Biology subjects

Mohammad, S.

Publications and source records attributed to Mohammad, S..

6 recordsLinked to original sources

bioRxiv2026

Nanoarchaeosome-mediated epirubicin delivery induces sustained intracellular stress and suppresses adaptive glioblastoma phentoypes

Although anthracyclines such as epirubicin are potent DNA-damaging agents, their application in glioblastoma (GBM) is limited by poor intracellular penetration, lack of durable responses and rapid emergence of adaptive tumor phenotypes. Here, we demonstrate that nanoarchaeosome-mediated delivery of epirubicin (NanoEpi) enables functional reprogramming of GBM survival under therapeutic stress. Nanoarchaeosomes composed of archaeal ether lipids exhibited high encapsulation efficiency ([~]96%) and nanoscale stability. Although both Epi and NanoEpi showed similar bulk uptake, both in established (U251-MG) and patient-derived (Gli5) glioblastoma models, NanoEpi induced significantly greater cytotoxicity than free epirubicin, indicating enhanced intracellular drug engagement. NanoEpi induced enhanced DNA damage, elevated reactive oxygen species, and mitochondrial depolarisation, leading to cytoskeletal collapse. In 3D gliomasphere systems, NanoEpi showed improved penetration and sustained retention, resulting in suppression of core viability and invasion. This correlates with its increased uptake by the lysosomes. Notably, even a transient exposure led to depletion of sphere-initiating capacity and complete loss of clonogenic recovery, indicating targeting of the stem-like compartment. This was accompanied by attenuation of MMP-2/9 activity and reduced angiogenic signalling in a chorioallantoic membrane model. These findings establish nanoarchaeosomes as a robust lysosome-directed delivery platform that extends beyond passive drug transport to sustain intracellular stress and suppress invasive adaptation and limit recurrence in GBM.

cancer biology↗

bioRxiv2026

Evaluating image upsampling strategies for downstream microscopy image classification

Microscopy images are frequently downsampled due to acquisition and computational constraints, requiring reconstruction before downstream analysis. While super-resolution (SR) is typically assessed using pixel-level fidelity metrics, its impact on deep learning (DL) model behavior remains insufficiently understood. In this work, we present a study that examines how different upsampling strategies affect image quality and classification performance. Using the BloodMNIST dataset, we construct matched 224x224 datasets from 64x64 images via bicubic interpolation, SwinIR Classical, and SwinIR RealGAN DL SR models, alongside the original 224 ground-truth images. We evaluate reconstruction quality using the Structural Similarity Index Measure (SSIM) and Peak Signal-to-Noise Ratio (PSNR) scores and assess downstream classification performance using ResNet-50 and Vision Transformer models, with accuracy, macro-F1 score, and a confidence-aware metric, the area under the receiver operating curve for successful prediction (AUPR Success). Our results demonstrate that bicubic interpolation significantly degrades classification performance, whereas SR methods can recover class-relevant information, even better than the ground-truth data. These findings emphasize the importance of confidence-aware evaluation and unambiguous reporting of reconstruction pipelines in microscopy-based DL studies.

cell biology↗

bioRxiv2024

A humanized neuronal model system reveals key roles for manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics

Manganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinsons and Alzheimers disease. Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood. We established an induced pluripotent stem cells-derived midbrain neuronal system from SLC39A14, SLC39A8, and SLC30A10 patients to better understand the neuronal sequelae of Mn dysregulation. By integrating transcriptomic and functional approaches, we show that Mn dyshomeostasis leads to dysregulation of key cellular pathways that are crucial to normal neuronal function, including defects in mitochondrial bioenergetics, calcium signalling, endocytosis, and glycosylation, as well as cellular stress and early neurodegeneration. Our humanized model has enhanced understanding of the role of Mn in the human brain, and the consequences of both acquired and genetic disorders associated with Mn dysregulation. Better understanding of these underlying pathophysiological processes will identify potential targets for future therapeutic intervention.

neuroscience↗

bioRxiv2024

The Association between the JAK-STAT Pathway and Hypertension among Kenyan Women Diagnosed with Breast Cancer

BackgroundBreast cancer is the most common malignant tumor in women worldwide, and disproportionately affects Sub-Saharan Africa compared to high income countries. The global disease burden is growing, with Sub-Saharan Africa reporting majority of the cases. In Kenya, breast cancer is the most commonly diagnosed cancer, with an annual incidence of 7,243 new cases in 2022, representing 25.5% of all reported cancers in women. Evidence suggests that women receiving breast cancer treatment are at a greater risk of developing hypertension than women without breast cancer. Hypertension prevalence has been on the rise in SSA, with poor detection, treatment and control. The JAK-STAT signaling is activated in hormone receptor-positive breast tumors, leading to inflammation, cell proliferation, and treatment resistance in cancer cells. We sought to understand the association between the expression of JAK-STAT Pathway genes and hypertension among Kenyan women diagnosed with breast cancer. MethodsBreast tumor and non-tumor tissues were acquired from patients with a pathologic diagnosis of invasive breast carcinoma. RNA was extracted from fresh frozen tumor and adjacent normal tissue samples of 23 participants who had at least 50% tumor after pathological examination, as well as their corresponding adjacent normal samples. Differentially expressed JAK-STAT genes between tumor and normal breast tissues were assessed using the DESEq2 R package. Pearson correlation was used to assess the correlation between differentially expressed JAK-STAT genes and participants blood pressure, heart rate, and body mass index (BMI). Results11,868 genes were differentially expressed between breast tumor and non-tumor tissues. Eight JAK-STAT genes were significantly dysregulated (Log2FC [≥] 1.0 and an Padj [≤] 0.05), with two genes (CISH and SCNN1A) being upregulated. Six genes (TGFBR2, STAT5A, STAT5B, TGFRB3, SMAD9, and SOCS2) were downregulated. We identified STAT5A and SOCS2 genes to be significantly correlated with elevated systolic pressure and heart rate, respectively. ConclusionsOur study provides insights underlying the molecular mechanisms of hypertension among Kenyan women diagnosed with breast cancer. Understanding these mechanisms may help develop targeted treatments that may improve health outcomes of Kenyan women diagnosed with breast cancer. Longitudinal studies with larger cohorts will be needed to validate our results.

cancer biology↗

bioRxiv2022

A suberized exodermis is required for tomato drought tolerance

Plant roots integrate environmental signals and developmental programs using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates the entry and exit of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation, but we find that it is absent in the tomato endodermis during normal development. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here, we uncover genes driving exodermal suberization and describe its effects on drought responses in tomato, unravelling the similarities and differences with the paradigmatic Arabidopsis endodermis. Cellular resolution imaging, gene expression, and mutant analyses reveal loss of this program from the endodermis, and its co-option in the exodermis. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response. Controlling the degree of exodermal suberization could be a new strategy for breeding climate-resilient plants.

plant biology↗

bioRxiv2022

Fatty acid metabolism changes in association with neurobehavioral deficits in animal models of fetal alcohol spectrum disorders

Fetal alcohol spectrum disorders (FASD) show various behavioral problems due to prenatal alcohol exposure (PAE). Our previous study found significant changes in gene expressions linked to fatty acid metabolism in the brain of the PAE mouse model. Given the importance of fatty acids in normal brain functions and the contributions to neurodegenerative diseases, we hypothesized that the fatty acids changed by PAE contribute to neurobehavioral deficits in FASD. This study found an increase of palmitic acid and arachidonic acid in phospholipid compositions in the cerebral cortex of PAE at postnatal day 30. The increase of palmitic acid was consistent with the increase of the producing enzyme, fatty acid synthase (Fasn). The decrease of 26:6 fatty acid was also found in phospholipid. It is consistent with the increase of the Elongation of very long chain fatty acids protein 4 (ELOVL4) which uses 26:6 as a substrate for making very long chain fatty acids. However, there was no increase in the elongated products. Rather, we found an accumulation of the lipid droplets (LDs) in the PAE brain, suggesting changes in fatty acid metabolism that lead to the accumulation of excessive fatty acids. Although metabolic measurements, including plasma triglyceride level, were not affected by PAE, the abundance of fatty acid-related gut microbiota was altered. Interestingly, multi-omics association analysis revealed a potential contribution of the altered gut microbiota, primarily Ruminococcaceae that produces short chain fatty acid, to LD formation in the PAE brain and the behavioral problems, suggesting that the gut microbiome could serve as a tool to facilitate uncovering the brain pathophysiology of FASD and a potential target to mitigate neurobehavioral problems.

neuroscience↗