Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang's therapeutic effects against neutrophilic asthma.

BACKGROUND: Xiao-Qing-Long-Tang (XQLT), a classical Chinese herbal medicine formula, has been extensively used for allergic asthma treatment. However, there is limited research on its anti-inflammatory effects and mechanisms specifically in neutrophilic asthma (NA). PURPOSE: This study aims to investigate the potential therapeutic effects of XQLT against NA using a combination of network pharmacology and experimental validation. STUDY DESIGN: By utilizing traditional Chinese medicine and disease databases, we constructed an XQLT-asthma network to identify potential targets of XQLT for NA. In the experimental phase, we utilized an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced model for neutrophilic asthma and examined the therapeutic effects of XQLT. RESULTS: Our research identified 174 bioactive components within XQLT and obtained 140 target genes of XQLT against asthma. Functional enrichment analysis revealed that these target genes were primarily associated with inflammation and cytokines. In the experimental validation, mice induced with OVA-LPS showcased eosinophilic and neutrophilic cell infiltration in peri-bronchial areas, elevated levels of IL-4 and IL-17 in both serum and lung, increased percentages of Th2 and Th17 cells in the spleen, as well as elevated levels of CD11b+ and CD103+ dendritic cells (DCs) within the lung. Treatment with XQLT effectively reduced IL-4 and IL-17 levels, decreased the percentages of Th2, Th17, CD11b+, and CD103+ DCs, and improved inflammatory cell infiltrations in lung tissues. These findings serve as a foundation for the potential clinical application of XQLT in neutrophilic asthma.

Coexistence of primary thyroid diffuse large B cell lymphoma and papillary thyroid carcinoma in a patient with Hashimoto's thyroiditis: a case report and literature review.

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare and has a poor prognosis. The co-occurrence of both malignancies is extremely rare, and the preoperative diagnosis is rather difficult. We report the case of a patient with both PTC and PTL in the setting of Hashimoto's thyroiditis (HT). A 59-year-old female patient was referred to our department for progressive enlargement of the thyroid gland over a few months. The imaging results demonstrated an enlarged thyroid and a mass in the thyroid. Total thyroidectomy and bilateral central neck node dissection were conducted. The final diagnosis of the coexistence of thyroid diffuse large B cell lymphoma and PTC was confirmed by histopathology and immunohistochemistry. The patient received radiation therapy and six cycles of chemotherapy combined with targeted therapy, including rituximab, cyclophosphamide, doxorubicin, vindesine, and prednisone (R-CHOP). After 6 months of follow-up, neither tumor has recurred. It is important for physicians to keep PTL in mind for differential diagnosis in HT patients with sudden thyroid enlargement.

Action recognition based on multimode fusion for VR online platform.

The current popular online communication platforms can convey information only in the form of text, voice, pictures, and other electronic means. The richness and reliability of information is not comparable to traditional face-to-face communication. The use of virtual reality (VR) technology for online communication is a viable alternative to face-to-face communication. In the current VR online communication platform, users are in a virtual world in the form of avatars, which can achieve "face-to-face" communication to a certain extent. However, the actions of the avatar do not follow the user, which makes the communication process less realistic. Decision-makers need to make decisions based on the behavior of VR users, but there are no effective methods for action data collection in VR environments. In our work, three modalities of nine actions from VR users are collected using a virtual reality head-mounted display (VR HMD) built-in sensors, RGB cameras and human pose estimation. Using these data and advanced multimodal fusion action recognition networks, we obtained a high accuracy action recognition model. In addition, we take advantage of the VR HMD to collect 3D position data and design a 2D key point augmentation scheme for VR users. Using the augmented 2D key point data and VR HMD sensor data, we can train action recognition models with high accuracy and strong stability. In data collection and experimental work, we focus our research on classroom scenes, and the results can be extended to other scenes.

Influence of cigarettes on myocardial injury in healthy population after exposure to high altitude over 5000 m.

BACKGROUND: Myocardial injury (MI) is a severe complication once subjected to hypoxic condition at high altitude. Little evidence exists about the association of cigarettes and MI at high altitude, especially over 5000 m. In the present study, we intend to explore the influence of cigarettes on MI in healthy population after travelling to this extreme environment. METHODS: Physical examination was performed in population at Pamirs plateau during November and December 2020. All participants were divided into cigarette group or control group. MI was diagnosed based on lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB) and aspartate amino transferase (AST). RESULTS: 311 people were included, 58 of whom developed MI, accounting for 18.6 %. Participants in cigarette group were all male, and younger than those in control group. There was longer exposure time in cigarette group. Compared with control group, red blood cell counting, hemoglobin (HGB) and hematocrit in cigarette group were significantly increased, while heart rate was significantly decreased. Cigarettes were found to significantly upregulate the level of CK-MB and LDH. After adjustment with age, sex, body mass index, altitude and exposure time as covariables, 108 male participants remained in each group, showing that none of clinical indexes had significant difference between the two groups. Logistic regression analysis revealed that female sex and oxygen saturation (SO2) were independent risk factors for MI in non-smokers while HGB was independent risk factor in smokers. By using Spearman correlation analysis, four myocardial enzymes were not relevant with the level of SO2 in non-smokers. For smokers, HGB was found to be in significant positive correlation with LDH. CONCLUSION: Our study suggested that exposure to high altitude over 5000 m could abrogate the impact of cigarettes on MI in healthy population. The independent factors affecting the occurrence of MI were distinctive depending on current smoking status.

Impact of high altitude on the incidence of postoperative venous thromboembolism and its genetic susceptibility: A meta-analysis and systematic review.

BACKGROUND: The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic review to evaluate the incidence of VTE at HA and comparatively low altitude (LA) and figure out the intrinsic risk factors such as susceptibility genes of patients with VTE at HA. METHODS: We selected studies that explored the risk factors for HA and VTE by searching PubMed, Embase, and Web of Science to analyze the impact of HA on VTE. All relevant studies before August 2021 were screened using the terms ([high altitude] OR [plateau] OR [mountain]) AND ([venous thromboembolism] OR [deep vein thrombosis] OR [pulmonary embolism]). Latest studies on the gene of HA-VTE patients were also summarized and analyzed. RESULTS: Fifteen studies were eventually assessed, and the overall numbers of subjects with and without VTE were 1475 and 286,926 respectively. The overall incidence of VTE, deep vein thrombosis (DVT) and pulmonary embolism (PE) in the HA group was significantly higher than that in the LA group (P < 0.01). The overall incidence of VTE, DVT and PE in the HA group was significantly higher than that in the LA group at 30 days post operation (P < 0.05, P < 0.05 and P < 0.01, respectively). At 90 days post operation, incidence of VTE and PE in the HA group was higher than that in the LA group (P < 0.01and P < 0.01, respectively), but there was no difference in the incidence of DVT (P = 0.07). Regarding endogenous factors, the analysis of genes in patients with HA-VTE revealed numerous targeted genes such as ANG, ACE, lncRNA-LINC00 659/UXT-AS1 and GP4. CONCLUSIONS: We observed a significant association between HA and the overall incidence of VTE and that at 30/90 days post operation, indicating that HA may be a risk factor for VTE.

Factors Influencing Delayed Treatment in Patients With Breast Cancer During COVID-19 Pandemic.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has endangered human health and life. This pandemic has changed people's lifestyle and affected the regular delivery of standard cancer treatment. In the present study, we aimed to explore the influencing factors of delayed treatment in patients with breast cancer during COVID-19 pandemic. Methods: This study was a cross-sectional investigation, and the subjects were patients who were discharged from the department of burn and plastic surgery after February 2020. All participants completed this study's online questionnaire based on the WeChat and Wenjuanxing platforms. Levels of anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Patients were divided into a delay group and non-delay group according to the occurrence of delayed treatment. Univariate analysis was performed by using the t test or chi-square test. A logistic regression model was employed to determine factors associated with delayed treatment. Results: The present study included a total of 397 patients with breast cancer, among whom delayed treatment occurred in 76 patients, accounting for 19.1%. Scores on both the anxiety subscale and depression subscale in delay group were significantly higher than those in non-delay group. Compared with non-delay group, we found that patients in delay group usually had a higher level of education (P = 0.020), worse self-feeling (P = 0.030), poor compliance of medical order (P = 0.042), and a higher prevalence of anxiety (P = 0.004) and depression (P = 0.012). Traffic inconvenience was also an important relevant factor for delayed treatment (P = 0.001). The prevalence of recurrence in delay group was higher than that in non-delay group (P = 0.018). By using logistic multivariate regression analysis, the results revealed that level of education and traffic inconvenience were independent factors influencing delayed treatment in patients with breast cancer during COVID-19 pandemic. Conclusion: The prevalence of delayed treatment in patients with breast cancer during COVID-19 pandemic is relatively high. Our findings reveal several influencing factors closely associated with delayed treatment, which is useful information that will be beneficial for patients to receive standardized therapy by taking targeted measures.

Preoperative prediction of central lymph node metastasis in cN0T1/T2 papillary thyroid carcinoma: A nomogram based on clinical and ultrasound characteristics.

BACKGROUND: Preoperative status of central lymph nodes is a key determinant of the initial surgical extent for papillary thyroid carcinoma (PTC). We aimed to develop and validate a nomogram based on preoperative clinical characteristics and ultrasound features to predict central lymph node status in patients with clinically lymph node-negative (cN0) T1/T2 PTC. METHODS: This retrospective study included 729 patients with cN0T1/T2 PTC who were treated between January 2015 and March 2020. Based on the ratio of 6:4, 431 patients who underwent surgeries relatively earlier comprised the training set to develop the nomogram, while the other 298 who underwent surgeries relatively later comprised validation set to validate the performance of nomogram. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify predictors of central lymph node metastasis (CLNM). These variables were used to construct a nomogram for predicting the risk of CLNM. The predictive performance, discriminative ability, calibration, and clinical utility of the nomogram model were evaluated in both sets. RESULTS: A total of 313 (42.9%) PTC patients were identified with CLNM. On multivariate logistic regression analyses, malegender, younger age, larger maximum diameter, multifocality, capsular invasion, infiltrative margins, intra-nodular vascularity, and aspect ratio >1 were independent risk factors for CLNM. Nomogram integrating these 8 factors showed excellent discrimination in the training [area under the curve (AUC): 0.788] and validation (AUC: 0.829) sets, and obtained well-fitted calibration curves. The cut-off value of this nomogram was 0.410 (∼245 points). Decision curve analysis confirmed the clinical utility of the nomogram. CONCLUSION: The CLNM-predicting nomogram can facilitate stratification of cN0T1/T2 PTC patients. Prophylactic central neck lymph node dissection can be considered for those with high nomogram scores.

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude.

Objective: Myocardial injury is a severe complication in population exposed to high altitude. As a new biomarker for inflammatory response, neutrophil to lymphocyte ratio (NLR) has been widely used to predict the prognosis of various diseases. In this study, we intend to explore the risk factors for myocardial injury at high altitude and examine the relationship between NLR level and development of myocardial injury. Methods: Consecutive patients admitted to a secondary general hospital at high altitude from June 2019 to May 2020 were selected into this retrospective study. Clinical and biochemical data were collected. According to the results of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and aspartate amino transferase (AST), patients were divided into myocardial injury group and normal group. Results: A total of 476 patients were enrolled in this study. Myocardial injury occurred in 158 patients (33.2%). We found that altitude, NLR, hemoglobin, total bilirubin, total cholesterol, and lipoprotein A in myocardial injury group were significantly higher than that in normal group (P < 0.05), while platelet count in myocardial injury group was significantly lower than that in normal group (P < 0.05). Logistic multivariate regression analysis revealed that there was an independent relationship between myocardial injury and smoke, NLR, hemoglobin (P < 0.05). By using Spearman correlation analysis, NLR was proved to have a significant positive correlation with LDH, CK, and CK-MB (P < 0.05) instead of AST. A receiver operating characteristic (ROC) curve was drawn to demonstrate that NLR could significantly predict the occurrence of myocardial injury with an area under the curve (AUC) of 0.594 (95% CI: 0.537-0.650, P < 0.05), and the level of 2.967 (sensitivity = 38.0%, specificity = 83.6%) was optimal cutoff value. Conclusion: The incidence of myocardial injury is high in population at high altitude. Smoke, hemoglobin, and NLR are independent factors related to myocardial injury. As a convenient and efficient marker, NLR is found to be closely associated with myocardial enzymes and have a predict role in the occurrence of myocardial injury. This study will provide a theoretical basis on NLR for the early diagnosis of myocardial injury at high altitude.

Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, ß-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer: Association with clinicopathological characteristics.

ABSTRACT: Excision repair cross complementing 1 (ERCC1), ribonucleotide reductase M1 (RRM1), ß-tubulin III (TUBB3), thymidylate synthetase (TYMS), and topoisomerase IIα (TOP2A) genes have been shown to be associated with the pathogenesis and prognosis of various types of carcinomas; however, their roles in breast cancer have not been fully validated. In this study, we evaluated the correlations among these biomarkers and the associations between their expression intensity and the clinicopathological characteristics to investigate whether the above genes are underlying biomarkers for patients with breast cancer.Ninety-seven tissue specimens collected from breast cancer patients. The expression levels of these biomarkers were measured by the multiplex branched DNA liquidchip (MBL) technology and clinicopathological characteristics were collected simultaneously.The expression levels of ERCC1, TUBB3, TYMS, and TOP2A were significantly associated with the characteristics of menopausal status, tumor size, lymph node metastasis, hormone receptor status, triple-negative status, Ki-67 index, and epidermal growth factor receptor. The expression intensity of ERCC1 negatively associated with that of TUBB3 and TYMS, and positively associated with that of RRM1. The expression intensity of TOP2A positively associated with that of TYMS. Hierarchical clustering analysis and difference test indicated that breast cancer with higher levels of TUBB3, TYMS, and TOP2A, as well as lower levels of ERCC1 and RRM1 tended to have higher histological grade and Ki-67 index.Our studies showed that ERCC1, TYMS, TUBB3, and TOP2A may be potential biomarkers for prognosis and individualized chemotherapy guidance, while there may be interactions between ERCC1 and RRM1, or TUBB3, or TYMS, as well as between TOP2A and TYMS in pathogenesis and development of breast cancer.

Individualized chemotherapy guided by the expression of ERCC1, RRM1, TUBB3, TYMS and TOP2A genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study.

ERCC1, RRM1, TUBB3, TYMS and TOP2A genes have been shown to be associated with drug resistance in various types of tumors; however, their roles in breast cancer chemotherapy have not been fully validated. In the present study, 140 well-matched patients with breast cancer, comprising 70 patients receiving individualized chemotherapy and 70 receiving classic chemotherapy, were analyzed. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS and TOP2A in breast cancer tissues were measured using multiplex branched DNA liquidchip technology prior to chemotherapy; an individualized chemotherapy regimen was developed for each patient according to the results. As a control, patients in the classic chemotherapy group received a docetaxel + epirubicin + cyclophosphamide regimen. Survival analyses were performed using the Kaplan-Meier method. The prognostic factors for disease-free survival (DFS) and overall survival (OS) in the patients were identified via Cox's proportional hazards regression model. Adverse reactions were evaluated according to the National Cancer Institute Common Toxicity Criteria 4. Compared with the classic chemotherapy group, the DFS and OS of the individualized chemotherapy group were significantly longer (DFS, 77.4 vs. 67.1 months, P=0.039; OS, 81.4 vs. 75.4 months, P=0.031), and the incidence of grade 2 or 3 palpitations and chest tightness was lower (12.9 vs. 27.1%, P=0.035). The chemotherapy strategy guided by genetic detection was an independent protection factor for DFS [hazard ratio (HR)=0.389, 95% confidence interval (CI): 0.153, 0.989, P=0.047], but not an independent protection factor for OS (HR=0.340, 95% CI: 0.107, 1.078, P=0.067). The results indicate that the combined detection of ERCC1, RRM1, TUBB3, TYMS and TOP2A gene expression and use of the results to guide individualized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.

miR-34a-5p up-regulates the IL-1ß/COX2/PGE2 inflammation pathway and induces the release of CGRP via inhibition of SIRT1 in rat trigeminal ganglion neurons.

Migraine is a debilitating neurological condition, with a global prevalence rate of 10.68% in men and 18.79% in women. Elucidation of the molecular mechanisms underlying migraines is of great importance for improving the quality of life of patients. The release of the neuropeptide calcitonin gene-related peptide (CGRP) from trigeminal nerve terminals is involved in the pathogenesis of migraine. Recent studies have shown that up-regulation of miR-34a-5p expression is associated with acute migraine attacks. Here, we investigated whether alteration of the expression of miR-34a-5p induces the release of the vasoactive peptide CGRP. We isolated primary rat trigeminal ganglion neurons and performed gain- and loss-of-function assays to alter the expression level of miR-34a-5p. Down-regulation of miR-34a-5p inhibited the expression of interleukin-1ß (IL-1ß)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), decreased IL-1ß, PGE2 and CGRP release, and up-regulated the expression of silencing information regulator 1 (SIRT1) in trigeminal ganglion, whereas overexpression of miR-34a-5p enhanced the expression of IL-1ß/COX2/PGE2, increased the release of IL-1ß, PGE2 and CGRP, and decreased the expression of SIRT1 in trigeminal ganglion. In addition, overexpression of miR-34a-5p induced apoptosis in primary rat trigeminal neurons. In summary, these findings suggest that miR-34a-5p up-regulates the IL-1ß/COX2/PGE2 inflammation pathway, induces apoptosis and enhances release of CGRP via inhibition of SIRT1 expression in trigeminal ganglion neurons; thus, miR-34a-5p may have potential as a therapeutic target for the treatment of migraine.

[Effects of electroacupuncture on miR-34a-5p/SIRT1 signaling in the trigeminal ganglion of rats with migraine].

OBJECTIVE: To investigate the effect of electroacupuncture(EA) on miR-34a-5p, silent mating type information regulation 2 homolog-1 (SIRT1) and nuclear factor-κB subunit p65 (NF-κB p65) in the trigeminal ganglion of rats with migraine, so as to explore the mechanisms of EA underlying prevention of migraine. METHODS: Male SD rats were randomly divi-ded into normal, sham operation, model, EA, and EA plus EX527(a SIRT1 inhibitor) groups, with 10 rats in each group. The rat model of migraine was established by electrical stimulation of the trigeminal ganglion. Before modeling, EA was applied at "Waiguan"(TE5) and "Fengchi"(GB20) for 20 min each time, once a day for 5 consecutive days, and intraperitoneal injection of EX527 (5 mg/kg) every day simultaneously. Serum prostaglandin E2 (PGE2) and calcitonin gene-related peptide (CGRP) concentrations were measured by enzyme-linked immunosorbent assay. The levels of miR-34a-5p, SIRT1 and interleukin-1ß (IL-1ß) mRNA，and protein expression of SIRT1, IL-1ß, NF-κB p65, NF-κB Ac-p65 and cyclooxygenase-2 （COX2） in trigeminal ganglia were detected by real-time quantitative PCR and Western blot, separately. RESULTS: The serum concentrations of PGE2 and CGRP， the expression of miR-34a-5p, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expression in the trigeminal ganglion were remarkably increased (P<0.05), while the SIRT1 mRNA and protein decreased (P<0.05) in the model group in contrast to the normal group. Following EA intervention， the serum PGE2 and CGRP concentrations, miR-34a-5p expression, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expression were significantly down-regulated (P<0.05), and SIRT1 mRNA and protein significantly up-regulated (P<0.05). Compared with the EA group, the serum concentrations of PGE2 and CGRP, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expressions increased (P<0.05), and SIRT1 protein decreased (P<0.05) in the EA plus EX527 group. CONCLUSION: In migraine rats, EA can inhibit miR-34a-5p expression in the trigeminal ganglion, increase SIRT1 expression, down-regulate IL-1ß/COX2 inflammation signals, reduce PGE2 synthesis, and thus redue CGRP released from the peripheral terminals, which may be one of the mechanisms of EA in preventing migraine.

Notch1 regulates endothelial apoptosis via the ERK pathway in chronic obstructive pulmonary disease.

The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis. In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD). We obtained surgical specimens from 10 patients with COPD and 10 control participants. Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells. Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE. The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis. However, this activation can be abolished by N1ICD overexpression. Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis. These results suggest that CS alters Notch signaling in pulmonary endothelial cells. Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor.

5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue.

BACKGROUND: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE), and further to search for a potential candidate agent protecting against emphysema induced by CSE. MATERIALS AND METHODS: An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR) was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively. RESULTS: CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE. CONCLUSION: 5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue.

Antagonism of cannabinoid receptor 1 attenuates the anti-inflammatory effects of electroacupuncture in a rodent model of migraine.

BACKGROUND: The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials. Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor. OBJECTIVE: To investigate whether CB1 receptors mediate the anti-inflammatory effects of EA on migraine attacks. METHODS: A migraine model was produced in Sprague-Dawley rats by unilateral electrical stimulation of the trigeminal ganglion (TGES). Rats received EA daily on the 5 days preceding TGES with (TGES+EA+SR141716 group) or without (TGES+EA group) intraperitoneal injections of the CB1 receptor antagonist SR141716. Another group of TGES rats (TGES+MA group) and a non-TGES sham-operated group of rats (Sham+MA group) received minimal acupuncture (MA). Calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) concentrations were determined in serum obtained from the ipsilateral jugular vein at initiation of TGES and 5 min after. Postmortem interleukin (IL)-1ß and cyclooxygenase (COX)2 protein levels in the trigeminal ganglion (TG) and plasma protein extravasation (PPE) in the dura mater were assessed. RESULTS: TGES induced increases in serum CGRP and PGE2 levels (TGES+MA vs baseline and vs Sham: all p<0.001), as well as IL-1ß and COX2 protein expression in the TG, and neurogenic PPE levels (TGES+MA vs Sham+MA: all p<0.001). EA attenuated TGES-induced increases in the levels of these proteins (TGES+EA vs TGES+MA: all p<0.001). CB1 receptor antagonism reversed the effects of EA (TGES+EA+SR141716 vs TGES+EA: all p<0.05). CONCLUSIONS: CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.

Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model.

Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice.

The up-regulation of long non-coding RNA AFAP1-AS1 is associated with the poor prognosis of NSCLC patients.

Long non-coding RNA (lncRNA) is actively transcribed from human genome and has been considered to participate in many processes of various cancers. The purpose of this study was to investigate the expression of LncRNA AFAP1-AS1 and its prognostic value in NSCLC. LncRNA AFAP1-AS1 expression was detected by qRT-PCR which demonstrated that the expression was significantly increased in tumor tissues compared with the adjacent non-cancerous tissues and healthy tissues. The clinical stage, smoking history, infiltration degree, lymph node metastasis and distant metastasis were all proved to impact the expression of LncRNA AFAP1-AS1 (P<0.05). Kaplan-Meier analysis was performed to evaluate the overall survival of NSCLC patients with different expression level of LncRNA AFAP1-AS1, and results showed that patients with high LncRNA AFAP1-AS1 expression lived shorter than those with low LncRNA AFAP1-AS1 expression (Log rank test, P<0.001). Besides, the prognostic value of LncRNA AFAP1-AS1 as well as the clinical features was assessed by Cox regression analysis. The outcome revealed that LncRNA AFAP1-AS1 was closely related to the prognosis of NSCLC. Taken together, LncRNA AFAP1-AS1 was up-regulated in NSCLC tissues and it could be an independent prognostic indicator for NSCLC patients.

Comparison between cigarette smoke-induced emphysema and cigarette smoke extract-induced emphysema.

BACKGROUND AND OBJECTIVE: Emphysema is the main pathological feature of COPD and also is the focus of the related research. Although several emphysema animal models have been established, exact comparison of findings is seldom. The present study aimed to compare cigarette smoke (CS) exposure-induced emphysema model and intraperitoneal injection of cigarette smoke extract (CSE)-induced emphysema model to evaluate the effectiveness of the two different modeling methods. METHODS: Six-week-old male C57BL/6 J mice were used and randomly divided into two groups: CS exposure and intraperitoneal injection of CSE. Each group was subdivided into two subgroups: control and CS or CSE. Lung function, mean linear intercept (MLI), destructive index (DI), apoptotic index (AI), total and differential cells count in broncholavolar lavage fluid (BALF), SOD and IL-6 concentration in serum were measured. RESULTS: Compared with their respective controls, lung function was significantly decreased in CS and CSE groups (P < 0.01); MLI, DI, and AI of lung tissue were significantly higher in CS and CSE groups (P < 0.01); total number of leukocytes, the number and percentage of neutrophils (NEUs), and the number of macrophages (MAC) in BALF were significantly higher in CS and CSE groups (P < 0.01); SOD concentration in serum was significantly decreased in CS and CSE groups (P < 0.01); IL-6 concentration in serum was significantly increased in in CS and CSE groups (P < 0.01). There was no significant difference between CS group and CSE group in any of the parameters described above. CONCLUSIONS: Both CS exposure and intraperitoneal injection of CSE could induce emphysema and the effectiveness of the two different modeling methods were equal.

Dual effects of cigarette smoke extract on proliferation of endothelial progenitor cells and the protective effect of 5-aza-2'-deoxycytidine on EPCs against the damage caused by CSE.

UNLABELLED: Cigarette smoke is a major public health problem associated with multitude of diseases, including pulmonary and vascular diseases. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of these diseases. The effect of CSE on EPCs is seldom studied. The aim of the current study is to observe the effect of CSE on biological behavior of EPCs and, further, to search for potential candidate agent in protection of proliferation of EPCs against the damage caused by CSE exposure in vitro. METHODS: The proliferations of EPCs isolated from bone marrow of C57BL/6J mice were assessed by MTT after incubating the EPCs with a series of concentrations of CSE (1.0%, 2.5%, 5.0%, and 10.0%) for different times (3, 6, and 24 hours) as well as with 1.0% CSE in presence of 5-AZA-CdR for 24 hours. RESULTS: The proliferations of EPCs were significantly enhanced after 3 hours of exposure to concentrations of 1.0% and 2.5% CSE but depressed when exposed to concentrations of 5.0% and 10.0% CSE. Furthermore, the 5-AZA-CdR in concentrations of 2.0 µmol/L and 5.0 µmol/L partly protected against the depression of proliferation of EPCs caused by CSE exposure. CONCLUSIONS: The CSE showed dual effects on proliferation of EPCs isolated from mice. The 5-AZA-CdR partly protected the proliferation of EPCs against the damage caused by CSE exposure in vitro, suggesting that DNA methylation may be involved in the dysfunction of EPCs induced by CSE.

C-Kit/c-Kit ligand interaction of bone marrow endothelial progenitor cells is influenced in a cigarette smoke extract-induced emphysema model.

BACKGROUND: Smoking causes lung endothelial cell apoptosis and emphysema. Derived from bone marrow, circulating endothelial progenitor cells (EPCs) maintain vascular integrity by replacing and repairing damaged endothelial cells. Smoking influences the number of circulating EPCs. Recruitment of EPCs from bone marrow to peripheral blood depends on the interaction of c-Kit/soluble c-Kit ligand (sKitL). We hypothesized that smoking might influence c-Kit(+) EPCs/sKitL interaction in bone marrow in the development of smoking-related emphysema. In this study, we used a cigarette smoke extract (CSE)-induced emphysema model. METHODS: Mice were injected intraperitoneally with PBS/CSE and sacrificed at day 28. Lung function and pathology of lung tissue were measured to characterize the model. Expressions of c-Kit in the lung tissue were assayed. Bone marrow cells were isolated by red blood cell lysis. EPCs/c-Kit(+) EPCs in nonred blood cells were analyzed by flow cytometry. Expressions of KitL and MMP-9, and activity MMP-9 in bone marrow were measured. RESULTS: Our data demonstrated that gene and protein expressions of c-Kit were decreased in the lung tissue in this model. Compared with the control group, the number of bone marrow nonred blood cells was unchanged following CSE treatment, while the depletion of bone marrow EPCs/c-Kit(+) EPCs was significant. The level of sKitL was reduced in the bone marrow in the model. The reduction of sKitL was associated with deregulated KitL expression and decreased MMP-9 activity. CONCLUSIONS: The interaction between c-Kit and sKitL in bone marrow EPCs, a critical step in endothelial repair, is negatively affected in a CSE-induced emphysema model.