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SIRT1 inhibition in pancreatic cancer models: contrasting effects in vitro and in vivo

Oon CE, Strell C, Yeong KY, Östman A, Prakash J

Eur J Pharmacol, 2015 Jun 15;757:59-67.
PMID: 25843411 DOI: 10.1016/j.ejphar.2015.03.064

Gemcitabine remains the standard treatment for pancreatic cancer, although most patients acquire resistance to the therapy. Up-regulated in pancreatic cancer, SIRT1 is involved in tumorigenesis and drug resistance. However the mechanism through which SIRT1 regulates drug sensitivity in cancer cells is mainly unknown. We hypothesise that inhibiting SIRT1 activity may increase sensitivity of pancreatic cancer cells to gemcitabine treatment through the regulation of apototic cell death, cell cycle, epithelial-mesenschymal-transition (EMT) and senescence. We demonstrate that gemcitabine or 6-Chloro-2,3,4,9-tetrahydro-1 H-Carbazole-1-carboxamide (EX527) SIRT1 inhibitor reduces PANC-1 cell proliferation in vitro. EX527 enhanced sensitivity of PANC-1 cells to gemcitabine treatment through increased apoptosis. However, EX527 displayed no beneficial effect either as a monotreatment or in combination with gemcitabine in the modulation of cell cycle progression. Combination treatment did not reverse the two phenomena known to affect drug sensitivity, namely EMT and senescence, which are both induced by gemcitabine. Unexpectedly, EX527 promoted PANC-1 xenograft tumour growth in SCID mice compared to control group. Dual tX527 and gemcitabine displayed no synergistic effect compared to gemcitabine alone. The study reveals that SIRT1 is involved in chemoresistance and that inhibiting SIRT1 activity with EX527 sensitised PANC-1 cells to gemcitabine treatment in vitro. Sensitisation of cells is shown to be mainly through induction of micronuclei formation as a result of DNA damage and apoptosis in vitro. However, the absence of positive combinatorial effects in vivo indicates possible effects on cells of the tumor microenvironment and suggests caution regarding the clinical relevance of tissue culture findings with EX527.
Effect of bidi cigarette smoking on interleukin-1β and 8 levels in chronic periodontitis patient

Nath S, Prakash J, Prajapati VK, Sharma N, Pulikkotil SJ

Indian J Dent Res, 2020 8 10;31(3):433-438.
PMID: 32769279 DOI: 10.4103/ijdr.IJDR_783_17

Introduction: Bidi, a leaf rolled cigarette, is the most popular form of smoking in India. Bidi cigarette contains higher tar, ammonia, and nicotine content than a conventional cigarette and is more hazardous.
Aim of Study: The aim of this study was to determine the effect of bidi smoking on periodontitis by assessing the interleukin (IL)-1β and IL-8 from a gingival crevicular fluid (GCF).
Materials and Methods: A total of 60 patients were selected, which included 40 patients diagnosed with chronic periodontitis (20 bidi smokers and 20 non-bidi smokers) and 20 periodontal healthy controls. Diseased and healthy sites were selected from each of the chronic periodontitis subjects. Clinical parameters assessed were plaque index (PI), gingival index (GI), periodontal probing depth (PPD), recession (RC), and clinical attachment level (CAL). Pooled GCF samples were taken from the same site and analyzed for IL-1β and IL-8 using enzyme-linked immunosorbent assay.
Results: Bidi smokers displayed decreased levels of IL-1β and IL-8 than non-bidi smokers for both healthy and diseased sites and significantly reduced IL-8 levels among bidi smokers when compared to controls. Among bidi smokers, the diseased site had significantly higher levels of IL-8 than the healthy site. Non-smoker subjects with chronic periodontitis especially diseased sites contained significantly higher amounts of IL-1β and IL-8 than smokers and controls. The PI scores were highest among bidi smokers with reduced BOP and GI scores.
Conclusions: Bidi smoking influenced the cytokine profile among periodontitis patients exhibiting decreased levels of IL-1β and IL-8.
Fulltext Taste pathway: what do we teach?

Kamath MG, Prakash J, Tripathy A, Concessao P

J Clin Diagn Res, 2015 Jan;9(1):CL01.
PMID: 25737982 DOI: 10.7860/JCDR/2015/11021.5471
Insights into the enhanced photocatalytic degradation of congo red using advanced BaDyxFe12-xO19 catalytic hexamaterials

Himanshi, Makasana J, Ganesan S, Lal B, Naidu KS, Ahmed J, et al.

Sci Rep, 2025 Mar 15;15(1):8978.
PMID: 40089536 DOI: 10.1038/s41598-025-92145-y

Water pollution from the industrial dyes is a serious hazard to ecosystems, and addressing this issue is a significant challenge. To address these issues, we are fabricated BaDyxFe12-xO19 (x = 0.02 to 0.06) by sol-gel auto-ignition (SGA) technique. Several characterizations were used to scrutinize the structural, optical, photocatalytic, and magnetic traits of the produced samples. The X-ray diffraction (XRD) of the sample revels the hexagonal crystal structure. The field emission scanning electron microscopy (FESEM) of both samples reveal the existence of agglomerated grains showing hexagonal shapes. X-ray photoelectron spectroscopy (XPS) analyses confirm the oxidation state of every element present in the synthesized nanomaterials. The specific surface area was found to be 1.069 m2/g for BDF1 and 1.466 m2/g for BDF3. The band gap of the BDF1, BDF2, and BDF3 samples are found 2.16, 2.12, and 1.99 eV. The photocatalytic efficacy of the catalysts was examined by removal of the CR in natural light. A notable degradation efficiency of 89.29% are achieved by the BDF3 catalyst within 90 minutes under natural sunlight irradiation. The results demonstrate a straightforward and efficient approach for producing photocatalytic materials that are highly effective for the elimination of dye pollutants in wastewater treatment.