Angiotensin-converting Enzyme Research Articles

Heterologous expression of a recombinant ACE inhibitory peptide LYPVK and its potential antihypertensive action mechanism.

Enzymatic hydrolysis approach is commonly employed for preparation of active peptides, while the limited purity and yield of produced peptides hinder further development of action mechanisms. This study presents the biotechnological approach for the efficient production of recombinant angiotensin converting enzyme (ACE) inhibitory peptide LYPVK and investigates its potential antihypertensive action mechanism. DNA encoding sequence of recombinant peptide was designed to form in tandem, which was expressed in Escherichia coli BL21 (DE3). The expressed tandem repeat protein with molecular weight of 13.4 kDa was verified by high performance liquid chromatography (HPLC) and amino acid composition. Subsequently, LYPVK was generated following His-tag removal and trypsin-mediated cleavage of the purified protein, which was performed HPLC and liquid chromatography-mass spectrometry (LC-MS) analysis. LYPVK exhibited an IC50 value of 10.6 ± 0.86 μg/mL, demonstrating a non-competitive mode of action and resistance to gastrointestinal enzyme hydrolysis and heat conditions. Molecular docking results showed that LYPVK interacted with ACE through conventional hydrogen bonds and hydrophobic interactions. Except for ACE, ALB, SRC, PPARG, and MMP9 are identified as potential key targets for its antihypertensive activity by network pharmacological analysis. This study provides a promising biotechnological approach for the preparation of active peptides with high purity and yield.

Clinical studies in Myxomatous Mitral Valve Disease dogs: most prescribed ACEI inhibits ACE2 enzyme activity and ARB increases AngII pool in plasma.

Thehypertension patient population has doubled since 1990, affecting 1.3 billion globally and >75% live in low-and middle-income countries. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are themost prescribed drugs(>160 million times in the US), but mortality increased >30% since 1990s globally. Clinical relevance of Myxomatous Mitral Valve Disease (MMVD) is directly linked to WHO group 2 pulmonary hypertension, with no disease specific therapies. Therefore, MMVD pet dogs with elevated systolic blood pressure treated with ACEI/ARB, were supplemented with oral ACE2 enzyme and Angiotensin1-7 (Ang1-7) bioencapsulated in plant cells. The oral ACE2/Ang1-7 was well tolerated by healthy and MMVD dogs with no adverse events and increased sACE2 activity by 670-755% with ARB (Telmisartan) than with ACEI (Enalapril) background therapy. In vitro rhACE2 activity was inhibited >90% by ACEIs enalapril/benazeprilat at higher doses but lisinopril inhibited at much lower doses. Membrane ACE2 activity evaluated in exosomes was 43-fold higher than the sACE2 and this was also inhibited 211% by ACEI, when compared to ARB. Background ACEI treatment reduced the Ang-II pool by 11-20-fold and proportionately decreased the abundance of Ang1-7 + Ang1-5 peptides. In contrast, ARB treatment increased Ang-II pool 11-20-fold and Ang1-7 + Ang1-5 by 160-260%. Systolic blood pressure was regulated by ARB better than ACEI, despite very high Ang-II levels. This first report on evaluation of metabolic pools in the RAS pathway identifies surprising interactions between ACEI/ARB/ACE2 and significant changes in key molecular dynamics. Affordable biologics developed in plant cells may offer potential new treatment options for hypertension.

Identification of barley-derived peptides with angiotensin converting enzyme inhibitory activity

Identification of barley-derived peptides with angiotensin converting enzyme inhibitory activity

Changes in Phenylacetylglutamine Levels Provide Add-On Value in Risk Stratification of Hypertensive Patients: A Longitudinal Cohort Study.

Despite antihypertensive treatment, some high-risk hypertensive patients still experience major adverse cardiovascular events (MACEs). Current risk stratification tools may underestimate the presence of metabolites in hypertension and thereby risk of MACEs. We aimed to explore the potential value of gut microbiota-derived metabolite phenylacetylglutamine (PAGln) in risk stratification of hypertension. We measured plasma PAGln levels using liquid chromatography tandem mass spectrometry in 1543 high-risk hypertensive patients, dividing them into a discovery cohort (n = 792) and a validation cohort (n = 751). After follow-up, the Kaplan-Meier curve and the Cox regression model were utilized to determine the correlation between PAGln and MACEs (death, non-fatal ischemic stroke and hemorrhagic stroke, non-fatal acute coronary syndrome and unplanned revascularization). We examined the predictive performance of PAGln in different subgroups and evaluated the incremental predictive value of PAGln as an addition to the ASCVD risk assessment model. Among all high-risk hypertensive patients, 148 patients experienced MACEs after a mean follow-up of 3.02 years. In both cohorts, after adjusting other confounding risk factors, PAGln remained an independent risk factor the MACEs in hypertensive patients. Patients with plasma PAGln ≥ 1.047 μmol/L have a higher risk of MACEs. PAGln concentration provided incremental predictive value to the ASCVD risk model, with better performance in the discovery cohort. It was most effective in female, patients with a systolic blood pressure (SBP) ≥ 130 mmHg and taking angiotensin-converting enzyme inhibitors (ACEIs). PAGln was associated with an increased risk of MACEs in hypertension, especially in women or in subgroups with SBP ≥ 130 mmHg and taking ACEIs. PAGln should be considered as an independent predictor in risk stratification to improve prognosis.

An Open-Label, Non-randomized, Drug-Repurposing Study to Explore the Clinical Effects of Angiotensin II Type 1 (AT1) Receptor Antagonists on Anxiety and Depression in Parkinson's Disease.

The cerebral Renin-Angiotensin System might have a role in anxiety and depression development. We explored the effects of Angiotensin II Type 1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) on anxiety and depression in Parkinson's Disease (PD). Four hundred and twenty-three newly diagnosed drug-naïve PD patients were evaluated using the State-Trait Anxiety Inventory (STAI) and Geriatric Depression Scale (GDS-15) tests and were monitored at baseline and for up to 3 years. Twelve patients were treated with ARBs and 42 with ACE-Is. ARB-treated patients had lower anxiety STAI scores than those on ACE-Is or drug-free at baseline (17.2 ± 1.3 vs. 21.3 ± 1.3, or 23.8 ± 0.5, respectively, P = 0.021) and during the follow-up (P < 0.01). Depression scores were unaffected by any of the drugs throughout the study. This small sample of ARB-treated PD patients displayed lower levels of anxiety. Randomized clinical trials are warranted.

Investigating the impact of Multiwalled Carbon Nanotubes exposure on enzymatic activities and histopathological variations in Swiss albino mice

Present study was conducted to evaluate the detrimental impacts of exposure of Multi-walled Carbon Nanotubes (MWCNT-NP) on enzymatic activities and tissue structures in Swiss albino mice. The experimental groups of mice received MWCNT-NP for specific time period (seven or fourteen days). Two distinct doses of the MWCNT-NP solution were given orally: 0.45 µg and 0.90 µg, and the distilled water was given to the control group. Serum samples were extracted at 7 and 14 days after the experiment by centrifuging whole blood for 15 min at 3,000 rpm. An enzyme-linked immunosorbent test (ELISA) was used to measure many enzyme assays, such as Angiotensin Converting Enzymes (ACE), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase enzyme. Hematoxylin and Eosin (H&E) staining of tissue samples was done along with a histopathological examination. During a 14-day exposure, ACE, NADPH Oxidase, ALT, and AST enzyme levels were significantly higher in the exposed groups (0.45 µg and 0.90 µg) than in the control group (p < 0.05). Male mice exposed to MWCNT-NP showed substantial histological damage in the relevant organs as well as elevated enzyme activity levels. Present study showed a comprehensive and practical assessment of the toxicity associated with MWCNT-NP of different geometries and functionalization.

Broad-spectrum affinity chromatography of SARS-CoV-2 and Omicron vaccines from ligand screening to purification.

Emerging variants of SARS-CoV-2 pose great technological and regulatory challenges to vaccine manufacturing, especially in downstream processing. To address this dilemma, the development of broad-spectrum affinity chromatography for the purification of wild-type SARS-CoV-2 and its variants is crucial. We propose a comprehensive strategy to achieve this goal via the identification of high-affinity peptides by affinity selection of phage display and next-generation sequencing (NGS) and the evaluation of chromatographic performance. Two peptides targeting the angiotensin-converting enzyme 2 (ACE2)-binding motif on the receptor-binding domain (RBD), HFVKTPARWAWG (SP-HFV) and HYRTSHWHHLLG (SP-HYR), were obtained from the most abundant sequences of the enriched phage library. They exhibited nanomolar affinity for the RBD and trimeric spike protein (Trimer S), and had broad-spectrum affinity for all the RBDs from the variants. Molecular dynamics simulations revealed the different binding regions of SP-HFV and SP-HYR in the ACE2-binding motif and key residues contributing to binding. After SP-HYR was coupled onto agarose matrices, chromatographic results showed that the RBD and Trimer S from the wild-type and Omicron variant could be adsorbed at pH 6.0-6.5 and eluted by increasing the salt concentration, exhibiting broad-spectrum and mild-elution characteristics of affinity chromatography. Finally, the affinity chromatography was applied for the purification of inactivated SARS-CoV-2 and Omicron vaccines, affording high yields (84.5-93.0 %) and purities (81.3-98.0 %), and great resistance to harsh cleaning-in-place in 20 cycles. This work clearly demonstrated the commercial potential of broad-spectrum affinity chromatography for vaccine purification to address the rapid variation of pathogenic viruses.

Efficacy and safety of tripterygium glycosides combined with ACEI/ARB on diabetic nephropathy: a meta-analysis

AimsThis study aims to evaluate the efficacy and safety of tripterygium glycosides combined with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in treating Diabetic nephropathy and provide high-level evidence to support its standardized application.MethodsLiteratures were retrieved from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wanfang and VIP databases, the search time frame was defined as from the time of establishment to April 2023. This study only included randomized controlled trials of tripterygium glycosides combined with ACEI/ARB in the treatment of diabetic nephropathy, and the final included studies were identified according to the inclusion and exclusion criteria, and meta-analysis of data was performed using RevMan 5.3 software.ResultsA total of 44 RCTs with 3537 DN patients were included in the study. Compared with the control group, tripterygium glycosides combined with ACEI/ARB significantly reducing 24 h-UTP (24 h urine total protein) [SMD = −1.46, 95% CI (−1.70, −1.23), P &amp;lt; 0.00001], increasing effective rate [RR = 1.23, 95% CI (1.17,1.29), P &amp;lt; 0.00001], elevating serum albumin [SMD = 0.85, 95% CI (0.69, 1.02), P &amp;lt; 0.00001], improving serum creatinine [SMD = −0.35, 95% CI (−0.59, −0.11), P = 0.004], with no difference in BUN (blood urea nitrogen) [SMD = −0.17, 95% CI (−0.48,0.13), P = 0.27], the adverse reactions rate was higher than those of the control group [RR = 1.96, 95%CI (1.43, 2.68), P &amp;lt; 0.0001].ConclusionThis study showed that the combination of tripterygium glycosides and ACEI/ARB was more effective than ACEI/ARB alone. However, the side effects of the combined treatment group were higher than those of the control group, especially liver function damage, which also suggested that its safety in the treatment of diabetic nephropathy was worth considering. Therefore, although tripterygium glycosides provided a choice for the clinical treatment of diabetic nephropathy, its side effects limited its clinical application. In future studies, we need to further optimize tripterygium glycosides and reduce its side effects to ensure the safety of clinical application.

Predictive Value of ACEF I and II Scores for Postoperative Atrial Fibrillation in Isolated On-Pump Coronary Artery Bypass Grafting Surgery: A Multicenter Retrospective Study.

This study evaluated the predictive performance of age, creatinine, and ejection fraction (ACEF) I and II scores for the development of postoperative atrial fibrillation (PoAF) after isolated on-pump coronary artery bypass grafting (CABG) surgery and compared them with a novel nomogram model developed for PoAF prediction. This retrospective multicenter study involved 511 patients who underwent isolated on-pump CABG. Their ACEF scores were calculated, and multivariate logistic regression analysis was performed to develop a nomogram model. The discriminative performance of the ACEF scores and the novel nomogram model was assessed using the area under the receiver operating characteristic curve (AUC). Of the 511 patients, 169 (33.1%) developed PoAF. The ACEF I and II scores showed moderate discriminative ability (AUC = 0.642 and 0.647, respectively), with no significant difference between them (p = 0.787). Logistic regression analyses identified age, preoperative hemoglobin levels, emergency procedure, chronic kidney disease or need for dialysis, preoperative beta-blocker use, preoperative angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, inotrope requirement, postoperative stroke, and postoperative potassium levels as independent predictors of PoAF. The novel nomogram model demonstrated greater predictive ability than the ACEF scores (AUC = 0.742, p < 0.001). ACEF scores could be helpful risk stratification tools for PoAF after on-pump CABG procedures. Additional validation studies are required to confirm their clinical utility in diverse surgical procedures and patient populations.

Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study

BackgroundAcute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of the renin–angiotensin system (RAS) is linked to COVID-19, but also to non-COVID-19 ARDS. It is still unclear whether changes in the RAS are associated with prognosis of severe COVID-19.MethodsIn this prospective exploratory study, blood samples of 94 patients with COVID-19 were taken within 48 h of admission to a medical ward or an ICU. In ICU patients, another blood sample was taken seven days later. Angiotensin (Ang) I-IV, Ang 1–7, Ang 1–5 and aldosterone concentrations were measured with liquid chromatography tandem mass spectrometry (LC–MS/MS) followed by calculation of markers for activities of renin (PRA-S) and ACE (ACE-S), alternative RAS activation (ALT-S) as well as the ratio of aldosterone to Ang II (AA2R). Angiotensin-converting enzyme (ACE) and ACE2 concentrations were measured by LC–MS/MS-based assays. All RAS parameters were evaluated as predictors of 28-day and 60-day survival using receiver operating characteristic and multivariate logistic regression analysis.ResultsAA2R at inclusion was a predictor of 60-day survival for ICU patients with an AUROC of 0.73. Ang II and active ACE2 were inversely associated with survival (OR 0.07; 95%CI 0.01, 0.39 and OR 0.10; 95%CI 0.01, 0.63) while higher Ang 1–7 predicted favorable outcome (OR 6.8; 95%CI 1.5, 39.9). ICU patients showed higher concentrations of all measured angiotensin metabolites, PRA-S, ALT-S and active ACE2, and lower ACE-S and AA2R than patients in the medical ward at inclusion. After seven days in the ICU, Ang I, Ang II, Ang III and Ang IV concentrations decreased, while ACE and ACE2 levels increased. Ang I, PRA-S, Ang 1–7 and Ang 1–5 concentrations correlated with the SOFA score both at the time of inclusion and after seven days, and driving pressure after seven days.ConclusionsAA2R at inclusion predicted 60-day survival with moderate sensitivity, revealing a dissociation between unchanged aldosterone and increased Ang II levels in the most severely ill COVID-19 patients. After adjustment for confounders, Ang 1–7 as the final metabolite of alternative RAS was predictive for survival.

Alaria esculenta, Ulva lactuca, and Palmaria palmata as Potential Functional Food Ingredients for the Management of Metabolic Syndrome.

Hypertension, type 2 diabetes (T2D), and obesity raise an individual's risk of suffering from diseases associated with metabolic syndrome (MS). In humans, enzymes that play a role in the prevention and development of MS include angiotensin converting enzyme (ACE-1) associated with hypertension, α-amylase associated with T2D, and lipase linked to the development of obesity. Seaweeds are a rich source of bioactives consisting of proteins/peptides, polysaccharides, and lipids. This study examined the potential of seaweed-derived bioactives from Alaria esculenta, Ulva lactuca, and Palmaria palmata as inhibitors of ACE-1, α-amylase, and lipase. In vitro enzyme inhibitory assays were used to quantify the bioactivity of the seaweed extracts and compare their half-maximal inhibitory (IC50) values to recognised positive control enzyme inhibitory drugs captopril© (an ACE-1 inhibitor), acarbose (an α-amylase inhibitor), and orlistat (a lipase inhibitor). Three seaweed extracts displayed enzyme inhibitory activities equal to, or more effective than, the reference positive control drugs. These were P. palmata peptides (ACE-1 IC50 94.29 ± 3.07 µg/mL, vs. captopril© 91.83 ± 2.68 µg/mL); A. esculenta polyphenol extract (α-amylase IC50 147.04 ± 9.72 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL, and lipase IC50 106.21 ± 6.53 µg/mL vs. orlistat 139.74 ± 9.33 µg/mL); and U. lactuca polysaccharide extract (α-amylase IC50 168.06 ± 10.53 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL). Proximate analysis also revealed that all three seaweeds were a good source of protein, fibre, and polyunsaturated essential fatty acids (PUFAs). These findings highlight the potential of these seaweeds in the management of diseases associated with MS and as foods.

The Effect of the Concurrent Use of Angiotensin-Converting Enzyme Inhibitors or Receptor Blockers on Toxicity and Outcomes in Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis.

Background/Objectives: ACEIs protect against radiation pneumonitis by reducing angiotensin II production, oxidative stress, and inflammation. This study highlights the significance of concurrent angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in radiotherapy by evaluating its impact on radiotherapy-related side effects and survival outcomes, addressing the gap in existing research and providing insights to guide clinical practice in oncology. Methods: The literature was retrieved from the MEDLINE, EMBASE, Web of Science, and Scopus databases from January 2000 to October 2024. Studies on adults (≥18 years) with histologically confirmed cancer, receiving ACEIs or ARBs during radiotherapy, were included. Radiotherapy-related side effects and clinical outcomes were analysed using odds ratios (ORs) and 95% confidence intervals (95%CIs), comparing ACEI/ARB users to non-users. Differences in the median survival time, recurrence, and death rates were also calculated. Results: Sixteen studies (14 cohort studies and two randomised trials) were included. ACEI users exhibited a 50% reduction in the risk of ≥grade 2 radiation pneumonitis (OR: 0.50, 95%CI: 0.32-0.77) in lung cancer and significant reductions in the odds of proctitis (80%, OR: 0.20, 95%CI: 0.12-0.33), haematuria (75%, OR: 0.25, 95%CI: 0.16-0.41), and rectal bleeding (61%, OR: 0.39, 95%CI: 0.30-0.51) in prostate cancer. ACEI/ARB users showed reduced symptomatic radiation necrosis in brain metastases and better 6-month functional independence in supratentorial glioblastoma. Among six studies reporting survival, ACEI/ARB users had longer median survival in early-stage non-small-cell lung cancer and glioblastoma but shorter survival in small cell lung cancer and brain metastases. ARB users had inconsistent survival rates for lung cancer. The varying survival outcomes suggest that ACEIs/ARBs have different effects depending on the cancer type and stage, potentially influenced by cancer-specific factors, treatment protocols, or disease progression. Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival outcomes remains inconsistent across cancer types and severities. Further research should carefully control for confounders.

Blood Pressure Management Strategies and Podocyte Health.

Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective blood pressure (BP) management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current BP management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics, as well as newer therapies (sodium-glucose cotransporter-2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.

Establishment of a Yeast Two-Hybrid-Based High-Throughput Screening Model for Selection of SARS-CoV-2 Spike-ACE2 Interaction Inhibitors.

The recent coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted considerable impact on global health. To prepare for rapidly mutating viruses and for the forthcoming pandemic, effective therapies targeting the critical stages of the viral life cycle need to be developed. Viruses are dependent on the interaction between the receptor-binding domain (RBD) of the viral Spike (S) protein (S-RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor to efficiently establish infection and the following replicate. Targeting this interaction provides a promising strategy to inhibit the entry process of the virus, which in turn has both preventive and therapeutic effects. In this study, we developed a robust and straightforward assay based on the Yeast-Two Hybrid system (Y2H) for identifying inhibitors targeting the S-RBD-ACE2 interaction of SARS-CoV-2. Through high-throughput screening, two compounds were identified as potential entry inhibitors. Among them, IMB-1C was superior in terms of pseudovirus entry inhibition and toxicity. It could bind to both ACE2 and S-RBD and induce conformational change in the S-RBD+ACE2 complex. This is the first study to verify the feasibility of utilizing the Y2H system to discover potent SARS-CoV-2 inhibitors targeting the receptor recognition stage. This approach may also be applied in the discovery of other virus receptor recognition inhibitors.

Structure characterization and mechanism of angiotensin I-converting enzyme (ACE) inhibitory peptides modified by plastein reaction derived from tiger nut (Cyperus esculentus)

The development of peptides derived from plants, which have potential anti-angiotensin converting enzyme (ACE) activity and other bioactivities, are of scientific interest. ACE inhibitory peptide (CLPP, the ACE inhibitory rate is 76.52 ± 1.07%) was obtained by hydrolysis of tiger nut (Cyperus esculentus) protein with alkaline protease. The plastein product (PCLPP, the ACE inhibitory rate is 85 ± 2.33%) was prepared by modifying CLPP with a plastein reaction. The results of SEM, IR, and XRD show that the structure of PCLPP is different from that of CLPP. The results of differential scanning calorimetry, fluorescence, and free amino analysis showed that the reaction was carried out by aggregation and condensation. These results suggest that the plastein reaction may be an effective method to increase the variety of bioactive peptides.

Captopril attenuates oxidative stress and neuroinflammation implicated in cisplatin-induced cognitive deficits in rats.

One of the most debilitating drawbacks of cisplatin chemotherapy is neurotoxicity which elicits memory impairment and cognitive dysfunction (chemobrain). This is primarily triggered by oxidative stress and inflammation. Captopril, an angiotensin-converting enzyme inhibitor, has been reported as a neuroprotective agent owing to its antioxidant and anti-inflammatory effects. We examined the possible neuroprotective effect of captopril against cisplatin-induced neurological and behavioral abnormalities in rats. Chemobrain was induced in rats by cisplatin (5mg/kg, i.p.) on the 7th and 14th days of the study while captopril was administered orally (25mg/kg) daily for three weeks. The effects of captopril were assessed by performing behavioral tests, histological examination, and evaluation of oxidative stress and inflammatory markers. Cisplatin caused learning/memory dysfunction assessed by passive avoidance and Y-maze tests, decline in locomotion, and rotarod motor balance loss which were further verified by neurodegeneration observed in histological examination. Also, cisplatin aggravated oxidative stress by elevating lipid peroxidation (MDA) levels and diminishing catalase activity. Moreover, cisplatin upregulated the neuroinflammatory markers (TNF, IL-6, GFAP, and NF-κB). Captopril successfully ameliorated cisplatin damage on the levels of neurobehavioral and histopathological changes. Mechanistically, captopril significantly diminished MDA production and preserved catalase antioxidant activity. Captopril also counteracted neuroinflammation through inhibiting NF-κB and its downstream proinflammatory cytokines besides repressing astrocyte activity by reducing GFAP expression. Our findings revealed that captopril could abrogate cisplatin neurotoxicity via reducing oxidative stress and neuroinflammation thus enhancing cognitive and behavioral performance. This could suggest the repurposing of captopril as a neuroprotective agent, especially in hypertensive cancer patients receiving cisplatin.

Chinese and western medicine treatment of myocardial fibrosis drugs

Myocardial fibrosis (MF) is a common pathological manifestation of many cardiovascular diseases, such as myocardial infarction, myocardial ischemia, and sudden cardiac death. It is characterized by excessive proliferation and activation of fibroblasts, transformation into myofibroblasts, and, eventually, excessive deposition of the extracellular matrix, resulting in heart damage. Currently, modern drugs such as angiotensin-converting enzyme inhibitors, diuretics, and β-blockers can improve myocardial fibrosis in clinical treatment, but their therapeutic effect on this disease is limited, with obvious side effects and high cost. Traditional Chinese medicine (TCM) has the advantages of multiple targets, low cost, and few side effects. Traditional Chinese medicines, such as Salvia miltiorrhiza, Astragalus, and Angelica extracts, and patent Chinese medicines, such as Qiliqiangxin capsules, Shenqi Yiqi dropping pills, and Tongxinluo capsules, can improve myocardial fibrosis. In this review, current Chinese and Western medicine methods for treating myocardial fibrosis are discussed. The signaling pathways and targets of Chinese and Western medicine are involved in the treatment of myocardial fibrosis. This review aimed to provide valuable insights and ideas for both clinical treatment and basic research on myocardial fibrosis.

Efficacy of the Optimal Dosage of Lisinopril in Inhibiting Myofibroblast Differentiation for Attenuating Rheumatic Heart Disease Progression: An in Vitro Study

Background: Rheumatic heart disease (RHD) is exacerbated by chronic inflammation that stimulates the release of proinflammatory cytokines, most notably transforming growth factor-beta 1 (TGF-β1), which promotes myofibroblast differentiation. This study aims to determine the optimal dosage of Lisinopril, an angiotensin-converting enzyme inhibitor, for mitigating the fibrotic changes associated with RHD. Methods: This in vitro, posttest-only control group study involved obtaining valvular interstitial cells from the heart valves of 25 male New Zealand rabbits (Oryctolagus cuniculus). Valvular interstitial cells were divided into 5 groups: a control group exposed to TGF-β1, and 4 experimental groups exposed to various Lisinopril doses (1 µM, 10 µM, and 100 µM) in addition to TGF-β1. The effect of Lisinopril on myofibroblast differentiation was assessed by measuring alpha-smooth muscle actin (αSMA) expression through immunocytochemical methods. Statistical significance was determined using an independent T-test with a P value of less than 0.050. Results: Independent T-tests conducted on 25 male Oryctolagus cuniculus demonstrated significantly lower αSMA expression in the groups treated with various Lisinopril doses (1 µM, 10 µM, and 100 µM) compared with the TGF-β1-induced control group (P&lt;0.050). The most significant reduction in αSMA expression was observed in the group treated with the highest Lisinopril dose of 100 µM. Conclusion: Lisinopril demonstrates a significant ability to inhibit TGF-β1-induced myofibroblast differentiation in rabbit valve interstitial cells, with the 100 µM dose proving most effective. These results suggest that Lisinopril may have the potential to curb RHD progression, warranting further investigations in vivo.

Green Synthesis of Tetrahydropyrazino[2,1-a:5,4-a']diisoquinolines as SARS-CoV-2 Entry Inhibitors.

A class of tetrahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives were synthesized under environmentally friendly conditions using water as the solvent. The 3-D structures of some synthesized compounds were determined by X-ray diffraction. Since naturally occurring isoquinoline alkaloids have significant antiviral activities against a wide range of viruses, including coronaviruses, the synthesized compounds were assayed for their inhibitory activities against SARS-CoV-2. Our results showed that the active compounds 50 and 96 blocked the delta SARS-CoV-2 entry into VeroE6 cells to display EC50 of 26.5 ± 6.9 and 17.0 ± 3.7 μM, respectively, by inhibiting the interaction between SARS-CoV-2 Spike's receptor binding domain (RBD) and human receptor angiotensin-converting enzyme 2 (ACE2), and CC50 greater than 100 μM. This study provides a green synthesis method of tetrahydropyrazinodiisoquinoline for antiviral or other applications.

Immunoinformatics-guided design of a multiepitope peptide vaccine targeting the receptor-binding domain of SARS-CoV-2 spike glycoprotein: insights from Indonesian samples.

The emergence of new variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta, Omicron variants, and XBB sub-variants, contributes to the number of coronavirus cases worldwide. SARS-CoV-2 is a positive RNA virus with a genome of 29.9 kb that encodes four structural proteins: spike glycoprotein (S), envelope glycoprotein (E), membrane glycoprotein (M), and nucleocapsid glycoprotein (N). These proteins are vital for viral activity, with the S protein facilitating attachment and membrane fusion through the receptor-binding domain (RBD) located in the S1 subunit. The RBD recognizes and binds to the human angiotensin-converting enzyme 2 (ACE-2) protein. An immunoinformatic-aided design of a peptide-based multiepitope vaccine candidate targeting the RBD glycoprotein is constructed from the SARS-CoV-2 sequence data base from various regions of Indonesia (Jakarta, West Java, and Bali). The results show that the RBD region of with accession ID EPI_ISL_15982641 from West Java had the highest antigenicity of 0.5904. This isolate is non-toxic and non-allergenic and shows a total of 18 LBL epitopes, 72 CTL epitopes, and 98 HTL epitopes. The epitope that has the best overall binding affinity was GCHNKCAY for MHC-I and GGCVFSYVGCHNKCAYWV for MHC-II which show a binding affinity of -13.6 and -15.5 (kcal/mol), respectively. Therefore, this study aims to design an epitope vaccine candidate based on samples from Indonesia that has good characteristics and may have the potential to stimulate an immune response against SARS-CoV-2.