Molecules involved in drug resistance can be targeted for better therapeutic efficacies. Research on midkine (MDK) has escalated in the last few decades, which affirms a positive correlation between disease progression and MDK expression in most cancers and indicates its association with multi-drug resistance in cancer. MDK, a secretory cytokine found in blood, can be exploited as a potent biomarker for the non-invasive detection of drug resistance expressed in various cancers and, thereby, can be targeted. We summarize the current information on the involvement of MDK in drug resistance, and transcriptional regulators of its expression and highlight its potential as a cancer therapeutic target.

The tropospheric NO₂ concentration from OMI AURA always shows high concentrations of NO₂ at a few locations in India, one of the high concentrations of NO₂ hotspots is associated with the locations of seven coal-fired Thermal Power plants (TPPs) in Singrauli. Emissions from TPPs are among the major sources of black carbon (BC) soot in the atmosphere. Knowledge of BC emissions from TPPs is important in characterizing regional carbonaceous particulate emissions, understanding the fog/haze/smog formation, evaluating regional climate forcing, modeling aerosol optical parameters and concentrations of black carbon, and evaluating human health. Furthermore, elevated BC concentrations, over the Indo-Gangetic Plain (IGP) and the Himalayan foothills, have emerged as an important subject to estimate the effects of deposition and atmospheric warming of BC on the accelerated melting of snow and glaciers in the Himalaya. For the first time, this study reports BC concentrations and aerosol optical parameters near dense coal-fired power plants and open cast coal mining adjacent to the east IGP. In-situ measurements were carried out in Singrauli (located in south-east IGP) at a fixed site about 10 km from power plants and in transit measurements in close proximity to the plants, for few days in the month of January and March 2013. At the fixed site, BC concentration up to the 95 μgm⁻³ is observed with strong diurnal variations. BC concentration shows two maxima peaks during early morning and evening hours. High BC concentrations are observed in close proximity to the coal-fired TPPs (>200 μgm⁻³), compared to the outside domain of our study region. Co-located ground-based sunphotometer measurements of aerosol optical depth (AOD) show strong spatial variability at the fixed site, with AOD in the range 0.38–0.58, and the highest AOD in the range 0.7–0.95 near the TPPs in transit measurements (similar to the peak of BC concentrations). Additionally, the Angstrom exponent was found to be in the range 0.4–1.0 (maximum in the morning time) and highest in the proximity of TPPs (~1.0), suggesting abundance of fine particulates, whereas there was low Angstrom exponent over the surrounding coal mining areas. Low Angstrom exponent is characterized by dust from the unpaved roads and nearby coal mining areas. MODIS derived daily AOD shows a good match with the MICROTOPS AOD. The CALIPSO derived subtypes of the aerosol plot shows that the aerosols over Singrauli region are mainly dust, polluted dust, and elevated smoke. The preliminary study for few days provides information about the BC concentrations and aerosol optical properties from Singrauli (one of the NO₂ hotspot locations in India). This preliminary study suggests that long-term continuous monitoring of BC is needed to understand the BC concentrations and aerosol optical properties for better quantification and the estimation of the emission to evaluate radiative forcing in the region.

Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α_1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α_1A/B-AR heteromers are important for α₁-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α_1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α_1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca²⁺-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α_1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α_1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α_1A-AR heteromers are important for intrinsic α₁-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC.

Lipoxygenase (LOX) pathway has emerged to have a role in carcinogenesis. There is an evidence that both 12-LOX and 5-LOX have pro-carcinogenic role. We have previously reported the elevated level of serum 12-LOX in breast cancer patients. This study evaluated the serum level of 5-LOX in breast cancer patients and its in-vitro inhibition assessment with peptide inhibitor YWCS. The level of 5-LOX was determined by surface Plasmon resonance (SPR). The peptide inhibitor of 5-LOX was designed by molecular modeling and kinetic assay was performed by spectrophotometry. The siRNA mediated 5-LOX gene silencing was performed to investigate the effect on proliferation of MDA-MB-231, breast cancer cell line. The serum 5-LOX level in breast cancer (5.69±1.97 ng/μl) was almost 2-fold elevated compared to control (3.53±1.0 ng/μl) (p <0.0001). The peptide YWCS had shown competitive inhibitory effects with IC50, 2.2 μM and dissociation constant (K_D), 4.92 x 10^-8 M. The siRNA mediated knockdown of 5-LOX, resulted in the decreased gene expression for 5-LOX and increased cell death in MDA-MB-231 cell line and thereby play a key role in reducing tumor proliferation. Thus, it can be concluded that 5-LOX is one of the potential serum protein marker for breast cancer and a promising therapeutic target for the same.