Yousof Gheisari

Isfahan University of Medical Sciences

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates...

Target discovery is crucial in drug development, especially for complex chronic diseases. Recent advances in high-throughput technologies and the explosion of biomedical data have highlighted the potential of computational druggability prediction methods. However, most current methods rely on sequence-based features with machine learning, which oft...

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...

Background: Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods: Protein expression profiles of...

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...

A population of resistant multinucleated cells reside in the BM that serves as the common origin of stromal and hematopoietic lineages with a key role in tissue regeneration. Furthermore, this study underscores the contribution of adipocytes in BM reconstruction.

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 o...

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. Previo...

Background: Focal segmental glomerulosclerosis (FSGS) - a histologic pattern of injury in the glomerulus - is one of the leading glomerular causes of ESRD worldwide. Despite vigorous research, the underlying biological alterations causing FSGS remain to be understood. Studying the variations in gene expression profiles is one of the promising appro...

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 ce...

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. Hence, the construction o...

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 pathoge...

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...

ContextLupus 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 t...

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 primar...

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 multinuclear cells (LMCs) in long-term culture of bone marrow (BM) mesenchymal cells has been reported, the presence and characteristics of...

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 pathogen...

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 previ...

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...

Background Modern medicine is equipped with huge amounts of big biological datasets and a wide range of computational methods to understand the molecular events underlying complex disorders. The recent availability of omics data allows a holistic view towards the interactions of various biomolecule types. However, the constructed maps are static, i...

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 sy...

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 essentia...

Lupus nephritis (LN) is a kidney disease caused by systemic lupus erythematosus in which kidneys are attacked by the immune system. MiRNAs participate in the pathogenesis of LN as modulatory effectors in immune responses and nephrogenesis pathways. Despite the large number of miRNAs that are expressed deferentially, identifying the most suitable bi...

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)...

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 pathw...

Background Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods Protein expression profiles of kidn...

Despite enormous achievements in production of high throughput datasets, constructing comprehensive maps of interactions remains a major challenge. The 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 constr...

Background and Aims 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 biomar...

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 wa...

Background Tumor recurrence as a main cause of cancer death is a big barrier in cancer complete treatment. Various studies denote for 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 (PGC...

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 pat...

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 pat...

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 disaste...

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...

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 is remained to be more explored and still there is an urgent need for discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach wa...

Background: In vitro 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 o...

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 whic...

The olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are distributed 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...

The multidimensional destructions caused by Covid-19 have been compared to that of World War II. What makes the situation even more complicated is the ambiguity regarding the duration and the final size of the pandemic. It is critical especially for the governments, healthcare systems, and economic sectors to have an estimation of the future of thi...

Background and purpose: Stromal-derived factor (SDF)-1, a chemokine recruiting leucocytes and stem cells, plays an essential role in tissue regeneration. In a previous study, we have unexpectedly found that the expression of this chemokine declines following kidney ischemia reperfusion (IR). To explain this observation, a mathematical model was co...

Background: Despite huge efforts, the underlying molecular mechanisms of diabetic nephropathy (DN) are yet elusive, and holistic views have rarely been generated. Considering the complexity of DN pathogenesis, the integration of datasets from different molecular types to construct a multilayer map of DN can provide a comprehensive insight toward t...

Background: Acute kidney injury is a high-risk complication in a variety of clinical situations mostly due to ischemia-reperfusion (IR) injuries. The novel idea of remote ischemic preconditioning (rIPC) was proposed to prevent serious ischemia sequels. To address the controversy of previous reports, the current study was performed to assess the ef...

Many biological processes show switching behaviors in response to parameter changes. Although numerous surveys have been conducted on bifurcations in biological systems, they commonly focus on over-represented parts of signaling cascades, known as motifs, ignoring the multi-motif structure of biological systems and the communication links between t...

Macrophages play a key role in tissue regeneration by polarizing to different destinies and generating various phenotypes. Recognizing the underlying mechanisms is critical in designing therapeutic procedures targeting macrophage fate determination. Here, to investigate the macrophage polarization, a nonlinear mathematical model is proposed in whic...

The omics technologies provide an invaluable opportunity to employ a global view toward human diseases. However, the appropriate translation of big data to knowledge remains a major challenge. In this study, we have performed quality control assessments for 91 transcriptomics datasets deposited in gene expression omnibus database and also have eval...

Background Acute kidney injury is a common debilitating disease with no curative treatment. The recent development of big biological data is expected to expand our understanding of the disorder if appropriately analyzed to generate translational knowledge. We have here re-analyzed a time-course microarray data on mRNA expression of rat kidneys expo...

The transforming growth factor (TGF)‐β signaling pathway plays a key role in various cellular processes. However, insufficient knowledge about the complex and sometimes paradoxical functions of this pathway hinders its therapeutic targeting. In this study, the transcriptional profile of seven mediators and downstream elements of the TGF‐β pathway w...

High-throughput time-series data have a special value for studying the dynamism of biological systems. However, the interpretation of such complex data can be challenging. The aim of this study was to compare common algorithms recently developed for the detection of differentially expressed genes in time-course microarray data. Using different meas...

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage renal disease. Although imaging techniques are a means of accurate diagnosis when the cysts appear in the third or fourth decades of the patient's life, they are of little value for early diagnosis. Genetic tests are required for preimplant...

Cell therapy, a promising method for treatment of incurable diseases, has been moving fast from basic research laboratories to clinical practice in recent years. Defining clear and strict regulations for manufacturing of cell therapy products in clinical applications is the best way to give assurance to the public sector for safe usage, harmonizing...

Background Selection of stably expressing housekeeping genes (HKGs) is a crucial step in gene expression analysis. However, there are no universal HKGs for all experiments, and they should be determined by each biologic condition. The aim of this study was to detect appropriate HKGs for kidney cells cultured in long-term hypoxia. Materials and Met...

Objective Despite the huge efforts, chronic kidney disease (CKD) remains as an unsolved problem in medicine. Many studies have shown a central role for transforming growth factor beta-1 (TGFβ-1) and its downstream signaling cascades in the pathogenesis of CKD. In this study, we have reanalyzed a microarray dataset to recognize critical signaling pa...

Bone marrow mesenchymal stem cells (BM-MSCs) are commonly known as nonhematopoietic-nonendothelial cells based on in vitro expressed markers and properties. Despite the massive research on ex vivo expanded MSCs, their in vivo identity remains elusive. In this study, we report the existence of large multinuclear CD31 positive cells in the beginning...

Hematopoietic stem and progenitor cells (HPC) niche, consisting of HPC and their surrounding stromal components, is the fundamental unit for bone marrow (BM) tissue engineering. Previously mouse BM-derived cell complexes with HPC niche unit properties called "niche-like units" were isolated and characterized. The current study was aimed to evaluate...

Homing of stem cells to the sites of injury is crucial for tissue regeneration. Stromal derived factor 1 (SDF-1) is among the most important chemokines recruiting these cells. Unexpectedly, our previous experimental data on mouse models of acute kidney injury showed that SDF-1 has a declining trend following ischemic kidney insult. To describe this...

In spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critical signaling pathways related to diabetic nephropat...

Background Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals...

Background: Kidney failure is a debilitating disorder with limited treatment options. The kidney-protective effects of stem cells have been vastly investigated and promising results have been achieved with various sources of stem cells. However, in spite of beneficial effects on other disease models, the renoprotective potential of human cord bloo...

Although the unique role of hematopoietic stem cell (HSC) niche in hematopoiesis has long been recognized, unsuccessful isolation of intact niche units limited their in vitro study, manipulation and therapeutic application. We here isolated cell complexes based on size fractionation from mouse bone marrow (BM), characterized the derived cells, and...

The clinical application of mesenchymal stromal cells (MSC) faces several obstacles, such as the lack of a standard method for direct isolation as well as a low frequency and concern about the safety of their in vitro expansion. Although the density-gradient separation technique is used as the first step in most methods of MSC isolation to enrich m...

Recent findings have demonstrated that stem cells can differentiate into mature tissue when supplied with a niche containing factors identical to those in the normal developmental program. A niche for the development of an organ can be provided by xenotransplantation of a similar developing organ. However, this process has many technical, safety, a...

The therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in kidney failure has been examined in some studies. However, recent findings indicate that after transplantation, these cells home to kidneys at very low levels. Interaction of stromal derived factor-1 (SDF-1) with its receptor, CXCR4, is of pivotal importance in migration and...

During the last few years, the Islamic republic of Iran has consistently grown in nearly all scientific fields and achieved considerable success in producing science and developing technology. The Iranian government and scientific community have jointly started programs to support the creation of new scientific opportunities and technology platform...

Application of biomaterials in combination with stem cells is a novel tissue engineering approach to regenerate cartilage. The objective of this study was to investigate the potential of poly(vinyl alcohol)/polycaprolactone (PVA/PCL) nanofiber scaffolds seeded with rabbit bone marrow-mesenchymal stem cell (BM-MSC) for cartilage tissue engineering i...

The expression pattern and regulatory functions of microRNAs (miRNAs) are intensively investigated in various tissues, cell types and disorders. Differential miRNA expression signatures have been revealed in healthy and unhealthy tissues using high-throughput profiling methods. For further analyses of miRNA signatures in biological samples, we desc...

Bone marrow-derived mesenchymal stem cells (BM-MSC) have been widely used for cell therapy and tissue engineering purposes. However, there are still controversies concerning safety of application of these cells after in vitro expansion. Therefore, we aimed to investigate the characteristics of rabbit BM-MSC during long-term culture. In this study,...

Special features of mesenchymal stem cells (MSCs) have made them a popular tool in cell therapy and tissue engineering. Although mouse animal models and murine MSCs are common tools in this field, our understanding of the effect of in vitro expansion on the behavior of these cells is poor and controversial. In addition, in comparison to human, isol...