Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Mepiquat chloride increases the Cry1Ac protein content of Bt cotton under high temperature and drought stress by regulating carbon and amino acid metabolism

The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the genes encoding glutamate synthase,pyrrolidine-5-carboxylic acid dehydrogenase,glutamate oxaloacetate transaminase,and N-acetylglutamate synthetase,while it downregulated the genes encoding glutamine synthetase.Therefore,the synthesis of aspartic acid,glutamic acid,pyruvate,and arginine increased after treatment with DPC,and the Cry1Ac protein content was increased by regulating carbon and amino acid metabolism.

Global research trends and prospects of cellular metabolism in colorectal cancer

BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

Characteristics of amino acid metabolism in colorectal cancer

In recent years,metabolomics research has become a hot spot in the screening and treatment of cancer.It is a popular technique for the quantitative characterization of small molecular compounds in biological cells,tissues,organs or organisms.Further study of the tumor revealed that amino acid changes may occur early in the tumor.The rapid growth and metabolism required for survival result in tumors exhibiting an increased demand for amino acids.An abundant supply of amino acids is important for cancer to maintain its proliferative driving force.Changes in amino acid metabolism can be used to screen malignant tumors and improve therapeutic outcomes.Therefore,it is particularly important to study the characteristics of amino acid metabolism in colorectal cancer.This article reviews several specific amino acid metabolism characteristics in colorectal cancer.

Impacts of cold exposure on energy metabolism

Cold stimulation has been shown to regulate glucose,lipid,and amino acid metabolism,while also increasing heat production and energy expenditure in the body.Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes,obesity,and cardiovascular disease.Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism.This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways.Furthermore,it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases.

Dietary Enteromorpha polysaccharide-Zn supplementation regulates amino acid and fatty acid metabolism by improving the antioxidant activity in chicken

Background:Enteromorpha prolifera(E.prolifera)polysaccharide has become a promising feed additive with a variety of physiological activities,such as anti-oxidant,anti-cancer,anti-diabetic,immunomodulatory,hypolipidemic,and cation chelating ability.However,whether Enteromorpha polysaccharide-trace element complex supplementation regulates amino acid and fatty acid metabolism in chicken is largely unknown.This study was conducted to investigate the effects of E.prolifera polysaccharide(EP)-Zn supplementation on growth performance,amino acid,and fatty acid metabolism in chicken.Methods:A total of 184 one-day-old Ross-308 broiler chickens were randomly divided into two treatment groups with 8 replicates,12 chickens per replicate,and fed either the basal diet(control group)or basal diet plus E.prolifera polysaccharide-Zinc(400 mg EP-Zn/kg diet).Results:Dietary EP-Zn supplementation significantly increased(P<0.05)the body weight,average daily gain,muscle antioxidant activity,serum HDL level,and reduced serum TG and LDL concentration.In addition,dietary EPZn supplementation could modulate ileal amino acid digestibility and upregulate the mRNA expression of amino acid transporter genes in the jejunum,ileum,breast muscle,and liver tissues(P<0.05).Compared with the control group,breast meat from chickens fed EP-Zn had higher(P<0.05)Pro and Asp content,and lower(P<0.05)Val,Phe,Gly,and Cys free amino acid content.Furthermore,EP-Zn supplementation upregulated(P<0.05)the mRNA expressions of mTOR and anti-oxidant related genes,while down-regulated protein degradation related genes in the breast muscle.Breast meat from EP-Zn supplemented group had significantly lower(P<0.05)proportions ofΣn-3 PUFA,and a higher percentage ofΣn-6 PUFA and the ratio of n-6/n-3 PUFA.Besides,EP-Zn supplementation regulated lipid metabolism by inhibiting the gene expression of key enzymes involved in the fatty acid synthesis and activating genes that participated in fatty acid oxidation in the liver tissue.Conclusions:It is concluded that EP-Zn complex supplementation regulates apparent ileal amino acid digestibility,enhances amino acid metabolism,and decreases oxidative stress-associated protein breakdown,thereby improving the growth performance.Furthermore,it promotes fatty acid oxidation and restrains fat synthesis through modulating lipid metabolism-related gene expression.

Effects of adding sodium dichloroacetate to low-protein diets on nitrogen balance and amino acid metabolism in the portaldrained viscera and liver of pigs

Background:Identifying regulatory measures to promote glucose oxidative metabolism while simultaneously reducing amino acid oxidative metabolism is one of the foremost challenges in formulating low-protein(LP)diets designed to reduce the excretion of nitrogen-containing substances known to be potential pollutants.In this study,we investigated the effects of adding sodium dichloroacetate(DCA)to a LP diet on nitrogen balance and amino acid metabolism in the portal-drained viscera(PDV)and liver of pigs.To measure nitrogen balance,18 barrows(40±1.0 kg)were fed one of three diets(n=6 per group):18%crude protein(CP,control),13.5%CP(LP),and 13.5%CP+100 mg DCA/kg dry matter(LP-DCA).To measure amino acid metabolism in the PDV and liver,15 barrows(40±1.0 kg)were randomly assigned to one of the three diets(n=5 per group).Four essential amino acids(Lys,Met,Thr,and Trp)were added to the LP diets such that these had amino acid levels comparable to those of the control diet.Results:The LP-DCA diet reduced nitrogen excretion in pigs relative to that of pigs fed the control diet(P<0.05),without any negative effects on nitrogen retention(P>0.05).There were no differences between the control and LP-DCA groups with respect to amino acid supply to the liver and extra-hepatic tissues in pigs(P>0.05).The net release of ammonia into the portal vein and production rate of urea in the liver of pigs fed the LP-DCA diet was reduced relative to that of pigs fed the control and LP diets(P<0.05).Conclusion:The results indicated that addition of DCA to a LP diet can efficiently reduce nitrogen excretion in pigs and maximize the supply of amino acids to the liver and extra-hepatic tissues.

Endothelial cell metabolism in sepsis

BACKGROUND:Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure.Endothelial cells(ECs)exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis.METHODS:Web of Science and PubMed were searched from inception to October 1,2022.The search was limited to the English language only.Two reviewers independently identified studies related to EC metabolism in sepsis.The exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Sixty articles were included,and most of them were cell and animal studies.These studies reported the role of glycolysis,oxidative phosphorylation,fatty acid metabolism,and amino acid metabolism in EC homeostasis.including glycolysis,oxidative phosphorylation,fatty acid metabolism and amino acid metabolism.However,dysregulation of EC metabolism can contribute to sepsis progression.CONCLUSION:There are few clinical studies on EC metabolism in sepsis.Related research mainly focuses on basic research,but some scientific problems have also been clarified.Therefore,this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.

Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy

Cancer stem cells(CSCs)possess self-renewal and differentiation potential,which may be related to recurrence,metastasis,and radiochemotherapy resistance during tumor treatment.Understanding the mechanisms via which CSCs maintain self-renewal may reveal new therapeutic targets for attenuating CSC resistance and extending patient life-span.Recent studies have shown that amino acid metabolism plays an important role in maintaining the self-renewal of CSCs and is involved in regulating their tumorigenicity characteristics.This review summarizes the relationship between CSCs and amino acid metabolism,and discusses the possible mechanisms by which amino acid metabolism regulates CSC characteristics particularly self-renewal,survival and stemness.The ultimate goal is to identify new targets and research directions for elimination of CSCs.

From the imbalance of tumor amino acid metabolism,the application of fuzheng detoxification method in interfering with the transformation of colitis cancer was discussed

Objective:From the perspective of tumor amino acid metabolism imbalance,the application of fuzheng detoxification method in intervening in the transformation of colitis cancer was discussed.Methods:By consulting CNKI's concept of tumor microenvironment,energy metabolism,amino acid metabolism,and colitis cancer transformation,it provides theoretical and data support for research purposes.Results:The study found that the transformation of colitis cancer refers to the metabolic imbalance of the tumor microenvironment under the condition of repeated stimulation of chronic inflammatory responses of colon tissue,which is mainly related to energy metabolism,sugar metabolism,fat metabolism,and amino acid metabolism imbalance,which promotes the transformation of the inflammatory microenvironment to the tumor microenvironment.Amino acids as an important source of nutrients for cells,its metabolic imbalance is an important cause of inflammation and cancer transformation.Conclusion:Chinese medicine believes that the transformation of inflammation and cancer is mainly related to the incurable treatment of evil in the internal organs,the loss of Qi,and the poison damage to the blood network.Colon cancer disease mechanism is always positive deficiency and stasis,the pathogenesis is based on the virtual standard,the virtual and real are mixed,and the clinical use of correct detoxification to adjust the balance of the body.

Lipid metabolism, amino acid metabolism, and prostate cancer: a crucial metabolic journey

Prostate cancer(PCa)is one of the most common malignancies in males worldwide,and its development and progression involve the regulation of multiple metabolic pathways.Alterations in lipid metabolism affect the proliferation and metastatic capabilities of PCa cells.Cancer cells increase lipid synthesis and regulate fatty acid oxidation to meet their growth and energy demands.Similarly,changes occur in amino acid metabolism in PCa.Cancer cells exhibit an increased demand for specific amino acids,and they regulate amino acid transport and metabolic pathways to fulfill their proliferation and survival requirements.These changes are closely associated with disease progression and treatment response in PCa cells.Therefore,a comprehensive investigation of the metabolic characteristics of PCa is expected to offer novel insights and approaches for the early diagnosis and treatment of this disease.

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria

We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochondria. Human mitochondrial proteins determined by experimental and computational methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mitochondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which predicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we reconstructed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.

Relationship between the incidence of non-hepatic hyperammonemia and the prognosis of patients in the intensive care unit

BACKGROUND Ammonia is a normal constituent of body fluids and is found mainly through the formation of urea in the liver.Blood levels of ammonia must remain low as even slightly elevated concentrations(hyperammonemia)are toxic to the central nervous system.AIM To examine the relationship between the incidence of non-hepatic hyperammonemia(NHH)and the prognosis of patients who were admitted to the intensive care unit(ICU).METHODS This is a prospective,observational and single-center study.A total of 364 patients who were admitted to the ICU from November 2019 to February 2020 were initially enrolled.Changes in the levels of blood ammonia at the time of ICU admission and after ICU admission were continuously monitored.In addition,factors influencing the prognosis of NHH patients were analyzed.RESULTS A total of 204 patients who met the inclusion criteria were enrolled in this study,including 155 NHH patients and 44 severe-NHH patients.The incidence of NHH and severe-NHH was 75.98% and 21.57%,respectively.Patients with severe-NHH exhibited longer length of ICU stay and higher Acute Physiologic Assessment and Chronic Health Evaluation and Sequential Organ Failure Assessment scores compared to those with mild-NHH and non-NHH.Glasgow Coma Scale scores of patients with severe-NHH were than those of non-NHH patients.In addition,the mean and initial levels of ammonia in the blood might be helpful in predicting the prognosis of NHH.CONCLUSION High blood ammonia level is frequent among NHH patients admitted to the ICU,which is related to the clinical characteristics of patients.Furthermore,the level of blood ammonia may be helpful for prognosis prediction.

Evaluation of the Anti-Trypanosoma cruzi Effects of the Antipsychotic Drug Levomepromazine

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a relevant parasitic disease in the Americas. Current chemotherapy relies on Nifurtimox and Benznidazole, which present serious drawbacks, including high toxicity, low efficiency and the emergence of resistant strains. In the present work, the perspectives of levomepromazine, a tri-cyclic compound belonging to the family of phenotiazines with well-known properties as antipsychotics were evaluated as a potential anti-T. cruzi drug. We show that this drug is able to inhibit the proliferation of epimastigotes (IC50 = 0.41 ± 0.01 mM) and to interfere with the infection of the host cells (IC50 = 0.34 ± 0.01 mM). Interestingly, the treatment with levomepromazine affected the ability of metabolites such as glucose, proline and glutamate to fuel the recovery of epi-mastigotes after being submitted to metabolic stress. These findings prompt levomepromazine as a promising leader drug to obtain new trypanocidal activities.

Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

Amino acid metabolic remodeling is a hallmark of cancer,driving an increased nutritional demand for amino acids.Amino acids are pivotal for energetic regulation,biosynthetic support,and homeostatic maintenance to stimulate cancer progression.However,the role of phenylalanine in multiple myeloma(MM)remains unknown.Here,we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow(BM)cells.After the treatment,phenylalanine levels increase in plasma and decrease in BM.This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression.The requirement for phenylalanine by MM cells exhibits a similar pattern.Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib(BTZ)treatment in vitro and murine models.Mechanistically,phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3eCHOPeDR5 pathway.Interference with ATF3 significantly affects phenylalanine deprivation therapy.In conclusion,we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling.Phenylalanine is necessary for MM proliferation,and its aberrant demand highlights the importance of lowphenylalanine diets as an adjuvant treatment for MM.

Cellular metabolism and homeostasis in pluripotency regulation

Pluripotent stem cells(PSCs)can immortally self-renew in culture with a high proliferation rate,and they possess unique metabolic characteristics that facilitate pluripotency regulation.Here,we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation,with particular emphasis on pathways involving amino acid metabolism,lipid metabolism,the ubiquitin-proteasome system and autophagy.Metabolism of amino acids and lipids is tightly coupled to epigenetic modification,organelle remodeling and cell signaling pathways for pluripotency regulation.PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis.These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment.A more complete understanding of this balance will pave new ways to manipulate PSC fate.

UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis

Up-frameshift 1(UPF1),as the most critical factor in nonsense-mediated messenger RNA(mRNA)decay(NMD),regulates tumor-associated molecular pathways in many cancers.However,the role of UPF1 in lung adenocarcinoma(LUAD)amino acid metabolism remains largely unknown.In this study,we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics.We further confirmed that UPF1 knockdown inhibited activating transcription factor 4(ATF4)and Ser51 phosphorylation of eukaryotic translation initiation factor 2α(eIF2α),the core proteins in amino acid metabolism reprogramming.In addition,UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells,which depends on the function of ATF4.Clinically,UPF1 mRNA expression is abnormal in LUAD tissues,and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival(OS)in LUAD patients.Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.

Evaluation of the Mechanisms Underlying Amino Acid and Microbiota Interactions in Intestinal Infections Using Germ-Free Animals

Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases.As an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections.In turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic bacteria.As a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies.This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms.The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.