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Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro‐inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well‐known antioxidant and anti‐inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin‐induced canonical and cytosolic lipopolysaccharide (LPS)‐induced non‐canonical pyroptosis and alleviates LPS‐induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS‐challenged mice and blocked proinflammatory cytokine secretion. The anti‐pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis‐associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N‐GSDMD pore construction and less cellular content release. In LPS‐induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin‐1β and tumor necrosis factor‐α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis‐associated disease.

Background Treatment options for advanced colon cancer are mainly combinations of chemotherapy and targeted drugs. However, poor physical health and medication intolerance limit the choice of anticancer drugs. Colon cancer with cirrhosisis a particular patient group that poses a challenge to clinical treatment. Case presentation This article presents a case of a patient in the decompensated stage of cirrhosis who was diagnosed with advanced colon cancer. The initial presentation was a nodule on his navel named the Sister Mary Joseph’s nodule, which was later confirmed by biopsy and PET-CT as one of the metastases of colon cancer. The patient was treated with Cetuximab and 5-Fluorouracil at a below-guideline dose, however, portal vein thrombosis developed and led to death. This entire process, from diagnosis to death, occurred within a span of three months. Conclusion Cancers with cirrhosis are a special group that deserves more attention. There is no unified treatment guideline for these patients, especially those with extrahepatic primary tumors. We should be more cautious when choosing treatment for such patients in the future. Both chemotherapy and targeting may potentially induce portal vein thrombosis, which appears to have a higher incidence and worse prognosis than other diseases.

Background: Sepsis commonly leads to acute and long-term cognitive and affective impairments which are associated with increased mortality in patients. Neuroinflammation characterized by excessive cytokine release and immune cell activation underlies the behavioral changes associated with sepsis. We previously reported that the administration of a traditional Chinese herbal Qiang Xin 1 (QX1) formula improves survival in septic mice. This study was performed to better understand the effects and the mechanisms of QX1 formula treatment on behavioral changes in septic model. Methods: A preclinical septic model was induced by cecal ligation and puncture in mice. QX1 formula was orally administrated daily. Behavior test including Morris water maze, novel object recognition testing, elevated plus maze and open field testing was performed. Elisa, immunofluorescence, microarray analysis, and Real-time PCR were analyzed. Results: QX1 formula administration significantly improved survival, alleviated overall cognitive impairment and emotional dysfunction in septic mice. QX1 formula administration dramatically inhibited short and long-term excessive pro-inflammatory cytokine production both peripherally and centrally, and was accompanied by diminished microglial activation in septic mice. Biological processes including synaptic transmission, microglia cell activation, cytokine production, microglia cell polarization, as well as inflammatory responses related to signaling pathways including the MAPK signaling pathway and the NF-κB signaling pathway were altered prominently by QX1 formula treatment in the hippocampus of septic mice. In addition, QX1 formula administration decreased the expression of the M1 phenotype microglia gene markers such as Cd32, Socs3, and Cd68, while up-regulated M2 phenotype marker genes including Myc, Arg-1, and Cd206. Conclusions: QX1 formula administration attenuates cognitive deficits, emotional dysfunction, and reduces neuroinflammatory responses to improve survival in septic mice. Diminished microglial activation and altered microglial polarization are involved in the neuroprotective mechanism of QX1 formula.

Objective To develop a reliable and noninvasive method to evaluate the renal perfusion in a porcine model of septic shock and investigate the effect of UTI on it. Methods Thirty-two healthy male domestic pigs were randomly assigned to one of four groups: a sham group (SH, n=5); a septic shock group (SS, n=9); a septic shock group treated with vancomycin (15mg/kg) (VAN, n=9) and a septic shock group treated with UTI (50,000U/kg) + vancomycin (UTI, n= 9). Contrast-enhanced ultrasound (CEUS) of kidney at the baseline and the end of protocol (24h) were performed. The spectrum of interlobar or arcuate artery was selected to calculate the corrected resistive index (cRI). Sulphur hexafluoride (SF6) microbubbles were bolus injected via venous catheter. The peak intensity (Pi) and area under curve (AUC) were calculated by a time-intensity curve (TIC). Results cRI increased significantly at the end of the protocol except the SH groups, significant difference was found between each experimental group and the SH group. Linear regression was found between the cardiac output (CO) and Pi (Pi = 7.082 × CO + 5.026, R2=0.752, F=84.878, P < 0.001). The AUC decreased significantly post-injury in the SS and VAN group. All above parameters were improved by the UTI treatment, significant differences were found between the UTI and SS or VAN group respectively (P<0.05). Conclusions Septic shock occasionally accompanies with a significant low perfusion in renal microcirculation and UTI can improve it significantly.