Biology subjects

Ghorbani, M.

Publications and source records attributed to Ghorbani, M..

12 recordsLinked to original sources

bioRxiv2025

Identifying Molecular Determinants and Therapeutic Targets in Luminal B Breast Cancer: A Systems Biology Approach

Luminal B breast cancer (LBBC) is on the rise worldwide, with both incidence and mortality rates steadily increasing. Early detection proves difficult due to its aggressive characteristics, most notably its heightened proliferation rate and the complex interplay of molecular biomarkers, particularly in more advanced stages. In the present study, we conducted an in silico analysis of LBBC cell lines using the Gene Expression Omnibus (GEO) microarray dataset, which includes 30 LBBC and 11 normal samples. Differentially expressed genes (DEGs) were identified using RStudio. A series of analyses, including cancer data interrogation via pan-cancer analysis, eXpression2Kinases (X2K), and the Cancer Dependency Map (DepMAP), was carried out to elucidate the underlying signaling pathways, transcription factors (TFs), and kinases, as well as to perform stemformatics analysis. Protein-protein interaction (PPI) networks were reconstructed using STRING and Cytoscape, enabling the identification of co-expressed and hub genes through the cytoHubba plug-in. Of note, FGF2, EGFR, ADIPOQ, LIPE, MET, IGF1, FGF1, EGF, FGF7, and PPARG were identified as the top 10 driver genes; RELA, PPARG, CTCF, EGR1, and NFE2L2 were detected as predominant TFs in LBBC; and CDK1, CDK2, MAPK3, CSNK2A1, and MAPK14 were identified as potential biomarkers through hub gene clustering. Further analysis indicated hsa-mir-221-3p and hsa-mir-29a-3p as key miRNAs targeting LBBC-related genes. Collectively, our findings highlighted LBBC-associated genes, TFs, miRNAs, and pathways as prospective biomarkers, providing insights into LBBC diagnosis and therapeutic approaches.

bioinformatics↗

bioRxiv2025

The effects of mindfulness on working memory: a systematic review and meta-analysis

ObjectivesMindfulness is a promising health intervention, showing potential effects on cognitive functions like memory. Despite evidence suggesting mindfulness improves working memory, inconsistencies in results and methodologies prevent definitive conclusions. This meta-analysis examines the effects of mindfulness interventions on working memory across clinical and healthy populations, and various age groups. MethodsA systematic search for relevant English and Persian articles was conducted in WOS, Scopus, PsycINFO, and PubMed databases, along with nine meta-analyses up to February 2023. Included studies consisted of randomized controlled trials (RCTs), controlled trials (CTs), and single-group studies. Overall, 29 studies with 2076 participants aged 5-85 years were analyzed. ResultsMindfulness interventions demonstrated a medium effect size on working memory: RCT two-group studies (Hedges g = 0.438, p < 0.001), CT two-group studies (Hedges g = 0.385, p < 0.005), and single-group studies (Hedges g = 0.583, p < 0.001). These findings confirm the effectiveness of mindfulness interventions in improving working memory. ConclusionsMindfulness interventions exhibit promising effects on working memory. However, further primary research, particularly rigorous RCTs, is needed to better understand their impacts on clinical versus healthy populations and across diverse age groups.

neuroscience↗

bioRxiv2024

Genderized Gut and Oral Microbiome Shifts: Uncovering Sex-Specific Dysbiosis in Pancreatic Cancer

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, responsible for approximately 466,000 deaths globally in 2020. Its incidence increases by about 1% annually, with a higher occurrence in males than females. While differences in immune responses and tumor biology between sexes have been explored, the role of the microbiome in gender-specific PDAC progression is still unclear. Investigating these differences could offer crucial insights for personalized treatment strategies for males and females. MethodsThis study reanalyzed oral and gut microbiome data from BioProject: PRJNA832909, comprising 191 samples from PDAC patients and healthy controls. Using shotgun metagenomic sequencing, we examined gender-specific bacterial signatures. Alpha diversity (richness) and beta diversity (community composition) were analyzed. Differentially abundant bacterial taxa were identified via LEfSe, and gender-specific bacterial panels were validated using CombiROC. ResultsAlpha diversity analysis revealed significant differences in microbial richness, particularly between male and female PDAC patients and their healthy controls. Beta diversity demonstrated distinct microbial shifts between the PDAC and control groups across genders. LEfSe identified several pathogenic bacteria contributing to gender-specific dysbiosis, including Streptococcus, Fusobacterium, and Prevotella. Shared and sex-specific bacterial species in PDAC were highlighted through Venn diagram analysis. CombiROC validated the predictive ability of these bacterial markers, with AUC values exceeding 0.90 for both sexes. ConclusionThis study uncovered gender-specific microbial patterns in PDAC patients, potentially influenced by sex-specific immune responses. These findings provide important insights into the progression of PDAC and support sex-targeted diagnostic and therapeutic interventions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/616338v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@4b1d97org.highwire.dtl.DTLVardef@183c267org.highwire.dtl.DTLVardef@1500547org.highwire.dtl.DTLVardef@8a854c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Chlorpromazine inhibits EAG1 channels by altering the coupling between the PAS, CNBH and pore domains

EAG1 depolarization-activated potassium selective channels are important targets for treatment of cancer and neurological disorders. EAG1 channels are formed by a tetrameric subunit assembly with each subunit containing an N-terminal Per-Arnt-Sim (PAS) domain and C-terminal cyclic nucleotide-binding homology (CNBH) domain. The PAS and CNBH domains from adjacent subunits interact and form an intracellular tetrameric ring that regulates the EAG1 channel gating, including the movement of the voltage sensor domain (VSD) from closed to open states. Small molecule ligands can inhibit EAG1 channels by binding to their PAS domains. However, the allosteric pathways of this inhibition are not known. Here we show that chlorpromazine, a PAS domain small molecule binder, alters interactions between the PAS and CNBH domains and decreases the coupling between the intracellular tetrameric ring and the pore of the channel, while having little effect on the coupling between the PAS and VSD domains. In addition, chlorpromazine binding to the PAS domain did not alter Cole-Moore shift characteristic of EAG1 channels, further indicating that chlorpromazine has no effect on VSD movement from the deep closed to opened states. Our study provides a framework for understanding global pathways of EAG1 channel regulation by small molecule PAS domain binders.

biophysics↗

bioRxiv2023

The reuniens nucleus of the thalamus facilitates hippocampo-cortical dialogue during sleep

Memory consolidation during sleep depends on the interregional coupling of slow waves, spindles, and sharp wave-ripples (SWRs), across the cortex, thalamus, and hippocampus. The reuniens nucleus of the thalamus, linking the medial prefrontal cortex (mPFC) and the hippocampus, may facilitate interregional coupling during sleep. To test this hypothesis we used intracellular, extracellular unit and local field potential recordings in anesthetized and head restrained non-anesthetized cats as well as computational modelling. Electrical stimulation of the reuniens evoked both antidromic and orthodromic intracellular mPFC responses, consistent with bidirectional functional connectivity between mPFC, reuniens and hippocampus in anesthetized state. The major finding obtained from behaving animals is that at least during NREM sleep hippocampo-reuniens-mPFC form a functional loop. SWRs facilitate the triggering of thalamic spindles, which later reach neocortex. In return, transition to mPFC UP states increase the probability of hippocampal SWRs and later modulate spindle amplitude. During REM sleep hippocampal theta activity provides periodic locking of reuniens neuronal firing and strong crosscorrelation at LFP level, but the values of reuniens-mPFC crosscorrelation was relatively low and theta power at mPFC was low. The neural mass model of this network demonstrates that the strength of bidirectional hippocampo-thalamic connections determines the coupling of oscillations, suggesting a mechanistic link between synaptic weights and the propensity for interregional synchrony. Our results demonstrate the presence of functional connectivity in hippocampo-thalamo-cortical network, but the efficacy of this connectivity is modulated by behavioral state. Impact StatementThe nucleus reuniens of the thalamus play a central role in synchronizing the mPFC-hippocampal network during sleep and integrates converging activity from hippocampal and mPFC oscillations.

neuroscience↗

bioRxiv2022

Deep attention based variational autoencoder for antimicrobial peptide discovery

Antimicrobial peptides (AMPs) have been proposed as a potential solution against multiresistant pathogens. Designing novel AMPs requires exploration of a vast chemical space which makes it a challenging problem. Recently natural language processing and generative deep learning have shown great promise in exploring the vast chemical space and generating new chemicals with desired properties. In this study we leverage a variational attention mechanism in the generative variational autoencoder where attention vector is also modeled as a latent vector. Variational attention helps with the diversity and quality of the generated AMPs. The generated AMPs from this model are novel, have high statistical fidelity and have similar physicochemical properties such as charge, hydrophobicity and hydrophobic moment to the real to the real antimicrobial peptides.

bioinformatics↗

bioRxiv2021

Enhancement of hippocampal-thalamocortical temporal coordination during slow-frequency long-duration anterior thalamic spindles

Temporal nesting of cortical slow oscillations (SO), thalamic spindles and hippocampal ripples indicates the succession of regional neuronal interactions required for memory consolidation. However how the thalamic activity during spindles organizes hippocampal dynamics remains largely undetermined. We analyzed simultaneous recordings of anterodorsal thalamus and CA1 in mice to determine the contribution of thalamic spindles in cross-regional synchronization. Our results indicated that temporal hippocampo-thalamocortical coupling were more enhanced during slower and longer thalamic spindles. Additionally, spindles occurring closer to SO trough were more strongly coupled to ripples. We found that the temporal association between CA1 spiking/ripples and thalamic spindles was stronger following spatial exploration compared to baseline sleep. We further developed a hippocampal-thalamocortical model to explain the mechanism underlying the duration and frequency-dependent coupling of thalamic spindles to hippocampal activity. Our findings shed light on our understanding of the functional role of thalamic activity during spindles on multi-regional information transfer.

neuroscience↗

bioRxiv2021

Replicative senescence dictates the emergence of disease-associated microglia and contributes to Abeta pathology

The sustained proliferation of microglia is a key hallmark of Alzheimers disease (AD), accelerating its progression. Here, we sought to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesising that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We found that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterised by increased {beta}gal activity, a senescence-associated transcriptional signature and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. Prevention of early microglial proliferation hindered the development of senescence and DAM, impairing the accumulation of A{beta} and associated neuritic damage. Overall, our results support that excessive microglial proliferation leads to the generation of senescent DAM, which contribute to early A{beta} pathology in AD.

neuroscience↗

bioRxiv2020

A comprehensive investigation of colorectal cancer progression, from the early to late-stage, a systems biology approach

Colorectal cancer is a widespread malignancy with a concerning mortality rate. It could be curable at the first stages, but the progress of the disease and reaching to the stage-4 could make shift the treatments from curative to palliative. In this stage, the survival rate is meager, and therapy options are limited. The question is, what are the hallmarks of this stage and what genes are involved? What mechanism and pathways could drive such a malign shift from stage-1 to stage-4? In this study, first we identified the core modules for both the stage-1 and stage-4 which four of them have a significant role in stage-1 and two of them have a role in stage-4. Then we investigated the gene ontology and hallmarks analysis for each stage. According to the results, the immune-related process, especially interferon-gamma, impacts stage-1 in colorectal cancer. Concerning stage-4, extracellular matrix ontologies, and metastatic hallmarks are in charge. At last, we performed a differentially expressed gene analysis of stage-4 vs. stage-1 and analyzed their pathways which reasonably undergone a hypo/hyperactivity or being abnormally regulated through the cancer progression. We found that lncRNA in canonical WNT signaling and colon cancer has the most significant pathways, followed by WNT signaling, which means that these pathways may be the driver for the development from early-stage to late-stage. Of these lncRNAs, we had two upregulated kind, H19, and HOTAIR, which both can be involved and mediate metastasis and invasion in colorectal cancer.

systems biology↗

bioRxiv2020

Combination of arsenic trioxide epigallocatechin-3-gallate and Resveratrol synergistically suppresses the growth and invasion in Brain tumor cell lines

The glioblastoma multiform has some properties including rapid growth, invasion, treatment resistance, and recurrence. Therefore, new therapies need to be developed that can be approved for using in patients. The previous study showed Arsenic Trioxide inhibits aggressive behavior in glioblastoma cells. Also, (-)-epigallocatechin-3-gallate prevents cellular proliferation, and invasion in multiple glioma cells. Resveratrol decreases cellular proliferation, induces cell death, and impaired the invasiveness of glioma cells. Combination therapy to inhibit cancer cells may have important clinical implications. Therefore, to assess the combination therapy of 2M Arsenic trioxide, 100M EGCG, and 100M Resveratrol, we examined the metabolic activity, colony formation, media pH, cell proliferation, Caspase 3 activity, and gene expression analysis of BCL2, Caspase 3, MMP2, MMP9, CA9, u-PA, u-PAR, and Cathepsin B genes in apoptosis and invasion by both quantitative PCR experiments and Western blot assay. Systems biology tools also were used to obtain, the related network, involved pathways, and identifying the key genes in our selected criteria. The results of the study confirmed that the combined therapy prevents cell proliferation and induces of apoptosis in the Brain tumor cell lines including: U87-MG, A-172, and 1321N1. Furthermore, over-expression of caspase-3 and down-regulation of BCL-2, MMP-2, and MMP-9 confirmed that combination therapy leads to induces apoptosis and decreases invasion. Nevertheless, the lowering of pharmacological doses and improving therapeutic efficacy through combination therapy may provide advantages to treat resistance cancer cells with lower side effects. Finally, the results might suggest new modality for Glioblastoma treatment.

cancer biology↗

bioRxiv2020

Exploring dynamics and network analysis of spike glycoprotein of SARS-COV-2

The ongoing pandemic caused by coronavirus SARS-COV-2 continues to rage with devastating consequences on human health and global economy. The spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all current antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein, we performed microsecond-long MD simulation in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the spike trimer. Role of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis, where the high betweenness centrality of glycans at the apex revealed their importance and function in the glycan shield. Microdomains of glycans were identified featuring a high degree of intra-communication in these microdomains. An antibody overlap analysis revealed the glycan microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Overall, the results of this study provide detailed understanding of the spike glycan shield, which may be utilized for therapeutic efforts against this crisis.

biophysics↗

bioRxiv2020

Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations

The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virions surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious.

biophysics↗