2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-β Glycyrrhetinic acid (18 β-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18 β-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18 β-GA at two different doses (45 and 75 mg kg⁻¹ b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18 β-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18 β-GA. Our findings suggest that pretreatment with 18 β-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation.

A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10^-09; rs12008279—OR 1.56, P = 1.53 x 10^-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10^-09; rs6622126—OR 1.75, P = 4.04x10^-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10^-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10^-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

Nanotechnology as a field of knowledge is burgeoning day by day, making an impact in all spheres of human life. Biological methods of synthesis have paved way for the “greener synthesis” of nanoparticles. The “green synthesis” has proven to be a better method due to their slower kinetics, better manipulation, control over crystal growth and stabilization. Recent advancement in the field includes enzymatic method of synthesis suggesting the enzymes to be responsible for the nanoparticle formation. The biomedical applications of silver nanoparticle (AgNPs) can be effective by the use of biologically synthesized nanoparticles which minimize the factors like cost of synthesis and toxicity of product. These are further found to be exceptionally stable when compared with the nanoparticles prepared through other methods. In the present study, silver nanoparticles were biologically synthesized using pure enzyme α-amylase and the other one by using soluble proteins of neem leaf extracts. The nanoparticles were characterized by UV-Visible absorption, Transmission Electron Microscopy (TEM) and X-ray Diffraction (XRD). In addition to the normal cell line (INT-407), the cytotoxicity of the prepared nanoparticles was evaluated on human cervical cancer cells (SiHa) as well. The results indicated that the IC₅₀ of neem extracted AgNPs and α-amylase were at marginally variable concentrations that is; lower concentration of ≤4.25 μg/ml for the former and ≤32.5 μg/ml for the latter. In addition, our results also demonstrated that in vitro cytotoxicity assessment of the AgNPs has significant correlation with the total protein concentration in treated cells. These findings confirm the cytotoxic properties of AgNPs, and suggest that they may be cost-effective and an alternative measure in the field of cancer therapeutics.

Purpose: Mesenchymal stem cells (MSC) are an essential component of the bone marrow microenvironment and have shown to support cancer evolution in multiple myeloma. Despite the increasing evidence that multiple myeloma MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of this study was to determine the importance of MSCs in disease progression and outcome in multiple myeloma. Experimental Design: To determine the impact of MSCs on multiple myeloma outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in plasma cells (PC) or other cells present in bone marrow aspirates. We then applied this MSC gene signature to whole bone marrow biopsies of multiple myeloma patients compared with healthy controls and determined MSC expression scores specific to multiple myeloma and predictive of outcome. Results: We show that multiple myeloma MSC gene expression signatures can differentiate multiple myeloma from monoclonal gammopathy and smoldering multiple myeloma (SMM) as well as from healthy controls and treated multiple myeloma patients who have achieved a complete remission. We identified a prognostic gene score based on three MSC specific genes, COL4A1, NPR3 and ITGBL1, that was able to predict progression-free survival in multiple myeloma patients and progression into multiple myeloma from SMM. Conclusions: Our findings show that progression of multiple myeloma and of SMM into multiple myeloma does not rely solely on intrinsic PC factors, but is independently affected by the biology of the surrounding microenvironment. Clin Cancer Res; 24(12); 2913–9. ©2018 AACR.

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.