Xiang Kong,Song Luo,Shi Yao Wu,Jun Zhang,Gui Fen Yang,Guang Ming Lu,Long Jiang Zhang
Introduction Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [ 18 F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [ 18 F]PBR146 micro-PET/CT. Methods Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. Results The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [ 18 F]PBR146 in BDL+NS group was significantly higher than other groups ( p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. Conclusions RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [ 18 F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.
Surgical sutures close wounds and promote healing. Sutures need to meet appropriate mechanical properties and biocompatibility, so complex and high-cost braiding processes have been developed for better mechanical properties. However, they still cannot work ideally in some scenarios, such as pain and infection. Pain is the most common symptom in almost all injuries, infections, and diseases. Inadequate management of pain leads to untoward physical and psychological outcomes in patients. For these purposes, we designed a multifunctional composite suture of micro silk fibroin fiber (SF). It was extracted in situ ultra-long and ultra-fine SFs where a single thread can reach hundreds of meters from a cocoon. The suture can adsorb anti-infection vancomycin by turning pH and then coated with methacrylated gelatin as a sheath to load a pain-killer ibuprofen (SMG-VC-IB). SMG-VC-IB can withstand a tension force of nearly 18 N, two times the Mersilk® suture. SMG-VC-IB can maintain prolonged release for efficient pain management and anti-infection. We applied PET/CT to investigate objective metabolic data in brain regions and found that the pain-killer reached efficacy in our built pain model of quadriceps femoris incision in rats. We found SMG-VC-IB reduced metabolic levels in pain-related brain regions, including the classical pain matrix. It was also verified that the pain-killer ibuprofen from sutures helps to pass through the postoperative inflammatory period to a comfortable recovery period. Our research presented an eco-friendly manufacturing solution for designing multifunctional composite sutures for pain management and infection control.
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