Efficacy and safety of autologous chondrocyte implantation for osteochondral defects of the talus: a systematic review and meta-analysis.

INTRODUCTION: Studies have reported various effects of autologous chondrocyte implantation (ACI) on osteochondral defects of the talus. Therefore, to assess the effectiveness of ACI for osteochondral defects of the talus, we used the meta-analytic approach. MATERIALS AND METHODS: Electronic databases PubMed, Embase, and the Cochrane Library were systematically searched to identify eligible studies from their inception until November 2020. The random-effects model was used to calculate the incidence of success rate and American Orthopaedic Foot and Ankle Society (AOFAS) score for patients after ACI treatment. Subgroup analyses were also conducted based on age, technique, indication, size, and follow-up duration. RESULTS: For the final meta-analysis, we selected 23 case series studies with a total of 458 patients with osteochondral defects of the talus. Overall, after ACI for patients with osteochondral defects of the talus, we noted that the incidence of success rate was 89% (95% confidence interval (95% CI) 85%-92%; P < 0.001). Moreover, after ACI for patients with osteochondral defects of the talus, the AOFAS score was 86.33 (95% CI 83.33-89.33; P < 0.001). Subgroup analysis showed that the AOFAS score after ACI is significantly different when stratified by the mean age of the patients (P = 0.006). CONCLUSIONS: This study revealed that the use of ACI could provide a relatively high success rate and improve the AOFAS score for patients with osteochondral defects of the talus, which should be recommended in clinical practice.

Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels.

BACKGROUND: Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood. METHODS: In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms. RESULTS: We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2. CONCLUSIONS: The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.

Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers.

BACKGROUND: Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear. METHODS: Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays. RESULTS: The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form. CONCLUSION: Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.

Large duplication in LMBR1 gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome.

Polydactyly and syndactyly are digital abnormalities in limb-associated birth defects usually caused by genetic disorders. In this study, a five-generation Chinese pedigree was found with triphalangeal thumb polysyndactyly syndrome (TPTPS), showing an autosomal dominant pattern of inheritance. We utilized linkage analysis and whole genome sequencing (WGS) for the genetic diagnosis of this pedigree. Linkage analysis was performed using a genome-wide single nucleotide polymorphism (SNP) chip and three genomic regions were identified in chromosomes 2, 6, and 7 with significant linkage signals. WGS discovered a copy number variation (CNV) mutation caused by a large duplication region at the tail of chromosome 7 located in exons 1-5 of the LMBR1 gene, including the zone of polarizing activity regulatory sequence (ZRS), with a length of approximately 180 kb. A real-time polymerase chain reaction (PCR) assay confirmed the duplication. The findings of our study supported the notion that large duplications including the ZRS caused TPTPS. Our study showed that linkage analysis in combination with WGS could successfully identify the disease locus and causative mutation in TPTPS, which could help elucidate the molecular mechanisms and genotype-phenotype correlations in polydactyly.

HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17.

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 µM to 9.2 µM.

Treatment of Chronic Subluxation of the Peroneal Tendons Using a Modified Posteromedial Peroneal Tendon Groove Deepening Technique.

The present study investigated the clinical efficacy of a modified approach for the treatment of chronic subluxation of the peroneal tendons using posteromedial peroneal tendon groove deepening. We retrospectively analyzed the data from 21 patients who had undergone posteromedial peroneal tendon groove deepening combined with repair of the tendon sheath for the treatment of chronic subluxation of the peroneal tendons from March 2006 to October 2012. The lateral edge of the peroneal tendon groove was left untouched. A posterior osteocartilaginous flap was detached from the posterior fibula from medially to laterally. The retromalleolar groove was deepened through impaction of the posterior fibula. A visual analog scale and the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale were used. All patients achieved healing after the first surgery. No postoperative complications developed. Sixteen patients were followed up for 24 to 69 months. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot scale score improved from 55.0 to 93.6 points after surgery. The mean visual analog scale score decreased from 5.3 to 1.2 points. Five patients had moderate hindfoot rigidity and achieved improvements after rehabilitation training. None of the patients had specific requirements for shoes and ground flatness. All patients had a normal gait. No case of recurrent subluxation developed. These results indicate that posteromedial peroneal tendon groove deepening combined with repair of the tendon sheath can achieve satisfactory efficacy.

Optimization of hindfoot alignment radiography.

Background Cobey and Buck described methods to evaluate hindfoot alignment, but it is still unclear which method is better and easier to perform in clinical practice. Purpose To evaluate the optimal method for radiography of hindfoot alignment. Material and Methods We randomly selected 50 patients visiting the foot and ankle surgery outpatient department who underwent hindfoot alignment radiography between 1 July and 31 August 2015. Radiographs were taken using both Cobey's and Buck's methods. The patients were divided into three groups by calcaneal inclination angle. We assessed the calcaneotibial angle, calcaneovertical angle, and the distance from the bottom of the calcaneus to the mid-tibial axis. A comparative analysis was performed separately using the t-test. Results One hundred pairs of data for Cobey's and Buck's methods were obtained. The angles were analyzed separately in valgus, normal, and varus situations. The results showed no significant difference between Cobey's method and Buck's method regardless of any situation ( P > 0.05). Regarding the distance between the bottom of the calcaneus and the mid-tibial axis, the average result of Buck's method was about 1 mm larger than that of Cobey's method in the valgus and normal cases ( P < 0.05), except for varus cases ( P > 0.05). Conclusion Cobey's and Buck's techniques are the classic and popular hindfoot alignment assessment methods. The use of Buck's technique resulted in a better image with a less technical procedure and less time requirement. It is worthy of being popularized and used routinely for hindfoot radiography.

Factors driving the use of warfarin and non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

BACKGROUND/PURPOSE: In the past, warfarin was the drug of choice for stroke prevention in patients with atrial fibrillation (AF). Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have been approved as an alternative to warfarin in nonvalvular AF. However, there is a limited amount of real-world data on how NOACs are currently being used in Taiwan. This study was conducted to investigate the factors driving the initiation of anticoagulants and the selection of different anticoagulants in patients with AF. METHODS: We used National Taiwan University Hospital's electronic database to identify all nonvalvular AF patients from January 1, 2007 to December 31, 2013. Multivariate logistic regression models were used to examine the factors driving the initiation of anticoagulants and the selection of different anticoagulants. RESULTS: Among AF patients, 66.4% of anticoagulants users used NOACs instead of warfarin after the era of NOACs. Patients with female sex, hypertension, ischemic heart disease, cancer, hepatic disease, renal disease, bleeding history, and aspirin use were less likely to be anticoagulant users but are more likely to be anticoagulant users with a history of stroke (odds ratio = 2.64; 95% confidence interval, 2.02-3.45). Older age, ischemic heart disease, and aspirin use were the factors associated with NOACs usage, whereas hepatic disease showed the opposite results (odds ratio = 0.09; 95% confidence interval, 0.02-0.42). CONCLUSION: Stroke history was associated with anticoagulant use, whereas comorbidities associated with increased risk of bleeding showed the opposite result. Patients with hepatic disease were less likely to use NOACs.

Reliability of measurements on lateral ankle radiographs.

BACKGROUND: The aims of our study were to evaluate the validation of measurement of weight-bearing lateral radiographs. Two hypotheses were tested: the measurements on the lateral radiographs are reliable, and a theoretical limit could be identified when a surgeon can "eyeball" an incongruous ankle joint on lateral radiographs. METHODS: To test the first hypothesis, 3 experienced ankle surgeons evaluated 50 normal weight-bearing lateral radiographs of patients. The measurements assessed were the tibial lateral surface angle (TLS), the distance from the center of the talar joint circle to the longitudinal axis of the tibia (x) and the displacement from the center of the talar articular joint circle to the center of the distal tibia articular joint circle (d). To test the second hypothesis, we used CAD software to create schematic diagrams on which lateral radiographs of the ankle joint were not parallel (d = 1, 2, 3, 4 mm). Five experienced ankle surgeons were asked to judge whether the ankle articular surfaces were parallel. Intraobserver reliability was determined using the intraclass correlation coefficients (ICCs) and interobserver agreement by the Kendall coefficient of concordance. RESULTS: First, the intraobserver reliability was high (Cronbach's alpha >0.80) with regard to radiographic measurements according to the ICC. Significant interobserver disagreement was found (Kendall tauB, p < 0.01) using the Kendall concordance coefficient. Second, when the d-value was 4 mm, all the observers identified the incongruous ankle joint at two separate times. CONCLUSIONS: Consultation with experienced foot and ankle surgeons and precise definitions for lateral measurement assessments do not guarantee a high level of agreement. Surgeons can observe an incongruous ankle joint on lateral radiographs when the d-value is 4 mm.

Introducing diagnosis-related groups: is the information system ready?

Diagnosis-related group (DRG) system is a classification system widely used in health managements, the foundation of which lies in the medical information system. A large effort had been made to improve the quality of discharge data before the introduction of DRGs in Beijing. We extract discharge data from 108 local hospitals spanning 4 years before and after standardization to evaluate the impact of standardization on DRG grouping performance. The data was grouped on an annual basis in accordance with Beijing's local DRG system. Proportion of ungrouped data, coefficient of variation (CV) and reduction in variance (RIV) were used to measure the performance of the DRG system. Both the descriptive and regression analysis indicate a significant reduction in terms of ungrouped data and CV for expenditure, increase of RIV for expenditure and length of stay. However, when there was no intervention, that is, between 2005 and 2006 and between 2008 and 2009, changes in these indicators were all insignificant. Therefore, the standardization of discharge data did improve data quality and consequently enhanced the performance of DRGs. Developing countries with a relatively weak information infrastructure should strengthen their medical information system before the introduction of the DRG system.

Increased lung cancer mortality rates in the Chinese population from 1973-1975 to 2004-2005: An adverse health effect from exposure to smoking.

BACKGROUND: Lung cancer incidence and mortality rates have increased substantially in China despite improvements in clinical diagnosis and treatment approaches as well as significant advances in the implementation of tobacco-control policies in recent decades. METHODS: Age-standardized mortality rates and age-specific rates of lung cancer in China were estimated for the periods 1973 to 1975, 1990 to 1992, and 2004 to 2005 using data from 3 National Death Surveys. Among patients with lung cancer who were identified from a hospital-based information system, the percentages of ever-smokers were analyzed according to histologic and demographic variables. RESULTS: Age-standardized mortality from lung cancer in China dramatically increased from 7.30 per 100,000 during 1973 through 1975 to 27.62 per 100,000 during 2004 through 2005. Increases in lung cancer age-standardized mortality were consistent among men and women in urban and rural populations. Among men ages 75 to 79 years, lung cancer mortality increased remarkably to 453.67 per 100,000 in 2004 and 2005 (from 246.78 per 100,000 during 1990-1992 and from 53.65 per 100,000 during 1973-1975). Among 6674 patients with lung cancer who were identified from 2003 to 2007 from a hospital-based database, 82.97% of men were ever-smokers (73.35% of men with adenocarcinoma and 91.8% of men with squamous cell carcinoma), and 11.18% of women were ever-smokers (6% of women with adenosquamous carcinoma and 39.02% of women with squamous cell carcinoma). Differences in the numbers of ever-smokers were observed between age groups but not according to the year of diagnosis. CONCLUSIONS: The consistent and rapid increases in lung cancer mortality rates observed in the Chinese population and the high prevalence of exposure to smoking in China prompt a strong call for the implementation of a comprehensive tobacco-control policy and specific public health educational strategies.

Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer.

Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis.

Simultaneous removal of ammonium and nitrate by HDTMA-modified zeolite.

In this study, surfactant (hexadecyltrimethylammonium, HDTMA) modified zeolite (clinoptilolite) (SMZ) was used for simultaneous removal of ammonium and nitrate in wastewater, and the sorption properties of SMZ were determined. Results showed that natural clinoptilolite had good affinity for ammonium, but low sorption ability for nitrate, and the ammonium sorption process was well described by the pseudo-second order kinetic model. The SMZ had a significant enhancement on nitrate sorption and could simultaneously remove ammonium and nitrate at specific conditions, with removal efficiency up to 93.6% and 81.8%, respectively. The sorption process fitted well with the Langmuir isotherm. Orthogonal experiments showed that ammonium concentration was the most important factor for ammonium sorption on SMZ. However, surfactant loading was the major factor for nitrate sorption. Meanwhile, phosphate did not interfere with nitrate removal. Semi-empirical quantum mechanics molecular simulation indicated that electrostatic attraction existed between HDTMA and nitrate. Results of this study demonstrated that SMZs may have great potential for removing cations and anions simultaneously in the aquatic environment.

[Experience of surgical treatment of huge mediastinal tumors].

OBJECTIVE: The diagnosis and surgical treatment of 36 huge mediastinal tumors were summarized in order to evaluate the effect and safety of the operation. METHODS: Thirty-six huge mediastinal tumor patients treated in our department from June 2006 to June 2013 were retrospective analyzed, of whom clinical manifestations, diagnosis, surgical treatment and prognosis were carefully collected. Twenty-three cases were men and 13 were women. The average age was 39.2 years old. The pathology turned out to be benign in 23 cases and malignant in 13 cases. RESULTS: Complete resection was achieved in 34 cases while palliative resection in 2 cases with no perioperative death. Six cases had developed postoperative complications but all recovered after active treatment. Patients who had been diagnosed with benign tumors were all alive after follow-up periods of 6 months to 7 years. Nine malignat tumor patients developed recurrence or metastasis, including seven deaths. CONCLUSION: Surgery played a vital role in the diagnosis and treatment of huge mediastinal tumors. Preoperative diagnosis, accurate surgical approach and careful operation were the key to successful treatment. Benign huge mediastinal tumors had excellent prognosis with surgery.

The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Reduced lung cancer incidence attributable to decreased tobacco use in urban Shanghai.

BACKGROUND: Lung cancer has been the most common type of cancer in the world for several decades, and by 2008, there were approximately 1.61 million new cases, representing 12.7 % of all new cancers. It has been well known for many years that smoking causes lung cancer. Tobacco control measures have been regarded as the principal causes of the declines in smoking-related mortality, including mortality from lung cancer. METHODS: The Joinpoint Regression Program was used to analyze the long-term trends in lung cancer incidence rates from 1983 to 2008 in urban Shanghai. In addition, this study estimates how many fewer cases of lung cancer have occurred in urban Shanghai because of tobacco control activities. RESULTS: The lung cancer incidence rate among males decreased slightly by 0.6 % [95 % confidence interval (95 % CI) -0.1 to 1.3 %] from 1983 to 1999 and then declined rapidly at a rate of 3.8 % (95 % CI 2.1-5.4 %). Among females, the cancer incidence rate decreased by 0.1 % (95 % CI -0.2 to 0.5 %) from 1983 to 2008. Overall, we estimated that approximately 2,711 cases of lung cancer were averted among urban men in Shanghai between 2000 and 2008 because of the reduction in tobacco smoking. CONCLUSION: The reduction in tobacco smoking is a major factor in the decrease in the incidence rate of lung cancer. Sustained progress in tobacco control is essential.

The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions.

BACKGROUND: Psoriasin (S100A7) is a member of the S100 gene family. Alteration of Psoriasin expression has previously been reported to play an important role in cancer aggressive behaviour. The current study sought to investigate the level of Psoriasin expression at the mRNA level in a cohort of patients with non-small cell lung cancer (NSCLC), the association with clinical implication and outcomes, and the molecular and cellular impact of the protein on lung cancer cells. METHODS: Fresh frozen NSCLC cell carcinoma tissues, along with matched normal tissues were obtained from 83 NSCLC patients who received curative resection from January 2003 to December 2011. The expression of Psoriasin in the NSCLC specimens was assessed using both quantitative real time PCR (QPCR) and immunochemical staining. Knockdown and forced expression of Psoriasin in NSCLC cell lines were carried out using constructed plasmid vectors carrying either ribozyme transgenes targeting human Psoriasin or full-length coding sequence, respectively. The effect of Psoriasin on the functions of NSCLC cells was determined using a variety of in vitro cell function assays. RESULTS: Higher mRNA levels of Psoriasin were observed in tumour tissues when compared to both the paired normal background tissues and none paired normal tissues (p = 0.0251 and 0.0195). The mRNA level of Psoriasin was found to be higher in the squamous carcinoma (P=0.035). Higher Psoriasin expression is associated with poor prognosis. The cell function tests had supportive results to the clinical findings. Over-expression of Posriasin in lung cancer cells (SK-MES-1) resulted in an increase in in vitro growth and invasiveness. In contrast, Psoriasin knockdown suppressed cell growth and invasion (P<0.05), but increased cell adhesion (P<0.05). CONCLUSIONS: Psoriasin expression is increased in lung cancer, more specifically in lung squamous carcinoma compared with adenocarcinoma, and is associated with poor prognosis. Psoriasin plays crucial roles in regulating the growth and invasion of lung cancer cells.

Ankle joint pressure change before and after subtalar joint arthrodesis in varus and valgus malalignment of the tibia.

Purpose: The compensation mechanism of subtalar joint in ankle with varus or valgus deformity is controversial and not well established. This biomechanical study aims to investigate how subtalar joint arthrodesis will affect the ankle joint pressure in varus and valgus malalignment of the tibia. Methods: Eight fresh-frozen human cadaver legs were tested in this study. A custom-made fixture was utilized and a total of 600N was applied to simulate weight-bearing. Intra-articular sensors (TeckScan) were inserted in the ankle joint to demonstrate the ankle joint pressure. Conditions include: Neutral, 5°, 10°, 15° and 20° varus, 5°, 10°, 15° and 20° valgus. Results: After the fusion of the subtalar joint, when the tibia is gradually inverted, the inside pressure of the ankle joint gradually increases, and the pressure on the outside of the ankle joint gradually decreases. When the tibia is gradually eversion, the pressure on the outside of the ankle joint gradually increases, and the inside of the ankle joint gradually decreases. Conclusions: After the subtalar joint is fused, the compensatory activity of the subtalar joint disappears, and the regulation of the pressure in the ankle joint will be lost. We hypothesized that the inversion compensation of the subtalar joint is more likely to occur than the eversion compensation.

Effect of α-tocopherol in alleviating the lipopolysaccharide-induced acute lung injury via inhibiting nuclear factor kappa-B signaling pathways.

Acute respiratory distress syndrome (ARDS) leads to the acute lung injury (ALI), a form of diffused alveolars injury, accompanied by severe inflammation and oxidative damage of alveolar epithelial cells. α-Tocopherol (α-TOH), one of the eight isoforms of vitamin E, is a natural antioxidant-free radical. We aimed to understand the effect of α-TOH and mechanism involved in inducing the ALI. Lipopolysaccharide (LPS) is injected into the trachea of mice to generate ALI mouse models. α-TOH was used to administrate the mice intragastrically to detect the expression of inflammatory factors and antioxidant molecules by enzyme linked immunosorbent assay, hematoxylin-eosin staining and immunohistochemical staining. Mouse alveolar epithelial cell line (MLE-12 cells) was used to determine the effect of α-TOH on alveolar epithelial cells. Inflammatory factors such as, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α shows significant increase in the lung tissues of the mice induced by LPS and reduction in the expressions of superoxide dismutase (SOD)1/2 and glutathione peroxidase (GSH-Px). After treatment with α-TOH, the inflammation and oxidative stress levels shows substantial reduction in the lung tissues of the mice. Moreover, α-TOH also increases the proliferation ability of MLE-12 cells in vitro and reduces apoptosis level. In addition, α-TOH reduces p65 phosphorylation and nuclear translocation in alveolar epithelial cells in vivo and in vitro, thus, inhibiting the activity of the nuclear factor kappa-B (NF-κB) signaling pathway. α-TOH reduces the inflammation and oxidative stress of lung tissue by inhibiting the NF-κB signaling pathway, thereby alleviating the LPS-induced ALI.

Isoorientin suppresses sepsis-induced acute lung injury in mice by activating an EPCR-dependent JAK2/STAT3 pathway.

Sepsis is a systemic inflammatory syndrome, and acute lung injury (ALI) is one of the most common fatal complications of sepsis. Isoorientin (ISO) exerts a momentous role in the regulation of inflammation. However, whether ISO has a protective effect on sepsis-induced ALI remains unknown. This research aimed to elucidate the function of ISO on sepsis-induced ALI and its mechanism. In this study, the sepsis-induced ALI was established in the male C57BL/6 J mice. Functionally, ISO reduced the total protein concentration in BALF, lung wet/dry ratio and the numbers of neutrophils and macrophages in BALF as well as ameliorated lung injury. Besides, ISO treatment decreased the cytokine expressions and oxidative stress, and repressed the adhesion and migration of inflammatory cells induced by CLP. Mechanistically, ISO reduced the shedding of EPCR in the endothelial cell membrane; ISO treatment activated the JAK2/STAT3 signaling pathway through EPCR and the JAK2/STAT3 pathway inhibitors repressed the anti-inflammatory and antioxidant effects of ISO. In general, ISO suppressed sepsis-induced ALI in mice by activating an EPCR-dependent JAK2/STAT3 pathway.