Military Medical Research最新文献

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Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives. 胃肠胰神经内分泌肿瘤:当前发展、挑战和临床前景。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-06-04 DOI: 10.1186/s40779-024-00535-6
Xian-Bin Zhang, Yi-Bao Fan, Rui Jing, Mikiyas Amare Getu, Wan-Ying Chen, Wei Zhang, Hong-Xia Dong, Tikam Chand Dakal, Akhtar Hayat, Hua-Jun Cai, Milad Ashrafizadeh, A M Abd El-Aty, Ahmet Hacimuftuoglu, Peng Liu, Tian-Feng Li, Gautam Sethi, Kwang Seok Ahn, Yavuz Nuri Ertas, Min-Jiang Chen, Jian-Song Ji, Li Ma, Peng Gong
{"title":"Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.","authors":"Xian-Bin Zhang, Yi-Bao Fan, Rui Jing, Mikiyas Amare Getu, Wan-Ying Chen, Wei Zhang, Hong-Xia Dong, Tikam Chand Dakal, Akhtar Hayat, Hua-Jun Cai, Milad Ashrafizadeh, A M Abd El-Aty, Ahmet Hacimuftuoglu, Peng Liu, Tian-Feng Li, Gautam Sethi, Kwang Seok Ahn, Yavuz Nuri Ertas, Min-Jiang Chen, Jian-Song Ji, Li Ma, Peng Gong","doi":"10.1186/s40779-024-00535-6","DOIUrl":"10.1186/s40779-024-00535-6","url":null,"abstract":"<p><p>Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"35"},"PeriodicalIF":21.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248357","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}
引用次数: 0
Advances in the isolation, cultivation, and identification of gut microbes. 肠道微生物的分离、培养和鉴定方面的进展。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-06-03 DOI: 10.1186/s40779-024-00534-7
Meng-Qi Xu, Fei Pan, Li-Hua Peng, Yun-Sheng Yang
{"title":"Advances in the isolation, cultivation, and identification of gut microbes.","authors":"Meng-Qi Xu, Fei Pan, Li-Hua Peng, Yun-Sheng Yang","doi":"10.1186/s40779-024-00534-7","DOIUrl":"10.1186/s40779-024-00534-7","url":null,"abstract":"<p><p>The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"34"},"PeriodicalIF":21.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237759","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}
引用次数: 0
Advancing skeletal health and disease research with single-cell RNA sequencing. 利用单细胞 RNA 测序推进骨骼健康和疾病研究。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-05-30 DOI: 10.1186/s40779-024-00538-3
Peng Lin, Yi-Bo Gan, Jian He, Si-En Lin, Jian-Kun Xu, Liang Chang, Li-Ming Zhao, Jun Zhu, Liang Zhang, Sha Huang, Ou Hu, Ying-Bo Wang, Huai-Jian Jin, Yang-Yang Li, Pu-Lin Yan, Lin Chen, Jian-Xin Jiang, Peng Liu
{"title":"Advancing skeletal health and disease research with single-cell RNA sequencing.","authors":"Peng Lin, Yi-Bo Gan, Jian He, Si-En Lin, Jian-Kun Xu, Liang Chang, Li-Ming Zhao, Jun Zhu, Liang Zhang, Sha Huang, Ou Hu, Ying-Bo Wang, Huai-Jian Jin, Yang-Yang Li, Pu-Lin Yan, Lin Chen, Jian-Xin Jiang, Peng Liu","doi":"10.1186/s40779-024-00538-3","DOIUrl":"10.1186/s40779-024-00538-3","url":null,"abstract":"<p><p>Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"33"},"PeriodicalIF":21.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180084","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}
引用次数: 0
Mitochondrial quality control in human health and disease 人类健康和疾病中的线粒体质量控制
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-05-29 DOI: 10.1186/s40779-024-00536-5
Bo-Hao Liu, Chen-Zhen Xu, Yi Liu, Zi-Long Lu, Ting-Lv Fu, Guo-Rui Li, Yu Deng, Guo-Qing Luo, Song Ding, Ning Li, Qing Geng
{"title":"Mitochondrial quality control in human health and disease","authors":"Bo-Hao Liu, Chen-Zhen Xu, Yi Liu, Zi-Long Lu, Ting-Lv Fu, Guo-Rui Li, Yu Deng, Guo-Qing Luo, Song Ding, Ning Li, Qing Geng","doi":"10.1186/s40779-024-00536-5","DOIUrl":"https://doi.org/10.1186/s40779-024-00536-5","url":null,"abstract":"Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"67 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141167518","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}
引用次数: 0
Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine. 时空多组学:探索衰老和再生医学中的分子景观。
IF 16.7 2区 医学
Military Medical Research Pub Date : 2024-05-27 DOI: 10.1186/s40779-024-00537-4
Liu-Xi Chu, Wen-Jia Wang, Xin-Pei Gu, Ping Wu, Chen Gao, Quan Zhang, Jia Wu, Da-Wei Jiang, Jun-Qing Huang, Xin-Wang Ying, Jia-Men Shen, Yi Jiang, Li-Hua Luo, Jun-Peng Xu, Yi-Bo Ying, Hao-Man Chen, Ao Fang, Zun-Yong Feng, Shu-Hong An, Xiao-Kun Li, Zhou-Guang Wang
{"title":"Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.","authors":"Liu-Xi Chu, Wen-Jia Wang, Xin-Pei Gu, Ping Wu, Chen Gao, Quan Zhang, Jia Wu, Da-Wei Jiang, Jun-Qing Huang, Xin-Wang Ying, Jia-Men Shen, Yi Jiang, Li-Hua Luo, Jun-Peng Xu, Yi-Bo Ying, Hao-Man Chen, Ao Fang, Zun-Yong Feng, Shu-Hong An, Xiao-Kun Li, Zhou-Guang Wang","doi":"10.1186/s40779-024-00537-4","DOIUrl":"10.1186/s40779-024-00537-4","url":null,"abstract":"<p><p>Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"31"},"PeriodicalIF":16.7,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155418","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}
引用次数: 0
P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway. 口腔-前列腺轴中的牙龈脓疱通过 IL-6/IL-6R 途径加剧良性前列腺增生。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-05-20 DOI: 10.1186/s40779-024-00533-8
Shuang-Ying Wang, Yi Cai, Xiao Hu, Fei Li, Xin-Hang Qian, Ling-Yun Xia, Bo Gao, Lan Wu, Wen-Zhong Xie, Jia-Min Gu, Tong Deng, Cong Zhu, Hai-Chang Jia, Wan-Qi Peng, Jiao Huang, Cheng Fang, Xian-Tao Zeng
{"title":"P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.","authors":"Shuang-Ying Wang, Yi Cai, Xiao Hu, Fei Li, Xin-Hang Qian, Ling-Yun Xia, Bo Gao, Lan Wu, Wen-Zhong Xie, Jia-Min Gu, Tong Deng, Cong Zhu, Hai-Chang Jia, Wan-Qi Peng, Jiao Huang, Cheng Fang, Xian-Tao Zeng","doi":"10.1186/s40779-024-00533-8","DOIUrl":"10.1186/s40779-024-00533-8","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.</p><p><strong>Methods: </strong>The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.</p><p><strong>Results: </strong>P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.</p><p><strong>Conclusion: </strong>P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"30"},"PeriodicalIF":21.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065962","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}
引用次数: 0
Biomaterials science and surface engineering strategies for dental peri-implantitis management. 牙科种植体周围炎管理的生物材料科学和表面工程策略。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-05-13 DOI: 10.1186/s40779-024-00532-9
Ya-Meng Yu, Yu-Pu Lu, Ting Zhang, Yu-Feng Zheng, Yun-Song Liu, Dan-Dan Xia
{"title":"Biomaterials science and surface engineering strategies for dental peri-implantitis management.","authors":"Ya-Meng Yu, Yu-Pu Lu, Ting Zhang, Yu-Feng Zheng, Yun-Song Liu, Dan-Dan Xia","doi":"10.1186/s40779-024-00532-9","DOIUrl":"10.1186/s40779-024-00532-9","url":null,"abstract":"<p><p>Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"29"},"PeriodicalIF":21.1,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916887","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}
引用次数: 0
D-mannose alleviates intervertebral disc degeneration through glutamine metabolism. D-mannose 可通过谷氨酰胺代谢缓解椎间盘退化。
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-05-06 DOI: 10.1186/s40779-024-00529-4
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
{"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;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}
引用次数: 0
Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain 神经元 Panx1 驱动实验性足底炎症性疼痛的外周敏感化
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-04-29 DOI: 10.1186/s40779-024-00525-8
Qu Xing, Antonio Cibelli, Greta Luyuan Yang, Preeti Dohare, Qing-Hua Li, Eliana Scemes, Fang-Xia Guan, David C. Spray
{"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 &lt; 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 &lt; 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 &lt; 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P &lt; 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 &lt; 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 &lt; 0.05 vs. Panx1 KO group; P &lt; 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P &lt; 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P &lt; 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P &lt; 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}
引用次数: 0
N-terminal pro-brain natriuretic peptide – a significant biomarker of disease development and adverse prognosis in patients with exertional heat stroke N 端前脑钠肽--劳累性中暑患者疾病发展和不良预后的重要生物标志物
IF 21.1 2区 医学
Military Medical Research Pub Date : 2024-04-23 DOI: 10.1186/s40779-024-00531-w
Long Feng, Jian-Yuan Yin, Yao-Hong Liu, Pei Zhang, Ya-Li Zhao, Qing Song, Ping Ping, Shi-Hui Fu
{"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":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;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&lt;i&gt;,&lt;/i&gt; 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.&lt;/p&gt;&lt;p&gt;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 &gt; 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.&lt;/p&gt;&lt;p&gt;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}
引用次数: 0
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