Immunostimulatory effect of chitosan conjugated green copper oxide nanoparticles in tumor immunotherapy.

Current study demonstrates the immunogenic role of biopolymer coated green synthesized copper oxide nanoparticles by the induction of cellular immunity through the activation immune cells. Alongside humoral immunity response was triggered by the surface coated NPs through IgG response which indicate the adjuvanic role of the nano conjugate. Th1 (Type 1 and Type 2 helper T cells) and Th2 cells were activated after the treatment with nano conjugate and act as an immunostimulant which would inhibit the proliferation of breast cancer (MCF-7) and cervical cancer (HeLa) cells in in vitro. Solid tumor induced by 4 T1 cells were also inhibited in in vivo Balb/C mice model. Secretion of pro-inflammatory cytokines and the increase in CD + 4 populations indicate the activation of immune cells in the current study. Immunotherapy by the help of metal nano conjugate can be an effective tool to eradicate the cancer cells from the system.

Novel pfkelch13 Gene Polymorphism Associates With Artemisinin Resistance in Eastern India.

BACKGROUND: Artesunate-sulfadoxine-pyrimethamine (ASSP) is the frontline artemisinin combination therapy (ACT) in India. Random, irrational, subtherapeutic artemisinin doses and self-medication with ACT along with predominance of sulfadoxine-pyrimethamine resistance parasite invoked a strong possibility of emerging artemisinin-resistant malaria parasites. METHODS: This study involved 226 patients with uncomplicated Plasmodium falciparum infection who had successfully completed the 42 days follow-up after ASSP combination therapy from April 2014 to January 2016. We assessed the ASSP treatment efficacy by evaluating parasite clearance half-life, pfkelch13, and other (pfdhfr, pfdhps, pfmdr1, pfcrt) gene mutations and survival of parasites as detected by an ex vivo ring-stage survival assay (RSA). FINDINGS: Slow-clearing infections with longer parasite clearance half-lives (>5 hours) were observed in 12% isolates. Cure rate after ASSP treatment was declining to about 84.1%. ASSP failure was recorded in 15.9% (early treatment failure, 7.9%; late treatment failure, 7.9%) of isolates. In sum, 24 patients (10.6%) had parasite clearance half-lives greater than 5 hours with pfkelch13 polymorphism after 441 codon; in 15 of those patients (6.6%), parasites had not cleared by 72 hours after initiation of therapy. Median ex vivo ring-stage survival rate of these isolates was very high (12.2%; 95% confidence interval [CI], 10.9-13.8) from that of cured patients (0.9%; 95% CI, 0.09-1.07). Of these 15 patients, 13 patients had pfkelch13 G625R polymorphism, whereas 2 patients contained R539T polymorphism. As per the World Health Organization guideline, these 15 isolates were true artemisinin-resistant isolates. INTERPRETATION: Identification of artemisinin-resistant isolates in India together with new mutations and increasing combination therapy failures blow alarms for urgent malaria control.

Investigation of aqueous phase dynamics in a uranium stripping unit using radioactive tracer.

Mixer-setters units are widely used in uranium purification processes. For efficient operations of mixer-settler units, it is essential to measure the hydrodynamics parameters of the different phases involved. The residence time distribution (RTD) measurement is commonly used method to estimate the hydrodynamics parameters of process reactors. In the present study, RTD of the aqueous phase was measured in different stages mixer-settler unit (mixers, settlers and mixer-settler units) used for stripping operation using Iodine-131 as a radiotracer. For the RTD measurements, radiotracer was injected as an impulse in aqueous phase feed line and its movement was monitored at different locations in the stripping unit using NaI(Tl) detectors. The mean residence times (MRTs) of the aqueous phase were estimated from measured RTD curves. For quantification of the degree of mixing, suitable flow models were proposed based on design and nature of the measured RTD curves and subsequently used for simulation. Based on the results of the RTD study, the mixing of aqueous phase was characterized and design of the stripping unit and its sub-units were validated. The optimum conditions were identified for efficient for the operation of the stripping unit.

Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India.

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr-dhps (A16I51R59N108I164-S436G437K540G581T613) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13-independent artemisinin-resistance.

Self assembled arjunolic acid acts as a smart weapon against cancer through TNF- α mediated ROS generation.

Arjunolic acid (AA) a plant derived pentacyclic triterpenoid which showed effective anticancer activity against MCF-7 and HeLa cells as well as no significant toxic effect was observed against normal lymphocytes. In the current study the self assemble property of arjunolic acid gives an extra emphasis on anticancer activity which was proved by several fluorescence studies like ROS generation, EtBr/AO and DAPI staining. At a selected dose of 50µg/ml AA disrupt the redox balance inside the cancer cells by producing reactive oxygen species. The apoptotic event was mediated by two key regulator proteins TNF-α and NF-κß which was proved here. The increment of the pro-inflammatory cytokines indicates the ROS mediated pathway of cancer cell apoptosis.

Biodistribution and toxickinetic variances of chemical and green Copper oxide nanoparticles in vitro and in vivo.

In this study, chemical (S1) and green (S2) Copper Oxide nanoparticles (NPs) were synthesized to determine their biodistribution and toxicokinetic variances in vitro and in vivo. Both NPs significantly released Copper ions (Cu) in lymphocytes and were primarily deposited in the mononuclear phagocyte system (MPS) such as the liver and spleen in mice. In particular, S2NPs seemed to be prominently stored in the spleen, whereas the S1NPs were widely stored in more organs including the liver, heart, lungs, kidney and intestine. The circulation in the blood and fecal excretions both showed higher S2NPs contents respectively. Measurements of cell viability, Hemolysis assay, Reactive Oxygen Species (ROS) generation, biochemical estimation and apoptotic or necrotic study in lymphocytes after 24 h and measurements of body and organ weight, serum chemistry evaluation, cytokines level, protein expressions and histopathology of Balb/C mice after 15 days indicated significant toxicity difference between the S1NPs and S2NPs. Our observations proved that the NPs physiochemical properties influence toxicity and Biodistribution profiles in vitro and in vivo.

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity.

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated.