Mechanistic enzyme-oriented investigation of benzimidazole derivatives associated with kidney dysfunction: synthesis, molecular docking and in vivo toxicological evaluation.

Insilico engineering of transaminase variants for enhanced biocatalytic conversion of an ACE inhibitor precursor.

Identification and mechanistic characterization of novel ACE-inhibitory peptides derived from Nattokinase.

Metagenomics-based insights into the microbial community composition and quality characteristics development potentiality in traditional dry-cured ham.

Identification and mechanistic characterization of digestion-stable angiotensin-converting enzyme inhibitory peptides from Sophora moorcroftiana seed protein

Preparation methods, inhibitory activity, and regulatory mechanisms of angiotensin-converting enzyme inhibitory peptides derived from eggs

Anaphylaxis Epidemiology and Risk Factors.

Insights into the inhibition mechanism of angiotensin-converting enzyme by FPGAKP based on multispectroscopy and molecular dynamics

BACKGROUND Heart failure (HF) is prevalent worldwide; however, due to the absence of a dedicated monitoring system in India, an adequate assessment of epidemiological trends in HF remains unaccomplished. Determining the profile of patients with HF facilitates early detection and therapy, minimising the disease burden. AIM To describe the demographics, clinical characteristics, haematological and biochemical parameters, electrocardiogram and echocardiogram findings and recognise the various causes of HF in India. METHODS This was an observational study conducted between May 2019 and December 2020 at a tertiary-care institution in North India. Consecutive adult patients with clinically stable chronic HF were enrolled. Demographic characteristics, clinical features, laboratory parameters, electrocardiographic findings, echocardiographic data, and HF etiology were recorded using a standardised questionnaire. RESULTS This study enrolled a total of 407 chronic HF patients with a mean age of 58.8 years, 64.4% of whom were male. The mean left ventricular ejection fraction was 38.47%. Ischemic heart disease is the leading cause of HF, accounting for 53.6% of the population. Diabetes was the most prevalent linked co-morbidity (28.6%), followed by hypertension (21.5%). The majority of individuals had HF with reduced ejection fraction (58.5%), and the most frequent presenting symptom was exertional dyspnea. Complete guideline-directed medical therapy, defined as concurrent use of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta blocker, and mineralocorticoid receptor antagonist (in any dose), was achieved in 64% of patients. Newer therapies like angiotensin receptor-neprilysin inhibitors were prescribed in only 6.6% of patients. Of 95.6% patients were in sinus rhythm (atrial fibrillation in 4.4%). The other findings included left bundle branch block (21.1%), left anterior hemiblock with right bundle branch block (10.2%), and right bundle branch block (7.6%). CONCLUSION HF in this cohort occurred at a younger age and was predominantly ischemic in etiology, with most patients having HF with reduced ejection fraction. Despite reasonable guideline-directed medical therapy prescription rates, suboptimal dosing and low uptake of newer therapies highlight the need for structured HF care and improved access to evidence-based treatment in India.

Background: Renin-Angiotensin-Aldosterone System (RAAS) acceleration commonly occur in Heart Failure (HF). Drugs such as Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor-Neprilysin Inhibitors (ARNI) become essential part of HF treatment. Long-term consumption may impair kidney function and potassium imbalance, which could potentially limit the therapy, therefore we conducted this study to assess the effects of ACEI and ARNI on renal function and potassium level in Indonesian patients with heart failure with reduced ejection fraction (HFrEF), as no local studies exist. Method: A prospective cohort was performed in Banda Aceh, which comprise of 40 ACEI and 40 ARNI patients on standard therapy. Left ventricular ejection fraction (LVEF), serum creatinine level then converted into estimated Glomerular Filtration Rate (eGFR), and serum potassium level were measured at baseline and after 3 months into the therapy. Independent t-test was applied to compare groups. Result: Both ARNI and ACEI groups showed significant improvement in eGFR (p < 0.005). The intergroup difference was 11 mg/dL (p = 0.038) showed that ACEI had a better outcome in eGFR improvement compare with ARNI. Potassium rose slightly in both groups, with an intergroup difference of 0.082 mmol/L (p = 0.623), indicating no meaningful difference. Conclusion: Both ACEI and ARNI improved eGFR after 3 months, with a modest potassium increase. Keyword : ACEI; ARNI; Heart Failure; Potassium; Renal Function.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infects host cells by binding to angiotensin-converting enzyme 2 (ACE2). Stilbamidine (SDC), a compound identified in Malaysian Kelulut honey (KH), has been reported to exhibit favourable binding affinity towards ACE2. This study aims to determine the effects of KH and SDC on the binding of spike protein to the ACE2 receptor, as well as to assess their modulatory potential on ACE2 gene and protein expression in lung and kidney cells. KH, SDC, and MLN 4760 (ACE2 inhibitor) were tested using an in vitro spike S1:ACE2 inhibition assay. Their modulatory effects on the ACE2 gene and protein expression were further examined through real-time PCR and western blot analysis. KH inhibited the binding of Spike S1 to ACE2, surpassing MLN4760, with maximum effects (Emax) of 82.66 ± 0.24% and 59.81 ± 8.00%, respectively, while the Emax for SDC was 19.93 ± 0.4%. KH caused a significant, dose-dependent downregulation of ACE2 gene expression in kidney-derived Vero E6 cells after 24h of treatment, whereas SDC reduced ACE2 gene expression in lung-derived A549-ACE2-TMPRSS2 cells after 72h. Nevertheless, ACE2 protein expression remained unchanged following both treatments. KH and SDC inhibit the binding of the SARS-CoV-2 spike S1 protein to the ACE2 receptor and reduce ACE2 gene expression. The efficacy of ACE2-targeted interventions may be limited by ACE2 polymorphisms and inter-individual expression differences. Further in vivo studies are needed to confirm their prophylactic and therapeutic potential against SARS-CoV-2 infection.

In vitro protein evolution can provide powerful insights into the amino acid sequences that underlie key biological functions. Here, we use this to explore the evolutionary trajectories of the SARS-CoV-2 spike protein receptor-binding motif (RBM) binding the human angiotensin-converting enzyme 2 (ACE2), an essential first step in viral infection. Applying stringent selection pressures starting from the Wuhan or another non-Omicron variant protein-coding sequence results in rapid convergence towards Omicron characteristic mutations and its sub-lineages. Conversely, under mild selection, only some Omicron-like mutations are selected, however at lower frequencies and with incomplete representation. Stringent selection results in fewer, but dominant, non-synonymous mutations mirroring Omicron mutations and their variations within its sub-lineages. Notably, initiating evolution from Omicron itself results in maintenance of Omicron-defining mutations under both conditions. This evolutionary pattern parallels global SARS-CoV-2 mutation trends as well as in silico simulations, emphasizing the critical role of receptor-binding constraints in shaping viral adaptation. Mutations primarily associated with immune evasion are not selected by in vitro evolution. Our findings demonstrate the predictive capacity of in vitro evolution, suggesting Omicron RBM to be the humanized binding motif, emerging from high-stringency selection, superimposed on milder background pressures.

Abstract Background Sarcoidosis-associated hypercalcemia can cause acute kidney injury (AKI); however, reports of severe cases superimposed on advanced chronic kidney disease (CKD) stage G4 requiring hemodialysis (HD) are rare. We report a case that offers important clinical insights into diagnostic pitfalls in patients with CKD and the clinical approach to identify reversible “treatable AKI.” Case presentation A man in his seventies with baseline CKD stage G4 (serum creatinine [Cr] 2.3–2.6 mg/dL, estimated glomerular filtration rate [eGFR] 19.0–23.0 mL/min/1.73m 2 ) due to nephrosclerosis was emergently admitted for moderate hypercalcemia (corrected serum calcium 13.3 mg/dL) and AKI (Cr 5.15 mg/dL, eGFR 9.3 mL/min/1.73m 2 ). Endocrinological examination revealed suppressed intact parathyroid hormone (PTH) and elevated 1,25-dihydroxyvitamin D (1,25(OH) 2 D), leading to a diagnosis of PTH-independent, vitamin D-dependent hypercalcemia. Although serum angiotensin-converting enzyme (ACE) levels were within the normal range, this was considered to be masked by the chronic use of an ACE inhibitor (imidapril). A clinical diagnosis of sarcoidosis was made on the basis of markedly elevated soluble IL-2 receptor and lysozyme levels and mediastinal lymphadenopathy. Owing to his poor general condition, tissue biopsy could not be performed. Emergency HD was promptly initiated, followed by corticosteroid therapy with prednisolone (30 mg/day) once the clinical diagnosis was strongly suspected. Following treatment, hypercalcemia normalized rapidly, and kidney function gradually improved, allowing liberation from dialysis after five HD sessions. Conclusions When encountering unexplained AKI with hypercalcemia in patients with CKD, clinicians should consider sarcoidosis as a potential underlying cause. Additionally, clinicians will perform a multifaceted evaluation including 1,25(OH) 2 D measurement. Even in severe cases requiring dialysis, early diagnosis and appropriate treatment can render the condition a “treatable AKI.”

The SARS-CoV-2 spike protein is heavily glycosylated. These post-translational modifications aid in interactions with human angiotensin-converting enzyme 2 (hACE2), assist in antibody evasion, and help facilitate protein dynamics. However, the exact role glycans play in maintaining the protein structure and conformation is not fully understood. In this study, we elucidated the structural function of these polysaccharides in the recombinant 614G HexaPro spike ectodomain protein by PNGase F glycosidase treatment and evaluated the subsequent effects on protein conformational dynamics via hydrogen/deuterium exchange-mass spectrometry. Our results show that enzymatic deglycosylation led to widespread conformational changes, both in regions with glycosylation sites and those without. Notably, the 630 loop, which mediates the receptor-binding domain (RBD) up/down position, became disordered, overcoming the rigidification that resulted from the D614G mutation. Additionally, heptad repeat 2, which plays a role in viral fusion machinery, also exhibited an increase in deuteration. Regions that showed a decrease in deuteration after treatment include subdomain 1, the fusion peptide proximal region, and the coiled coil. We also provide insights into the reduced thermal stability and altered binding behavior of antibodies and hACE2 in addition to changes in deuteration following enzymatic glycan removal.

Abstract Background: Hypertension remains one of the most prevalent chronic diseases globally. Despite several evidence-based guidelines, blood pressure (BP) control remains suboptimal, particularly in developing countries. Objectives: To study the demographic, clinical profile, and treatment practice pattern in patients of systemic hypertension attending LNCT Medical College and Sewakunj Hospital, Indore. Materials and Methods: A cross-sectional study was conducted at LNCT Medical College and Sewakunj Hospital, Indore, between January 2023 and December 2023. A total of 401 consenting hypertensive adults were enrolled. Clinical data and complete drug-prescription details were recorded. Results: Among the 401 patients, 52.6% were male and 44.4% belonged to the middle-aged group (46–64 years). Diabetes mellitus was present in 19%, coronary artery disease in 18%, and cerebrovascular accidents in 13.7%. Only 10.2% of patients had adequately controlled BP, while 71.3% had stage 2 hypertension. Target organ damage was present in 32.1% of patients, most commonly left ventricular strain pattern (20.7%), followed by retinopathy (16.5%) and nephropathy (12%). Angiotensin-converting enzyme (ACE) inhibitors were the most commonly prescribed class (15.7% as monotherapy). However, diuretics were markedly underused and absent as monotherapy. Combination therapy was widely used, particularly ACE inhibitor + beta-blocker (10.4%), calcium channel blocker (CCB) monotherapy (9.9%), and CCB + diuretic (9.4%). Conclusion: Despite the availability of effective medications, BP control in this tertiary care setting remains poor. Diuretics—strongly recommended as the first-line therapy—were significantly underutilized. Greater physician awareness, adherence to guidelines, and improved patient education are required to achieve better hypertension control.

Enterococci are found not only in warm-blooded animals but also as a resident population of water and an indicator of fecal pollution. The species Enterococcus haemoperoxidus and E. moraviensis are relatively new, having been detected in water. Strains with genes for biofilm formation can serve as reservoirs for gene transfer. The aim and novelty of this study were to determine whether the postbiotic substance (PS) of proteinaceous character (Durancin-like) produced by our strain Enterococcus durans ED26E/7 can inhibit in vitro the growth of biofilm-forming E. haemoperoxidus and E. moraviensis isolated from water sources. E. haemoperoxidus and E. moraviensis lacked the biofilm-forming genes ica, bap, ace, and fsrA. The bopD gene was found only in three strains of E. haemoperoxidus. The srtA gene was present in two strains of E. haemoperoxidus and E. moraviensis. Using the quantitative test, three strains showed low-grade biofilm-forming ability. They exhibited ɤ-hemolysis, and they were mostly susceptible to antibiotics. However, they were susceptible to PS Durancin-like ED26E/7. E. haemoperoxidus, the strains EHae466 and EMo494, showed the highest susceptibility to Durancin-like ED26E/7.

Fine particulate matter (PM2.5) deposition in the lungs can induce pulmonary injury. Histone deacetylase 6 (HDAC6), a critical member of the histone deacetylase family, plays a key role in regulating lung diseases. In this study, we explored the mechanism of HDAC6 in PM2.5 (10mg/kg)-induced pulmonary injury using an HDAC6 knockout (KO) mouse model, employing immunohistochemical, western blot, and transcriptome analyses. Results indicated that HDAC6 KO exacerbated PM2.5-induced epithelial barrier dysfunction by altering the expression of zonula occludens-1 (ZO-1) and zonula occludens-2 (ZO-2). Moreover, HDAC6 KO increased the susceptibility of lung tissue to PM2.5 by inhibiting E-cadherin expression and promoting N-cadherin expression. Transcriptome analysis of PM2.5-treated lungs in the HDAC6 KO group revealed significant alterations in the renin-angiotensin system (RAS). The expression levels of RAS components, including angiotensin-converting enzyme II (ACE2), angiotensin II (Ang II), renin, and Agtrl1b, were quantified. Notably, both PM2.5 and HDAC6 KO disrupted RAS balance. The PM2.5-treated HDAC6 KO group exhibited a pronounced reduction in ACE2 and elevation in Ang II, suggesting increased susceptibility to PM2.5. These results indicate that HDAC6 KO exacerbates PM2.5-induced pulmonary injury by affecting RAS balance. This study provides a theoretical foundation for understanding the role of HDAC6 in PM2.5-induced pulmonary injury.

Hypertension is a risk factor for urological tumors. However, the impact of antihypertensive drugs on these tumors is unclear. We used summary statistics from genome-wide association studies (GWASs) of urological tumors, along with expression data for antihypertensive drug target genes from GWASs and eQTLGen. We employed two-sample Mendelian randomization and summary-based Mendelian randomization (SMR) to assess the associations between antihypertensive drugs, target genes, and urological tumors. Two-step MR analysis was performed to investigate the mediating role of protein in these associations. We further verified this finding through co-localization analysis and differential expression analysis. We also mined the US Food and Drug Administration Adverse Event Reporting System database and Phenome-Wide Association Study to study the adverse effects of antihypertensive drugs and their target genes. Angiotensin-II receptor antagonist, PSDs, and aldosterone antagonists increase the risk of testicular cancer. Angiotensin-converting enzyme inhibitors decrease the risk for prostate cancer. Genetically, PPARG increases the risk of testicular cancer, as confirmed by SMR (PPARG: P = 2.1×10-2, odds ratio [OR] 1.91; 95% confidence interval [CI] 1.11-3.30), two-sample Mendelian randomization (PPARG: P = 0.01, OR 2.74, 95% CI 1.23-6.11), co-localization analysis, and differential expression analysis. PPP1R1A and TAPBPL mediate the effects of PPARG on testicular cancer. The adverse reactions of antihypertensive drugs mainly affect the digestive system, especially digestive system tumors. Antihypertensive drugs and target genes are significant in the development of urological tumors and crucial for the development of treatment strategies.

Hypertension in the elderly increases the risk of cardiovascular disease and reduces quality of life. In addition to pharmacological therapy, garlic (Allium sativum) as a complementary herbal therapy has the potential to lower blood pressure through its allicin and S-allylcysteine ​​content, which act as vasodilators, antioxidants, and angiotensin-converting enzyme inhibitors. This study aims to systematically review the effectiveness of garlic therapy in lowering blood pressure in the elderly with hypertension. The research method used was a literature review with a narrative-descriptive approach. Articles were searched through PubMed, ScienceDirect, Google Scholar, and Scopus databases for publications from 2020 to 2025. A total of 19 articles that met the inclusion criteria were analyzed, including randomized controlled trial designs, quasi-experimental, and pre-experimental. The variables studied included dosage form, dose, duration of administration, changes in systolic and diastolic blood pressure, and side effects. Results showed that various forms of garlic, such as tea, decoction, capsules, black garlic, and aged garlic extract, consistently lowered systolic blood pressure by 10–30 mmHg and diastolic blood pressure by 5–20 mmHg in older adults with hypertension. Reported side effects were generally mild. It was concluded that garlic is potentially effective and safe as a complementary therapy for hypertension in older adults, although further standardized research is needed.

False-positive iFOBT in colorectal cancer screening: Association with prescription drug use in The Malaysian Cohort.