Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Angiotensin-converting enzyme 2 receptors,chronic liver diseases,common medications,and clinical outcomes in coronavirus disease 2019 patients

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for coronavirus disease 2019(COVID-19),enters affected cells through the angiotensin-converting enzyme 2(ACE2)receptor,which is highly expressed in type II alveolar cells,enterocytes,and cholangiocytes.SARS-CoV-2 infection causes fever,dry cough,and breathing difficulty,which can progress to respiratory distress due to interstitial pneumonia,and hepatobiliary injury due to COVID-19 is increasingly recognized.The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression.The development of more severe clinical outcomes in patients with chronic liver diseases(CLD)with or without cirrhosis infected with SARS-CoV-2 has not been elucidated.Moreover,there is limited data related to common medications that affect the disease severity of COVID-19 patients.Additionally,ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified.This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications.Furthermore,the association between ACE2 receptor expression and disease severity in these patients is discussed.

Effects of the Mixture of <i>Cichorium intybus</i>L. and <i>Cinnamomum zeylanicum</i>on Hepatic Enzymes Activity and Biochemical Parameters in Patients with Nonalcoholic Fatty Liver Disease

The prevalence of nonalcoholic fatty liver disease (NAFLD) as a metabolic disorder affecting the liver function is rapidly increasing and there is a need to develop new and more efficient treatment. This study was designed to evaluate the protective effect of Cichorium intybus L. and Cinnamon mixture infusion (2.5 and 0.5 g/100mL and twice/day) on patients with NAFLD. This before-after clinical trial study was performed on 25 patients with NAFLD. They were administered the mixture of extract prepared in special bags twice a day for 30 days. Hepatic and metabolic markers of NAFLD like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), fasting blood sugar (FBS), cholesterol (chol), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in plasma and also, fatty liver ultrasonographic grading were determined before and after using the extracts. 30-day treatment with extracts in NAFLD patients resulted in a significant decrease in ALT and AST. FBS, TG and ALP were also decreased after administration of the extracts but not significantly. A significant linear correlation was found between age and ALP, and between gender and liver enzymes. It is concluded that the mixture of Cichorium intybus L. and Cinnamon extracts has some benefits in NAFLD patients making them valuable for future investigations.

New perspectives on angiotensin-converting enzyme 2 and its related diseases

Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the same time,as a key enzyme in the renin-angiotensin-system,ACE2 is considered to be an endogenous negative regulator of vasoconstriction,proliferation,fibrosis,and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis.ACE2 is now implicated as being closely connected to diabetes,cardiovascular,kidney,and lung diseases,and so on.This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans.

Enzyme replacement therapy in two patients with classic Fabry disease from the same family tree:Two case reports

BACKGROUND The pathophysiology of Fabry disease(FD)-induced progressive vital organ damage is irreversible.Disease progression can be delayed using enzyme replacement therapy(ERT).In patients with classic FD,sporadic accumulation of globotriaosylceramide(GL-3)in the heart and kidney begins in utero;however,until childhood,GL-3 accumulation is mild and reversible and can be restored by ERT.The current consensus is that ERT initiation during early childhood is paramount.Nonetheless,complete recovery of organs in patients with advanced FD is challenging.CASE SUMMARY Two related male patients,an uncle(patient 1)and nephew(patient 2),presented with classic FD.Both patients were treated by us.Patient 1 was in his 50s,and ERT was initiated following end-organ damage;this was subsequently ineffective.He developed cerebral infarction and died of sudden cardiac arrest.Patient 2 was in his mid-30s,and ERT was initiated when the patient was diagnosed with FD,during which the damage to vital organs was not overtly apparent.Although he had left ventricular hypertrophy at the beginning of this treatment,the degree of hypertrophy progression was limited to a minimal range after>18 years of ERT.CONCLUSION We obtained discouraging ERT outcomes for older patients but encouraging outcomes for younger adults with classic FD.

Some Antioxidant Enzymes among Children with Sickle Cell Disease Attending Usmanu Danfodiyo University Teaching Hospital Sokoto, North Western Nigeria

Sickle Cell Disease (SCD) is one of the most common genetic diseases in the world. It is associated with oxidative stress which occurs as a result of HbS unstable character causing a rise in the formation of free radicals. The aim of this study was to determine some antioxidant enzymes activities among patients with SCD. We investigated the superoxide dismutase (SOD), and glutathione peroxidases (GPx) levels among 60 children aged 1 - 14 years with SCD. Twenty-two age-matched non-SCD children served as control. The study subjects were divided into two groups;steady state A (n = 30) and vaso- occlusive crisis (VOC) B (n = 30). The SOD, and GPx levels were significantly lower among the SCD subjects compared to controls (p = 0.000). There were no statistically significant differences in the SOD and GPX levels between sickle cell disease patient in steady state (A) and those in crisis (B) (p = 0.998 and 0.555) respectively. There was a statistically significant difference between the SOD and GPX levels between sickle cell disease patient in steady state (A) and non-sickle cell controls (p = 0.005 and 0.000) respectively as well as between sickle cell disease patient in VOC (B) and non-sickle cell controls (p = 0.000). There were no statistically significant differences in the SOD and GPX levels of sickle disease subjects based on age, gender, maternal level of educational attainment, occupational group and income (p = 0.629 and 0.476;p = 0.382 and 0.417;p = 0.450 and 0.314 and p = 0.397 and 0.762 and p = 0.553 and 0.929) respectively. There were no statistically significant differences in the SOD and GPX levels of sickle disease subjects of Hausa/Fulani extraction versus Yoruba (p = 0.714 and 0.856), between Hausa/Fulani extraction versus Igbo (0.917 and 0.486) and between Yoruba extraction versus Igbo (p = 0.740 and 0.965) respectively. This study confirms that SCD children have lower values of antioxidant enzymes compared to controls. SOD and GPX levels in sickle cell disease patient in steady state and vaso-occlusive crisis are significantly lower compared that of non-sickle cell controls. Patients with SCD may benefit from substances with antioxidant properties which can potentially reduce the complications associated with the disease.

Correlation of serum Aβ1-42 content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease

Objective: To investigate the correlation of serum β-amyloid 1-42 (Aβ1-42) content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease. Methods: A total of 48 patients with Parkinson's disease who were treated in this hospital between December 2014 and October 2017 were selected as Parkinson's disease group, and 50 healthy volunteers who received physical examination in this hospital during the same period were selected as normal control group. The differences in serum contents of Aβ1-42, inflammatory factors and receptors as well as antioxidant enzymes were compared between the two groups, and Pearson test was used to assess the correlation between serum Aβ1-42 content and illness in patients with Parkinson's disease. Results: Serum Aβ1-42 content of Parkinson's disease group was lower than that of normal control group;serum inflammatory factors and receptors IL-2, sIL-2R, IL-6 and sIL-6R contents were higher than those of normal control group;serum antioxidant enzymes SOD, GSH-Px, CAT and TPX contents were lower than those of control group. Pearson test showed that serum Aβ1-42 content of patients with Parkinson's disease was directly correlated with the contents of inflammatory factors and receptors as well as antioxidant enzymes. Conclusions: Serum Aβ1-42 content decreases in patient with Parkinson's disease, and the specific content is directly correlated with the condition of Parkinson's disease, and can be used as an important auxiliary indicator for diagnosis and judgment of Parkinson's disease.

Motor Development as a Potential Marker to Monitor Infantile Pompe Disease on Enzyme Replacement Therapy

After Enzyme Replacement Therapy (ERT) using recombinant human acid alpha-glucosidase (rhGAA), survival of Infantile Pompe Disease (IPD) patients through the first 18 months of age has been documented and acquisitions of motor development are an important outcome, but description of its course is scarce. Objective: To describe the motor development in an IPD patient and its correlation with clinical conditions during the first 18 months on ERT with rhGAA. Methods: By longitudinal observational study of an IPD case at early stage. Clinical and biochemical characteristics were obtained from patient records. Echocardiogram assessed cardiac indexes and the urinary biomarker—glucose tetrasaccharide (Glc4)—was obtained by HPLC/UV, following sample derivatization with butyl 4-amino benzoate and analysis on a C18 stationary phase column. Motor skills were evaluated with Alberta Infant of Motor Scale (AIMS) and motor delay was considered as motor percentile (p) below 10. Descriptive statistical analysis was carried out and t-test was used to calculate the differences among means, with significance level defined as p value < 0.05. Results: After ERT beginning amelioration of the cardiomyopathy with reduced left ventricle mass index (LVMI) from the 2nd month onwards was observed, but above the upper normal limit for healthy children and CRIM-positive IPD patients. Although GAA antibodies level remained above the recommended titers and fluctuating elevation of Glc4 quantified, motor development analysis showed an ascendant curve expected for age within achievement of independent ambulation. Motor delay after pneumonia and maintenance of hypotonia were noted. Variation of Glc4 appeared long after a transitory intercurrence. Conclusion: In an IPD case, motor development can have normal evolution despite hypotonia. Motor analysis seems to be sensitive to follow-up clinical intercurrences. To elucidate the interaction among prognostic factors and outcomes, further clinical studies need to be conducted.

Clinical and Technological Dependence Characteristics on a Series of Brazilian Cases with Infantile Onset Pompe Disease in Enzyme Replacement Therapy

Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as 80% (motor, respiratory or nutritional fields) of the patients. After the third year of ERT, motor disabilities were lost in 50% of ambulated patients. The overall characteristics were similar to international studies. Conclusion: Despite ERT benefits in cardiac involvement, motor disabilities seem to be much more compromised in IOPD patients, with high technology dependence, especially after three years of age.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

《健康和疾病中的酶(Enzymes in Health and Disease)》——第一届国际临床酶学会科学会议论文集简介

1976年4月第七届国际临床酶学专题讨论会在威尼斯召开,会议决定成立国际临床酶学会。第一届国际临床酶学会科学会议于1977年9月19日至21日在伦敦举行,来自20多个国家的与会者约200人,讨论了有关酶的病理生理学、方法学及其标准化、细胞酶类、临床解释以及酶的治疗学的新方向等问题。《健康和疾病中的酶》一书,就是这次会议的论文集,它由Goldberg与Wikinson主编,于1978年出版。全书共237页,分九个专题,共有42篇论文,内容比较丰富。

Enzymatic antioxidant system in vascular inflammation and coronary artery disease

In biological systems there is a balance between the production and neutralization of reactive oxygen species(ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes suchas superoxide dismutase(SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis.Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease(CAD). Some observation indicated that in the early stages of the disease there is a homeostatic upregulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage.As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.

Fabry Disease: Update, Focusing on Heart Disease by Multimodal Imaging

Fabry disease (FD) is a rare X-linked lysosomal accumulation disorder caused by a deficiency in the enzyme alpha-galactosidase A (Gal A), resulting in excessive storage of glycosphingolipids, particularly globotriaosylceramide (Gb3). This leads to cellular dysfunction in various organs, with cardiovascular compromise being the major cause of morbidity and mortality. This study aimed to provide a comprehensive overview of FD focusing on its genetic, epidemiological, clinical, diagnostic, and therapeutic aspects. This study explored the genetic mutations associated with FD, its epidemiology, clinical phenotypes, cardiac manifestations, diagnostic approaches, and current treatment options. Background: FD is caused by mutations in GLA on the X chromosome, with over 1000 identified variants. Neonatal screening and specific studies have shown an increased incidence of FD. The clinical presentation varies between classic and late phenotypes, with cardiac involvement being a major concern, particularly in late-onset FD. Purpose: This study aimed to summarize the current knowledge on FD, emphasizing cardiac involvement, diagnostic modalities, and treatment options. Methods: A literature review of relevant studies on FD, including genetics, epidemiology, clinical presentation, diagnostic methods, and treatment options, was conducted. Results: Cardiac manifestations of FD included left ventricular hypertrophy (LVH), heart failure, arrhythmias, and sudden death. Diagnostic approaches such as electrocardiography, echocardiography, and cardiac magnetic resonance imaging play crucial roles in the early detection and monitoring of cardiac involvement. Enzyme replacement therapy (ERT) and emerging treatments have shown promise in managing FD, although challenges remain. Conclusions: FD remains a challenging condition in cardiology, with under-diagnosis being a concern. Early detection and specific therapy are essential to improve patient outcomes. Echocardiography and cardiac MRI are valuable tools for diagnosis and follow-up. Despite the advances in treatment, accessibility remains an issue. More research is needed to deepen our understanding of FD and to improve therapeutic strategies.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis

BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.

Distribution of Calcium in Bagged Apple Fruit and Relationship between Antioxidant Enzyme Activity and Bitter Pit

[Objective]The aim was to study the distribution of Ca in bagged apple fruit and the relationship between antioxidant enzyme activity and bitter pit disease,which will provide a basis for resolving Ca metabolism disorder in apple cultivation. [Method]With Fuji Apple as the tested material,the changes of Ca2＋ content and antioxidant enzyme activity in different parts of apple fruit after picking bags and storage period were determined. [Result]The results showed that Ca contents in the light surface of fruits were higher than that in the backlight surface. The Ca contents of stalk cavity were higher than that of calyx-end. The activities of SOD,POD,CAT and APX in the light surface of fruits were higher than that in the backlight surface. The activities of SOD,POD,CAT and APX of stalk cavity were higher than that of calyx-end. The contents of MDA in the light surface of fruits were lower than that in the backlight surface. The contents of MDA of stalk cavity were lower than that of calyx-end. [Conclusion]The incidence rate of bitter pit in the light surface of fruits were lower than that in the backlight surface,and the incidence rate of bitter pit of stalk cavity were lower than that of calyx-end.

Main Diseases and Pests of Lonicerae japonica in Guangxi Province and Fluctuation Pattern of Their Natural Enemies

[ Objective ] The paper was to study the main diseases and pests in Lonicerae japonica in Guangxi Province and fluctuation pattern of their natural ene- mies. [Method] The population change of main diseases and pests, and main predatory naturaI enemies of pests in different species of Lonicerae japonica in Xincheng County of Guangxi Province were systematically investigated during 2008 -2010. [ Result ] The variation cycle of population number of Semiaphis heraclei （Takahashi） belongs to single peak type, and it has large occurrence in April. The variation cycle of population number of Franklinlella sp. and Haptonchus luteo- ius （Erichson） belongs to double peak type, and they have large occurrence at April and September. The variation cycle of disease severity of Microsphaera lonicerae （ Wint. ） belongs to double peak type, and the disease index will be larger at April and September. The variation cycle of diseased shoot rate belongs to single peak type; diseased shoot rote of Lonicera dasystyla Rehd. and Loniccra hvpolzlauca Miquel is relatively high during April to June, while the index of Lonice- ra confusa （Sweet） DC. is relatively high during February to May. The variation cycle of population number of main natural enemies such as Lemnia biplagiata （ Swartz）, Coccinella septcmpunctata （ Linnaeus ） and Harmonia axyridis （Pallas） belongs to double peak type, and they have large occurrence at April and Sep- tember. [ Conclusion] The results could provide scientific basis for determination of optimum control period against major diseases and pests in Loniceraejaponica and development of integrated control programs.

Concepts of oxidative stress and antioxidant defense in Crohn's disease

Oxygen free radical and lipid peroxides(oxidative stress)are highly reactive and represent very damaging compounds.Oxidative stress could be a major contributing factor to the tissue injury and fibrosis that characterize Crohn’s disease.An imbalance between increased reactive oxygen species levels and decreased antioxidant defenses occurs in Crohn’s patients.Decreased blood levels of vitamins C and E and decreased intestinal mucosal levels of CuZn superoxide dismutase,glutathione,vitamin A,C,E,andβ-carotene have been reported for Crohn’s patients.Increased levels of proinflammatory cytokines,such as interleukin-1 and-8 and tumor necrosis factor,have been detected in inflammatory bowel disease.Oxidative stress significantly increased the production of neutrophils,chemokines,and interleukin-8.These effects were inhibited by antioxidant vitamins and arachidonic acid metabolite inhibitors in human intestinal smooth muscle cells isolated from the bowels of Crohn’s disease patients.The main pathological feature of Crohn’s disease is an infiltration of polymorphonuclear neutrophils and mononuclear cells into the affected part of the intestine.Activated neutrophils produce noxious substances that cause inflammation and tissue injury.Due to the physiological and biochemical actions of reactive oxygen species and lipid peroxides,many of the clinical and pathophysiological features of Crohn’s disease might be explained by an imbalance of increased reactive oxygen species and a net decrease of antioxidant molecules.This review describes the general concepts of free radical,lipid peroxide and antioxidant activities and eventually illustrates their interferences in the development of Crohn’s strictures.

Nonalcoholic fatty liver disease and the renin-angiotensin system:Implications for treatment

Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.

Aquatic exercise program-modulated oxidative stress markers in patients with Parkinson's disease

Parkinson's disease is a neurodegenerative disease.Oxidative stress,i.e.,the imbalance between the generation of reactive oxygen species and the antioxidant defense capacity of the body,plays an important role in the pathogenesis of this disease.Physical exercise can regulate oxidative stress.The purpose of this study was to analyze the short-and long-term effects of an aquatic exercise program on oxidative stress levels in patients with Parkinson's disease.The aquatic exercise program was carried out during 1 month with two sessions per week(1 hour/session).Blood samples were collected at four different time points:pre-intervention,immediately,48 hours,and 30 days after the first session of aquatic exercise program.Our results revealed that water-based programs modulated antioxidant enzyme activity,increased superoxide dismutase activity,reduced catalase activity,and increased the ratio of superoxide dismutase activity to catalase activity in patients with Parkinson's disease.Compared with pre-intervention and 48 hours after the first session of aquatic exercise program,superoxide dismutase activity was higher and catalase activity was lower immediately and 30 days after the first session.Our results demonstrated that aquatic exercise program could modulate oxidative stress,mainly by the effect of antioxidant enzyme activity.These results could better help understand the target of oxidative stress in Parkinson's disease.This study was approved by the Ethics Committee of Centro Universitário Metodista IPA(approval No.1.373.911)on August 9,2019 and registered with REBEC(registration number:RBR-6 NJ4 MK).