B lymphopoiesis declines with age, and in rabbit this occurs by 8 weeks of age. We found that colony-forming units fibroblasts (CFU-F) in the bone marrow (BM) decrease 10-fold by a few weeks of age, and that the CFU-Fs preferentially differentiate into adipocytes instead of osteoblasts. BM becomes filled with fat spaces during this time, making rabbit a unique model to study the effects of accelerated fat accumulation on B lymphopoiesis. We show that adipocytes of both rabbit and human secrete a soluble factor(s) that inhibits B lymphopoiesis and we tested if this inhibition was due to effects on the BM stroma or hematopoietic progenitors. Pre-treatment of BM mononuclear cells (MNCs) with adipocyte conditioned medium (CM) dramatically inhibited their differentiation into proB cells in co-cultures with OP9 stromal cells. In contrast, pre-treatment of OP9 stromal cells with adipocyte CM had no effect on B lymphopoiesis. Using human HSCs we show that inhibition by the adipocyte-derived factor occurred at the common lymphoid progenitor (CLP) to pre-proB cell stage. We propose that the age-related decline in B lymphopoiesis is due to a decrease in CFU-F, an increase in adipocytes, and an adipocyte-derived factor that blocks B lymphopoiesis at the CLP to pre-proB cell stage.
Prostate cancer is one of the most common cancers in men. Recent estimates suggest that over a million men are diagnosed with the disease annually. Prostate cancer pathogenesis involves both heritable and environmental factors. The molecular events involved in the development or progression of prostate cancer are still unclear. Recent body of literature highlights the role of viral infections in initiation or progression of prostate cancer. In this regard, certain viruses have been reported to interact with host proteins and bring about changes in genetic, immunological and inflammatory events that lead to initiation or progression of prostate cancer. We conducted a comprehensive PubMed database search to identify publications relevant to viruses associated with prostate cancer. In this review, we discuss the possible viral etiology of prostate cancer and evidence of viral-mediated genetic changes, and immune dysregulation involved in initiation or progression of prostate cancer.
Aim
Variations of dopamine receptor type 2 (DRD2) are among the key factors involved in the pathology of schizophrenia. Presence of certain SNPs in DRD2 gene also amend patients’ response to antipsychotics. Keeping in view the genetic diversity among populations and important role of DRD2 polymorphisms in schizophrenia, we aimed to study two of its SNPs rs1801028 and rs6277 in patients with schizophrenia from Pakistan.
Methods
A total of 100 schizophrenia cases and 100 healthy controls were recruited. DNA was extracted from whole blood followed by PCR, Sanger sequencing and genotyping of two SNPs, that is, rs1801028 and rs6277.
Results
No association of rs1801028 and rs6277 was found with schizophrenia in Pakistani population (P > .05). Highlight of our study is the association of polymorphism rs201256011 with schizophrenia (P = .001), which is being reported for the first time. Significant association of rs201256011 was also found with Positive and Negative Syndrome Scale negative, cognitive and total score (P < .05).
Conclusion
In conclusion, genetic variants rs1801028 and rs6277 of DRD2 are not associated with schizophrenia in Pakistani population. While, previously unreported polymorphism rs201256011 have shown significant association with schizophrenia and its severity. A large scale multicentre replication study is required to confirm the association of this SNP with schizophrenia.
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