Hypertension is one of the major health problems leading to the development of cardiovascular diseases. Despite a rapid expansion in global hypertension prevalence, molecular mechanisms leading to hypertension are not fully understood largely due to the complexity of pathogenesis involving several factors. Salt intake is recognized as a leading determinant of blood pressure, since reduced dietary salt intake is related to lower morbidity and mortality, and hypertension in relation to cardiovascular events. Compared with salt-resistant populations, salt-sensitive individuals exhibit high sensitivity in blood pressure responses according to changes in salt intake. In this setting, the kidney plays a major role in the maintenance of blood pressure under the hormonal control of the renin–angiotensin–aldosterone system. In the present review, we summarize the current overview on the molecular mechanisms for modulation of blood pressure associated with renal ion channels/transporters including sodium–hydrogen exchanger isoform 3 (NHE3), Na⁺-K⁺-2Cl^– cotransporter (NKCC2), sodium–chloride cotransporter (NCC), epithelial sodium channel (ENaC) and pendrin expressed in different nephron segments. In particular, recent studies on experimental animal models with deletion of renal ion channels led to the identification of several crucial physiological mechanisms and molecules involved in hypertension. These findings could further provide a potential for novel therapeutic approaches applicable on human patients with hypertension. Hypertension is one of the major health problems leading to the development of cardiovascular diseases. However, the molecular mechanisms leading to hypertension are not fully understood largely due to the complexity of pathogenesis involving several factors. Salt intake is recognized as a leading determinant of blood pressure. Kidney plays a major role on the maintenance of blood pressure under the hormonal control of renin–angiotensin–aldosterone system. In the present review, we summarize the current overview on the molecular mechanisms for modulation of blood pressure associated with renal ion channels/transporters including NHE3, NKCC2, NCC, ENaC and pendrin. In particular, recent studies on experimental animal models targeting renal ion channels/transporters led to the identification of several crucial physiological mechanisms and molecules involved in hypertension. These findings could further provide a potential for novel therapeutic approaches applicable on human patients with hypertension.

Mitogen-activated protein kinases (MAPKs) are intracellular molecules regulating a wide range of cellular functions, including proliferation, differentiation, apoptosis, cytoskeleton remodeling and cytokine production. MAPK activity has been shown in normal kidney, and its over-activation has been demonstrated in several renal diseases. The extracellular signal-regulated protein kinases (ERK 1,2) signalling pathway is the first described MAPK signaling. Intensive investigations have demonstrated that it participates in the regulation of ureteric bud branching, a fundamental process in establishing final nephron number; in addition, it is also involved in the differentiation of the nephrogenic mesenchyme, indicating a key role in mammalian kidney embryonic development. In the present manuscript, we show that ERK1,2 signalling mediates several cellular functions also in mature kidney, describing its role along the nephron and demonstrating whether it contributes to the regulation of ion channels and transporters implicated in acid-base and electrolytes homeostasis.

Increasing attention is more and more directed toward the thermostable Phosphotriesterase-Like-Lactonase (PLL) family of enzymes, for the efficient and reliable decontamination of toxic nerve agents. In the present study, the DNA Staggered Extension Process (StEP) technique was utilized to obtain new variants of PLL enzymes. Divergent homologous genes encoding PLL enzymes were utilized as templates for gene recombination and yielded a new variant of SsoPox from Saccharolobus solfataricus. The new mutant, V82L/C258L/I261F/W263A (4Mut) exhibited catalytic efficiency of 1.6 × 10⁵ M⁻¹ s⁻¹ against paraoxon hydrolysis at 70°C, which is more than 3.5-fold and 42-fold improved in comparison with C258L/I261F/W263A (3Mut) and wild type SsoPox, respectively. 4Mut was also tested with chemical warfare nerve agents including tabun, sarin, soman, cyclosarin and VX. In particular, 4Mut showed about 10-fold enhancement in the hydrolysis of tabun and soman with respect to 3Mut. The crystal structure of 4Mut has been solved at the resolution of 2.8 Å. We propose that, reorganization of dimer conformation that led to increased central groove volume and dimer flexibility could be the major determinant for the improvement in hydrolytic activity in the 4Mut.

Cognitive decline is frequently seen in patients with chronic kidney disease (CKD). The causes of cognitive decline in these patients are likely to be multifactorial, including vascular disease, uraemic toxins, blood–brain barrier leakage, and metabolic and endocrine changes. Gut dysbiosis is common in patients with CKD and contributes to the increase in uraemic toxins. However, the gut microbiome modulates local and systemic levels of several metabolites such as short-chain fatty acids or derivatives of tryptophan metabolism, neurotransmitters, endocannabinoid-like mediators, bile acids, hormones such as glucagon-like peptide 1 (GLP1) or cholecystokinin (CCK). These factors can affect gut function, immunity, autonomic nervous system activity and various aspects of brain function. Key areas include blood–brain barrier integrity, nerve myelination and survival/proliferation, appetite, metabolism and thermoregulation, mood, anxiety and depression, stress and local inflammation. Alterations in the composition of the gut microbiota and the production of biologically active metabolites in patients with CKD are well documented and are favoured by low-fiber diets, elevated urea levels, sedentary lifestyles, slow stool transit times and polypharmacy. In turn, dysbiosis can modulate brain function and cognitive processes, as discussed in this review. Thus, the gut microbiome may contribute to alterations in cognition in patients with CKD and may be a target for therapeutic interventions using diet, prebiotics and probiotics.

Introduction: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time. Methods: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood. Results: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. Discussion/Conclusion: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose.

Background: Cystinuria is a rare genetic tubulopathy caused by mutations on SLC7A9 and SLC3A1 genes encoding for the apical membrane rBAT/b0,+AT transporter. The mean worldwide frequency of cystinuria is estimated to be 1:7,000 with significant ethnogeographic variation in prevalence. Cystine builds up in the urine as a result of the transporter deficit, which can cause cystine crystals to form or even stones. Several strategies must be used in treatment to stop the growth or creation of stones. Although the prognosis is favourable, renal insufficiency can very rarely be brought on by poor patient compliance, stone formation recurrence, and subsequent interventions. Summary: All the identified mutations of these genes to be responsible for the genotype have been reported, and many aspects of the disease phenotype are yet unclear and need to be elucidated. The molecular mechanism of the rBAT/b0,+AT is described under both physiological and pathological conditions. Its dysfunction in cystinuria leads to the accumulation of cystine and subsequent stone formation, which is detailed through the steps involved in stone development. In vitro studies using different cell lines enable to identify potential methodologies for generating cellular models of cystinuria and to assess therapeutic approaches. In vivo studies done on mice and rats have created different models of cystinuria, including types A, B, and AB, to find the best way to make a model that closely resembles human cystinuria. Key Message: To turn the light on the disease progression and potential treatments, we outlined and carefully examined some of the animal and cellular models of cystinuria.