neutrophils. In the chronic stage, the \"FOXO1-transferrin receptor (TFRC)\" mechanism contributes to FOXO1^high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI.</p><p><strong>Conclusions: </strong>FOXO1^high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"20"},"PeriodicalIF":16.7,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cells: potential carriers or agents for drug delivery to the central nervous system.","authors":"Shan-Shan Zhang, Ruo-Qi Li, Zhong Chen, Xiao-Ying Wang, Aaron S Dumont, Xiang Fan","doi":"10.1186/s40779-024-00521-y","DOIUrl":"10.1186/s40779-024-00521-y","url":null,"abstract":"<p><p>Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood-brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"19"},"PeriodicalIF":21.1,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10979586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart-brain axis: low blood pressure during off-pump CABG surgery is associated with postoperative heart failure","authors":"Xiu-Yun Liu, Jing-Jing Mu, Jian-Ge Han, Mei-Jun Pang, Kuo Zhang, Wen-Qian Zhai, Nan Su, Guang-Jian Ni, Zhi-Gang Guo, Dong Ming","doi":"10.1186/s40779-024-00522-x","DOIUrl":"https://doi.org/10.1186/s40779-024-00522-x","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;The primary objective of the letter is to emphasize the importance of personalized management of arterial blood pressure (ABP) in the context of off-pump coronary artery bypass grafting (CABG) surgery. Coronary artery disease, a leading global cause of mortality, necessitates a substantial number of cardiac surgeries, with approximately 400,000 CABG operations conducted annually in the United States. Postoperative heart failure (HF) is a common occurrence after CABG surgery, with readmission rates within 30 d due to HF ranging from 12 to 16%. Researchers have highlighted the critical role of HF management before, during and after CABG surgery, identifying hemodynamic instability, perioperative myocardial injury, and low cardiac output syndrome as predictive factors for postoperative HF. In 2023, Han et al. [1] found that factors such as pulse index failure and composite grafting are independent predictors of CABG failure. Additionally, a study reported by Loncar et al. [2] revealed a significant relationship between reduced cerebral blood flow (CBF) and the severity of HF in elderly males. Moreover, Hartono et al. [3] pointed out that perioperative myocardial injury and pre-existing left ventricular systolic dysfunction can contribute to post-CABG HF. In the surgical setting, the reduction of mean arterial pressure (MAP) to minimize collateral bleeding and enhance surgical visualization often leads to low systemic perfusion. Currently, the prevailing approach in CABG surgeries involves a uniform MAP management strategy, typically targeting a range of 60 to 70 mmHg for most patients. However, given the varying clinical backgrounds of patients and their diverse tolerance to low MAP levels, there is an urgent need for personalized MAP management during CABG surgery to ensure adequate blood flow and prevent postoperative complications.&lt;/p&gt;&lt;p&gt;The brain maintains stable perfusion through cerebral autoregulation (CA), which allows it to regulate CBF despite changes in ABP. Rhee et al. [4] have previously demonstrated that under severe hypoperfusion, the body may prioritize protecting the brain over peripheral organs such as the kidneys. By inducing continuous blood loss in piglets, they observed a reduction in kidney blood flow preceding a decrease in CBF. Previous studies by our researchers and others have established a correlation between low blood pressure and reduced cerebral perfusion during CABG and postoperative complications, including delirium, acute kidney injury, major morbidity, and operative mortality [5,6,7]. However, the specific MAP target most strongly associated with HF remains unknown. Therefore, the hypothesis of our current study is that low MAP and reduced cerebral perfusion to the brain might be a strong indicator of systemic ischemia and HF.&lt;/p&gt;&lt;p&gt;Various parameters have been developed to monitor intraoperative CA in real-time, including cerebral oxygen saturation index (COx), which is determined by the corr","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"4 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}