Biology subjects

Javan, M.

Publications and source records attributed to Javan, M..

4 recordsLinked to original sources

bioRxiv2026

A Collagen-Based 3D Microtissue Platform Preserves Structural, Molecular, and Therapeutic Heterogeneity in Ovarian Cancer

Background: Ovarian cancer is comprised of biologically diverse tumour histotypes that are difficult to represent using conventional two-dimensional (2D) culture. These systems lack the tissue organization and extracellular matrix interactions found in native tumours. We developed a type I collagen-based three-dimensional (3D) microtissue model to determine whether a tumor supportive matrix environment could maintain key characteristics of different ovarian cancer histotypes. Methods: 3D collagen microtissues were generated using five ovarian cancer cell lines: OVCAR3, SNU119, KURAMOCHI, OVTOKO, and SKOV3. Long-term growth, viability, and morphology were assessed using quantitative growth analysis, confocal microscopy, and longitudinal bright-field imaging. Tumour architecture and histotype-associated phenotypes were evaluated by hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). Therapeutic responses to carboplatin, paclitaxel, olaparib, and niraparib were compared between 3D microtissues and corresponding 2D monolayer cultures. Results: All five models remained viable and showed sustained growth within the collagen scaffold, supported by growth-curve analysis and confocal imaging. Despite being maintained in the same matrix environment, the models developed distinct 3D architectures. OVCAR3, KURAMOCHI and SNU119 formed prominent papillary-like structures of high-grade serous carcinoma (HGSC), while OVTOKO and SKOV3 displayed distinct surface-associated growth patterns of clear cell and endometrioid ovarian carcinomas, respectively. H&E analysis confirmed these architectural differences, and IHC profiling demonstrated preservation of selected histotype-associated features, including distinct PAX8, WT1, and p53 expression patterns. Therapeutic responses varied across cell lines and treatments, with 3D microtissues generally maintaining greater viability following treatment than corresponding 2D cultures. These findings indicate that the collagen environment supports long-term tumour growth while preserving ovarian cancer histotype specific structural, molecular, and therapeutic heterogeneity. Conclusions: The collagen-based microtissue platform preserved structural, molecular, and therapeutic heterogeneity across distinct ovarian cancer models within a shared 3D environment. By maintaining tumour-associated architecture, distinct immunophenotypic features, and model-specific therapeutic responses, the platform captures key aspects of ovarian cancer biology that are not adequately represented in conventional 2D culture. These findings support its use as a physiologically relevant system for investigating ovarian cancer heterogeneity, tumour-matrix interactions, and therapeutic response.

cancer biology↗

bioRxiv2024

Olfactory bulb stimulation mitigates Alzheimer-like disease progression

BackgroundDeep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimers disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits. AimsOur study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (A{beta}) AD model rats. MethodsMale Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimers-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by evaluations of histological, behavioral, and local field potential signal processing. ResultsOB stimulation counteracted A{beta} plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task. ConclusionThis preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.

neuroscience↗

bioRxiv2021

Hotair and Malat1 Long Noncoding RNAs regulate Bdnf Expression and Oligodendrocyte Precursor Cells Differentiation

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cells survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression. Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the neurodegenerative disorders pathogenesis and designing more effective treatments.

neuroscience↗

bioRxiv2021

Fingolimod Regulates BDNF-AS and HOTAIR Expression in Multiple Sclerosis Patients

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is expressed by neurons and glial cells in the central nervous system (CNS). In the CNS, BDNF is responsible for neuroprotection and neurogenesis. Recent studies showed that the Fingolimod, the first oral medicine for relapsing-remitting multiple sclerosis (RR-MS), induces BDNF expression. Besides, It is well demonstrated that long noncoding RNAs (lncRNAs) have a pivotal role in gene regulation. This study is mainly focused on how Fingolimod treatment plays role in BDNF regulation in coordination with lncRNAs. An in-silico study was performed to predict BDNF-regulatory candidate lncRNAs using online tools. Then, the expression of BDNF-related lncRNAs was analyzed in patients with relapsing-remitting multiple sclerosis (RRMS) at baseline and after three months of Fingolimod treatment. Based on in silico results, two lncRNAs with potential regulatory functions on the BDNF including, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX Transcript Antisense RNA (HOTAIR), and also natural antisense of BDNF were selected. Fingolimod treatment increased the expression of HOTAIR lncRNA; however, the BDNF antisense RNA (BDNF-AS) expression was reduced dramatically. Furthermore, the results indicate a positive correlation between HOTAIR and MALAT1 lncRNAs and BDNF. Also, after Fingolimod treatment, the patients EDSS scores were declined or remained unchanged, indicating disease hindrance by Fingolimod therapy. Altogether, fingolimod exerts protective roles in RRMS patients probably by the mediation of HOTIAR and BDNF-AS lncRNAs.

genetics↗