Biology subjects

Velayutham, R.

Publications and source records attributed to Velayutham, R..

4 recordsLinked to original sources

bioRxiv2026

Cannabidiol rescues age-associated cognitive decline in mouse model

This study addresses key gaps in our understanding of the cognitive changes associated with normal brain aging and their underlying structural and functional correlates. Declining levels of brain endocannabinoids (eCB), particularly 2-arachidonoylglycerol (2-AG), are thought to contribute to age-related cognitive impairment, but the mechanisms involved remain poorly understood. Here, we show that levels of 2-AG and its synthesizing enzyme, diacylglycerol lipase- (DAGL-), are significantly reduced in the medial prefrontal cortex (mPFC) of aged mice. This decline is associated with impairments in mood and memory, as demonstrated by behavioral analyses. Immunofluorescence studies further revealed reduced expression of cannabinoid receptors CB1 and CB2 on microglia in aged brains, suggesting that diminished eCB signaling may contribute to enhanced neuroinflammation. Consistent with this idea, microglia from aged mice exhibited increased HMGB1-TLR4-NF-{kappa}B signaling, indicative of a pro-inflammatory state. LC-HR-MS analysis also showed elevated glutamate levels and reduced glutamine and GABA levels in the mPFC, linking impaired eCB signaling to excitotoxic imbalance during aging. Importantly, intraperitoneal administration of cannabidiol (CBD) to aged mice reversed mood and memory deficits, restored CB1 and CB2 receptor expression, attenuated HMGB1-TLR4-NF-{kappa}B signaling, and normalized the glutamate-glutamine/GABA balance in the mPFC. Collectively, these findings identify eCB signaling as a critical regulator of age-associated cognitive decline and support CBD as a potential therapeutic strategy to promote healthy brain aging. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/711942v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@e9c9ddorg.highwire.dtl.DTLVardef@c3fbd2org.highwire.dtl.DTLVardef@c9d5eforg.highwire.dtl.DTLVardef@fc4371_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIReduction of 2-AG in the brains medial prefrontal cortex (mPFC) over time is a hallmark of cognitive decline. C_LIO_LIPro-inflammatory signalling such as HMGB1 (High Mobility Group Box 1)-TLR4 (Toll-like receptor 4)-NF-kB (Nuclear Factor kappa B) signalling are elevated in aged brain. C_LIO_LIAltered glutamine-glutamate/GABA cycle associated with reduced 2-AG levels. C_LIO_LICBD administration mitigates cognitive decline associated with aging and diminishes neuroinflammation. C_LI

neuroscience↗

bioRxiv2026

The Ets transcription factor ETV4 regulates FGF1-dependent proliferation and glycolysis in ER-positive breast cancer

Obesity is a risk factor for estrogen receptor (ER) positive breast cancer. Beyond body mass index, adult weight gain increases breast cancer risk. During weight gain, hypertrophic adipocytes produce fibroblast growth factor 1 (FGF1), which drives estrogen-independent growth of ER-positive tumors. Effects of FGF1 on breast cancer cells include elevated proliferation and enhanced glycolytic activity. We identified the Ets transcription factor ETV4 as a target of FGF1 treatment across multiple breast cancer cell lines. Our objective was to define the role of ETV4 in mediating the tumor-promotional effects of FGF1, to better understand how weight gain and obesity drive breast cancer risk and progression. Here, we determined that ETV4 directly associates with a poor prognosis for patients with ER-positive tumors and positively correlates with FGF1 levels in the context of obesity. We demonstrate that ETV4 is required to mediate the pro-tumorigenic effects of FGF1 on cell proliferation, glycolytic reprogramming, and tamoxifen sensitivity in vitro, and on tumor growth in the presence of estrogen in obese mice. In vitro, ETV4 overexpression enhances proliferation and metabolic activity, mimicking effects of FGF1 on breast cancer cells, but it is not sufficient to promote ER-positive tumor growth before or after estrogen deprivation in vivo in lean females. This study reveals a potentially novel mechanism through which weight gain, characterized by excess FGF1 production, drives the development of aggressive features in the prevalent ER-positive breast cancer subtype.

cancer biology↗

bioRxiv2025

Cystathionine Beta-Synthase Promotes Anoikis Resistance and Transcoelomic Metastasis in Ovarian Cancer via the SP1-ITGB1 axis

Anoikis resistance is crucial for ovarian cancer (OvCa) transcoelomic metastasis, during which exfoliated OvCa cells survive as spheroids before invading the omentum. Here, we demonstrate that cystathionine {beta}-synthase (CBS), an H2S-producing transsulfuration pathway enzyme, is a key determinant of OvCa spheroidal viability and metastatic potential. Analysis of publicly available patient datasets, as well as an in-house tissue microarray, revealed that high CBS expression positively correlates with both poor progression-free survival and clinically observed peritoneal/omental metastasis. Integrated functional and proteomic analyses indicated that CBS silencing induces apoptosis in 2D monolayers. Consistent with this, CBS silencing in spheroids caused apoptosis and disrupted spheroid architecture. Mechanistically, this phenotype was associated with downregulation of oncogenic stemness and epithelial-mesenchymal transition. Further, through proteomic and bioinformatic analyses, we identified ITGB1 to be the hub protein in OvCa spheroidogenesis. Interestingly, knockdown of CBS led to abrogation of the ITGB1-mediated downstream pathway. Moreover, by proteomic and network analyses, we identified SP1 as a key transcriptional regulator of CBS-induced pro-spheroidal transcriptional programs of stemness and invasiveness. Stabilization of SP1 through persulfidation by H2S supplementation restored spheroidal viability and underlying protein signaling. Further, our results reveal that loss of CBS, through ITGB1 repression, disrupts spheroid architecture, leading to reduced metastatic docking on the murine omental surface in vivo. Collectively, these findings identify CBS as a central regulator of anoikis resistance and OvCa transcoelomic metastasis, highlighting the therapeutic potential of targeting CBS-dependent SP1-ITGB1 regulation to control metastatic spread.

cancer biology↗

bioRxiv2021

Possible Interference in Protein - Protein interaction as a new approach in microinhibition of respiratory pathogens on nasal- oral epithelium: An early on-screen study with reference toSARS-Cov-2-ACE2 binding interference

Upper and lower respiratory pathogens - both microbes and viruses -are responsible for very high morbidity, man-hour loss, residual long term clinical conditions and even mortality. In india only, high incidence of annual respiratory infections - both UT and LT - demands prophylactic intervention in addition to all therapeutic interventions available.The issue of respiratory infections is more pronounced now in the backdrop of nearly uncontrolled high incidences of SARS-Cov-2 affection resulting in death and damage of human lives to the extent of hundreds of millions spreading over entire world, with incidence variations from country to country. After the initial unanswered phase of spread of SARS-Cov-2 virus with attendant unseen mortalities, quickest invention of a series of unusual vaccines have stemmed the lethal progress to a very significant extent, although vaccinating each and every human subject - nearly 8 to 9 bn in supremely divided world -economically-- is an unthinkable proposition where economic disparity dictates vaccine availability and implementation.Moreover, being of highly unstable nucleic acid composition, the original virus, by now has a thick set of variants around the globe with variable clinical outcome. Given this complex background of scanty availability and inefficient implementation, there always is a need of a preventive approach which can possibly micro-fix the pathogens, including SARS-2 on nasal epithelium so as to interfere with viral [or any pathogen] entry through specified receptor gate[s] or any other ways. The present formulation is under study -- as a candidate of interference on nasal / oral mucosa for all respiratory pathogens. This brief report describes dry on-screen studies of protein - protein interaction as well as its possible interference by an amino acid Lysine. Phospholipid bilayerresponses in presence of added loads of the same essential amino acid -Lysine - showed unusual and unexplained behavior both in structural integrity as well in spatial orientation.

biochemistry↗