Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of Alzheimer's disease by modulating glutamine metabolism of the gut microbiome

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.

Effects of Supplemental Glutamine and Lysine on Growth Performance of Broiler Chickens

The optimum levels of Lysine and Glutamine needed for growth performance and maintenance of the chicken broilers were evaluated in a randomized 3 × 4 factorial arrangement of dietary treatments. The battery cages measured 99 × 66 × 25 cm that can be sufficient for 5 birds. Day old Chicken broilers totaling 180 were assigned to dietary treatments comprising of 3 concentrations of Lysine (0.85, 1.14, and 1.42) each in combination with 4 concentrations of Glutamine (0, 1, 2, and 3). Each dietary treatment was replicated 3 times and each replication had 5 birds. The birds were given feed and water ad libitum with a 23-hour light regimen for a period of 4 weeks. Then, the experimental birds were evaluated for body weight gain, feed consumption, and feed conversion in order to determine their optimum requirement for dietary Lysine and Glutamine. Based on the findings of this study, the highest performance was observed in birds fed the diet supplemented with 1.42 lysine and 1% glutamine, but the highest improvement in feed conversion was observed in diet contain 1.14 and 1.42 with 1% and 3% glutamine, respectively. Birds fed 1.42 lysine and 1% glutamine had the highest total body weight gain and feed consumption. The lysine requirements in the diet for Chicken are between 1.14 and 1.42 with glutamine level of 1%.

Dynamics of glutamine synthetase expression in hepatic ischemiareperfusion injury: Implications for therapeutic interventions

BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression during hepatic IRI remain unclear.AIM To investigate the dynamic expression of GS during hepatic IRI.METHODS Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,section-ing.Hematoxylin and eosin staining and GS staining were performed.RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually recovers.CONCLUSION GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

基于GINS家族成员在胶质瘤组织中的表达水平对其进行分型及其临床意义

目的:基于GINS家族成员在胶质瘤组织中表达水平对其分型,探究此分型预测胶质瘤患者的预后、免疫治疗疗效的有效性,采用TCMOI数据库虚拟筛选可靶向GINS的中药小分子。方法:数据库分析GINS基因组学、胶质瘤组织中差异表达基因与患者预后的关系,基于GINS家族成员基因表达对胶质瘤进行分型并分析各亚型的预后情况,数据库数据分析各亚型中的基因突变、基因富集、肿瘤纯度和免疫细胞浸润评分,以及与GINS2可能相互作用的中药小分子,最后用qPCR法检测中国人胶质瘤组织中GINS1~4 mRNA的表达水平以验证其与数据库数据的一致性。结果:GINS家族各成员间的基因、蛋白结构和功能相似,胶质瘤组织中GINS家族成员呈高表达且与患者不良预后密切相关(P<0.05),基于GINS家族成员在胶质瘤组织中表达水平的S1、S2亚型分类能较好地预测胶质瘤患者的预后,S1亚型主要突变基因为CDKN2A/B、EGFR、PTEN而S2亚型的突变基因为IDH1、TP53和ATRX,GINS家族可能通过调控免疫微环境影响胶质瘤患者预后,CD276和CX3CL1可能是S1亚型胶质瘤患者实施免疫治疗的潜在靶点,CHEMBL66033、266935、293914、436859、1594881可能是潜在的靶向GINS2的中药小分子。结论:基于GINS家族构建的胶质瘤分子分型有助于识别更适合免疫治疗的高风险患者,筛选出的中药小分子可为胶质瘤患者分子靶向治疗和免疫治疗提供参考。

Gin+GORM通用MIS系统设计

文章旨在介绍一种基于Go语言中的Gin和GORM框架开发的通用管理信息系统(Management Information System,MIS)的设计与实现。MIS系统在各种组织中发挥着关键作用,用于处理、管理和分析各种信息,通过Gin和GORM这两个流行的开源框架,可以快速搭建一个稳定、高效的MIS系统,以满足企业管理信息系统的需求,并提供友好的用户界面和可靠的数据管理。该方案可针对不同的业务需求进行快速定制和扩展功能,具有高度可扩展性和灵活性。

Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats

BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every day.Three hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the rats.The small intestine tissue was stained to analyze pathological structural changes and apoptosis.Finally,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc comparisons.RESULTS:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the criterion.Glutamine supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal levels.The intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG group.Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression.CONCLUSION:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

Characterization of prognosis and immune infiltration by a novel glutamine metabolism-related model in cutaneous melanoma

Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.

Glutamine addiction and therapeutic strategies in pancreatic cancer

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis,early metastasis,and poor prognosis.Because current therapeutic options are limited,there is an urgent need to investigate novel targeted treatment strategies.Pancreatic cancer faces significant metabolic challenges,principally hypoxia and nutrient deprivation,due to specific microenvironmental constraints,including an extensive desmoplastic stromal reaction.Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation.Increased glucose uptake and glycolytic pathway activity during this process have been extensively described.However,growing evidence suggests that pancreatic cancer cells are glutamine addicted.As a nitrogen source,glutamine directly(or indirectly via glutamate conversion)contributes to many anabolic processes in pancreatic cancer,including amino acids,nucleobases,and hexosamine biosynthesis.It also plays an important role in redox homeostasis,and when converted toα-ketoglutarate,glutamine serves as an energy and anaplerotic carbon source,replenishing the tricarboxylic acid cycle intermediates.The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer,focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

Methods for the Determination of Stable Isotopes of Carbon and Nitrogen Directly in Valine, Proline, Glutamine, and Glutamic Acid

Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can be synthesized either naturally or artificially. To examine the metabolism and regulate the synthesis process, compounds labeled with nitrogen or carbon isotopes need to be used. These isotopic compounds allow for more extensive research and enable studies that would otherwise be impossible. However, their use is dependent on the availability of simple, efficient methods for isotopic analysis. Currently, the determination of the atomic fraction of carbon and nitrogen isotopes is only possible through their conversion into molecular nitrogen or carbon monoxide or carbon dioxide. This leads to the loss of information about isotopic enrichment in specific centers of the molecule. This article explores a new direct approach to determining the atomic fraction of carbon and nitrogen isotopes in the isotope-modified or identical centers of these compounds. This method eliminates the transfer process and dilution due to nitrogen and carbon impurities. It is now possible to simultaneously determine the atomic fraction of nitrogen and carbon isotopes in the research substance. This method can be applied to amino acids, making it an effective tool for proposing new research methods. Several articles [1] [2] [3] have proposed similar methods for organic compounds and amino acids.

Prognostic model and treatment plan analysis of hepatocellular carcinoma based on genes related to glutamine metabolism

Objective:To identify the prognosis of hepatocellular carcinoma(HCC)and the effect of anti-cancer drug therapy by screening glutamine metabolism-related signature genes because glutamine metabolism plays an important role in tumor development.Methods:We obtained gene expression samples of normal liver tissue and hepatocellular carcinoma from the TCGA database and GEO database,screened for differentially expressed glutamine metabolismrelated genes(GMRGs),constructed a prognostic model by lasso regression and step cox analysis,and assessed the differences in drug sensitivity between high-and low-risk groups.Results:We screened 23 differentially expressed GMRGs by differential analysis,and correlation loop plots and PPI protein interaction networks indicated that these differential genes were strongly correlated.The four most characterized genes(CAD,PPAT,PYCR3,and SLC7A11)were obtained by lasso regression and step cox,and a risk model was constructed and confirmed to have reliable predictive power in the TCGA dataset and GEO dataset.Finally,immunotherapy is better in the high-risk group than in the low-risk group,and chemotherapy and targeted drug therapy are better in the low-risk group than in the high-risk group.Conclusion:In conclusion,we have developed a reliable prognostic risk model characterized by glutamine metabolism-related genes,which may provide a viable basis for the prognosis and Treatment options of HCC patients.

国际水电项目GIN参数设计方法研究

在Lombardi博士的GIN理论基础上,结合世界大坝委员会的坝基设计公报及以往国际水电站工程采用GIN灌浆取得的经验,依托科特迪瓦波波里水电站土石坝帷幕灌浆的实践,阐述了基于坝基岩石质量与压水试验成果的GIN设计值的取值方法,提出了P_(max)、V_(max)值设计时需要考虑的两种边界条件,并通过理论公式计算及实践经验提出了浆液扩散半径的安全保证系数。

国际水电站GIN稳定浆液配比设计方法研究

在GIN灌浆理论中,浆液是单一配比的稳定浆液,浆液在2h内的沉淀率应小于5%。在高压力灌浆条件下,稳定浆液可以避免在岩石裂隙中出现水浆分离的现象,更好地保证灌浆质量。本文在Lombardi博士研究成果的基础上,结合以往现场浆液试验与实践经验,从浆液2h沉淀率、7d抗压强度、稠度等指标,以科特迪瓦波波里水电站项目为依托,研究在坝基强弱风化岩石条件下GIN稳定浆液配合比设计方法。

Effects of Neuromuscular Electrical Stimulation in Combination with Glutamine Administration on Skeletal Muscle Atrophy in Colon-26 Tumor-Bearing Mice

The depressed protein synthetic response,a phenomenon termed anabolic resistance,has been shown to be involved in muscle wasting induced by cancer cachexia.Moreover,a positive relationship between the protein synthetic rate and intracellular glutamine(GLN)concentration has been found in skeletal muscles.This study investigated the effects of neuromuscular electrical stimulation(ES)and GLN administration on muscle wasting and GLN metabolism in colon-26(C-26)tumor-bearing mice.CD2F1 mice were divided into 8 groups:control(CNT),CNT+ES,CNT+GLN,CNT+ES+GLN,C-26,C-26+ES,C-26+GLN,C-26+ES+GLN.Cancer cachexia was induced by subcutaneous injection of C-26 cells and developed for four weeks.ES was performed on the left plantar flexor muscles every other day,and GLN(1 g/kg)was administered daily intraperitoneally starting one day after the C-26 injection.Tumor-free body mass and fast-twitch gastrocnemius(Gas)muscle weight were lower in the C-26 group than in the CNT group(-19%and-17%,respectively).Neither ES training nor GLN administration,alone or in combination,ameliorated the loss of Gas muscle weight in the C-26 mice.However,ES training in combination with GLN administration inhibited the increased expression of GLN synthetase(GS)in the C-26 muscles.Thus,it is likely that GLN plays a critical role in muscle protein metabolism and,therefore,can be targeted as a tentative treatment of cancer cachexia.

Glutamine Metabolism: A New Target Pathway for PET Imaging and Cancer Therapy

Individuals with metabolic syndrome will have increased risk for cardiovascular disease, diabetes and cancer. Based on abnormal glucose metabolism, or called Warburg effect in cancer cells, positron emission tomography (PET) imaging using 18F-FDG has achieved a great success in diagnosis and monitoring therapeutic responds for cancer patients. Beyond glucose metabolism, resurgence of glutamine metabolism in cancer research has recently broadened interests. Observations of addiction to glutamine in cancer cells lead to considering contribution of glutaminolysis in cancer cell growth, differentiation and proliferation. Furthermore, oncogenes have been found to be major factors in modulating abnormal glutamine metabolism in cancer cells. PET imaging probes and therapeutic agents targeting glutamine metabolic and signaling pathways have been proposed and investigated.

The Absorption and Transportation of Glutamine Containing Small Peptides-Arg-Gly-GIn and Gly-GIn in Jejunum of Weaned Piglets

In order to research the absorption and transportation differences ofglutamine containing small peptides and free glutamine in intestine of weaned piglets, 28-day-old weaned piglets were selected to get the sample for jejunum culture in vitro in this study. Trial 1 was conducted to study the stability of tripeptide （Arg-Gly-Gln） in the jejunum to determine the ideal culture time. It was designed into 2 treatments： control group （Kreb＇s solution, GC） and tripeptide group （by adding 556μmol/L of Arg-Gly-Gln to Kreb＇s solution, GP）. They were cultured for 60 min. The absorption and transportation differences ofglutamine existing as Arg-Gly-Gln, Gly-Gln and free Gin were studied in trial 2. It was designed into 4 treatments： group 1 （G1, control group）, Kreb＇s solution; Group 2 （G2）, Kreb＇s solution＋556 μmol/L Arg-Gly-Gln; group 3 （G3）, Kreb＇s solution＋556 μmol/L Gly-Gln and Arg; group 4 （G4）, Kreb＇s solution＋556 μmol/L arginine, glycine and glutamine. They were cultured for 40 minutes. The results indicated that the absorption and transportation of glutamine existing as Arg-Gly-Gln was more efficient than those of Gly-Gln while Gly-Gln was more efficient than free glutamine. Arg-Gly-Gln may be more excellent than Gly-Gln in physiological functions and nutrition potential.

基于生物信息技术分析GINS1基因在肺癌中的表达及意义

背景与目的 肺癌是全球最常见的恶性肿瘤,大多数患者初次诊断时已发生转移,因此寻找肺癌新的诊断标志物并探索其在肺癌发生中的作用具有重要价值。基于生物信息数据探讨分析肺癌中GINS1基因与肺癌预后的相关性具有重要意义。方法 检索Oncomine、EGPIA、TCGA、Human protein atlas等基因数据库,分析GINS1基因在肺癌中的表达差异。应用蛋白质免疫印记法检测肺癌及癌旁组织中GINS1蛋白的表达水平,应用Kaplan-Meier进行患者生存分析,并利用String-DB数据库分析GINS1蛋白相互作用网络。结果 对Oncomine、GEPIA和The Human Protein Atlas数据库中肺癌与癌旁组织蛋白表达数据进行差异性分析,发现GINS1蛋白在肺癌组织中显著高表达,特别以肺腺癌、肺鳞癌中表达明显增加;通过生存分析发现高表达GINS1肺腺癌患者生存期明显低于低表达者,高表达患者预后更差;利用String-DB数据库发现与GINS1蛋白关联最为密切的为GINS蛋白家族(GINS2、GINS3、GINS4),其次为CDC45、MCM蛋白家族(MCM2、MCM3、MCM4、MCM5、MCM6、MCM7),富集分析发现互作蛋白主要参与DNA复制和细胞周期。结论GINS1基因在肺癌组织中显著高表达,与患者预后相关,其有可能成为肺癌诊断及药物治疗的新靶点。

稳定浆液在GIN灌浆法中的应用

稳定浆液是近些年发明的新材料,其在国外灌浆工程得到了广泛应用。介绍了乌干达纳录巴奥水电站修复工程现场GIN灌浆法稳定浆液试验,开展稳定浆液试验的机理研究,并通过运用合理、科学的施工工艺进行GIN灌浆法施工,灌浆质量检查成果显示取得了理想的灌浆效果。稳定浆液具有较好的流动性,对裂隙细小处灌浆效果良好,但是漏水处及特殊情况处理还需要积累经验。

GINS1基因在恶性肿瘤中的研究进展

GINS1基因是GINS复合体的一个重要成员,发挥着许多重要的生物学功能,包括调控多功能蛋白、生长因子信号、受体分子等,参与DNA复制和细胞周期进展的启动。GINS1基因在大多数人体肿瘤中呈现异常表达,通过不同的分子机制及信号转导通路影响肿瘤进展和预后。近年来,GINS1基因作为恶性肿瘤潜在的治疗和预后生物标志物被广泛研究。本文就GINS1基因在恶性肿瘤中的研究进展进行综述,旨在为GINS1基因在恶性肿瘤靶向治疗中的应用提供理论依据。

Analysis of the Effect of GINS4 Regarding the Proliferation and Invasion of Breast Cancer Cells

Objective: To analyze the role and influence of the GINS4 gene in breast cancer progression and to explore its expression in triple-negative and non-triple-negative breast cancer cell lines. Methods: Single-gene analysis of GINS4 was performed by breast cancer RNA transcriptome data from The Cancer Genome Atlas (TCGA). Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of GINS4 in triple-negative and non-triple-negative breast cancer cell lines. The knockdown effects of GINS4 in MDA-MB-231 and MCF-7 cell lines on the proliferation and invasion of breast cancer cells were examined by cell counting kit 8 (CCK8) and Transwell assays. Results: Bioinformatics analysis showed that the expression of GINS4 in breast cancer was significantly higher than that in normal breast tissues (P > 0.05). At the same time, cell experiments confirmed that GINS4 was highly expressed in human breast cancer cell lines with normal breast cells as reference and in MDA-MB-231 and MCF-7 cell lines as reference, where the ability of proliferation and invasion of MDA-MB-231 and MCF-7 cells decreased after GINS4 knockdown. Conclusion: GINS4 is a gene associated with breast cancer malignancy, which can act as a novel tumor marker and has the potential as a new therapeutic target for breast cancer.

传统灌浆和GIN灌浆在卢旺达电站中的应用比较

卢旺达那巴龙格河二号水电站坝肩主要由黏土、粉土和砂等组成。灌浆试验区内地层从上至下依次为覆盖层、全风化岩石、强风化岩石和弱风化岩石。针对灌浆方法,业主意大利咨询坚持采用GIN灌浆;中方则对传统灌浆的施工方法更熟悉,认为对大坝的质量更有保证。为确认哪一种方案更适应本项目的地质条件,项目部进行两种方案试验,以确认哪一种方案将用于后续的大坝坝肩及坝体灌浆,并能获得更好的施工质量,确保大坝的稳定安全。