Expression level of myocardial enzymes in patients with schizophrenia: Predictive value in the occurrence of violence

BACKGROUND Schizophrenic patients are prone to violence,frequent recurrence,and difficult to predict.Emotional and behavioral abnormalities during the onset of the disease,resulting in active myocardial enzyme spectrum.AIM To explored the expression level of myocardial enzymes in patients with schizo-phrenia and its predictive value in the occurrence of violence.METHODS A total of 288 patients with schizophrenia in our hospital from February 2023 to January 2024 were selected as the research object,and 100 healthy people were selected as the control group.Participants’information,clinical data,and labo-ratory examination data were collected.According to Modified Overt Aggression Scale score,patients were further divided into the violent(123 cases)and non-violent group(165 cases).RESULTS The comparative analysis revealed significant differences in serum myocardial enzyme levels between patients with schizophrenia and healthy individuals.In the schizophrenia group,the violent and non-violent groups also exhibited different levels of serum myocardial enzymes.The levels of myocardial enzymes in the non-violent group were lower than those in the violent group,and the patients in the latter also displayed aggressive behavior in the past.CONCLUSION Previous aggressive behavior and the level of myocardial enzymes are of great significance for the diagnosis and prognosis analysis of violent behavior in patients with schizophrenia.By detecting changes in these indicators,we can gain a more comprehensive understanding of a patient’s condition and treatment.

Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.

Effects of different doses of ticagrelor on coronary blood flow, inflammatory response and myocardial enzyme spectrum in patients with acute myocardial infarction

Objective:To investigate the effects of different doses of ticagrelor on coronary blood flow, inflammatory response and myocardial enzyme spectrum in patients with acute myocardial infarction.Methods: A total of 180 patients with acute myocardial infarction who were treated in our hospital between December 2015 and March 2017 were reviewed and divided into the routine dose group (n=87) who accepted routine dose of ticagrelor therapy and loading dose group (n=93) who accepted loading dose of ticagrelor therapy. The differences in coronary blood flow, inflammatory response and myocardial enzyme spectrum were compared between the two groups before and after treatment.Results: Immediately after admission, there was no statistically significant difference in the coronary blood flow levels, inflammatory response and myocardial enzyme spectrum contents between the two groups. At 24 h after percutaneous coronary intervention (PCI), the coronary blood flow parameters SPV, DPV and CFVR levels in loading dose group were higher than those in routine dose group;serum inflammatory factors PCT, IL-6 and CRP contents were lower than those of routine dosage group;myocardial enzyme spectrum indexes cTnⅠ, LDH, HBDH and MB contents were lower than those of routine dose group.Conclusion: Loading dose of ticagrelor therapy before PCI can effectively optimize the coronary blood flow after PCI, reduce the systemic inflammatory response and protect the myocardial function in patients with acute myocardial infarction.

Effect of ursodeoxycholic acid combined with bifidobacterium quadruple preparations on myocardial enzyme, immune function and inflammatory response of hyperbilirubinemia neonatal

Objective: To investigate the effects of myocardial enzyme, immune function and inflammatory response by ursodeoxycholic acid combined with bifidobacterium quadruple preparations on hyperbilirubinemia neonatal. Methods: A total of 100 cases of neonatal hyperbilirubinemia in our hospital from June 2016 to May-2017 were selected and divided into control group and observation group by random number table, 50 cases in each group. Two groups of neonatal were given routine symptomatic treatment. The control group was treated with ursodeoxycholic acid and the observation group was treated with Bifidobacterium tetralogy of live bacteria on the basis of the control group. The two groups of neonatal were both treated for 7 d. The serum levels of CK-MB, CK, LDH, AST, CD3+, CD4+, CD4+/CD8+, CD8+, CRP and TNF-α were measured before and after the treatment of the two groups. Results: Before treatment, there was no significant difference in serum CK-MB, CK, LDH, AST, CD3+, CD4+, CD4+/CD8+, CD8+, CRP and TNF-α levels between the 2 groups. After treatment: 2 groups of serum CK-MB, CK, LDH, AST, CD8+, CRP, TNF-α levels significantly decreased compared with the group before treatment, CD3+, CD4+ and CD4+/CD8+ levels were significantly increased after treatment, and the observation group with serum CK-MB, CK, LDH, AST, CD8 +, CRP, TNF-α levels were significantly lower than the control group, CD3+, CD4+ and CD4+/CD8+ levels were significantly higher than the control group, the differences were statistically significant. Conclusion: Ursodeoxycholic acid combined with Bifidobacterium quadruple viable tablets can can reduce the activity of myocardial enzyme, improve the state of spectrum index of neonatal hyperbilirubinemia.

Myocardial enzyme activities of black bears and comparison with those of human beings

According to the principle of enzyme reaction rate, healthy pent black bears’ myocardial enzyme activity is assayed by visual colorimetry and compared with that of healthy human beings. The determination at 37 °C and the statistic analysis of the experimental data work out the following findings. For male black bears, the average CK activity is 163.20 U/L, the confidence interval of its expected value (127.70 to 198.70) U/L, and the coefficient of variation 39.2%; the average CK-MB activity 21.62 U/L, the confidential interval (17.72 to 25.51) U/L, and the coefficient of variation 34.26%; the average LDH activity 604.20 U/L, the confidence interval (524.56 to 683.83) U/L, and the coefficient of variation 23.80%; the average HBDH activity 516.70 U/L, the confidence interval (453.06 to 580.34) U/L, and the coefficient of variation 22.24%; the average GOT activity 69.70 U/L, the confidence interval (60.21 to 79.19) U/L, and the coefficient of variation 24.59%. For female black bears, the average CK activity is 145.50 U/L, the confidence interval (114.59 to 176.21) U/L, and the coefficient of variation 38.27%; the average CK-MB activity 18.84 U/L, the confidence interval (14.64 to 23.04) U/L, and the coefficient of variation 40.34%; the average LDH activity 563.70 U/L, the confidence interval (473.80 to 652.60) U/L, and the coefficient of variation 28.80%; the average of HBDH activity 475.50 U/L, the confidence interval (412.10 to 538.40) U/L, and the coefficient of variation 24.07%; the average of GOT activity is 62.37 U/L, the confidential interval (52.54 to 72.20) U/L, and the coefficient of variation 28.46%. The male black bear’s average myocardium enzyme activities are slightly higher than those of the female. But the statistical results indicate that the difference is not significant.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome

BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.

Clinical significance of NT-proBNP, myocardial enzymes, and inflammatory cytokines in diagnosis of acute coronary syndrome

Objective:To explore the clinical significance of NT-proBNP, myocardial enzymes, and inflammatory cytokines in diagnosis of acute coronary syndrome (ACS).Methods: A total of 120 patients with ACS confirmed by CAG who were admitted in our hospital from December, 2014 to December, 2016 were included in the study and divided into UAP group (n=28), NSTEMI group (n=41), and STEMI group (n=51) according to different lesion degrees. Moreover, 40 cases with negative CAG results were served as the control group. The standard Judkins method was used for CAG examination. Multi-position projection was performed to confirm the coronary lesion degrees. The peripheral venous blood was collected on admission, and the serum was separated. The fluorescence immunoassay was used to detect NT-proBNP and CK-MB levels. The chemiluminiscence was used to detect cTnI level. The immunoturbidimetry was used to detect hs-CRP level. ELISA was used to detect IL-18, TNF-α, and MMP-9 levels.Results:The serum NT-proBNP, CK-MB, cTnI, hs-CRP, IL-18, TNF-α, and MMP-9 levels were graudally increased in the control group, UAP group, NSTEMI group, and STEMI group, and the comparison among each group was statistically significant.Conclusions: The combined detection of serum NT-proBNP, CK-MB, cTnI, hs-CRP, IL-18, TNF-α, and MMP-9 is of great significance in diagnosis of ACS, evaluation of severity degree, risk stratification, and formulation of therapeutic schemes.

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.

Engineering high amylose and resistant starch in maize by CRISPR/Cas9-mediated editing of starch branching enzymes

To improve the amylose content(AC)and resistant starch content(RSC)of maize kernel starch,we employed the CRISPR/Cas9 system to create mutants of starch branching enzyme I(SBEI)and starch branching enzyme IIb(SBEIIb).A frameshift mutation in SBEI(E1,a nucleotide insertion in exon 6)led to plants with higher RSC(1.07%),lower hundred-kernel weight(HKW,24.71±0.14 g),and lower plant height(PH,218.50±9.42 cm)compared to the wild type(WT).Like the WT,E1 kernel starch had irregular,polygonal shapes with sharp edges.A frameshift mutation in SBEIIb(E2,a four-nucleotide deletion in exon 8)led to higher AC(53.48%)and higher RSC(26.93%)than that for the WT.E2 kernel starch was significantly different from the WT regarding granule morphology,chain length distribution pattern,X-ray diffraction pattern,and thermal characteristics;the starch granules were more irregular in shape and comprised typical B-type crystals.Mutating SBEI and SBEIIb(E12)had a synergistic effect on RSC,HKW,PH,starch properties,and starch biosynthesis-associated gene expression.SBEIIa,SS1,SSIIa,SSIIIa,and SSIIIb were upregulated in E12 endosperm compared to WT endosperm.This study lays the foundation for rapidly improving the starch properties of elite maize lines.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes

BACKGROUND Coronary heart disease and type 2 diabetes mellitus(T2DM)frequently coexist,creating a complex and challenging clinical scenario,particularly when complicated with acute myocardial infarction(AMI).AIM To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion.METHODS In total,98 patients were categorized into control(n=47)and observation(n=51)groups.The control group received noxital,while the observation group was treated with dapagliflozin combined with noxital for 6 months.Changes in myocardial microperfusion,blood glucose level,cardiac function,N-terminal prohormone of brain natriuretic peptide(NT-proBNP)level,growth differentiation factor-15(GDF-15)level,and other related factors were compared between the two groups.Additionally,the incidence of major adverse cardiovascular events(MACE)and adverse reactions were calculated.RESULTS After treatment,in the observation and control groups,the corrected thrombolysis in myocardial infarction frame counts were 37.12±5.02 and 48.23±4.66,respectively.The NT-proBNP levels were 1502.65±255.87 and 2015.23±286.31 pg/mL,the N-terminal pro-atrial natriuretic peptide(NT-proANP)levels were 1415.69±213.05 and 1875.52±241.02 ng/mL,the GDF-15 levels were 0.87±0.43 and 1.21±0.56 g/L,and the high-sensitivity C-reactive protein(hs-CRP)levels were 6.54±1.56 and 8.77±1.94 mg/L,respectively,with statistically significant differences(P<0.05).The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group(P<0.05).The incidence of adverse reactions was 13.73%(7/51)in the observation group and 10.64%(5/47)in the control group,with no statistically significant difference(P>0.05).CONCLUSION Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM.The underlying mechanism may be related to the reduction in the expression levels of NT-proANP,GDF-15,and hs-CRP.

Successful emergency surgical intervention in acute non-STsegment elevation myocardial infarction with rupture:A case report

BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with non-STEMI.Types of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle rupture.The FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be effective.Ventricular septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair options.CASE SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary angiography.Prompt resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient recovery.CONCLUSION This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.

Enhanced Angiotensin-Converting Enzyme 2 Attenuates AngiotensinⅡ-Mediated Hypertension,Myocardial Fibrosis,and Hypertrophy in Mice

Background Activation of the renin-angiotensin system and the subsequent generation of angiotensin（Ang）Ⅱis an important mediator of myocardial fibrosis,pathological hypertrophy and heart failure.Angiotensin-converting enzyme 2（ACE2） has recently been identified as AngⅡ-degrading enzyme capable of generating Ang（1 -7） and as a negative regulator of the renin-angiotensin system.We assessed the hypothesis that ACE2 mediates its anti-fibrotic and anti-hyper-trophic effects through the modulation of AngⅡsignaling. Methods We implanted mini-osmotic pumps with AngⅡ(1.5 mg·kg-1·d-1) for 14 days in male wildtype（WT） mice which were then treated with recombinant human ACE2(rhACE2;2 mg·kg-1,d i.p.) or placebo.Systolic blood pressure of mouse was measured using the tail cuff method with the IITC Blood Pressure Monitoring Systems.Results Chronic AngⅡinfusion resulted in a predicted pressor response（peak SBP:163±7 mm Hg,n=8,P【0.01）,treatment with rhACE2 reduced the pressor response（139±4 mm Hg;n=6,P【0.05）and reduced the hypertrophic response based on left ventricular mass and expressions of atrial natriuretic factor,brain natriuretic peptide andα-skeletal actin（P【0.05,respectively）.Interestingly,echocardiographic assessment including tissue Doppler measurement revealed attenuated ventricular hypertrophy and improvement in diastolic dysfunction in AngⅡ-treated mice injected with rhACE2.Trichrome and picrosirius red staining showed a marked increase in myocardial fibrosis in response to AngⅡwhich was suppressed by rhACE2（collagen volume fraction; 7.3%±1.3%vs.4.1%±1.1%;n=6～7,P【0.05） with reduced expression of collagenⅠandⅢ,fibronectin and transforming growth factor-P in response to rhACE2.In male ACE2 knockout mice（Ace2-/y）,AngⅡinfusion resulted in greater pressor response（186±8 mm Hg;re=8,P【0.01） and worsening diastolic dysfunction compared to WT mice infused with AngⅡ.Conclusions In the setting of elevated AngⅡ,loss of ACE2 increases AngⅡ-induced hypertension and diastolic dysfunction. In contrast,recombinant human ACE2 prevents AngⅡ-mediated hypertension,myocardial hypertrophy and fibrosis.We conclude that ACE2 plays a pivotal role in the prevention of hypertension,myocardial hypertrophy and fibrosis acting as a protective mechanism in the heart to limit the pathological effects of an activated systemic and/or local RAS and ACE2 represents a novel therapeutic strategy for cardiovascular disorders.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.

Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

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.

Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway

The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

Aldo-Keto reductase 1C3 reduces myocardial cell damage after acute myocardial infarction by activating the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant response element pathway to inhibit ferroptosis

Background Acute myocardial infarction(AMI)is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress.Aldo-Keto Reductase 1C3(AKR1C3)is a stress-regulating gene.Nevertheless,its specific role and mechanisms regarding AMI remain unclear.Methods We assessed cardiac function through echocardiography;tissue damage was evaluated using Hematoxylin and Eosin(HE)and Masson trichrome staining.AKR1C3 expression levels were measured through Reverse transcription-quantitative polymerase chain reaction and western blot.Assessed cell viability using Cell Counting Kit-8 and lactate dehydrogenase(LDH)assays.The extent of ferroptosis was determined by measuring the levels of Fe2+,boron-dipyrromethane(BODIPY)and malondialdehyde(MDA),the glutathione/glutathione disulfide(GSH/GSSG)ratio,and the expression of Glutathione Peroxidase 4(GPX4)and Solute carrier 7A11(SLC7A11).Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2-Antioxidant response element(Keap1-Nrf2-ARE)pathway activation was analyzed through western blotting.Nrf2 was inhibited with ML385and activated with(R)-Sulforaphane to investigate the Keap1-Nrf2-ARE pathway.Results The rats in the AMI group displayed reduced heart function,more tissue damage,and lower AKR1C3 expression compared to the Sham group.Similarly,hypoxia-treated H9C2 cells showed reduced viability,and decreased AKR1C3 expression.Overexpressing AKR1C3 in H9C2 cells enhanced viability.Knocking down AKR1C3 exhibited the opposite effect.Of the inhibitors tested,Ferrostatin-1 most effectively restored cell viability in hypoxia-treated H9C2 cells.Moreover,H9C2 cells subjected to hypoxia suggested Keap1-Nrf2-ARE pathway inhibition.Overexpressing AKR1C3 reduced ferroptosis and activated the Keap1-Nrf2-ARE pathway in hypoxia-treated cells,knocking down AKR1C3 exhibited the opposite effect.Further experiments using ML385 in hypoxia-treated H9C2 cells with overexpressed AKR1C3 showed decreased viability and increased ferroptosis compared to the control.Using(R)-Sulforaphane in hypoxia-treated H9C2 cells with knocked-down AKR1C3 exhibited the opposite effect.Conclusion This study's findings indicate that AKR1C3 plays a role in regulating ferroptosis in myocardial cells,with the Keap1-Nrf2-ARE pathway likely being a key mechanism behind it.

Processing Effects on Selected Antioxidant Activities and Metabolizing Enzyme Inhibition of M. Koneigii (Curry Leaves) Extracts

Curry leaves, scientifically termed Murraya koenigii, are renowned in South Asian cuisine for their flavor enhancement and potential health benefits, including antioxidative, anti-inflammatory, and antidiabetic properties. This study aimed to evaluate the impact of thermal processing methods on curry leaves by analysing Total Phenolic Content (TPC), Total Flavonoid Content (TFC), antioxidant activity, and metabolizing enzyme inhibition. Fresh curry leaves were subjected to thermal treatments: Oven-dried at 60˚C and Air-dried at 25˚C for 2 weeks. Extracts were prepared using Ethanol and water solvents. Results indicated that Air-dried leaves exhibited significantly higher TPC (5132.65 mg GAE/100 g) and TFC (243.13 mg CE/100 g) compared to Fresh and Oven-dried leaves. Antioxidant assays show that oven-dried curry leaves at 60˚C displayed higher results in NORS, FRAP, and TEAC assays compared to Fresh and Air-dried leaves. Ethanol extracts showed better extraction of bioactive compounds than aqueous extracts. Moreover, Lipase inhibition activity was notably high, indicating potential health benefits. This study provides valuable insights into the effects of processing methods on curry leaf extracts, emphasizing the importance of solvent selection for optimal extraction of bioactive compounds.

A Comparative Study of Myocardial Damage Caused by Novel Coronavirus Infection and Influenza A Virus Infection in Children during the COVID-19 Epidemic Period

Objective: To explore the comparative study of myocardial damage in children infected with COVID-19 and influenza A virus during the COVID-19 pandemic. Method: Retrospective analysis of myocardial injury caused by COVID-19 infection and influenza A virus infection in children during the COVID-19 from October 2022 to May 2023, including 106 cases of COVID-19 infection, that is, the COVID-19 group;And 164 cases of influenza A virus infection, namely, H1N1 group;Two groups were tested for various indicators of myocardial enzyme spectrum, and the situation of myocardial injury was compared between the two groups. Result: In the enrolled cases, there was no statistically significant difference in the prevalence rate of men and women in the COVID-19 group (P > 0.05);There was no statistically significant difference in the average age between men and women (P > 0.05);The comparison of the incidence rates between males and females in the H1N1 group showed a statistically significant difference (P 0.05);There was no statistically significant difference in the average age between the two groups of girls (P > 0.05). A comparison between two groups of various indicators of myocardial enzyme spectra showed that the results of AST, -HBDH and LDH were statistically significant (P 0.05). Conclusion: Both COVID-19 infection and influenza A virus infection in children have different degrees of myocardial damage, but COVID-19 infection causes more myocardial damage than influenza A virus infection, and influenza A virus is more prone to myocardial infarction, which deserves our attention.

The Efficacy and Safety of Drug-Coated Balloons in the Treatment of Acute Myocardial Infarction

The incidence of acute myocardial infarction (AMI) is increasing year by year, which seriously endangers human health around the world. The preferred treatment strategy for AMI patients is the use of drug-eluting stents (DES), as there is ample evidence to suggest that stent implantation can reduce major adverse cardiovascular events (MACEs). With the application of drug-coated balloons (DCBs) and the enhancement of the concept of interventional without implantation, the question is whether DCBs can be safely and effectively used in patients with AMI? The purpose of this study was to investigate the safety and effectiveness of DCBs in the treatment of AMI. A retrospective review of clinical data was conducted on 55 AMI patients who underwent primary percutaneous coronary intervention (PCI) from January 2020 to December 2021. Of these patients, 25 were treated with DCBs and 30 were treated with DESs. Optical coherence tomography (OCT) was used to measure the minimum lumen diameter, lumen stenosis, and coronary artery dissection before and after surgery, and angina pectoris attacks and various MACEs were recorded at 1, 6, and 12 months after surgery. The results showed that there were no significant differences in clinical baseline data between the two groups. However, the minimum lumen diameter of the DCB group immediately after the operation was smaller than that of the DES group, and the stenosis degree of the lumen in the DCB group was higher than that in the DES group. The incidence of coronary artery dissection in the DCB group was significantly higher than that in the DES group, but the majority of them were type B. At 1, 6, and 12 months after treatment, there was no significant difference in the occurrence of MACEs between the two groups. In conclusion, DCBs is a safe and effective treatment for AMI. However, the incidence of coronary artery dissection in DCB patients is higher than that in DES patients, but the majority of them are type B. .