Azadiradione exerts anti-inflammatory and anti-oxidant effects, alleviates dopaminergic neurodegeneration and reduces α-synuclein levels in MPTP-induced mouse model of Parkinson’s disease

Purpose: To determine the effects of azadiradione (AZD), a tetracyclic triterpenoid, in 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)–induced experimental rodent model of Parkinson’s disease (PD). Methods: C57BL/6 mice were intraperitoneally injected MPTP at a dose of 20 mg/kg body weight in saline (4 times at 2-h intervals). Azadiradione (AZD) at doses of 12.5, 25 or 50 mg/kg were administered to separate groups of mice via oral gavage for 6 days prior to MPTP injection. Results: Azadiradione (AZD) reduced loss of tyrosine hydroxylase (TH)-positive neurons. TH-positive counts increased to 91.44 % on treatment with 50 mg/kg AZD. Significantly (p < 0.05) down-regulated α-synuclein levels were seen following MPTP induction and AZD administration. Expressions of Bax, Bcl-2 and cleaved-caspase-3 were significantly downregulated (p < 0.05). Treatment with AZD inhibited the translocation of Cyt-C to the mitochondria, thereby preventing activation of apoptotic cascade. Oxidative stress induced by MPTP was significantly reduced by AZD via up-regulation of glutathione levels and SOD1/HO-1 expression. Azadiradione, at a dose of 50 mg/kg, significantly (p < 0.05) reduced ROS levels from 210.6 19.23%, and also reduced the levels of inflammatory cytokines. Conclusion: These results indicate the anti-inflammatory, anti-oxidative and neuroprotective properties of AZD in mice. Thus, AZD is a potential candidate drug for the management of PD. However, further studies are required to ascertain this

Peripheral Sensitization

Peripheral sensitization indicates increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation, which usually occurs after peripheral tissue injury and inflammation. As an integral part of pain, peripheral sensitization and its mechanisms have received much attention, and numerous types of neurotransmitters and chemicals related to peripheral sensitization were investigated. We developed an animal model of peripheral sensitization, and it provides evidence that some neurotransmitters, such as glutamate and substance P, release from adjacent peripheral nerves contributing to the peripheral sensitization of pathological pain. In this chapter, we reviewed the advances in peripheral sensitization, and it will provide a basis for new targets to attenuate pain of peripheral origin

Environmental Finance:An Interdisciplinary Review

Environmental finance has gained considerable attention globally as an emerging interdisciplinary research area. This study uses bibliometric analysis to systematically review major studies on environmental finance-related areas published since the 1970s. Through a bibliometric analysis of 892 environmental finance-related articles sourced from the Web of Science database, we identified the main research streams and illustrated the trending research themes of environmental finance. We find that publications related to environmental finance have increased exponentially over the past decade. Current research streams include corporate and social re- sponsibility (CSR), climate negotiations, natural gas price volatility, national policy, and cost comparisons. Further analysis of the recent five years of literature shows that emerging research topics include climate finance, sustainable finance, firm value, climate risk, and green bonds. Finally, we conclude with a future research agenda for environmental finance

Effects of triazolodiazepine on the production of interleukin-6 from murine spleen cells and rabbit synovial cells in vitro

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase anaphylactic reaction, and haematopoiesis. Lipopolysaccharide (6–24 μg/ml) significantly induced IL-6 release from murine spleen cells. In cultured rabbit synovial cells interleukin-1 (IL-1, 1–10 U/ml) induced IL-6 production in a concentration-dependent manner. Triazolodiazepine (Tri) is a hetrazepine platelet-activating factor antagonist. In this study we found that Tri (0.1–10 μmol/l) exerted strong inhibitory effects on LPS stimulated IL-6 production in murine spleen cells. Kinetic studies showed that the inhibition of IL-6 release was time-independent. In rabbit synovial cells Tri also reduced IL-6 release induced by IL-1 and tumour necrosis factor. Inhibition of cytokine production by Tri may partially explain its wide and strong anti-inflammatory effects

Antibody dependent enhancement infection of Enterovirus 71 in vitro and in vivo

BACKGROUND: Human enterovirus 71 (EV71) has emerged as a significant cause of acute encephalitis and deaths in young children. The clinical manifestations caused by EV71 varied from mild hand, foot and mouth disease to severe neurological complications and deaths, but its pathogenesis remains elusive. Antibody dependent enhancement (ADE) infection has been reported in various viruses and has been shown to contribute to disease severity. RESULTS: In this study, the presence of sub-neutralizing antibody was demonstrated to enhance EV71 infection in THP-1 cells and increase the mortality of EV71 infection in a suckling mouse model. Further, a secondary infection model was established to characterize the correlation between ADE and disease severity, and primary asymptomatic EV71 infection was shown to increase the mortality of the secondary EV71 infection in suckling mice. CONCLUSIONS: Together, these in vitro and in vivo experiments strongly supported the hypothesis of ADE infection of EV71. The present findings indicate ADE might contribute to the pathogenesis of severe EV71 infection, and raise practical issues of vaccine development and antibody-based therapy