Effects of dietary supplement of ε-polylysine hydrochloride on laying performance, egg quality, serum parameters, organ index, intestinal morphology, gut microbiota and volatile fatty acids in laying hens.

BACKGROUND: ε-polylysine hydrochloride (ε-PLH) is a naturally occurring antimicrobial peptide extensively utilized in the food and medical industries. However, its impact on animal husbandry remains to be further explored. Therefore, the present study aimed to determine the effect of ε-PLH on laying hens' health and laying performance. RESULTS: Dietary supplementation with ε-PLH to the diet significantly increased average egg weight during weeks 1-8. Meanwhile, compared with the control group, supplementation with ε-PLH decreased the feed egg ratio during weeks 9-12 and egg breakage rate during weeks 9-16 ，whereas it increased eggshell strength during weeks 1-4 and 13-16 . The ε-PLH 0.05% group increased yolk percentage during weeks 5-8 and yolk color during weeks 1-4 . Furthermore, ε-PLH supplementation significantly increased the concentrations of total protein, albumin, globulin and reproductive hormones estradiol, as well as decreased interleukin-1 beta and malondialdehyde in the serum. Compared with the control group, supplementation with 0.05% ε-PLH significantly increased the relative abundance of Cyanobacteria and Gastranaerophilales and decreased the abundance of Desulfovibrio and Streptococcus in the cecum microbiota. In addition, ε-PLH 0.1% supplementation also increased acetic acid content in the cecum. CONCLUSION: Dietary supplementation with ε-PLH has a positive impact on both productive performance and egg quality in laying hens. Furthermore, ε-PLH can also relieve inflammation by promoting the immunity and reducing oxidative damage during egg production. ε-PLH has been shown to improve intestinal morphology, gut microbial diversity and intestinal health. © 2023 Society of Chemical Industry.

Prognostic significance of frailty status in patients with primary lung cancer.

Lung cancer has one of the highest morbidity and mortality rates in the world. Frailty is common in many countries and is a major cause of premature functional decline and premature death in older adults, and may affect the treatment and prognosis of lung cancer patients. To investigate the predictive value of frailty at diagnosis on all-cause mortality in lung cancer patients, this study retrospectively collected and analysed clinical information on lung cancer patients from 2015-2018. A total of 1667 patients with primary lung cancer were finally included in this study. The median follow-up time of patients was 650 (493, 1001.5) days. A total of 297(17.8%) patients had FI-LAB(the frailty index based on laboratory test) status of frail at the moment of diagnosis and the all-cause mortality rate for all patients was 61.1% (1018/1667). In a univariate model, we found a higher total all-cause mortality risk in frail patients (frail vs. robust, HR(hazard ratio) = 1.616, 95% CI(confidence interval) = 1.349,1.936), after balancing other variables combined into model 1 to model 6. The results were analyzed visually using ROC(Receiver operating characteristic) curves with nomogram and the AUC values ranged from 0.866-0.874. The final inclusion of age, TNM stage, CCI(Charlson comorbidity index) score, surgery history and chemotherapy into a multifactorial model balanced the predictive power of frailty grading on all-cause mortality. The study showed that for lung cancer patients, the higher the level of frailty at diagnosis, the higher the risk of all-cause mortality. In the context of widespread electronic medical records in hospitals, it is convenient and feasible to use FI-LAB to assess the prognosis of lung cancer patients.

Prognostic significance of frailty in hospitalized elderly patients with community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Frailty is associated with poor prognosis in a wide range of illnesses. However, its prognostic implications for older patients with community-acquired pneumonia (CAP) are not adequately addressed. METHODS: In this study, patients were classified into 3 groups according to the frailty index based on standard laboratory tests (FI-Lab) score: robust (FI-Lab < 0.2), pre-frail (FI-Lab 0.2-0.35), and frail (FI-Lab ≥ 0.35). The relationships between frailty and all-cause mortality and short-term clinical outcomes (length of stay, duration of antibiotic therapy, in-hospital mortality) were examined. RESULTS: Finally, 1164 patients were included, the median age was 75 years (interquartile range: 69, 82), and 438 patients (37.6%) were women. According to FI-Lab, 261(22.4%), 395(33.9%), and 508(43.6%) were robust, pre-frail, and frail. After adjustment for confounding variables, frailty was independently associated with prolonged antibiotic treatment (p = 0.037); pre-frailty and frailty were independently associated with longer inpatient days (p < 0.05 for both). The risk of in-hospital mortality was independently increased in frail patients (HR = 5.01, 95% CI = 1.51-16.57, p = 0.008) but not pre-frail patients (HR = 2.87, 95% CI = 0.86-9.63, p = 0.088) compared to robust patients. During a median follow-up of 33.9 months (interquartile range: 32.8 to 35.1 months), 408 (35.1%) patients died, of whom 29 (7.1%) were robust, 112 (27.5%) were pre-frail, and 267 (65.9%) were frail. Compared to robust patients, frail and pre-frail were significantly associated with increased risk for all-cause death (HR = 4.29, 95%CI: 1.78-10.35 and HR = 2.42 95%CI: 1.01-5.82, respectively). CONCLUSIONS: Frailty is common among older patients with CAP and is strongly associated with increased mortality, longer length of stay, and duration of antibiotics. A routine frail assessment at the admission of elderly patients with CAP is necessary as the first step for appropriate multidisciplinary interventions.

Single-cell transcriptomics highlights immunological dysregulations of monocytes in the pathobiology of COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, whose pathogenetic complexity was strongly associated with aging/smoking and poorly understood. METHODS: Here we performed single-cell RNA sequencing (scRNA-seq) analysis of 66,610 cells from COPD and age-stratified control lung tissues of donors with different smoking histories to prioritize cell types most perturbed in COPD lungs in aging/smoking dependent or independent manner. By performing an array of advanced bioinformatic analyses, such as gene set enrichment analysis, trajectory analysis, cell-cell interactions analysis, regulatory potential analysis, weighted correlation network analysis, functional interaction analysis, and gene set variation analysis, we integrated cell-type-level alterations into a system-level malfunction and provided a more clarified COPD pathological model containing specific mechanisms by which aging and smoking facilitate COPD development. Finally, we integrated the publicly available scRNA-seq data of 9 individuals, resulting in a total of 110,931 cells, and replicated the analyses to enhance the credibility of our findings. RESULTS: Our study pointed to enrichment of COPD molecular alteration in monocytes, which further induced a previously unrecognized pro-inflammatory effect on alveolar epithelial cells. In addition, aged monocytes and club cells facilitated COPD development via maintaining an autoimmune airway niche. Unexpectedly, macrophages, whose defect to resolve inflammation was long-recognized in COPD pathogenesis, primarily induced an imbalance of sphingolipids rheostat in a smoking-dependent way. These findings were validated in a meta-analysis including other public single-cell transcriptomic data. CONCLUSIONS: In sum, our study provided a clarified view of COPD pathogenesis and demonstrated the potential of targeting monocytes in COPD diagnosis and treatment.

Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF-ß/Smad Pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia disease with no cure. Communication between injured cells is triggered and maintained by a complicated network of cytokines and their receptors. IL-19 is supported by increasing evidences for a deleterious role in respiratory diseases. However, its potential role in lung fibrosis has never been explored. Methods: Bioinformatic, immunohistochemistry and western blot analysis were used to assess the expression of IL-19 in human and mouse fibrosis lung tissues. CCK-8, transwell and flow cytometry assay were utilized to analyze the effect of IL-19 on biological behaviors of lung fibroblasts. Histopathology was used to elucidate profibrotic effect of IL-19 in vivo. Results: IL-19 was upregulated in fibrosis lung tissues. IL-19 promoted lung fibroblasts proliferation and invasion, inhibited cell apoptosis, and induced differentiation of fibroblasts to the myofibroblast phenotype, which could be revised by LY2109761, a TGF-ß/Smad signaling pathway inhibitor. Furthermore, we found that IL-19 aggravated lung fibrosis in murine bleomycin-induced lung fibrosis. Conclusions: Our results imply the profibrotic role for IL-19 through direct effects on lung fibroblasts and the potential of targeting IL-19 for therapeutic intervention in pulmonary fibrosis.

YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas.

BACKGROUND: Autophagy is a double-edged sword during the initiation and progression of multiple tumors. The Hippo pathway effector YAP has been proved to be involved in autophagy processes. The present study aimed to investigate how YAP regulates cell proliferation via autophagy in lung adenocarcinomas (LUAD). METHODS: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in LUAD cell lines. CCK-8 assay, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor treatment and rescue experiments were carried out to elucidate the mechanism by which YAP manipulates autophagy in LUAD cells. RESULTS: YAP was significantly overexpressed in samples of LUAD patients and its expression level is related to 5-year survival. YAP manipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo. CONCLUSIONS: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.

miRNA sequencing reveals miRNA-4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica-related pulmonary fibrosis: A multistage study.

BACKGROUND AND OBJECTIVE: This study aimed to identify miRNA as potential diagnostic biomarkers for silica-related pulmonary fibrosis (SPF). METHODS: We first performed a comprehensive miRNA-seq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). RESULTS: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10-3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10-17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure. CONCLUSION: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated.

An Edge Based Multi-Agent Auto Communication Method for Traffic Light Control.

With smart city infrastructures growing, the Internet of Things (IoT) has been widely used in the intelligent transportation systems (ITS). The traditional adaptive traffic signal control method based on reinforcement learning (RL) has expanded from one intersection to multiple intersections. In this paper, we propose a multi-agent auto communication (MAAC) algorithm, which is an innovative adaptive global traffic light control method based on multi-agent reinforcement learning (MARL) and an auto communication protocol in edge computing architecture. The MAAC algorithm combines multi-agent auto communication protocol with MARL, allowing an agent to communicate the learned strategies with others for achieving global optimization in traffic signal control. In addition, we present a practicable edge computing architecture for industrial deployment on IoT, considering the limitations of the capabilities of network transmission bandwidth. We demonstrate that our algorithm outperforms other methods over 17% in experiments in a real traffic simulation environment.

Real-Time Queue Length Detection with Roadside LiDAR Data.

Real-time queue length information is an important input for many traffic applications. This paper presents a novel method for real-time queue length detection with roadside LiDAR data. Vehicles on the road were continuously tracked with the LiDAR data processing procedures (including background filtering, point clustering, object classification, lane identification and object association). A detailed method to identify the vehicle at the end of the queue considering the occlusion issue and package loss issue was documented in this study. The proposed method can provide real-time queue length information. The performance of the proposed queue length detection method was evaluated with the ground-truth data collected from three sites in Reno, Nevada. Results show the proposed method can achieve an average of 98% accuracy at the six investigated sites. The errors in the queue length detection were also diagnosed.

Vehicle Detection under Adverse Weather from Roadside LiDAR Data.

Roadside light detection and ranging (LiDAR) is an emerging traffic data collection device and has recently been deployed in different transportation areas. The current data processing algorithms for roadside LiDAR are usually developed assuming normal weather conditions. Adverse weather conditions, such as windy and snowy conditions, could be challenges for data processing. This paper examines the performance of the state-of-the-art data processing algorithms developed for roadside LiDAR under adverse weather and then composed an improved background filtering and object clustering method in order to process the roadside LiDAR data, which was proven to perform better under windy and snowy weather. The testing results showed that the accuracy of the background filtering and point clustering was greatly improved compared to the state-of-the-art methods. With this new approach, vehicles can be identified with relatively high accuracy under windy and snowy weather.

Towards Attention-Based Convolutional Long Short-Term Memory for Travel Time Prediction of Bus Journeys.

Travel time prediction is critical for advanced traveler information systems (ATISs), which provides valuable information for enhancing the efficiency and effectiveness of the urban transportation systems. However, in the area of bus trips, existing studies have focused on directly using the structured data to predict travel time for a single bus trip. For state-of-the-art public transportation information systems, a bus journey generally has multiple bus trips. Additionally, due to the lack of study on data fusion, it is even inadequate for the development of underlying intelligent transportation systems. In this paper, we propose a novel framework for a hybrid data-driven travel time prediction model for bus journeys based on open data. We explore a convolutional long short-term memory (ConvLSTM) model with a self-attention mechanism that accurately predicts the running time of each segment of the trips and the waiting time at each station. The model is more robust to capture long-range dependence in time series data as well.

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

OBJECTIVES: In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported. METHODS: We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases. RESULTS: We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls. CONCLUSIONS: The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

Membrane-Bound CD40L Promotes Senescence and Initiates Senescence-Associated Secretory Phenotype via NF-κB Activation in Lung Adenocarcinoma.

BACKGROUND/AIMS: Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). METHODS: CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry. Senescent cells and tissues were identified via SA-ß-gal activity. Cell proliferation was visualized by EdU labeling. qRT-PCR, Western blotting, and immunofluorescence staining were conducted to assess mRNA and protein expression levels of CD40L, γ-H2A.X, p65, p-p65, IκBα, p53, p21 and p16. Cytokines secreted from transfected cells were tested by ELISA and cell migration assay. Capsid tyrosine-modified rAAV5-CD40L-M was packaged and carried out in vivo. RESULTS: Overexpression of CD40L-M promoted senescence, inhibited proliferation, increased DNA damage-associated γ-H2A.X, and initiated the SASP in CD40-positive NSCLC cells. NF-κB signaling was activated by CD40L-M overexpression in these cells. Knockdown of NF-κB partially overcame senescence and failed to induce SASP. Furthermore, increased p53 and p21 protein levels induced by CD40L-M were also reduced following NF-κB suppression. CONCLUSIONS: These data showed that the membrane-bound CD40L mutant may promote cellular senescence and initiate the SASP of NSCLC cells in an NF-κB-dependent manner. Therefore, CD40L-M-induced senescence may be a potential approach to protect against lung adenocarcinoma.

The miR-608 rs4919510 polymorphism may modify cancer susceptibility based on type.

Previous meta-analysis has not shown different effects of miR-608 rs4919510 polymorphism in specific cancer types and reported no significant association between rs4919510 and cancer risk among Chinese. However, more recent findings have been inconsistent. Therefore, we performed an updated meta-analysis to examine whether this polymorphism is associated with cancer risk based on ethnicity and type. A total of 18 case-control studies, comprising 12,517 cases and 15,624 controls, were included in our study. Surprisingly, in contrast with previous meta-analysis, a significant association between the rs4919510 polymorphism and cancer risk was observed in Chinese (CG vs CC: odds ratio = 1.11; 95% confidence interval = 1.04-1.19). In further stratified analyses based on cancer type, rs4919510 was significantly associated with an increased risk of papillary thyroid cancer (CG vs CC: odds ratio = 1.25; 95% confidence interval = 1.01-1.54) and exhibited borderline significant associations with increased risk of gastric cancer (GG vs CC: odds ratio = 1.27; 95% confidence interval = 1.00-1.62) and lung cancer (CG vs CC: odds ratio = 1.14; 95% confidence interval = 0.99-1.32), but a decreased risk of colorectal cancer (GG vs CC: odds ratio = 0.74; 95% confidence interval = 0.60-0.91). Moreover, the RegulomeDB database indicated that rs4919510 may affect the expression of two nearby genes ( SEMA4G and MRPL43), and the Cancer Genome Atlas database revealed that the expression level of SEMA4G was significantly lower in colorectal cancer and lung cancer tissues than that in adjacent non-tumour tissues, while the expression level of SEMA4G was significantly higher in gastric cancer tissues than that in adjacent non-tumour tissues. These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.

Estimating glomerular filtration rate by serum creatinine or/and cystatin C equations: An analysis of multi-centre Chinese subjects.

AIM: Various equations based on serum creatinine or/and cystatin C, required further validation in a Chinese population. We compared the performance of six Chinese equations (Mascr, Peiscr, Macys, Fengcys, Mascr-cys and Fengscr-cys) with the CKD-EPI equations in multi-centre Chinese subjects and evaluated their applicability in clinical practice. METHODS: A total of 1522 adult patients from four different hospitals of China were enrolled in the study. (99m) Tc-DTPA renal dynamic imaging was used as the reference GFR (rGFR), and serum creatinine and cystatin C were measured by standardized assays. An optimal score system was implemented in the study. RESULTS: The average rGFR of recruited subjects was 67.30±28.89 mL/min per 1.73m(2) . All estimated GFR (eGFR) correlated well with rGFR. In accordance with Bland-Altman analysis, the Fengscr-cys equations achieved optimal overall performance (score 14 vs 0-6), with least bias (median difference, -0.57 mL/min per 1.73m(2) ; median absolute difference, 8.83 mL/min per 1.73m(2) ), best precision (17.99 mL/min per 1.73m(2) ), highest accuracy (percentage of eGFR within 15%, 30% and 50% of the rGFR (P15 , P30 and P50 ; 49.7%, 78.7% and 91.8%, respectively); root-mean-square-error (RMSE, 16.28)). The Fengcys equation, a typical cystatin C based equation, was another well-behaved formula with an impressive performance. The Ma equations performed much poorer than the CKD-EPI equations. Consistent results can be observed in the GFR- /age- and sex-specific subgroups, while none equation yielded ideal accuracy in GFR<60 mL/min per 1.73 m(2) subgroup. CONCLUSION: The Fengscr-cys equation appeared to achieve the best performance for GFR estimation in overall Chinese adult patients. However, further research is warranted to improve the accuracy of available equations in GFR less than 60 mL/min per 1.73 m(2) individuals.

Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem worldwide with dramatically increasing incidence and prevalence. Serum cystatin C (sCysC) has been clarified by many studies as a relatively accurate marker to evaluate renal function. STUDY DESIGN: Meta-analysis of diagnostic test studies. SETTING AND POPULATION: Various clinical settings of CKD, including adult patients with diabetes, renal transplant patients, and so on. SELECTION CRITERIA: A computerized search of PubMed, Cochrane clinical trial database, and Current Contents (from inception until June 16, 2014) was performed to identify potentially relevant articles. INDEX TESTS: Increased sCysC concentration. REFERENCE TESTS: The measured glomerular filtration rate measured by nuclear medicine techniques such as 99Tc-diethylene triamine pentacaetic acid (99Tc-DTPA) or 51Cr-ethylenediamine tetra-acetic acid (51Cr-EDTA), or calculated by Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula or 24 hours creatinine clearance rate. RESULTS: In total 19 studies were included in this study. Across all settings, the diagnostic odds ratio (DOR) of sCysC in predicting CKD was 40 (95% CI, 26 - 61) when sensitivity and specificity was 0.85 (95% CI, 0.81 - 0.89) and 0.87 (95% CI, 0.84 - 0.90), respectively. The area under the curve for the receiver-operating characteristic (AUROC) of sCysC to predict CKD was 0.92 (95% CI, 0.90 - 0.94). For the diagnostic value of sCysC in diabetics with CKD, the DOR was 51 (95% CI, 22 - 122), with sensitivity and specificity of 0.89 and 0.87, respectively. Subgroup analysis showed that sCysC was of better diagnostic value in the West than in Asia, and the diagnostic value of sCysC assayed by particle-enhanced nephelometric immunoassay (PENIA) was higher than sCysC assayed by particle-enhanced turbidimetric immunoassay (PETIA). CONCLUSION: SCysC appears to be a good biomarker in the definition of CKD. However, its performance is different in subgroups restricted by clinical settings, race, and sCysC assay.

Synthesis of novel galactose functionalized gold nanoparticles and its radiosensitizing mechanism.

BACKGROUND: Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability. RESULTS: This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing. CONCLUSION: GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.

Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing.

AIMS: Micro-vesicles (MVs) from bone mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of damaged kidney. The aims of the present study are to investigate the biological effects and repair mechanisms of MVs. METHODS: Micro-vesicles were obtained from MSC supernatants. In vitro, the proximal tubular epithelial cells (HK-2) were treated with transforming growth factor (TGF-ß1). The expressions of E-cadherin and α-smooth muscle actin (α-SMA) were evaluated. In vitro, the mice were divided into: control, unilateral ureteral obstruction (UUO), UUO+MSC, and UUO+MV group. MVs and MSCs were injected after surgery. The mice were killed 7/14 days after surgery and handled for further tests. The micro-RNA expressions were labeled using the miRCURY Hy3/Hy5 Power labeling kit and hybridized on the miRCURY LNA Array. RESULTS: In vitro, MV reversed transforming growth factor-ß1 (TGF-ß1)-induced morphological changes, and firmed the expression of E-cadherin and reduced the secretion of α-SMA in HK2 cells. In vivo, the level of blood urea nitrogen (BUN) in the MV and MSC group was lower than the UUO (P < 0.01). The Scr level decreased after 7 days of MV treatment (P < 0.05). Administration of MSC and MV reduced Scr level at day 14 (P < 0.05). The level of serum UA decreased with MV administration (day 7,14, P < 0.01). Herein, a total of 503 expressed miRNAs were detected, of which, 266 were in MSC, including 237 in MVs. CONCLUSION: Micro-vesicles (MVs) protect kidneys both in vivo and vitro, and MVs are superior to MSCs in some respects. MVs can be a potential therapy in treatment of kidney diseases.

Relationships between interleukin-12B and interleukin-10 gene polymorphisms and hepatitis C in Chinese Han hemodialysis patients.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) commonly causes a chronic infection but portion of hemodialysis patients are able to resistant to HCV infection, even clear the virus naturally. Interleukin-10 (IL-10) and interleukin-12 (IL-12) are crucial regulators of the immune response to T-helper 1 (Th1) or T-helper 2 (Th2) categories and play a role in autoimmune and infectious diseases. This study was undertaken to investigate the possible association of genetic polymorphisms of 3' untranslated region (3'UTR) of the IL-12B (-1188) and IL-10 (-592 and -819) and hepatitis C in Chinese Han hemodialysis (HD) patients. METHODS: The genotyping of IL-12B 3'UTR and IL-10 -592 and -819 were performed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: Compared with the IL-12B-AA genotype, CC and combined CC/AC genotypes were associated with a significant decreased risk of HCV infection in Chinese hemodialysis patients (p < 0.001). However, the IL-10-592 and -819 genotypes were not found significant difference both between the anti-HCV (+) and anti-HCV (-) patients (p > 0.05) and the persistent infection and viral clearance HD patients (p > 0.05). CONCLUSIONS: The present study indicated that the polymorphisms of IL-12B 3'UTR might contribute to the susceptibility of HCV infection in Chinese HD population.

GATA2 downregulation contributes to pro-inflammatory phenotype and defective phagocytosis of pulmonary macrophages in chronic obstructive pulmonary disease.

Pulmonary macrophages from COPD patients are characterized by lower phagocytic and bactericidal activity whereas there is hypersecretion of pro-inflammatory cytokines. The prominent decline of GATA2 expression in pulmonary macrophages from COPD patients inspired us to figure out its role during COPD development. The expression levels of GATA2 were decreased in alveolar macrophages isolated from cigarette smoke (CS)-induced COPD mice and cigarette smoke extract (CSE)-treated macrophages. In vitro, both CSE and GATA2 knockdown via siRNAs elevated pro-inflammatory cytokines expression whereas inhibiting phagocytosis in macrophages. Integrated analysis of transcriptomics of GATA2-knockdown macrophages and the results of ChIP sequencing of GATA2 together with dual-luciferase reporter assay identified Abca1 and Pacsin1 as functional target genes of GATA2. Mechanistically, ABCA1 mediates the pro-inflammatory secretion phenotype and the dysfunction in early stage of phagocytosis of macrophages through TLR4/MyD88 and MEGF10/GULP1 pathways, respectively. PACSIN1/SUNJ1 partially mediates the disruption effects of GATA2 downregulation on maturation of phagolysosomes in macrophages. Together, our study suggests that GATA2 influences multiple functions of pulmonary macrophages by simultaneous transcriptional regulation of several target genes, contributing to the dysfunctions of pulmonary macrophages in response to CS, which provides an impetus for further investigations of GATA2 or other underappreciated transcription factors as regulatory hubs in COPD pathogenesis.