Abstract Background Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. Methods This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. Results A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. Conclusions Our multi–omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.
Cognitive decline and memory impairment are subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs has been implicated in the pathogenesis of Alzheimer's disease (AD) and may play a pivotal role in the early stages of the disease. In this study, we identified the critical role of miR-4763-3p in AD pathogenesis, focusing on early-stage mild cognitive impairment (AD-MCI). Leveraging fluorescence in situ hybridization, we observed miR-4763-3p upregulation in AD hippocampal tissue, colocalizing with A beta and Tau. Antagomir-mediated inhibition of miR-4763-3p ameliorated cognitive decline in AD-MCI mice. RNA-seq and functional assays revealed that miR-4763-3p targets ATP11A, and antagomir enhancing inward flipping of the "eat me" phosphatidylserine signal on the surface of neuronal cells, autophagy, and clearance of A beta/lipofuscin, while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI, offering a novel strategy to enhance neuronal autophagy, alleviate inflammation, and improve cognitive function.
Backgrounds : Tumor necrosis factor receptor type II (TNFR2) has pleiotropic biological functions involved in a variety of diseases. However, there are few studies on the knowledge structure of the academic output, research hotspots and research trends of TNFR2.Methods: We obtained the data of publications regarding TNFR2 from the Web of Science Core Collection (WoSCC) on July 31st, 2022. We used CiteSpace and VOSviewer software to analyze networks and hotspots of the annual publications, authors, countries/regions and institutions, journals, references, and keywords. The history of the citation and citation networks were analyzed by using Histcite.Results: A total of 3,340 articles and reviews were included. The number of publications regarding TNFR2 was significantly increased yearly. These publications mainly come from 87 countries and 3,401 institutions, primarily from the USA, the Peoples R China and Germany. Harvard University, the University of Stuttgart, and Genentech Inc etc. are among the most influential institutions in the field. Goeddel David V.’s team, Wajant Harald’s team, Pfizenmaier Klaus’s team, Vandenabeele Peter’s team, and Chen Xin’s team etc. are outstanding contributors to TNFR2. The Journal of Immunology was the most productive journal with 132 publications and the most cited journal. The article “The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor” by Grell M et al. was the most frequently cited literature with 351times. Inflammation, regulatory T cell, progression etc. are burst keywords, which continued until 2022.Conclusion: There is a continuous trend of increasing literature related TNFR2. The cross-talk between TNFR2, immune, and inflammation has attracted more and more attention in inflammatory diseases. As an ideal immune system brake switch, the interpretation of TNFR2 anti-tumor immune, TNFR2 targeting drugs, and related strategies gradually become hot topics.
Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.
Objective This study determined for the first time the distribution of intravenous nicotinamide mononucleotide (NMN) and its metabolite nicotinamide adenine dinucleotide (NAD) in normal and ischemic stroke mice, examined the therapeutic effect of NMN on ischemic brain infarction, and evaluated acute toxicity of NMN after intravenous injection of NMN. Methods NMN and NAD levels were determined using ultra-high-performance liquid chromatography tandem mass spectrometry in biological samples from mice with or without middle cerebral artery occlusion (MCAO) at different time points post intravenous NMN injection (300 mg/kg). Brain infarction was evaluated 24 h post-MCAO. 2 g/kg NMN was used in the acute toxicity test. Results Under either normal or MCAO conditions, serum NMN levels sharply increased after intravenous NMN administration and then decreased rapidly within 15 min, while serum NAD levels remained unchanged during 30 min observation. Both substances displayed tissue accumulation over time and stored faster under MCAO conditions, with kidney having the highest concentrations. Particularly, NMN accumulated earlier than NAD in the brain. Moreover, NMN reduced cerebral infarction at 24 h post-MCAO. No acute toxicity was observed for 14 days. NRK1 and SLC12A8 involved in two pathways of NMN uptake exhibited the highest expressions in kidney and colon, respectively, among 11 different tissues. Conclusion NMN distributes to various tissues after intravenous injection and has the ability to enter the brain to boost NAD levels, and exhibits safety and therapeutic effect on acute ischemic stroke injury. High renal distribution of NMN indicates its importance in the kidney.
Alzheimer's disease (AD) is regarded as a progressive neurodegenerative dementia, characterized by degeneration of distinct neuronal populations. A case-control study was carried out using high-resolution mass spectrometry to explore AD-associated urinary metabolic biomarkers from 30 AD patients and 30 cognitively normal (CN) individuals. In total, 49 metabolites were determined and validated as known compounds using LC/MS analysis. Using the two-sample t-test statistical analysis (P < 0.05), 19 metabolites were shown to be significantly different from AD to CN. A diagnostic model of the receiver operating characteristic curve was constructed with a combination of nine molecules out of 19 metabolites, it yielded a separation with an area under the curve value of 0.976 between the two groups. This study indicated that urinary metabolites showed a significant expression between AD and CN. AD-related metabolites enable to satisfy the diagnostic power of disease discrimination. In addition, as a noninvasive approach, urine collection is done easily in clinical diagnosis of AD.
Metabolomics, as an emerging technology, has been demonstrated to be a very powerful tool in the study of the host metabolic responses to infections by parasites. Schistosomiasis is a parasitic infection caused byschistosomaworm via the direct contact with the water containing cercaria, among whichSchistosoma japonicum(S. japonicum) is endemic in Asia. In order to characterize the schistosome-induced changes in the host metabolism and further to develop the strategy for early diagnosis of schistosomiasis, we performed comprehensive LC-MS-based metabolomics analysis of serum from mice infected byS. japonicumfor 5 weeks. With the developed diagnosis strategy based on our metabolomics data, we were able to successfully detect schistosomiasis at the first week post-infection, which was 3 weeks earlier than "gold standard" methods and 2 weeks earlier than the methods based on(1)H NMR spectroscopy. Our metabolomics study revealed thatS. japonicuminfection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, DNA and RNA biosynthesis, phospholipid metabolism, depression of energy metabolism, glucose uptake and metabolism, and disruption of gut microbiota metabolism. In addition, we identified seventeen specific metabolites whose down-regulated profiles were closely correlated with the time-course of schistosomiasis progression and can also be used as an indicator for the worm-burdens. Interestingly, the decrease of these seventeen metabolites was particularly remarkable at the first week post-infection. Thus, our findings on mechanisms of host-parasite interaction during the disease process pave the way for the development of an early diagnosis tool and provide more insightful understandings of the potential metabolic process associated with schistosomiasis in mice. Furthermore, the diagnosis strategy developed in this work is cost-effective and is superior to other currently used diagnosis methods.
Background Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44-2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85-5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37-2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39-0.60)]. Conclusions Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.
Tabson-2 decoction is the traditional Mongolian formula for anti-osteoporosis, and the ambiguous of active ingredient is an important factor in restricting its modernization and globalization. Although pharmacokinetic profiles research is a viable approach to find the components being responsible for formula efficacy, the pharmacokinetics study of Tabson-2 decoction has not been elucidated yet. Owing to the existence of isomers, low bioavailability of some small molecule and interference of endogenous, the pharmacokinetics study of Tabson-2 decoction are more difficult than that of chemical drugs. In our experiment, a specific and sensitive LC-MS/MS method was developed and validated for simultaneous determination of sixteen active ingredients in Tabson-2 decoction, which could fulfill the requirements of multi-compounds pharmacokinetic study of Tabson-2 decoction. Additionally, the ingredients with significant distributions in rats were gentianic acid, chlorogenic acid, and aucubin, which could be the main potential active components in Tabson-2 decoction. The components with a significant bioavailability difference between normal and D-galactose induced osteoporosis rats were achieved as well. These data offer useful information for screening the active ingredients in Tabson-2 decoction, and assessing the bioavailability of these active ingredients in different physiological status, which might provide a possible mechanism of anti-osteoporosis efficacy of Tabson-2 decoction. This article is protected by copyright. All rights reserved.
目的 了解上海市城乡居民急救能力现状,为有针对性地展开急救能力干预、提高整体居民急救能力提供决策支持.方法 采取分层整群随机抽样的方法,对上海市6个行政区以及开放大学共7个单位开展问卷调查,并对调查结果进行统计学分析.结果 居民紧急情况下急救正确处理率为44.27%;正确处理率最高的为骨折急救处理(60.5%),其次为触电急救处理(56.3%).正确处理率较低的为火灾(35.1%),最低的为心跳骤停急救处理(18.3%);居民对于呼吸心跳骤停的正确处理知晓率达到45%,但正确处理率(紧急进行心肺复苏)仅为18%;行政区域与文化程度是影响城乡居民急救能力的主要两个因素.结论 上海市城乡居民总体急救水平较高,但在个别急救行为方面表现出高知晓率与低正确处理率的知行不一致情况;应针对城乡居民急救能力建立研究与有效的宣传教育模式.
目的 通过研究草酸钙结石小鼠尿液中代谢物的变化,探究草酸钙结晶导致肾损伤的内在机制。 方法 以乙醛酸盐诱导的小鼠草酸钙结晶模型为对象,采用基于超高效液相-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)的代谢组学方法测定尿液中内源性代谢物的变化,并采用SIMCA-P进行多元统计分析,Metabo Analyst软件进行代谢物通路分析。 结果 与正常组相比,模型组小鼠的肾组织出现明显的钙盐沉积且血清中的肌酐和尿素氮含量异常升高,肾脏出现损伤;从尿液中筛选出尿酸、牛磺酸、苯丙氨酸等21个差异代谢物。 结论 通过代谢物通路分析,差异代谢物主要涉及氨基酸代谢、能量代谢、牛磺酸代谢、嘌呤代谢和VB6代谢,为进行结石疾病机制研究以及早期标志物的筛选提供了重要参考。
目的 了解我海军某水面舰艇部队官兵卫生服务需求与利用情况,为提高水面舰艇部队卫勤保障能力提供决策依据.方法 采用分层整群抽样方法,共抽取某水面舰艇支队175名官兵进行问卷调查,采用统计软件进行分析.结果 该水面舰艇官兵两周患病率为34.12%,所患疾病以骨骼肌肉系统疾病最常见,其次是呼吸系统疾病.两周患病就诊率为12.35%,门诊就诊主要选择到舰艇医护室和地方医院.半年内慢性病患病率为3.53%;1年内住院率为6.47%,主要选择到驻军医院和支队医院.41.18%的官兵表示近1个月压力很大或较大;半年内患牙病率为35.29%.结论 该水面舰艇官兵卫生服务需求量大,但利用率有待提高;建议卫生决策机构应及时制定相关政策,积极改善基层医疗机构条件,更好满足官兵的医疗需求.
Nephrolithiasis is one of the world's major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.
目的 了解上海市居民饮酒健康知识的掌握情况,为在社区范围内开展饮酒行为的健康教育和干预活动提供依据.方法 采取分层整群随机抽样的方法,对上海市6个行政区以及开放大学共7个单位开展问卷调查,并对调查结果进行统计学分析.结果 居民对成年男性一天合理饮用酒精量为25克的掌握程度较低(25.2%);男性被调查人群由于受到饮酒相关行为的参与度较高等原因的影响,选择正确率高于女性被调查人群(27.7%);居民对饮酒与驾车相关知识的掌握程度较好(99.3%);关于“少喝点酒驾车没关系”说法的选择中,男性被调查人群的选择率较高(1.05%),青年人群的选择率较高(0.88%);“不识字或识字很少”和“大专/本科及以上”调查人群的选择率较高(3.70%、0.71%);饮酒文化与健康知识的了解意愿方面,“饮酒与健康”“酒文化的渊源”选项的选择排在前两名(25.1%、24.2%).结论 上海市居民尚未形成良好的饮酒行为习惯,饮酒与健康相关的科普教育工作有待加强,应针对居民饮酒现状建立与健康相关的宣传教育模式.
Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC-MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms. We detected 44 metabolites and 304 proteins with different levels in the hippocampus samples from VD mice using a combination of metabolomic and proteomics analyses with an isobaric tags for relative and absolute quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory network by correlating and integrating the differential metabolites and proteins using ingenuity pathway analysis. Then we quantitatively validated the levels of the bimolecules shown in the bioinformatics analysis using LC-MS/MS and Western blotting. Validation results suggested changes in the regulation of neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and apoptosis, and disorders of amino acids, lipids and energy metabolism. These proteins and metabolites involved in these dis-regulated pathways will provide a more targeted and credible direction to study the mechanism of VD. Therefore, this paper presents an approach and strategy that was applied in integrative proteomics and metabolomics for research and screening potential targets and biomarkers of VD, which could be more precise and credible in a field lacking adequate basic research.
分析化学是医学院校药学专业的重要专业基础课,分析化学实验是整个课程的重要组成部分.针对目前分析化学仪器分析实验教学中存在的一些问题,提出了能体现专业特点,具有综合性和可实践性的实验教学模式,对仪器分析实验课教学的改革与探索提出了一些建议,意在锻炼学生分析问题、解决问题的能力,培养良好的学习态度和习惯,提高综合素质和创新能力.
为实现大型仪器资源最优化配置,构建实验室仪器管理系统,包括用户模块和管理员模块,在用户模块中,注册用户可进行样品登记和预约测试项目,并通过条形码扫描系统自动获得测试报告,真正实现自动化送样及取样.在管理员模块中,管理员可对注册用户及大型仪器设备进行全方位管理.
目的 运用代谢组学方法测定年轻小鼠与衰老小鼠血清源性物质谱的变化.方法 收集4周龄(青年组)和40周龄(衰老组)野生型雄性C57BL/6小鼠外周血清,利用超高效液相色谱串联四级杆-飞行时间质谱(UHPLC/Q-TOF)技术对上述两组老鼠的血清进行代谢轮廓分析,利用正交偏最小二乘法进行多变量分析,找出4周龄(青年组)与40周龄(衰老组)小鼠中含量差异显著的内源性物质.结果 衰老组,6种不饱和脂肪酸含量低于青年组,而饱和脂肪酸,主要为硬脂酸和软脂酸,均高于青年组;十二种溶血磷脂胆碱也明显降低,长链肉碱、黄嘌呤、次黄嘌呤、视黄醛、牛磺酸和牛磺胆酸均低于青年组,而谷氨酸、色氨酸等氨基酸也出现不同幅度下降.结论 代谢组学可以找出衰老过程中的一些潜在标志物,从而推测衰老在代谢水平上的变化机制.这主要体现在脂肪酸代谢和蛋白质代谢中.
It has been well accepted that inflammation is a critical stage in the wound healing process and the paracrine effects between macrophages and repairing cells play critical roles in wound healing. Although bioactive glass (BG), such as 45S5 bioglass, has been reported to be able to accelerate skin regeneration through enhancing angiogenesis and collagen deposition in the proliferation stage of the wound healing process, the effects of BG on the inflammation responses of wound healing have rarely been studied. To further elucidate the mechanism of BG enhancing wound healing, in this study, the effects of BG on the phenotype switch of macrophages and paracrine effects between the macrophages and repairing cells in wound healing were investigated. The results showed that BG ionic products activated macrophages towards the M2 phenotype and stimulated macrophages to express more anti-inflammatory and angiogenic growth factors compared to control medium. Conditioned medium of macrophages cultured with BG accelerated the migration of endothelial cells and fibroblasts, thus increasing the capillary-like network formation of endothelial cells and the extracellular matrix protein deposition of fibroblasts. When BG powders were applied to full-thickness excisional wounds of rats, the wound closure was accelerated by BG as compared to the control group. Reduced inflammation during initial stages of healing was observed, which was evidenced by fewer neutrophils and more M2 macrophages in the wound sites treated with BG compared to those without any treatment. All these results indicate that modulating the inflammatory response is one of the critical mechanisms for BG enhancing wound healing.
Objective To establish a method for determining volatile components from Actinidia valvata Dunn .Methods A static headspace‐gas chromatography‐mass spectrometry (HS‐GC‐MS) method was used to analyze volatile components , and the separated peaks were identified by mass spectal library searching combined with retention index comparison .Results 42 volatile components were separated from Actinidia valvata Dunn and 25 of them were identified ,mainly including alcohols ,es‐ters ,aldehydes ,hydrocarbons and so on .Conclusion Combined with retention index calculation ,this method improved accuracy of qualitation of HS‐GC‐MS and provided scientific proof for the exploitation and utilization of Actinidia valvata Dunn .