Angiotensin-converting Enzyme Research Articles

SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice

Patients with coronavirus disease 2019 (COVID-19) often experience acute kidney injury, linked to disease severity or mortality, along with renal tubular dysfunction and megalin loss in proximal tubules. Megalin plays a crucial role in kidney vitamin D metabolism. However, the impact of megalin loss on vitamin D metabolism during COVID-19 is unclear. This study investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection reduces megalin expression in proximal tubules and its subsequent effect on vitamin D metabolism in mice expressing human angiotensin converting enzyme 2 (K18-hACE2 mice). Histological and immunohistochemical staining analyses revealed glomerular and capillary congestion, and elevated renal neutrophil gelatinase-associated lipocalin levels, indicative of acute kidney injury in K18-hACE2 mice. In SARS-CoV-2-infected mice, immunohistochemical staining revealed suppressed megalin protein levels. Decreased vitamin D receptor (VDR) localization in the nucleus and increased mRNA expression of VDR, CYP27B1, and CYP24A1 were observed by quantitative PCR in SARS-CoV-2-infected mice. Serum vitamin D levels remained similar in infected and vehicle-treated mice, but an increase in tumor necrosis factor-alpha and a decrease in IL-4 mRNA expression were observed in the kidneys of the SARS-CoV-2 group. These findings suggest that megalin loss in SARS-CoV-2 infection may impact the local role of vitamin D in kidney immunomodulation, even when blood vitamin D levels remain unchanged.

A Systematic Literature Review and Network Meta-analysis of Azilsartan Medoxomil Compared to Other Anti-hypertensives Efficacy in Lowering Blood Pressure Amongst Mild to Moderate Hypertensive Patients.

A systematic literature review and network meta-analysis was conducted on azilsartan medoxomil (AZL-M) versus other antihypertensive drugs' efficacy in hypertensive patients. The search utilized English platforms, from January 2000 until December 2023, resulting in 10,380 articles being screened. Screening criteria included hypertension (mild or moderate); first-line treatment and washout periods; studies (monotherapy) with AZL-M, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta-blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; and antihypertension efficacy as an outcome measure. Study design was randomized clinical trials. Efficacy variables included absolute office systolic and diastolic blood pressure (BP) reductions. A total of 21 publications provided adequate data for analysis, of which 20 studies reported both systolic and diastolic BP and one study reported only the diastolic BP. In 21 studies on systolic BP, against the common comparator placebo, the differences in systolic BP were significantly in favor of AZL-M, amlodipine, candesartan, irbesartan, nebivolol, nifedipine, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The surface under the cumulative ranking curve (SUCRA) ranking shows that AZL-M 80mg had the highest ranking, with a possibility of 93% being the best in all other included treatments. In 20 studies on diastolic BP, against the common comparator placebo, the differences in diastolic BP were significantly in favor of AZL-M, amlodipine, bisoprolol, nebivolol, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The SUCRA ranking shows that AZL-M 80mg had the highest ranking, with a possibility of 90% being the best in all other included treatments. AZL-M at 40mg and 80mg shows favorable efficacy compared to other anti-hypertensives, and the 80mg dosage seemed to be the most efficacious of all the included treatments in reducing both office systolic and diastolic BP in patients with mild-to-moderate hypertension.

Comparative Analysis of First-Line Antihypertensive Treatment Classes

BackgroundThe best first-line monotherapy for hypertension remains uncertain, as current guidelines suggest that thiazides, angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB) are appropriate in the absence of specific comorbidities. We aimed to compare the outcomes of first-line antihypertensive classes in a real-life setting with a long follow-up period. MethodsThis nationwide retrospective new-user cohort study included patients insured by the largest health maintenance organization in Israel. We included patients with a new diagnosis of hypertension between 2008 and 2021 who initiated treatment with a single first-line drug for hypertension. Outcomes were assessed with and without propensity score matching for confounding factors. The primary composite outcome was the first occurrence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, or heart failure (HF). ResultsA total of 97,639 patients initiated antihypertensive treatment with a single drug as first-line therapy. The most commonly prescribed class was ACEi/ARB (66,717, 68.3%), followed by CCBs (15,922, 16.3%), beta-blockers (BBs, 12,869, 13.2%), and thiazides (2,131, 2.2%). For the primary outcome, the hazard ratios (HRs) for BBs, CCBs, and ACEi/ARBs were 1.44 (95% CI 1.25 - 1.66), 1.10 (95% CI 0.96 - 1.27), and 1.13 (95% CI 0.99 - 1.29), respectively, when compared to thiazides. ConclusionWhen initiating pharmacotherapy for hypertension with a single drug, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers were associated with similar risk of MI, ACS, stroke, or HF when compared to thiazides, while beta-blockers were associated with increased risk.

A Narrative Review on Broken Heart Syndrome: A Guide for Clinicians to Understand Takotsubo Cardiomyopathy

Abstract Takotsubo cardiomyopathy (TCM) is a transient and reversible cardiomyopathy which exhibits regional wall motion abnormalities in the absence of obstructive coronary artery disease. While TCM is a rare condition (incidence <1%), its diagnosis has increased since its initial description in 1990. While many cases may follow an acute physical or emotional stressor, pathophysiology is likely multifactorial including factors such as catecholamine surges and microvascular dysfunction. On initial presentation, TCM often mimics acute coronary syndrome but may be differentiated with coronary angiography. Additional laboratory testing and imaging including transthoracic echocardiography may help with diagnosis and identification of complications such as left ventricular (LV) outflow obstruction and LV thrombus. Treatment is supportive, although medications such as angiotensin-converting enzyme inhibitors and beta-blockers have shown some benefit in improving long-term outcomes. Acute complications may include arrhythmia, LV or systemic thrombus, and cardiogenic shock, but most patients do well and experience rapid recovery. TCM continues to be an active area of research as there is still much to be learned regarding its pathogenesis, diagnosis, and treatment. This review analyzes the latest research to provide insight into the presentation, pathophysiology, diagnosis, and management of TCM.

Peptide-Based Inhibitors of Protein-Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2).

Protein-protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (hACE2), which initiates a series of events leading to viral replication. Interrupting this interaction offers a promising strategy for blocking or significantly reducing infection, highlighting its potential as a target for anti-SARS-CoV-2 therapies. This review focuses on the hACE2 and SARS-CoV-2 spike protein interaction, exemplifying the latest advancements in peptide-based strategies for developing PPI inhibitors. We discuss various approaches for creating peptide-based inhibitors that target this critical interaction, aiming to provide potential treatments for COVID-19.

The metalloproteinase ADAM10 sheds angiotensin-converting enzyme (ACE) from the pulmonary endothelium as a soluble, functionally active convertase.

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the regulation of blood pressure and fluid balance, with angiotensin-converting enzyme (ACE) being a key transmembrane enzyme that converts angiotensin I to angiotensin II. Hence, ACE activity is an important drug target in cardiovascular pathologies such as hypertension. Our study demonstrates that human pulmonary microvascular endothelial cells (HPMECs) are an important source of proteolytically released ACE. The proteolytic release of transmembrane proteins, a process known as ectodomain shedding, is facilitated by membrane proteases called sheddases. By knockout and inhibition studies, we identified ADAM10 (A disintegrin and metalloprotease 10) as a primary sheddase responsible for ACE release in HEK293 cells. The function of ADAM10 as primary, constitutive sheddase of ACE was confirmed in HPMECs. Moreover, we demonstrated the physiological relevance of ADAM10 for ACE shedding in exvivo precision cut lung slices (PCLS) from human and mouse lungs. Notably, ADAM17 activity is not directly involved in ACE shedding but indirectly by regulating ACE mRNA and protein levels, leading to increased ADAM10-mediated ACE shedding. Importantly, soluble ACE generated by shedding is enzymatically active and can thereby participate in systemic RAAS functions. Taken together, our findings highlight the critical role of ADAM10 (directly) and ADAM17 (indirectly) in ACE shedding and RAAS modulation.

Highly efficient synthesis of the chiral ACE inhibitor intermediate (R)-2-hydroxy-4-phenylbutyrate ethyl ester via engineered bi-enzyme coupled systems

(R)-2-Hydroxy-4-phenylbutyric acid ethyl ester ((R)-HPBE) is an essential chiral intermediate in the synthesis of angiotensin-converting enzyme (ACE) inhibitors. Its production involves the highly selective asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE), catalyzed by carbonyl reductase (CpCR), with efficient cofactor regeneration playing a crucial role. In this study, an in-situ coenzyme regeneration system was developed by coupling carbonyl reductase (CpCR) with glucose dehydrogenase (GDH), resulting in the construction of five recombinant strains capable of NADPH regeneration. Among these, the recombinant strain E. coli BL21-pETDuet-1-GDH-L-CpCR, where CpCR is fused to the C-terminus of GDH, demonstrated the highest catalytic activity. This strain exhibited an enzyme activity of 69.78 U/mg and achieved a conversion rate of 98.3%, with an enantiomeric excess (ee) of 99.9% during the conversion of 30 mM OPBE to (R)-HPBE. High-density fermentation further enhanced enzyme yield, achieving an enzyme activity of 1960 U/mL in the fermentation broth, which is 16.2 times higher than the volumetric activity obtained from shake flask fermentation. Additionally, the implementation of a substrate feeding strategy enabled continuous processing, allowing the strain to efficiently convert a final OPBE concentration of 920 mM, producing 912 mM of (R)-HPBE. These findings highlight the system’s improved catalytic efficiency, stability, and scalability, making it highly suitable for industrial-scale biocatalytic production.

Association of Angiotensin Converting Enzyme Phenotypes and Polymorphisms with Clinical Outcomes in SARS-CoV2 Patients with Hypertension in an Urban Emergency Department.

The role of Angiotensin-converting enzyme (ACE and ACE2) phenotypes and polymorphisms in modulating severe acute respiratory syndrome coronavirus (SARS-- CoV2) infection in hypertensive patients remains unclear. Our objective was to determine the distribution of ACE and ACE2 receptor phenotypes by patient demographics and correlate ACE and ACE2 levels of activity with SARS-CoV-2 outcomes. Hypertensive patients treated for SARS-CoV-2 at an urban emergency department (ED) were prospectively enrolled in a cohort study between August 2020 and April 2021. Blood samples were collected during ED visits or hospitalization. Outcome measures including hospitalization, intensive care unit (ICU) admission, and 30-day mortality were obtained from electronic health records. Multivariable logistic regression was used. Of the 150 patients enrolled, 60% were Black, 32% Hispanic/Latinx, 4% Non-Hispanic Whites, and 4% others. The mean age was 59 (+/-14) years. The rate of hospitalization was high (86%) and Hispanic/Latinx had a higher likelihood of ICU admission. Patients harboring the rs2285666 genotype TT, AA, and GC alleles were more likely to be admitted to ICU, and those with TT and AA had higher mortality. The ACE level was a significant predictor of hospitalization with a protective effect in both unadjusted and adjusted results. Hispanics/Latinx had a four times higher likelihood of ICU admission compared to all others, and age was significantly associated with 30-day mortality. Our results show that even after adjusting for age, race, and sex, ACE levels remained a predictor of hospitalization. ACE/ACE2 phenotypes and genotypes potentially play an important role in disease progression in SARS-CoV-2 patients.

Five-year outcomes of a holistic programme for managing early chronic kidney disease in primary care.

Holistic Approach in Lowering and Tracking Chronic Kidney Disease (HALT-CKD) is a nationwide programme that was introduced in 2017 to combat CKD in Singapore. This study aims to evaluate outcomes of the HALT-CKD programme and identify factors influencing disease progression among early CKD patients. We conducted a retrospective cohort study involving adult patients aged 21 to 80 with CKD stages G1-G3A, recruited from 5 Singapore polyclinics between 2017 and 2018. The primary outcome-time to progression to advanced CKD (G3B-G5)-was tracked until March 2023, based on patients' last known serum creatinine levels. Descriptive statistics and Cox regression were used. Patients who followed up with other institutions, were deceased or defaulted without developing (or experiencing) the outcome were censored. We studied 3800 patients (mean age: 61.9 years) for a median of 4.7 years. Among them, 12.6% developed advanced CKD despite statistically significant improvements in HbA1c, blood pressure and albuminuria levels. Increasing age, female sex, clinic, baseline creatinine, diastolic blood pressure and HbA1c significantly shortened time to CKD progression. Macro-albuminuria at baseline (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.19- 2.61) and at analysis (HR 2.22, 95% CI 1.55-3.19) significantly accelerated advanced CKD progression. Patients who had their angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) dose reduced or discontinued progressed to advanced CKD earlier (HR 1.92, 95% CI 1.50-2.45). Counselling and sodium-glucose cotransporter-2 inhibitor (SGLT2i) use did not significantly delay CKD progression. Maintaining optimal ACEi/ARB dosage is essential to delay CKD progression. Premature cessation or reduction of this dosage should be discouraged. Further research on counselling and SGLT2i use in early CKD is needed to address the growing burden of CKD.

Protein Nanoparticles for Targeted SARS-CoV-2 Trapping and Neutralization.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge global health despite widespread vaccination efforts, underscoring the need for innovative strategies to combat emerging infectious diseases effectively. Herein, LCB1-NPs and LCB3-NPs are engineered as a novel class of protein-only nanoparticles formed through coiled coil-driven self-assembly and tailored to interact specifically with the SARS-CoV-2 spike protein. The multivalency of LCB1-NPs and LCB3-NPs offers a strategy for efficiently targeting and neutralizing SARS-CoV-2 both in solution and when immobilized on surfaces. It is demonstrated that LCB1-NPs and LCB3-NPs bind to the SARS-CoV-2 spike protein's receptor-binding domain (RBD) with high affinity, effectively blocking the entry of SARS-CoV-2 virus-like particles into angiotensin-converting enzyme 2 (ACE2)-coated human cells. The cost-effectiveness, scalability, and straightforward production process of these protein nanoparticles make them suitable for developing novel anti-viral materials. Accordingly, it is shown how these nanostructures can be packed into columns to build up economic and highly potent trapping devices for SARS-CoV-2 adsorption.

Abortive infection of bat fibroblasts with SARS-CoV-2

Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat (Rhinolophus ferrumequinum) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.

Investigation of the Effects Of ACE Gene Polymorphism on Athletic Performance in Active Adult Males

Studying genes associated with exercise-related physiological systems and metabolic pathways has proven to be an effective method for identifying genetic markers associated with enhanced athletic performance. One of the extensively studied genes in genetics is "Angiotensin I-converting enzyme (ACE)" which has a significant role in regulating blood pressure, plasma volume, and the development of cardiac and skeletal muscle. The objective of this study was to determine the different results and genetic variations in the effects of ACE gene polymorphisms on the performance of the 30m sprint test and the arrowhead agility drill test in active adult males after a 6-week training program. Following the manufacturer's instructions, genomic DNA was extracted from participant mouth swab samples using the Buccalyse DNA Extraction Kit from Isohelix. The Statistical Package for the Social Sciences (SPSS) 25 application was used to perform statistical analysis on the research data. The findings indicate that 45.7% of the participants possess the I/D genotype, 31.4% possess the I/I genotype, and 22.9% possess the D/D genotype. There was no notable disparity in the performance of the arrowhead agility test and the 30 m sprint test among the different genotype groups (p<0.05). Our analysis revealed a lack of association between genetic variants and the values obtained from performance measurements in the test outcomes. Due to the involvement of various genes and variables, further research is needed to improve the predictability of approaches to ACE gene variations, considering their performance-enhancing benefits.

Emergence of lineage ST150 and linezolid resistance in Enterococcus faecalis: a molecular epidemiology study of UTIs in Tehran, Iran.

Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections, with Enterococcus species now recognized as the second leading cause of these infections. This study focused on symptomatic UTI cases to investigate the risk factors associated with Enterococcus faecalis clinical isolates in patients from Tehran, Iran. Urine samples were collected from patients presenting with symptomatic UTIs. The identification of E. faecalis isolates was performed using standard microbiological techniques, with confirmation via polymerase chain reaction (PCR). Antibiotic susceptibility testing was conducted using the Kirby-Bauer disc diffusion method. The presence of virulence genes was determined through PCR, and biofilm formation was assessed using the microtiter plate method. Additionally, multi-locus sequence typing (MLST) was utilized to genotype linezolid-resistant isolates. Out of 300 UTI cases, E. faecalis was identified as the causative agent in 160 instances. Notably, a high proportion of these isolates exhibited resistance to tetracycline (83.8%) and minocycline (82.5%). Linezolid resistance was observed in 1.3% (n = 2) of the isolates. Conversely, the highest susceptibility rates were observed for vancomycin, penicillin G, ampicillin, and nitrofurantoin, each demonstrating a 98.8% susceptibility rate. Biofilm formation was detected in 25% of the E. faecalis isolates. A significant majority (93.8%) of the isolates harbored the efbA and ace genes, with varying frequencies of esp (72.5%), asa1 (61.2%), cylA (52.5%), and gelE (88.8%) genes. MLST analysis demonstrated that both linezolid-resistant isolates, characterized by strong biofilm formation and the presence of virulence genes, were assigned to the ST150 lineage, which has not been previously documented in clinical settings. The emergence of the ST150 clonal lineage, underscores its clinical significance, particularly in relation to linezolid resistance in E. faecalis. This study adds to the growing body of evidence linking specific clonal lineages with antibiotic resistance, highlighting the critical need for ongoing surveillance and molecular characterization of resistant pathogens.

Machine learning-based prediction of mortality in acute myocardial infarction with cardiogenic shock.

In the ICU, patients with acute myocardial infarction and cardiogenic shock (AMI-CS) often face high mortality rates, making timely and precise mortality risk prediction crucial for clinical decision-making. Despite existing models, machine learning algorithms hold the potential for improved predictive accuracy. In this study, a predictive model was developed using the MIMIC-IV database, with external validation performed on the eICU-CRD database. We included ICU patients diagnosed with AMI-CS. Feature selection was conducted using the Boruta algorithm, followed by the construction and comparison of four machine learning models: Logistic Regression (LR), eXtreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), and Gaussian Naive Bayes (GNB). Model performance was evaluated based on metrics such as AUC (Area Under the Curve), accuracy, sensitivity, specificity, and so on. The SHAP method was employed to visualize and interpret the importance of model features. Finally, we constructed an online prediction model and conducted external validation in the eICU-CRD database. In this study, a total of 570 and 391 patients with AMI-CS were included from the MIMIC-IV and eICU-CRD databases, respectively. Among all machine learning algorithms evaluated, LR exhibited the best performance with a validation set AUC of 0.841(XGBoost: 0.835, AdaBoost: 0.839, GNB: 0.826). The model incorporated five variables: prothrombin time, blood urea nitrogen, age, beta-blockers and Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers. SHAP plots are employed to visualize the importance of model features and to interpret the results. An online prediction tool was developed, externally validated with the eICU-CRD database, achieving an AUC of 0.755. Employing the LR algorithm, we developed a predictive model for assessing the mortality risk among AMI-CS patients in the ICU setting. Through model predictions, this facilitates early detection of high-risk individuals, ensures judicious allocation of healthcare resources.

Oxoammonium salts exert antiviral effects against coronavirus via denaturation of their spike proteins

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) infection has forced social changes worldwide. Development of potent antiviral agents is necessary to prevent future pandemics. Titanium oxide, a photocatalyst, is a long-acting antiviral agent; however, its effects are weakened in the dark. Therefore, new antiviral substances that can be used in the dark are needed. Two types of nitroxyl radicals, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and 2-azaadamantane N-oxyl (AZADO), are commonly used as oxidation catalysts utilizing oxygen in the air as the terminal oxidant. Therefore, in this study, we aimed to evaluate the potential of these radicals as antiviral compounds with sustained activity even in the dark. We evaluated the antiviral effects of oxoammonium salts corresponding to TEMPO and AZADO (TEMPO-Oxo and AZADO-Oxo, respectively), which are the active forms of nitroxyl radicals in oxidation reactions. TEMPO-Oxo and AZADO-Oxo inhibited the binding of SARS-CoV2 spike protein receptor-binding domain (S-RBD) to angiotensin-converting enzyme 2. Notably, AZADO-Oxo exhibited a 10-fold stronger inhibitory effect than TEMPO-Oxo. TEMPO-Oxo and AZADO-Oxo also denatured S-RBD; however, effects of AZADO-Oxo were 10-fold stronger than those of TEMPO-Oxo and did not change in the dark. Some S-RBD peptides treated with AZADO-Oxo were cleaved at the N-terminal side of tyrosine residues. TEMPO-Oxo and AZADO-Oxo exhibited concentration-dependent antiviral effects against feline coronavirus. In conclusion, active forms of the nitroxyl radicals, TEMPO-Oxo and AZADO-Oxo, exerted antiviral effects by denaturing S-RBD, regardless of the presence or absence of light, suggesting their potential as novel antiviral agents.

Study of the Phenolic Compounds and Biological Activities of the Wild Fruits of Vaccinium leucanthum Schltdl.

Around 450 species of blueberries of the genus Vaccinium are known, of which some have gained preferential breeding, such as the ‘Biloxi’ variety. Some little studied species, such as Vaccinium leucanthum Schltdl. located in Mexico, could be a potential source of bioactive compounds. In this study, the phenolic compounds (chlorogenic acid content, hyperoside, phenols, flavonoids, tannins and total anthocyanins content) as well as the potential biological activity (antioxidant, antimicrobial, xanthine oxidase converting enzyme inhibition and angiotensin I inhibition) of Vaccinium leucanthum Schltdl. were studied, making a comparison with the Biloxi variety, which is the most widely cultivated one. The extract of V. leucanthum showed the highest content of flavonoids (4.853 ± 0.341 mg QE/g DW), total anthocyanins (0.303 ± 0.008 mg CGE/g DW), petunidin-3-glucoside (6.92 ± 0.12 mg PGE/g DW), malvidin-3-glucoside (11.80 ± 0.10 mg MGE/g DW) and hyperoside (5.137 ± 0.100 mg HE/g DW). It should be noted that V. leucanthum showed the same total tannin content and the same efficacy in the inhibition of Angiotensin I-converting enzyme as ‘Biloxi’, as well as the same antibacterial effect against the enterobacteria Salmonella choleraesuis ATCC 12022, Escherichia coli ATCC 12792and Shigella flexneri ATCC 10708. These findings demonstrate that V. leucanthum extracts could be an important source of preservatives as well as nutraceutical compounds for use in foods and medicines.

Alterations in the Renin-Angiotensin System in Experimental Septic Shock.

To analyze dynamic changes in the renin-angiotensin system (RAS) during septic shock, focusing on angiotensin-converting enzyme (ACE) activity and the balance between angiotensin peptides, using a mass spectrometry method. Experimental septic shock model induced by peritonitis in swine. Experimental Laboratory, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles. Forty time points from eight mechanically ventilated pigs. Septic shock was induced using intraperitoneal instillation of autologous feces, followed by standardized fluid resuscitation, norepinephrine infusion, antibiotic administration, and peritoneal lavage. The induction of sepsis resulted in a significant increase in plasma renin activity and levels of angiotensin I and II, with a significant decrease in ACE activity observed from 4 hours post-resuscitation and a notable rise in the angiotensin I/angiotensin II ratio at 12 hours. Additionally, a shift toward the angiotensin-(1-7) axis was observed, evidenced by an increased angiotensin-(1-7)/angiotensin II ratio. The study highlighted dynamic shifts in the RAS during septic shock, characterized by reduced circulating ACE activity, elevated angiotensin I/II ratio, and a shift toward the angiotensin-(1-7) axis. These findings suggest an adaptive response within the RAS, potentially offering new insights into sepsis management and therapeutic targets.

Bioactive compounds and in vitro biological properties of Arthrospira platensis and Athrospira maxima: a comparative study

Cyanobacteria, especially Arthrospira, are valuable resources of nutrients and natural pigments with many beneficial health-related properties. This study optimized the extraction conditions of Arthrospira to achieve high phenolic contents and antioxidant activities. Under optimized extraction conditions, the bioactive compounds (phenolics and pigment components), antioxidant activities, and inhibitions of the key enzymes relevant to some non-communicable diseases were compared between Arthrospira platensis and Arthrospira maxima. Optimized extraction conditions were determined as 2 h shaking time, 50 °C extraction temperature, and 1% (w/v) solid-to-liquid ratio, giving effective phenolic and phycocyanin contents using aqueous extraction, while 80% (v/v) aqueous ethanolic extraction provided high total chlorophyll content. Most antioxidant activities were higher using 80% (v/v) aqueous ethanolic extracts. Both Arthrospira species inhibited the key enzymes involved in controlling non-communicable diseases including hyperlipidemia (lipase), diabetes (α-amylase, α-glucosidase, and dipeptidyl peptidase-IV), Alzheimer’s disease (acetylcholinesterase, butyrylcholinesterase and β-secretase), and hypertension (angiotensin-converting enzyme). High inhibitory activities were detected against β-secretase (BACE-1), the enzyme responsible for β-amyloid plaque formation in the brain that acts as a significant hallmark of Alzheimer’s disease. Arthrospira extract and donepezil (Alzheimer’s disease drug) synergistically inhibited BACE-1, suggesting the potential of Arthrospira extracts as effective BACE-1 inhibitors. Interestingly, A. maxima exhibited higher bioactive compound contents, antioxidant activities, and key enzyme inhibitions than A. platensis, indicating high potential for future food and medicinal applications.

Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement.

Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.

On the pathogenesis of COVID-19: the role of transforming growth factor beta

Proteins of the transforming growth factor beta (TGF-β) family regulate numerous cellular processes that are essential in the pathogenesis of acute respiratory distress syndrome (ARDS), contributing to increased alveolar epithelial permeability, activation of fibroblasts, and extracellular matrix remodeling. TGF-β is involved in the pathogenesis of inflammatory respiratory diseases during the development of COVID-19. SARS-CoV-2 leads to complex immune responses that include the release of inflammatory cytokines, increased activity of mast cells, and the release of mast cell secretome, in particular profibrotic enzymes and cytokines, including TGF-β.Tryptaseand chymase-positive mast cells play a major role in pulmonary fibrosis and embolism in COVID-19. Mast cell chymase is angiotensin-converting enzyme 2-independent due to extracellular formation of angiotensin II in the interstitium; it also activates TGF-β and other molecules, thereby playing a role in tissue remodeling. Mast cell β-tryptase increases the secretion of TGF-β1 by airway smooth muscle tissue and the expression of α-smooth muscle actin (α-SMA). TGF-β also induces the generation of mitochondrial reactive oxygen species (ROS), which enhances the production of ROS in lung fibroblasts. TGF-β is crucial for induing the synthesis of extracellular matrix components by fibroblasts.The review is devoted to the structure of TGF-β, the sources of its secretion and functions, the mechanism of its involvement in the pathogenesis of COVID-19, and the possibility of its use as a prognostic marker of COVID-19 severity.