Despite these acute changes, no lasting renal injury was observed (assessed over 3 days). To determine whether Iso directly impacts tubular cell integrity, cultured proximal tubule (HK-2) cells were exposed to Iso. Substantial Fe dependent cell injury (decreased MTT uptake), and Fe independent increases in HO-1/IL-6 mRNA expression were observed. We conclude that Iso-induced AHF is a useful reversible model of CRS-1. Despite its largely hemodynamic ('pre-renal') nature, Fe-mediated oxidative stress and pro-inflammatory reactions are induced. These arise, at least in part, from direct Iso- induced tubular cell toxicity, rather than simply being secondary to Iso-mediated hemodynamic events. Finally, Iso-triggered renal cytokine production can potentially contribute to 'organ cross talk' and a systemic pro-inflammatory state. Identifying new approaches to lessen inflammation, as well as the associated malignant consequences, remains crucial to improving the lives and prognosis of patients diagnosed with inflammatory bowel diseases. Although it previously has been suggested as a suitable biomarker for monitoring disease activity in patients diagnosed with Crohn's disease, the role of the acute-phase protein serum amyloid A (SAA) in inflammatory bowel disease remains unclear. In this study, we aimed to assess the role of SAA in colitis-associated cancer. We established a model of colitis-associated cancer in wild-type and SAA double-knockout (Saa1/2 ) mice by following the azoxymethane/dextran sulfate sodium protocol. Disease activity was monitored throughout the study while colon and tumor tissues were harvested for subsequent use in cytokine analyses, Western blot, and immunohistochemistry experiments. We observed attenuated disease activity in mice deficient for Saa1/2 as evidenced by decreased weight loss, increased stool consistency, decreased rectal bleeding, and decreased colitis-associated tissue damage. Macrophage infiltration, including CD206 M2-like macrophages, also was attenuated in SAA knockout mice, while levels of interleukin 4, interleukin 10, and tumor necrosis factor-ɑ were decreased in the distal colon. Mice deficient for SAA also showed a decreased tumor burden, and tumors were found to have increased apoptotic activity coupled with decreased expression for markers of proliferation. Based on these findings, we conclude that SAA has an active role in inflammatory bowel disease and that itcould serve as a therapeutic target aimed at decreasing chronic inflammation and the associated risk of developing colitis-associated cancer.Based on these findings, we conclude that SAA has an active role in inflammatory bowel disease and that it could serve as a therapeutic target aimed at decreasing chronic inflammation and the associated risk of developing colitis-associated cancer. Rapid gastric epithelial progenitor cell (EPC) proliferation and inflammatory response inhibition play key roles in promoting the repair of gastric mucosal damage. However, specific targets inducing these effects are unknown. In this study, we explored the effects of a potential target, Ankyrin repeat domain 22 (ANKRD22). An acute gastric mucosal injury model was established with Ankrd22 and Ankrd22 mice by intragastric administration of acidified ethanol. Organoid culture and flow cytometry were performed to evaluate the effects of ANKRD22 on leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5 ) gastric EPC proliferation. The mechanisms by which ANKRD22 affects gastric EPC proliferation and inflammatory responses were explored by mitochondrial Ca influx and immunoblotting. Candidate ANKRD22 inhibitors then were screened virtually and validated invitro and invivo. After acute gastric mucosal injury, the number of Lgr5 gastric EPCs was increased significantly in Ankrd22 mice compared with that in Ankrd22 mice. Moreover, Ankrd22 knockout attenuated inflammatory cell infiltration into damaged gastric tissues. ANKRD22 deletion also reduced mitochondrial Ca influx and cytoplasmic nuclear factor of activated T cells in gastric epithelial cells and macrophages, which further induced Lgr5 gastric EPC proliferation and decreased macrophage release of tumor necrosis factor-α and interleukin 1α. In addition, a small molecule, AV023, was found to show similar effects to those produced by ANKRD22 deletion invitro. Intraperitoneal injection of AV023 into the mouse model promoted the repair of gastric mucosal damage, with increased proliferation of Lgr5 gastric EPCs and visible relief of inflammation. ANKRD22 inhibition is a potential target-based therapeutic approach for promoting the repair of gastric mucosal damage.ANKRD22 inhibition is a potential target-based therapeutic approach for promoting the repair of gastric mucosal damage. To evaluate the significance of anti-thyroglobulin and anti-thyroid peroxidase antibody levels in locoregional metastatic disease in patients with well-differentiated thyroid cancer. Included patients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected age, sex, pre-operative thyroid stimulating hormone (TSH), thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb), anti-thyroid peroxidase antibody (TPOAb); extent of surgery; T-stage; N-stage; extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion (LVI), and multifocal disease. The relationships between pre-operative TPOAb, TgAb, Tg, and TSH and disease status were analyzed. 405 patients were included in the study. 66.4% were female. Mean age was 52 years. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (p<0.01), with stronger correlation with N1b compared with N1a disease (p=0.03). Presence of ETE was inversely associated with TgAb titer (p=0.03). TPOAb was associated with lower T- stage, fewer LNM, and lower likelihood of ETE (p=0.04, p=0.04, p=0.02). In multivariable analysis, TgAb≥40 IU/mL was an independently predictive factor of higher N-stage (p<0.01 for N0 v. N1 and p=0.01 for N1a v. N1b), and for ENE (p<0.01). TPOAb≥60 IU/mL was associated with lower T-stage (p=0.04 for T< 3) and absence of ETE (p=0.01). Elevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T and N stage. click here Pre-operative anti-thyroid antibody titers may be useful to inform disease extent and features.Elevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T and N stage. Pre-operative anti-thyroid antibody titers may be useful to inform disease extent and features.