Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Purpose: Intra-abdominal infections (IAI) are gradually becoming common in the emergency department, though the incidence is low and the prognosis is fair, as the symptoms are similar to other intra-abdominal diseases, rapid and accurate diagnosis of the causative agents is essential for clinical management. This study aimed to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) in detecting IAI in the emergency department. Patients and Methods: This was a retrospective, single-centered study including patients admitted to the emergency department from January 1st, 2021 to August 31st, 2022 with diagnosis of IAI. The comparison between mNGS and microbial culture using paracentesis fluid samples was performed to evaluate the diagnostic performance of mNGS for IAI. Meanwhile, paracentesis fluid and peripheral blood mNGS were compared to explore the sample specificity. Further, the microbial community structure of the patients with pyogenic liver abscesses (PLA) was analyzed. Results: Thirty-four IAI patients including 23 with pyogenic liver abscesses (PLA), 3 with parapancreatic abscesses, and 8 with other IAI were included in this study. Compared with the conventional microbial culture of paracentesis fluid, mNGS using paracentesis fluid detected more positive cases of IAI (93.75% vs 81.25%), and identified more species of pathogens, especially in obligate anaerobes and viral pathogens. Peripheral blood mNGS presented a relatively high consistency with the paracentesis fluid mNGS (91% mutual positive). The microbial community structure of PLA patients with diabetes is less diverse than that of those without diabetes. Patients with diabetes are at high risk of PLA caused by Klebsiella pneumonia. Conclusion: mNGS has advantages in detecting IAI in the emergency department, and peripheral blood mNGS can be a non-invasive choice for early diagnosis.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is an early characteristic of multiple organ dysfunction, responsible for high mortality and poor prognosis in patients. The present study aims to evaluate therapeutic effects and mechanisms of pyrrolidine dithiocarbamate (PDTC) on ALI.

Lung injury occurring in the early stage of heat stroke (HS) leads to hypoxia and further aggravation of other organic damage. Lactoferrin (LF) is an iron binding protein with anti-inflammatory and antioxidant effects. This study focuses on the protection of preadministration of bovine lactoferrin (BLF) against lung injury in rats with HS. Sixty-four Sprague-Dawley male rats were divided into four groups randomly: control (CON)+phosphate-buffered saline (PBS) ( n = 16), HS+PBS ( n = 16), HS+low-dose BLF (LBLF) ( n = 16), and HS+high-dose BLF (HBLF) ( n = 16). CON+PBS and HS+PBS were preadministered 10 mL/kg PBS for 1 week. HS+LBLF and HS+HBLF were preadministered 100 and 200 mg/kg BLF for 1 week, respectively. The HS onset time and the survival rate were recorded, and bronchoalveolar lavage fluid was obtained to measure protein concentration. Lung was obtained for pathological analysis and wet/dry weight ratio measurement; later, the content of malondialdehyde (MDA), activity of myeloperoxidase (MPO), and superoxide dismutase (SOD) were measured in lung tissue homogenate. The results indicated that BLF preadministration could delay the HS onset time, enhance the survival rate, the levels of serum inflammatory cytokine and MDA content in HS+LBLF and HS+HBLF showed significant reduction compared with HS+PBS, while a significant elevation of SOD activity and reduction of MPO activity in HS+HBLF. Our results demonstrate that BLF preadministration could relieve lung injury in HS rats by enhancing thermal endurance, and alleviating serum inflammatory response and pulmonary oxidative stress damage.

Acute pancreatitis (AP) is an inflammatory pancreatic disorder characterized by tissue damage and necrosis. It not only affects the pancreas but also triggers systemic inflammatory responses, leading to multiorgan failure and potentially death. In recent years, microRNA (miRNA) sponges have demonstrated promise to enhance AP treatment outcomes by inhibiting specific miRNAs. However, the clinical implementation of these inhibitors is often compromised by their structural instability. In this study, we developed a tetrahedron DNA nanostructure (TDN) with a single-stranded DNA segment designed to capture miR-21-3p, a potential therapeutic target for AP, forming a robust miRNA inhibitor. The TDNs exhibited enhanced stability compared to conventional single-stranded miRNA inhibitors, allowing for efficient delivery in vivo and maximizing therapeutic efficacy. Following treatment with the TDN miRNA inhibitor, we observed significant changes in serum levels of biomarkers associated with pancreatitis. Notably, there was a decrease in the expression of specific cytokines associated with both local and systemic inflammatory responses, alongside changes in proteins related to cell death and apoptosis. The mechanism of action involves RNase H-mediated cleavage, which facilitates the inhibition of the target miRNA. Overall, our findings suggest that the TDN miRNA inhibitor can mitigate acute pancreatitis and subsequent multiorgan damage in mice, presenting an effective approach for the future management of AP.