Search

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is prevalent in chronic obstructive pulmonary disease (COPD) and associated with adverse outcomes, while COPD is intricately linked to cardiovascular disease (CVD), sharing common risk factors. The controlling nutritional status (CONUT) score, a promising tool for assessing malnutrition, warrants investigation into its predictive ability for cardiovascular disease prevalence and mortality in COPD patients. Methods: Based on the National Health and Nutrition Examination Survey (NHANES), this study analyzed 1501 adult COPD patients from 1999 to 2018. The endpoints were CVD prevalence, mortality related to CVD, and overall mortality. We evaluated the correlation of the CONUT score with each outcome using logistic regression and Cox regression models. The prognostic evaluation of patients was conducted using Kaplan-Meier curves in accordance with the CONUT score. We formed the receiver operating characteristic (ROC) curves for evaluating the CONUT score's discriminative capability. Results: The prevalence of malnutrition was 21.31% in COPD populations. Logistic analyses suggested a distinct connection between the CONUT score and CVD prevalence (OR:1.86, 95%CI:1.28-2.70) in individuals with COPD. The CONUT score demonstrated a significant correlation with a heightened risk of CVD mortality (HR: 1.86, 95%CI: 1.27-2.74) and overall mortality (HR: 1.50, 95%CI: 1.18-1.91). The prognostic outcomes might be effectively discriminated by the CONUT score, as seen by the Kaplan-Meier curves. Conclusions: In summary, the CONUT score provides an uncomplicated and readily attainable marker for forecasting CVD prevalence, total mortality, and mortality from CVD among COPD patients. [ABSTRACT FROM AUTHOR]

Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self‐assembled three‐dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high‐throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient‐derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling. [ABSTRACT FROM AUTHOR]

Although immunotherapy has revolutionized bladder cancer (BLCA) therapy, only few patients demonstrate durable clinical benefits due to the heterogeneity. Emerging evidence has linked pyroptosis to shaping tumor microenvironment (TME) and predicting therapy response. However, the relationship between pyroptosis and immunotherapy response in BLCA remains elusive. In this study, we performed a comprehensive bioinformatic analysis to dissect the role of pyroptosis in BLCA. Differentially expressed pyroptosis-related genes (DEPRGs) between tumor and normal tissues were identified using publicly available datasets. Kaplan–Meier analysis was performed to screen for DEPRGs associated with survival. Consensus clustering was used for BLCA subtyping. TME characteristics were evaluated by CIBERSORT, ESTIMATE and immune checkpoint genes (ICGs). Following univariate COX regression and LASSO analyses with pyroptosis-related DEGs, the risk model and nomogram were constructed with TCGA dataset and validated in the GEO dataset. Furthermore, therapeutic responses in high- and low-risk groups were compared using TIDE and GDSC databases. Two pyroptosis-related subtypes (Cluster 1 and 2) were identified based on expression patterns of GSDMA and CHMP4C. Bioinformatic analyses showed that cluster 1 had poor survival, more M0/M1/M2 macrophages, higher immune/stromal/ESTIMATE scores, and higher expression levels of ICGs. A 15-gene signature for predicting prognosis could classify patients into high- and low-risk groups. Furthermore, the correlation of risk scores with TIDE score and IC50 showed that patients in low-risk group were more sensitive to immunotherapy, whereas patients in high-risk group could better benefit from chemotherapy. Our study identified two novel pyroptosis-related subtypes and constructed a risk model, which can predict the prognosis, improve our understanding the role of PRGs in BLCA, and guide chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

The ring with inner grid ribs (RWIGR) is a key mechanical part. Because of its light structure, high strength, high stiffness, and high carrying capacity, it is widely used in aerospace, special transporting equipment, and petrochemical and nuclear energy industries. Currently, the manufacturing of complex grid ribs mainly adopts cutting methods, which has low material utilization rate and low processing efficiency. Therefore, this paper proposes a novel forming method of radial constraining based on the current technical problem of the difficulty in integral forming of such RWIGR. That is, on the basis of the cylindrical ring rolling process, the continuous partial radial constraining squeezing process (CPRCSP) is adopted, so that the RWIGR can be integrally formed. The paper mainly does the following research work: (1) the process principle of the radial constraining squeezing forming is expounded, and the design method of squeezing molds is proposed. In addition, the squeezing deformation process of RWIGR is simulated and analyzed by the ABAQUS software. (2) Through the FE simulation results, the flow law and strain distribution of metal in the CPRCSP of RWIGR are analyzed. (3) The squeezing forming process of RWIGR is simulated under different squeezing process parameters, and the effects of different squeezing process parameters on RWIGR forming are revealed. (4) The experiment of CPRCSP is designed and implemented, which fully verifies the feasibility of the forming process. [ABSTRACT FROM AUTHOR]

The research on surface texture is developing from single macro-texture to composite micro-nano texture. The current research on the anti-friction mechanism and theoretical models of textures is relatively weak. Studying the characteristics of different types of surface textures and determining the applicable working conditions of each texture is the focus of current research. In this paper, a mathematical model of hydrodynamic lubrication is established based on Navier–Stokes equations. The FLUENT software is used to simulate and analyze the four texture models, explore the dynamic pressure lubrication characteristics of different texture types, and provide data support for texture optimization. The key variable values required by the mathematical model are obtained through the simulation data. The friction coefficient of the texture under different working conditions was measured through friction and wear experiments, and the mathematical model was verified by the experimental results. The research results show that circular texture is suitable for low to medium speed and high load conditions, chevron texture is suitable for medium to high speed and medium to high load conditions, groove texture is suitable for high speed and low load conditions, and composite texture is suitable for high speed and medium to high load conditions. Comparing the experimental results with the results obtained by the mathematical model, it is found that the two are basically the same in the ranking of the anti-friction performance of different textures, and there is an error of 10%−40% in the friction coefficient value. In this study, a mathematical model of hydrodynamic lubrication was proposed, and the solution method of the optimal surface texture model was determined. [ABSTRACT FROM AUTHOR]

Background : Radiofrequency ablation (RFA) effectively treats arrhythmia. Steam pop (SP) is a dangerous complication of RFA, which can lead to pericardial tamponade or even death. Objective : This study aimed to explore the electro-characteristics of myocardial pouches, and the relationship between SP, pouch, and impedance. Methods : Swine myocardium was divided into the pouch group and smooth myocardium group. Continuous RFA at 50 W was applied. The initial impedance reduction within the first 3 s of ablation and the time from the start of ablation to SP were recorded. After enabling the delta impedance cutoff function, RFA was performed at different percentage of delta impedance (PDI) cutoff thresholds. Results : The impedance was higher for the pouch myocardium compared to the smooth myocardium (123.22 ± 8.63 Ω and 95.75 ± 4.75 Ω, respectively; p < 0.001). The RFA duration before SPs was shorter in the pouch group compared to the smooth myocardium group [9 s (interquartile range, IQR: 6.25–13 s) and 33 s (IQR: 26.25–40.75 s), respectively; p < 0.001]. Within the first 3 s of RFA, impedance reduction (24.65 ± 6.57 Ω and 12.78 ± 3.35 Ω, respectively; p < 0.001) and PDI [19.18% (IQR: 16.39–24.20%) and 12.96% (IQR: 11.17–14.39%), respectively; p < 0.001] were greater in the pouch group compared to the smooth myocardium group. A PDI of 15% and delta time of 3 s effectively reduced the frequency of SPs without seriously affecting RFA use. Conclusion : SPs occur more frequently in the pouch area during RFA. Appropriate delta impedance cutoff settings (PDI: 15%; delta time: 3 s) can reduce the frequency of SPs and improve the RFA safety. [ABSTRACT FROM AUTHOR]

Wood is favored by furniture and decorative materials due to its beautiful color and texture, lightweight and high strength, but the thermal stability and flame retardants of wood have not been well solved. In this paper, metal salt-doped ammonium polyphosphate silicon gel (Cu, Mn/APP/Gel) was trapped in the wood cell wall and cell cavity by vacuum-pressure infusion method and vacuum drying method. Compared with unmodified wood, Cu, Mn/APP/Gel impregnated wood can rapidly enhance the flame retardant and smoke suppression capability of wood due to the catalysis of Cu2+ and Mn2+, and the total heat release rate, heat release rate peak value, mean heat release rate, smoke produce rate, total smoke release, CO and CO2 yield (YCO, YCO2) are obviously reduced. The electronic microscope picture of the burned carbon layer shows that the Cu, Mn/APP/Gel doped wood no longer has a clear and beautiful carbon layer formed by cell structure, but completely forms a whole. It is this dense and firm carbon layer structure that effectively inhibits the thermal decomposition of wood and has a role in flame retardant and smoke suppression. This study proposed an environment-friendly and green scheme for flame retardant modification of wood. [ABSTRACT FROM AUTHOR]

Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. The present study investigated the P2X7 receptor antagonist brilliant blue G (BBG) whether inhibits endoplasmic reticulum stress and pyroptosis (a necrotic form of cell death) and alleviates PHN. Varicella zoster virus (VZV)-infected CV-1 cells were used to induce PHN model. Mechanical paw withdrawal thresholds were measured using an ascending series of von Frey filaments. Immunohistochemistry was used to detect the expression of P2X7R in nerve tissues. Western blot was used to determine the expression of endoplasmic reticulum (ER) stress and pyroptosis-related molecules. The expression of IL-1β and IL-18 in tissue homogenate was detected by ELISA. The PHN rat has the lower paw withdrawal threshold, but higher expression of P2X7 in nerve tissues. And, endoplasmic reticulum stress was activated and pyroptosis was increased in PHN rats. BBG can decrease pain thresholds and reduce ER stress and pyroptosis in PHN rats. In addition, ER stress activator tunicamycin (TM) can reverse the effect of BBG on the paw withdrawal thresholds, endoplasmic reticulum stress, and pyroptosis. Therefore, P2X7 receptor antagonist BBG alleviates PHN by activating ER stress and reducing pyroptosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the properties and functions of polysaccharide-based porous microsphere (PPM) for drug delivery, as well as its inhibitory effect on malignant tumors. Materials and Methods: PPM was prepared using the inverse emulsion polymerization method. FT-IR measurements were conducted to measure the wavenumber of PPM. Particle size distribution was tested with a particle analyzer, and surface morphologies of PPM were observed using a scanning electron microscope (SEM). Dialysis method, Cell Counting Kit-8 (CCK-8), and cell apoptosis analysis were adopted to evaluate the drug release, cytotoxicity and biocompatibility of mitomycin-C (MMC), respectively. Finally, an in vivo study was performed in C57BL/6 mice to confirm the function of MMC-loaded PPM on tumor growth. Results: FT-IR spectra proved the successful preparation of MMC-loaded PPM. PPM had an average size of 25.90 ± 0.34 μm and then increased to 30.10 ± 0.20 μm after drug loading. Under SEM, the surface morphology was lotus seedpod surface-like, with macropits on the surface and micropores in macropits. Compared with the free MMC group, MMC-loaded PPM exhibited a delayed drug release rate in a pH-dependent manner and higher cell viability. Flow cytometry results showed that the cell apoptosis in the PPM/MMC group was lower than that in the free MMC group. In vivo experiment revealed the inhibitory efficacy of MMC-loaded PPM on malignant tumors. Conclusion: In summary, MMC-loaded PPM exhibited favorable surface morphology, sustained drug release ability, nontoxicity and excellent biocompatibility, suggesting that PPM might be a potential drug carrier for tumor treatment. [ABSTRACT FROM AUTHOR]

The Massachusetts Eye and Ear Infirmary (MEEI) database is an international-standard training database for voice pathology detection (VPD) systems. However, there is a class-imbalanced distribution in normal and pathological voice samples and different types of pathological voice samples in the MEEI database. This study aimed to develop a VPD system that uses the fuzzy clustering synthetic minority oversampling technique algorithm (FC-SMOTE) to automatically detect and classify four types of pathological voices in a multi-class imbalanced database. The proposed FC-SMOTE algorithm processes the initial class-imbalanced dataset. A set of machine learning models was evaluated and validated using the resulting class-balanced dataset as an input. The effectiveness of the VPD system with FC-SMOTE was further verified by an external validation set and another pathological voice database (Saarbruecken Voice Database (SVD)). The experimental results show that, in the multi-classification of pathological voice for the class-imbalanced dataset, the method we propose can significantly improve the diagnostic accuracy. Meanwhile, FC-SMOTE outperforms the traditional imbalanced data oversampling algorithms, and it is preferred for imbalanced voice diagnosis in practical applications. [ABSTRACT FROM AUTHOR]

Sulcus vocalis is an indentation parallel to the edge of vocal fold, which may extend into the cover and ligament layer of the vocal fold or deeper. The effects of sulcus vocalis depth d on phonation and the vocal cord vibrations are investigated in this study. The three-dimensional laryngeal models were established for healthy vocal folds (0 mm) and different types of sulcus vocalis with the typical depth of 1 mm, 2 mm, and 3 mm. These models with fluid-structure interaction (FSI) are computed numerically by sequential coupling method, which includes an immersed boundary method (IBM) for modelling the glottal airflow, a finite-element method (FEM) for modelling vocal fold tissue. The results show that a deeper sulcus vocalis in the cover layer decreases the vibrating frequency of vocal folds and expands the prephonatory glottal half-width which increases the phonation threshold pressure. The larger sulcus vocalis depth makes vocal folds difficult to vibrate and phonate. The effects of sulcus vocalis depth suggest that the feature such as phonation threshold pressure could assist in the detection of healthy vocal folds and different types of sulcus vocalis. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed selective B(3)–H arylation of o-carboranes at room temperature has been developed using readily available arylboronic acids as the aryl source, and the corresponding 3-aryl-o-carboranes were obtained in good to excellent yields. This method provides a powerful synthetic route for constructing polysubstituted o-carborane derivatives. [ABSTRACT FROM AUTHOR]

1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a lipophilic phenolic agent, has an antioxidant activity and reactive oxygen species (ROS) scavenging property. However, the role of HTHQ on cerebral ischaemic/reperfusion (I/R) injury and the underlying mechanisms remain poorly understood. In the present study, we demonstrated that HTHQ treatment ameliorated cerebral I/R injury in vivo, as demonstrated by the decreased infarct volume ration, neurological deficits, oxidative stress and neuronal apoptosis. HTHQ treatment increased the levels of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant protein, haeme oxygenase‐1 (HO‐1). In addition, HTHQ treatment decreases oxidative stress and neuronal apoptosis of PC12 cells following hypoxia and reperfusion (H/R) in vitro. Moreover, we provided evidence that PC12 cells were more vulnerable to H/R‐induced oxidative stress after si‐Nrf2 transfection, and the HTHQ‐mediated protection was lost in PC12 cells transfected with siNrf2. In conclusion, these results suggested that HTHQ possesses neuroprotective effects against oxidative stress and apoptosis after cerebral I/R injury via activation of the Nrf2/HO‐1 pathway. [ABSTRACT FROM AUTHOR]

Circulating cells have a pathogenic role in the development of hypertensive nephropathy. However, how these cells infiltrate into the kidney are not fully elucidated. In this study, we investigated the role of CXCR6 in deoxycorticosterone acetate (DOCA)/salt-induced inflammation and fibrosis of the kidney. Following uninephrectomy, wild-type and CXCR6 knockout mice were treated with DOCA/salt for 3 weeks. Blood pressure was similar between wild-type and CXCR6 knockout mice at baseline and after treatment with DOCA/salt. Wild-type mice develop significant kidney injury, proteinuria, and kidney fibrosis after three weeks of DOCA/salt treatment. CXCR6 deficiency ameliorated kidney injury, proteinuria, and kidney fibrosis following treatment with DOCA/salt. Moreover, CXCR6 deficiency inhibited accumulation of bone marrow–derived fibroblasts and myofibroblasts in the kidney following treatment with DOCA/salt. Furthermore, CXCR6 deficiency markedly reduced the number of macrophages and T cells in the kidney after DOCA/salt treatment. In summary, our results identify a critical role of CXCR6 in the development of inflammation and fibrosis of the kidney in salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Background: The mTOR pathway is altered in a multitude of cancers, including lung cancer; however, abnormal activation in this pathway is less common in lung adenocarcinoma (LUAD) than in lung squamous cell carcinoma (LUSC). Gephyrin is a highly conserved and widely expressed ancient protein in vertebrate tissues. Its role and molecular mechanism in lung cancer development are largely unknown. Method: We analyzed the expression profile of gephyrin and overall survival rates in LUAD and LUSC. The LUSC cells (H520 and SK-MES-1) were transfected with pLV-gephyrin to establish gephyrin stable overexpression cell lines. Real-time quantitative PCR and Western blot were performed to detect the mRNA and protein levels. The cell growth and cell cycle were detected by the MTT assay and flow cytometry. Finally, a xenograft tumor model was established to determine cell tumorigenesis in vivo. Results: Our results show that gephyrin was reduced in LUAD and LUSC, and its low expression in LUSC patients indicated poor prognosis. Gephyrin overexpression suppressed LUSC cell proliferation, arrested cell cycle progression, and decreased the expression of cell-cycle related proteins such as cyclin D1, cyclin-dependent kinase-2 (CDK2), and proliferation-related protein proliferating cell nuclear antigen (PCNA). Conversely, knockdown of gephyrin promoted LUSC cell growth. Moreover, gephyrin reduced mTOR pathway activation to inhibit cyclin D1 and CDK2 translation. Mechanistically, gephyrin suppressed mTOR pathway activation by promoting mTOR degradation. Furthermore, gephyrin overexpression suppressed LUSC tumorigenesis. Conclusion: Gephyrin suppressed LUSC development by reducing mTOR pathway activation, implicating gephyrin as a potential molecular target for LUSC management. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium. Methods: In this study, oxygen-glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot. Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production. Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury. [ABSTRACT FROM AUTHOR]

In this paper, the effects of heteropolyacids on pyrolysis process of poplar powder and is mechanism were studied by comparing the pyrolyiis process and characteiistic parameters of heat and smoke release of pop- ar powder treated with H3PMO12O40 (PMA), H3PW12O40 (PTA) and H3SiW12O40 (TSA). The TG and DTG curves of samples were determined by thermogravimetiic analyzer. And the heat release rate(HRR), total heat release (THR), smoke produce release (SPR) and total smoke produce (TSP) were measured by cone calorimetry (CONE). Besides, the FT-IR and Raman spectrometers were used to characterize the residual char. TGA results showed that three heteropolyacids could effectively decrease the initial pyrolylis temperature (Ti), the maximum weight loss temperature(Tmax) and the maximum weight loss rate(Rmax) of poplar wood and increase the char yeeld at 740 °C(CR740 °C). S-wood/PMA had the lowest Tmax and Rmax among all samples, which were decreased by 17.5% and 23.3% than S-wood, respeciively. And S-wood/PTA had the highest CR 740 °C, followed by S-wood/TSA. The CONE resuts ihowed that parameters of HRR, THR, SPR, TSP, and COY of the het- eropolyacid/poplar samples were significantly reduced. S-wood/PMA also had the lowest parameters of heat and smoke rdease, whose peak heat release rate(PHRR) and THR were decreased by 31.6% and 67.5% and the TSR and TSP were 86.01% and 87.5% lower than those of S-wood, respeciively. And FTIR and Roman spectrums showed that the content of assodated O--H and unsaturated C=C in the reiidual char of the heteropoly- acid/poplar samples were increased significantly, and ester bonds, MoO3, WO3 and SiO2 formed. Furthermore, A d/Ag of heteropolyacid/popaar samples was decreased. Therefore, heteropolyacids catalyze the dehydration of poplar powder into esters and the solidify of poplar powder into carbon by pyrolylis, which effectively llows down the pyrolylis rate and inhibits the pyrolylis process of poplar powder, exhibiting good lame retardancy and excellent smoke suppression effect. And H3PMO12O40 has the best flame retardant and smoke suppression effects on poplar powder among the three heteropolyacids. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of miR-192 in differentiation of T follicular helper cells in childhood asthma. Blood samples were taken from eighteen children with acute asthma attacks and fifteen healthy children (HC). Quantitative real-time PCR and Western blotting were used to detect the expression levels of miR-192, C-X-C chemokine receptor type 5 (CXCR5), B-cell lymphoma 6 (BCL-6) and inducible T-cell costimulator (ICOS). The flow cytometry was performed to detect the proportion of CD4 + CXCR5+ Tfh cells on CD4 + T lymphocytes. The enzyme-linked immunosorbent assay (ELISA) was carried out to determine the plasma concentrations of total IgE and IL-21. The effect of miR-192 on the T follicular helper cells differentiation by targeting CXCR5 was determined by dual-luciferase reporter assay. Children with asthma had lower levels of miR-192 than HC. The proportion of CD4 + CXCR + Tfh cells was significantly higher in the acute asthma group than HC. Similarly, the plasma concentration of total IgE and IL-21 in the acute group markedly increased compared with the HC, and IgE concentration was positively correlated with the proportion of CD4 + CXCR5 + Tfh cells. Furthermore, the expression levels of CXCR5, Bcl-6 and ICOS were significantly higher in the acute group than in the HC. While the proportion of CD4 + CXCR5 + Tfh cells, IL-21, CXCR5, Bcl-6 and ICOS were obviously lower in the CD4 + T cells transfected with miR-192 plasmid than that in miR-192 + CXCR5 group and control group. In conclusion, miR-192 blocks the activation pathway of Tfh cells by targeting CXCR5, which is a reasonable cellular target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium. Methods: In this study, oxygen–glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot. Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production. Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury. [ABSTRACT FROM AUTHOR]

Background & Aims: It has been reported that Wnt/β-catenin signalling pathway played a key role in liver fibrosis and that Pygo2 was an important mediator in β-catenin induced pathway. However, the role of Pygo2 in liver fibrogenesis was unknown. Our study was to investigate the expression of Pygo2 and its diagnostic value in patients with HBV-related liver fibrosis. Methods: Hundred and sixty-four patients with HBV infection underwent liver biopsy and liver stiffness measurement (LSM) by transient elastography (Fibroscan®; Echosens). Liver function was tested by routine biochemical examinations. Liver condition was assessed by haematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Pygo2 in liver tissue was measured by Real-time PCR and immunohistochemistry, respectively, while the serum levels of Pygo2 were detected by ELISA. The relationship between degree of liver fibrosis and Pygo2 expression was assessed by correlation analysis. Receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of serum Pygo2, LSM and their combination. Results: The mRNA and protein levels of Pygo2 in HBV-infected patients were all higher than in normal persons (P < 0.05 respectively). Moreover, Pygo2 expression increased along with the progression of liver fibrosis (P < 0.05 respectively). The trend of serum Pygo2 agreed with its expression in liver tissue. The combination of serum Pygo2 and LSM had a significantly higher area under the curve than Pygo2 or LSM alone (P < 0.05 respectively). Conclusions: This study suggested that Pygo2 was involved in HBV-induced liver fibrogenesis. Pygo2 is a valuable biomarker for the evaluation of fibrosis in HBV-infected patients. [ABSTRACT FROM AUTHOR]