Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.

Personal glucose meters coupled with signal amplification technologies for quantitative detection of non-glucose targets:Recent progress and challenges in food safety hazards analysis

Ensuring food safety is paramount worldwide.Developing effective detection methods to ensure food safety can be challenging owing to trace hazards,long detection time,and resource-poor sites,in addition to the matrix effects of food.Personal glucose meter(PGM),a classic point-of-care testing device,possesses unique application advantages,demonstrating promise in food safety.Currently,many studies have used PGM-based biosensors and signal amplification technologies to achieve sensitive and specific detection of food hazards.Signal amplification technologies have the potential to greatly improve the analytical performance and integration of PGMs with biosensors,which is crucial for solving the challenges associated with the use of PGMs for food safety analysis.This review introduces the basic detection principle of a PGM-based sensing strategy,which consists of three key factors:target recognition,signal transduction,and signal output.Representative studies of existing PGM-based sensing strategies combined with various signal amplification technologies(nanomaterial-loaded multienzyme labeling,nucleic acid reaction,DNAzyme catalysis,responsive nanomaterial encapsulation,and others)in the field of food safety detection are reviewed.Future perspectives and potential opportunities and challenges associated with PGMs in the field of food safety are discussed.Despite the need for complex sample preparation and the lack of standardization in the field,using PGMs in combination with signal amplification technology shows promise as a rapid and cost-effective method for food safety hazard analysis.

Clinical profile,etiology,management and outcome of empyema thoracis associated with COVID-19 infection:A systematic review of published case reports

Objective:To explore the clinical features,diagnosis,etiology,treatment,and outcomes of COVID-19 related empyema.Methods:Using PRISMA statement,a systematic search of relevant case reports published between December 2019 and April 2023 was performed through seven databases.The collected data included demographics,clinical manifestations,diagnostic findings,treatment,and outcomes.Results:Thirty-six case reports were identified with 43 cases of empyema.The included cases had a median age of 55 years(range:12-78 years)and 79.1%(34/43)were males.The majority of cases presented during hospitalization for management of acute COVID-19 infection(29/43,67.4%)and Charlson comorbidity index<3(40/43,93.0%).Pseudomonas aeruginosa was the most commonly isolated microorganism from the pleural fluid(9/43,20.9%)and 16.3%of the cases(7/43)had polymicrobial infections.Chest drainage was performed in all cases while surgery was indicated in 24 cases(55.8%).The most common complication of COVID-19-related empyema was broncho-pleural fistula(2/43,4.7%).The mortality rate was 23.3%(10/43).Sepsis and/or multi-organ failure were the most commonly reported causes of death.On univariate analysis,no statistically significant risk factor for mortality was identified.Conclusions:COVID-19-associated empyema has a variety of predisposing factors,time of presentation,clinical features,and causative organisms.Invasive or minimally invasive surgical procedures are performed more frequently than isolated chest drainage.Empyema in COVID-19 patients worsens their prognosis and can lead to serious complications.

Defining the awareness and attitude of the clinicians through pharmacovigilance in Turkey

BACKGROUND Pharmacovigilance(PV)is the activities and scientific studies conducted to detect,evaluate,understand or prevent adverse reactions and other drug-related problems.AIM To define the awareness and experiences of the clinicians on PV and adverse drug reactions(ADRs)in Turkey.METHODS The study was cross-sectional and analytical.Data were obtained through a questionnaire.The questionnaire was sent via e-mail.The survey was sent to 2030 physicians and 670 participated.RESULTS The most appropriate definition of PV was correctly defined by 53.9%of the participants.The most important goal of PV was correctly defined by 54.9%of the participants,and 27.3%of the participants were aware of the Turkish Pharmacovigilance Center.Nonsurgical physicians had better PV knowledge than surgical physicians.A total of 80.9%of the physicians who encountered ADRs,filled in the ADR notification form,and 8.8%received training on how to fill in the form.PV knowledge of the clinicians was not sufficient.Although half of the physicians encountered ADRs,the rates of seeing and filling in the ADR form were low.CONCLUSION Few of the physicians followed the current information about PV.The results provide more comprehensive data on PV practices and ADR reporting at a national level.

Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish:Possible involvement of GABAergic and serotonergic pathways

Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases.The hydroethanolic extract(PME)from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models.However,its effects in chronic anxiety models and possible mechanism(s)of action were not studied.Therefore,the current study evaluated the anxiolytic-like mechanisms of PME in zebrafish models of anxiety.The zebrafish light dark test(LDT)and novel tank test(NTT)were employed to assess the anxiolytic-like effects of PME(0.1,0.3,1.0 mg mL^(−1)),fluox-etine(3×10^(−5)mg mL^(−1))and diazepam(1.5×10^(−7)mg mL^(−1)).The chronic unpredictable stress(CUS)test was used to further evaluate the extract’s anxiolytic-like properties.The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with flumazenil,granisetron,methysergide,or pizotifen,all at 1×10^(−3)mg mL^(−1).The extract significantly decreased anxiety behaviours in the NT and LD tests.These observed effects of the extract were however counteracted by flumazenil,granisetron,methysergide and pizotifen pre-treatment.In addition,PME treatment significantly reversed CUS-induced anxiety behaviours in zebrafish.Results show that PME possesses anxiolytic-like effects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathways.

Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

Epigenetic effects of ethanol on liver and gastrointestinal injury

Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.

Contribution of oxidative stress to pulmonary arterial hypertension

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators

AIM To investigate the roles of the neuropeptides vasoactive intestinal peptide(VIP), substance P(SP), and calcitonin gene-related peptide(CGRP) in chronic gastritis and duodenitis in children.METHODS Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels.RESULTS We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observedin neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis.CONCLUSION Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects.

Development of an analytical method for multi-residue quantification of 18 anthelmintics in various animal-based food products using liquid chromatography-tandem mass spectrometry

In this study,we developed a simple screening procedure for the determination of 18 anthelmintics(including benzimidazoles,macrocyclic lactones,salicylanilides,substituted phenols,tetrahydropyrimidines,and imidazothiazoles)in five animal-derived food matrices(chicken muscle,pork,beef,milk,and egg)using liquid chromatography-tandem mass spectrometry.Analytes were extracted using acetonitrile/1% acetic acid(milk and egg)and acetonitrile/1% acetic acid with 0.5 mL of distilled water(chicken muscle,pork,and beef),and purified using saturated n-hexane/acetonitrile.A reversed-phase analytical column and a mobile phase consisting of(A)10 mM ammonium formate in distilled water and(B)methanol were used to achieve optimal chromatographic separation.Matrix-matched standard calibration curves(R^(2)≥0.9752)were obtained for concentration equivalent to ×1/2,×1,×2,×3,×4,and×5 fold the maximum residue limit(MRL)stipulated by the Korean Ministry of Food and Drug Safety.Recoveries of 61.2e118.4%,with relative standard deviations(RSDs)of ≤19.9%(intraday and interday),were obtained for each sample at three spiking concentrations(×1/2,×1,and ×2 the MRL values).Limits of detection,limits of quantification,and matrix effects were 0.02e5.5 mg/kg,0.06e10 mg/kg,and -98.8 to 13.9%(at 20 μg/kg),respectively.In five samples of each food matrix(chicken muscle,pork,beef,milk,and egg)purchased from large retailers in Seoul that were tested,none of the target analytes were detected.It has therefore been shown that this protocol is adaptable,accurate,and precise for the quantification of anthelmintic residues in foods of animal origin.

A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence antiquenching

Balancing the risks and benefits of organophosphate pesticides(OPs)on human and environmental health relies partly on their accurate measurement.A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs(triazophos,parathion,and chlorpyrifos)in apples,turnips,cabbages,and rice.Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs.DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification.The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore.The resulting fluorescence signal enables multiplexed quantification of triazophos,parathion,and chlorpyrifos residues over the concentration range of 0.01-25,0.01-50,and 0.1-50 ng/mL with limits of detection of 0.014,0.011,and 0.126 ng/mL,respectively.The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%,which correlate well with results obtained by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The proposed bio-barcode immunoassay is stable,reproducible and reliable,and is able to detect low residual levels of multi-residue OPs in agricultural products.

Comparison of the effect of intravitreal bevacizumab and intravitreal fasudil on retinal VEGF,TNFα,and caspase 3 levels in an experimental diabetes model

AIM: To evaluate the influence of an intravitreal injection of bevacizumab and fasudil on the retinal vascular endothelial growth factor(VEGF),tumor necrosis factor alpha(TNFα),and caspase 3 levels in a diabetic rabbit model. · METHODS: The study included 6 healthy rabbits(Group 1),6 rabbits with experimentally induced diabetes mellitus(DM)(Group 2),7 rabbits with experimentally induced DM to which intravitreal bevacizumab was administered(Group 3),and 7 rabbits with experimentally induced DM to which intravitreal fasudil was administered(Group 4). An intravitreal injection of 1.25mg/50μL bevacizumab in the right eye of rabbits in Group 3 and an intravitreal injection of 0.0064mg/50μL fasudil in the right eye of rabbits in Group 4 were administered on day 21 after the induction of DM. The studied eyes of the rabbits were enucleated three days after the intravitreal injection. The TNFα,VEGF,and caspase 3 levels were determined using the ELISA method. · RESULTS: There was a statistically significant difference in the VEGF and caspase 3 levels between groups(P =0.005 and P =0.013,respectively),but the TNF α level did not differ significantly between groups(P = 0.792). It was found that VEGF levels were significantly lower in Group 1 and Group 3 than in Group 2 using the Mann-Whitney U test with the Bonferroni correction(P = 0.004 for both comparison). There was no statistically significant difference between other groups with regard to VEGF levels(the P value ranged between 0.015 and 0.886). Although the P values of the caspase 3 levels were 0.015 for Group 1 and Group 4,0.038 for Group 2and Group 3,and 0.018 for Group 3 and Group 4,these P values remained above the threshold P value of 0.0083,which was the statistically significant level for post hoc tests. ·CONCLUSION: An intravitreal injection of bevacizumab decreased both the VEGF level,which plays a role in angiogenesis,and the caspase 3 level,which plays a role in apoptosis. Although not as effective as bevacizumab,fasudil had a beneficial effect on the VEGF levels but significantly increased the caspase 3 levels.

Anti-HIV-1 Activities of 4 Telomerase Restrictors

MTT Cell Proliferation Assay was used to optimize the concentration of Telomerase Restrictors（TRs） with minimum toxicity to the selected cells. FACSort flow cytometer and Innotest P24 HIV（Human immtmodeficiency Virus） antigen mAb ELISA Kit were used to investigate the anti-HIV-1 activities of TRs. The results showed that TRs had low cytotoxicity to the PBMC （Peripheral Blood mononuclear cells） and CEM/GFP if the concentration of TRs was at 50μmol/L or below, and the supernatant from PBMC pretreated with SHIV and TR1-001 /TR1-002 could not infect the PBMC, while can infect the C8166 with reduced infectivity, which suggested that the TRs may be one of the novel resources for screening anti-HIV-1 agents.

Causes of failure in acute respiratory distress syndrome modeling and treatment in animal research and new approaches

Acute respiratory distress syndrome(ARDS) is a major cause of morbidity, death and cost in intensive careunits. Despite intensive research, pharmacotherapy has not passed the experimental stage and mortality rates are still high. Animal models provide a bridge between patients and the laboratory bench. Different animal models have been developed in order to mimic human ARDS, but they have limitations. The purpose of this review was to summarize the properties of the most commonly used experimental animal models mimicking the causes and pathology of human ARDS, the limitations of ARDS models, treatment failure and new therapeutic approaches.

Simple, Reliable Isolation, Purification and Cultivation of Murine Skeletal Muscle Microvascular Endothelial Cells

Objectives: Microvascular dysfunction in skeletal muscle is involved in metabolic and vascular diseases. Microvascular endothelial cells (MEC) are poorly characterized in the progression of associated diseases in part due to lack of availability of MEC from various animal models. The objective was to provide a fast, simple, and efficient method to isolate murine MEC derived from skeletal muscle. Methods: Dissected abdominal skeletal muscles from C57BL/6J mice at 8 - 12 weeks of age were enzymatically dissociated. MEC were isolated using a modified two-step Dynabeads™-based purification method. With a combination of Dynabeads™ - Griffonia simplicifolia lectin-I and Dynabeads™ - monoclonal antibody against CD31/PECAM-1, MEC were isolated and purified twice followed by cultivation. Results: Isolated and purified cells were viable and cultured. MEC were characterized by using immunofluorescence to identify CD31/PECAM-1, an EC marker, and two specific functional assays, which include a capillary-like tube formation and the uptake of Dil-Ac-LDL. The purity of isolated cell populations from skeletal muscle microvessels, which was assessed by flow cytometry, was 88.02% ± 2.99% (n = 6). Conclusions: This method is simple, fast, and highly reproducible for isolating MEC from murine skeletal muscle. The method will enable us to obtain primary cultured MEC from various genetic or diseased murine models, contributing to insightful knowledge of diseases associated with the dysfunction of microvessels.

Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction

Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN®, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN® 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN® significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p < 0,05), reflex control of SSNA (+29.4%, p < 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

Atomic force microscopy reveals new mechanisms of increased aortic stiffness in hypertension

Hypertension is an important global health problem that continues increase in incidence.Increased vascularstiffness has been identified as an important component of the pathogenesis of hypertension(HT).Based on theresults of recent Framingham studies,it appears that aortic increased stiffness may precede hypertension suggest-ing that controlling arterial stiffness may

Aluminum Toxicity:A Case Study on Tobacco(Nicotiana tabacum L.)

Aluminum is an abundant metal in the earth’s crust that turns out to be toxic in acidic environments.Many plants are affected by the presence of aluminum at the whole plant level,at the organ level,and at the cellular level.Tobacco as a cash crop(Nicotiana tabacum L.)is a widely cultivated plant worldwide and is also a good model organism for research.Although there are many articles on Al-phytotoxicity in the literature,reviews on a single species that are economically and scientifically important are limited.In this article,we not only provide the biology associated with tobacco Al-toxicity,but also some essential information regarding the effects of this metal on other plant species(even animals).This review provides information on aluminum localization and uptake process by different staining techniques,as well as the effects of its toxicity at different compartment levels and the physiological consequences derived from them.In addition,molecular studies in recent years have reported specific responses to Al toxicity,such as overexpression of various protective proteins.Besides,this review discusses data on various organelle-based responses,cell death,and other mechanisms,data on tobacco plants and other kingdoms relevant to these studies.

Soy-based renoprotection

Chronic kidney disease （CKD） is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global po-pulation. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insuffciency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain phy-siological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic infammation in early and late stage CKD pati-ents. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated prog-ressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target（s） of soy protein in main-taining renal function.

Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and increases angiotensinogen gene expression

AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angioten-sinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.