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BackgroundChronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR).MethodsThe research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software.ResultsThe IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β = 0.015, 95% CI: 0.005–0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β = 0.02, 95% CI: 0.010–0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO.ConclusionGenetic evidence indicates a positive correlation between CHF and pars opercularis TH.

To find the predictors of early HCC based on the dynamic changes of HBV quasispecies, this study utilizing the second-generation sequencing (NGS) and high-order multiplex droplet digital PCR (ddPCR) technology to examine the HBV quasispecies in serum of total 247 subjects recruited from high-incidence area of HCC. In the discovery stage, 15 non-synonymous Single Nucleotide Polymorphisms (SNPs) with higher variant proportion in HCC case group were founded (all P

The clinical application of reactive oxygen species (ROS)-mediated tumor treatment has been critically limited by inefficient ROS generation. Herein, we rationally synthesized and constructed the three-dimensional PdMo nanoflowers through a one-pot solvothermal reduction method for elaborately regulated peroxidase-like enzymatic activity and glutathione peroxidase-like enzymatic activity, to promote oxidation ROS evolvement and antioxidation glutathione depletion for achieving intensive ROS-mediated tumor therapy. The three-dimensional superstructure composed of two-dimensional nanosheet subunits can solve the issues by avoiding the appearance of tightly stacked crystalline nanostructures. Significantly, Mo is chosen as a second metal to alloy with Pd because of its more chemical valence and negative ionization energy than Pd for improved electron transfer efficiencies and enhanced enzyme-like activities. In addition, the photothermal effect generated by PdMo nanoflowers could also enhance its enzymatic activities. Thus, this work provides a promising paradigm for achieving highly ROS-mediated tumor therapeutic efficacy by regulating the multi-enzymatic activities of Pd-based nanoalloys.

Mounting evidence has demonstrated that fatty acid binding protein 5 (FABP5) is commonly upregulated in many human malignancies. However, the mechanisms explaining the involvement of FABP5 in hepatocellular carcinoma (HCC) remain unclear. In this study, we demonstrated the involvement of FABP5 and its downstream signaling molecules in HCC progression. We first confirmed that FABP5 expression was upregulated in HCC. Additionally, FABP5 promoted HCC cells proliferation, migration, and invasion. Mechanistic investigation showed that FABP5 could improve cAMP-response element binding protein (CREB) phosphorylation. Meanwhile, CREB, as a transcription factor, upregulated the miR-889-5p expression by binding to the miR-889-5p promoter region. Consequently, miR-889-5p led to downregulation of Krüppel-like factor 9 (KLF9) by binding to the 3ʹ-UTR of the KLF9 mRNA, potentiating the PI3K/AKT signaling pathway and promoting the proliferation, migration, and invasion of HCC cells. Our findings have identified a FABP5/CREB/miR-889-5p/KLF9 axis for HCC progression, and we postulate that blocking this key signaling pathway may represent a promising strategy for HCC treatment.

Abstract Background Kidney cancer originates from the urinary tubule epithelial system of the renal parenchyma, accounting for 20% of all urinary system tumors. Approximately 70% of cases are localized at diagnosis, and 30% are metastatic. Most localized kidney cancers can be cured by surgery, but most metastatic patients relapse after surgery and eventually die of kidney cancer. Therefore, accurately predicting patient survival and identifying high‐risk metastatic patients will effectively guide interventions and improve prognosis. Methods This study used the data of 12,394 kidney cancer patients from the surveillance, epidemiology, and end results database to construct a research cohort related to kidney cancer survival and metastasis. Eight machine learning models (including support vector machines, logistic regression, decision tree, random forest, XGBoost, AdaBoost, K‐nearest neighbors, and multilayer perceptron) were developed to predict the survival and metastasis of kidney cancer and six evaluation indicators (accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic [AUROC]) were used to verify, evaluate, and optimize the models. Results Among the eight machine learning models, Logistic Regression has the highest AUROC in both prediction scenarios. For 3‐year survival prediction, the Logistic Regression model had an accuracy of 0.684, a sensitivity of 0.702, a specificity of 0.670, a precision of 0.686, an F1 score of 0.683, and an AUROC of 0.741. For tumor metastasis prediction, the Logistic Regression model had an accuracy of 0.800, a sensitivity of 0.540, a specificity of 0.830, a precision of 0.769, an F1 score of 0.772, and an AUROC of 0.804. Conclusion In this study, we selected appropriate variables from both statistical and clinical significance and developed and compared eight machine learning models for predicting 3‐year survival and metastasis of kidney cancer. The prediction results and evaluation results demonstrated that our model could provide decision support for early intervention for kidney cancer patients.

Abstract Background Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. Methods Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. Results In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. Conclusion In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract

Prescribed burning is a widely used fuel management employed technique to mitigate the risk of forest fires. The Pinus yunnanensis Franch. forest, which is frequently prone to forest fires in southwestern China, serves as a prime example for investigating the effects of prescribed burning on the flammability of surface dead fuel. This research aims to establish a scientific foundation for managing dead fuel in forests, as well as fire prevention and control strategies. Field data was collected from P. yunnanensis forests located in central Yunnan Province in 2021 and 2022. The study implemented a randomized complete block design with two blocks and three treatments: an unburned control (UB), one year after the prescribed burning (PB1a), and three years after the prescribed burning (PB3a). These treatments were evaluated based on three indices: surface dead-bed structure, physicochemical properties, and potential fire behavior parameters. To analyze the stand characteristics of the sample plots, a paired t-test was conducted. The results indicated no significant differences in the stand characteristics of P. yunnanensis following prescribed burning (p > 0.05). Prescribed burning led to a significant decrease in the average surface dead fuel load from 10.24 t/ha to 3.70 t/ha, representing a reduction of 63.87%. Additionally, the average fire−line intensity decreased from 454 kw/m to 190 kw/m, indicating a decrease of 58.15%. Despite prescribed burning, there were no significant changes observed in the physical and chemical properties of dead fuels (p > 0.05). However, the bed structure of dead fuels and fire behavior parameters exhibited a significant reduction compared with the control sample site. The findings of this study provide essential theoretical support for the scientific implementation of prescribed burning programs and the accurate evaluation of ecological and environmental effects post burning.

Objective: Pancreatic cancer (PC) is an extremely malignant tumor with similar morbidity and mortality and lack of an effective treatment. This study explored the prognostic value and molecular mechanisms of proteasome 26S subunit, non-ATPase (PSMD) family genes in pancreatic ductal adenocarcinoma (PDAC). Methods: Survival analyses were performed to elucidate the relationship between prognosis and the level of PSMD expression. ROC curves and nomograms were constructed to predict the prognosis. A bioinformatics analysis was used to explore the co-expression and complex interaction networks of PSMDs. The potential mechanisms were further explored via gene set enrichment analysis (GSEA). Results: We find high levels of PSMD6, PSMD9, PSMD11, and PSMD14 expression were significantly associated with a poorer OS. High PSMD6 and PSMD11 expression was associated with a poorer relapse-free survival (RFS). A risk score model was constructed based on prognosis-related genes. The area under ROC curves (AUC) was 53.3%, 59.3%, and 62.9% for 1-, 2-, 3 years, respectively. Conclusion: GSEA revealed that PSMD6 and PSMD11 play a role in PDAC through various biological processes and signaling pathways, including TP53, CDKN2A, MYC pathway, DNA repair, KRAS, cell cycle checkpoint, NIK, NF-κB signaling pathway, and proteasomes. This study demonstrated that PSMD6 and PSMD11 could serve as a potential prognostic and diagnostic biomarkers for patients with early-stage PDAC after pancreaticoduodenectomy.

Objective: Reflux esophagitis animal models represent an important component in the preclinical study of digestive system drugs, and the aim of this study was to determine the best modeling method. Methods: Female Wistar rats were used to establish reflux esophagitis models by employing the following methods: improved chemical burn, external pyloric clamp plus anterior gastric ligation, cardiomyotomy plus semipyloric ligation, cardiomyotomy plus internal pyloric ligation, cardiomyotomy plus external pyloric ligation, and cardioplasty plus pyloric ligation plus gastrojejunal Roux-en-Y anastomosis. The body weight, lower esophageal pH and esophageal mucosal injury of the rats were observed. Results: The model formation rate was 83% based on cardiomyotomy plus external pyloric ligation. On the 3rd day after the operation, lower esophageal mucosa congestion occurred, and the model was successfully established. On the 7th day, mucosal hyperemia and erosion were observed in the most serious lesions, indicating optimal model conditions. On the 14th day, the lower esophageal mucosa remained congested, suggesting that the model was useful from the 3rd to the 14th day. The method caused less trauma to the animals. The ligation diameter was uniform, and the model was more stable. Conclusion: Cardiomyotomy plus external pyloric ligation is the best method.

Based on daily data about Bitcoin and six other major financial assets (stocks, commodity futures (commodities), gold, foreign exchange (FX), monetary assets, and bonds) in China from 2013 to 2017, we use a VAR-GARCH-BEKK model to investigate mean and volatility spillover effects between Bitcoin and other major assets and explore whether Bitcoin can be used either as a hedging asset or a safe haven. Our empirical results show that (i) only the monetary market, i.e., the Shanghai Interbank Offered Rate (SHIIBOR) has a mean spillover effect on Bitcoin and (ii) gold, monetary, and bond markets have volatility spillover effects on Bitcoin, while Bitcoin has a volatility spillover effect only on the gold market. We further find that Bitcoin can be hedged against stocks, bonds and SHIBOR and is a safe haven when extreme price changes occur in the monetary market. Our findings provide useful information for investors and portfolio risk managers who have invested or hedged with Bitcoin. Keywords: Bitcoin, Spillover effects, Hedging asset, Safe haven, JEL classification: C10, G11

The olfactory system of insects is important for behavioral activities as it recognizes internal and external volatile stimuli in the environment. Insect odorant degrading enzymes (ODEs), including antennal-specific carboxylesterases (CXEs), are known to degrade redundant odorant molecules or to hydrolyze important olfactory sex pheromone components and plant volatiles. Compared to many well-studied Type-I sex pheromone-producing lepidopteran species, the molecular mechanisms of the olfactory system of Type-II sex pheromone-producing Hyphantria cunea (Drury) remain poorly understood. In the current study, we first identified a total of ten CXE genes based on our previous H. unea antennal transcriptomic data. We constructed a phylogenetic tree to evaluate the relationship of HcunCXEs with other insects’ CXEs, and used quantitative PCR to investigate the gene expression of H. cunea CXEs (HcunCXEs). Our results indicate that HcunCXEs are highly expressed in antennae, legs and wings, suggesting a potential function in degrading sex pheromone components, host plant volatiles, and other xenobiotics. This study not only provides a theoretical basis for subsequent olfactory mechanism studies on H. cunea, but also offers some new insights into functions and evolutionary characteristics of CXEs in lepidopteran insects. From a practical point of view, these HcunCXEs might represent meaningful targets for developing behavioral interference control strategies against H. cunea.

Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of hepatocellular carcinoma; however, the underlying mechanisms involved are not fully understood. In this study, using a customized, pressure-loading device, we assess the effect of pressure loading on DNA damage in human hepatocytes. We show that pressure loading leads to DNA damage and S-phase arresting in the cell cycle, and activates the DNA damage response in hepatocytes. Meanwhile, pressure loading upregulates Dicer expression, and its silencing exacerbates pressure-induced DNA damage. Moreover, pressure loading also activates ERK1/2 signaling molecules. Blockage of ERK1/2 signaling inhibits pressure-upregulated Dicer expression and exacerbates DNA damage by suppressing DNA damage response in hepatocytes. Our findings demonstrate that compressive stress loading induces hepatocyte DNA damage through the ERK1/2–Dicer signaling pathway, which provides evidence for a better understanding of the link between the altered mechanical environment and liver diseases.

Background: COVID-19 has been quickly spreading, making it a serious public health threat. It is important to identify phenotypes to predict the severity of disease and design an individualized treatment.Methods: We collected data from 213 COVID-19 patients in Wuhan Pulmonary Hospital from January 1 to March 30, 2020. Principal component analysis (PCA) and cluster analysis were used to classify patients.Results: We identified three distinct subgroups of COVID-19. Cluster 1 was the largest group (52.6%) and characterized by oldest age, lowest cellular immune function, and albumin levels. 38.5% of subjects were grouped into Cluster 2. Most of the lab results in Cluster 2 fell between those of Clusters 1 and 3. Cluster 3 was the smallest cluster (8.9%), characterized by youngest age and highest cellular immune function. The incidence of respiratory failure, acute respiratory distress syndrome (ARDS), heart failure, and usage of non-invasive mechanical ventilation in Cluster 1 was significantly higher than others (P < 0.05). Cluster 1 had the highest death rate of 30.4% (P = 0.005). Although there were significant differences in age between Clusters 2 and 3 (P < 0.001), we found that there was no difference in demand for medical resources.Conclusions: We identified three distinct clusters of the COVID-19 patients. The results show that age alone could not be used to assess a patient's condition. Specifically, management of albumin, and immune function are important in reducing the severity of disease.

C-terminally truncated hepatitis B virus (HBV) X (ctHBx) infection and exposure to microcystins-LR (MC-LR) can lead to human hepatitis and liver cancer, but the mechanism associated with their synergistically effects not been fully elucidated. The ctHBx (HBxΔ4 and HBxΔ32) lentivirus were constructed and transfected into the HepG2 cells. Then we investigated the function of MC-LR and ctHBx using the molecular biology approaches, including enzyme-linked immunosorbent assay, clone formation assay, scratch wound testing, transwell assays, carried out flow cytometry respectively to examine cell cycle and apoptosis in each group, and detected the related proteins of HBx, MEK/ERK/JNK/p38 in mitogen-activated protein kinase (MAPK) pathway and the downstream proteins such as cdc2, cdc25C, and p53 by western blotting. We found that the protein phosphorylase 2A (PP2A) enzyme activity in MC-LR and HBxΔ32/HBxΔ4 groups decreased more than in MC-LR and HBx group at the same time point and MC-LR concentration (P < 0.05). Meanwhile the proliferation, migration, invasion and colony formation capability of HepG2 cells were significantly enhanced in MC-LR and ctHBx groups (P < 0.05). In addition the proportion of S stage cells in the MC-LR-treated HBxΔ32/HBxΔ4 groups was significantly greater than that in the untreated groups (P < 0.05). Furthermore, the protein expression of MAPK signaling pathway including phospho-MEK1/2, ERKl/2, p38, and JNK were up-regulated by MC-LR and HBxΔ32, and the expression of cyclin-related proteins, including p53, cdc25C, and cdc2 were also activated (P < 0.05). Taken together, our findings revealed the essential significance of the MC-LR and ctHBx on the PP2A/MAPK/p53, cdc25C and cdc2 axis in the formation and development of HCC and identified MC-LR and ctHBx as potential causal cofactors of hepatocarcinogenesis.

As the first-line treatment, sorafenib has been used for advanced hepatocellular carcinoma (HCC), but the chemoresistance commonly restricts to the clinical efficiency. In this study, we intend to investigate the genome-wide expression pattern of long noncoding RNAs (lncRNAs) in sorafenib-resistant HCC. Herein, we identified thousands of differentially expressed lncRNAs in sorafenib-resistant HCC cells by high-throughput sequencing compared to the parental. Besides, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the sorafenib-resistant Huh7 cells (Huh7-S) and sorafenib-resistant HepG2 cells (HepG2-S) compared to the parental cells. Moreover, when analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, the differentially expressed genes were significantly related to the tight junction. Among them, the expression of TCONS_00284048 and TCONS_00006019 was consistently up-regulated in sorafenib-resistant HCC cell lines, whereas when either was knocked down, the sensitivity of Huh7-S and HepG2-S cells to sorafenib was increased. Taken together, our data demonstrate that the lncRNA expression profile is significantly altered in sorafenib-resistant HCC cells as well as differentially expressed lncRNAs may play crucial functions on HCC sorafenib resistance and HCC progression.

Abstract Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2. However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration‐enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)‐challenged mice, and protected mice against DSS or 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced colitis in D prostanoid receptor 1 (DP1)‐dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS‐induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro‐inflammatory cytokine secretion of macrophages, respectively. Niacin treatment improved vascular permeability, reduced apoptotic epithelial cells, promoted epithelial cell update, and suppressed pro‐inflammatory gene expression of macrophages. Moreover, treatment with niacin‐containing retention enema effectively promoted UC clinical remission and mucosal healing in patients with moderately active disease. Therefore, niacin displayed multiple beneficial effects on DSS/TNBS‐induced colitis in mice by activation of PGD2/DP1 axis. The potential efficacy of niacin in management of IBD warrants further investigation.

Campylobacter jejuni is considered as the leading cause of gastroenteritis all over the world. This bacterium has the CRISPR–cas9 system, which is used as a gene editing technique in different organisms. However, its role in bacterial virulence has just been discovered; that discovery, however, is just the tip of the iceberg. The purpose of this study is to find out the relationship between cas9 and virulence both phenotypically and genotypically in C. jejuni NCTC11168. Understanding both aspects of this relationship allows for a much deeper understanding of the mechanism of bacterial pathogenesis. The present study determined virulence in wild and mutant strains by observing biofilm formation, motility, adhesion and invasion, intracellular survivability, and cytotoxin production, followed by the transcriptomic analysis of both strains. The comparative gene expression profile of wild and mutant strains was determined on the basis of De-Seq transcriptomic analysis, which showed that the cas9 gene is involved in enhancing virulence. Differential gene expression analysis revealed that multiple pathways were involved in virulence, regulated by the CRISPR-cas9 system. Our findings help in understanding the potential role of cas9 in regulating the other virulence associated genes in C. jejuni NCTC11168. The findings of this study provide critical information about cas9's potential involvement in enhancing the virulence of C. jejuni, which is a major public health threat.

As the sports training predicting model based on chaos local predicting method still has the low predicting accuracy and the slow function speed problems, this paper proposes a sports training chaos predicting model based on weight control ant colony algorithm. It firstly uses the comprehensive weight factor to perform the weight control to the initial information of the new join node in the ant colony algorithm, and then performs the optimizing iteration to the pheromone of weight control optimization, and updates the pheromone of ant node according to its contribution. Then the paper performs the optimization selection to the pheromone persistence parameters, the normalized factors and the relative importance factors to reduce the computing time and optimal error rate of the ant colony algorithm. Finally, adopt the improved ant colony algorithm to optimize the sports training chaos predicting model. The experiments show that the proposed sports training chaos predicting model based on weight control ant colony algorithm has a higher accuracy than the standard ant colony algorithm and the sports training chaos local predicting model.

The challenge of visual tracking mainly comes from intrinsic appearance variations of the target and extrinsic environment changes around the target in a long duration, so the tracker that can simultaneously tolerate these variabilities is largely expected. In this study, the authors propose a new tracking approach based on discriminative stable regions (DSRs). The DSRs are obtained based on the criterion of maximal local entropy and spatial discrimination, which enables the tracker to handle well distractors and appearance variations. The collaborative tracking incorporated hierarchical clustering can tolerate motion noise and occlusions. In addition, as an efficient tool, the principle component analysis is used to discover the potential affine relation between DSR and the target, which timely adapts to the shape deformation of the target. Extensive experiments show that the proposed method achieves superior performance in many challenging target tracking tasks.

Objectives. The complimentary value of computed tomographic enterography (CTE) and double-balloon enteroscopy (DBE) combined with capsule endoscopy (CE) was evaluated in the diagnosis of obscure gastrointestinal bleeding (OGIB). Methods. Patients who received CE examinations at Ruijin Hospital between July 2007 and July 2014 with the indication of OGIB were identified, and those who also underwent DBE and/or CTE were included. Their clinical information was retrieved, and results from each test were compared with findings from the other two examinations. Results. The overall diagnostic yield of CE was comparable with DBE (73.9% versus 60.9%) but was significantly higher than the yield of CTE (87% versus 25%, p

Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS), and then culturing these microglia with BMSC-conditioned medium (BMSC-CM). We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO) were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation.

miRNAs have been found to repress gene expression at posttranscriptional level in cells. Studies have shown that expression of miRNAs is tissue-specific and developmental-stage-specific. The mechanism behind this could be explained by miRNA pathways. In this study, totally 54 miRNAs were analysed in 7 matched human foetal and adult organs (brain, colon, heart, kidney, liver, lung and spleen) using real-time PCR. Quantitative analysis showed that a big proportion of the 54 miRNAs have higher general expression in the organs of the foetal period than the adult period, with the exception of the heart. The miRNA gene promoter methylation level in the adult stages was higher than in the foetal stages. Moreover, there is a high general expression level of several miRNAs in both stages of brain, kidney, liver, lung and spleen, but not seen in colon and heart. Our results indicate that the miRNAs may play a bigger role in the foetal stage than the adult stage of brain, colon, kidney, liver, lung and spleen. The majority of the miRNAs analysed may play an important role in the growth and development of brain, kidney, liver, lung and spleen. However, a minority of the miRNAs may be functional in colon and heart.