Kidney and urine cell transcriptomics in IgA nephropathy and lupus nephritis: a narrative review.

This narrative review sheds light on the use of transcriptomics in the analysis of kidney biopsies and urinary cell samples from patients with immunoglobulin A nephropathy or lupus nephritis. The conventional methods of examining kidney biopsy through light microscopy, immunofluorescence and electron microscopy provide valuable clinical information for diagnosis and prognosis but have some limitations that transcriptomics can address. Some recent studies have reported that kidney transcriptomics has uncovered new molecular biomarkers implicated in the inflammatory process induced by the deposition of circulating immune complexes in the investigated kidney diseases.

Molecular Profiling of Tissue Samples with Chronic Rejection from Patients with Chronic Lung Allograft Dysfunction: A Pilot Study in Cystic Fibrosis Patients.

Chronic rejection (CR) is the main culprit for reduced survival and quality of life in patients undergoing lung transplantation (Ltx). High-throughput approaches have been used to unveil the molecular pathways of CR, mainly in the blood and/or in bronchoalveolar lavage. We hypothesized that a distinct molecular signature characterizes the biopsies of recipients with clinically confirmed histological signs of CR.

Post-hoc analysis of a tool to predict kidney failure in patients with IgA nephropathy.

Background: Recently, a tool based on two different artificial neural networks has been developed. The first network predicts kidney failure (KF) development while the second predicts the time frame to reach this outcome. In this study, we conducted a post-hoc analysis to evaluate the discordant results obtained by the tool.

Prediction of chronic kidney disease and its progression by artificial intelligence algorithms.

Background And Objective: Aim of nephrologists is to delay the outcome and reduce the number of patients undergoing renal failure (RF) by applying prevention protocols and accurately monitoring chronic kidney disease (CKD) patients. General practitioners and nephrologists are involved in the first and in the late stages of the disease, respectively. Early diagnosis of CKD is an important step in preventing the progression of kidney damage.

Erratum: Randomized clinical study to evaluate the effect of personalized therapy on patients with immunoglobulin A nephropathy.

[This corrects the article DOI: 10.1093/ckj/sfab263.].

Randomized clinical study to evaluate the effect of personalized therapy on patients with immunoglobulin A nephropathy.

Background: Randomized controlled trials (RCTs) have been conducted, stratifying idiopathic immunoglobulin A nephropathy (IgAN) patients based on the laboratory findings [serum creatinine, estimated glomerular filtration rate (eGFR) and daily proteinuria]. In contrast, data from kidney biopsy have been used only for clinical diagnosis. Therefore, IgAN patients with active or chronic renal lesions have been receiving the same therapy in experimental and control arms of randomized clinical trials (RCTs).

Artificial intelligence in glomerular diseases.

In this narrative review, we focus on the application of artificial intelligence in the clinical history of patients with glomerular disease, digital pathology in kidney biopsy, renal ultrasonography imaging, and prediction of chronic kidney disease (CKD). With the development of natural language processing, the clinical history of a patient can be used to identify a computable phenotype. In kidney pathology, digital imaging has adopted innovative deep learning algorithms (DLAs) that can improve the predictive capability of the examined lesions.

The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy : Gene involvement in the mechanisms of inflammation and scarring in kidney biopsy of IgAN patients.

Kidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions.

TRIM8 Blunts the Pro-proliferative Action of ΔNp63α in a p53 Wild-Type Background.

The p53 gene family network plays a pivotal role in the control of many biological processes and therefore the right balance between the pro-apoptotic and pro-survival isoforms is key to maintain cellular homeostasis. The stability of the p53 tumor suppressor protein and that of oncogenic ΔNp63α, is crucial to control cell proliferation. The aberrant expression of p53 tumor suppressor protein and oncogenic ΔNp63α contributes to tumorigenesis and significantly affects anticancer drug response.

Social Dysfunction in Older Age and Relationships with Cognition, Depression, and Apathy: The GreatAGE Study.

Background: Most studies focused on only one measure of social dysfunction in older age, without proper validation and distinction across different dimensions including subjectivity, structural, and functional aspects.

Objective: We sought to validate the Social Dysfunction Rating Scale (SDRS) and its factorial structure, also determining the association of SDRS with cognitive functions, global psychopathology, and social deprivation.

Methods: The SDRS was administered to 484 Italian community-dwelling elderly, recruited in the GreatAGE study, a population-based study on aging conducted in Castellana Grotte, Bari, Southern Italy.

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

Background: The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage.

Methods: This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD.

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review.

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e.

Additive Role of a Potentially Reversible Cognitive Frailty Model and Inflammatory State on the Risk of Disability: The Italian Longitudinal Study on Aging.

Objective: Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated.

Stimulation by pro-apoptotic valinomycin of cytosolic NADH/cytochrome c electron transport pathway-Effect of SH reagents.

Intrinsic and extrinsic apoptosis are both characterised by the presence of cytochrome c (cyto-c) in the cytosol. We present data on the extra-mitochondrial NADH oxidation catalysed by exogenous (cytosolic) cyto-c, as a possible answer to the paradox of apoptosis being an energy-dependent program but characterized by the impairment of the respiratory chain. The reduction of molecular oxygen induced by the cytosolic NADH/cyto-c pathway is coupled to the generation of an electrochemical proton gradient available for ATP synthesis.

Site-dependent biological activity of valinomycin analogs bearing derivatizable hydroxyl sites.

Valinomycin (VLM, 1) is a K(+) ionophore cyclodepsipeptide capable of depolarizing mitochondria and inducing apoptosis to several mammalian cell types, including a number of tumor cell lines. With the aim of creating VLM-based ligand-targeted anticancer drugs that may selectively convey VLM to pathological cells, we have previously introduced derivatizable hydroxyl handles into the VLM structure, allowing to access a three-entity library of monohydroxyl VLMs (HyVLMs) bearing the OH group at the isopropyl side chain of a D-Hyi, D-Val, or L-Val residue (analogs 2-4, respectively). Herein, the levels of bioactivity retained by the conjugable HyVLMs have been assessed on the basis of their ability to alter the functionality of isolated rat-liver mitochondria.

Malate-aspartate shuttle and exogenous NADH/cytochrome c electron transport pathway as two independent cytosolic reducing equivalent transfer systems.

In mammalian cells aerobic oxidation of glucose requires reducing equivalents produced in glycolytic phase to be channelled into the phosphorylating respiratory chain for the reduction of molecular oxygen. Data never presented before show that the oxidation rate of exogenous NADH supported by the malate-aspartate shuttle system (reconstituted in vitro with isolated liver mitochondria) is comparable to the rate obtained on activation of the cytosolic NADH/cytochrome c electron transport pathway. The activities of these two reducing equivalent transport systems are independent of each other and additive.

Valinomycin induced energy-dependent mitochondrial swelling, cytochrome c release, cytosolic NADH/cytochrome c oxidation and apoptosis.

In valinomycin induced stimulation of mitochondrial energy dependent reversible swelling, supported by succinate oxidation, cytochrome c (cyto-c) and sulfite oxidase (Sox) [both present in the mitochondrial intermembrane space (MIS)] are released outside. This effect can be observed at a valinomycin concentration as low as 1 nM. The rate of cytosolic NADH/cyto-c electron transport pathway is also greatly stimulated.

Ceramide-induced activation of cytosolic NADH/cytochrome c electron transport pathway: An additional source of energy for apoptosis.

We have investigated whether increase in the oxidation rate of exogenous cytochrome c (cyto-c), induced by long-chain ceramides, might be due to an increased rate of cytosolic NADH/cyto-c electron transport pathway. This process was identified in isolated liver mitochondria and has been studied in our laboratory for many years. Data from highly specific test of sulfite oxidase prove that exogenous cyto-c both in the absence and presence of ceramide cannot permeate through the mitochondrial outer membrane.