Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects. OBJECTIVE: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI. MATERIALS AND METHODS: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 µg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 µg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation. RESULTS: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 µg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results. DISCUSSION AND CONCLUSION: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

Single-Atom Catalysts in Environmental Engineering: Progress, Outlook and Challenges.

Recently, single-atom catalysts (SACs) have attracted wide attention in the field of environmental engineering. Compared with their nanoparticle counterparts, SACs possess high atomic efficiency, unique catalytic activity, and selectivity. This review summarizes recent studies on the environmental remediation applications of SACs in (1) gaseous: volatile organic compounds (VOCs) treatment, NOx reduction, CO2 reduction, and CO oxidation; (2) aqueous: Fenton-like advanced oxidation processes (AOPs), hydrodehalogenation, and nitrate/nitrite reduction. We present the treatment activities and reaction mechanisms of various SACs and propose challenges and future opportunities. We believe that this review will provide constructive inspiration and direction for future SAC research in environmental engineering.

De Winter electrocardiogram pattern due to type A aortic dissection: a case report.

BACKGROUND: De Winter electrocardiograph (ECG) pattern is an atypical presentation of acute myocardial infarction (AMI) due to severe stenosis of the left anterior descending (LAD). Complications of acute aortic dissection (AD) in the setting of acute myocardial infarction (AMI) with de Winter sign are relatively rare and physicians may easily miss the diagnosis of AD. We report a case of patient with acute chest pain and de Winter ECG pattern due to AD involving the left main coronary artery (LM), LAD and left circumflex artery (LCX). CASE PRESENTATION: A 57-year-old male patient was initially diagnosed with AMI and then the diagnosis of acute AD was supported by transthoracic echocardiograph (TTE). After two stents were implanted respectively into the proximal LM-LAD and LM-LCX, he recovered from cardiogenic shock. Two months later, the patient underwent the surgery of ascending aorta replacement. After the surgery, there was no obvious chest discomfort during follow-up. CONCLUSIONS: When an ECG shows a "de Winter pattern", we should also consider the possibility of AD which result in LAD occlusion. TTE is a useful tool in screening for AD. Further research is needed to prove that percutaneous coronary intervention (PCI) may be a useful treatment strategy in the case of AD leading to severe LAD occlusion and unstable hemodynamics when there's no condition to perform aortic replacement surgery immediately.

Potential biomarkers for inflammatory response in acute lung injury.

Acute lung injury (ALI) is a severe respiratory disorder occurring in critical care medicine, with high rates of mortality and morbidity. This study aims to screen the potential biomarkers for ALI. Microarray data of lung tissues from lung-specific geranylgeranyl pyrophosphate synthase large subunit 1 knockout and wild-type mice treated with lipopolysaccharide were downloaded. Differentially expressed genes (DEGs) between ALI and wild-type mice were screened. Functional analysis and the protein-protein interaction (PPI) modules were analyzed. Finally, a miRNA-transcription factor (TF)-target regulation network was constructed. Totally, 421 DEGs between ALI and wild-type mice were identified. The upregulated DEGs were mainly enriched in the peroxisome proliferator-activated receptor signaling pathway, and fatty acid metabolic process, while downregulated DEGs were related to cytokine-cytokine receptor interaction and regulation of cytokine production. Cxcl5, Cxcl9, Ccr5, and Cxcr4 were key nodes in the PPI network. In addition, three miRNAs (miR505, miR23A, and miR23B) and three TFs (PU1, CEBPA, and CEBPB) were key molecules in the miRNA-TF-target network. Nine genes including ADRA2A, P2RY12, ADORA1, CXCR1, and CXCR4 were predicted as potential druggable genes. As a conclusion, ADRA2A, P2RY12, ADORA1, CXCL5, CXCL9, CXCR1, and CXCR4 might be novel markers and potential druggable genes in ALI by regulating inflammatory response.

Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice.

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase.

Background: Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority. Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined. Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activity Conclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats.

Salidroside regulates inflammatory pathway of alveolar macrophages by influencing the secretion of miRNA-146a exosomes by lung epithelial cells.

The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPS-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The exosomes from RLE-6TN are extracted and identified by transmission electron microscopy, particle size analysis and protein marker detection, and co-cultured with NR8383 cells. The ALI/ARDS model of SD rats was established by LPS (10 mg/kg) intratracheal instillation. Following a four-hour intratracheal instillation of LPS, 50 µl of RLE-6TN exosomes were injected through the tail vein. After that, SAL and miR-146a antagomir were injected into the tail vein for 72 h, respectively. As the changes of HE stain, body weight and ALI score are observed. The expression of miR-146a, TLR4, NF-kB, IRAK1, TRAF6 and their related proteins were detected by RT-PCR and Western blot, respectively. TNF-α, IL-6, IL-8 and IL-1 ß inflammatory factors were detected by ELISA. The expression of miR-146a, NF-kB, IRAK, TRAF6 and related inflammatory factors in LPS-induced NR8383 was significantly higher than that in the control group, while SAL has greatly reduced the expression of TLR4 mediated NF-kB inflammatory pathway and related inflammatory factors. SAL can significantly improve the LPS-induced lung morphological abnormalities, slowed down the rate of weight loss in rats, and reducing the ALI score. The expression trend of NF-kB, IRAK, TRAF6 and related inflammatory factors in rats' lung tissues was consistent with that in NR8383 cells. SAL has a protective effect on ALI/ARDS caused by sepsis, which is likely to be developed to a potential treatment for the disease. To sum up, this study provides a new theoretical basis for the treatment of ALI/ARDS with SAL.

Acquired hemophilia A presenting as progressive intra-abdominal hemorrhage, muscle hemorrhage and hemothorax postpartum: A case report and literature review.

Acquired hemophilia A (AHA) is a rare antibody-mediated condition in which autoantibodies form against a coagulation factor, most commonly factor VIII (FVIII), causing severe coagulopathy. Here the present report presents a case of AHA in a 35-year-old postpartum woman with continuous polyserous bloody effusions who was admitted to the First Affiliated Hospital of Zhejiang Chinese Medical University (Hangzhou, China) in October 2017 without a history of trauma, anticoagulation treatment or coagulopathy. At presentation, the patient's hemoglobin level was low (70 g/l; normal range: 115-150 g/l) g/l, blood pressure was 89/58 mmHg (normal range, 90-140/60-90 mmHg), and activated partial thromboplastin time was 68.4 sec (normal range: 25.0-36.0 sec), with a normal international normalized ratio (0.94; normal range, 0.8-1.2). The reaction time in thrombography was prolonged (35.8 min; normal range: 5-10 min), coagulation FVIII had markedly decreased activity (12.6%; normal range, 60-150%), and FVIII inhibitor had a high titer [7.4 Bethesda units (BU)/ml; normal range, 0-0.6 BU/ml]. Notably, the patient's autoantibody level was markedly higher than normal (1:320; normal range: <1:100). The patient was successfully treated with bleeding control, eradication of FVIII inhibitor, and treatment of the underlying disease. To the best of our knowledge, this is the first case of AHA with polyserous bloody effusions in a patient with an autoimmune disorder during the postpartum period. Reports of such rare cases will aid the characterization of disease pathogenesis, which may in turn lead to the recognition and timely treatment of this rare disorder.

Biotransformation and tissue distribution of protopine and allocryptopine and effects of Plume Poppy Total Alkaloid on liver drug-metabolizing enzymes.

In this study, the biotransformation in the plasma, urine and feces of rats following oral administration of protopine (PRO) and allocryptopine (ALL)were explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of tissues was developed and applied to the tissue distribution study in rats following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks. A total of ten PRO metabolites and ten ALL metabolites were characterized in rats in vivo. Among these metabolites, six PRO metabolites and five ALL metabolites were reported for the first time. The predicated metabolic pathways including ring cleavage, demethylation following ring cleavage, and glucuronidation were proposed. The low-concentration residue of PRO and ALL in various tissues was detected at 24 h and 48 h after dosing, which indicated that both compounds could be widely distributed in tissues and exist as low levels of residue. The activities of erythromycin N-demethylase, aminopyrine N-demethylase and NAD (P)H quinone oxidoreductase in female rats can be induced post-dose, but these activities were inhibited in male rats. The proposed biotransformation and residues of PRO and ALL and their effects on enzymes may provide a basis for clarifying the metabolism and interpreting pharmacokinetics.

Case report of primary splenic angiosarcoma with hepatic metastases.

Primary splenic angiosarcoma (PSA) is the most unusual type of malignancy with early multifocal metastasis through hematogenous spread. PSA is generally believed to originate from splenic sinusoidal vascular endothelium with a high rate of metastasis and to have a poor prognosis. Its etiology and pathogenetic mechanisms have not yet been clearly described. Thus far, only approximately 200 cases have been reported. PSA has variable symptomatology with the potential to present with life-threatening complications. The diagnosis of PSA is challenging; and often late. PSA should be considered in the differential diagnosis of patients with splenomegaly and anemia of unknown etiology. Surgical treatment with splenectomy is considered the only curative intervention for potential long-term disease-free survival. Early diagnosis and treatment are very important. It is important that clinical doctors improve the understanding of PSA. Herein, we report one rare case of PSA with hepatic metastases, along with a review of the current literature.

Salidroside alleviates paraquat-induced rat acute lung injury by repressing TGF-ß1 expression.

OBJECTIVE: This study was designed to investigate the protective effects of salidroside (SDS) via suppressing the expression of transforming growth factor-ß1 (TGF-ß1) in rat acute lung injury (ALI) induced by paraquat (PQ) and to explore the potential molecular mechanisms. METHODS: A total of 90 male rats (190-210 g) were randomly and evenly divided into 9 groups: control group, PQ groups (4 groups), and PQ + SDS groups (4 groups). The rats in control group were treated with equal volume of saline intraperitoneally. The rats in PQ groups were exposed to PQ solution (20 mg/kg) by gastric gavage for 1, 6, 24, and 72 hours, respectively. The rats in PQ + SDS groups were intraperitoneally injected once with SDS (10 mg/kg) every 12 hours after PQ perfusion. Pulmonary pathological changes were observed by hematoxylin and eosin (HE) staining. The expression of TGF-ß1 and the mRNA were evaluated by immunohistochemical (IHC) scoring and real time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR), respectively. RESULTS: SDS alleviated the symptoms of PQ induced ALI. Moreover, SDS reduced the expression of the inflammatory cytokine TGF-ß1 including TGF-ß1 IHC scores (at each time point from 6 to 72 hours after PQ perfusion) and mRNA level (at each time point from 1 to 72 hours after PQ perfusion) compared with PQ groups (P < 0.05). CONCLUSION: SDS alleviated the pulmonary symptoms of PQ-induced ALI, at least partially, by repressing inflammatory cell infiltration and the expression of TGF-ß1 resulting in delayed lung fibrosis.