Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.

Copper (Cu) is an essential trace element involved in the normal physiological processes of animals. However, excessive exposure to Cu can produce numerous detrimental impacts. The aim of this study was to investigate the effects of Cu on oxidative stress and apoptosis as well as their relationship in the mouse liver. Four-week-old ICR mice (n=240) were randomly assigned to different Cu (Cu2+-CuSO4) treatment groups (0, 4, 8, and 16 mg/kg) for periods of 21 and 42 days. The high doses of Cu exposure could induce oxidative stress, by increasing the levels of reactive oxygen species (ROS) and protein carbonyls (PC) and decreasing the activities of antisuperoxide anion (ASA) and antihydroxyl radical (AHR) and content of glutathione (GSH), as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Moreover, high doses of Cu exposure induced hepatic apoptosis via the mitochondrial apoptotic pathway, as characterized by the depolarization of mitochondrial membrane potential (MMP); significantly increased mRNA and protein expression levels of cytosolic cytochrome (Cyt c), apoptosis-inducing factor (AIF), endonuclease G (Endo G), apoptosis protease-activating factor-1 (Apaf-1), cleaved caspase-9, cleaved caspase-3, cleaved PARP, Bcl-2 antagonist killer (Bak), Bcl-2-associated X protein (Bax), and Bcl-2-interacting mediator of cell death (Bim); and decreased mRNA and protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-extra-large (Bcl-xL). Furthermore, the activation of the tumor necrosis factor receptor-1 (TNF-R1) signaling pathway was involved in Cu-induced apoptosis, as characterized by the significantly increased mRNA and protein expression levels of TNF-R1, Fas-associated death domain (FADD), TNFR-associated death domain (TRADD), and cleaved caspase-8. These results indicated that exposure to excess Cu could cause oxidative stress triggered by ROS overproduction and diminished antioxidant function, which in turn promoted hepatic apoptosis via mitochondrial apoptosis and that the TNF-R1 signaling pathway was also involved in the Cu-induced apoptosis.

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.

Background Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients. Methods IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University. Results This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally. Conclusion These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.

Nickel (Ni) is known to be a major carcinogenic heavy metal. Occupational and environmental exposure to Ni has been implicated in human lung and nasal cancers. Currently, the molecular mechanisms of Ni carcinogenicity remain unclear, but studies have shown that Ni-caused DNA damage is an important carcinogenic mechanism. Therefore, we conducted a literature search of DNA damage associated with Ni exposure and summarized known Ni-caused DNA damage effects. In vitro and vivo studies demonstrated that Ni can induce DNA damage through direct DNA binding and reactive oxygen species (ROS) stimulation. Ni can also repress the DNA damage repair systems, including direct reversal, nucleotide repair (NER), base excision repair (BER), mismatch repair (MMR), homologous-recombination repair (HR), and nonhomologous end-joining (NHEJ) repair pathways. The repression of DNA repair is through direct enzyme inhibition and the downregulation of DNA repair molecule expression. Up to now, the exact mechanisms of DNA damage caused by Ni and Ni compounds remain unclear. Revealing the mechanisms of DNA damage from Ni exposure may contribute to the development of preventive strategies in Ni carcinogenicity.