ABSTRACT
O sistema imunológico é formado por um conjunto de células que protege o organismo contra patógenos e outros agentes estranhos. A imunidade pode atuar de maneira correta e eficaz, entretanto é necessário o consumo adequado de alimentos que têm como função fortalecer e regular o sistema imunológico. Dessa forma, questiona-se: qual o conhecimento dos estudantes universitários de uma faculdade em Sete Lagoas/MG acerca dos alimentos, fontes de vitaminas A, C, D, zinco, glutamina e ômega-3, como nutrientes reguladores na manutenção do sistema imune? Trata-se de um estudo de natureza descritiva e exploratória, por meio de uma pesquisa de campo, realizada com 50 acadêmicos matriculados em uma faculdade localizada em Sete Lagoas/MG. Dos entrevistados, a maioria reconheceu os grupos de alimentos que possuíam os nutrientes estudados: vitamina A (76%), vitamina C e D (70%), zinco (52%), glutamina e ômega-3 (76%). Os resultados evidenciaram que a maioria dos estudantes universitários (84%) apresentou conhecimento acerca da relação entre os nutrientes e suas ações regulatórias no sistema imune. Conclui-se que é importante a pesquisa de temáticas como esta, no sentido de informar e conscientizar os indivíduos sobre os benefícios da ingestão de vitaminas e minerais e sua relação com a manutenção do sistema imune, a fim de influenciar em melhores escolhas alimentares.
The immune system is made up of a set of cells that protect the body against pathogens and other foreign agents. Immunity can act correctly and effectively, however, adequate consumption of foods that have the function of strengthening and regulating the immune system is necessary. Thus, the question is: what is the knowledge of academics from a college in Minas Gerais about food, sources of vitamins A, C, D, zinc, glutamine and omega-3 as regulatory nutrients in the maintenance of the immune system? This is a descriptive and exploratory study, through field research, carried out with 50 academics enrolled in a college located in a municipality of Minas Gerais. Of the respondents, most recognized the food groups that had the nutrients studied: vitamin A (76%), vitamin C and D (70%), zinc (52%), glutamine and omega-3 (76%). The results showed that most academics (84%) had accurate knowledge of the relationship between nutrients and their regulatory actions in the immune system. It is concluded that it is important to research topics such as these, in order to inform and make individuals aware of the benefits of the intake of vitamins and minerals and their relationship with the maintenance of the immune system, in order to influence better food choices.
El sistema inmunológico está formado por un conjunto de células que protegen al organismo contra patógenos y otros agentes extraños. La inmunidad puede actuar de forma correcta y efectiva, sin embargo, es necesario consumir alimentos adecuados cuya función sea fortalecer y regular el sistema inmunológico. Por lo tanto, surge la pregunta: ¿qué conocimiento tienen los estudiantes universitarios de una facultad de Sete Lagoas/MG sobre alimentos, fuentes de vitaminas A, C, D, zinc, glutamina y omega-3, como nutrientes reguladores en el mantenimiento del sistema inmunológico? Se trata de un estudio descriptivo y exploratorio, a través de investigación de campo, realizado con 50 académicos matriculados en una facultad ubicada en Sete Lagoas/MG. De los entrevistados, la mayoría reconoció los grupos de alimentos que contenían los nutrientes estudiados: vitamina A (76%), vitamina C y D (70%), zinc (52%), glutamina y omega-3 (76%). Los resultados mostraron que la mayoría de los estudiantes universitarios (84%) tenía conocimiento sobre la relación entre los nutrientes y sus acciones reguladoras sobre el sistema inmunológico. Se concluye que es importante investigar temas como este, con el fin de informar y concientizar a los individuos sobre los beneficios de la ingesta de vitaminas y minerales y su relación con el mantenimiento del sistema inmunológico, para incidir en mejores elecciones alimentarias.
ABSTRACT
Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.
ABSTRACT
@#Objective To investigate the expression of methyltransferase like-3(METTL3)in esophageal cancer tissues and its effects on the proliferation,migration,apoptosis and glutamine metabolism of cells.Methods The expression of METTL3 in esophageal cancer and paraneoplastic tissues was detected by qRT-PCR,Western blot and Immunohistochemistry. The effects of METTL3 inhibitor STM2457 on cell proliferation and migration of human esophageal squamous carcinoma cell lines Eca109 and KYSE150 were detected by CCK8,cloning assay,scratch test and Transwell assay. The effects on cell cycle and cell apoptosis were measured by flow cytometry and TUNEL experiment. TMT/iTRAQ quantitative proteomics experiment was used to identify the effects on downstream related signaling pathways. Glutamine assay,glutamate assay and Western blot were used to analyze the effect on glutamine metabolism in esophageal cancer cells.Results METTL3 gene expression was significantly upregulated in esophageal cancer tissues(t = 5. 024,P < 0. 000 1). STM2457 inhibited METTL3 expression in Eca109 and KYSE150 cells,significantly inhibited the cell proliferation and migration,blocked the cell cycle in G0/G1 phase,increased the cell apoptosis,decreased the glutamine uptake and glutamate production,and down-regulated the expression of glutamine-related proteins alanine-serine-cysteine transporter 2(ASCT2),glutaminase(GLS)and glutamate dehydrogenase 1(GLUD1). The glutamine uptake and glutamate production in Eca109 and KYSE150 cells decreased significantly after METTL3 knockdown(glutamine uptake:t = 24. 52-41. 01,each P < 0. 01;glutamate production:t = 8. 431-11. 83,each P < 0. 01);After METTL3 overexpression,the glutamine uptake and glutamate production in Eca109 and KYSE150 cells increased significantly(glutamine uptake:t = 5. 803 and 56. 13,respectively,each P < 0. 01;glutamate production:t = 11. 06 and 4. 695,respectively,each P < 0. 01). After METTL3 knockdown,the expression levels of glutamine metabolism related proteins ASCT2,GLS and GLUD1 in Eca109 and KYSE150 cells were significantly down-regulated,while after METTL3 overexpression,the expression levels of ASCT2,GLS and GLUD1 were significantly up-regulated.Conclusion METTL3 is highly expressed in esophageal cancer and may promote cell proliferation by mediating glutamine metabolism in esophageal cancer cells.
ABSTRACT
Objective:To explore the correlation between c-myc and glutaminase(GLS)and glutamine synthase(GS)in oral epider-moid carcinoma cells in animal models.Methods:Immunohistochemistry was used to detect the expression of c-myc,GLS and GS in clinical samples of oral cancer.KB cell model with stable and high expression of c-myc was established and verified,then the KB cells were transplanted into nude mice to establish mouse tumorigenic models.The cells and nude mouse models were respectively diveded into 3 groups(n=6):normal cotnrol,empty vector and c-myc overexpression groups.The tumor growth was observed.The expression of c-myc,GLS and GS in the cells and the tumor samples was detected by immunohistochemistry.Results:c-myc,GLS and GS were highly expressed in clinical samples of oral cancer.In the cells of c-myc overexpression group c-myc mRNA expression level was sig-nificantly higher than that of empty vector control group.The tumorigenic models were formed in all nude mice of the groups,and the volume and weight of the c-myc overexpression group increased more significantly(P＜0.01),in the c-myc overexpression group c-myc was overexpressed,the expression of GLS and GS was significantly higher than that in the other 2 groups.Conclusion:c-myc is highly expressed in oral cancer,and may up-regulate GLS and GS expression.
ABSTRACT
Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.
ABSTRACT
Objective To investigate the effect of berberine hydrochloride tablets combined with compound glutamine in treating ulcerative colitis(UC).Methods One hundred and two patients with UC admitted to our hospital were collected and grouped into two groups according to the random number table.Fifty-one patients in the control group were given conventional treatment+compound glutamine,and 51 patients in the experimental group were given berberine hydrochloride tablets based on the control group.Both groups were treated for 8 weeks.The efficacy,modified Mayo score,intestinal mucosal barrier function,soluble late glycation end product receptor(sRAGE),interleukin-17(IL-17),IL-6 and incidence of untoward reactions were compared between the two groups.Results The total effective rate of the experimental group was higher than that of the control group(92.2%vs.76.5%,P＜0.05).After treatment,scores of defecation frequency,blood in stool,endoscopic findings,physician's overall evaluation,diamine oxidase(DAO),D-lactic acid,endotoxin,sRAGE,IL-17 and IL-6 were lower in both groups than those before treatment(P＜0.05),and the research group was lower than the control group(P＜0.05).There was no significant difference in the total incidence of untoward reactions between the experimental group and the control group(P＞0.05).Conclusion Berberine hydrochloride tablets combined with compound glutamine are effective in treating UC,which can reduce the activity of UC,improve the intestinal mucosal barrier function,regulate serum sRAGE,IL-17 and IL-6 levels,without increasing adverse reactions.
ABSTRACT
Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.
Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.
ABSTRACT
Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.
Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.
Subject(s)
Animals , Male , Rats , Burns/drug therapy , Glutamine , Rats, Wistar , Dipeptides , Disease Models, Animal , Amino AcidsABSTRACT
The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.
Subject(s)
Escherichia coli/genetics , Glutamine , Zeolites/chemistry , Amino AcidsABSTRACT
Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Subject(s)
Male , Humans , Glutamine/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapyABSTRACT
The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
ABSTRACT
As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses use the energy and precursors provided by the metabolic network of the host cells to drive their replication, assembly and release. Namely, viruses hijack the host cells metabolism to achieve their own replication and proliferation. In addition, viruses can also affect host cell metabolism by the expression of auxiliary metabolic genes (AMGs), affecting carbon, nitrogen, phosphorus, and sulfur cycles, and participate in microbial-driven biogeochemical cycling. This review summarizes the effect of viral infection on the host's core metabolic pathway from four aspects: cellular glucose metabolism, glutamine metabolism, fatty acid metabolism, and viral AMGs on host metabolism. It may facilitate in-depth understanding of virus-host interactions, and provide a theoretical basis for the treatment of viral diseases through metabolic intervention.
Subject(s)
Humans , Metabolic Networks and Pathways , Virus Diseases , Carbohydrate Metabolism , Host Microbial Interactions , Lipid MetabolismABSTRACT
Radiotherapy is an important treatment method for malignant tumors. Radiation resistance is the main obstacle to the therapeutic effect of radiotherapy. Cellular metabolic reprogramming is one of the main features of cancer, and it may have an important effect on the therapeutic effect of radiotherapy. Glutamine is closely related to tumor cell biosynthesis and growth. It affects radiotherapy sensitivity by producing antioxidants through decomposition. In addition, the expression patterns and functions of two isoenzymes of glutamine, namely, glutaminase (GLS) and glutaminase 2 (GLS2), are different and have an important influence on the sensitivity of radiotherapy. The utilization of glutamine metabolism in the tumor microenvironment has great research value to improve the efficacy of radiotherapy. This review describes the metabolic characteristics of glutamine in malignant tumors and the sensitization effect of glutamine inhibitors on the efficacy of radiotherapy.
ABSTRACT
This study was performed to explore the impact of glutamine(Gln)on the anti-tumor immune response of CD8+ T cells and its mechanism.TCGA database was used to analysis the relationship between tumor Gln metabolism and the quantity and functionality of infiltrating CD8+ T cells.CRISPR/Cas9 was employed to knock down GLS expression in mouse MC38 cells,and a mouse tumor model was established.Flow cytometry was conducted to assess tumor proliferation,apoptosis,and the quantity and functionality of tumor-infiltrating immune cells.Lymphocytes isolated from health individuals were treated with Gln-deficient media,complete media or media supplemented with GSH,RSL3 in vitro.Then the apoptosis,the expression levels of GPX4,Lipid-ROS,and effector function protein of CD8+ T cells were detected by flow cytometry.Furthermore,RNA-seq was performed to analyze the differential gene expression on the Gln-depleted CD8+ T cells.Data showed that tumor Gln metabolism was inversely associated with the quantity and functionality of tumor-infiltrating CD8+ T cells.Low expression of GLS in MC38 cells could inhibit C57BL/6 tumor growth,decrease Ki-67 expression,promote casepase-3 expression,increase the amount of tumor-infiltrating immune cells,suppress PD-1,TIM-3,and LAG-3 expression,and enhance CD137,CD107a,IFN-γ and TNF-α expression in tumor-infiltrating CD8+ T cells.RNA-seq results indicated an upregulation of ferroptosis genes TFRC,HMOX1,CYBB and SLC7A11 in CD8+ T cells following glutamine deficiency.Gln deficiency led to lower CD137,CD107a,IFN-γ,GSH,GPX4 expression,increased Lipid-ROS level,and caused cell death in CD8+ T cells.Supplementation of GSH upregulated GPX4 expression,downregulated Lipid-ROS level,and increased IFN-γ secretion in CD8+ T cells.In conclusion,Gln deficiency inhibits the effector function of CD8+ T cells by inducing ferroptosis,and promotes tumor growth.
ABSTRACT
Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.
ABSTRACT
Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.
Subject(s)
Animals , Rats , Carcinoma 256, Walker , Rats, Wistar , Glutamine , Kidney Glomerulus , AntioxidantsABSTRACT
Background: Cancer cells addiction to glutamine, an essential non-essential amino acid, has stirred up the interest in researchers across the globe. Increased glutamine metabolism (glutaminolysis) is a hallmark of cancer. Targeting glutaminolysis via glutaminase inhibition emerges as a promising strategy to disrupt cancer metabolism and tumor progression. Diallyl disulfide (DADS), a major organosulfur compound derived from garlic, is known for its anticancer properties. The mechanisms of action of DADS include activation of metabolic enzymes that detoxify carcinogens, suppression of the formation of DNA adducts, antioxidant effects, regulation of cell-cycle progression, induction of apoptosis, and inhibition of angiogenesis and metastasis. Aim: to assess the effect of diallyl disulfide on liver glutaminase activity in experimentally induced hepatoma in mice. Materials & Methods: Swiss albino male mice were divided into four groups - normal, control, preventive and curative groups. Hepatoma was induced by intraperitoneal injection of Ehrlich ascites carcinoma (EAC) cells. DADS (100 mg/kg body weight/mouse/day) was orally fed to protective and curative group mice for a stipulated time period. Mice of all the groups were sacrificed, and liver tissue glutaminase activity were measured. Results: The present study shows a significant decrease in glutaminase activity in protective (p >0.001) and curative groups (p >0.001) as compared to control group. Conclusion: DADS at the dosage employed shows inhibitory effects on liver glutaminase activity which may be attributed to anti-inflammatory properties of DADS, specifically in suppression of NF-kB signalling pathway.
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SUMMARY OBJECTIVE: The aim of this study was to explore the efficacy of imipenem combined with glutamine in the treatment of severe acute pancreatitis with abdominal infection in mainland China using meta-analysis. METHODS: We searched China National Knowledge Network, Wanfang Medical Network, Chinese Science Citation Database, PubMed, and Embase Databases for publications of imipenem combined with glutamine in the treatment of severe acute pancreatitis abdominal infection. The search time limit was from the establishment of the database to April 10, 2021. Stata software version 12.0 was used for statistical analysis; the combined effect size odds ratio and standardized mean difference values were calculated for the count data and measurement data, respectively; and the heterogeneity test was performed in this study. RESULTS: A total of five randomized controlled trials were included. A total of 499 cases were included, with 251 in the observation group and 248 in the control group. Meta-analysis results showed that the efficacy of imipenem combined with glutamine in the treatment of severe acute pancreatitis with abdominal infection was significantly better than that of imipenem alone (odds ratio=0.78, 95%CI 0.71-0.86, p=0.040). CONCLUSION: Imipenem combined with glutamine can significantly improve the efficacy in the treatment of severe acute pancreatitis with abdominal cavity infection.
ABSTRACT
OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.
Subject(s)
Humans , Chromatography, High Pressure Liquid , Core Binding Factor Alpha 3 Subunit/genetics , Glutathione Disulfide , Metabolomics , NADP , Stomach Neoplasms/genetics , Tandem Mass Spectrometry , Trastuzumab/pharmacologyABSTRACT
The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.