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Background: Gas6 is a product of growth arrest-specific gene 6 and is mostly expressed by the growth-arrested organs and is implicated in thrombosis, various inflammation, and age-related diseases. However, its role in chronic obstructive pulmonary disease has not been investigated yet. Methods: We developed lipopolysaccharide-induced mouse model of chronic lung inflammation to study its involvement. Therefore, male C57BL/6 mice (20–25 g) were grouped into control and LPS group; each group having 15 animals each. LPS group was nebulized with LPS (1 mg/ml) for 45 min, once a week for 8 weeks to induce chronic inflammatory conditions in the lungs by use of nebulizer. The mice model was validated by assessing infiltration of various immune cells (T-cells, B-cells, and neutrophils) into the lungs and pro-inflammatory and anti-inflammatory cytokine profile by cytokine bead array kit by flow cytometry. Lung deterioration was assessed by lung histology. The level of gas6 protein from the lung homogenate was measured by quantikine enzyme-linked immunosorbent assay kit. Furthermore, lung homogenate was analyzed by Western blotting for expression profile of gas6 protein. Results: There was significant increase in the level of T-cells (19±8% vs 65±11%), B-cells (24±7% vs 64±10%), and neutrophils (22±9% vs 57±10%) and significant increase in the level of tumor necrosis factor (200 ± 17 pg/ml vs. 1222 ± 152 pg/ml) and IL-6 (106 ± 13 pg/ml vs. 448 ± 122 pg/ml). Lung deterioration was observed in LPS group. We observed significant increase in the level of gas6 protein in lung homogenate in LPS group (0.16 ± 0.1 ng/ml vs. 4.2 ± 0.1 ng/ml). Furthermore, we found significant increase in gas6 protein in the lung homogenate of LPS-treated group by Western blotting. Conclusion: The current study establishes the involvement gas6 protein in lung inflammation.

Abstract Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first‐in‐class small molecule inhibitor, RK‐33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK‐33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3‐overexpressing cells. Importantly, RK‐33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK‐33 impaired Wnt signaling through disruption of the DDX3–β‐catenin axis and inhibited non‐homologous end joining—the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK‐33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy.

Health monitoring is an integral part of laboratory animal quality standards. However, current or past prevalence data as well as regulatory requirements dictate the frequency, type and the expanse of health monitoring. In an effort to understand the prevalence of rodent pathogens in India, a preliminary study was carried out by sero-epidemiology. Sera samples obtained from 26 public and private animal facilities were analyzed for the presence of antibodies against minute virus of mice (MVM), ectromelia virus (ECTV), lymphocytic choriomeningitis virus (LCMV), mouse hepatitis virus (MHV), Sendai virus (SeV), and Mycoplasma pulmonis in mice, and SeV, rat parvo virus (RPV), Kilham's rat virus (KRV) and sialodacryoadenitis virus (SDAV) in rats, by sandwich ELISA. It was observed that MHV was the most prevalent agent followed by Mycoplasma pulmonis and MVM in mice, and SDAV followed by RPV were prevalent in rats. On the other hand, none of the samples were positive for ECTV in mice, or SeV or KRV in rats. Multiple infections were common in both mice and rats. The incidence of MHV and Mycoplasma pulmonis was higher in facilities maintained by public organizations than in vivaria of private organizations, although the difference was not statistically different. On the other hand the prevalence of rodent pathogens was significantly higher in the northern part of India than in the South. These studies form the groundwork for detailed sero-prevalence studies which should further lay the foundations for country-specific guidelines for health monitoring of laboratory animals.

Synthesis of the title compound,1-(2'-O-methyl-ß-D-ribofuranosyl)-1H-imidazo-[4,5-d]pyridazine-4,7(5H,6H)-dione (1), is reported. It was synthesized in four steps, starting from methyl 1-(ß-D-ribofuranosyl)imidazo-4,5-dicarboxylate (2). The 3',5'-hydroxyl groups of 2 was protected with a bis-silylating agent to form 3, which was then methylated to form the corresponding 2'-O-methyl derivative 5. The silyl deprotection of the latter (to form 6), followed by treatment with hydrazine afforded the target nucleoside 1. The reported nucleoside has potentially beneficial applications in biomedicine based on antisense and triple-helical nucleic acid technologies.

Synthesis of the title compound,1-(2'-deoxy-b-D-ribofuranosyl)-1H-imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione (1), is reported. It was synthesized in five steps, commencing with methyl 1-(b-D-ribofuranosyl)imidazo-4,5-dicarboxylate (2). The 3',5'-hydroxyl groups of 2 were protected with a bis-silylating agent to form 3, which was then converted into the corresponding 2'-thionocarbonate derivative 5. The reduction of the latter with tri-n-butyltin hydride (to form 6), followed by silyl deprotection with tetra-nbutylammonium fluoride, afforded 7. Treatment of the latter with hydrazine hydrate yielded the target nucleoside 1.

Synthesis of trans-1,2-bis(4-nitro-1-p-methoxybenzylimidazol-5-yl)ethene (1) as an imidazole analogue of stilbene has been reported. In order to confirm the trans geometry of the product using an UV spectral comparison, a mixture of both trans (1) and cis isomer (3) was also prepared. The synthesis involved one-step dimerization of the precursor, 4-nitro-1-p-methoxybenzyl-5-methyl-1H-imidazole (2), using N-chlorosuccinimide catalyzed by potassium t-butoxide.

A study concerning isomeric stabilities of 1,3- and 1,4-diheterocycloclohexanes is presented. Experiments include the measurement of the formation enthalpies.