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Abstract. The aim of the present study was to investigate the effect of curcumin on acute renal injury in a rat model of severe acute pancreatitis (SAP). A SAP model with acute kidney injury was established in rats by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The serum amylase, creatinine (Cr) and blood urea nitrogen (BUN) levels in rats were measured. Hematoxylin and eosin staining was used to assess pancreatic and renal histological changes. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured using ELISA kits. Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. The results showed that curcumin significantly decreased serum amylase, Cr and BUN levels, and alleviated pancreatic and renal histological changes in SAP rats. Furthermore, curcumin markedly decreased serum TNF-α and IL-6 levels and downregulated renal protein levels of JAK2/STAT3 pathway components. These results proved that curcumin ameliorates acute renal injury in a rat model of SAP. The molecular mechanism of its effect may be associated with the suppression of the JAK2/STAT3 pathway to reduce TNF-α and IL-6 levels in SAP-induced acute renal injury. Therefore, the findings of the present study revealed the potential use of curcumin for the prevention and treatment of SAP and the associated renal injury. IntroductionSevere acute pancreatitis (SAP), an acute inflammatory condition of the pancreas, is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute renal injury (ARI) is one of the main complications of SAP and significantly increases the mortality rate of patients with AP (66.6 vs. 14.5%) (1). However, the underlying mechanisms of ARI occurring in patients with SAP have remained to be clarified. Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure (2-4). Therefore, inhibiting the transcription and translation of mediators to reduce the secretion of pro-inflammatory factors may ameliorate inflammation and renal failure in SAP.Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, -2, -3, -4, -5a, -5b and -6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription (5). The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 (6). In addition, evidence derived from numerous clinical and experimental studies suggests the involvement of the JAK2/STAT3 pathway in pancreatitis (7-9) or renal diseases (10-12).Curcumin (diferuloylmethane), the active phytochemical component of turmeric (a spice used mostly in Asia) h...

Morusin has been traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount of M. pneumoniae decreased by 24.6 ± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (P<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/β-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/β-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.

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Background The gut-lung axis is a crucial interface in the complex interplay between microbial communities and their human hosts. Despite being two of the most important microbial populations in the human body, there is still a significant knowledge gap regarding the distinct variations between lung and gut microbiota and how they affect clinical outcomes in critically ill patients.Methods A retrospective observational cohort study was conducted in the intensive care unit (ICU) of an affiliated university hospital. Sequential specimens were collected from two anatomical sites, namely the respiratory and intestinal tracts, at two time points: within 48 hours and on day 7 after intubation. These specimens underwent comprehensive analysis to characterize microbial profiles and assess concentrations of fecal short-chain fatty acids (SCFAs) using 16S ribosomal RNA (rRNA) gene sequencing. Lung and gut microbial diversity, along with indicator species, served as the primary predictors in this investigation. The primary outcome of interest was survival status at 28 days after mechanical ventilation.Results A total of 247 specimens, comprising 123 bronchoalveolar lavage and 124 fecal samples, were meticulously collected from 62 critically ill patients in the intensive care unit (ICU). Our analysis revealed significant differences in the composition of respiratory and intestinal microflora between the deceased and survivor groups. Specifically, the alpha diversity of respiratory and intestinal microorganisms was significantly reduced in the deceased group with prolonged mechanical ventilation compared to the survivor group (p < 0.05). Furthermore, there were significant disparities in respiratory and intestinal β-diversity observed among the surviving and deceased groups (p < 0.05). Interestingly, Enterobacteriaceae exhibited enrichment in the respiratory tract (p < 0.05), while Enterococcaceae were enriched in the intestine (p < 0.05) in the deceased group. Notably, lower concentrations of short-chain fatty acids (SCFAs) were detected in the fecal samples from patients who succumbed. Leveraging a multivariate Cox regression analysis, we established robust associations between lung microbial diversity and Enterococcaceae abundance in the intestine with a risk ratio for mortality at day-28 adjusted for confounding factors (aHR = 0.773; CI:95%: [0.652 ~ 0.916], p = 0.003; and aHR = 1 .022; CI:95%: [1 .008 − 1 .037], p = O.OO2). These findings underscored potential clinical significance of microbial profiling to predict critical outcomes among ICU patients.Conclusion Following mechanical ventilation in critically ill patients within the ICU, we observed a significant decline in respiratory microbial diversity, accompanied by an imbalance in the intestinal flora, resulting in the predominant proliferation of Enterococcaceae. This dysbiotic shift holds predictive value for adverse clinical outcomes. Furthermore, the levels of short-chain fatty acids (SCFAs) serve as an indicator of the balance between commensal and pathogenic flora within the gut, signifying its protective role against respiratory diseases. Such insights could pave the way for future strategies aimed at mitigating adverse outcomes in critically ill patients.