Establishment and genomic characterization of gingivobuccal carcinoma cell lines with smokeless tobacco associated genetic alterations and oncogenic PIK3CA mutation.

Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) -01 to -04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.

Role of Forkhead Box O Transcription Factors in Oxidative Stress-Induced Chondrocyte Dysfunction: Possible Therapeutic Target for Osteoarthritis?

Chondrocyte dysfunction occurs during the development of osteoarthritis (OA), typically resulting from a deleterious increase in oxidative stress. Accordingly, strategies for arresting oxidative stress-induced chondrocyte dysfunction may lead to new potential therapeutic targets for OA treatment. Forkhead box O (FoxO) transcription factors have recently been shown to play a protective role in chondrocyte dysfunction through the regulation of inflammation, autophagy, aging, and oxidative stress. They also regulate growth, maturation, and matrix synthesis in chondrocytes. In this review, we discuss the recent progress made in the field of oxidative stress-induced chondrocyte dysfunction. We also discuss the protective role of FoxO transcription factors as potential molecular targets for the treatment of OA. Understanding the function of FoxO transcription factors in the OA pathology may provide new insights that will facilitate the development of next-generation therapies to prevent OA development and to slow OA progression.

Crocin, a natural product attenuates lipopolysaccharide-induced anxiety and depressive-like behaviors through suppressing NF-kB and NLRP3 signaling pathway.

Depression is one of the foremost psychological illness which is closely leagued with inflammation. Crocin is a natural product that exhibits both anti-inflammatory and anti-oxidant activities. However, little is known about anti-inflammatory mechanisms of crocin on LPS-induced anxiety and depressive-like behaviors. The objective of this study is emphasized on neuroprotective role of crocin against LPS-induced anxiety and depressive-like behaviors in mice. It is observed that crocin inhibited LPS-induced production of NO, TNF-α, IL-1ß and ROS in BV-2 microglial cells. Moreover, crocin significantly declined the expression of iNOS, NF-κB p65 and CD16/32 (M1 marker), as well as elevated the expression of CD206 (M2 marker) in BV-2 cell line with decreased LPS-induced anxiety and depressive-like behaviors by improved locomotor activity, reduced sucrose intake, and decreased immobility time in forced swim and tail suspension test in Kunming mice. Expression of NLRP3, ASC and caspase-1 by i.p administration of LPS found to be neutralized with reduction in level of IL-1ß, IL-18 and TNF-α in mouse hippocampus. In conclusion, these results suggested that crocin as a potential therapeutic candidate for neuro-inflammation and depressive-like behaviors induced by LPS. The effect was found to be due to inhibition of NLRP3 inflammasome and NF-κB and its promoted M1 to M2 phenotypic conversion of microglia.