A 3'-pre-tRNA-derived small RNA tRF-1-Ser regulated by 25(OH)D promotes proliferation and stemness by inhibiting the function of MBNL1 in breast cancer.

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.

The mechanism by which piR-000699 targets SLC39A14 regulates ferroptosis in aging myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

Unveiling the role of ABI3 and hub senescence-related genes in macrophage senescence for atherosclerotic plaque progression.

BACKGROUND: Atherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity and mortality. Senescent foamy macrophages are considered to be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed to explore the senescence-related genes in macrophages diagnosis for atherosclerotic plaque progression. METHODS: The atherosclerosis-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and cellular senescence-associated genes were acquired from the CellAge database. R package Limma was used to screen out the differentially expressed senescence-related genes (DE-SRGs), and then three machine learning algorithms were applied to determine the hub DE-SRGs. Next, we established a nomogram model to further confirm the clinical significance of hub DE-SRGs. Finally, we validated the expression of hub SRG ABI3 by Sc-RNA seq analysis and explored the underlying mechanism of ABI3 in THP-1-derived macrophages and mouse atherosclerotic lesions. RESULTS: A total of 15 DE-SRGs were identified in macrophage-rich plaques, with five hub DE-SRGs (ABI3, CAV1, NINJ1, Nox4 and YAP1) were further screened using three machine learning algorithms. Subsequently, a nomogram predictive model confirmed the high validity of the five hub DE-SRGs for evaluating atherosclerotic plaque progression. Further, the ABI3 expression was upregulated in macrophages of advanced plaques and senescent THP-1-derived macrophages, which was consistent with the bioinformatics analysis. ABI3 knockdown abolished macrophage senescence, and the NF-κB signaling pathway contributed to ABI3-mediated macrophage senescence. CONCLUSION: We identified five cellular senescence-associated genes for atherogenesis progression and unveiled that ABI3 might promote macrophage senescence via activation of the NF-κB pathway in atherogenesis progression, which proposes new preventive and therapeutic strategies of senolytic agents for atherosclerosis.

Identification of the Maize LEA Gene Family and Its Relationship with Kernel Dehydration.

Maize, the most widely planted and highest yielding of the three major crops in the world, requires the development and breeding of new varieties to accommodate the shift towards mechanized harvesting. However, the moisture content of kernels during harvest poses a significant challenge to mechanized harvesting, leading to seed breakage and increased storage costs. Previous studies highlighted the importance of LEA (Late Embryogenesis Abundant) members in regulating kernel dehydration. In this study, we aimed to gain a better understanding of the relationship between the LEA family and grain dehydration in maize. Through expression pattern analysis of maize, we identified 52 LEA genes (ZmLEAs) distributed across 10 chromosomes, organized into seven subgroups based on phylogenetic analysis, gene structure, and conserved motifs. Evolutionary and selective pressure analysis revealed that the amplification of ZmLEA genes primarily resulted from whole-genome or fragment replication events, with strong purifying selection effects during evolution. Furthermore, the transcriptome data of kernels of two maize inbred lines with varying dehydration rates at different developmental stages showed that 14 ZmLEA genes were expressed differentially in the two inbreds. This suggested that the ZmLEA genes might participate in regulating the kernel dehydration rate (KDR) in maize. Overall, this study enhances our understanding of the ZmLEA family and provides a foundation for further research into its role in regulating genes associated with grain dehydration in maize.

Nanoparticle albumin-bound paclitaxel-based neoadjuvant regimen: A promising treatment option for HER2-low-positive breast cancer.

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

Combination of a Push-Pull-Block Strategy with a Heterologous Xylose Assimilation Pathway toward Lipid Overproduction from Lignocellulose in Yarrowia lipolytica.

The production of biodiesel using microbial lipids derived from renewable lignocellulosic biomass is considered a promising strategy to reduce environmental pressure and promote the green energy transition. The hydrolysates of lignocellulosic biomass are rich in glucose and xylose, which makes it crucial to efficiently utilize both sugars. Here, we combined metabolic engineering and adaptive laboratory evolution (ALE) to construct an engineered Yarrowia lipolytica strain that can efficiently produce lipids from glucose and xylose. First, the "Push-Pull-Block" strategy was adopted to increase lipid content to 73.42% of the dry cell weight (DCW). Then, a heterologous xylose-utilization pathway was integrated into the engineered strain, which was subjected to ALE. The final evolved strain could accumulate 53.64% DCW of lipids from xylose, and the lipid titer reached 16.25 g/L. This work sheds light on the potential of microbial lipid overproduction from lignocellulose using engineered Y. lipolytica.

Impact of Anaemia on HbA1c Interpretation Among Normogylcaemic Individuals With Diabetes Mellitus: A Clinical Laboratory Observational Study.

BACKGROUND AND AIM: Over the past decades, glycosylated haemoglobin (HbA1c) has been a gold standard for monitoring diabetes control over a long period, relative to blood glucose level (BGL) which measures short-term results. It is speculated that anaemia and factors that induce haemolysis may cause falsely elevated HbA1c leading to 'false positive' interpretations. This study aimed to investigate how anaemia impacts HbA1c. METHODS: This was a pathology-based observational pilot study using archived data of diabetic subjects monitored with both BGL and HbA1c in regional New South Wales (NSW), Australia. A total of 28,487 cases of blood glucose results were pooled and those with HbA1c and anaemia results were evaluated for correlation with the BGL results. Data collection was limited to de-identified information from the laboratory information system, hence details on the ethnicity and medical history were unavailable. Descriptive frequencies and Pearson correlations were performed. RESULTS: In the pooled data, 53.36% of individuals were females, and 50.54% had BGL ≥5.6 mmol/L. In the pilot dataset, the majority (64.86%) were males, 18.92% with BGL ≤5.6 mmol/L and 67.57% had HbA1c (≥6.5%). In the entire dataset, BGL was moderately and positively correlated with HbA1c (r = 0.6), whereas in the subset of individuals with normo-BGL and anaemia, the correlation was negative (r = -0.2). DISCUSSION: This pilot investigation observed a pertinent issue, which is a negative correlation between glycaemia and HbA1c in patients with anaemia. HbA1c was falsely increased despite normal blood glucose levels in individuals with anaemia. This advances the speculation that anaemia falsely increases HbA1c. Therefore, caution is necessary while interpreting HbA1c results for patients with anaemia, and new methods for interpretation are required.

Evidence Based Management of Acute Heart Failure in the Era of COVID-19 Pandemic.

This editorial is to highlight current issues of heart failure management during COVID-19 pandemic.

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. METHODS: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). RESULTS: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. CONCLUSIONS: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

Association Between Prior Calcium Channel Blocker Use and Mortality in Septic Patients: A Meta-Analysis of Cohort Studies.

Background: The aim of this study was to comprehensively review the literature and synthesize the evidence concerning the relationship between prior calcium channel blocker (CCB) use and mortality in patients with sepsis. Methods: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cochrane CENTRAL, and Web of Science databases were searched from their inception to April 9, 2020. Cohort studies related to prior calcium channel blocker use in patients with sepsis were analyzed. Pairs of reviewers independently screened the studies, extracted the data, and assessed the risk of bias. The primary outcome of 90-days mortality or secondary outcome of short-term mortality, including 30-days, Intensive Care Unit (ICU), and in-hospital mortality, were analyzed. Heterogeneity among studies was assessed using the I 2 statistic and was considered moderate if I 2 was 50-75% and high if I 2 was ≥75%. Random-effects models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). The quality of the studies was evaluated with the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were performed to examine the robustness of the results. Results: In total, 639 potentially relevant studies were identified, and the full texts of 25 articles were reviewed. Ultimately, five cohort studies involving 280,982 patients were confirmed to have a low risk of bias and were included. Prior CCB use was associated with a significantly lower 90-days mortality in sepsis patients [OR, 0.90 (0.85-0.95); I 2 = 31.9%]. Moreover, prior CCB use was associated with a significantly reduced short-term mortality rate in septic shock patients [OR, 0.61 (0.38-0.97); I 2 = 62.4%] but not in sepsis patients [OR, 0.83 (0.66-1.04); I 2 = 95.4%]. Conclusion: This meta-analysis suggests that prior CCB use is significantly associated with improved 90-days mortality in sepsis patients and short-term mortality in septic shock patients. This study provides preliminary evidence of an association between prior CCB use and mortality in sepsis patients.

Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies.

INTRODUCTION: Cefprozil, an oral second-generation semi-synthetic cephalosporin, possesses a broad spectrum of antimicrobial activity. A granule formulation has been developed to improve medication adherence of the patients. This study was conducted to assess the bioequivalence of the granule formulation to a dry suspension in healthy Chinese volunteers and estimate the pharmacokinetic (PK) profiles of cefprozil. METHODS: An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 60 healthy Chinese volunteers under fasted or fed conditions (30 volunteers for each condition) to assess the bioequivalence between two formulations of cefprozil. Blood samples were collected at specified time intervals, and the plasma concentrations of cis- and trans-cefprozil were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events (AEs) were also recorded. RESULTS: Under fasted conditions, the mean Cmax was (3534.70 ± 634.67) ng/ml, Tmax was (0.98 ± 0.25) h, t1/2 was (1.37 ± 0.13) h and AUC0-t was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean Cmax was (2438.80 ± 493.78) ng/ml, Tmax was (1.66 ± 0.76) h, t1/2 was (1.36 ± 0.24) h and AUC0-t was (9332.36 ± 1373.61) ng·h/ml, respectively. The PK parameters of the granule formulation of cefprozil were similar to those of the suspension. The 90% CI values of the GMRs of Cmax, AUC0-t and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence range (80.00-125.00%). CONCLUSIONS: According to the criteria for bioequivalence, the test granule formulations of cefprozil and "Cefprozil for Suspension®" were determined to be bioequivalent whether under fasted or fed conditions by measurement of cis-, trans- and total cefprozil. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04414254.

Icariin treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function.

Icariin, a flavonoid isolated from traditional oriental herbal medicines, has been demonstrated to exhibit several health benefits in animal models and in humans. The aim of the present study was to investigate the effect of Icariin on hyperglycemia in type 2 diabetes mellitus (T2DM) in rats. A model of diabetes was established in 50 Sprague Dawley rats using a high-sugar and high-fat diet and peritoneal injection of streptozotocin. Diabetic rats were divided into five groups: Diabetic control; metformin; and rats treated with three different doses of Icariin, 5, 10 and 20 mg/kg. Body weight and blood glucose levels were measured, and serum adiponectin levels, expression of phospho-AMP mediated protein kinase (p-AMPK) and glucose transporter isoform 4 (GLUT-4) were measured using ELISA, Realtime PCR and western blotting, respectively. Diabetic rats without drug treatment exhibited reduced body weight, increased blood glucose levels and decreased the number of islets. In T2DM rats treated with 10 or 20 mg/kg Icariin, the blood glucose levels were reduced, whereas serum adiponectin levels were not affected. Additionally, the mRNA and protein expression levels of p-AMPK and GLUT-4 protein were increased in the T2DM rats treated with Icariin. In conclusion, in the diabetes rat model, Icariin alleviated the severity of diabetes, and the effects may be associated with reduction of hyperglycemia by activating an AMPK/GLUT-4 pathway.

Nurse-led psychological intervention reduces anxiety symptoms and improves quality of life following percutaneous coronary intervention for stable coronary artery disease.

OBJECTIVE: To study the effect of nurse-led counselling on the anxiety symptoms and the quality of life following percutaneous coronary intervention for stable coronary artery disease. DESIGN: Randomised control trial. SETTING: Rural and remote China. PARTICIPANTS: Rural and remote patients were consecutively recruited from a medical centre located in China between January and December 2014. INTERVENTIONS: The control group received standard pre-procedure information from a ward nurse on the processes of the hospitalisation and percutaneous coronary intervention, and post-procedural care. The intervention group received a structured 30-minute counselling session the day before and 24 hours after the percutaneous coronary intervention, by nurse consultants with qualifications in psychological therapies and counselling. The health outcomes were assessed by a SF-12 scale and the Seattle Angina Questionnaire at 6 and 12 months after percutaneous coronary intervention. The anxiety and depression symptoms were evaluated by a Zung anxiety and depression questionnaire. MAIN OUTCOME MEASURES: Cardiac outcomes, quality of life and mental health status. RESULTS: Eighty patients were randomly divided into control (n = 40) and intervention groups (n = 40). There was a significant increase in the scores of the three domains of Seattle Angina Questionnaire 12 months after percutaneous coronary intervention in the intervention group (P < .01). The mental health and physical health scores also increased (P < .01). In the control group, the mean scores of Zung self-rating anxiety scale 12 months following percutaneous coronary intervention were higher than the baseline scores, and higher than in the intervention group (P < .01). CONCLUSIONS: Counselling by a clinician qualified in psychological therapies and counselling significantly reduces anxiety symptoms and improves quality of life.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction.

BACKGROUND/OBJECTIVES: Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3η signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 (Cav-1F92A) gene may enhance NO production. This study explored the effect of Cav-1F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1F92A) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3η signal transduction in a rat model of monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). METHOD: PAH was induced in rats through the subcutaneous injection of MCT. Next, rBMSC/Vector (negative control), rBMSC/Cav-1, rBMSC/Cav-1F92A, or rBMSC/Cav-1F92A+L-NAME were administered to the rats. Changes in pulmonary hemodynamic and vascular morphometry and oxidative stress levels were evaluated. CA1/kininogen and SelW/14-3-3η signal transduction, endothelial nitric oxide synthase (eNOS) dimerization, and eNOS/NO/sGC/cGMP pathway changes were determined through real-time polymerase chain reaction, Western blot, or immunohistochemical analyses. RESULTS: In MCT-induced PAH rats, rBMSC/Cav-1F92A treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3η signal transduction; and reactivated the NO pathway. CONCLUSIONS: In a rat model of MCT-induced PAH, rBMSC/Cav-1F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.

Vascular Morphology has No Direct Relationship with Atherosclerotic Plaque Burden in Patients with Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND: The vascular morphology and the characteristics of atherosclerotic plaques in the middle cerebral artery (MCA) have not been fully studied with high-resolution magnetic resonance imaging (HR-MRI). OBJECTIVE: HR-MRI was applied to investigate vascular morphology and atherosclerotic plaque in patients with symptomatic MCA stenosis. MATERIALS AND METHODS: A total of 343 patients with symptomatic MCA stenosis were enrolled in this study. All the patients were examined by HR-MRI to analyze the morphology of MCA and the M1 segment (MCA-M1), the characteristics and the location of the plaques. RESULTS: The proportion of L-shaped MCA-M1 decreased, while the proportion of S-shaped MCAM1 increased with age. The anterior plaques were the most common in all the patients. The superior plaques were relatively common in patients with L-shaped and U-shaped MCA-M1, while the inferior plaques were relatively common in patients with inverted U-shaped and S-shaped MCAM1. Among all the plaques, the majority were isointense or heterogeneous. The MCA-M1 morphology had no direct relationship with the common risk factors of atherosclerosis and the clinical outcomes of the patients after 12 months of follow up. CONCLUSION: The morphology of MCA-M1 is not directly related to the plaque burden or the degree of stenosis in patients with symptomatic MCA stenosis. The morphology of MCA-M1 is not associated with the risk factors of atherosclerosis, or the clinical outcomes of the patients.

Adipose-derived mesenchymal stem cells ameliorate acute liver injury in rat model of CLP induced-sepsis via sTNFR1.

Sepsis is characterized as exceed inflammation response and multiple organs dysfunction. Many articles suggested that mesenchymal stem cells can alleviate the inflammation and improve the survival rate of inflammatory animal models, however, the mechanism is still unclear. This study aimed to test the hypothesis that rat adipose-derived mesenchymal stem cells (ADMSCs) produce a amount of soluble tumour necrosis factor receptor 1 (sTNFR1), which ameliorated liver injury and inflammation and increased the survival rate of septic rat model.120 adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated (Sham), sepsis-induced by cecal ligation and puncture (CLP), shNC (injected 1 × 106 ADMSCs with transfected with scramble shRNA 1 h after CLP), and shsTNFR1 (injected 1 × 106 ADMSCs with transfected with sTNFR1 1 h after CLP). The serum sTNFR1 levels were the lowest in Sham and highest in shNC group. ADMSCs could decrease the levels of pro-inflammatory cytokines such as TNF-α, IL-6, AP-1 c-jun and NF-κB p56 after CLP administration, whereas this result was weaken by shsTNFR1 administration. Moreover, shNC had an increased levels of the anti-inflammatory factor IL-10 compared with CLP, and this change could be weakened in shsTNFR1 administration. More importantly, ADMSCs could improve the survival rate of CLP-induced septic rats. Therapeutically administered ADMSCs secrete sTNFR1, which alleviated the liver injury and inflammatory response. Additionally, ADMSCs also ameliorated the systematic inflammation and increased the survival rate of septic rats.

A Bacillus-based Coxsackie virus A16 mucosal vaccine induces strong neutralizing antibody responses.

The purpose of this study was to construct a Coxsackie virus A16 (CA16) mucosal vaccine and evaluate its ability to induce immune response. VP1 gene of CA16 was inserted into the genome of Bacillus subtilis via recombination and displayed on the surface of the spores. This Bacillus-based vaccine was used for intranasal immunization of mice and the serum antibody titer was determined by enzyme-linked immunosorbent assay (ELISA). Neutralization activity of the serum from immunized mice was analyzed by an in vitro neutralizing test. VP1 gene was successfully integrated into the genome of Bacillus subtilis and was expressed on the surface of Bacillus spores. Intranasal immunization of mice with this vaccine induced a higher level of VP1 specific IgA and IgG than in mice of the control group (p < 0.05). The neutralizing antibody titer in the spore immunization group was 1 : 169, which was higher than that in the control group (p < 0.05). We concluded that vaccine prepared by displaying CA16 VP1 protein on the surface of Bacillus subtilis spores can stimulate mice to produce protective neutralizing antibodies, which provides foundations for the development of CA16 mucosal vaccine.