👤 Imran Kazmi

Huntington's Disease (HD) is a neurodegenerative ailment characterized by progressive motor, cognitive, and psychiatric decline, linked with mitochondrial dysfunction, oxidative stress, and neuroinflammation. Few effective treatments are available for Huntington's. Additionally, the therapeutic effects of natural polysaccharides against neurodegenerative disorders have not yet been fully explored. This study aimed to investigate the neuroprotective potential of Aloe Polysaccharides (APs) against 3-Nitropropionic Acid (3- NPA)-initiated HD-like symptoms in rats. Adult male rats were allocated to control, 3-NPA-treated, and APs-treated groups (100 and 200 mg/kg orally) following 3-NPA administration. Behavioral assessments (rotarod, open field, narrow beam walking) and biochemical analyses, including neurotransmitters [Acetylcholinesterase (AChE), Acetylcholine (ACh), Dopamine (DA), Norepinephrine (NE), Serotonin (5-HT), Gamma-Aminobutyric Acid (GABA), Glutamate (Glu)], oxidative/nitrative stress markers [Malondialdehyde (MDA, Nitric Oxide (NO)], antioxidant enzymes [Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH)], mitochondrial enzyme [Succinate Dehydrogenase (SDH)], inflammatory mediators [Nuclear Factor Kappa B (NF-κB), Tumor Necrosis Factor Alpha (TNF-α), Interleukin- 1 Beta (IL-1β), Cyclooxygenase-2 (COX-2)], neurotrophic factor [Brain-Derived Neurotrophic Factor (BDNF)], and apoptotic markers (caspase-3, caspase-9, B-Cell Lymphoma 2 (Bcl-2), Bcl-2-Associated X Protein (Bax)] were performed. Additionally, the impact of APs on regulators of mitochondrial biogenesis and antioxidant response [Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Sirtuin 1 (Sirt1), Heme Oxygenase-1 (HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PGC-1α), Adenosine Monophosphate-Activated Protein Kinase (AMPK), Uncoupling Protein 1 (UCP1), Uncoupling Protein 2 (UCP2)] was evaluated. Histopathological examination of the striatum was conducted. Statistical analysis was performed using one-way ANOVA followed by Tukey's post hoc test. 3-NPA administration induced significant motor deficits, neurotransmitter imbalance, elevated oxidative stress, inflammation, mitochondrial impairment, BDNF depletion, apoptosis, and striatal degeneration (P < 0.01). APs treatment significantly (P < 0.01; P < 0.001) reversed 3-NPA effects and improved behavioral performance (rotarod latency, OFT exploratory activity, and beam walk score); restored neurotransmitter balance; improved antioxidant enzymes (SOD, CAT, and GSH); mitigated MDA and NO effects; suppressed NF-κB, TNF-α, IL-1β, and COX-2; elevated BDNF and SDH activities; mitigated apoptosis (caspase-3 and 9, BAX, and BCl-2); and preserved striatal structure. APs showed neuroprotective potential in 3-NPA-induced HD rats by modulating the BDNF/NF-κB/Nrf2 pathway, controlling oxidative stress and neuroinflammation, restoring neurotransmitter function, and arresting striatal damage. Treatment with Aps markedly upregulated the levels of mitochondrial biogenesis-related proteins (Sirt1, PGC-1α, AMPK, UCP1, and UCP2) and antioxidant defense mediators (HO-1 and NQO1). In addition to behavioral and biochemical improvements, this study uniquely demonstrates that APs upregulate genes central to the mitochondrial biogenesis pathway, suggesting a new mechanistic basis for their neuroprotective effects in 3-NPA-induced HD. The study results showed that Applied Physiology Solution (APS) enhanced behavioural characteristics and neurotransmission function while simultaneously reducing the inflammatory response and cell stress and preserving striatal tissue structure. These findings reveal that APs promote neuroprotection not only by modulating oxidative stress, neuroinflammation, neurotransmission, and apoptosis, but also by specifically upregulating genes in the mitochondrial biogenesis pathway, highlighting their potential as a natural therapeutic candidate for HD management. Show less

Tuberculosis (TB) has remained an unsolved problem and a major public health issue, particularly in developing countries. Pakistan is one of the countries with the highest tuberculosis infection rates globally. However, methods or biomarkers to detect early signs of TB infection are limited. Here, we characterized the mRNA profiles of immune responses in unstimulated Peripheral blood mononuclear cells obtained from treatment naïve patients with early signs of active pulmonary tuberculosis without previous history of clinical TB. We identified a unique mRNA profile in active TB compared to uninfected controls, including cytokines such as IL-27, IL-15, IL-2RA, IL-24, and TGFβ, transcription factors such as STAT1 and NFATC1 and immune markers/receptors such as TLR4, IRF1, CD80, CD28, and PTGDR2 from an overall 84 different transcripts analyzed. Among 12 significant differentially expressed transcripts, we identified five gene signatures which included three upregulated IL-27, STAT1, TLR4 and two downregulated IL-24 and CD80 that best discriminate between active pulmonary TB and uninfected controls with AUC ranging from 0.9 to 1. Our data identified a molecular immune signature associated with the early stages of active pulmonary tuberculosis and it could be further investigated as a potential biomarker of pulmonary TB. Show less

Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools. Show less