Atherosclerosis ; etiology ; metabolism ; Humans ; Inflammation

Burns ; complications ; metabolism ; Humans ; Inflammation ; etiology ; metabolism ; prevention & control

Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.
Acute Lung Injury ; etiology ; metabolism ; Autophagy ; Cytokines ; metabolism ; Inflammation ; metabolism ; Lung ; metabolism ; Lung Injury ; Sepsis ; complications ; metabolism

OBJECTIVETo study single wall carbon nanotubes (SWCNT) and its role in inducing inflammatory cytokines in the cruor-fibrinolysis system of rat.

METHODSTwenty one Wistar rats were divided into four groups: 1) control; 2) low-dose SWCNT (0.15 mg/kg BW); 3) medium-dose SWCNT (0.75 mg/kg BW); 4) high-dose SWCNT (1.5 mg/kg BW). Intratracheal instillation of SWCNT suspensions was administered to rats once per day for 21 days. In order to assess the exposure effect of SWCNT to the rats, activity of Inflammatory cytokine was measured and markers of cruor-fibrinolysis system were studied via ELSIA. Also, change in clotting time was recorded and histopathology was studied.

RESULTSIL-6 and IL-8 concentrations of rats exposed to SWCNT were significantly higher than those in controls (P<0.05). The activity of inflammatory cytokines and histopathological change indicated that oxidative damage occurred. Change in clotting time in rats exposed to SWCNT decreased compared with controls. Meanwhile, t-PA (tissue-tupe plassminogen activator) and AT-III (antithrombin-III) levels in rats exposed to particulates increased or decreased significantly compared with controls (P<0.05). A similar trend was observed for D-dimer (D2D) levels, indicating that SWCNT can impact the cruor-fibrinolysis system of rat.

CONCLUSIONThe results from our study suggest that an increased procoagulant activity and reduced fibrinolytic activity in rats exposed to SWCNT can cause pulmonary oxidative stress and inflammation, due to the release of pro-thrombotic and inflammatory cytokines into the blood circulation of rat.

Animals ; Blood Coagulation ; Body Weight ; Cytokines ; metabolism ; Fibrinolysis ; Inflammation ; etiology ; metabolism ; Nanotubes, Carbon ; Rats ; Rats, Wistar

Despite a higher incidence and less favorable outcome of malignant tumors in obese patients, much less recognized is the link between obesity and cancer. The mechanism of the association of obesity with carcinogenesis remains incompletely understood. Postulated mechanisms include insulin resistance, insulin-like growth factor signaling, chronic inflammation, immunomodulation, hyperglycemia-induced oxidative stress, and changes of intestinal microbiome. Insulin resistance leads to direct mitogenic and antiapoptotic signaling by insulin and the insulin-like growth factor axis. Obesity can be considered to be a state of chronic low-grade inflammation. In obesity, numerous proinflammatory cytokines are released from adipose tissue which may involve in carcinogenesis. Hyperglycemia in susceptible cells results in the overproduction of superoxide and this process is the key to initiating all damaging pathways related to diabetes. This hyperglycemia-induced oxidative stress could be one possible link among obesity, diabetes, and cancer development. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention.
Adipokines/metabolism/physiology ; Gastrointestinal Neoplasms/*etiology/microbiology ; Humans ; Inflammation/etiology ; Insulin/metabolism/physiology ; Leptin/metabolism/physiology ; Obesity/*complications/immunology/metabolism ; Oxidative Stress ; Somatomedins/metabolism/physiology

Colon cancer is the 3rd common malignancy and 4th common cause of cancer death in Korea. Recent studies have shown that abnormal inflammatory response plays a critical role in colon carcinogenesis. A striking example of connection between inflammation and cancer is NF-kappaB, in which key regulator of inflammation and immune response is associated with target for colon cancer treatment. Constitutive NF-kappaB expression in colon cancer is 40-80% in vivo as well as in vitro, and the inactivation of IKKbeta subunit can reduce tumor multiplicity. The possible mechanisms by which NF-kappaB can contribute to colon carcinogenesis include the activator of antiapoptotic gene expression, enhanced cell survival and proliferation, regulation of angiogenesis and promotion of metastasis of cancer cells. Recent insights into the role of NF-kappaB involved in colon cancer development as well as their relevance as therapeutic targets are herein discussed.
Colonic Neoplasms/*etiology/metabolism ; Humans ; I-kappa B Kinase/metabolism/physiology ; Inflammation ; NF-kappa B/metabolism/*physiology

Chronic inflammation has been known to be a risk for many kinds of cancers, including pancreatic and biliary tract cancer. Recently, inflammatory process has emerged as a key mediator of cancer development and progression. Many efforts with experimental results have been given to identify the underlying mechanisms that contribute to inflammation-induced tumorigenesis. Diverse inflammatory pathways have been investigated and inhibitors for inflammation-related signaling pathways have been developed for cancer treatment. This review will summarize recent outcomes about this distinctive process in pancreatic and biliary tract cancer. Taking this evidence into consideration, modulation of inflammatory process will provide useful options for pancreatic and biliary tract cancer treatment.
Biliary Tract Neoplasms/*etiology/metabolism ; Cell Transformation, Neoplastic ; Cyclooxygenase 2/metabolism ; Cytokines/metabolism ; Humans ; *Inflammation ; Matrix Metalloproteinases/metabolism ; NF-kappa B/metabolism ; Pancreatic Neoplasms/*etiology/metabolism ; Receptor, Epidermal Growth Factor/metabolism

Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e.g., asbestos, nanomaterials, and inflammatory diseases such as Barrett's esophagus and oral leukoplakia). Interestingly, several of our studies suggested that inflammation-associated DNA damage in cancer stem-like cells leads to cancer development with aggressive clinical features. Reactive oxygen/nitrogen species from inflammation damage not only DNA but also other biomacromolecules, such as proteins and lipids, resulting in their dysfunction. We identified oxidatively damaged proteins in cancer tissues by 2D Oxyblot followed by MALDI-TOF/TOF. As an example, oxidatively damaged transferrin released iron ion, which may mediate Fenton reactions and generate additional reactive oxygen species. Dysfunction of anti-oxidative proteins due to this damage might increase oxidative stress. Such damage in biomacromolecules may form a vicious cycle of oxidative stress, leading to cancer development. Epigenetic alterations such as DNA methylation and microRNA dysregulation play vital roles in carcinogenesis, especially in inflammation-related cancers. We examined epigenetic alterations, DNA methylation and microRNA dysregulation, in Epstein-Barr virus-related nasopharyngeal carcinoma in the endemic area of Southern China and found several differentially methylated tumor suppressor gene candidates by using a next-generation sequencer. Among these candidates, we revealed higher methylation rates of RAS-like estrogen-regulated growth inhibitor (RERG) in biopsy specimens of nasopharyngeal carcinoma more conveniently by using restriction enzyme-based real-time PCR. This result may help to improve cancer screening strategies. We profiled microRNAs of nasopharyngeal carcinoma tissues using microarrays. Quantitative RT-PCR analysis confirmed the concordant downregulation of miR-497 in cancer tissues and plasma, suggesting that plasma miR-497 could be used as a diagnostic biomarker for nasopharyngeal carcinoma. Chronic inflammation promotes genetic and epigenetic aberrations, with various pathogeneses. These changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.
Animals ; DNA Damage ; Epigenesis, Genetic ; Humans ; Inflammation ; etiology ; immunology ; Mice ; Neoplasms ; etiology ; genetics ; immunology ; Reactive Nitrogen Species ; metabolism ; Reactive Oxygen Species ; metabolism

BACKGROUND/AIMS: Nonalcoholic steatohepatitis can develop from nonalcoholic fatty liver and progress to severe liver disease such as cirrhosis. The mechanism determining the progression from fatty liver to steatohepatitis is unknown. Iron is suspected to enhance hepatic damage associated with nonalcoholic fatty liver disease (NAFLD). The aims of this study were to evaluate the relationship of serum iron indices and hepatic iron deposition with hepatic fibrosis or inflammation, and to assess whether the increased hepatic iron deposition is an independent predictor of progression to liver injury. METHODS: The biochemical and histopathological data of thirty-nine patients with NAFLD were analyzed. Liver biopsy findings were graded according to the method described by Brunt, et al. Hepatic iron concentration was available in 29 of 39 patients. RESULTS: The mean hepatic iron concentration and hepatic iron indices were 1,349+/-1,188 microgram/g dry weight and 0.9+/-0.7 microgram/g/age. Serum ferritin and body mass indices were associated with hepatic inflammation (p=0.001, p=0.006) and fibrosis (p=0.005, p=0.013). Hepatic iron concentration and hepatic iron index were not associated with hepatic inflammation and fibrosis. Multivariate analysis did not identify serum ferritin or body mass index as an independent predictor of liver injury. CONCLUSIONS: Hepatic iron deposition shows no association with the degree of hepatic inflammation or fibrosis. Hepatic iron is not an independent predictor of hepatic injury in patients with NAFLD.
Adolescent ; Adult ; Fatty Liver/complications/*metabolism ; Female ; Ferritins/blood ; Humans ; Inflammation ; Iron/blood/*metabolism ; Liver/*metabolism/pathology ; Liver Cirrhosis/*etiology/metabolism/pathology ; Male ; Middle Aged

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.
Acute Disease ; Disease Progression ; Endotoxins ; metabolism ; Hepatic Insufficiency ; etiology ; physiopathology ; Humans ; Inflammation Mediators ; metabolism ; Multiple Organ Failure ; etiology ; Pancreatitis ; complications ; metabolism ; physiopathology ; Pancreatitis, Acute Necrotizing ; complications ; metabolism ; physiopathology ; Reactive Oxygen Species ; metabolism