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.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

Objective The activities and products of carbohydrate metabolism are involved in key processes of cancer.However,its relationship with hepatocellular carcinoma(HCC)is unclear.Methods The cancer genome atlas(TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases.Differentially expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk score.Next,gene set enrichment analysis(GSEA)was performed on the risk model genes.The sensitivity of the risk model to immunotherapy and chemotherapy was also explored.Results A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2,ACYP1,OGDHL,ACADS,and TKTL1,were identified.Moreover,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC patients.Both the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy sensitivity.Furthermore,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy sensitivity.Eventually,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy drugs.The results of the experiments in HCC tissue samples validated the expression of the risk model genes.Conclusion Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

Effects of mepiquat chloride and plant population density on leaf photosynthesis and carbohydrate metabolism in upland cotton

Background Mepiquat chloride(MC)application and plant population density(PPD)increasing are required for modern cotton production.However,their interactive effects on leaf physiology and carbohydrate metabolism remain obscure.This study aimed to examine whether and how MC and PPD affect the leaf morpho-physiological characteristics,and thus final cotton yield.PPD of three levels(D1:2.25 plants·m^(-2),D2:4.5 plants·m^(-2),and D3:6.75 plants·m^(-2))and MC dosage of two levels(MC0:0 g·ha^(-2),MC1:82.5 g·ha^(-2))were combined to create six treatments.The dynamics of nonstructual carbohydrate concentration,carbon metabolism-related enzyme activity,and photosynthetic attributes in cotton leaves were examined during reproductive growth in 2019 and 2020.Results Among six treatments,the high PPD of 6.75 plants·m^(-2)combined with MC application(MC1D3)exhibited the greatest seed cotton yield and biological yield.The sucrose,hexose,starch,and total nonstructural carbohydrate(TNC)concentrations peaked at the first flowering(FF)stage and then declined to a minimum at the first boll opening(FBO)stage.Compared with other treatments,MC1D3 improved starch and TNC concentration by 5.4%~88.4%,7.8%~52.0% in 2019,and by 14.6%~55.9%,13.5%~39.7% in 2020 at the FF stage,respectively.Additionally,MC1D3 produced higher transformation rates of starch and TNC from the FF to FBO stages,indicating greater carbon production and utilization efficiency.MC1D3 displayed the maximal specific leaf weight(SLW)at the FBO stage,and the highest chlorophyll a(Chl a),Chl b,and Chl a+b concentration at the mid-late growth phase in both years.The Rubisco activity with MC1D3 was 2.6%~53.2% higher at the flowering and boll setting stages in both years,and 2.4%~52.7% higher at the FBO stage in 2020 than those in other treatments.These results provided a explanation of higher leaf senescence-resistant ability in MC1D3.Conclusion Increasing PPD coupled with MC application improves cotton yield by enhancing leaf carbohydrate production and utilization efficiency and delaying leaf senescence.

Selenium Alleviates Carbohydrate Metabolism and Nutrient Composition in Arsenic Stressed Rice Plants

This study reported the influence of selenium(Se)on carbohydrate composition and some related enzymes and nutrient compositions of arsenic(As)stressed rice plants.Rice plants of cultivar PR126 were grown on soil amended with As in a range of 25-100μmol/kg with and without 0.5 or 1.0 mg/kg Se.Total soluble sugars(TSS)and reducing sugars(RS)increased in leaves of As stressed plants at the tillering and grain filling stages whereas sucrose and starch contents showed the reverse trend.Se supplementation to As stressed plants further increased TSS and RS,and enhanced sucrose phosphate synthase activity in rice leaves,thus improving sucrose content and the tolerance to As stress of the plants.Se alone or in combination with As resulted in lower As accumulation in rice husk and grains,and the highest reduction was observed in Se applied at 1.0 mg/kg compared to the corresponding As treatments alone.As may limit the accumulations of Na,Mg,K,Ca,Fe,Zn and Mn in rice grains,which are essential for humans.Binary application of different combinations of As and Se protected the plants against As and increased the mineral content in rice grains.Addition of Se in As treated soil significantly alleviated As stress by enhancing grain yields compared to the corresponding As treatment.It is concluded that Se induced amelioration of the toxic impact of As in rice either by modulating carbohydrate composition and/or nutrient uptake is one of the mechanisms to alleviate As stress in plants.

Response of carbohydrate metabolism-mediated sink strength to auxin in shoot tips of apple plants

Auxin(indole-3-acetic acid, IAA) has a considerable impact on the regulation of plant carbohydrate levels and growth, but the mechanism by which it regulates sugar levels in plants has received little attention. In this study, we found that exogenous IAA altered fructose(Fru), glucose(Glc), and sucrose(Suc) concentrations in shoot tips mainly by regulating MdSUSY1, MdFRK2, MdHxK1 and MdSDH2 transcript levels. Additionally, we used 5-year-old ’Royal Gala’ apple trees to further verify that these genes play primary roles in regulating sink strength. The results showed that MdSUSY1, MdFRK2, MdHxK1/3 and MdSDH2 might be major contributors to sink strength regulation. Taken together, these results provide new insight into the regulation of the carbohydrate metabolism mechanism, which will be helpful for regulating sink strength and yield.

PCSK9 and carbohydrate metabolism:A double-edged sword

Proprotein convertase subtilisin/kexin type 9(PCSK9) plays a paramount role in the degradation of lowdensity lipoprotein(LDL) receptors(LDLR) on the hepatic cells surface and subsequently affects LDL particles catabolism and LDL cholesterol(LDL-c) levels. The anti-PCSK9 monoclonal antibodies lead to substantial decrease of LDL-c concentration. PCSK9(which is also expressed in pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. Thus, a possible adverse effect of PCSK9 inhibitors on carbohydrate metabolism may be expected by this mechanism, which has been supported by the mendelian studies results. On the other hand, clinical data have suggested a detrimental association of PCSK9 with glucose metabolism. So, the inhibition of PCSK9 may be seen as a double-edged sword regarding carbohydrate metabolism. Completed clinical trials have not shown a detrimental effect of PCSK9 inhibitors on diabetes risk, but their short-term duration does not allow definite conclusions.

Effects of Salt Stress on Carbohydrate Metabolism in Desert Soil Alga Microcoleus vaginatus Gom

The effects of salt stress on carbohydrate metabolism in Microcoleus vaginatus Gom., a cyanobacterium isolated from desert algal crusts, were investigated in the present study. Extracellular total carbohydrates and exopolysaccharides （EPS） in the culture medium produced by M. vaginatus increased significantly during the growth phase and reached a maximum during the stationary phase. The production of extracellular carbohydrates also significantly increased under higher salt concentrations, which was attributed to an increase in low molecular weight carbohydrates. In the presence of NaCI, the production of cellular total carbohydrates decreased and photosynthetic activity was impaired, whereas cellular reducing sugars, water-soluble sugars and sucrose content and sucrose phosphate synthase activity increased, reaching a maximum in the presence of 200 mmol/L NaCI. These parameters were restored to original levels when the algae were transferred to a non-saline medium. Sodium and K＋ concentrations of stressed cells decreased significantly and H＋-ATPase activity increased after the addition of exogenous sucrose or EPS. The results suggest that EPS and sucrose are synthesized to maintain the cellular osmOtic equilibrium between the intra-and extracellular environment, thus protecting algal cells from osmotic damage, which was attributed to the selective exclusion of cellular Na＋ and K＋ by H＋-ATPase.

New insights into the influence of myo-inositol on carbohydrate metabolism during osmoregulation in Nile tilapia (Oreochromis niloticus)

A two-factor(23)orthogonal testwas conducted to investigate the effects of dietary myo-inositol(MI)on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia(Oreochromis niloticus)under sustained hypertonic stress(20 practical salinity units[psu]).6 diets containing either normal carbohydrate(NC,30%)or high carbohydrate(HC,45%)levels,with 3 levels(0,400 and 1,200 mg/kg diet)of MI,respectively,were fed to 540 fish under 20 psu for 8 weeks.Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish,and decreased the content of crude lipid of whole fish(P<0.05).Curled,disordered gill lamella and cracked gill filament cartilage were observed in the gill of fish fed diets without MI supplementation.The ion transport capacity in gill was significantly improved in the 1,200 mg/kg MI supplementation groups compared with the 0 mg/kg MI groups(P<0.05).Moreover,the contents of Na^(+),K^(+),Cl^(-)in serum weremarkedly reduced with the dietary MI supplementation(P<0.05).The fish fed 1,200 mg/kg MI supplementation had the highest MI content in the gills and the lowest MI content in the serum(P<0.05).Additionally,the fish fed with 1,200 mg/kg MI supplementation had the highest MI synthesis capacity in gills and brain(P<0.05).Dietary MI markedly promoted the ability of carbohydrate metabolism in liver(P<0.05).Moreover,fish in the 1,200 mg/kg MI groups had the highest antioxidant capacity(P<0.05).This study indicated that high dietary carbohydrate would intensify stress,and impair the ability of osmoregulation in tilapia under a long-term hypersaline exposure.The supplementation of MI at 1,200 mg/kg in the high carbohydrate diet could promote carbohydrate utilization and improve the osmoregulation capacity of tilapia under long-term hypertonic stress.

EFFECT OF ANTIHYDATID DRUGS ON CARBOHYDRATE METABOLISM OF METACESTODE OF ECHINOCOCCUS GRANULOSUS

A biochemical some enzymes of glycolysis and a partial reversed tricarboxylic acid cycle together with hydrolytic enzymes in the cyst wall of Echinococcus granulosus was carried out. Lactate dehydrogenase (LDH), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and adenosine triphosphatase (ATPase) showed their high level of activity, suggesting that the proliferation of E. granulosus cyst wall is an energy-dependent process and the major pathways for glucose metabolism is glycolysis. Treatment of E. granulosus-in-fected mice with mebendazole and albendazole resulted in marked inhibition of PK, PEPCK and ATPase of E. granulosus cyst wall, whereas praziquantel had no effect, indicating that PK, PEPCK, and ATPase might be chemotherapeutic targets and the differences in the inhibitory effects might account for the efficacy of the three antihydatid drugs.

A Transcriptomic Analysis of Physiological Significance of Hypoxia-inducible Factor-1α in Myogenesis and Carbohydrate Metabolism of Genioglossus in Mice

Background： Chronic intermittent hypoxia is the most remarkable feature of obstructive sleep apnea/hypopnea syndrome and it can induce the change of hypoxia-inducible factor-1α （H IF-1α） expression and contractile properties in the genioglossus. To clarify the role of HIF-lot in contractile properties of the genioglossus, this study generated and compared high-throughput RNA-sequencing data from genioglossus between HIF-1α conditional knockout （KO） mice and littermate wild-type （WT） mice. Methods： KO mice were generated with cre-loxP strategy. Gene expression profile analysis was performed using gene enrichment analysis. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses of differently expressed messenger RNAs were performed to identify the related pathways and biological lhnctions. Six differentially expressed genes （DEGs） were validated by qualitative reverse transcription polymerase chain reaction. Results： A total of 142 （77 upregulated and 65 downregulated） transcripts were found to exhibit statistically significant difference between the HIF-la-KO and WT mice. GO and KEGG analyses indicated that DEGs included genes involved in ＂skeletal muscle cell differentiation,＂ ＂muscle organ development,＂ ＂glucose metabolic process,＂ ＂glycogen biosynthetic and metabolic process,＂ etc. Conclusion： This study might provide evidence that H IF-lot affects the expression of multiple genes involved in the myogenesis, muscle developrnent, and carbohydrate metabolism through transcriptome analysis in conditional HIE-1α-KO mice.

Changes of carbohydrate and protein metabolism in seedling leaves of a temperature-induced greenable albino mutant line W25 of rice

W25 is a low-temperature-sensitive albino mu-tant line. Temperature not only controls thealbino phenotype expression of W25, but alsodetermines whether it could survive. When thetemperature is lower than 25℃, the leaves ofW25 shows complete albino, but they exhibitsnormal green when temperature is higher than30℃. Meanwhile, at 25℃, it can be greenable

Chrysoeriol ameliorates hyperglycemia by regulating the carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats

The present study aimed to evaluate the effects of chrysoeriol from Cardiospermum halicacabum in streptozotocin induced Wistar rats.Thirty rats were categorized as control,diabetic control supplemented with 0,20 mg/kg chrysoeriol and 600μg/kg BW of glibenclamide for 45-day trial period.Our results indicated that the inclusion of chrysoeriol(20 mg/kg)showed a significant reduction in plasma glucose,hemoglobin and glycosylated hemoglobin level with a rising of plasma insulin sensitivity.Further,downregulated enzymes including glucose 6-phosphatase,fructose 1,6-bisphosphatase,and glycogen phosphorylase as well upregulated enzymes such as hexokinase,glucose-6-phosphate dehydrogenase,pyruvate kinase,and hepatic glycogen content.There was a diminish action found in liver glycogen synthase of tested rat with a rise in gamma-glutamyl transpeptidase,towards normal levels upon treatment with chrysoeriol.The histopathological study confirmed that renewal of the beta cells of pancreatic of chrysoeriol and glibenclamide treated rats.In addition,the molecular docking of chrysoeriol against glycolytic enzymes including hexokinase,glucose-6-phosphate dehydrogenase,pyruvate kinase,using Argus software shows chrysoeriol had greatest ligand binding energy as equivalent to glibenclamide,as a standard drug.Thus,chrysoeriol found to be non-toxic with potential regulation on glycemic control and upregulation of the carbohydrate metabolic enzymes.

Is intraspecific trait differentiation in Parthenium hysterophorus a consequence of hereditary factors and/or phenotypic plasticity?

Of the various strategies adopted by an invasive plant species for expanding its niche breadth,phenotypic differentiation(either due to plasticity and/or adaptive evolution) is proven to be the most successful.Lately,we studied the persistence of substantial morpho-functional variations within the individuals of alien invasive plant,Parthenium hysterophorus in Chandigarh,India,through field surveys.Based on observed differences,the individuals were categorized into two morphotypes,PAand PB.PAhad higher leaf area,leaf biomass,and chlorophyll content as compared with PB.However,PBhad a higher stem circumference,stem specific density,twig dry matter content,profuse branching,bigger canopy,and better reproductive output than PA.To substantiate the persistence of intraspecific variations in P. hysterophorus and to deduce the possible genesis of these variations,we propagated both the morphotypes under experimental conditions in winter and summer.Apart from the key morpho-functional differences observed during the field studies,protein and carbohydrate metabolism were studied in leaves and roots of the propagated plants.Differences in plant metabolism were observed only during the early growth period,whereas the morpho-functional traits varied in the mature flowering plants.The effect of growth season was highly significant on all the studied morpho-functional and biochemical parameters(p ≤0.05).Parent morphotypes(P) and interactions between morphotypes and seasons significantly affected several growth parameters(p ≤0.05).The analyses revealed that the contrasting growth conditions at the time of transplantation and early growth may regulate the phenotype of P. hysterophorus.The pattern of intraspecific variations observed during the study is justified to consider morphotype PAas winter biotype and morphotype PBas summer biotype of P. hysterophorus.The study points towards the role of plasticity or a combination of genetic and environmental(G×E) factors in producing the phenotypic variability observed in the population of P. hysterophorus.

Bionics and Structural Biology:A Novel Approach for Bio-energy Production

Cellular metabolism is a very complex process. The biochemical pathways are fundamental structures of biology. These pathways possess a number of regeneration steps which facilitate energy shuttling on a massive scale. This facilitates the biochemical pathways to sustain the energy currency of the cells. This concept has been mimicked using electronic circuit components and it has been used to increase the efficiency of bio-energy generation. Six of the carbohydrate biochemical pathways have been chosen in which glycolysis is the principle pathway. All the six pathways are interrelated and coordinated in a complex manner. Mimic circuits have been designed for all the six biochemical pathways. The components of the metabolic pathways such as enzymes, cofactors etc., are substituted by appropriate electronic circuit components. Enzymes are related to the gain of transistors by the bond dissociation energies of enzyme-substrate molecules under consideration. Cofactors and coenzymes are represented by switches and capacitors respectively. Resistors are used for proper orientation of the circuits. The energy obtained from the current methods employed for the decomposition of organic matter is used to trigger the mimic circuits. A similar energy shuttle is observed in the mimic circuits and the percentage rise for each cycle of circuit functioning is found to be 78.90. The theoretical calculations have been made using a sample of domestic waste weighing 1.182 kg. The calculations arrived at finally speak of the efficiency of the novel methodology employed.

Bioinformatics Analysis of HKDC1 Expression in Non-small Cell Lung Cancer and Its Relationship to Survival

Lung cancer has become one of the most common types of cancer,and has the highest morbidity and mortality rates.We herein performed a bioinformatic analysis to explore the gene expression of hexokinase domain containing 1(HKDC1)to further illuminate the molecular mechanisms involved in non-small cell lung cancer(NSCLC).We also examined the relationship between HKDC1 expression and patient survival.The Oncomine and cBioPortal cancer genomics databases were used to investigate the expression of HKDC1 in NSCLC.Then the protein-protein interaction network and protein expression intensity of HKDC1 were examined with the Gene MANIA and The Human Protein Atlas databases.Finally,the prognostic impact of HKDC1 was evaluated via the GEPIA,Oncolnc and Kaplan-Meier Plotter online tools.HKDC1 was significantly up-regulated in NSCLC patients.In addition,the mutation frequency of HKDC1 in NSCLC was high in a large number of studies.Moreover,HKDC1 expression was correlated with a poor prognosis in NSCLC patients.These findings suggest that HKDC1 represents a novel therapeutic target for NSCLC.

Metabolism of carbohydrate in alimentary tract of reindeer in winter

The study was conducted on six reindeers in December.It was established that concentration of reducing sugars in the chyme of jejunum increases substantially(6 times in comparison with abomasum),whereas concentration cellulose,on the contrary,decreases(4.5 times).The maximal increase of monosaccharides in the small intestine testifies to formation of metabolic fund of sugars in this part of the alimentary tract due to high degree of polysaccharides hydrolysis of exogenous,as well as endogenous,microbial formation.Obtained data assume that the need of the reindeer for glucose is provided for not only by gluconeogenesis as it was considered before,but also by absorption of monosaccharides from the alimentary tract.

Insulin Resistance in Pregnancy Is Correlated with Decreased Insulin Receptor Gene Expression in Omental Adipose: Insulin Sensitivity and Adipose Tissue Gene Expression in Normal Pregnancy

Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-Insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.

Gut bacterium promotes host fitness in special ecological niche by affecting sugar metabolism in Drosophila suzukii

As an important fruit pest of global significance,Drosophila suzukii occupies a special ecological niche,with the characteristics of high sugar and low protein contents.This niche differs from those occupied by other fruit-damaging Drosophila species.Gut bacteria substantially impact the physiology and ecology of insects.However,the contribution of gut microbes to the fitness of D.suzukii in their special ecological niche remains unclear.In this study,the effect of Klebsiella oxytoca on the development of D.suzukii was examined at physiological and molecular levels.The results showed that,after the removal of gut microbiota,the survival rate and longevity of axenic D.suzukii decreased significantly.Reintroduction of K.oxytoca to the midgut of D.suzukii advanced the development level of D.suzukii.The differentially expressed genes and metabolites between axenic and K.oxytoca-reintroduced D.suzukii were enriched in the pathways of carbohydrate metabolism.This advancement was achieved through an increased glycolysis rate and the regulation of the transcript level of key genes in the glycolysis/gluconeogenesis pathway.Klebsiella oxytoca is likely to play an important role in increasing host fitness in their high-sugar ecological niche by stimulating the glycolysis/gluconeogenesis pathway.As a protein source,bacteria can also provide direct nutrition for D.suzukii,which depends on the quantity or biomass of K.oxytoca.This result may provide a new target for controlling D.suzukii by inhibiting sugar metabolism through eliminating the effect of K.oxytoca and thus disrupting the balance of gut microbial communities.

Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

Background and Aims:Hepatocellular ballooning is a common finding in chronic liver disease,mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies(MDB).Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes(BH)are damaged cells on the path to death or rather viable cells,possibly involved in neoplastic development.Methods:Using specimens from 96 cirrhotic human livers,BH characteristics were assessed for their glycogen/lipid stores,enzyme activities,and proto-oncogenic signaling cascades by enzyme-and immunohistochemical approaches with serial paraffin and cryostat sections.Results:BH were present in 43.8%of cirrhotic livers.Particularly pronounced excess glycogen storage of(glycogenosis)and/or lipids(steatosis)were characteristic,ground glass features and MDB were often observed.Decreased glucose-6-phosphatase,increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis,lipid metabolism,and cholesterol biosynthesis were discovered.Furthermore,components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis.Conclusions:BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis,many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases.Hence,BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming,indicative of a preneoplastic nature.