IKKβ regulates antimicrobial innate immune responses in the yellow mealworm, Tenebrio molitor.

Toll and IMD pathways regulate antimicrobial innate immune responses in insect model systems. The transcriptional activation of antimicrobial peptides (AMPs) confers humoral immunity in the host against invaded pathogens. The IKK kinase complex (IKKα, IKKβ, and the regulatory subunit IKKγ/NEMO) centrally regulates the NF-κB response to various stimuli.

Spiraea prunifolia leaves extract inhibits adipogenesis and lipogenesis by promoting β-oxidation in high fat diet-induced obese mice.

Spiraea prunifolia has been used in Korean traditional medicine to treat malaria, fever, and emetic conditions. Previous investigation reported that several parts of Spiraea prunifolia show various functional effects. However, the effect of Spiraea prunifolia leaves extract (SPE) on anti-obesity remains unclear.

IKKε Is Required to Confer Protection Against Gram-Negative Bacteria, by the Regulation of Antimicrobial Peptide Production in the Fat Body.

The inhibitor of nuclear factor-kappa B (NF-κB) kinase (IKK) is the core regulator of the NF-κB pathway against pathogenic invasion in vertebrates or invertebrates. IKKβ, -ε and -γ have pivotal roles in the Toll and immune deficiency (IMD) pathways. In this study, a homolog of IKKε (IKKε) was identified from RNA sequence database and functionally characterized for its role in regulating immune signaling pathways in insects.

Improvement of Obesity and Dyslipidemic Activity of in C57BL/6 Mice Fed a High-Carbohydrate Diet.

Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups ( = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days.

IKKγ/NEMO Is Required to Confer Antimicrobial Innate Immune Responses in the Yellow Mealworm, .

IKK/NEMO is the regulatory subunit of the IκB kinase (IKK) complex, which regulates the NF-κB signaling pathway. Within the IKK complex, IKK/NEMO is the non-catalytic subunit, whereas IKK and IKK are the structurally related catalytic subunits. In this study, was screened from the RNA-Seq database and functionally characterized using RNAi screening for its role in regulating antimicrobial peptide (AMP) genes after microbial challenges.

Autophagy-Related Gene 8 () Is Required to Confer Anti-Bacterial Gut Immunity.

Autophagy is an important process by which pathogens and damaged or unused organelles are eliminated. The role of autophagy in development and the immune response to pathogens is well established. Autophagy-related protein 8 (Atg8) is involved in the formation of the autophagosome and, with the help of the serine protease Atg4, mediates the delivery of both vesicles and the autophagosome to the vacuole.

Author Correction: TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor.

Relish, a transcription factor, is a critical downstream component of the immune deficiency (Imd) pathway and regulates host defense against bacterial infection by mediating antimicrobial peptide (AMP) synthesis. Understanding the immunological function of the mealworm beetle, Tenebrio molitor Relish (TmRelish) will be instructive in understanding insect immunity. In the present study, full-length ORF of TmRelish was retrieved from T.

TmDorX2 positively regulates antimicrobial peptides in Tenebrio molitor gut, fat body, and hemocytes in response to bacterial and fungal infection.

Dorsal, a member of the nuclear factor-kappa B (NF-κB) family of transcription factors, is a critical downstream component of the Toll pathway that regulates the expression of antimicrobial peptides (AMPs) against pathogen invasion. In this study, the full-length ORF of Dorsal was identified from the RNA-seq database of the mealworm beetle Tenebrio molitor (TmDorX2). The ORF of TmDorX2 was 1,482 bp in length, encoding a polypeptide of 493 amino acid residues.

Regulation of the expression of nine antimicrobial peptide genes by TmIMD confers resistance against Gram-negative bacteria.

Immune deficiency (IMD) is a death domain-containing protein that is essential for the IMD/NF-κB humoral and epithelial immune responses to Gram-negative bacteria and viruses in insects. In the immune signaling cascade, IMD is recruited together with FADD and the caspase DREDD after the mobilization of PGRP receptors. Activated IMD regulates the expression of effector antimicrobial peptides (AMP) that protect against invading microorganisms.

Korean red ginseng water extract alleviates atopic dermatitis-like inflammatory responses by negative regulation of mitogen-activated protein kinase signaling pathway in vivo.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Korean red ginseng is a Korean traditional medicine. In this study, we estimated the effects of Korean red ginseng water extract (RGE) in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced BALB/c mouse model which develops AD-like lesions.

TmToll-7 Plays a Crucial Role in Innate Immune Responses Against Gram-Negative Bacteria by Regulating 5 AMP Genes in .

Although it is known that the Toll-7 receptor plays a critical role in antiviral autophagy, its function in other insects has not yet been reported. Here, we have identified a Toll-like receptor 7 gene, , in the coleopteran insect and examined its potential role in antibacterial and antifungal immunity. We showed that expression was significantly induced in larvae 6 h after infection with and and 9 h after infection with .

Molecular Cloning and Effects of -Silencing on Larval Survivability Against and in .

The 14-3-3 family of proteins performs key regulatory functions in phosphorylation-dependent signaling pathways including cell survival and proliferation, apoptosis, regulation of chromatin structure and autophagy. In this study, the zeta isoform of 14-3-3 proteins (designated as Tm14-3-3ζ) was identified from the expressed sequence tags (ESTs) and RNA sequencing (RNA-Seq) database of the coleopteran pest, . messenger RNA (mRNA) is expressed at higher levels in the immune organs of the larval and adult stages of the insect and exhibit almost five-fold induction within 3 h post-infection of the larvae with and .

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor.

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp.

Marmesin-mediated suppression of VEGF/VEGFR and integrin β1 expression: Its implication in non-small cell lung cancer cell responses and tumor angiogenesis.

In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2.

Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis.

In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo.

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression.

Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest.

Novel roles of ginsenoside Rg3 in apoptosis through downregulation of epidermal growth factor receptor.

Ginsenoside Rg3 (Rg3), a pharmacologically active compound from red ginseng, has been reported to induce cell death in various cancer cell lines, although the specific mechanisms have not been well established. In the present study, Rg3 treatment to A549 human lung adenocarcinoma led to cell death via not only apoptotic pathways but also the downregulation of epidermal growth factor receptor (EGFR). We used cross-linker and cell enzyme-linked immunosorbent assays to show that Rg3 inhibited EGFR dimerization by EGF stimulation and caused EGFR internalization from the cell membrane.

Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K‑dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation.

Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins.

Antagonism of VEGF-A-induced increase in vascular permeability by an integrin α3β1-Shp-1-cAMP/PKA pathway.

In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A-induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells.

COX-2 expression and inflammatory effects by diesel exhaust particles in vitro and in vivo.

Recent studies have shown that diesel exhaust particles (DEP) have adverse effects on the respiratory tract in vitro and in vivo, related to various pro-inflammatory cytokines and inflammatory mediators. The inflammation induced by the production of cyclooxygenase (COX)-2, an important mediator of inflammation and tumor promotion, and excess eicosanoids may be central to the pathogenesis of DEP-induced airway inflammation. However, the role of COX-2 in the pathogenesis of DEP-induced lung inflammation remains unclear, especially in vivo.