Biology subjects

Nagpal, R.

Publications and source records attributed to Nagpal, R..

4 recordsLinked to original sources

bioRxiv2026

Sex Effect of E-liquid Constituents on Atherosclerosis and Gut Dysbiosis in ApoE-/- Mice

RationaleThe role of sex in the effects of vaping and individual aerosolized e-liquid constituents on atherosclerosis, vascular aging, and gut microbiome remodeling remains poorly characterized. ObjectiveTo determine the contribution of e-cigarette aerosol components to vascular senescence, atherosclerosis, and gut microbiome dysbiosis in ApoE-/- mice and vascular smooth muscle cell (VSMC) viability and senescence. MethodsMale and female ApoE-/- mice were exposed to e-liquid constituents (vehicle, vehicle plus nicotine, and vehicle plus nicotine plus menthol) for 48 minutes per day, 5 days per week for 16 weeks, with vascular pathology assessed in vivo. VSMCs isolated from aortas of wild-type and ApoE-/- male and female mice were exposed to aerosolized e-liquids and evaluated for cellular senescence. ResultsExposure to all tested e-liquid formulations, including vehicle, nicotine-containing, and menthol-containing aerosols, increased atherosclerosis in both male and female mice, with the most robust effects observed in the nicotine-containing formulation and in the descending aorta. Females exhibited greater sensitivity to e-liquid exposure, with increased plaque accumulation in both the aortic arch and descending aorta, while the addition of menthol was associated with reduced plaque burden compared with nicotine alone in both sexes. Novel findings show that e-liquid exposure also altered gut microbial composition in a sex- and exposure-dependent manner, with nicotine causing the greatest dysbiosis and menthol exerting modulatory, but not restorative, effects. Notably, Alloprevotella emerged as a key discriminating genus associated with reduced plaque burden, supporting a potential link between gut microbial remodeling, inflammatory regulation, and atherosclerosis. ConclusionsThese findings demonstrate that individual e-liquid aerosol components increase atherosclerosis and alter the gut microbiome in a sex-specific manner, with nicotine producing the most pronounced pro-atherogenic effects and the addition of menthol reducing these effects, without eliminating overall atherosclerotic risk.

physiology↗

bioRxiv2025

Single-cell multiomics identifies both shared and unique features of immune dysfunction in the colon, plasma and stool from individuals diagnosed with Parkinson's disease or inflammatory bowel disease

Parkinsons disease (PD) is the fastest growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2,3,4. We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

neuroscience↗

bioRxiv2024

Beyond planar: fish schools adopt ladder formations in 3D

The coordinated movement of fish schools has long captivated researchers studying animal collective behavior. Classical literature from Weihs and Lighthill suggests that fish schools should favor planar diamond formations to increase hydrodynamic efficiency, inspiring a large body of work ranging from fluid simulations to hydrofoil experiments. However, whether fish schools actually adopt and maintain this idealized formation remains debated and unresolved. When fish schools are free to self-organize in three dimensions, what formations do they prefer? By tracking polarized schools of giant danios (Devario aequipinnatus) swimming continuously for ten hours, we demonstrate that fish rarely stay in a horizontal plane, and even more rarely, in the classical diamond formation. Of all fish pairs within four body-lengths from each other, only 25.2% are in the same plane. Of these, 54.6% are inline, 30.0% are staggered, and 15.4% are side-by-side. The diamond formation was observed in less than 0.1% of all frames. Notably, a "ladder formation" emerged as the most probable formation for schooling giant danios, appearing in 79% of all fish pairs and fish schools elongate at higher swimming speeds. These findings highlight the dynamic and three-dimensional nature of fish schools and suggest that hydrodynamic benefits may be obtained without requiring fixed positions. This research provides a foundation for future studies that examine the hydrodynamics and control of underwater collectives in 3D formations.

biophysics↗

bioRxiv2021

Microbiota induces aging-related leaky gut and inflammation by dampening mucin barriers and butyrate-FFAR2/3 signaling

Increased chronic inflammation is one of the key risk factors of aging-related disorders although its precise etiology remains elusive. Here, we demonstrate that aged, but not young, microbiota triggers inflammation by promoting gut permeability (leaky gut) via disruption of mucus barriers. Levels of the beneficial short-chain fatty acid, butyrate, are suppressed in the aged gut. Consistent with feedback regulation, the expression of butyrate-sensing receptors, free fatty acid receptor 2/3 (FFAR2/3), are also reduced in aged gut. Butyrate treatment of aged mice revereses the reduced mucin production, increased gut permeability and inflammation associated with low butyrate levels. In agreement, intestine-specific FFAR2/3 knockout mice manifest a compromised gut phenotype typically seen in aged mice,, such as increased gut permeability and inflammation with reduced mucin production. Taken together, our results demonstrate that an aged gut microbiota causally instigates inflammation by increasing gut permeability due to reduced butyrate levels, FFAR2/3 expression, and mucin barriers. Thus, butyrate-FFAR2/3 agonism could ameliorate the deleterious effects seen in aged gut and their implications on metabolic health.

physiology↗