Different environmental and genetic factors have been attributed to the etiology of colorectal cancer. Dysbiotic gut microbiota is associated with initiation and progression of colon carcinogenesis. Hyperactivation of STAT3 promotes carcinogenesis by upregulating cell proliferation, survival, tumor-induced immunosupression and angiogenesis. IRAK-M is a negative regulator of toll-like receptor signaling and inhibits innate immune response. The cancer cell may exploit this property of IRAK-M and evade host immune surveillance. Recently, it has been found that IRAK-M provide controlled feed back to bacteria involved in colorectal cancer by reducing antibacterial response in mice. Furthermore, IRAK-M increased the stability of STAT3 in tumor cells that support tumor promotion by upregulating cell proliferation and survival. Thus, it is suggested that IRAK-M promotes colitis associated colon cancer by enhancing bacterial colonization and stabilization of STAT3.
Animals ; Bacteria ; Carcinogenesis* ; Cell Proliferation ; Colitis ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Gastrointestinal Microbiome ; Immunity, Innate ; Mice ; Microbiota ; Toll-Like Receptors

In the present study we evaluated the anti-inflammatory potential of 3-hydroxy-4,7-megastigmadien-9-one (Comp) isolated from Ulva pertusa Kjellman, in LPS-stimulated bone marrow-derived dendritic cells (BMDCs). Comp treatment exhibited strong dose dependent inhibition of IL-12 p40 and IL-6 cytokine production with IC₅₀ values of 7.85 ± 0.32 and 7.86 ± 0.18, respectively in LPS-stimulated BMDCs. Treatment of Comp inhibited MAPKs and NF-κB pathways in LPS-stimulated BMDCs by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκB. Thus, these results suggest that Comp have a significant anti-inflammatory property and affirm further studies concerning the potentials of Comp for medicinal use.
Dendritic Cells ; Interleukin-12 ; Interleukin-6 ; Phosphorylation ; Protein Kinases* ; Ulva*

Marine algae exhibit broad spectrum anti-bacterial and anti-inflammatory activities. Acrosorium polyneurum (A. polyneurum) is a marine red alga and belongs to the family Delesseriaceae. The present research evaluates the antiinflammatory effects of A. polyneurum extract (APE) on pro-inflammatory cytokine production. APE demonstrated substantial inhibitory effects on production of pro-inflammatory cytokine in bone marrow-derived macrophages (BMDMs). APE pre-treatment in the lipopolysaccharide (LPS)-stimulated BMDMs exhibited a robust inhibitory effect on production of interleukin (IL)-12, IL-6 and tumor necrosis factor (TNF)-α. It revealed a robust inhibitory effect on phosphorylation of ERK1/2, JNK1/2 and p38. APE also showed remarkable inhibitory effect on phosphorylation and degradation of IκBα. Furthermore, APE pre-treatment demonstrated substantial inhibition of LPS-induced production of nitric oxide and inducible nitric oxide synthase. Collectively, these data suggest that APE has a noteworthy anti-inflammatory property and deserve further studies concerning its potential use as a medicinal agent for inflammation-related disorders.
Hominidae ; Humans ; Interleukin-6 ; Interleukins ; Macrophages ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; Tumor Necrosis Factor-alpha

Gut microbiota play a critical role in the development of intestinal cancer. Dietary changes cause dysbiosis of gut microbiota that mediates production of dietary factors triggering intestinal cancer. Genetic and dietary factors work in different combinatorial ways in initiation and progression of intestinal cancer, one of which is changes in gut microbiota. Recently, it has been found that high-fat-diet promote intestinal tumorigenesis in a genetically susceptible K-ras(G12Dint) mice without induction of obesity. High-fat-diet along with oncogene activation dampened paneth-cell mediated immunity and thus shift bacterial communities in such a way that promotes intestinal cancer.
Animals ; Carcinogenesis* ; Dysbiosis ; Intestinal Neoplasms ; Mice ; Microbiota* ; Obesity ; Oncogenes

The nucleotide-binding oligomerization domain-like receptors (NOD-like receptors, NLRs) are intracellular sensors. Most of them positively affect inflammatory responses, particularly the inflammasome forming NLRs. On the other hand, several studies on gene-deficient mice have revealed that several NLRs negatively influence innate immune responses. Some recent studies have identified a novel sub-group of non-inflammasome forming NLRs that negatively influence different pathways related to inflammation and carcinogenesis. Cytosolic pattern recognition receptor NRLC3 is a negative regulator of innate immune response. In this review we will discuss finding related with NLRC3 and its mechanism by which it alter cancer pathogenesis. Recently, it has been found that mice deficient in Nlrc3 are hyper-susceptible to colitis and colitis-associated colon carcinogenesis. Oncogenic inhibitory effect of NLRC3 is more dominant in epithelial compartment than hematopoietic compartment. It down regulates mTOR signaling and reduce cell proliferation. NLRC3 interact with PI3Ks and suppress activation of PI3K dependent kinase AKT. Understanding the role of NLRC3 in cancer may facilitate the recognition of new therapeutic strategies.
Animals ; Carcinogenesis ; Cell Proliferation ; Colitis ; Colon* ; Colonic Neoplasms* ; Cytosol ; Hand ; Immunity, Innate ; Inflammasomes ; Inflammation ; Mice ; Phosphotransferases

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.
Alzheimer Disease ; Arthritis, Rheumatoid ; Cardiovascular Diseases ; Cimicifuga ; Cytokines ; Dendritic Cells ; Immune System ; In Vitro Techniques ; Inflammation ; Interleukin-6 ; Interleukins ; Korea ; Primary Cell Culture ; Ranunculaceae ; Tumor Necrosis Factor-alpha

Objectives Blood stream infections (BSIs) are the main cause of morbidity and mortality in children worldwide. The present study was carried out to determine the prevalence of BSI with a focus on the identification of the causative agent of BSI, and to further evaluate the antibiotic susceptibility profile of the causing bacterial pathogens.Methods A cross-section study was carried out at the tertiary care hospital in Peshawar, Pakistan from January to December, 2018. Blood samples were collected in BACTEC