Biology subjects

Hasanuzzaman, M.

Publications and source records attributed to Hasanuzzaman, M..

5 recordsLinked to original sources

bioRxiv2026

Chemotherapy-Induced Oral Mucosal Injury Is Defined by p53 Activation, Cell Cycle Arrest and Diverse Epithelial Progenitor Dynamics

Chemotherapy-induced oral mucositis is a common and debilitating complication, yet the mechanisms underlying oral mucosa injury and repair remain poorly defined. Using a mouse model of 5-fluorouracil (5-FU)-induced mucositis, we define gene networks and oral mucosal cellular landscape dynamics in response to chemotoxic stress. We show that 5-FU-induced epithelial atrophy is driven primarily by cell cycle arrest rather than apoptosis, despite concurrent activation of p53-dependent transcriptional programs linked to both cell fates within individual cells. Relative to intestine, the recovering oral mucosa exhibits a more effective cell cycle checkpoint response and uniquely undergoes metabolic reprogramming toward lipid oxidation. Single-cell RNA sequencing revealed putative epithelial progenitor populations with distinct responses to chemotherapy, including chemoresistant cells with a p53- and AP-1 complex gene signature, reminiscent of lung transitional cell states. These findings define diverse progenitor dynamics and p53-driven responses as key determinants of oral mucosal injury and repair following chemotherapy.

cell biology↗

bioRxiv2026

Integrated physiological performance and Nax1-mediated sodium exclusion reveal mechanisms of salinity tolerance in spring wheat (Triticum aestivum L.)

Soil salinity is a rapidly intensifying abiotic stress that significantly limits wheat productivity, particularly in coastal and irrigated agroecosystems. Although sodium (Na+) ion exclusion has been recognized as a key tolerance mechanism, the integration of physiological performance with Nax1-mediated molecular regulation among regionally adapted wheat genotypes remains insufficiently characterized. The present study aimed to dissect salinity tolerance by combining hydroponic phenotyping, multivariate trait analysis, molecular marker profiling, and quantitative expression analysis of the Na+ ion transporter gene Nax1. Seventeen spring wheat genotypes were evaluated under four salinity levels (0.0, 10, 12, and 14 dS m-{superscript 1}). Germination and survival rate, shoot and root growth, and biomass accumulation were measured. Principal component analysis (PCA) and hierarchical clustering were performed to classify genotypes, while SSR (simple sequence repeat) and Nax-linked markers assessed genetic diversity. Relative Nax1 expression was quantified using qRT-PCR (quantitative real-time polymerase chain reaction). Salinity significantly reduced germination, survival, elongation, and biomass, with strong genotype-dependent variation. Multivariate analyses clearly separated tolerant and sensitive genotypes, with biomass retention and survival contributing most to total variation. Marker analysis revealed moderate genetic polymorphism. Notably, tolerant genotypes exhibited 3-6-fold induction of Nax1 under severe salinity, positively correlating with biomass maintenance. These findings demonstrate that salinity tolerance in wheat is associated with coordinated physiological resilience and enhanced Nax1-mediated Na ion exclusion, thereby advancing mechanistic understanding and supporting molecular-assisted breeding for salt-affected environments.

plant biology↗

bioRxiv2024

Exploring Harmala Alkaloids as Novel Antimalarial Agents against Plasmodium falciparum through Bioinformatics Approaches

Malaria, caused by the Plasmodium falciparum, remains a significant global health challenge, with Plasmodium falciparum accounting for approximately 50% of cases and posing a considerable threat. Despite advances in control measures, malaria continues to cause an estimated one million deaths annually. The complex lifecycle of P. falciparum, involving both vertebrate hosts and Anopheles mosquitoes, complicates eradication efforts. The parasites resistance to existing antimalarial drugs, along with medication toxicity, necessitates innovative therapeutic approaches. Recent research has revealed that harmine, an alkaloid produced by an endophytic gut bacterium of Anopheles mosquitoes, can impede the transmission of the malarial parasite to humans by inhibiting a crucial life stage. This study investigates harmala alkaloids, sourced from plants and bacteria such as Peganum harmala, as potential alternatives to conventional antimalarial drugs. Notably, harmine and harmaline have shown promising antimalarial activity by inhibiting the essential enzyme protein kinase 4 (PK4), which is vital for the parasites survival. These compounds exhibit lower toxicity, effectively inhibiting both the blood stage growth and transmission of the parasite. Using in silico methodologies, including ADME analysis, molecular docking, MD simulation, and toxicity analysis, this study identifies harmala alkaloids as potential inhibitors against crucial P. falciparum proteins. Targeting proteins essential for the parasites survival, similar to established drugs like pfCRT protein, lays the foundation for developing effective antimalarial treatments. The comprehensive screening of harmala alkaloid molecules opens avenues for the pharmaceutical industry to tackle challenges related to drug resistance and toxicity, offering a promising route for the biorational management of malaria.

bioinformatics↗

bioRxiv2023

Vascular and neural transcriptomics reveal stage-dependent pathways to inflammation and cognitive dysfunction in a rat model of hypertension

Chronic arterial hypertension causes cerebral microvascular dysfunction and doubles dementia risk in aging. However, cognitive health preservation by therapeutic blood pressure lowering alone is limited and depends on disease duration, the degree of irreversible tissue damage and whether microvascular function can be restored. This study aimed to understand molecular and cellular temporo-spatial pathomechanisms in the course of hypertension. We investigated the effects of initial, early chronic and late chronic hypertension in the frontal brain of rats by applying behavioral tests, histopathology, immunofluorescence, FACS, microvascular/neural tissue RNA sequencing as well as 18F-FDG PET imaging. Chronic hypertension caused frontal brain-specific behavioral deficits. Our results highlight stage-dependent responses to continuous microvascular stress and wounding by hypertension. Early responses included a fast recruitment of activated microglia to the blood vessels, immigration of peripheral immune cells, blood-brain-barrier leakage and an energy-demanding hypermetabolic state. Vascular adaptation mechanisms were observed in later stages and included angiogenesis and vessel wall strengthening by upregulation of cellular adhesion molecules and extracellular matrix. Additionally, we identified late chronic accumulation of Igfbp-5 in the brains of hypertensive rats, which is also a signature of Alzheimers dementia and attenuates protective Igf-1 signaling. Our study advances the knowledge of involved pathomechanisms and highlights the stage-dependent nature of hypertensive pathobiology. This groundwork might be helpful for basic and clinical research to identify stage-dependent markers in the human disease course, investigate stage-dependent interventions besides blood pressure lowering and better understand the relationship between poor vascular health and neurodegenerative diseases.

neuroscience↗

bioRxiv2019

Unbiased metagenomic sequencing for pediatric meningitis in Bangladesh reveals neuroinvasive Chikungunya virus outbreak and other unrealized pathogens

The disease burden due to meningitis in low and middle-income countries remains significant and failure to determine an etiology impedes appropriate treatment for patients and evidence-based policy decisions for populations. Broad-range pathogen surveillance using metagenomic next-generation sequencing (mNGS) of RNA isolated from cerebral spinal fluid (CSF) provides an unbiased assessment for possible infectious etiologies. In this study, our objective was to use mNGS to identify etiologies of pediatric meningitis in Bangladesh.\n\nWe conducted a retrospective case-control mNGS study on CSF from patients with known neurologic infections (n=36), idiopathic meningitis (n=25), without infection (n=30) and six environmental samples collected between 2012-2018. Using an open-access, cloud-based bioinformatics pipeline (IDseq) and machine learning, we identified potential pathogens which were confirmed through qPCR and Sanger sequencing. These cases were followed-up through phone/home-visits. The CSF samples were collected from children with WHO-defined meningeal signs during prospective meningitis surveillance at the largest pediatric referral hospital in Bangladesh.\n\nThe 91 participants (42% female) ranged in age from 0-160 months (median: 9 months). In samples with known infectious causes of meningitis and without infections (n=66), there was 83% concordance between mNGS and conventional testing. In idiopathic cases (n=25), mNGS identified a potential etiology in 40% (n=10), including bacterial and viral pathogens. There were three instances of neuroinvasive Chikungunya virus (CHIKV). The CHIKV genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause systemic illness in 2017. CHIKV qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital (n=472) revealed 17 additional CHIKV meningitis cases. Orthogonal molecular confirmation of each mNGS-identified infection, case-based clinical data, and follow-up of patients substantiated the key findings.\n\nUsing mNGS, we obtained a microbiological diagnosis for 40% of idiopathic meningitis cases and identified a previous unappreciated pediatric CHIKV meningitis outbreak. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis and facilitate informed policy decisions.

genomics↗