Ruthenium-Catalyzed Chemo-Selective Carbene Insertion into C-H Bond of Styrene over Cyclopropanation: C-C Bond Formation.

The C-C bond formation reactions are important in organic synthesis. Heck reaction is known to arylate the terminal carbon of olefins; however, direct alkylation of the terminal carbon of olefin is limited. Herein, we report a novel ruthenium-catalyzed selective cross-coupling reaction of styrene and α-diazoesters to form a new C-C bond over cyclopropanation via the C-H insertion process for the first time. Using this novel methodology, a wide variety of substrates have been utilized and a variety of α-vinylated benzylic esters and densely functionalized olefins have been synthesized with good stereoselectivity under mild reaction conditions. The overall reaction process proceeds through the carbene insertion into styrene to form the desired products in good to excellent yields with proper stereoselectivity. The selective C-H inserted product, wide substrate scope, and excellent functional group tolerance are the best features of this work.

IL-33 ameliorates liver injury and inflammation in Poly I:C and Concanavalin-A induced acute hepatitis.

The IL-33/ST2 axis is known to be involved in liver pathologies and IL-33 is over-expressed in mouse hepatitis models. We aimed to investigate the proposed protective effect of IL-33 in murine fulminant hepatitis induced by a Toll like receptor 3 (TLR3) viral mimetic, Poly I:C or by Concanavalin-A (ConA). The Balb/C mice were administered intravenously with ConA (15 mg/kg) or Poly I:C (30 µg/mouse) to induce acute hepatitis along with vehicle control. The recombinant mouse IL-33 (rIL-33) was injected (0.2 µg/mouse) to mice 2 h prior to ConA or Poly I:C injection to check its hepato-protective effects. The gross lesions, level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), histopathology (H&E staining) and levels of IFNγ and TNFα were measured by ELISA. The gross pathological liver injury induced by Poly I:C or ConA was reduced by rIL-33 administration in mice. The levels of AST and ALT were significantly (P ≤ 0.05) higher in mice challenged with Poly I:C or ConA in comparison to control mice. The rIL-33 pre-treated mice in both Poly I:C and ConA challenge groups showed significantly (P ≤ 0.05) lower levels of AST and ALT, and decreased liver injury (parenchymal and per-vascular necrotic areas) in histological liver sections. The soluble levels of TNFα and IFNγ were significantly (P ≤ 0.05) raised in Poly I:C or ConA challenged mice than control mice. The levels of TNFα and IFNγ were significantly reduced (P ≤ 0.05) in rIL-33 pre-treated mice. In conclusion, the exogenous IL-33 administration mitigated liver injury and inflammation (decreased levels of IFNγ and TNFα) in Poly I:C and ConA-induced acute hepatitis in mice.

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance.

BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions. DATA SOURCES: The data of mouse hepatic models and relevant human liver diseases presented in this review are systematically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CCl4, acetaminophen or alcohol represent necrotic cell death with activation of cytochrome pathway, formation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-alpha induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrated the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The alpha-GalCer-induced liver injury was mediated by TNF-alpha. The LPS-induced hepatitis involved TNF-alpha, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-alpha signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune cells and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcoholic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS: The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.

Bioremediation of polycyclic aromatic hydrocarbons: An updated microbiological review.

A class of organic priority pollutants known as PAHs is of critical public health and environmental concern due to its carcinogenic properties as well as its genotoxic, mutagenic, and cytotoxic properties. Research to eliminate PAHs from the environment has increased significantly due to awareness about their negative effects on the environment and human health. Various environmental factors, including nutrients, microorganisms present and their abundance, and the nature and chemical properties of the PAH affect the biodegradation of PAHs. A large spectrum of bacteria, fungi, and algae have ability to degrade PAHs with the biodegradation capacity of bacteria and fungi receiving the most attention. A considerable amount of research has been conducted in the last few decades on analyzing microbial communities for their genomic organization, enzymatic and biochemical properties capable of degrading PAH. While it is true that PAH degrading microorganisms offer potential for recovering damaged ecosystems in a cost-efficient way, new advances are needed to make these microbes more robust and successful at eliminating toxic chemicals. By optimizing some factors like adsorption, bioavailability and mass transfer of PAHs, microorganisms in their natural habitat could be greatly improved to biodegrade PAHs. This review aims to comprehensively discuss the latest findings and address the current wealth of knowledge in the microbial bioremediation of PAHs. Additionally, recent breakthroughs in PAH degradation are discussed in order to facilitate a broader understanding of the bioremediation of PAHs in the environment.

Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases.

PURPOSE: The purpose of this review was to examine the comprehensively accumulated data regarding potential therapeutic aspects of exogenous administration of interleukin 33 (IL-33) or its antagonists in allergic, cancerous, infectious, and inflammatory diseases. METHODS: A selected review was undertaken of publications that examined the protective and exacerbating effects of IL-33 or its inhibitors in different diseases. Mechanisms of action are summarized to examine the putative role of IL-33 in various diseases. FINDINGS: IL-33 promoted antibacterial, antiviral, anti-inflammatory, and vaccine adjuvant functions. However, in TH2-biased respiratory, allergic, parasitic, and inflammatory conditions, IL-33 exhibited disease-sensitizing effects. The alarmin cytokine IL-33 induced protective effects in diseases via recruitment of regulatory T cells; antiviral CD8(+) cells, natural killer cells, γδ T cells, and nuocytes; antibacterial and antifungal neutrophils or macrophages; vaccine-associated B/T cells; and inhibition of nuclear factor-κB-mediated gene transcription. In contrast, IL-33 exacerbated the disease process by increasing TH2 cytokines, IgE and eosinophilic immune responses, and inhibition of leukocyte recruitment in various diseases. IMPLICATIONS: The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process.