Transcriptome meta-analysis and validation to discovery of hub genes and pathways in focal and segmental glomerulosclerosis.

Background: Focal segmental glomerulosclerosis (FSGS), a histologic pattern of injury in the glomerulus, is one of the leading glomerular causes of end-stage renal disease (ESRD) worldwide. Despite extensive research, the underlying biological alterations causing FSGS remain poorly understood. Studying variations in gene expression profiles offers a promising approach to gaining a comprehensive understanding of FSGS molecular pathogenicity and identifying key elements as potential therapeutic targets.

Proteomics to Metabolomics: A New Insight into the Pathogenesis of Hypertensive Nephropathy.

Background: Hypertensive nephropathy (HN) is a high-burden disorder and a leading cause of end-stage renal disease. Despite huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to providing a comprehensive insight into this complex disorder.

The potential of cardiac biomarkers, NT-ProBNP and troponin T, in predicting the progression of nephropathy in diabetic patients: A meta-analysis of prospective cohort studies.

Aims: A meta-analysis was done to investigate the association of two cardiac biomarkers of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and circulating troponin T (TnT) with the progression of diabetic nephropathy (DN).

Methods: A thorough search of the PubMed, Scopus, and Web of Science databases was done until June 2022. The outcome (progression of DN) was described as either of the followings: a) eGFR decline, b) albuminuria, c) end-stage renal disease, or d) mortality.

miR-802-5p is a key regulator in diabetic kidney disease.

Background: Diabetic kidney disease has substantial burden and limited therapeutic options. An inadequate understanding of the complex gene regulatory circuits underlying this disorder contributes to the insufficiency of current treatment strategies. MicroRNAs (miRNAs) play a crucial role as regulators of functionally related gene networks.

Regenerative potential of multinucleated cells: bone marrow adiponectin-positive multinucleated cells take the lead.

Background: Polyploid cells can be found in a wide evolutionary spectrum of organisms. These cells are assumed to be involved in tissue regeneration and resistance to stressors. Although the appearance of large multinucleated cells (LMCs) in long-term culture of bone marrow (BM) mesenchymal cells has been reported, the presence and characteristics of such cells in native BM and their putative role in BM reconstitution following injury have not been fully investigated.

Cisplatin-Resistant Ovarian Cancer Cells Reveal a Polyploid Phenotype with Remarkable Activation of Nuclear Processes.

Background: Tumor recurrence as one of the main causes of cancer death is a big barrier to cancer complete treatment. Various studies denote the possible role of therapeutics in tumor relapse. Cisplatin as one of the generally used chemotherapy agents is supposed to be the source of therapy resistance through formation of polyploid giant cancer cells (PGCCs).

A novel strategy for dynamic modeling of genome-scale interaction networks.

Motivation: The recent availability of omics data allows the construction of holistic maps of interactions between numerous role-playing biomolecules. However, these networks are often static, ignoring the dynamic behavior of biological processes. On the other hand, dynamic models are commonly constructed on small scales.

Identification of key genes and biological regulatory mechanisms in diabetic nephropathy: Meta-analysis of gene expression datasets.

Background: Diabetic nephropathy (DN) which refers to the cases with biopsy proven kidney lesions, is one of the main complications of diabetes all around the world; however, the underlying biological changes causing DN remain to be understood. Studying the alterations in gene expression profiles could give a holistic view of the molecular pathogenicity of DN and aid to discover key molecules as potential therapeutic targets. Here, we performed a meta-analysis study that included microarray gene expression profiles coming from glomerular samples of DN patients in order to acquire a list of consensus Differentially Expressed Genes (meta-DEGs) correlated with DN.

Zoledronic acid targets chemo-resistant polyploid giant cancer cells.

Although polyploid giant cancer cells (PGCCs) are known as a key source of failure of current therapies, sufficient drugs to target these cells are not yet introduced. Considering the similarities of polyploid cells in regeneration and cancer, we hypothesized that zoledronic acid (ZA), an osteoclast-targeting agent, might be used to eliminate PGCCs. The 5637-bladder cancer cell line was treated with various doses of cisplatin to enrich polyploid cells and the efficacy of different concentrations of ZA in reducing this population was assessed.

Candidate MicroRNA Biomarkers in Lupus Nephritis: A Meta-analysis of Profiling Studies in Kidney, Blood and Urine Samples.

Context: Lupus nephritis (LN) is a kidney disease caused by systemic lupus erythematosus in which kidneys are attacked by the immune system. So far, various investigations have reported altered miRNA expression profiles in LN patients and different miRNAs have been introduced as biomarkers and/or therapeutic targets in LN. The aim of this study was to introduce a consensus panel of potential miRNA biomarkers by performing a meta-analysis of miRNA profiles in the LN patients.

Circulating β2 and α1 microglobulins predict progression of nephropathy in diabetic patients: a meta-analysis of prospective cohort studies.

Aims: To study the association of circulating β2 (B2M) and α1 microglobulins (A1M) with diabetic nephropathy (DN) progression, a meta-analysis was performed on the prospective cohort studies.

Methods: Up to October 2021, a comprehensive search of the PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases was performed. The primary outcome (progression of DN) was defined as a decrease in eGFR or the occurrence of end stage renal disease or DN-related mortality.

Discovering driver nodes in chronic kidney disease-related networks using Trader as a newly developed algorithm.

Thanks to the advances in the field of computational-based biology, a huge volume of disease-related data has been generated so far. From the existing data, the disease-related protein-protein interaction (PPI) networks seem to yield effective treatment plans due to the informative/systematic representation of diseases. Yet, a large number of previous studies have failed due to the complex nature of such disease-related networks.

Olfactory receptors contribute to progression of kidney fibrosis.

Olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are shown to be expressed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis.

A deep learning approach to predict inter-omics interactions in multi-layer networks.

Background: Despite enormous achievements in the production of high-throughput datasets, constructing comprehensive maps of interactions remains a major challenge. Lack of sufficient experimental evidence on interactions is more significant for heterogeneous molecular types. Hence, developing strategies to predict inter-omics connections is essential to construct holistic maps of disease.

Systems biology and machine learning approaches identify drug targets in diabetic nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, has become a massive global health burden. Despite considerable efforts, the underlying mechanisms have not yet been comprehensively understood. In this study, a systematic approach was utilized to identify the microRNA signature in DN and to introduce novel drug targets (DTs) in DN.

Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study.

Background: Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis and a serious health concern worldwide; though still the underlying molecular mechanisms of IgAN are yet to be known and there is no efficient treatment for this disease. The main goal of this study was to explore the IgAN underlying pathogenic pathways, plus identifying the disease correlated modules and genes using the weighted gene co-expression network analysis (WGCNA) algorithm.

Results: GSE104948 dataset (the expression data from glomerular tissue of IgAN patients) was analyzed and the identified differentially expressed genes (DEGs) were introduced to the WGCNA algorithm for building co-expression modules.

Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double-blinded clinical trial.

Background: This study aimed to investigate the effect of melatonin supplementation on endothelial function in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: This is an analysis of the MeHR trial, a randomized double-blinded placebo-controlled clinical trial with two parallel arms of 1:1. Oral 10 mg melatonin tablets or placebo was administered for 24 weeks.

Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies.

Aim: Diabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN.

Optimization of Mouse-on-Mouse Immunohistochemistry by Utilizing Fluorescent-dye Conjugated Secondary Anti-Mouse Antibody.

The application of mouse monoclonal antibody for immunostaining the mouse tissues results in a high rate of background noise because of the interaction of the secondary antibody with endogenous immunoglobulins and other immune components. The most advised blocking strategy for the mouse-on-mouse immunostaining is the use of anti-mouse Fab fragments. Nevertheless, the commercial kits containing Fab fragment are costly and unavailable in many research laboratories.

Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents.

Background: IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN.

Inefficiency of SIR models in forecasting COVID-19 epidemic: a case study of Isfahan.

The multifaceted destructions caused by COVID-19 have been compared to that of World War II. What makes the situation even more complicated is the ambiguity about the duration and ultimate spread of the pandemic. It is especially critical for the governments, healthcare systems, and economic sectors to have an estimate of the future of this disaster.

versus models of kidney fibrosis: Time-course experimental design is crucial to avoid misinterpretations of gene expression data.

Background: models are common tools in nephrology research. However, their validity has rarely been scrutinized.

Materials And Methods: Considering the critical role of transforming growth factor (TGF)-β and hypoxia pathways in kidney fibrosis, kidney-derived cells were exposed to TGF-β and/or hypoxic conditions and the expression levels of some genes related to these two signaling pathways were quantified in a time-course manner.

Cancer regeneration: Polyploid cells are the key drivers of tumor progression.

In spite of significant advancements of therapies for initial eradication of cancers, tumor relapse remains a major challenge. It is for a long time known that polyploid malignant cells are a main source of resistance against chemotherapy and irradiation. However, therapeutic approaches targeting these cells have not been appropriately pursued which could partly be due to the shortage of knowledge on the molecular biology of cell polyploidy.

Effect of melatonin on heart failure: design for a double-blinded randomized clinical trial.

Aims: Current studies indicate that melatonin can counteract renin-angiotensin-aldosterone system and sympathetic over activity in heart failure (HF) and might have a protective and repairing effect on cardiovascular injuries, skeletal muscle weakness, and metabolic abnormalities, which are common pathological processes in patients with HF. The MeHR trial (Melatonin for Heart Failure with Reduced Ejection Fraction) aims to evaluate the effect of oral melatonin on myocardial, skeletal muscle, and metabolic dysfunctions in HF, which leads to lower quality of life and increased morbidity and mortality in these patients.

Methods And Results: This is a double-blind randomized clinical trial with two parallel arms of 1:1 allocation, which recruits 90 outpatients with HF with reduced ejection fraction.