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Inflammation is much more intrinsic to hernia then is what is generally appreciated. The occurrence of hernias is associated with swelling, stress and inflammation. Surgery remains an important intervention to treat hernias and for many years, post-surgical levels of inflammatory cytokines have been evaluated to compare the different strategies for their comparative advantages. All surgical procedures elicit some sort of inflammatory response and moreover the meshes used for hernia repair are also associated with elevated inflammatory response, although some favor predominantly a pro-inflammatory response while the other meshes favor anti-inflammatory response. An estimated more than 90% of hernia repairs involve some meshes with polypropylene considered as the gold standard. Efforts are underway to modulate polypropylene meshes associated inflammation through use of alternative materials as well as modifications to polypropylene meshes themselves. In the last one decade, miRNAs have entered hernia research and the data on a role of miRNAs in different hernias is slowly emerging, providing the first evidence of epigenetics in hernia. Some reports are connecting miRNAs with inflammation in hernia. All these aspects, such as, surgery-related to mesh-related inflammation as well as miRNA-related inflammation, are discussed in this article to present an up-to-date information on the topic. [ABSTRACT FROM AUTHOR]

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control_0h (Con_0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 μL of water or APS (250 μg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1β, and IL-6) and IFN-β by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks. [ABSTRACT FROM AUTHOR]

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR / SREBP-1c and PPARα / γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB , IL-6 , IL-8 , IL-1β , and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR / SREBP-1c / PPARα / γ and NF-κB signaling pathways. This research showed that DEHP could induce lipid metabolism disorder and inflammatory response via LXR / SREBP-1c / PPARα / γ / NF-κB signal pathways. This study provides new evidence for the mechanisms of DEHP-induced hepatotoxicity. [Display omitted] • DEHP exposure caused hepatotoxicity. • DEHP induced lipid metabolism disorders in liver. • DEHP disrupted lipid metabolism to induce lipotoxicity in liver. • DEHP exposure caused inflammation response in liver. [ABSTRACT FROM AUTHOR]

Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28 -O-caffeoyl betulin (B- CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B- CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B- CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B- CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b 5 (Cyt b 5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H 2 O 2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity. Cadmium (Cd) enters the heart through cell membranes and disrupts the metabolic system. Findings from the present study provide new evidence that Cd exposure affects the modulation of Cytochrome P450 Systems and Nrf2 mediated antioxidant defense in the heart. Cd exposure resulted in oxidative stress via disrupting the homeostasis of CYP450s, activating Nrf2 signaling. All data supplied in the present study contribute to broadening knowledge on the mechanisms of Cd-induced cardiotoxicity. Image 1 • Cadmium exposure caused cardiotoxicity. • Cadmium induced cardiac inflammation. • Cadmium disturbed the Cytochrome P450 homeostasis in heart. • Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense. [ABSTRACT FROM AUTHOR]