LncRNA KCNQ10T1 shuttled by bone marrow mesenchymal stem cell-derived exosome inhibits sepsis via regulation of miR-154-3p/RNF19A axis.

This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan-Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.

MiR-146a-5p accelerates sepsis through dendritic cell activation and glycolysis via targeting ATG7.

To unveil the role and regulatory mechanism of miR-146a-5p in sepsis. A sepsis cell model was established via lipopolysaccharide (LPS)-induction in dendritic cells (DCs). The maturation of DCs was evaluated via flow cytometry. Gene expression was measured through reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The concentrations of inflammation biomarkers were revealed via enzyme-linked immunosorbent assay (ELISA). The pathological and histological changes in lungs in the sepsis mice model were analyzed via hematoxylin and eosin (H&E) staining. In this study, the miR-146a-5p level was elevated in the serum of sepsis patients and LPS-induced DCs but decreased in the serums of cured sepsis patients. Furthermore, miR-146a-5p deletion alleviated the activation of T cells and attenuated the imbalance of Th17/Treg. Besides, ATG7 was validated as a target of miR-146a-5p. ATG7 elevation enhanced lactate production and glucose uptake in LPS-triggered DCs. Additionally, upregulation of ATG7 suppressed the protein levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), phospho protein kinase B (p-AKT), and phosphorylated signal transducer and activator for transcription 3 (p-STAT3). In addition, miR-146a-5p downregulation alleviated T-cell activation, inflammation, lactate production, and glucose uptake in sepsis mice. Moreover, the lung injury due to sepsis was also attenuated as a result of miR-146a-5p silencing. MiR-146a-5p aggravates sepsis through DCs activation and glycolysis via targeting ATG7.

Effects of administration of estradiol and progesterone on ovarian stimulation response, and in vitro developmental competence of oocytes in CIDR-treated calves.

The present study was conducted to investigate the effects of administering estradiol (estradiol-17ß, 2.5 mg) plus progesterone (P4, 50 mg) as a part of a controlled internal drug release (CIDR)-based superovulation protocol on ovarian follicles development, and oocyte recovery as well as on in vitro development in prepubertal calves after follicle stimulating hormone (FSH) stimulation. Calves in the treatment group exhibited significantly decreased (P < 0.05) numbers of both small and large antral follicles compared to the control group A and B (<3 mm in diameter [small], 3.4 versus 12.8, 11.6; > 7 mm in diameter [large], 0 versus 7.6, 7.2). The treated animals also exhibited an increased (P < 0.05) proportion of usable oocytes from the total oocytes recovered compared with those of the control group A and B (77% versus 50.2%, 47.8%). Moreover, the rate of cleavage and the percentage of blastocysts displayed an increased trend in the treatment group compared to controls A and B (59.2% versus 50.5%, 50.8%; 15% versus 12.4%, 11.6%, respectively). In conclusion, the application of estradiol-17ß plus P4 at CIDR insertion prior to FSH stimulation affected ovarian follicles development and exerted a beneficial effect on the in vitro development of calf oocytes.

Rate and Associated Factors of Fatigue in Chinese Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Survey.

Purpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients' quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients. Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ2 tests and logistic regression models. Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue. Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.

Prediction analysis of TBI 24-h survival outcome based on machine learning.

Background: Traumatic brain injury (TBI) is the major reason for the death of young people and is well known for its high mortality and morbidity. This paper aim to predict the 24h survival of patients with TBI. Methods: A total of 1224 samples were involved in this analysis, and the clinical indicators involved included age, gender, blood pressure, MGAP and other fields, among which the target variable was "outcome", which was a binary variable. The methods mainly involved in this paper include data visualization analysis, single factor analysis, feature engineering analysis, random forest model (RF), K-Nearst Neighbors (KNN) model, and so on. Logistic regression model (LR) and deep neural network model (DNN). We will oversample the training set using the SMOTE method because of the very unbalanced labeling of the sample itself. Results: Although the accuracy of all models is very high, the recall rate is relatively low. The DNN model with the best performance only reaches 0.17, and the corresponding AUC is 0.80. After resampling, we find that the recall rate of positive samples of all models has increased a lot, but the AUC of some models has decreased. Finally, the optimal model is LR, whose positive sample recall rate is 0.67 and AUC is 0.82. Conclusion: Through resampling, we obtained that the best model is the RF model, whose recall rate and AUC are the best, and the AUC level is about 0.87, indicating that the accuracy performance of the model is still good.

Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of FOXO1.

BACKGROUND: It has been reported that inhibition of Fucosyltransferase4 (FUT4) to activate Forkhead box O1 (FOXO1) can lead to apoptosis of cancer cells, however, the mechanism in osteosarcoma is still unclear. OBJECTIVE: To explore the biological significance of the connection between FUT4 and FOXO1 in osteosarcoma growth. METHODS: In vitro tests were conducted using the human osteoblast cell line and the osteosarcoma cell lines. QRT-PCR assay as well as western blot assay were used to ascertain the relative expression levels of FUT4 and FOXO1 in the cells. By using the CCK-8 assay, colony assay, EDU assay, wound healing assay and Transwell assay, osteosarcoma cells' ability to proliferate, migrate and invade were examined in relation to si- FUT4. TUNEL test was used to evaluate Si-impact FUT4's on KHOS and U2OS apoptosis in osteosarcoma cells. Western blot assay was used to identify the expression of proliferative, migrating and apoptosis-related protein markers in osteosarcoma cells KHOS and U2OS and the expression of important proteins in the Wnt/ ß-catenin signaling pathway. RESULTS: In comparison with osteoblasts, osteosarcoma cells expressed more FUT4. The osteosarcoma cells' capacities to proliferate, invade, and migrate were markedly inhibited by the inhibition of FUT4 expression, which also increased osteosarcoma cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by upregulating FOXO1 expression, which was in turn inhibited by inhibiting FUT4 expression. CONCLUSION: Osteosarcoma cells express more FUT4. The Wnt/ß-catenin signaling pathway has a significant effect on osteosarcoma cell death, and inhibition of FUT4 expression may target FOXO1 activation to decrease osteosarcoma cells' ability to proliferate, invade, and migrate.

Mapping Asia Plants: The Threat Status and Influencing Factors of Rare and Endangered Vascular Plant Species in North Asia (Asian Russia).

In order to effectively protect rare and endangered plants, 27 provincial-level administrative regions in North Asia (the Asian part of Russia) have compiled and published local Red Data Books. In this study, the names (with synonyms) of vascular plants in the 27 provincial Red Books were digitalized and merged into a database of rare and endangered vascular plants in North Asia. The purpose is to reflect the species composition, geographic distribution pattern, and protection level of these plants and their inclusion in the national Russian Red Data Book and the IUCN Red List, and provide a reference for formulating conservation strategies. The dataset has a total of 2079 species, 160 subspecies, and 53 varieties belonging to 667 genera and 143 families. It contains data on 2292 taxa, including family name, genus name, species name and synonyms, protection level, and other information. We also analyzed the main influencing factors, existing problems of rare and endangered vascular plant species, and suggestions for addressing them. We conclude that, to date, the IUCN criteria have not been applied consistently in all regions, leading to an excessive number of species being recorded in the Red Data Books of Asian Russia; specifically, one-third of all floral species are in the regional Red Data Books.

Integrated analysis of multiple transcriptomic data identifies ST8SIA6­AS1 and LINC01093 as potential biomarkers in HBV­associated liver cancer.

The mechanisms of long-non-coding RNAs (lncRNAs) in hepatitis B virus (HBV) infection-associated liver cancer remain largely unclear. Therefore, the aim of the present study was to investigate the regulatory mechanisms of lncRNAs in this disease. HBV-liver cancer related transcriptome expression profile data (GSE121248 and GSE55092) from the Gene Expression Omnibus database and survival prognosis information from The Cancer Genome Atlas (TCGA) database were obtained for analysis. The limma package was used to identify the overlapped differentially expressed RNAs (DERs), including DElncRNAs and DEmRNAs, in the GSE121248 and GSE55092 datasets. The screened optimized lncRNA signatures were used to develop a nomogram model based on the GSE121248 dataset, which was validated using the GSE55092 and TCGA datasets. A competitive endogenous RNA (ceRNA) network was constructed based on the screened prognosis-associated lncRNA signatures from TCGA dataset. In addition, the levels of specific lncRNAs were evaluated in HBV-infected human liver cancer tissues and cells, and Cell Counting Kit-8, ELISA and Transwell assays were performed to evaluate the effects of the lncRNAs in HBV-expressing liver cancer cells. A total of 535 overlapped DERs, including 30 DElncRNAs and 505 DEmRNAs, were identified in the GSE121248 and GSE55092 datasets. An optimized DElncRNA signature comprising 10 lncRNAs was used to establish a nomogram. ST8SIA6-AS1 and LINC01093 were identified as lncRNAs associated with HBV-liver cancer prognosis in TCGA dataset, and were applied to construct a ceRNA network. Reverse transcription-quantitative PCR analysis showed that ST8SIA6-AS1 was upregulated and LINC01093 was downregulated in HBV-infected human liver cancer tissues and HBV-expressing liver cancer cells compared with non-HBV-infected controls. ST8SIA6-AS1 knockdown and LINC01093 overexpression independently reduced the number of copies of HBV DNA, the levels of hepatitis B surface antigen and hepatitis B e antigen, as well as cell proliferation, migration and invasion. In summary, the present study identified ST8SIA6-AS1 and LINC01093 as two potential biomarkers that may be effective therapeutic targets for HBV-associated liver cancer.

Tumor-derived exosomes promote macrophages M2 polarization through miR-1-3p and regulate the progression of liver cancer.

Hepatic carcinoma is one of the most life-threatening malignancies in the world. In the clinic, it is urgent to establish a clear mechanism of hepatic carcinoma development as the basis for intervention and treatment. The purpose of this study was to explore the regulatory effect of tumor-derived exosomes on the progression of hepatocellular carcinoma.qPCR was used to detect the expression of miR-1-3p. CCk-8 and EdU staining were used to detect the proliferation and activity of hepatocellular carcinoma cells under different conditions. Transwell assay was used to detect migration and invasion of hepatocellular carcinoma cells. The morphology and size of exosomes were detected by transmission electron microscope and nanoparticle tracking analysis. Western blot was used to detect the expression of markers of exosomes. Immunofluorescence staining was used to explore the location of exosomes in hepatocellular carcinoma cells.The results showed that the expression of miR-1-3p was significantly reduced in hepatocellular carcinoma cells, and the exosomes transfected with miR-1-3p could enter macrophages and express miR-1-3p in large quantities. Macrophages polarized to M2 type under the action of miR-1-3p. Polarized M2 macrophages further down-regulated the proliferation, migration and invasion of Huh-7 cells.In summary, miR-1-3p can enter macrophages through exosomes and affect their polarization, thus affecting the growth of hepatic carcinoma cells. miR-1-3p may be a potentially effective target for regulating liver cancer progression.

Gender differences among long-stay inpatients with schizophrenia in China: A cross-sectional study.

Objective: We sought to examine the independent correlates of long-term hospitalization in a sample of Chinese inpatients with schizophrenia (SCZ) from a gender-based perspective. Methods: This was a cross-sectional study that was carried out in a tertiary psychiatric hospital. All adult inpatients in this hospital were screened from January to March 2020, 251 of whom were identified as long-stay inpatients with SCZ (LSIS) and 224 as short-stay inpatients with SCZ (SSIS). Demographic and clinical information of the two groups was collected through medical records, scale assessments and interviews. Gender differences were analyzed, and independent correlates of long-stay between genders were explored by logistic regression analyses. Results: Compared to SSIS, greater proportions of LSIS patients were male (64.1%), single (82.1%), unemployed (81.7%) and had no family caregivers (54.2%). For LSIS per se, proportionally more males were single (88.8%), had no family caregiver (65.8%), had concomitant physical disease (65.2%) and had a history of hazardous behavior (27.3%) than their female counterparts. For females, the top independent risk factors for a long stay included poor functioning (OR = 5.9, 95% CI: 2.9-12.0), older age (OR = 4.3, 95% CI: 2.1-9.1) and being single (OR = 3.9, 95% CI: 1.8-8.4). Similar to women, both older age (OR = 5.3, 95% CI: 2.5-11.2) and poor functioning (OR = 4.0, 95% CI: 2.1-7.9) were also independent factors for long-term hospitalization of male patients; however, having no family caregiver (OR = 10.2, 95% CI: 4.6-22.6) was the primary risk factor for men. Conclusions: Both clinical and nonclinical factors play important roles in long-term hospitalization in Chinese patients with schizophrenia. There are overlaps and distinctions across genders with respect to the independent factors of long stays. These findings provide clues for developing better service strategies for this population, and highlight the importance of paying attention to gender differences in further research in this field.

MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters.

Background: The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear. Methods: To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites. Results: Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3'-UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter. Conclusion: miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter.

Peptidome analysis reveals critical roles for peptides in a rat model of intestinal ischemia/reperfusion injury.

Intestinal ischemia/reperfusion injury (IIRI) has the potential to be life threatening and is associated with significant morbidity and serious damage to distant sites in the body on account of disruption of the intestinal mucosal barrier. In the present study, we have explored this line of research by comparing and identifying peptides that originated from the intestinal segments of IIRI model rats by using liquid chromatography-mass spectrometry (LC-MS). We also analyzed the basic characteristics, cleavage patterns, and functional domains of differentially expressed peptides (DEPs) between the IIRI model rats and control (sham-operated) rats and identified bioactive peptides that are potentially associated with ischemia reperfusion injury. We also performed bioinformatics analyses in order to identify the biological roles of the DEPs based on their precursor proteins. Enrichment analysis demonstrated the role of several DEPs in impairment of the intestinal mucosal barrier caused by IIRI. Based on the results of comprehensive ingenuity pathway analysis, we identified the DEPs that were significantly correlated with IIRI. We identified a candidate precursor protein (Actg2) and seven of its peptides, and we found that Actg2-6 had a more significant difference in its expression, a longer half-life, and better lipophilicity, hydrophobicity, and stability than the other candidate Actg2 peptides examined. Furthermore, we observed that Actg2-6 might play critical roles in the protection of the intestinal mucosal barrier during IIRI. In summary, our study provides a better understanding of the peptidomics profile of IIRI, and the results indicate that Actg2-6 could be a useful target in the treatment of IIRI.

Polymorphic chloroplast microsatellite loci in Nelumbo (Nelumbonaceae).

PREMISE OF THE STUDY: To study population genetics, phylogeography, and hybridization of Nelumbo (Nelumbonaceae), chloroplast microsatellite markers were developed. METHODS AND RESULTS: Seventeen microsatellite loci were identified from the chloroplast genomes of N. nucifera and N. lutea. Polymorphisms were assessed in three populations of N. nucifera and one population of N. lutea. Nine loci were found to be polymorphic in N. nucifera, and all 17 loci were found to be polymorphic in N. lutea. In N. nucifera, the number of alleles per locus ranged from two to six, and the unbiased haploid diversity per locus ranged from 0.198 to 0.790. In N. lutea, the number of alleles ranged from two to four, and the unbiased haploid diversity per locus ranged from 0.245 to 0.694. CONCLUSIONS: The identified chloroplast simple sequence repeat markers will be useful for the study of genetic diversity, phylogeography, and identification of Nelumbo cultivars.

miR-135a-5p mediated down-regulation of STAT6 inhibits proliferation and induces apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA), as a chronic autoimmune disorder, seriously threatens human health. However, no study has thoroughly illustrated the etiology of RA. The present work focused on investigating the biological functions of STAT6 and the upstream miRNAs that regulate its expression. METHODS: Synovial tissues from rheumatoid arthritis (RA) patients and normal participants were acquired. Cell viability, proliferation, apoptosis, concentrations of cytokines, miRNA and protein levels, and relative luciferase activities were detected. RESULTS: WB and qRT-PCR showed that STAT6 was obviously up-regulated in synovial tissues of RA patients as well as RA fibroblast-like synoviocytes (RA FLSs). Functionally, down-regulation of STAT6 significantly inhibited the growth of RA FLSs as indicated by EdU and CCK-8 assays. In addition, inhibition of STAT6 remarkably promoted apoptosis of RA FLSs. Besides, silence of STAT6 notably suppressed inflammatory cytokine levels, such as TNF-α, IL-6 and IL-1ß. Mechanistically, STAT6 was predicted to be the direct target of and negatively regulated by miR-135a-5p. Moreover, STAT6 was involved in the regulation of miR-135a-5p on cell growth, apoptosis and inflammatory response of RA FLSs. CONCLUSION: miR-135a-5p/STAT6 is a potential novel therapeutic target for RA treatment.

Differential impacts of adult trees on offspring and non-offspring recruits in a subtropical forest.

An important mechanism promoting species coexistence is conspecific negative density dependence (CNDD), which inhibits conspecific neighbors by accumulating host-specific enemies near adult trees. Natural enemies may be genotype-specific and regulate offspring dynamics more strongly than non-offspring, which is often neglected due to the difficulty in ascertaining genetic relatedness. Here, we investigated whether offspring and non-offspring of a dominant species, Castanopsis eyrei, suffered from different strength of CNDD based on parentage assignment in a subtropical forest. We found decreased recruitment efficiency (proxy of survival probability) of offspring compared with non-offspring near adult trees during the seedling-sapling transition, suggesting genotype-dependent interactions drive tree demographic dynamics. Furthermore, the genetic similarity between individuals of same cohort decreased in late life history stages, indicating genetic-relatedness-dependent tree mortality throughout ontogeny. Our results demonstrate that within-species genetic relatedness significantly affects the strength of CNDD, implying genotype-specific natural enemies may contribute to population dynamics in natural forests.

The complete chloroplast genome sequences of Trapa quadrispinosa and T. bicornis var. taiwanensis.

The complete chloroplast genomes of Trapa quadrispinosa and T. bicornis var. taiwanensis were reported in this study. The chloroplast genome of T. quadrispinosa was 155,554 bp in length, containing an LSC of 88,506 bp, an SSC of 18,274 bp, and a pair of IR regions of 24,387 bp each. The chloroplast genome of T. bicornis var. taiwanensis was 155,543 bp in length, including an LSC of 88,497 bp, an SSC of 18,274 bp, and a pair of IR regions of 24,386 bp each. Both genomes had 112 genes, consisting of 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. The phylogenetic analysis revealed that the family Trapaceae was closely related to the family Sonneratiaceae.

Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1.

BACKGROUND: At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular mechanism. METHODS: The effects of MSCs-Exo and miR-146a-5p in LPS-induced cardiomyocytes (H9C2 cells) in vitro were verified by CCK-8, EdU assay, flow cytometry, Western blot assay, and RT-qPCR. The effect of MSCs-Exo in vivo was evaluated by CLP-induced sepsis model. The potential gene in MSCs-Exo was verified by bioinformatics analysis, and the potential target of miR-146a-5p was identified by bioinformatics analysis and luciferase reporter assay. At last, the function of miR-146a-5p and its target genes on LPS-induced cardiomyocytes (H9C2 cells) in vitro was validated by recuse experiment. RESULTS: Our findings revealed that MSCs-Exo could effectively protect cardiomyocytes of inflammation model in vitro and myocardial tissues of sepsis model in vivo. Meanwhile, we found that miR-146a-5p was a potential gene in MSCs-Exo, and MYBL1 was the target gene of miR-146a-5p and negatively regulated by miR-146a-5p. In addition, miR-146a-5p overexpression promoted proliferation and inhibited apoptosis of LPS-induced cardiomyocytes. The rescue experiment demonstrated that miR-146a-5p could effectively repress the inflammatory response of cardiomyocytes via decreasing MYBL1 expression. CONCLUSION: This study suggests that miR-146a-5p-bearing MSC-derived exosomes may become an effective treatment for sepsis.

LncRNA NEAT1 Promotes Inflammatory Response in Sepsis via the miR-31-5p/POU2F1 Axis.

Sepsis is considered to be a systemic inflammatory response, which results in organ dysfunction. LncRNA nuclear-enriched abundant transcript 1 (NEAT1) involved in sepsis progression has been reported. However, the underlying mechanism of NEAT1 in sepsis-induced inflammatory response remains to be revealed. In this study, NEAT1 and POU domain class 2 transcription factor 1 (POU2F1) were highly expressed in LPS-induced septic RAW264.7 cells, opposite to miR-31-5p expression. Furthermore, we found that NEAT1 silencing inhibited LPS-induced inflammatory response and cell proliferation, and promoted cell apoptosis. Subsequently, we found that miR-31-5p interacted with NEAT1 and targeted the 3'UTR of POU2F1, and in LPS-induced RAW264.7 cells, the inhibition of NEAT1 silencing was reversed by miR-31-5p knockdown, while POU2F1 downregulation could cover the functions of miR-31-5p knockdown. In a word, this study indicates that NEAT1 inhibits the LPS-induced progression of sepsis in RAW264.7 cells by modulating miR-31-5p/POU2F1 axis, suggesting that NEAT1 will be the potential therapeutic target for sepsis.

Efficacy of erzhu jiedu recipe on hepatitis B cirrhosis with hyperalphafetoproteinemia: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Hepatitis B cirrhosis with hyperalphafetoproteinemia is the intermediate stage of liver cirrhosis progressing to hepatocellular carcinoma (HCC), there is no effective way to treat precancerous lesions of liver in modern medicine. In recent decades, clinical and experimental evidence shows that Chinese medicine (CM) has a certain beneficial effect on Hepatitis B Cirrhosis. Therefore, this trial aims to evaluate the efficacy and safety of a CM erzhu jiedu recipe (EZJDR) for the treatment of Hepatitis B Cirrhosis with Hyperalphafetoproteinemia. METHODS: We designed a randomized, double blind, placebo-controlled clinical trial. A total of 72 patients of Hepatitis B Cirrhosis with hyperalphafetoproteinemia were randomized in 2 parallel groups. Patients in the control group received placebo granules similar to the EZJDR. In the EZJDR group, patients received EZJDR twice a day, after meals, for 48 weeks. The primary efficacy measures were changes in serum alpha-fetoprotein (AFP) and alpha-fetoprotein alloplasm (AFP-L3); The secondary indicators of efficacy are changes in liver function indicators, HBV-DNA level; Liver stiffness measurement (LSM); Hepatic portal vein diameter; T lymphocyte subgroup indexes during treatment. All data will be recorded in case report forms and analyzed by Statistical Analysis System software. Adverse events will also be evaluated. RESULTS: The results showed that EZJDR can significantly inhibit the levels of AFP and AFP-L3 in patients with hepatitis B cirrhosis and hyperalphafetoproteinemia and have good security. ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Ethics Committee of Shuguang Hospital, affiliated with University of Traditional Chinese Medicine, Shanghai (NO.2018-579-08-01). TRIAL REGISTRATION: This trial was registered on Chinese Clinical Trial Center (NO.ChiCTR1800017165).

miR-371b-5p-Engineered Exosomes Enhances Tumor Inhibitory Effect.

Background: Exosomes are well-known natural nanovesicles, that represent one of the recently discovered modes of intercellular communication due to their ability to transmit cellular components. Exosomes have been reported to have potential as natural vectors for carrying functional small RNAs and delivering chemotherapeutic agents to diseased cells. In this study, we aimed to investigate the role of exosomes in carrying miRNA for targeting tumor cells. Methods: We present a novel method for engineering exosomes with functional miR-317b-5b to target tumor cells. MiR-317b-5b exerts its anti-tumor function via its expression in tumors. RT-qPCR was performed to assess the levels of miR-371b-5p, FUT-4. Western blot was performed to measure the levels of CD9, CD81, and FUT-4 proteins. Confocal microscopy was used to observe the internalization of miR-317b-5b in tumor cells. CCK-8, EdU, flow cytometry, wound-healing migration and transwell assays were performed to evaluate cell viability, proliferation, migration, and invasion, respectively. Results: Our findings illustrated that miR-317b-5b-loaded engineered exosomes were internalized by tumor cells. MiR-317b-5b was overexpressed in tumor cells treated with miR-317b-5b-loaded engineered exosomes. The internalization of miR-317b-5b in tumor cells was accompanied by changes of cell viability, proliferation, apoptosis, and migratory and invasive capability. We found that miR-317b-5b-loaded engineered exosomes were presence in tumor tissue sections and miR-317b-5b was overexpressed in tumor tissues of osteosarcoma tumor-bearing mice infected with miR-317b-5b-loaded engineered exosomes. MiR-317b-5b-loaded engineered exosomes had the anti-tumor efficiency in vivo. Conclusion: Our findings show that miR-317b-5b-loaded engineered exosomes can be used as nanocarriers to deliver drug molecules such as miR-317b-5b both in vitro and in vivo to exert its anti-tumor functions.