Lack of renoprotective effects by long-term PCSK9 and SGLT2 inhibition using alirocumab and empagliflozin in obese ZSF1 rats.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). Despite the entry of sodium glucose cotransporter 2 (SGLT2) inhibitors, CKD persists as a medical challenge. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition reduces low-density lipoprotein (LDL)-cholesterol, a major risk factor of CVD.

Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection.

Background: Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection.

A Contribution to a Better Understanding of the Group (Charales, Charophyceae): A Taxonomic Re-Examination of the Collected in the Province of Ferrara, Italy.

The identification of a charophyte population found in a rice field in Ferrara, North Italy, collected in 1999 and initially identified as , has been reevaluated. Detailed morphological observations here reported have suggested that the specimen displays characteristics more akin to , particularly in the structure of its bicellular dactyls and axillary heads. Additional examinations, including scanning electron microscopy (SEM) of oospores and analyses of herbarium specimens-encompassing original materials of , f.

Correction: Blindow et al. Re-Establishment Techniques and Transplantations of Charophytes to Support Threatened Species. 2021, , 1830.

In the original publication [...

Amiloride Reduces Urokinase/Plasminogen-Driven Intratubular Complement Activation in Glomerular Proteinuria.

Significance Statement: Proteinuria predicts accelerated decline in kidney function in CKD. The pathologic mechanisms are not well known, but aberrantly filtered proteins with enzymatic activity might be involved. The urokinase-type plasminogen activator (uPA)-plasminogen cascade activates complement and generates C3a and C5a in vitro / ex vivo in urine from healthy persons when exogenous, inactive, plasminogen, and complement factors are added.

The Multicomponent Medicinal Product Hepar Compositum Reduces Hepatic Inflammation and Fibrosis in a Streptozotocin- and High-Fat Diet-Induced Model of Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD)-formerly known as non-alcoholic fatty liver disease (NAFLD)-is the most common chronic liver disease worldwide. Since there is currently no approved pharmacotherapy for MASLD, there is an urgent unmet need for efficacious therapeutics for this disease. Hepar compositum (HC-24) is a multicomponent medicinal product that consists of 24 natural ingredients.

Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome.

Proteinuria is a prominent feature of chronic kidney disease. Interventions that reduce proteinuria slow the progression of chronic kidney disease and the associated risk of cardiovascular disease. Here, we propose a mechanistic coupling between proteinuria and proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of cholesterol and a therapeutic target in cardiovascular disease.

Targeting PCSK9 to tackle cardiovascular disease.

Lowering blood cholesterol levels efficiently reduces the risk of developing atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD), which is the main cause of death worldwide. CAD is caused by plaque formation, comprising cholesterol deposits in the coronary arteries. Proprotein convertase subtilisin kexin/type 9 (PCSK9) was discovered in the early 2000s and later identified as a key regulator of cholesterol metabolism.

Vertigoheel promotes rodent cognitive performance in multiple memory tests.

Introduction: Cognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development.

Plastid DNA sequences and oospore characters of some European taxa of section (Characeae) identify five clusters, including one new cryptic taxon from Sardinia, but they do not coincide with current morphological descriptions.

In Europe, the genus (Characeae) comprises four to eight taxa in sections and that have been distinguished by vegetative morphology and gametangial characters such as antheridial size and oospore wall ornamentation. However, morphological differentiation is difficult in some cases due to overlapping and variable vegetative features, which in many cases are difficult to observe clearly. To clarify the taxonomic status of the five European taxa of in section , sequence data of the plastid genes B, L and C for (Desv.

The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus.

Introduction: Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.

Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats.

The aim of this study was to assess the effect of Vertigoheel on central vestibular compensation and cognitive deficits in rats subjected to peripheral vestibular loss. Young adult male Long Evans rats were subjected to bilateral vestibular insults through irreversible sequential ototoxic destructions of the vestibular sensory organs. Vestibular syndrome characteristics were monitored at several time points over days and weeks following the sequential insults, using a combination of behavioral assessment paradigms allowing appreciation of patterns of change in static and dynamic deficits, together with spatial navigation, learning, and memory processes.

Megalin-Mediated Endocytosis in the Kidney Proximal Tubule: Relevance to Regulation of the Renal Renin-Angiotensin System.

The kidney proximal tubule is a major target tissue of the renin-angiotensin system (RAS). Megalin is an endocytic multiligand receptor abundantly expressed in the proximal tubule where it drives reabsorption of peptides and proteins from the glomerular ultrafiltrate. All major RAS components are present in the kidney proximal tubules.

Re-Establishment Techniques and Transplantations of Charophytes to Support Threatened Species.

Re-establishment of submerged macrophytes and especially charophyte vegetation is a common aim in lake management. If revegetation does not happen spontaneously, transplantations may be a suitable option. Only rarely have transplantations been used as a tool to support threatened submerged macrophytes and, to a much lesser extent, charophytes.

Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin.

Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities.

Guidance for Studies Evaluating the Accuracy of Rapid Tuberculosis Drug-Susceptibility Tests.

The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support potential policy recommendations. The evidence necessary includes an assessment of the performance for TB and resistance detection as well as an assessment of the operational characteristics of these platforms.

Guidance for Studies Evaluating the Accuracy of Biomarker-Based Nonsputum Tests to Diagnose Tuberculosis.

The World Health Organization's (WHO) "End TB" strategy calls for development and implementation of novel tuberculosis (TB) diagnostics. Sputum-based diagnostics are challenging to implement and often less sensitive in high-priority populations. Nonsputum, biomarker-based tests may facilitate TB testing at lower levels of the healthcare system, accelerate treatment initiation, and improve outcomes.

Guidance for Studies Evaluating the Accuracy of Sputum-Based Tests to Diagnose Tuberculosis.

Tests that can replace sputum smear microscopy have been identified as a top priority diagnostic need for tuberculosis by the World Health Organization. High-quality evidence on diagnostic accuracy for tests that may meet this need is an essential requirement to inform decisions about policy and scale-up. However, test accuracy studies are often of low and inconsistent quality and poorly reported, leading to uncertainty about true test performance.

Guidance for the Evaluation of Tuberculosis Diagnostics That Meet the World Health Organization (WHO) Target Product Profiles: An Introduction to WHO Process and Study Design Principles.

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests.

Urokinase-type plasminogen activator contributes to amiloride-sensitive sodium retention in nephrotic range glomerular proteinuria in mice.

Aim: Activation of sodium reabsorption by urinary proteases has been implicated in sodium retention associated with nephrotic syndrome. The study was designed to test the hypothesis that nephrotic proteinuria in mice after conditional deletion of podocin leads to urokinase-dependent, amiloride-sensitive plasmin-mediated sodium and water retention.

Methods: Ten days after podocin knockout, urine and faeces were collected for 10 days in metabolic cages and analysed for electrolytes, plasminogen, protease activity and ability to activate γENaC by patch clamp and western blot.

Mutual Facilitation Among Invading Nuttall's Waterweed and Quagga Mussels.

Nuttall's waterweed () is the most abundant invasive aquatic plant species in several European countries. populations often follow a boom-bust cycle, but the causes and consequences of this dynamics are yet unknown. We hypothesize that both boom and bust periods can be affected by dreissenid mussel invasions.