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Background: Wiedemann-Steiner syndrome (WSS), a rare autosomal-dominant disorder caused by haploinsufficiency of the KMT2A gene product, is part of a group of disorders called chromatinopathies. Chromatinopathies are neurodevelopmental disorders caused by mutations affecting the proteins responsible for chromatin remodeling and transcriptional regulation. The resulting gene expression dysregulation mediates the onset of a series of clinical features such as developmental delay, intellectual disability, facial dysmorphism, and behavioral disorders. Aim of the Study: The aim of this study was to investigate a 10-year-old girl who presented with clinical features suggestive of WSS. Methods: Clinical and genetic investigations were performed. Whole exome sequencing (WES) was used for genetic testing, performed using Illumina technology. The bidirectional capillary Sanger resequencing technique was used in accordance with standard methodology to validate a mutation discovered by WES in all family members who were available. Utilizing computational protein modeling for structural and functional studies as well as in silico pathogenicity prediction models, the effect of the mutation was examined. Results: WES identified a de novo heterozygous missense variant in the KMT2A gene KMT2A(NM_001197104.2): c.3451C>G, p.(Arg1151Gly), absent in the gnomAD database. The variant was classified as Likely Pathogenetic (LP) according to the ACMG criteria and was predicted to affect the CXXC-type zinc finger domain functionality of the protein. Modeling of the resulting protein structure suggested that this variant changes the protein flexibility due to a variation in the Gibbs free energy and in the vibrational entropy energy difference between the wild-type and mutated domain, resulting in an alteration of the DNA binding affinity. Conclusions: A novel and de novo mutation discovered by the NGS approach, enhancing the mutation spectrum in the KMT2A gene, was characterized and associated with WSS. This novel KMT2A gene variant is suggested to modify the CXXC-type zinc finger domain functionality by affecting protein flexibility and DNA binding.

Focal segmental glomerulosclerosis (FSGS) is a complex disease which describes different kinds of kidney defects, not exclusively linked with podocyte defects. Since nephrin mutation was first described in association with early-onset nephrotic syndrome (NS), many advancements have been made in understanding genetic patterns associated with FSGS. New genetic causes of FSGS have been discovered, displaying unexpected genotypes, and recognizing possible site of damage. Many recent large-scale sequencing analyses on patients affected by idiopathic chronic kidney disease (CKD), kidney failure (KF) of unknown origin, or classified as FSGS, have revealed collagen alpha IV genes, as one of the most frequent sites of pathogenic mutations. Also, recent interest in complex and systemic lysosomal storage diseases, such as Fabry disease, has highlighted GLA mutations as possible causes of FSGS. Tubulointerstitial disease, recently classified by KDIGO based on genetic subtypes, when associated with UMOD variants, may phenotypically gain FSGS features, as well as ciliopathy genes or others, otherwise leading to completely different phenotypes, but found carrying pathogenic variants with associated FSGS phenotype. Thus, glomerulosclerosis may conceal different heterogeneous conditions. When a kidney biopsy is performed, the principal objective is to provide an accurate diagnosis. The broad spectrum of phenotypic expression and genetic complexity is demonstrating that a combined path of management needs to be applied. Genetic investigation should not be reserved only to selected cases, but rather part of medical management, integrating with clinical and renal pathology records. FSGS heterogeneity should be interpreted as an interesting opportunity to discover new pathways of CKD, requiring prompt genotype-phenotype correlation. In this review, we aim to highlight how FSGS represents a peculiar kidney condition, demanding multidisciplinary management, and in which genetic analysis may solve some otherwise unrevealed idiopathic cases. Unfortunately there is not a uniform correlation between specific mutations and FSGS morphological classes, as the same variants may be identified in familial cases or sporadic FSGS/NS or manifest a variable spectrum of the same disease. These non-specific features make diagnosis challenging. The complexity of FSGS genotypes requires new directions. Old morphological classification does not provide much information about the responsible cause of disease and misdiagnoses may expose patients to immunosuppressive therapy side effects, mistaken genetic counseling, and misguided kidney transplant programs., (© 2023. The Author(s).)

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more to understand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Between 15-20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases. We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease ( PAX2 : c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. The identification of the specific genetic background may provide an opportunity to evaluate the risk of recurrence of the primary disease, especially among patient candidates living with a donor kidney transplant.

Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants., Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated., Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure., Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 ( KCNN2 ) (NM_021614.3: c.1145G>A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The KCNN2 gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium.

Background: Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes., Methods: Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay. Magnetic resonance imaging parameters were used for total kidney volume calculation and the Mayo Clinic Imaging Classification defined slow (1A-1B) and fast progressors (1C-1E). Microarray and quantitative gene expression analysis were used to test epidermal growth factor and monocyte chemotactic peptide 1 gene expression., Results: Baseline ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 correlated with total kidney volume adjusted for height (r = - 0.6, p < 0.001), estimated glomerular filtration rate (r = 0.69 p < 0.001), discriminated between Mayo Clinic Imaging Classes (p < 0.001), and predicted the variation of estimated glomerular filtration rate at 10 years (r = - 0.51, p < 0.001). Conditional Inference Trees identified cut-off levels of the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for slow and fast progressors at > 132 (100% slow) and < 25.76 (89% and 86% fast, according to age), with 94% sensitivity and 66% specificity (p = 6.51E-16). Further, the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 at baseline showed a positive correlation (p = 0.006, r = 0.36) with renal outcome (delta-estimated glomerular filtration rate per year, over a mean follow-up of 4.2 ± 1.2 years). Changes in the urinary epidermal growth factor and monocyte chemotactic peptide 1 were mirrored by gene expression levels in both human kidney cysts (epidermal growth factor: - 5.6-fold, fdr = 0.001; monocyte chemotactic peptide 1: 3.1-fold, fdr = 0.03) and Pkd1 knock-out mouse kidney (Egf: - 14.8-fold, fdr = 2.37E-20, Mcp1: 2.8-fold, fdr = 6.82E-15)., Conclusion: The ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 is a non-invasive pathophysiological biomarker that can be used for clinical risk stratification in autosomal dominant polycystic kidney disease., (© 2022. The Author(s).)

Polydopamine (PDA) is a synthetic eumelanin polymer mimicking the biopolymer secreted by mussels to attach to surfaces with a high binding strength. It exhibits unique adhesive properties and has recently attracted considerable interest as a multifunctional thin film coating. In this study, we demonstrate that a PDA coating on silica- and polymer-based materials improves the entrapment and retention of uremic toxins produced in specific diseases. The low-cost natural nanotextured fossil diatomaceous earth (DE), an abundant source of mesoporous silica, and polyvinylpyrrolidone-co-Styrene (PVP-co-S), a commercial absorbent comprising polymeric particles, were easily coated with a PDA layer by oxidative polymerization of dopamine at mild basic aqueous conditions. An in-depth chemical-physical investigation of both the resulting PDA-coated materials was performed by SEM, AFM, UV-visible, Raman spectroscopy and spectroscopic ellipsometry. Finally, the obtained hybrid systems were successfully tested for the removal of two uremic toxins (indoxyl sulfate and p-cresyl sulfate) directly from patients' sera.

Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments. This review summarizes the development of in vitro human cancer models for biomedical applications. We first review the latest development in the field by detailing various types of in vitro human cancer models, including transwell-based models, tumor spheroids, microfluidic tumor-microvascular systems and scaffold-based models. The advantages and limitations of each model, as well as their biomedical applications, are summarized, including therapeutic development, assessment of tumor cell migration, metastasis and invasion and discovery of key cancer markers. Finally, the existing challenges and future perspectives are briefly discussed.

Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their self-renewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration ( i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases., Competing Interests: Conflict-of-interest statement: None of the authors have any conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Autosomal dominant polycystic kidney disease is the most common monogenic cause of ESKD. Genetic studies from patients and animal models have informed disease pathobiology and strongly support a "threshold model" in which cyst formation is triggered by reduced functional polycystin dosage below a critical threshold within individual tubular epithelial cells due to ( 1 ) germline and somatic PKD1 and/or PKD2 mutations, ( 2 ) mutations of genes ( e.g. , SEC63 , SEC61B , GANAB , PRKCSH , DNAJB11 , ALG8 , and ALG9 ) in the endoplasmic reticulum protein biosynthetic pathway, or ( 3 ) somatic mosaicism. Genetic testing has the potential to provide diagnostic and prognostic information in cystic kidney disease. However, mutation screening of PKD1 is challenging due to its large size and complexity, making it both costly and labor intensive. Moreover, conventional Sanger sequencing-based genetic testing is currently limited in elucidating the causes of atypical polycystic kidney disease, such as within-family disease discordance, atypical kidney imaging patterns, and discordant disease severity between total kidney volume and rate of eGFR decline. In addition, environmental factors, genetic modifiers, and somatic mosaicism also contribute to disease variability, further limiting prognostication by mutation class in individual patients. Recent innovations in next-generation sequencing are poised to transform and extend molecular diagnostics at reasonable costs. By comprehensive screening of multiple cystic disease and modifier genes, targeted gene panel, whole-exome, or whole-genome sequencing is expected to improve both diagnostic and prognostic accuracy to advance personalized medicine in autosomal dominant polycystic kidney disease., (Copyright © 2021 by the American Society of Nephrology.)

Proteolytic dysbiosis of the gut microbiota has been recognized as both a typical feature of chronic kidney disease (CKD) and a risk factor for its progression. Blood accumulation of gut-derived uremic toxins (UTs) like indoxyl sulfate (IS) and p-cresyl sulfate (PCS), intestinal permeability and constipation are typical features accompanying CKD progression and triggering chronic inflammation. In order to verify the efficacy of the innovative synbiotic formulation NATUREN G ® in modulating the levels of circulating UTs, intestinal permeability and gastrointestinal symptoms, we set up a randomized, single-blind, placebo-controlled, pilot trial in stage IIIb-IV CKD patients and in healthy controls. Two-month administration of the synbiotic resulted in a decrease of free IS, as compared with the placebo-treated arm, only in the CKD group. The other UTs did not significantly change, although different trends in time (increase in the placebo arm and decrease in the synbiotic arm) were observed. Moreover, after supplementation, reduction of small intestinal permeability and amelioration of abdominal pain and constipation syndromes were observed only in the CKD group. The obtained results suggest the specificity of action of NATUREN G ® in CKD and justify further validation in a wider study population.

Nutritional therapy (NT) is a therapeutic option in the conservative treatment of chronic kidney disease (CKD) patients to delay the start of dialysis. The aim of this study was to evaluate the specific effect of ketoanalogs (KA)-supplemented diets for gut microbiota modulation. In a previous study we observed that the Mediterranean diet (MD) and a KA-supplemented very-low-protein diet (VLPD) modulated beneficially gut microbiota, reducing indoxyl- and p-cresyl-sulfate (IS, PCS) serum levels, and ameliorating the intestinal permeability in CKD patients. In the current study, we added a third diet regimen consisting of KA-supplemented MD. Forty-three patients with CKD grades 3B-4 continuing the crossover clinical trial were assigned to six months of KA-supplemented MD (MD + KA). Compared to MD, KA-supplementation in MD + KA determined (i) a decrease of Clostridiaceae , Methanobacteriaceae , Prevotellaceae , and Lactobacillaceae while Bacteroidaceae and Lachnospiraceae increased; (ii) a reduction of total and free IS and PCS compared to a free diet (FD)-more than the MD, but not as effectively as the VLPD. These results further clarify the driving role of urea levels in regulating gut integrity status and demonstrating that the reduction of azotemia produced by KA-supplemented VLPD was more effective than KA-supplemented MD in gut microbiota modulation mainly due to the effect of the drastic reduction of protein intake rather than the effect of KA.

High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for albumin. This study evaluates the efficacy of a divinylbenzene-polyvinylpyrrolidone (DVB-PVP) cartridge and a synbiotic to reduce uremic toxins in HD patients. First, the in vitro efficacy of DVB-PVP in adsorbing IS and PCS was evaluated. Second, a randomized, placebo-controlled pilot study in HD patients was carried out to establish whether the administration of a synbiotic, either individually and in association with DVB-PVP-HD, could reduce the production of uremic toxins. In vitro data showed that DVB-PVP resin removed a mean of 56% PCS and around 54% IS, after 6 h of perfusion. While, in the in vivo study, the DVB-PVP cartridge showed its adsorbing efficacy only for IS plasma levels. The combination of synbiotic treatment with DVB-PVP HD decreased IS and PCS both at pre- and post-dialysis levels. In conclusion, this study provides the first line of evidence on the synergistic action of gut microbiota modulation and an innovative absorption-based approach in HD patients, aimed at reducing plasma levels of IS and PCS., Competing Interests: S.M. is an employeer of Aferetica and M.A. is its Scientific Director. S.F. is the AD of Farmalabor. The rest of the authors declare no conflict of interest.

In this contribution we report the design, preparation, and physico-chemical, photophysical and photochemical characterization of photoactivatable microemulsions (MEs) based on Labrasol®, isopropanol and Lauroglycol® FCC as a surfactant, co-surfactant and oily phase, respectively. The MEs co-incorporate, in their oil phase, two lipophilic guests such as a red emitting singlet oxygen ( 1 O 2 ) photosensitizer (PS) and a tailored green emitting nitric oxide (NO) photodonor (NOPD). These two chromofluorogenic units absorb in different spectral windows of the visible range, and their individual photophysical and photochemical properties are well-conserved when co-entrapped in the microemulsions. These features permit the PS and NOPD to operate either individually or in tandem resulting in (i) red, green or both fluorescence emission, (ii) photogeneration of cytotoxic 1 O 2 , NO or both and (iii) amplified photobactericidal action against Staphylococcus aureus due to the combined effect of these two antibacterial agents.

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B-4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium , as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus , Akkermansia , Streptococcus , and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD -36%, -40% and VLPD -69%, -73%, respectively) and PCS (MD -38%, -44% and VLPD -58%, -71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients.

We report herein on a novel water-soluble β-cyclodextrin-branched polymer covalently integrating a fluorescein moiety and a nitric oxide (NO) photodonor within its macromolecular skeleton. Photoexcitation with visible light induces the parallel activation of the two chromophores, which results in the green fluorescence emission suitable for imaging accompanied by NO release for therapy. In fact, this polymer internalizes in squamous carcinoma cancer cells in vitro, visualized by fluorescence microscopy, and induces cell mortality as result of the NO photo-decaging. The non-covalent drug delivery capability of this new material is also demonstrated using a hydrophobic photosensitizer for photodynamic therapy as a probe.

Combination cancer chemotherapy provides an important treatment tool, both as an adjuvant and neoadjuvant treatment, this shift in focus from mono to combination therapies has led to increased interest in drug delivery systems (DDS). DDSs, such as polymersomes, are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers and poor patient tolerance of the cytotoxic compounds utilised. In this article, we report the formulation and evaluation of a novel electroneutral polymersome capable of high encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and leucovorin). The in-vivo biodistribution of the polymersome were established and they were found to accumulate largely in tumour tissue. Polymersome encapsulating the three chemotherapeutic drugs were assessed both in-vitro (BxPC-3 cell line) and in-vivo (following intratumoral and intravenous administration) and compared with the same concentration of the three drugs in solution. We report better efficacy and higher maximum tolerated dose for our combination drug loaded polymersomes in all experiments. Furthermore, intratumorally injected combination drug loaded polymersomes exhibited a 62% reduction in tumour volume after 13 days when compared with the free combination solutions. A smaller differential of 13% was observed for when treatment was administered intravenously however, importantly less cardiotoxicity was displayed from the polymersomal DDS. In this study, expression of a number of survival-relevant genes in tumours treated with the free chemotherapy combination was compared with expression of those genes in tumours treated with the polymersomes harbouring those drugs and the significance of findings is discussed. STATEMENT OF SIGNIFICANCE: The shift in focus from mono to combination chemotherapies has led to an increased interest in the role of drug delivery systems (DDS). Liposomes, although commercialized for mono therapy, have lower loading capacities and stability than their polymeric counterpart, polymersomes. Polymersomes are growing in prevalence as their advantageous properties are better understood and exploited. Here we present a novel polymersome for the encapsulation of three anticancer compounds. This is the first time this particular polymersome has been used to encapsulate these three compounds with both an in-vitro and in-vivo evaluation carried out. This work will be of interest to those in the field of combination therapy, drug delivery, drug toxicity, multidrug resistance, liposomes, DDS and polymersomes., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) affects 8⁻16% of the population worldwide. In developed countries, the most important risk factors for CKD are diabetes, hypertension, and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced diet and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and can help to manage and curb the main risk factors for renal damage. While the concept of protein and salt restriction in nephrology is historically acknowledged, the role of some nutrients in renal health and the importance of nutrition as a preventative measure for renal care are less known. In this narrative review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals, and xenobiotics on renal health and function. The direct and indirect effects of fiber, protein, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol on kidney health are reviewed here. In view of functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions, including CKD, are related to systemic dysfunctions such as chronic low-grade inflammation.

The role of nitric oxide (NO) as an antimicrobial and anticancer agent continues to stimulate the search of compounds generating NO in a controlled fashion. Photochemical generators of NO are particularly appealing due to the accurate spatiotemporal control that light-triggering offers. This contribution reports a novel molecular construct in which multiple units of 3-(trifluoromethyl)-4-nitrobenzenamine NO photodonor are clustered and spatially organized by covalent linkage to a calix[4]arene scaffold bearing two quaternary ammonium groups at the lower rim. This multivalent calix[4]arene-NO donor conjugate is soluble in hydro-alcoholic solvent where it forms nanoaggregates able to release NO under the exclusive control of visible light inputs. The light-stimulated antibacterial activity of the nanoconstruct is demonstrated by the effective bacterial load reduction of Gram-positive Staphylococcus aureus ATCC 6538 and Gram-negative Escherichia coli ATCC 10536.

A hydrophobic N-dodecyl-3-(trifluoromethyl)-4-nitrobenzenamine has been synthesized as a suitable NO photodonor and encapsulated in a nanocontainer based on a polycationic calix[4]arene derivative, leading to a supramolecular micellar-like nanoassembly ca. 45 nm in diameter. Visible light excitation of this nanoconstruct triggers NO generation with an efficiency remarkably higher than that observed for the free NO photoreleaser. This amplified NO release results in considerable antibacterial activity against Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 9027) as representative Gram positive and Gram negative bacteria, respectively.

The controversy which followed the theory of emotions outlined by William James and Carl Lange saw also the active involvement of Charles Francois-Franck, Professor of Physiology at the "Collège de France". Nevertheless his refusal of the aforementioned theory is as yet unknown to the audience. In the light of his previous work on the vascular innervation of the organs, the French physiologist rejected firmly Lange's hemodynamics version, hence anticipating on many points the work of W.B. Cannon.

Studies of the life and work of Jean Martin Charcot (1825-1893) carried out over the last fifteen years all see in him one of the figures mainly responsible for the constitution of clinical neurology as a specific area of research, in particular in French-speaking areas. The aim of this study is to analyse, by the use of computational linguistic technique, the language of his lessons to demonstrate a rhetoric use of verbs to obtain the verdict from the jury of disciplines: the disease's name.

The almost total disinterest of legislators in the area of artificial fecundation has prompted the frequent involvement of magistrates thereby giving rise to innovations which depart from the previous tendencies of jurisprudence. The latest sentence of the Supreme Court on heterologous fecundation and the issue of paternity merits special attention because of its innovative principles.

Fifty six patients aged 17 to 45 years who had Ischemic Cerebral Infarction (I.C.I.) were studied. The following etiologies were established: 1. Juvenile atherosclerosis (21 patients); 2. Cerebral embolism either from cardiac (10 patients) and from unknown source (3 patients); 3. Secondary coagulopathies (4 patients); 4. Non atherosclerotic vasculopathies (6 patients); 5. Traumas of skull and neck (3 patients); 6. Migraine (2 patients); 7. Oral contraceptives use (1 patient). In 6 cases the etiology remained unknown. Young subjects with I.C.I. are a heterogeneous group: however in most of them a reasonable cause can be found. The occurrence of acute death (14%) was high, while recurrent stroke (5%) and non acute death (3%) were rare when compared to older patients. At the follow-up 80% had a very little residual motor deficit but only 43% were able to return to previous work.