Biology subjects

Baig, S.

Publications and source records attributed to Baig, S..

7 recordsLinked to original sources

bioRxiv2026

Telomere Length as an Indicator of Lifestyle-Related Biological Aging in Hypertensive Adults: A Pilot Exploratory Study

BackgroundMultiple epidemiological studies have given a global perspective that hypertension leads to changes in telomere length (TL). This study aimed to investigate the association between leukocyte telomere length and lifestyle factors among individuals with hypertension, a family history of the disease and healthy controls. MethodsThis pilot exploratory cross-sectional study included 45 participants (n = 15 per group) divided into hypertensive, familial hypertensive, and control groups. Lifestyle behaviors were assessed using the FANTASTIC Lifestyle Checklist, evaluating domains such as physical activity, diet, sleep, and stress. Relative telomere length (T/S ratio) of leucocytes was measured from peripheral blood samples using quantitative real-time PCR (qPCR). Data were analyzed using SPSS software, with ANOVA, Kruskal-Wallis test, and multivariable linear regression applied for statistical analysis. ResultsRelative telomere length differed significantly among the study groups (p = 0.008), with hypertensive participants demonstrating the highest median telomere-to-single-copy gene (T/S) ratio (2.66), followed by familial hypertensive (1.25) and control participants (0.87). Total lifestyle scores also varied significantly across groups (p < 0.001), with hypertensive individuals exhibiting higher mean scores (77.07 {+/-} 5.59) than familial hypertensive (67.20 {+/-} 3.00) and control participants (67.07 {+/-} 5.97). A modest positive correlation was observed between total lifestyle score and relative telomere length (r = 0.329, p < 0.05), suggesting that healthier lifestyle behaviors in diagnosed hypertensive subjects following healthy lifestyles and regular medications were associated with longer telomeres. However, in multivariable linear regression analyses, lifestyle score, age, gender, hypertension status, and family history of hypertension were not independently associated with telomere length (all p > 0.05). ConclusionLifestyle scores were positively associated with telomeres, and significantly higher telomere ratios in hypertensive subjects suggest complex biological interactions that require further investigation through larger longitudinal studies in the target population.

Molecular Biology↗

bioRxiv2026

Traumatic brain injury has a lasting impact on hippocampal neurogenesis and Notch1 is involved in regulating this injury response

Traumatic brain injury (TBI) induces a series of neuropathological changes in the brain including neurogenesis, an important cellular response involved in brain repair and regeneration. TBI-enhanced neurogenesis in the dentate gyrus (DG) of the hippocampus is of particular importance due its contribution to learning and memory functions. In the neurogenic process, proliferation and differentiation of neural stem cells (NSCs) follow a well-characterized sequence controlled by many factors including Notch1, which plays essential roles in regulating NSC fate determination under physiological conditions in both developing and adult brains. Following TBI, the dynamic changes of NSCs and the involvement of Notch1 on their development at different stages post-injury are not fully characterized. In the current study, we examined the impact of TBI and Notch1 on NSCs proliferation, survival and neuronal differentiation. Utilizing transgenic mice with tamoxifen-induced GFP expression and Notch1 knock-out in nestin+ NSCs, we examined DG neurogenic response at acute, subacute and chronic stages following a moderate lateral fluid percussion injury. We found that TBI enhanced a proliferative response in the DG at the acute stage following injury; however, this injury response was abolished when Notch1 was conditionally deleted from nestin+ NSCs. We also found that injury and Notch1 deletion drove NSCs committing fate choice towards neuronal differentiation. The results of this study provides further knowledge regarding TBI-induced neurogenic response and Notch1 as the key regulating mechanism.

neuroscience↗

bioRxiv2025

Small tau aggregates exhibit disease-specific molecular profiles across tauopathies

Tauopathies are neurodegenerative diseases marked by pathological tau aggregation. While disease-specific folds of insoluble tau filaments have been established, it remains unclear whether the smaller, earlier species also differ across tauopathies. Here, we characterise these small tau aggregates from post-mortem brain of individuals with Alzheimers disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration, Picks disease, and healthy controls. Using two complementary single-molecule assays, we confirm that small tau aggregates vary in abundance, morphology, and post-translational modifications. AD features specific long, fibrillar-shaped aggregates enriched in phospho-epitopes, while PSP aggregates are shorter, round, and selectively phosphorylated at serine-356, a site we identify as correlating with markers of inflammation and apoptosis. Aggregate properties co-vary with cellular stress signatures and align with disease-specific seeding profiles, suggesting distinct pathological mechanisms. These findings suggest that small tau aggregates are not a shared intermediate, but instead encode disease-specific mechanisms, with potential as both biomarkers and therapeutic targets. Key pointsSmall tau aggregates show disease-specific signatures across tauopathies, differing in abundance, morphology, and post-translational modifications. Tau aggregates in AD show enhanced phosphorylation density and structural heterogeneity, including a distinct population of long fibrillar species detectable in the soluble fraction. Alzheimers disease is characterised by specific long, fibrillar-shaped tau aggregates enriched in disease-relevant phospho-epitopes. PSP features round pSer356-positive aggregates that correlate with apoptotic and inflammatory markers, suggesting a distinct mechanism of toxicity. Isoform-specific biosensor assays reveal divergent seeding behaviour: CBD shows strong 4R seeding, while PSP lacks seeding activity. Features of small aggregates co-vary with distinct patterns of gliosis and cell stress, suggesting disease-specific mechanisms of tau-mediated toxicity.

neuroscience↗

bioRxiv2024

Reprogramming Human Inflammatory Macrophages in Symptomatic Carotid Stenosis: Potential Mechanisms for Stabilisation of Atherosclerotic Carotid Plaques

BackgroundInflammation is a precursor to atherosclerotic plaque destabilisation, leading to ischaemic events such as stroke. Macrophage phenotypes can be altered by the microenvironment, and certain anti-inflammatory agents may, therefore, stabilise plaques and reduce the risk of recurrent ischaemic events. MethodsThirteen carotid plaques were obtained from stroke/ Transient Ischaemic Attack (TIA) patients undergoing carotid endarterectomy. An immunofluorescence stain was used to identify common macrophage markers (pan macrophage: CD68, pro-inflammatory: CD86, anti-inflammatory: MRC1), and a novel analysis technique was used to measure the prevalence of macrophage phenotypes in carotid plaques in relation to other histological features of instability. An in vitro model of human blood-derived macrophages was also developed to evaluate the effect of statins and glucocorticoids on macrophage-specific markers using RT-qPCR, Western Blot and immunofluorescence stain. The physiological effect of dexamethasone was further evaluated on macrophages and human carotid plaques cultured ex vivo. ResultsThe macrophage population (CD68+) in the carotid plaques was dominated by "double-positive" (CD86+MRC1+) macrophages (67.8%), followed by "M1-like" (CD86+MRC1-) (16.5%), "M2-like" (CD86-MRC1+) (8.7%) and "double-negative" (CD86-MRC1-) (7.0%) macrophages. M1-like macrophages were more prevalent in unstable plaque sections than stable ones (p=0.0022). Exposure to dexamethasone increased macrophage MRC1 gene expression in vitro and ex vivo. Dexamethasone also reduced Oxidised Low-Density Lipoprotein Receptor 1 (OLR1) gene and protein expression, leading to a decreased ox-LDL uptake in foam cell assays. This was, in turn, associated with reduced lipid uptake in macrophages, as shown by Oil Red O staining. ConclusionsHuman macrophages may be "switched" to a less inflammatory phenotype by exposure to clinically relevant concentrations of glucocorticoid, potentially mediated by a reduction in Oxidised LDL uptake. This effect was not observed following macrophage exposure to statins. Glucocorticoids may have a future role in preventing ischaemic events in patients with advanced atherosclerosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/598440v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@bb389borg.highwire.dtl.DTLVardef@18151b8org.highwire.dtl.DTLVardef@11c28a1org.highwire.dtl.DTLVardef@1af6acd_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA high prevalence (68% in this study) of carotid plaque macrophages express both pro-inflammatory (CD86) and anti-inflammatory (MRC1) markers. These may represent a novel macrophage population. C_LIO_LIHuman macrophages may be "reprogrammed" to a less inflammatory phenotype following exposure to glucocorticoids. C_LIO_LIDexamethasone increased MRC1 and decreased OLR1 expression in macrophages derived from human blood samples in vitro and in cells derived from cultured human carotid plaque tissue ex vivo. This was associated with reduced oxLDL uptake and reduced lipid accumulation in the macrophages. C_LIO_LIDexamethasone has the potential to stabilise carotid atherosclerotic plaques in humans. C_LI

cell biology↗

bioRxiv2023

Neutralisation of SARS-CoV-2 Omicron subvariants BA.2.86 and EG.5.1 by antibodies induced by earlier infection or vaccination

Highly mutated SARS-CoV-2 Omicron subvariant BA.2.86 emerged in July 2023. We investigated the neutralisation of isolated virus by antibodies induced by earlier infection or vaccination. The neutralisation titres for BA.2.86 were comparable to those for XBB.1 and EG.5.1, by antibodies induced by XBB.1.5 or BA.4/5 breakthrough infection or BA.4/5 vaccination.

immunology↗

bioRxiv2023

Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone

The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

neuroscience↗

bioRxiv2018

Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development

SummaryCancer stem cells are critical for cancer initiation, development, and resistance to treatments. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA-sequencing on 38 296 glioblastoma cells and 22 637 normal human fetal brain cells. Using an unbiased approach, we mapped the lineage hierarchy of the developing human brain and compared the transcriptome of each cancer cell to this roadmap. We discovered a conserved neural trilineage cancer hierarchy with glial progenitor-like cells at the apex. We also found that this progenitor population contains the majority of cancers cycling cells and is the origin of heterogeneity. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, unravels the origin of glioblastoma heterogeneity, and helps to identify cancer stem cell-specific targets.

cancer biology↗