Elevated expression levels of the bcl-2 proto-oncogene have been extensively correlated with the appearance of androgen independence in prostate cancer. Although bcl-2 was first cloned as the t(14:18) translocation breakpoint from human follicular B cell lymphoma, the mechanism of overexpression of bcl-2 is largely undefined for advanced prostate cancer because there are no gross alterations in the gene structure. We investigated the role of the product of the prostate apoptosis response gene-4 (Par-4) and the product of the Wilms' tumor 1 gene (WT1) in the regulation of Bcl-2 expression in prostate cancer cell lines. We observed growth arrest and apoptosis, upon decreasing Bcl-2 protein and transcript in the high Bcl-2-expressing, androgen-independent prostate cancer cell line, by all-trans-retinoic acid treatment (ATRA), but this did not occur in the androgen-dependent cell line expressing low levels of Bcl-2. The decrease in the Bcl-2 protein and transcript following all-trans-retinoic acid treatment was accompanied by changes in localization of Par-4 and an induction in the expression of WT1 protein. In stable clones expressing ectopic Par-4 and in ATRA-treated cells, we observed decreased Bcl-2 protein and transcript. This was accompanied by an induction in WT1 expression. The involvement of WT1 in the Par-4-mediated down-modulation of Bcl-2 was further defined by blocking endogenous WT1 expression, which resulted in an increase in Bcl-2 expression. Finally, we detected Par-4 and WT1 proteins binding to a previously identified WT1-binding site on the bcl-2 promoter both in vitro and in vivo leading to a decrease in transcription from the bcl-2 promoter. We conclude that Par-4 regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter. These data also identify Par-4 nuclear localization as a novel mechanism for ATRA-mediated bcl-2 regulation.

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RNA intereference and short-interfering RNA (siRNA) have been proven to be effective at decreasing the expression of target genes and provide a valuable tool for promoting and directing the growth of functional tissues for repair and reconstructive tissue engineering applications. siRNA is a gene-silencing mechanism that involves double-stranded RNA-mediated sequence-specific mRNA degradation and is a powerful mechanism for controlling cell behavior. The use of siRNA to reduce the expression of a target gene can induce the expression of one or more tissue-inductive factors, direct the differentiation of stem or progenitor cells, or remove a factor that inhibits regeneration, which can be useful in fundamental studies of tissue formation or in applications to promote in vivo regeneration. The potential of siRNA is illustrated through specific examples within the fields of angiogenesis, bone and nerve regeneration, and wound healing. In addition, challenges to deliver siRNA effectively for tissue engineering applications are addressed. siRNA represents a powerful tool to investigate and/or promote tissue formation, and numerous opportunities exist for identifying targets that promote regeneration of tissue and developing effective delivery systems.

The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellular calcium from ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain leukemias. Presently, there is little information available on the factors that regulate the expression of CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of CD38 antigen by retinoids (vitamin A and related compounds). At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induced expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor.

Background: Mental health issues are the leading impediment to academic success. During COVID-19 pandemic, a decrease in well-being and an increase in mental health problems were registered. Younger people and women seemed to be particularly affected by the isolation strategies, leading to development of loneliness, anxiety, depression and extreme mental stress. The objectives of the present study were to assess the core symptoms of depression, anxiety and stress in students and teachers during covid pandemic second wave.Methods: An E-Performa was created as google form. All the students and Teachers were requested to fill this Performa and submit it. The collected responses were analyzed statistically and a p<0.05 was considered to be significant.Results: A total of 483 responses were collected. Death from COVID was reported either in the family/friend’s family or neighbourhood in 122 (27.1%) students and (45.5%) teachers which was very stressful for them and it was significantly associated with negative emotions arising out of depression, anxiety and stress. Sleep pattern was reported to be disturbed in 246 (54.6%) students and 57.6% teachers.Conclusions: Everyone around the globe was distressed and scared of deadly virus. But young generation was more effected mentally and some physically also. Teachers as well as students should be prepared for such type of disastrous management. Students from underprivileged families should be rehabilitated both for physical and mental health issues.