The Barrier Disruption and Pyroptosis of Intestinal Epithelial Cells Caused by Perfringolysin O (PFO) from Clostridium perfringens.

Clostridium perfringens (C. perfringens), a Gram-positive bacterium, produces a variety of toxins and extracellular enzymes that can lead to disease in both humans and animals. Common symptoms include abdominal swelling, diarrhea, and intestinal inflammation. Severe cases can result in complications like intestinal hemorrhage, edema, and even death. The primary toxins contributing to morbidity in C. perfringens-infected intestines are CPA, CPB, CPB2, CPE, and PFO. Amongst these, CPB, CPB2, and CPE are implicated in apoptosis development, while CPA is associated with cell death, increased intracellular ROS levels, and the release of the inflammatory factor IL-18. However, the exact mechanism by which PFO toxins exert their effects in the infected gut is still unidentified. This study demonstrates that a C. perfringens PFO toxin infection disrupts the intestinal epithelial barrier function through in vitro and in vivo models. This study emphasizes the notable influence of PFO toxins on intestinal barrier integrity in the context of C. perfringens infections. It reveals that PFO toxins increase ROS production by causing mitochondrial damage, triggering pyroptosis in IPEC-J2 cells, and consequently resulting in compromised intestinal barrier function. These results offer a scientific foundation for developing preventive and therapeutic approaches against C. perfringens infections.

Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro.

African swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use primary porcine alveolar macrophages to screen a kinase inhibitor library for anti-ASFV compounds. Six candidate compounds that inhibited ASFV infection with inhibition of > 90% were identified, among which brincidofovir exhibited optimal inhibitory effects on ASFV. Brincidofovir reduces ASFV replication in a dose-dependent manner (IC50 = 2.76 nM) without cytotoxicity (CC50 = 58 µM). It possesses the ability to reduce viral titres and inhibit viral structural protein expression. Time-of-addition assays suggest that the compound interferes with the post-invasion stage of the viral infection cycle. In pig challenge experiments, brincidofovir was indicated to protect pigs against ASFV-induced lethality by decreasing the viral load in organs and peripheral blood, while it alleviated the histopathological changes associated with ASFV infection. Furthermore, brincidofovir also decreased viral shedding in pigs with ASFV infection. Our data together demonstrate that brincidofovir may serve as a potentially effective agent for the prevention and control of ASFV infection, whereas further investigations are still required.

The role of preoperative ultrasound, contrast-enhanced ultrasound, and 99mTc-MIBI scanning with single-photon emission computed tomography/X-ray computed tomography localization in refractory secondary hyperparathyroidism.

OBJECTIVE: The aim of our study was to evaluate the role of preoperative US, CEUS, and 99mTc-MIBI scanning with SPECT/CT in localizing diseased parathyroid glands in cases of refractory secondary hyperparathyroidism (SHPT). MATERIAL AND METHODS: Using pathological results as the gold standard, we compared the operative findings with the preoperative localization of each modality in 73 nodules and evaluated the accuracy, and sensitivity of each modality and combinations of the four modalities. RESULTS: The sensitivity of US, CEUS, 99mTc-MIBI and SPECT/CT was 98.59%, 94.37%, 50.70% and 78.87%, respectively. US had the highest sensitivity of the four imaging methods and the diagnostic sensitivity of US and CEUS was superior to that of 99mTc-MIBI (p < 0.001 and p < 0.001) and SPECT/CT (p = 0.001 and p = 0.012). In addition, we found that the sensitivity of the combination of US with CEUS, US with 99mTc-MIBI and/or SPECT/CT, CEUS with 99mTc-MIBI and/or SPECT/CT, US with CEUS and two other imaging modalities (99mTc-MIBI and/or SPECT/CT) was 98.59%, 100%, 95.77%, and 100%, respectively. CONCLUSIONS: The combination of US with SPECT/CT is the best choice for the comprehensive preoperative localization of glands in refractory SHPT. CEUS can elevate the accuracy of US in differential diagnosis via the interpretation of dynamic microvascular features.