Impact of US China Trade War over Indian Economy

This research paper seeks to evaluate the spillover benefits and threats of the US-China trade war on India. The hypotheses that, can India take trade advantage and substitute US goods in China and vice versa is tested by data from various scholarly articles and carefully aligned with the present and probable policies prevailing in India. This paper gives insight on the multidimensional trade practices that India indulges in. It considers the factors like the exchange rate of Rupee and its military conditions too in order to have a holistic approach on the scenario. This research paper brings out that the fate of Indian economy is closely related to how individual domestic traders react to the economic pulses and the confidence of investors in substituting India as their investments" safe haven. Thus the paper revolves around the question “To what extent will the US-China Trade war benefit Indian economy?”

2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid (Activator-3) is a potent activator of AMPK

AMPK is considered as a potential high value target for metabolic disorders. Here, we present the molecular modeling, in vitro and in vivo characterization of Activator-3, 2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid, an AMP mimetic and a potent pan-AMPK activator. Activator-3 and AMP likely share common activation mode for AMPK activation. Activator-3 enhanced AMPK phosphorylation by upstream kinase LKB1 and protected AMPK complex against dephosphorylation by PP2C. Molecular modeling analyses followed by in vitro mutant AMPK enzyme assays demonstrate that Activator-3 interacts with R70 and R152 of the CBS1 domain on AMPK γ subunit near AMP binding site. Activator-3 and C2, a recently described AMPK mimetic, bind differently in the γ subunit of AMPK. Activator-3 unlike C2 does not show cooperativity of AMPK activity in the presence of physiological concentration of ATP (2 mM). Activator-3 displays good pharmacokinetic profile in rat blood plasma with minimal brain penetration property. Oral treatment of High Sucrose Diet (HSD) fed diabetic rats with 10 mg/kg dose of Activator-3 once in a day for 30 days significantly enhanced glucose utilization, improved lipid profiles and reduced body weight, demonstrating that Activator-3 is a potent AMPK activator that can alleviate the negative metabolic impact of high sucrose diet in rat model

Immunization with Brugia malayi Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against B. malayi Infection in Mastomys coucha.

The current control strategies employing chemotherapy with diethylcarbamazine, ivermectin and albendazole have reduced transmission in some filaria-endemic areas, there is growing interest for complementary approaches, such as vaccines especially in light of threat of parasite developing resistance to mainstay drugs. We earlier demonstrated recombinant heavy chain myosin of B. malayi (Bm-Myo) as a potent vaccine candidate whose efficacy was enhanced by heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo) vaccination in BALB/c mice. BALB/c mouse though does not support the full developmental cycle of B. malayi, however, the degree of protection may be studied in terms of transformation of challenged infective larvae (L3) to next stage (L4) with an ease of delineating the generated immunological response of host. In the current investigation, DNA vaccination with Bm-Myo was therefore undertaken in susceptible rodent host, Mastomys coucha (M. coucha) which sustains the challenged L3 and facilitates their further development to sexually mature adult parasites with patent microfilaraemia. Immunization schedule consisted of Myo-pcD and Myo-pcD+Bm-Myo followed by B. malayi L3 challenge and the degree of protection was evaluated by observing microfilaraemia as well as adult worm establishment. Myo-pcD+Bm-Myo immunized animals not only developed 78.5% reduced blood microfilarial density but also decreased adult worm establishment by 75.3%. In addition, 75.4% of the recovered live females revealed sterilization over those of respective control animals. Myo-pcD+Bm-Myo triggered higher production of specific IgG and its isotypes which induced marked cellular adhesion and cytotoxicity (ADCC) to microfilariae (mf) and L3 in vitro. Both Th1 and Th2 cytokines were significantly up-regulated displaying a mixed immune response conferring considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccination method against LF

Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model.

We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo) of Brugia malayi (B. malayi) in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo) and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo) in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+) and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32) against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23) and pcD-Myo (41.6%±2.45). In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC) to B. malayi infective larvae (L3). pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of providing high degree of protection against filarial larval invasion

Advancements in Cancer Immunotherapies

Recent work has suggested involvement of the immune system in biological therapies specifically targeting tumor microenvironment. Substantial advancement in the treatment of malignant tumors utilizing immune cells, most importantly T cells that play a key role in cell-mediated immunity, have led to success in clinical trials. Therefore, this article focuses on the therapeutic approaches and developmental strategies to treat cancer. This review emphasizes the immunomodulatory response, the involvement of key tumor-infiltrating cells, the mechanistic aspects, and prognostic biomarkers. We also cover recent advancements in therapeutic strategies

Immunization with <i>Brugia malayi</i> Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against <i>B</i>. <i>malayi</i> Infection in <i>Mastomys coucha</i> - Fig 3

<p><b>Antibody-dependent cell-mediated adhesion and cytotoxicity (ADCC) to (A) L3 and (B) mf.</b> Adhesion of PECs on the surface of <i>B</i>. <i>malayi</i> L3 and mfwas observed after 48 h microscopically in the presence of sera of different groups (a) pcD (b) Adj (c) pcD+Adj and (d) Myo-pcD (e) Bm-Myo (f) Myo-pcD+Bm-Myo. Photographs were captured on phase contrast fluorescent microscope (Nikon, Japan) at 40X magnification.</p

Additional file 1: Figure S1. of RNA interference mediated knockdown of Brugia malayi UDP-Galactopyranose mutase severely affects parasite viability, embryogenesis and in vivo development of infective larvae

The graph bars depict percent relative intensity of bands on western blot in comparison to medium control at different time points of exposure (24, 48, 72 h) and after exposure (96, 120 h) as quantified by imageJ version 1.47 software and the blot bands have been shown below each corresponding bar. Considering the medium control intensity to be 100% at each time points the relative intensities of treated ones have been evaluated. P-value < 0.05 was considered significant (*), P < 0.01 as highly significant (**) and P < 0.001 as very highly significant (***). (TIF 4078 kb

Microfilarial kinetics in different immunized group of <i>M</i>.<i>coucha</i>.

<p>Microfilaraemia in the tail blood of immunized and control groups of <i>M</i>. <i>Coucha</i> were determined after 90 days p.c L3. Micofilarial density was significantly reduced at 180 days in Myo-pcD+Bm-Myo compared to Bm-Myo(*P < 0.5) and Myo-pcD (***P < 0.001) and remained low throughout the observation period while all the control groups showed a sharp increasing trend in the following weeks. Myo-pcD+Bm-Myo, Bm-Myo and Myo-pcD groups exhibited 78.5±11.06%, 66.5±7.49%, 37.0±14.88% reduction in microfilarial burden compared to their respective control groups. Experiment was performed in duplicate and data of both were later merged as one. Each point represents a value of mean±SE of 10 animals and the statistical significance was indicated *P < 0.05, **P < 0.01, ***P < 0.001.</p

Intrauterine content of females recovered from control and immunized animals.

<p>Females from control groups <b>(A)</b>pcD<b>(B)</b>Adj<b>(C)</b>pcD+Adj were showed fertile eggs in uterine contained showing normal phenotype and developing stage. <b>(D)</b> Females from Myo-pcD group showed few degenerated eggs while the uteri of females recovered from <b>(E)</b>Bm-Myo and <b>(F)</b>Myo-pcD+Bm-Myo contained degenerated eggs.</p

Antibody-dependent cellular adherence and cytotoxicity (ADCC) to L3 using sera of immunized and control <i>M</i>. <i>coucha</i>.

<p>Antibody-dependent cellular adherence and cytotoxicity (ADCC) to L3 using sera of immunized and control <i>M</i>. <i>coucha</i>.</p