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Rotenone, a component of pesticides, is widely used in agriculture and potentially causes Parkinson's disease (PD). However, the regulatory mechanisms of rotenone-induced PD are unclear. Here, we revealed a novel feedback mechanism of p38-Parkin-ROS regulating rotenone-induced PD. Rotenone treatment led to not only the activation of p38 but also Parkin inactivation and reactive oxygen species (ROS) overproduction in SN4741 cells. Meanwhile, p38 activation regulated Parkin phosphorylation at serine 131 to disrupt Parkin-mediated mitophagy. Notably, both p38 inhibition and Parkin overexpression decreased ROS levels. Additionally, the ROS inhibitor N-acetyl-l-cysteine (NAC) inhibited p38 and activated Parkin-mediated mitophagy. Both p38 inhibition and the ROS inhibitor NAC exerted a protective effect by restoring cell death and mitochondrial function in rotenone-induced PD models. Based on these results, the p38-Parkin-ROS signaling pathway is involved in neurodegeneration. This pathway represents a valuable treatment strategy for rotenone-induced PD, and our study provides basic research evidence for the safe use of rotenone in agriculture.

Acute lung injury (ALI) is a severe disease with a high rate of morbidity and mortality, characterized by excessive and uncontrolled inflammatory response in lung. Recent studies demonstrated that serine arginine-rich splicing factor 1 (SRSF1) is involved in inflammation. However, whether SRSF1 modulates ALI remains to be determined. In this study, we established an ALI mouse model that induced by lipopolysaccharide (LPS), with or without the treatment of SRSF1 antibody. Our result showed that SRSF1 expression was elevated in LPS-induced ALI. Importantly, treatment with SRSF1 antibody notably ameliorated ALI in mice, as determined by reduction in lung W/D ratios, histopathological changes, lung inflammation and TSLP expression. Besides, exposure of human alveolar epithelial A549 cells to LPS enhanced the expression of both SRSF1 and TSLP, while knockdown or overexpression of SRSF1 significantly lowered or upregulated the expression of TSLP induced by LPS. Interestingly, the expression of SRSF1 and TSLP showed a positive correlation in normal human lung tissues. Mechanistically, we found that SRSF1 directly bound with the mRNA of TSLP and may exert its function by stabilizing the mRNA of TSLP in LPS-induced ALI. Therefore, our results indicated that SRSF1 may be an important contributor in lung inflammation of LPS-induced ALI and SRSF1 signaling blocking may serve as a potential treatment of ALI.

Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)‑induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial‑dependent apoptosis. It was revealed that LPS‑challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet‑to‑dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS‑induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS‑induced mitochondrial‑dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick‑end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl‑2 downregulation). Furthermore, DEX treatment markedly attenuated LPS‑induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS‑induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis.

OBJECTIVE: Procalcitonin is a reliable biomarker of infection and sepsis. We aimed to determine whether tracheotomy influences the procalcitonin concentrations in patients without sepsis and assess whether operative duration and procedure affect the peak procalcitonin level. METHODS: A total of 38 non-septic patients who required a tracheotomy underwent either a percutaneous dilatational tracheotomy (n=19) or a surgical tracheotomy (n=19). Procalcitonin levels were measured at the beginning of the tracheotomy and at 2 h, 4 h, 8 h, 24 h, 48 h and 72 h after the procedure. RESULTS: The baseline procalcitonin concentration before the tracheotomy was 0.24±0.13 ng/mL. The postoperative levels increased rapidly, with a 4-fold elevation after 2 h, reaching a peak 4 h later with a 5-fold increase over baseline. Thereafter, the levels gradually returned to 2-fold greater than the baseline level within 72 h. The peak levels of procalcitonin showed a significant positive correlation with operative durations (r=0.710, p

Background It is known that continuous venonenous hemofiltration (CVVH) does not affect the plasma level of neutrophil gelatinase-associated lipocalin (pNGAL) in acute kidney injury (AKI) patients. However, because of the unique pathophysiology underlying AKI caused by sepsis, the effect of CVVH on pNGAL in this clinical setting is less certain. The purpose of this study was to determine the effect of CVVH on pNGAL in sepsis-induced AKI patients. Methods Between August 1, 2014, and December 31, 2014, 42 patients with sepsis-induced AKI underwent CVVH in the general intensive care unit of our institution and were consecutively enrolled in this study. Prefilter, postfilter, and ultrafiltrate pNGAL measurements were taken at the initiation of continuous renal replacement therapy (CRRT) and repeated after 2, 4, 8, and 12 h (T0, T2h, T4h, T8h, and T12h, respectively). The mass transfer, plasma clearance, and sieving coefficient were calculated based on the mass conservation principle. Results Following CVVH initiation, we found that pNGAL in the ultrafiltrate decreased significantly (P = 0.013); however, levels at the inlet and outlet showed no significant change (P > 0.05 for both). Furthermore, there was no change in the total mass removal rate, total mass adsorption rate, and plasma clearance over time (P > 0.05 for all), and a significant decrease in the sieving coefficient (P = 0.007) was seen. Conclusions The results of this study show a limited effect of CVVH on pNGAL in sepsis-induced AKI patients. This suggests that pNGAL may be used as an indicator of renal progression in these patients. However, a larger study to confirm these findings is needed. Trial registration ClinicalTrials.gov, NCT02536027. Retrospectively registered on 20th August 2015.

Introduction Neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys-C), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are novel diagnostic biomarkers of acute kidney injury (AKI). We aimed to determine the diagnostic properties of these biomarkers for detecting AKI in critically ill patients with sepsis. Methods We divided 112 patients with sepsis into non-AKI sepsis (n = 57) and AKI sepsis (n = 55) groups. Plasma and urine specimens were collected on admission and every 24 hours until 72 hours and tested for NGAL, Cys-C, and TREM-1 concentrations. Their levels were compared on admission, at diagnosis, and 24 hours before diagnosis. Results Both plasma and urine NGAL, Cys-C, and sTREM-1 were significantly associated with AKI development in patients with sepsis, even after adjustment for confounders by using generalized estimating equations. Compared with the non-AKI sepsis group, the sepsis AKI group exhibited markedly higher levels of these biomarkers at diagnosis and 24 hours before AKI diagnosis (P Conclusion Plasma and urine NGAL, Cys-C, and sTREM-1 can be used as diagnostic and predictive biomarkers for AKI in critically ill patients with sepsis.