Manipur, an international border region has the highest incidence of human immunodeficiency virus (HIV)-1 infection in India. Nevertheless, there have been no analytical reviews of research article published within this region. In this review, the authors aim to draw the attention of policy makers, medical practitioners and researchers in adopting new strategies to limit the expansion of HIV/acquired immunodeficiency syndrome (AIDS) not only in Manipur but also in other international border areas. A systematic search for published literature in last decade was performed based on the keywords ‘Manipur’ and ‘HIV’ using the PubMed. Twenty-six articles were selected and reviewed. There were high incidence of drug resistance (53%), emergence of recombinant virus (32%) and increased incidence of co-infection with hepatitis C virus. The prime cause of the HIV is due to the uses of ‘heroin’ smuggled from the ‘South Asia Golden Triangle’ and complex patterns of cross-border movement for trade and commerce. The drug abuse, social stigma, geographical location and resource limitation and socio-political problem of the region have contributed strongly on spreading and failure of preventively programme of HIV/AIDS. This review will provide vital knowledge for the policy makers and clinicians for sentinel surveillance of AIDS pandemic in Manipur and other international border regions.

Increasing incidence of drug resistance is ascertained to be the main obstacles in limiting the virus among the human immunodeficiency virus (HIV) infected individuals. This study investigates the drug resistance mutations (DRMs), genetic variants and origin of transmitted drug resistance of HIV-1 among the HIV-1 infected wives of intravenous drug users (IDUs) in Manipur. 44 HIV pol gene sequences were generated from 56 blood samples by viral gene amplification and sequencing. Sequences were then analysed for drug resistance, genetic variants and origin. The result revealed that among the treatment naive cases, 35.7% had Transmitted Drug Resistance Mutations (TDRMs) while among treatment experienced cases, 50% had Acquired Drug Resistant Mutations (ADRMs). These TDRMs and ADRMs conferred resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and/or protease inhibitors (PIs). Majority of the isolated HIV-1 sequences (77.3%) were subtype C while 9.1% was discordant subtype, 6.8% was subtype B, 4.5% was CRF_01AE and 2.3% was URF_BC. TDRM strains were found to be introduced from Myanmar, Vietnam and mainland India. This study also reveals the appearance of CRF_01AE for the first time in Manipur. The finding of this study indicates high prevalence of drug resistant mutations and complex molecular epidemiology in Manipur.

Background: We have previously reported that a new intronless gene for casein kinase 2α (CK2α), CSNK2A3, is expressed in human cells. The promoter of the well-known CK2α, CSNK2A1, displays characteristics of a housekeeping gene, whereas CSNK2A3 has a characteristic of a regulated promoter with two TATA boxes and a CAAT box. GPR68, a family of the G protein-coupled receptors, is also known as ovarian cancer G protein-coupled receptor 1 (OGR1). In the current study, we analyzed the roles of CK2α genes and neutral endopeptidase (NEP), a key enzyme that influences a variety of malignancies, in the OGR1-induced inhibition of A549 cell migration. Methods: We analyzed the transcript expressions of both the CK2α genes (CSNK2A1 and CSNK2A3) and NEP upon OGR1 overexpression. Protein expression of CK2α and NEP were also analyzed. We further elucidated the functional roles of both CK2α and NEP in the OGR1-induced inhibition of A549 cell migration in vitro using a wound-healing assay. We also analyzed the molecular mechanisms involved in the OGR1-induced inhibition of lung cancer cell migration. Results: The findings of this study showed that OGR1 upregulated the expression of CSNK2A3 but not CSNK2A1 in the A549 cells. The findings further suggested OGR1 also upregulates the expression of NEP. The OGR1-induced inhibition of A549 cell migration was abrogated completely by inhibition of CK2α activity, whereas partial abrogation (~ 30%) was observed in the presence of NEP inhibition. The results also revealed that OGR1 regulates CSNK2A3 via activation of Rac1/cdc42 and MAPKs pathways. CK2 is ubiquitously expressed, and in contrast, is believed to be a constitutively active enzyme, and its regulation appears to be independent of known second messengers. Conclusion: In the current study, we report for the first time the OGR1-induced regulation of CSNK2A3, CK2αP, and NEP in A549 cancer cells. Our study also decoded the downstream cellular proteins of OGR1 as well as the molecular mechanism involved in OGR1-induced inhibition of A549 cell migration. The findings of this research suggest the potential therapeutic targets to inhibit lung cancer progression.

The leaf crude extract of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and the inhibition of cell proliferation in the prostate cancer cell line PC3, as assessed by agarose gel electrophoresis, comet assay and MTT assay, respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT assay. The light brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR), and electrospray ionization (ESI) mass spectrometry. The compound was identified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from Oroxylum indicum in this current study is oroxyquinone. The half-maximal inhibitory concentration (IC₅₀) of oroxyquinone on PC3 cells was 58.9 µM (95% CI = 54.5 to 63.7 µM). Treatment of PC3 cells with oroxyquinone induced genomic DNA fragmentation and chromatin condensation, increased in the annexin-V positive cells, arrested the cell cycle at S phases, and inhibited the cell migration; as assessed by comet assay, DAPI staining, flow cytometry and a wound healing assay, respectively. On the investigation of the molecular mechanism of the induction of apoptosis, the results indicated that oroxyquinone induced caspase-3 and PARP independent apoptosis but through the p38 pathway and the localization of AIF into the nucleus. The present study identifies a novel anticancer molecule and provides scientific evidence supporting the therapeutic potency of Oroxylum indicum for ethnomedicinal uses.

We have previously reported that ovarian cancer G protein-coupled receptor 1 (OGR1) is a new metastasis suppressor gene. We have also reported for the first time that a new intronless gene for casein kinase 2α ( CSNK2A3 ) is expressed in human cells. The promoter of the well-known casein kinase 2α ( CSNK2A1 ) displays characteristics of housekeeping gene whereas CSNK2A3 has a characteristic of a regulated promoter with two TATA boxes and a CAAT box. In this study, we found that OGR1 up-regulates expression of CSNK2A3 by about 3 folds in A549 cells but not CSNK2A1 . OGR1 also up-regulates expression of neutral endopeptidase (NEP). The OGR1 induced inhibition of A549 cell migration is completely abrogated by inhibition of casein kinase 2α activity, whereas partial abrogation (~ 30%) was observed in the presence of NEP inhibition. The results also revealed that OGR1 regulates CSNK2A3 via activation of Rac1/cdc42 and MAPKs pathways. CK2 is ubiquitously expressed and in contrast it is believed to be a constitutively active enzyme and its regulation appears to be independent of known second messengers. There is no previous report on how expression of CK2α in cancer cells is regulated although many studies have report of aberrant expression of the kinase in cancer. In the current study, we are reporting for the first time the regulation of intronless casein kinase 2α gene, CSNK2A3 in cancer cells. Our findings suggest that the aberrantly casein kinase 2α expression found in various cancer cells may the due to CSNK2A3 expression which is potentially regulated by several master regulators of the developmental pathways rather than well-known casein kinase 2α gene, CSNK2A1 .