Network pharmacology and molecular docking identify mechanisms of medicinal plant-derived 1,2,3,4,6-penta-O-galloyl-beta-D-glucose treating gastric cancer

Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).

Fecal microbiota transplantation:whole grain highland barley improves glucose metabolism by changing gut microbiota

Highland barley(HB)is a high-altitude cereal with rich nutritional components and potential health benefits.To clarify its hypoglycemic effect and mechanism,we investigated the effect of whole grain HB and fecal microbiota transplantation(FMT)on glucose metabolism and gut microbiota in high-fat diet and streptozotocin(HFD/STZ)-induced diabetic mice.The results showed that HB(40%)significantly decreased fasting blood glucose and the area under the glucose tolerance curve,significantly increased insulin secretion and improved insulin resistance in HFD/STZ-induced diabetic mice(P<0.05).Inflammatory factors and blood lipid indices were also significantly alleviated after 12 weeks of 40%HB intervention(P<0.05).Additionally,beneficial bacteria,such as Bifidobacterium and Akkermansia,were significantly enriched in the gut of diabetic mice after whole grain HB intervention.Meanwhile,the results of further FMT experiments verified that the fecal microbiota after the 40%HB intervention not only significantly increased the relative abundance of Bifidobacterium and Akkermansia but also effectively improved glucose metabolism and alleviated the inflammatory state in HFD/STZ-induced diabetic mice.Collectively,our study confirmed the bridge role of gut microbiota in improving glucose metabolism of whole grain HB,which could promote the development of precision nutrition.

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.

A Review: Biosensor Progression in Glucose Monitoring for Patients with Diabetes

Diabetes is a condition that can come to the surface at any point throughout a person’s life. Although Type 1 and Type 2 Diabetes have different triggers that cause them to arise, a person can experience similar complications from either if not monitored and treated accordingly. Through the Diabetes Control and Complications Trial, it was found that a significant way to monitor diabetes is through glucose levels in a person’s body. The research surrounding glucose monitoring dates to the mid-1800s, with the first successful reagent for glucose testing being developed in 1908. Since then, glucose sensing has become one of the most rapidly growing areas of research and development in biosensor technology, creating a competitive market for more advanced, accurate, and convenient glucose monitoring. This article reviews the history of biosensors used for glucose monitoring, and major advancements in biosensor technology to enhance performance and improve quality of life for patients with diabetes.

Periodic Addition of Glucose Suppressed Cyanobacterial Abundance in Additive Lake Water Samples during the Entire Bloom Season

Previously, we showed that prophylactic addition of glucose to Harsha Lake water samples could inhibit cyanobacteria growth, at least for a short period of time. The current study tested cyanobacterial control with glucose for the entire Harsha Lake bloom season. Water samples (1000 ml) were collected weekly from Harsha Lake during the algal-bloom season starting June 9 and lasting until August 24, 2022. To each of two 7-liter polypropylene containers, 500 ml of Harsha Lake water was added, and the containers were placed in a controlled environment chamber. To one container labeled “Treated,” 0.15 g of glucose was added, and nothing was added to the container labeled “Control.” After that, three 25 ml samples from each container were collected and used for 16S rRNA gene sequencing each week. Then 1000 ml of Harsha Lake water was newly collected each week, with 500 ml added to each container, along with the addition of 0.15 g glucose to the “Treated” container. Sequencing data were used to examine differences in the composition of bacterial communities between Treated and Control containers. Treatment with glucose altered the microbial communities by 1) reducing taxonomic diversity, 2) largely eliminating cyanobacterial taxa, and 3) increasing the relative abundance of subsets of non-cyanobacterial taxa (such as Proteobacteria and Actinobacteriota). These effects were observed across time despite weekly inputs derived directly from Lake water. The addition of glucose to a container receiving weekly additions of Lake water suppressed the cyanobacterial populations during the entire summer bloom season. The glucose appears to stimulate the diversity of certain bacterial taxa at the expense of the cyanobacteria.

Accuracy of FreeStyle Libre flash glucose monitoring in patients with type 2 diabetes who migrated from highlands to plains

BACKGROUND The FreeStyle Libre flash glucose monitoring(FGM)system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose.Due to its increased usage in clinics,the number of studies investigating its accuracy has increased.However,its accuracy has not been investigated in highland populations in China.AIM To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes(T2D)who had migrated within 3 mo from highlands to plains.METHODS Overall,68 patients with T2D,selected from those who had recently migrated from highlands to plains(within 3 mo),were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring(CGM)with the FreeStyle Libre FGM system for 14 d.Throughout the study period,fingertip capillary blood glucose was measured daily using the enzyme electrode method(Super GL,China),and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals.Moreover,the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to<5 min.The accuracy of the FGM system was evaluated according to the CGM guidelines.Subsequently,the factors influencing the mean absolute relative difference(MARD)of this system were analyzed by a multiple linear regression method.RESULTS Pearson’s correlation analysis showed that the fingertip and scanned glucose levels were positively correlated(R=0.86,P=0.00).The aggregated MARD of scanned glucose was 14.28±13.40%.Parker's error analysis showed that 99.30%of the data pairs were located in areas A and B.According to the probe wear time of the FreeStyle Libre FGM system,MARD_(1 d) and MARD_(2-14 d) were 16.55%and 14.35%,respectively(t=1.23,P=0.22).Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion(LAGE)was<5.80 mmol/L but negatively correlated with blood glucose when the LAGE was≥5.80 mmol/L.CONCLUSION The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains.This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains.MARD is mainly influenced by glucose levels and fluctuations,and the accuracy of the system is higher when the blood glucose fluctuation is small.In case of higher blood glucose level fluctuations,deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.

Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.

Effects of the kinetic pattern of dietary glucose release on nitrogen utilization, the portal amino acid profile, and nutrient transporter expression in intestinal enterocytes in piglets

Background Promoting the synchronization of glucose and amino acid release in the digestive tract of pigs could effectively improve dietary nitrogen utilization.The rational allocation of dietary starch sources and the exploration of appropriate dietary glucose release kinetics may promote the dynamic balance of dietary glucose and amino acid supplies.However,research on the effects of diets with different glucose release kinetic profiles on amino acid absorption and portal amino acid appearance in piglets is limited.This study aimed to investigate the effects of the kinetic pattern of dietary glucose release on nitrogen utilization,the portal amino acid profile,and nutrient transporter expression in intestinal enterocytes in piglets.Methods Sixty-four barrows(15.00±1.12 kg)were randomly allotted to 4 groups and fed diets formulated with starch from corn,corn/barley,corn/sorghum,or corn/cassava combinations(diets were coded A,B,C,or D respectively).Protein retention,the concentrations of portal amino acid and glucose,and the relative expression of amino acid and glucose transporter m RNAs were investigated.In vitro digestion was used to compare the dietary glucose release profiles.Results Four piglet diets with different glucose release kinetics were constructed by adjusting starch sources.The in vivo appearance dynamics of portal glucose were consistent with those of in vitro dietary glucose release kinetics.Total nitrogen excretion was reduced in the piglets in group B,while apparent nitrogen digestibility and nitrogen retention increased(P<0.05).Regardless of the time(2 h or 4 h after morning feeding),the portal total free amino acids content and contents of some individual amino acids(Thr,Glu,Gly,Ala,and Ile)of the piglets in group B were significantly higher than those in groups A,C,and D(P<0.05).Cluster analysis showed that different glucose release kinetic patterns resulted in different portal amino acid patterns in piglets,which decreased gradually with the extension of feeding time.The portal His/Phe,Pro/Glu,Leu/Val,Lys/Met,Tyr/Ile and Ala/Gly appeared higher similarity among the diet treatments.In the anterior jejunum,the glucose transporter SGLT1 was significantly positively correlated with the amino acid transporters B0AT1,EAAC1,and CAT1.Conclusions Rational allocation of starch resources could regulate dietary glucose release kinetics.In the present study,group B(corn/barley)diet exhibited a better glucose release kinetic pattern than the other groups,which could affect the portal amino acid contents and patterns by regulating the expression of amino acid transporters in the small intestine,thereby promoting nitrogen deposition in the body,and improving the utilization efficiency of dietary nitrogen.

Nanomaterial-assisted wearable glucose biosensors for noninvasive real-time monitoring:Pioneering point-of-care and beyond

This review explores glucose monitoring and management strategies,emphasizing the need for reliable and userfriendly wearable sensors that are the next generation of sensors for continuous glucose detection.In addition,examines key strategies for designing glucose sensors that are multi-functional,reliable,and cost-effective in a variety of contexts.The unique features of effective diabetes management technology are highlighted,with a focus on using nano/biosensor devices that can quickly and accurately detect glucose levels in the blood,improving patient treatment and control of potential diabetes-related infections.The potential of next-generation wearable and touch-sensitive nano biomedical sensor engineering designs for providing full control in assessing implantable,continuous glucose monitoring is also explored.The challenges of standardizing drug or insulin delivery doses,low-cost,real-time detection of increased blood sugar levels in diabetics,and early digital health awareness controls for the adverse effects of injectable medication are identified as unmet needs.Also,the market for biosensors is expected to expand significantly due to the rising need for portable diagnostic equipment and an ever-increasing diabetic population.The paper concludes by emphasizing the need for further research and development of glucose biosensors to meet the stringent requirements for sensitivity and specificity imposed by clinical diagnostics while being cost-effective,stable,and durable.

Retinal microcirculation changes in prediabetic patients with shortterm increased blood glucose using optical coherence tomography angiography

BACKGROUND Retinal microcirculation alterations are early indicators of diabetic microvascular complications.Optical coherence tomography angiography(OCTA)is a noninvasive method to assess these changes.This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA.AIM To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA.METHODS Fifty volunteers were divided into three groups:Group 1[impaired fasting glucose(IFG)or impaired glucose tolerance(IGT)],Group 2(both IFG and IGT),and a control group.Retinal microcirculation parameters,including vessel density(VD),perfusion density(PD),and foveal avascular zone(FAZ)metrics,were measured using OCTA.Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states.RESULTS One hour after glucose intake,the central VD(P=0.023),central PD(P=0.026),and parafoveal PD(P<0.001)were significantly greater in the control group than in the fasting group.In Group 1,parafoveal PD(P<0.001)and FAZ circularity(P=0.023)also increased one hour after glucose intake.However,no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake(P>0.05).Compared with the control group,Group 1 had a larger FAZ area(P=0.032)and perimeter(P=0.018),whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Compared with Group 1,Group 2 had greater central VD(P=0.013)and PD(P=0.008)and a smaller FAZ area(P=0.012)and perimeter(P=0.010).One hour after glucose intake,Group 1 had a larger FAZ area(P=0.044)and perimeter(P=0.038)than did the control group,whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Group 2 had greater central VD(P=0.042)and PD(P=0.022)and a smaller FAZ area(P=0.015)and perimeter(P=0.016)than Group 1.At fasting,central PD was significantly positively correlated with blood glucose levels(P=0.044),whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake.CONCLUSION A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

Boosted Electrocatalytic Glucose Oxidation Reaction on Noble-Metal-Free MoO_(3)-Decorated Carbon Nanotubes

Electrocatalytic glucose oxidation reaction(GOR)has attracted much attention owing to its crucial role in biofuel cell fabrication.Herein,we load MoO_(3)nanoparticles on carbon nanotubes(CNTs)and use a discharge process to prepare a noblemetal-free MC-60 catalyst containing MoO_(3),Mo_(2)C,and a Mo_(2)C–MoO_(3)interface.In the GOR,MC-60 shows activity as high as 745μA/(mmol/L cm^(2)),considerably higher than those of the Pt/CNT(270μA/(mmol/L cm^(2)))and Au/CNT catalysts(110μA/(mmol/L cm^(2))).In the GOR,the response minimum on MC-60 is as low as 8μmol/L,with a steady-state response time of only 3 s.Moreover,MC-60 has superior stability and anti-interference ability to impurities in the GOR.The better performance of MC-60 in the GOR is attributed to the abundant Mo sites bonding to C and O atoms at the MoO_(3)–Mo_(2)C interface.These Mo sites create active sites for promoting glucose adsorption and oxidation,enhancing MC-60 performance in the GOR.Thus,these results help to fabricate more effi cient noble-metal-free catalysts for the fabrication of glucose-based biofuel cells.

The Mechanism of Celastrol in the Treatment of Metastatic Lung Adenocarcinoma Revealed by Network Pharmacology and Molecular Docking

Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.

Effects of different doses of glucose and fructose on central metabolic pathways and intercellular wireless communication networks in humans

Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

Improvement of glucose metabolism in middle-aged mice on a high-fat diet by whole-grain highland barley is related to low methionine levels

Methionine restriction(MR)is an effective dietary strategy to regulate energy metabolism and alleviate oxidative stress and inflammation in the body,especially in the middle-aged and elderly population.However,the high methionine content of meat products makes this dietary strategy impossible to combine with protein supplementation and MR.Highland barley(HB),a low-methionine cereal,not only provides the body with protein but also has improved glucose metabolism and antioxidant and anti-inflammatory properties.Therefore,this study evaluated the feasibility of HB as a source of methionine-restricted dietary protein and the potential mechanisms.Middle-aged C57BL/6J mice were fed a control diet(CON),a high-fat diet(HFD),a whole-grain HB high-fat diet(HBHF),or a HBHF+methionine diet(HBHFmet)for 25 weeks.The results showed that the HBHF could keep the body weight,fasting glucose,insulin,homeostasis model assessment of insulin resistance(HOMA-IR),blood lipids,inflammation,and oxidative stress of HFD mice at normal levels.Compared with the HFD groups,HBHF inhibited pancreatic cell apoptosis and improved insulin secretion while improving hepatic and skeletal muscle glucose metabolism.However,these efficacies were attenuated in HBHFmet group mice.These findings suggest that HBHF has an MR strategy.

Advances in ethnopharmacology,phytochemistry and pharmacology of Erigerontis Herba and its Chinese medicine prescriptions

Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away cold.It has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and toothache.This review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of EH.Relevant information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic databases.EH is a member of Compositae family and is mainly grown in southern China.Traditional Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving pain.By now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other compounds.EH extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative diseases.Scutellarin,the major active compound of EH,has been used as a quality marker.And no obvious toxicity of EH has been reported.According to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine fields.While several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain elusive.To fully exploit the medicinal potential of EH,further studies on understanding the effective material basis and mechanisms are warranted.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.