Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism,inflammation reaction and bile acid metabolism in ApoE^(-/-)mice

Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.

Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway

Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of Bupleurum.The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling.SSD can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as Clostridium.Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal FXR.These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.

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.

Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

METTL5 promotes gastric cancer progression via sphingomyelin metabolism

BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

Synergistic effects of carbon cycle metabolism and photosynthesis in Chinese cabbage under salt stress

Chinese cabbage(Brassica rapa ssp. pekinensis) has a long cultivation history and is one of the vegetable crops with the largest cultivation area in China. However, salt stress severely damages photosynthesis and hormone metabolism, nutritional balances, and results in ion toxicity in plants. To better understand the mechanisms of salt-induced growth inhibition in Chinese cabbage, RNA-seq and physiological index determination were conducted to explore the impacts of salt stress on carbon cycle metabolism and photosynthesis in Chinese cabbage. Here, we found that the number of thylakoids and grana lamellae and the content of starch granules and chlorophyll in the leaves of Chinese cabbage under salt stress showed a time-dependent response, first increasing and then decreasing. Chinese cabbage increased the transcript levels of genes related to the photosynthetic apparatus and carbon metabolism under salt stress, probably in an attempt to alleviate damage to the photosynthetic system and enhance CO_(2) fixation and energy metabolism. The transcription of genes related to starch and sucrose synthesis and degradation were also enhanced;this might have been an attempt to maintain intracellular osmotic pressure by increasing soluble sugar concentrations. Soluble sugars could also be used as potential reactive oxygen species(ROS) scavengers, in concert with peroxidase(POD)enzymes, to eliminate ROS that accumulate during metabolic processes. Our study characterizes the synergistic response network of carbon metabolism and photosynthesis under salt stress.

Lipid metabolism analysis in esophageal cancer and associated drug discovery

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

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.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets

Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Current and future research directions in cellular metabolism of colorectal cancer:A bibliometric analysis

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.