Search Results (422)

The circulating renin–angiotensin–aldosterone system (RAAS) plays a key role in regulating blood volume and electrolyte levels. While important for the maintenance of intravascular volume systemically, the local activation of tissue RAAS and the generation of angiotensin II contribute to inflammation and fibrosis. In the kidney, angiotensin II plays a key role in the development and progression of glomerular injury. Angiotensin-converting enzyme 2 (ACE2), an enzyme that degrades angiotensin II, is expressed in the glomerulus, focusing attention not only on the complexity of the RAAS but also identifying a potential new determinant of glomerular injury. Accordingly, we performed a narrative review using the search terms ACE2 and glomerulus in PubMed and Google Scholar to summarize the current understanding of the role of ACE2 in glomerular injury. We also discuss the role of ACE2 as a cellular receptor for SARS-CoV-2 and the potential impact of this function on glomerular injury in the setting of COVID-19. Full article

Background/Objectives: Hemodynamic and neurohormonal factors, including renal perfusion and venous pressure, may affect diuretic response, which may be modulated by body position. This study aimed to assess whether supine versus upright positioning influences diuretic efficacy and neurohormonal activation during early decongestion in patients with AHF and reduced ejection fraction (HFrEF). Methods: This single-center, prospective, pilot randomized study enrolled 12 hospitalized patients with decompensated HFrEF receiving guideline-directed medical therapy. Participants were randomized (1:1) to remain in either the supine or upright/seated position during intravenous furosemide administration (1 mg/kg: half of the dose administered as a bolus, half as a 2-h infusion). Serial measurements of urine volume, electrolyte excretion, and neurohormonal biomarkers (renin, aldosterone, catecholamines) were performed at baseline, 2, and 6 h after diuretic administration. Results: No significant differences were found between supine and upright groups in total urine output, urine dilution, sodium excretion, or weight change after 6 h. There were no statistically significant differences in renin and aldosterone levels across subsequent timepoints; however, renin concentration tended to be higher in upright than in supine individuals. Interestingly, supine participants demonstrated greater urinary adrenaline concentration after furosemide administration, alone and after adjustment for urinary creatinine. Conclusions: No clinically meaningful differences were found between supine versus upright position patients with AHF, receiving neurohormonal blockade. Full article

Land surface temperature (LST) is fundamental for monitoring surface energy balance and environmental dynamics, with remote sensing providing the primary means of acquisition. However, directional anisotropy (DA) introduces systematic bias in satellite-derived LST products, particularly over complex landscapes. This study examines the impact of angular effects on LST retrievals from three leading East Asian geostationary satellites (FengYun 4A, FengYun 4B, and Himawari 9) across Hunan Province, China, using integrated comparison with in situ measurements and reanalysis data. Results show that all products exhibit a systematic cold bias, with FY4B achieving the highest accuracy. Diurnal retrieval precision increases with higher solar zenith angles (SZA), while no consistent relationship is observed between viewing zenith angle (VZA) and retrieval accuracy. Notably, the retrieval bias of the FY4 series increases significantly when the sun and sensor are aligned in azimuth, particularly when the relative azimuth angle (RAA) is less than or equal to 30°. Parametric modeling reveals that emissivity kernel-induced anisotropy is the principal driver of significant LST deviations in central Hunan, while solar kernel effects result in LST overestimation in mountainous regions and underestimation in plains. Increases in elevation or vegetation density reduce emissivity-induced errors but amplify errors caused by shadowing and sunlit effects. Emissivity anisotropy is thus identified as the primary source of LST DA. These findings deepen the understanding of LST DA in remote sensing and provide essential guidance for refining retrieval algorithms and improving the applicability of LST products in complex terrains. Full article

More than 30% of diabetic patients develop dermatopathies linked to inflammation and increased vascular permeability. Considering the role of the renin–angiotensin–aldosterone system (RAAS) in diabetic complications, this study examined whether aldosterone (ALDO) and the mineralocorticoid receptor (MR) contribute to diabetes-related skin microangiopathy. Vascular permeability was measured in normoglycemic rats and insulin-dependent (streptozotocin-induced) diabetic rats. The expression of MR, 11β-hydroxysteroid dehydrogenase type 2 (HSD11β2), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and the tight junction protein ZO-1 was determined by PCR and immunohistochemistry. Diabetic rats received the MR antagonist eplerenone (EPL, 100 mg/kg) for 10 days. Additionally, the effects of ALDO and EPL on endothelial permeability were evaluated in human dermal microvascular endothelial cells (HMEC-1) using a Transwell system. Diabetic rats showed skin atrophy, collagen damage, elevated ALDO levels, reduced MR and HSD11β2 expression, and increased vascular permeability, along with upregulation of VEGF and vWF. EPL markedly reduced these abnormalities. In vitro, ALDO increased endothelial permeability under hyperglycemia, and EPL counteracted this effect. These findings indicate that activation of the ALDO/MR pathway promotes skin vascular permeability in diabetes through VEGF- and vWF-dependent mechanisms. MR blockade limits these changes, suggesting therapeutic potential in preventing diabetes-associated skin complications. Full article

Background/Objectives: Human serum albumin (HSA) is a major endogenous inhibitor of angiotensin-converting enzyme (ACE) and helps fine-tune the activity of the renin–angiotensin–aldosterone system (RAAS), thereby potentially influencing the development of cardiovascular (CV) diseases. As the principal transport protein for free fatty acids (FFAs), HSA may have its ACE-inhibitory capacity modified by its FFA cargo and, through this mechanism, may also affect CV disease risk. We therefore tested the hypothesis that the composition of HSA-bound FFAs determines the magnitude of endogenous ACE inhibition. Methods: We quantified endogenous ACE inhibition and examined the effect of FFA concentration on this inhibition in clinical patients (n = 161 and n = 101, respectively). We measured the effects of HSA treated with saturated, monounsaturated, and polyunsaturated FFAs, as well as FFA-free HSA, on recombinant ACE and on tissue ACE. Results: Endogenous ACE inhibition was stronger in patients with higher serum HSA concentrations (Spearman’s rho = 0.422, 95% CI 0.281–0.544, p < 0.001), whereas total FFA concentration was not associated with endogenous ACE inhibition (Spearman’s rho = 0.088, p = 0.38, n = 101). However, removal of free fatty acids substantially worsened the ACE-inhibitory effect of HSA on recombinant ACE (charcoal-treated HSA: IC₅₀ = 23.24 [19.40–29.78] g/L vs. control HSA: 7.84 [6.58–9.75] g/L, p < 0.001) and on tissue ACE isolated from lung, heart, and lymph node. FFA chain length, degree and position of unsaturation, and cis/trans configuration all differentially modulated endogenous ACE inhibition. Among saturated fatty acids, stearic acid (IC₅₀ = 7.98 [7.04–9.23] g/L), and among omega-3 and omega-6 fatty acids, α-linolenic (IC₅₀ = 5.60 [4.28–6.15] g/L) and γ-linolenic acids (IC₅₀ = 5.09 [4.28–6.15] g/L) produced the greatest enhancement of the ACE-inhibitory capacity of HSA. Conclusions: The present results indicate that HSA concentration relates to endogenous ACE inhibition in serum, and in vitro experiments demonstrate that HSA-bound FFAs can modulate HSA-mediated ACE inhibition, a mechanism that may be relevant to cardiovascular physiology and disease. Full article

Overactivation of the renin–angiotensin–aldosterone system (RAAS) promotes haemodynamic overload, inflammation, and fibrosis in the heart and kidneys. Recently, sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone therapy in cardiorenal protection. Emerging data indicate that adding SGLT2 inhibitors to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, or angiotensin receptor–neprilysin inhibitors confers additional cardiorenal protection, yet their mechanistic basis and optimal clinical use in cardiovascular (CV) disease remain unclear. This review will integrate pre-clinical and clinical evidence on dual RAAS/SGLT2 modulation in CV disease, providing mechanistic insight into dual therapy. The review will finally outline priorities for future translational and outcome studies. Clinically, adding SGLT2 inhibitors to RAAS-based therapy reduces heart failure hospitalizations and slows kidney disease progression without new safety liabilities in type 2 diabetes, heart failure, and chronic kidney disease. Mechanistically, SGLT2 inhibition restores tubuloglomerular feedback and constricts the afferent arteriole; RAAS blockade dilates the efferent arteriole, and together, they lower intraglomerular pressure. Both classes also reduce oxidative stress, inflammatory signalling, and pro-fibrotic pathways, with SGLT2 inhibitors in several settings shifting RAAS balance toward the protective ACE2/angiotensin-(1–7)/Mas receptor axis. Key gaps include the scarcity of adequately powered trials designed to test combination therapy versus either component alone, limited evidence on timing and sequencing, incomplete characterization in high-risk groups, and mechanistic insight limited by study design in animal and cell models. Collectively, current data support layering SGLT2 inhibitors onto RAAS-based therapy, while definitive evidence from dedicated clinical trials is awaited. Full article

Background/Objectives: The renin–angiotensin–aldosterone system (RAAS) is pivotal for neonatal circulation and renal adaptation; however, postnatal changes in serum renin and aldosterone immediately after birth remain unclear. This study aimed to establish postnatal changes in these hormones at birth and over the first week of life. Methods: We retrospectively analyzed 374 neonates admitted to Kobe University Hospital between October 2020 and September 2023, with serum renin and aldosterone measured on days 0 and 5 of life. Exclusion criteria were multiple congenital anomalies, severe asphyxia, major peripartum hemorrhage, and in utero exposure to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Hormone levels were compared between term and preterm infants, and correlations with gestational age were assessed. Results: Serum renin concentrations were higher on day 0 than on day 5 (median 99.9 pg/mL [2.6–773.3] vs. 19.9 pg/mL [0.6–2304], p < 0.0001), and aldosterone concentrations similarly decreased (714 pg/mL [6.9–6334] vs. 551 pg/mL [0–11,930], p < 0.0001). At birth, renin and aldosterone levels did not differ significantly between groups. By day 5, both renin (32.8 pg/mL [0.6–2304] vs. 14.5 pg/mL [0.6–208]) and aldosterone (689 pg/mL [4–11,930] vs. 471 pg/mL [13–4697]) concentrations were significantly higher in preterm than in term neonates (p < 0.0001). Conclusions: This study describes early postnatal changes in renin and aldosterone, with higher concentrations at birth than on day 5 and persistently elevated levels in preterm infants. These findings indicate increased RAAS activity in preterm neonates and suggest a greater vulnerability to fluid, electrolyte, and blood pressure instability during early life. Full article

The renin–angiotensin–aldosterone system (RAAS) is essential for controlling blood pressure and maintaining fluid balance, driving significant structural changes throughout the cardiovascular system, including the heart and blood vessels. As a result, the RAAS is a key therapeutic target for various chronic cardiovascular diseases, ranging from arterial hypertension (AH) to heart failure (HF). In this review, one of our objectives is to describe the new evidence over the last 4 years regarding the RAAS. Moreover, we pay attention to the structure and function of the angiotensin II type 1 receptor (AT1R) and its role in hypertension, as well as define its active site. Later, we discuss the most potent, selective inhibitors of AT1 receptors, based on in vitro and in vivo experiments, from 2020 to 2024. Large peptide molecules, small non-peptide-like molecules, and sartan derivatives are analyzed. The low IC₅₀ values of the entities that do not resemble sartans showcase the vast chemical space that can be explored for the creation of more potent antihypertensive medications. We have also employed computational chemistry tools in order to identify key molecular interactions between the compounds of the literature studied in order to elucidate the underlying reasons why these different molecules exhibit variations in their binding energies and overall potency. Full article

Background/Objectives: We evaluated Goreisan, a traditional Chinese medicine, for its effects on nephrotic syndrome in a rat model. Methods: Male Sprague–Dawley rats underwent right nephrectomy at 5 weeks of age, followed by adriamycin administration (5 mg/kg) at 6 and 8 weeks of age to induce nephrotic syndrome. At 10 weeks, rats were divided into three groups: vehicle (control), Goreisan 0.5 g/kg (GL), and Goreisan 1.0 g/kg (GH). Goreisan was administered daily for 4 weeks. At 14 weeks, blood, urine, mRNA expressions, and kidney histopathology were analyzed. Data were analyzed using one-way ANOVA followed by Tukey–Kramer post hoc testing. Results: Goreisan prevented worsening kidney function, with reduced glomerular and tubulointerstitial damage, lower systemic and intrarenal 8-hydroxy-2′-deoxyguanosine levels, and lower plasma aldosterone levels and expression of intrarenal renin–angiotensin–aldosterone system (RAAS)-related factors. Urine volume significantly increased in GL and GH groups compared with the control group. In the GH group, urine volume increased markedly (Δ urine volume: 10.0 ± 2.6 mL/day), whereas it tended to decrease in the Vehicle group (Δ urine volume: −1.3 ± 2.5 mL/day). Urine osmolality was lower in the GH group, with a larger decrease in Δ urine osmolality (−616.3 ± 132.8 mOsm/L). These changes occurred without an increase in urinary sodium excretion, suggesting an aquaretic effect independent of natriuresis. Creatinine clearance (CCr/kg) declined markedly in the Vehicle group but was significantly preserved in the GH group (Δ CCr/kg: −2.2 ± 0.19 vs. −0.7 ± 0.28), indicating renoprotective effects. No differences were found in serum arginine–vasopressin levels. Real-time PCR and immunohistochemical staining showed no significant differences in aquaporin (AQP) mRNA expression (AQP1, AQP2, AQP3, and AQP4), but AQP2 localization to the apical membrane in the collecting ducts was reduced with Goreisan treatment. Conclusions: Goreisan demonstrates kidney-protective and diuretic effects in nephrotic syndrome, potentially through reducing systemic oxidative stress, modulating RAAS activation, and altering AQP2 trafficking. Full article

Background: Rapid pathogen detection is crucial for the timely containment of outbreaks, particularly for respiratory infectious diseases which are highly transmissible and possess high epidemic potential. Methods: We developed a sensitive reverse transcription recombinase-aided amplification (RT-RAA) assay for the rapid detection of six common respiratory viruses: respiratory syncytial virus type A (RSV A), influenza A virus (Flu A), influenza B virus (Flu B), human parainfluenza virus (HPIV), SARS-CoV-2 and adenovirus (ADV). The assay employs a single, standardized protocol for the on-demand detection of any one of the six targets. Its performance was validated using nucleic acid standards and clinical pharyngeal swab specimens. Results: The assay enables rapid detection within 20 min at 39 °C using a portable, self-powered device. It demonstrated high sensitivity, with detection limits below 10³ copies/mL for all targets and as low as 10¹ copies/mL for ADV. Cross-reactivity testing with 21 other pathogens confirmed excellent specificity. Validation with 85 clinical samples showed 100% concordance with RT-PCR, while offering significantly faster results and enhanced portability compared to RT-PCR. Conclusions: This sensitive, specific, and user-friendly RT-RAA assay provides a robust tool for rapid detection of respiratory viruses, particularly suitable for deployment in resource-limited settings and point-of-care testing during outbreaks. Full article

Potassium homeostasis is impaired in patients with chronic kidney disease (CKD) due to alterations in physiological mechanisms and use of agents that modulate the renin angiotensin aldosterone system (RAAS) to slow CKD progression and reduce cardiovascular risk. In recent years, a new paradox has emerged: while dietary potassium restriction has been dogmatically recommended to prevent hyperkalemia, emerging evidence suggests that a more liberated potassium intake may offer potential benefits, particularly in patients with early CKD. This has prompted a paradigm shift towards a more individualized approach to the management of hyperkalemia in CKD. This review aims to provide an overview of the latest management strategies for hyperkalemia in CKD and to summarize the current literature including publications and guidelines recommendations with respect to dietary potassium intake and use of potassium salt substitutes. Full article

Heart failure (HF) remains a prevalent, high-risk condition particularly common among the elderly population. The impairment of systolic function, secondary dysregulation of maladaptive neurohormonal systems and HF therapies lead to electrolyte disturbances. Hyponatremia is a well-studied, robust marker of adverse prognosis in HF. Serum chloride has emerged as a promising prognostic marker, accurately predicting adverse outcomes in both acute and chronic settings. Hypochloremia reflects a compound of maladaptive neurohormonal, renal and acid–base mechanisms, frequently worsened by diuretic therapy. In the context of HF, low chloride levels are independently associated with increased cardiovascular mortality, HF hospitalization and diuretic resistance. Urinary chloride (uCl⁻) has recently been shown to serve as a dynamic biomarker of HF severity, Renin–Angiotensin–Aldosterone-system (RAAS) activation, and poor outcomes, offering incremental prognostic value. Our review synthesizes the latest evidence on serum and urinary chloride disturbances in HF, framing key distinctions between acute versus persistent electrolyte disturbances. We also explore the interrelationship between chloride and sodium, the differential impact of hypochloremia in Heart Failure with Preserved Ejection Fraction (HFpEF) versus Heart Failure with Reduced Ejection Fraction (HFrEF), and clinical outcomes stratified by the temporary vs. persistent nature of chloride imbalance. We have also included visual flowcharts for classifying and managing hypochloremia based on the underlying etiology. Full article

Ebola virus (EBOV) infection constitutes a significant global public health threat, and no curative treatment is currently available for it. Rapid and accurate detection of EBOV nucleic acid is crucial for controlling the spread of Ebola virus disease (EVD). The gold standard for EBOV diagnosis is real-time reverse transcription polymerase chain reaction (RT-qPCR), which requires costly equipment and skilled personnel, potentially hindering its application for rapid detection, especially in resource-limited settings. Consequently, there is an urgent need to develop a simple, accurate, and rapid diagnostic method for EVD. In this study, a real-time reverse transcription recombinase-aided amplification (RT-RAA) assay was developed for the specific visual detection of the conserved region of the EBOV nucleoprotein (NP) gene. The RT-RAA assay can be completed within 30 min at 42 °C, and results can be visualized using a portable blue light imager. The assay exhibited strong analytical specificity toward EBOV. No cross-reactivity was observed with any of the other public-health-relevant viruses tested. The visual RT-RAA assay demonstrated sensitivity comparable to RT-qPCR, detecting 52 copies per reaction at a 95% probability level, whereas RT-qPCR required 74 copies per reaction. The RAA method demonstrated excellent repeatability and stability, with intra-assay and inter-assay CVs less than 5% and 7%, respectively. These results clearly indicate that the visual RT-RAA method is specific, accurate, simple, rapid, and reliable for EBOV detection. Full article

Dengue fever has become a major global public health challenge due to its rapidly in-creasing incidence. Rapid on-site detection of dengue virus (DENV) is critical for early diagnosis, timely patient isolation, and outbreak control. In this study, dengue virus serotype 2 (DENV-2), the predominant strain circulating in tropical and subtropical regions, was selected as the target pathogen. We established a one-tube rapid detection assay that integrates the HUDSON nucleic acid extraction-free protocol, reverse transcription recombinase-aided amplification (RT-RAA), and CRISPR/Cas12a-mediated trans cleavage activity. The method achieved a detection limit of 1 × 10² copies/μL for simulated infected samples and exhibited no cross-reactivity with other DENV serotypes (DENV-1, DENV-3, DENV-4) or with other arboviruses, including Zika, Japanese encephalitis, yellow fever, and chikungunya viruses. The assay demonstrated high sensitivity and specificity across various sample types, including mosquitoes, rodents, blood, and cultured cells, with results consistent with quantitative PCR (qPCR). Requiring only basic equipment such as a water bath, the system enables on-site detection of DENV-2 within 1 h. This simple, cost-effective, and reliable assay provides a practical tool for field-based DENV-2 surveillance and supports effective public health responses in resource-limited settings. Full article