Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and ß subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs.

FRP-XGBoost: Identification of ferroptosis-related proteins based on multi-view features.

Ferroptosis represents a novel form of programmed cell death. Pan-cancer bioinformatics analysis indicates that identifying and modulating ferroptosis offer innovative approaches for preventing and treating diverse tumor pathologies. However, the precise detection of ferroptosis-related proteins via conventional wet-laboratory techniques remains a formidable challenge, largely due to the constraints of existing methodologies. These traditional approaches are not only labor-intensive but also financially burdensome. Consequently, there is an imperative need for the development of more sophisticated and efficient computational tools to facilitate the detection of these proteins. In this paper, we presented a XGBoost and multi-view features-based machine learning prediction method for predicting ferroptosis-related proteins, which was referred to as FRP-XGBoost. In this study, we explored four types of protein feature extraction methods and evaluated their effectiveness in predicting ferroptosis-related proteins using six of the most commonly used traditional classifiers. To enhance the representational power of the hybrid features, we employed a two-step feature selection technique to identify the optimal subset of features. Subsequently, we constructed a prediction model using the XGBoost algorithm. The FRP-XGBoost achieved an accuracy of 96.74 % in 10-fold cross-validation and a further accuracy of 91.52 % in an independent test. The implementation source code of FRP-XGBoost is available at https://github.com/linli5417/FRP-XGBoost.

Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target.

Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients' response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy response and immune-related adverse events (irAEs). Unlike other -omics, the gut microbiome can serve as not only biomarkers but also potential targets for enhancing the efficacy of immunotherapy. Approaches for modulating the gut microbiome include probiotics/prebiotics supplementation, dietary interventions, fecal microbiota transplantation (FMT), and antibiotic administration. This review primarily focuses on elucidating the potential role of the gut microbiome in predicting the response to cancer immunotherapy and improving its efficacy. Notably, we explore reasons behind inconsistent findings observed in different studies, and highlight the underlying benefits of antibiotics in liver cancer immunotherapy.

Association of serum cytokines with coronary chronic total occlusion and their role in predicting procedural outcomes.

BACKGROUND: Cytokines are strongly associated with coronary artery disease (CAD); however, few studies have explored the relevance of cytokines in coronary chronic total occlusion (CTO). This study aimed to clarify the association of cytokines with CTO and its procedural outcomes. METHODS: A total of 526 patients with suspected CAD but not acute myocardial infarction were enrolled and divided into CTO (n = 122) and non-CTO (n = 404) groups based on coronary angiography. Furthermore, serum levels of 12 cytokines [Interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α (TNF-α), interferon-α (IFN-α), and IFN-γ] were measured for each patient. RESULTS: Patients with CTO had higher rates of male (P = 0.001), smoking (P = 0.014), and diabetes (P = 0.008); higher levels of IL-6 (P < 0.001), total triglycerides (P = 0.020), serum creatine (P = 0.001), and high-sensitivity troponin I (P = 0.001); and lower IL-4 (P < 0.001), total cholesterol (P = 0.027), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) levels compared to those without CTO. IL-4 (OR = 0.216, 95%CI:0.135-0.345, P < 0.001), IL-6 (OR = 1.248, 95%CI:1.165-1.337, P < 0.001), and HDL-C (OR = 0.047, 95%CI:0.010-0.221, P < 0.001) were identified as independent predictors of CTO. And good predictive performance (AUC = 0.876) for CTO, with a sensitivity of 81.96% and specificity of 81.19%, could be achieved by combining these three predictors. Furthermore, patients with procedural success had younger age (P = 0.004) and lower serum IL-6 levels (P = 0.039) compared to those with procedural failure, and IL-6 levels (OR = 0.962, 95%CI: 0.931-0.995, P = 0.023) were associated with procedural success. CONCLUSION: IL-4, IL-6, and HDL-C levels were strongly associated with CTO, and IL-6 also linked to procedural outcomes of CTO.

Treatment of a Patient With Meningioma With Complicated Blood Supply.

Meningiomas account for ~30% of primary intracranial tumors, making them the second most common type of brain tumor. Most meningiomas are benign, and surgical resection is curative. By utilizing 3-dimensional slicer technology for multimodal image fusion, a wealth of 3-dimensional anatomic information can be obtained, enabling more effective treatment of meningiomas with complex tumor locations and surrounding structures. Guided by the 3-dimensional structural models, we conducted detailed preoperative planning for 1 case of highly vascularized meningioma and utilized combined surgery for complete tumor removal, effectively avoiding intraoperative bleeding and postoperative complications.

Clinical efficacy of duloxetine in the treatment of axial symptoms after posterior cervical spine surgery: a retrospective study.

PURPOSE: To evaluate the efficacy of duloxetine in the treatment of patients with axial symptoms after posterior cervical spine surgery. METHODS: Patients with axial symptoms after posterior cervical spine surgery treated by duloxetine or non-drug therapy from 2018 to 2021 were reviewed. Duloxetine was administered gradually, with oral administration of 30 mg in the first week and oral administration of 60 mg from the second week. Visual analogue scale (VAS), 36-Item Short-Form Health Survey questionnaire (SF-36) and EuroQol-5 Dimensions (EQ-5D) questionnaire were used to evaluate the severity of AS at baseline and 1 week, 2 weeks, 1 month, 3 months and 6 months after medication. The occurrence of adverse reactions was recorded. RESULTS: A total of 63 eligible patients who received duloxetine therapy (n = 35) or non-drug therapy (n = 28) were included. All patients were followed up for 6 months. Significant improvements were found in VAS score compared with baseline in both groups (1.87 ± 0.81 vs 6.61 ± 1.16, 3.18 ± 0.67 vs 6.31 ± 1.40; P < 0.05 for all). Meanwhile, the VAS score of the duloxetine group was significantly better than that of the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05). Besides, according to 36-Item Short-Form Health Survey questionnaire (SF-36), the PCS score and MCS score are significantly higher than before the treatment in duloxetine group (PCS 62.82 ± 6.04 vs 44.36 ± 7.25, MCS 65.50 ± 4.53 vs 55.55 ± 6.06; P < 0.05 for all). And when we compared variables between the two groups, the PCS score of the duloxetine group was significantly better than that of the non-drug therapy group (P < 0.05), but there was no significant difference in MCS score between the two groups (P > 0.05). What's more, EQ-5D score had significant improvements in the duloxetine group compared with the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05). CONCLUSION: Oral duloxetine has a better short-term outcome than conventional non-drug therapy in patients with axial symptoms following posterior decompression surgery in the cervical spine.

Added value of spectral parameters in diagnosing metastatic lymph nodes of pT1-2 rectal cancer.

PURPOSE: To investigate the added value of spectral parameters derived from dual-layer spectral detector CT (SDCT) in diagnosing metastatic lymph nodes (LNs) of pT1-2 (stage 1-2 determined by pathology) rectal cancer. METHODS: A total of 80 LNs (57 non-metastatic LNs and 23 metastatic LNs) from 42 patients with pT1-T2 rectal cancer were retrospectively analyzed. The short-axis diameter of LNs was measured, then its border and enhancement homogeneity were evaluated. All spectral parameters, including iodine concentration (IC), effective atomic number (Zeff), normalized IC (nIC), normalized Zeff (nZeff), and slope of the attenuation curve (λ), were measured or calculated. The chi-square test, Fisher's exact test, independent-samples t-test, or Mann-Whitney U test was used to compare the differences of each parameter between the non-metastatic group and the metastatic group. Multivariable logistic regression analyses were used to determine the independent factors for predicting LN metastasis. Diagnostic performances were assessed by ROC curve analysis and compared with the DeLong test. RESULTS: The short-axis diameter, border, enhancement homogeneity, and each spectral parameter of LNs showed significant differences between the two groups (P < 0.05). The nZeff and short-axis diameter were independent predictors of metastatic LNs (P < 0.05), with areas under the curve (AUC) of 0.870 and 0.772, sensitivity of 82.5% and 73.9%, and specificity of 82.6% and 78.9%. After combining nZeff and the short-axis diameter, the AUC (0.966) was the highest with sensitivity of 100% and specificity of 87.7%. CONCLUSION: The spectral parameters derived from SDCT might help us to improve the diagnostic accuracy of metastatic LNs in patients with pT1-2 rectal cancer, the highest diagnostic performance can be achieved after combining nZeff with the short-axis diameter of LNs.

Optimization scheme of machine learning model for genetic division between northern Han, southern Han, Korean and Japanese.

Han Chinese, Korean and Japanese are the main populations of East Asia, and Han Chinese presents a gradient admixture from north to south. There are differences among the East Asian populations in genetic structure. To achieve fine-scale genetic classification of southern (S-) and northern (N-) Han Chinese, Korean and Japanese individuals in this study, we collected and analyzed 1185 ancestry informative SNPs (AISNPs) from previous literature reports and our laboratory findings. First, two machine learning algorithms, softmax and randomForest, were used to build genetic classification models. Then, phylogenetic tree, STRUCTURE and principal component analysis were used to evaluate the performance of classification for different AISNP panels. The 234-AISNP panel achieved a fine-scale differentiation among the target populations in four classification schemes. The accuracy of the softmax model was 92%, which realized the accurate classification of the S-Han, N-Han, Korean and Japanese individuals. The two machine learning models tested in this study provided important references for the high-resolution discrimination of close-range populations and will be useful tools to optimize marker panels for developing forensic DNA ancestry inference systems.

Intramammary edema of invasive breast cancers on MRI T2-weighted fat suppression sequence: Correlation with molecular subtypes and clinical-pathologic prognostic factors.

OBJECTIVE: To investigate the associations between different patterns of intramammary edema on preoperative 3.0 T magnetic resonance imaging (MRI) T2-weighted fat suppression sequence and invasive breast cancer molecular subtypes and clinical-pathologic prognostic factors. METHODS: Between May 2014 and December 2020, 191 patients with invasive breast cancer who had undergone preoperative MRI and mastectomy or breast-conserving surgery were retrospectively enrolled. The relationships between different patterns of intramammary edema and invasive breast cancer molecular subtypes and clinical-pathologic features were evaluated using the Student's t-test or Mann-Whitney U test and the χ2 test or Fisher's exact test. RESULTS: Patients with luminal B (HER2 positive), HER2-enriched and triple negative breast cancers respectively had different patterns of intramammary edema (P < 0.001). There was a significant association between intramammary edema and clinical-pathologic factors, including larger tumor size, higher Ki-67 index, lymph node metastasis and lymphovascular invasion (all P < 0.001). CONCLUSIONS: Intramammary edema may provide added values of predicting molecular subtypes and clinical-pathologic prognosis, enhancing the ability to individualize the treatment of patients with invasive breast cancer.

Quantitative parameters of magnetic resonance imaging cannot predict human epidermal growth factor receptor 2 (HER2) status in rectal cancer.

PURPOSE: To retrospectively investigate whether magnetic resonance imaging (MRI) quantitative parameters can differentiate human epidermal growth factor receptor 2 (HER2) status in rectal cancer. MATERIALS AND METHODS: This study included 89 patients with surgically confirmed rectal cancer who underwent preoperative MRI from June 2014 to May 2019. Patients were divided into three groups: HER2 negative (HER2-Neg); HER2-low expression (HER2-L); and HER2 positive (HER2-Pos). Quantitative perfusion parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) Tofts model (pharmacokinetic blood dual compartment model) were listed as follows: volume transfer constant (Ktrans), rate constant (Kep), and extracellular volume ratio (Ve). The mean, minimum, and maximum apparent diffusion coefficient (ADC) values at standard (800 s/mm2) b-values were obtained with diffusion-weighted imaging (DWI). Clinicopathologic characteristics and quantitative parameters were compared by Fisher's exact test and one-way analysis of variance (ANOVA), respectively. RESULTS: The 89 patients included 52 (58.4%) with HER2-Neg, 31 (34.8%) with HER2-L, and 6 (6.8%) with HER2-Pos states. Fisher's exact test showed that clinicopathologic characteristics among the three groups were not significantly different (p = 0.281 to 1.000). Likewise, there were no associations between HER2 status and any quantitative parameters, including Ktrans (p = 0.296), Kep (p = 0.290), Ve (p = 0.184), ADCmean (p = 0.181), ADCmin (p = 0.143), or ADCmax (p = 0.058). CONCLUSION: Quantitative perfusion parameters (Ktrans, Kep, Ve) and ADC values were not able to discriminate HER2 status in patients with rectal cancer or evaluate treatment response in real time.

Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma.

OBJECTIVE: Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors. DESIGN: Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines. RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites. CONCLUSIONS: The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.

Measurement of the Total Lung Volume Using an Adjusted Single-Breath Helium Dilution Method in Patients With Obstructive Lung Disease.

Background: Whole-body plethysmography (WBP) is the gold standard for measuring lung volume, but its clinical application is limited as it requires expensive equipment and is not simple to use. Studies have shown that the single-breath helium dilution (SBHD) method, which is commonly used in clinical practice, significantly underestimates lung volume in patients with obstructive lung disease (OLD). By comparing the differences in lung volume measured using SBHD and WBP, we aimed to establish a correction equation for the SBHD method to determine the total lung volume in patients with OLD of different severities. Methods: From 628 patients with OLD simultaneously subjected to SBHD and WBP, 407 patients enrolled between January 2018 and November 2019 were in the training group and 221 enrolled between December 2019 and December 2020 were in the prospective verification cohort. The multiple linear regression equation was used for data in the training group to establish a correction equation for SBHD to determine the total lung volume, and this was validated in the prospective validation cohort. Results: There was a moderate positive correlation between total lung capacity (TLC) determined using the SBHD [TLC (SBHD)] and WBP methods [TLC (WBP)] (r = 0.701; P < 0.05), and the differences between TLC (SBHD) and TLC (WBP) (ΔTLC) were related to the severity of obstruction. As the severity of obstruction increased, the TLC was underestimated by the SBHD method. We established the following correction equation: TLC (adjusted SBHD) (L) = -0.669 + 0.756*TLC(SBHD)(L) - 0.047* F E V 1 F V C +0.039*height (cm)-0.009*weight(kg)(r2 = 0.753 and adjusted r2 = 0.751). Next, we validated this equation in the validation cohort. With the correction equation, no statistical difference was observed between TLC (adjusted SBHD) and TLC (WBP) among the obstruction degree groups (P > 0.05). Conclusions: The SBHD method is correlated with WBP to measure the total lung volume, but the SBHD method presents limitations in determining the total lung volume in patients with obstructive lung disease. Here, we established an effective and reliable correction equation in order to accurately assess the total lung volume of patients with OLD using the SBHD method.

Increased internal cerebral vein diameter is associated with age.

OBJECTIVE: A recent study described the relationship between cerebral venous diameter and white matter hyperintensity (WMH) volume. However, the adults were not further grouped; therefore, we aimed to compare across age groups and use susceptibility-weighted imaging (SWI) to explore whether there is also a relationship between a larger cerebral draining venous diameter and age, which could provide evidence of a temporal relationship. METHODS: We retrospectively analysed data collected from 405 subjects (90 youths, 166 middle-aged participants, and 149 elderly subjects) and respectively used T2-weighted fluid-attenuated inversion recovery (FLAIR) and SWI to assess WMHs and venous diameter. RESULTS: An increased internal cerebral vein (ICV) diameter was associated with age in different WMH groups (F = 3.453, 10.437, 11.746, and 21.723, respectively, all p < 0.001; multiple comparisons all p < 0.05), whereas the effect of the anterior septal vein (ASV) was opposite (F = 1.046, 1.210, 0.530, and 0.078, respectively, p > 0.05). There was a positive correlation between the ICV diameter and age with increasing WMH severity (R = 0.727, 0.709, 0.754, and 0.830, respectively, all p < 0.001). A statistically significant relationship between the thalamostriate vein (TSV) diameter and age was observed only in the moderate and severe WMH groups (F = 4.070 and 3.427, respectively, all p < 0.05; multiple comparisons all p < 0.05). CONCLUSIONS: Our study demonstrates that increased TSV and ICV diameters are associated with age with increasing WMH severity, especially the ICV diameter using SWI.

The value of small airway function parameters and fractional exhaled nitric oxide for predicting positive methacholine challenge test in asthmatics of different ages with FEV1 ≥ 80% predicted.

BACKGROUND: Small airway function parameters (SAFPs) combined with fractional exhaled nitric oxide (FeNO) can predict a positive methacholine challenge test (MCT) for asthma diagnosis. However, their predictive utility in patients with forced expiratory volume in one second (FEV1 ) ≥80% predicted within different age ranges remains unclear. This study aimed to assess the utility of SAFPs, alone or combined with FeNO, to predict a positive MCT in patients in two age groups (<55 and ≥55 years) with asthma-suggestive symptoms and FEV1  ≥80% predicted. METHODS: We enrolled 846 Chinese patients with suspected asthma and standard spirometry, FeNO, and MCT findings. Using the area under the curves (AUCs), the utility of SAFPs, alone or combined with FeNO, for predicting a positive MCT was analyzed in a discovery (n = 534) and validation cohort (n = 312) in both age groups with FEV1 ≥80% predicted. RESULTS: In the discovery cohort, the optimal cut-off values for predicting a positive MCT in patients aged <55 years (74.2% and 74.9% for forced expiratory flow (FEF)50% and FEF25%-75% , respectively) were higher than those in patients aged ≥55 years (65.0% and 62.9% for FEF50% , FEF25%-75% , respectively). However, the optimal FeNO value in patients aged <55 years (43 ppb) was lower than that in patients aged ≥55 years (48 ppb). FeNO combined with SAFPs (FEF50% , FEF25%-75% ) significantly increased the AUCs in both groups (≥55 years [0.851 for FEF50% and 0.844 for FEF25%-75% ]; <55 years [0.865 for FEF50% and 0.883 for FEF25%-75% ]) compared with a single parameter (p < 0.05). These findings were confirmed in the validation cohort. Compared with patients ≥55 years, those aged <55 years had higher and lower optimal cut-off values for SAFPs and FeNO, respectively. The AUCs of FeNO combined with SAFPs for predicting a positive MCT for asthma diagnosis were significantly higher than those of the individual parameters (p < 0.05) in both age groups. CONCLUSIONS: There were age-group differences in the utility of SAFPs combined with FeNO for predicting a positive MCT. Patients with an asthma-suggestive history and a normal FEV1 should be stratified by age when using SAFPs combined with FeNO to predict a positive MCT.

Correlations of Mean and Mimimum Apparent Diffusion Coefficient Values With the Clinicopathological Features in Rectal Cancer.

RATIONALE AND OBJECTIVE: The study aimed to investigate the possible correlation between mean (MeanADC) and minimum (MinADC) apparent diffusion coefficient values with the clinicopathological features and evaluate the diagnostic potential of MinADC values and MeanADC values in predicting the behavior of rectal cancer. MATERIALS AND METHODS: In total, 148 pathologically verified lesions that were subjected to conventional MR imaging and diffusion weighted imaging prior to operation were included. The MeanADC values and MinADC values were calculated and their correlation with clinicopathological characteristics were investigated. RESULTS: Both MeanADC values and MinADC values correlated with T classification (MeanADC: t = 2.841, p = 0.005; MinADC: t = 2.356, p = 0.020), N classification (MeanADC: t = 3.468, p = 0.001; MinADC: t = 3.072, p = 0.003), tumor histological grade (MeanADC: F = 8.175, p = 0.000; MinADC: F = 22.038, p = 0.000), perineural invasion (MeanADC: t = 2.547, p = 0.012; MinADC: t = 3.081, p = 0.002), and extramural venous invasion (MeanADC: t = 2.157, p = 0.033; MinADC: t = 2.635, p = 0.009) in rectal cancer, but no significant correlation with gender, age, and tumor location (p > 0.05). The MinADC values showed a higher diagnostic efficacy in discriminating the well or poor differentiation of rectal cancer compared to MeanADC values, with a threshold value of ≥0.929 × 10-3 mm2/s (sensitivity, 80%; specificity, 88.1%) or ≤0.752 × 10-3 mm2/s (sensitivity, 94.1%; specificity, 74%). CONCLUSION: Both MeanADC values and MinADC values might be used as a quantitative parameter to evaluate the aggressiveness of rectal cancer. The MinADC values could be as the better predictor in identifying tumor differentiation compared to the MeanADC values.

Study on Novel Nanoparticle Slow-Release Drugs for Moyamoya Disease.

Spontaneous basilar artery occlusive disease is a disease characterized by thickening of the intima of the bilateral internal carotid artery and the anterior and middle cerebral arteries, gradually narrowing the arterial diameter, and compensatory dilatation of the perforating artery at the base of the brain. Aspirin (acetylsalicylic acid), as a classic non-steroidal anti-inflammatory drug, has been proven to have antiplatelet, anti-inflammatory, and immune-regulating effects. But how to achieve long-term sustained release of aspirin and achieve anti-platelet aggregation remains to be studied. This study intends to build a microsphere sustained-release system to achieve long-term stable and slow release of aspirin drug, thereby achieving a more ideal anti-platelet aggregation effect. The therapeutic effects of three groups of nanoparticle sustained-release drug regimens on platelet aggregation were compared. The results showed that the platelet inhibition rate and NIHSS scores before treatment were compared between the three groups; compared with the other groups, the PLGA group had higher AA and ADP pathway-induced platelet inhibition rates after treatment and lower plasma Lp-PLA2 and NIHSS scores. This shows that aspirin nanoparticle slow-release drugs can effectively increase platelet inhibition rate and improve the antiplatelet ability of patients with spontaneous basilar artery occlusive disease, which is beneficial to promoting prognosis recovery.

Inhibition of oxidative stress and NLRP3 inflammasome by Saikosaponin-d alleviates acute liver injury in carbon tetrachloride-induced hepatitis in mice.

NLRP3 inflammasome activation results in severe liver inflammation and injury. Saikosaponin-d (SSd) possesses anti-inflammatory and hepatoprotective effects. This study aimed to determine the protective effects of SSd on carbon tetrachloride (CCl4)-induced acute liver injury in mice, and whether oxidative stress and NLRP3 inflammasome activation participate in the process.The CCl4 mice model and controls were induced. The mice were treated with SSd at 1, 1.5, or 2.0 mg/kg in a total volume of 100 µl/25 g of body weight. Liver injury was assessed by histopathology. Oxidative stress was determined using mitochondrial superoxide production (MSP), malondialdehyde (MDA) content, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. NLRP3, ASC, and Caspase 1 were determined by real-time PCR and western blot. IL-1ß and IL-18 levels were determined by ELISA.Significantly elevated oxidative stress was induced in the liver by CCl4, as demonstrated by histopathology and increases of MDA and MSP levels and decreases of SOD, GPx, and CAT activities (all P < 0.01). SSd significantly decreased the MDA and MSP levels and increased the activities of SOD, GPx, and CAT (all P < 0.05). The mRNA expression of NLRP3, ASC, and Caspase 1, and the protein expression of Caspase 1-p10, NLRP3, ASC, IL-1ß, and IL-18 were significantly increased after CCl4 induction (all P < 0.01). These changes were reversed by SSd (all P < 0.05).Suppression of the oxidative stress and NLRP3 inflammasome activation were involved in SSd-alleviated acute liver injury in CCl4-induced hepatitis.

miR-126 Suppresses Invasion and Migration of Malignant Glioma by Targeting Mature T Cell Proliferation 1 (MTCP1).

BACKGROUND The aim of this study was to assess the utility of miR-126 in promoting malignant glioma progression and determine if miR-126 might be a target for malignant glioma treatment. MATERIAL AND METHODS The expression of miR-126 in malignant glioma tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot analysis was used to detect changes in protein levels. Transwell assay was applied to assess the migration and invasion in vitro. Luciferase reporter assay was used to confirm the binding of miR-126 and mature T cell proliferation 1 (MTCP1). A nude mouse tumor model was used to assess the molecular mechanism in vivo. RESULTS The expression level of miR-126 in patients with stage III~IV malignant glioma was significant lower than that in patients with stage I~II. In different malignant glioma cell lines, the expression was significantly reduced in U87MG. Compared with the control mimics group, the expression of MTCP1 was significantly decreased. The results of Transwell assay showed that the invasiveness and migration in the miR-126 mimics group was significantly lower than in the control mimics groups. miR-126 mimics did not affect luciferase activity in the Mut-miR-126/MTCP1 group, while miR-126 mimics reduced luciferase activity by 54% in the Wt-miR-126/MTCP1 group. The results of invasion showed that the invasion ability in the miR-126 inhibitor group was significantly increased compared with that in the normal control (NC) group, while the invasion and migration abilities in the MTCP1 siRNA group were significantly increased. After 6 weeks, the tumor volume in the miR-126 inhibitor group was significantly increased, while that in the MTCP1 siRNA group was significantly decreased. CONCLUSIONS miR-126 inhibits the migration of malignant glioma cells by inhibiting MTCP1.

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

BACKGROUND: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. METHODS: 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. RESULTS: There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. CONCLUSIONS: Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).