Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

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.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats

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.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats / O dipeptídeo de glutamina oral ou aminoácido livre de glutamina oral reduz a progressão da lesão por queimadura em ratos

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.

Effect of viral infection on host cell metabolism: a review / 生物工程学报

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.

Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment

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.

A metabolic intervention strategy to break evolutionary adaptability of tumor for reinforced immunotherapy

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.

The role of glutamine metabolism in castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

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.

Immobilizing engineered Escherichia coli cells into zeolitic imidazolate framework 8 for efficient biosynthesis of Ala-Gln / 生物工程学报

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.

Research Progress in Improving Efficacy of Radiotherapy by Targeting Glutamine Metabolism / 肿瘤防治研究

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.

L-glutamine supplementation reduced morphological damage in the renal glomerulus of rats with Walker-256 tumor

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.

Inhibition of liver glutaminase activity by Diallyl disulfide in experimentally induced hepatoma in mice

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.

Effects of imipenem combined with glutamine in the treatment of severe acute pancreatitis with abdominal infection in mainland China: a meta-analysis

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.

Progress in Research on Glutamine Metabolism in Energy Metabolism of Gastric Cancer / 胃肠病学

Gastric cancer is one of the most common malignant tumors of digestive system. Due to lack of early diagnosis methods, the mortality rate of gastric cancer is relatively high. For meeting their own needs, the tumor cells can reprogram their metabolism, and glutamine metabolism plays an important role in tumor cell growth and proliferation. Therefore, it needs to elucidate the new potential molecular mechanisms of gastric cancer and to discover the potential biomarkers related to glutamine metabolism, so as to provide new targets and schemes for the diagnosis and treatment of gastric cancer. This article reviewed the progress in research on glutamine metabolism in energy metabolism of gastric cancer.

The Role of KCNQ1OT1 in Gastric Cancer Based on Bioinformatics Analysis / 中国生物化学与分子生物学报

Long non-coding RNA KCNQ1OT1 is highly expressed in a variety of tumors, but there are few studies in gastric cancer and the results are inconsistent. The relevant research of its specific mechanism in gastric cancer is also scarce. Through the analysis of several TCGA public databases, we found that KCNQ1OT1 was generally highly expressed in gastric cancer, and the prognosis of gastric cancer patients with a high expression of KCNQ1OT1 was poor. The expression of KCNQ1OT1 is closely related to many clinical factors of gastric cancer, especially the mutation of TP53, and its expression is significantly related to immune cell infiltration. KCNQ1OT1 is generally highly expressed in gastric cancer cell lines. Knockdown of KCNQ1OT1 can inhibit the proliferation of gastric cancer cell lines. Co- expression network analysis showed that its expression was closely related to tumor metabolism. Glutaminase 1 (GLS1) is generally highly expressed in gastric cancer, which is closely related to a poor prognosis. There is a significant correlation between the expression of KCNQ1OT1 and GLS1. Knockdown of KCNQ1OT1 can inhibit the expression of GLS1 mRNA, and overexpression of GLS1 can partially rescue the proliferation of gastric cancer cells caused by knockdown of KCNQ1OT1. Therefore, we speculate that KCNQ1OT1 may regulate the growth of gastric cancer cells through GLS1. Our study explored the role of KCNQ1OT1 in gastric cancer through bioinformatics database and experiments, suggesting that KCNQ1OT1 may promote the development of gastric cancer by regulating glutamine metabolism, which provides a new target for the clinical research on targeted treatment in gastric cancer.

RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

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.

Validation of compound C19 as a glutaminase C inhibitor / 药学学报

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.

Expert consensus on clinical application of intravenous alanyl-glutamine dipeptide / 中华临床营养杂志

Alanyl-glutamine dipeptide is an important component in parenteral nutrition, which can be decomposed into alanine and L-glutamine in vivo. It plays multiple functions including maintaining intestinal barrier, improving immunity, promoting protein synthesis, and regulating the production and release of inflammatory mediators. Substantial clinical evidences have demonstrated its favorable effectiveness and safety. Rational application of alanyl-glutamine dipeptide can reduce postoperative complications, shorten hospital stay and save medical costs. There are still controversies at home and abroad on the applicable population and dosage of alanyl-glutamine dipeptide. Chinese Society of Parenteral and Enteral Nutrition organized China's experts of related disciplines to compile international standards in accordance with the latest guidelines and consensus, so as to achieve the goal of standardized application and patient benefits.

Different doses of ulinastatin combined with glutamine in treatment of acute severe pancreatitis / 中华内分泌外科杂志

Objective:To study the clinical effect of different doses of ulinastatin combined with glutamine in treatment of acute severe pancreatitis.Methods:70 patients with acute severe pancreatitis patients admitted in our hospital from Jan. 2017 to Oct. 2019 were enrolled. According to the different dosage of ulinastatin, these patients were divided into 200 000 IU ulinastatin combined with glutamine group (200 000 IU combination group) , 400 000 IU ulinastatin combined with glutamine group (400000 IU combination group) , and 600 000 IU ulinastatin combined with glutamine group (600 000 IU combination group) . The study compared the 1-week mortality rate, abdominal pain relief time, respiratory frequency and heart rate back to normal time, blood amylase, glucose, C-reactive protein, procalcitonin levels, and white blood cell (WBC) count among the different groups.Results:The mortality of 400 000 IU combined group and 600 000 IU combined group were 4.35% and 5.56% respectively, which were significantly lower than 31.58% and 35% of the control group and 200 000 IU combined group ( P< 0.05) . The time of abdominal pain relief, respiratory rate and heart rate returning to normal in the 400 000 IU combined group were (7.21±1.25) d, (8.54±1.83) d and (9.54±2.23) d respectively, and (7.52±1.83) d, (8.13±1.75) d and (9.37±2.31) d in the 600 000 IU combined group, which were significantly lower than (9.12±2.78) d, (9.85± 3.16) d and (10.86±2.68) d in the control group and (8.76±1.96) d, (8.76±1.96) d and (10.62±1.43) d in the 200 000 IU combined group ( P<0.05) , There was no significant difference between the control group and the 200 000 IU combination group ( P>0.05) . Compared with the control group, there were significant differences in blood glucose, CRP and leukocyte count in different doses of ulinastatin+ glutamine treatment group ( P<0.05) ; However, there was no significant difference in blood glucose and CRP levels between different doses of ulinastatin+ glutamine treatment group ( P>0.05) , but compared with 200 000 IU combination group and 400 000 IU combination group, the leukocyte level of 600 000 combination group was significantly higher ( P<0.05) . Conclusion:ulinastatin combined with glutamine can significantly improve the clinical prognosis of patients with severe acute pancreatitis, but the clinical effect varies with the dose of ulinastatin. Conclusion Ulinastatin combined with glutamine can significantly improve the clinical prognosis of patients with acute severe pancreatitis, but the clinical effect varies with the dose of ulinastatin.

Advances in the research on mechanism of tumor metabolism regulated by c-Myc / 中国药科大学学报

@#The transcription factor c-Myc regulates the proliferation, differentiation, metabolism and other key processes of normal cells extensively.The unleashed MYC oncogene frequently produces abundant c-Myc protein, which directly regulates the gene expression of key metabolic enzymes, or tumor-related metabolic pathways by inhibiting microRNA, leading to abnormal metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis, and elevated fatty acid and nucleotide synthesis.This paper briefly summarizes how c-Myc regulated metabolism on glycolysis, glutamine metabolism, tricarboxylic acid cycle, lipid metabolism and nucleotide synthesis in cancer cell,which provides some theoretical reference for the development of antitumor targets and drugs involving c-Myc.

Meta-analysis of Glutamine-supplemented Enteral Nutrition in Treatment of Severe Acute Pancreatitis / 胃肠病学

Background: Enteral nutrition is an essential component for treatment of severe acute pancreatitis (SAP), yet there is no consensus on whether glutamine should be added in the enteral nutrition. Aims: To systematically evaluate the effect of glutamine-supplemented enteral nutrition on the condition and prognosis of SAP. Methods: Randomized controlled trials (RCT) on the effect of glutamine-supplemented enteral nutrition in the treatment of SAP were retrieved from CNKI, Wanfang, VIP, SinoMed, The Cochrane Library, PubMed, Embase and Web of Science from the date of database foundation to June 2020. Literatures were enrolled according to the inclusion and exclusion criteria, and the quality was evaluated and data were extracted. RevMan 5.2 software was used to conduct meta-analysis. Results: A total of 18 RCT involving 1 119 patients were included. Meta-analysis showed that glutamine-supplemented enteral nutrition could decrease APACHEⅡ score (MD=-2.20, 95% CI: -2.70-1.71, P<0.000 01), CRP (SMD=-1.20, 95% CI: -1.37-1.02, P<0.000 1), IL-6 (SMD=-2.09, 95% CI: -2.31-1.87, P<0.000 01), TNF-α (SMD=-2.61, 95% CI: -2.82-2.39, P<0.000 01) when compared with conventional enteral nutrition, and could shorten the hospital stay (MD=-4.84, 95% CI: -8.08-1.60, P=0.003). However, no significant differences in the incidence of complications (RR=0.84, 95% CI: 0.66-1.06, P=0.15) and mortality (RR=0.88, 95% CI: 0.51-1.51, P=0.64) were found between the two groups. Conclusions: Glutamine-supplemented enteral nutrition can reduce the inflammation level and improve the severity of SAP, but it has no effect on the incidence of complications and mortality.