👤 Pooja A Chawla

Alzheimer's Disease (AD) is a serious neurodegenerative condition that predominantly impacts the cholinergic neurons of the entorhinal cortex and hippocampal regions, playing a critical role in learning, navigation, and brain processing. This paper aims to discuss the three main hypotheses of Alzheimer's disease, focusing on neurotoxicity and neurodegeneration caused by mitochondrial dysfunction and ROS production, particularly analyzing the susceptibility differences between genders. Our comprehensive review focuses on significant findings from the past five years, particularly on Cholinesterase (ChE) and BACE-1 inhibitors. Researchers have conducted a detailed analysis of Show less

An increasing number of university students report feeling lonely, a negative experience arising from a mismatch between perceived and actual social relationships. Loneliness has been linked to poorer mental health. However, the relationship between qualitative (sources of loneliness) and quantitative (high or low) differences in loneliness and mental health is under researched. The aims of this research were to (a) identify profiles of loneliness among university students across three indicators of loneliness, namely, social, family, and romantic indicators, using latent profile analysis (LPA); (b) examine the differences among identified profiles based on dimensions of mental health indicators (depression, anxiety, and stress), social support, and life satisfaction; and (c) assess profile membership based on demographic variables (gender, social isolation, relationship status, and education characteristics) and the Big Five personality traits (extraversion, agreeableness, openness, conscientiousness, and neuroticism). A cross-sectional survey was conducted on 912 university students from five cities in Uttar Pradesh, India. Participants completed questionnaires covering demographic details and validated measures assessing loneliness, depression, stress, anxiety, social support, life satisfaction, and the Big Five personality traits. Data were analyzed using the latent profile module in Jamovi and fit indices, namely, BIC, AIC, and BLRT, and entropy was used to select the best profile. The latent profile analysis identified four profiles for university student loneliness, including Social and emotional lonely (31.4%), Moderate romantic lonely (23.8%), Moderate social lonely (8.2%), and Severe romantic lonely (36.6%). Moreover, the Social and emotional lonely profile scored the highest on depression, anxiety, and stress. The Moderate romantic lonely profile scored the highest on life satisfaction and social support. Being in a relationship decreased the likelihood of being categorized as Severe romantic lonely. In terms of personality, neuroticism was the strongest predictor of profile membership. This study is a step towards identifying at-risk lonely individuals with varying sources of loneliness. Identifying different profiles of lonely individuals will have direct implications for designing interventions that cater to a particular group rather than a one-size-fits-all approach. Show less

Dendritic cell (DC) dysfunction is known to exacerbate intestinal pathologies, but the mechanisms compromising DC-mediated immune regulation in this context remain unclear. Here, we show that intestinal dendritic cells from a mouse model of experimental colitis exhibit significant levels of noncanonical NF-κB signaling, which activates the RelB:p52 heterodimer. Genetic inactivation of this pathway in DCs alleviates intestinal pathologies in mice suffering from colitis. Deficiency of RelB:p52 diminishes transcription of Axin1, a critical component of the β-catenin destruction complex, reinforcing β-catenin-dependent expression of Raldh2, which imparts tolerogenic DC attributes by promoting retinoic acid synthesis. DC-specific impairment of noncanonical NF-κB signaling leads to increased colonic numbers of Tregs and IgA+ B cells, which promote luminal IgA production and foster eubiosis. Experimentally introduced β-catenin haploinsufficiency in DCs with deficient noncanonical NF-κB signaling moderates Raldh2 activity, reinstating colitogenic sensitivity in mice. Finally, inflammatory bowel-disease patients also display a deleterious noncanonical NF-κB signaling signature in intestinal DCs. In sum, we establish how noncanonical NF-κB signaling in dendritic cells can subvert retinoic acid synthesis to fuel intestinal inflammation. Show less

Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer's disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats' performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function. Show less

Sedum species are reported to possess diverse pharmacological activities in various solid tumors. However, the anticancer functions of Sedum orizyfolium and its constituents have never been determined in human cancers. The present study focused on addressing the inhibition efficacy of the methanol extract of S. orizyfolium (MESO) and its constituents and the molecular mechanism underlying invasion and epithelial-to-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) cell lines. After MESO treatment, a wound-healing assay, an invasion assay, and immunocytochemistry were performed in OSCC cell lines, coupled with in silico analysis and immunohistochemistry in OSCC patient samples, to investigate the role of the EMT transcription factor Slug. Trehalose, an active component of MESO, was identified through gas chromatography-mass spectrometry. Among the methanol extracts of 18 various wild plants from South Korea, MESO exhibited the highest anticancer functionality in OSCC cells by downregulating Slug expression. In silico analysis and immunohistochemistry indicated that elevated Slug levels are remarkably associated with tumor progression and invasion in patients with OSCC, suggesting that changes in Slug expression alter EMT progression and invasion in OSCC. Notably, treatment with trehalose, a sugar component of MESO, inhibited invasiveness and Slug expression in OSCC cells. Cumulatively, this study highlighted the beneficial role of MESO and trehalose in the inhibition of invasiveness of OSCC cells via suppression of Slug expression and suggested a new design for potential chemotherapeutic drugs against OSCC. Show less

Anacetrapib is a novel cholesteryl-ester transfer protein (CETP) inhibitor in late-stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout after chronic dosing. Preclinical findings suggest that white adipose tissue is a potential depot and that accumulation into adipose tissue governs the long-term kinetics of anacetrapib in mice. A phase I study performed to test this hypothesis in humans revealed that plasma exposure was correlated with fat content in food administered with the drug. Plasma concentrations of anacetrapib seemed to reach plateau faster than adipose concentrations. Anacetrapib continued to accumulate in adipose during the treatment period despite apparent plateau in plasma with only minimal decline in adipose levels up to 1 year postdose. Because of its high lipophilicity, anacetrapib partitions into adipose tissue, this likely forms a drug reservoir that, in turn, contributes to the long residence time of the drug in plasma. Show less