Oxidative stress (OS) has been implicated in a wide array of diseases such as neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and cancer. OS is caused by an imbalance in production of Reactive Oxygen Species (ROS) and antioxidant defenses in the cell which results in the damage of cellular components, inactivate essential metabolic enzymes and disrupt signal transduction pathways. OS induces peroxidative damage to the sperm plasma membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes dysregulation in levels of mRNAs/transcripts. OS induced sperm DNA damage is associated with male infertility, recurrent pregnancy loss (RPL), congenital malformations and high frequency of childhood disorders. OS induced pathologies are caused by endogenous and exogenous factors, majority of which, are modifiable. Antioxidant supplementation could help in relieving OS, however, its long-term usage may disrupt the intricate oxidation-reduction balance and can lead to “Reductive Stress”. Adoption of simple lifestyle interventions may relieve OS and can also aid in its management. This may improve overall quality of life (QOL) and can reduce prevalence of OS induced diseases.

Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAF^V600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs. Cdx2-mediated proximal colon-specific transcriptional program concurrently is tumor suppressive, and Cdx2 loss sufficiently creates permissive state for BRAF^V600E-driven transformation. Human proximal colon cancers with CDX2 downregulation showed similar transcriptional program as in mouse proximal organoids with Cdx2 loss. Developmental transcription factors, such as CDX2, are thus critical in maintaining tissue-location specific transcriptional programs that create tissue-type origin specific dependencies for tumor development.

Childhood cancers are associated with a psychological burden to the parents and hence, decline their mental and physical health and overall quality of life. The purpose of the present study is to investigate the impact of 12-weeks yoga based lifestyle intervention on psychological stress and quality of life in the parents of children affected with retinoblastoma. Single arm prospective clinical trial conducted from October 2015 to October 2017 at the Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. A pre-tested 12-weeks yoga based lifestyle intervention included asanas (physical postures), pranayama (breathing exercises), dhyana (meditation), relaxation techniques, lectures and films on yoga, interactive sessions and individualized advice was administered to the participants. 12-weeks of yoga based lifestyle intervention programme leads to a significant improvement in psychological stress and overall quality of life in the parents of retinoblastoma patients. There was a significant improvement in all the domains (physical health, psychological health, social relationships, and environment) of WHOQOL-BREF from baseline (day 0) to 12-weeks of yoga based lifestyle intervention. Yoga based lifestyle intervention also led to a significant increase in the levels of brain derived neurotrophic factor, dehydroepiandrosterone sulphate, sirtuin 1 and decreased the cortisol and IL-6 levels. Yoga based lifestyle intervention reduced the severity of psychological stress and resulted in improvement in overall quality of life and upregulation in levels of systemic biomarkers of neuroplasticity. YBLI may serve as a beneficial therapy and may also act as an effective medium for better stress management to develop better coping strategies in the parents of retinoblastoma patients.