A review on heme oxygenase-1 induction: is it a necessary evil.

Heme oxygenase-1 (HO-1) is considered to be the main protein in diseases arising as a result of oxidative and inflammatory insults. Tremendous research has been carried out on HO-1 since years, pertaining its cytoprotective effect against oxidative injury and other cellular stresses. HO-1, by regulating intracellular levels of pro-oxidant heme, or by other benefits of its by-products such as carbon monoxide (CO) and biliverdin (BV) had become an important candidate protein to be up-regulated to combat diverse stressful events. Although the beneficial effects of HO-1 induction have been reported in a number of cells and tissues, a growing body of evidence indicates that this increased HO-1 expression may lead to the progression of several diseases such as neurodegeneration, carcinogenesis. But it is not clear, what accounts for the increased expression of HO-1 in cells and tissues. The observed friendly role of HO-1 in a wide range of stress conditions since times is now doubtful. Therefore, more studies are needed to elucidate the exact role of HO-1 in various stressful events. Being more concise, elucidating the effect of HO-1 up-regulation on critical genes involved in particular diseases such as cancer will help to a larger extent to comprehend the exact role of HO-1. This review will assist in understanding the dual role (protective and detrimental) of HO-1 and the signaling pathway involved and will help in unraveling the doubtful role of HO-1 induction.

Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5.

Escalated PD-L1 expression has been identified during malignant transformation in a number of cancer types and helps cancer cells escape an effective anti-tumor immune response. The mechanisms underlying escalated production of PD-L1 in many cancers, however, are still far from clear. We studied PD-L1, STAT3 and STAT5 mRNA expression using qRT-PCR in 72 BCR/ABL1 negative myeloproliferative neoplasm (MPN) patients (39 polycythemia vera and 33 essential thrombocythemia). Furthermore, phosphorylation status of STAT3 and STAT5 was studied using immunoblotting in the same patients. All MPN patients were first screened for JAK2 (V617F) mutation by tetra-primer ARMS-PCR, followed by quantification of JAK2 (V617F) mutation burden in all V617F positive MPN patients by ASO-PCR. Patients were screened for BCR/ABL1 fusion gene transcripts to rule out Ph positive status. Our findings showed that mRNA levels of PD-L1 and STAT3 were significantly higher in JAK2 (V617F) MPN patients, while as STAT5 was insignificantly upregulated. STAT3 and STAT5 phosphorylation was seen to be higher in JAK2 (V617F) MPN patients compared to the JAK2 (WT) patients. Upregulation of PD-L1, STAT3 and STAT5 was significantly associated with JAK2 (V617F) percentage in MPN patients. PD-L1, STAT3 and STAT5 expression significantly and positively correlated with JAK2 (V617F) allele burden. In addition, significant coexpression of PD-L1 with STAT3 and STAT5 was observed in MPN patients. In summary, JAK2 (V617F) mutation is accompanied by increased PD-L1 expression and this PD-L1 over expression is mediated by JAK2 (V617F) mainly through STAT3, while as STAT5 may play a minor role.

Correction to: Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5.

In the original publication, third author name was incorrectly published as "Ab Rashid Mir". The correct name should read as "Rashid Mir".

Association of GABAA Receptor Gene with Epilepsy Syndromes.

GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making α1, ϒ2, and δ subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders. We explored the association of GABAA receptor gene mutation/SNPs in JME and LGS patients in Indian population. A total of 100 epilepsy syndrome patients (50 JME and 50 LGS) and 100 healthy control subjects were recruited and analyzed by AS-PCR and RFLP-PCR techniques. In our study, GABRA1 965 C > A mutation and 15 A > G polymorphism gene may play an important role in modulating the drug efficacy in LGS patients. The GABRA1 15 A > G polymorphism may also play an important role in the susceptibility of LGS and the inheritance of GG genotype of this polymorphism may provide an increased risk of development of LGS. The GABRG2 588 C > T polymorphism may decrease the duration of seizures in JME patients. The GABRD 659 G > A polymorphism may play an important role in the susceptibility of JME and LGS and this polymorphism may also increase the duration of postictal period in JME patients but may decrease the duration of seizure in LGS patients.