The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system

BACKGROUND: Previous in vivo studies have shown that mesenchymal stem cell (MSC) transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus. METHODS: To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA). Orphan nuclear receptor gamma (ROR-γ) mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF-α) in the cell culture supernatant were measured using a flow cytometric bead capture method. RESULTS: After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p < 0.05). Moreover, the decrement was positively related to the disease activity of RA (p < 0.05). Decreased secretion of IL-17, TNF-α and IL-6 were also found in co-culture supernatants of PBMCs from patients with severe and moderate disease activity, but not in supernatant from PBMCs cultured alone. The decreased cytokine expression levels were positively correlated to the concentrations of MSCs. In contrast, PBMCs from healthy controls or patients with mild RA did not show significant differences in ROR-γ expression or cytokine secretion following co-culture with MSCs as compared with those cultured alone. CONCLUSIONS: In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators

Research progress of vascularization strategies of tissue-engineered bone

The bone defect caused by fracture, bone tumor, infection, and other causes is not only a problematic point in clinical treatment but also one of the hot issues in current research. The development of bone tissue engineering provides a new way to repair bone defects. Many animal experimental and rising clinical application studies have shown their excellent application prospects. The construction of rapid vascularization of tissue-engineered bone is the main bottleneck and critical factor in repairing bone defects. The rapid establishment of vascular networks early after biomaterial implantation can provide sufficient nutrients and transport metabolites. If the slow formation of the local vascular network results in a lack of blood supply, the osteogenesis process will be delayed or even unable to form new bone. The researchers modified the scaffold material by changing the physical and chemical properties of the scaffold material, loading the growth factor sustained release system, and combining it with trace elements so that it can promote early angiogenesis in the process of induced bone regeneration, which is beneficial to the whole process of bone regeneration. This article reviews the local vascular microenvironment in the process of bone defect repair and the current methods of improving scaffold materials and promoting vascularization

Epigenetic Enzyme Mutations: Role in Tumorigenesis and Molecular Inhibitors

Epigenetic modifications, such as DNA methylation and histone modification, result in heritable changes in gene expression without changing the DNA sequence. Epigenetic regulatory enzymes such as DNA methyltransferases, histone methyltransferases, and histone deacetylases are involved in epigenetic modification. Studies have shown that the dysregulation caused by changes in the amino acid sequence of these enzymes is closely correlated with tumor onset and progression. In addition, certain amino acid changes in the metabolic enzyme isocitrate dehydrogenase (IDH) are linked to altered epigenetic modifications in tumors. Some small molecule inhibitors targeting these aberrant enzymes have shown promising anti-cancer efficacy in preclinical and clinical trials. For example, the small molecule inhibitor ivosidenib, which targets IDH1 with a mutation at R132, has been approved by the FDA for the clinical treatment of acute myeloid leukemia. In this review, we summarize the recurrent “hotspot” mutations in these enzymes in various tumors and their role in tumorigenesis. We also describe candidate inhibitors of the mutant enzymes which show potential therapeutic value. In addition, we introduce some previously unreported mutation sites in these enzymes, which may be related to tumor development and provide opportunities for future study

Impact of family integrated care on infants’ clinical outcomes in two children’s hospitals in China: a pre-post intervention study

© 2018 The Author(s). Background: Most Neonatal Intensive Care Units (NICUs) in China have restricted visiting policies for parents. This also implicates that parents are not involved in the care of their infant. Family Integrated Care (FIC), empowering parents in direct care delivery and decisions, is becoming the standard in NICUs in many countries and can improve quality-of-life and health outcomes of preterm infants. The aim of this study was to evaluate the impact of a FIC intervention on the clinical outcomes of preterm infants with Bronchopulmonary Dysplasia (BPD). Methods: A pre-post intervention study was conducted at NICUs in two Chinese children's hospitals. Infants with BPD were included: pre-intervention group (n = 134) from December 2015 to September 2016, post-intervention (FIC) group (n = 115) and their parents from October 2016 to June 2017. NICU nurses were trained between July and September 2016 to deliver the FIC intervention, including parent education and support. Parents had to be present and care for their infant minimal three hours a day. The infants' outcome measures were length-of-stay, breastfeeding, weight gain, respiratory and oxygen support, and parent hospital expenses. Results: Compared with control group (n = 134), the FIC group (n = 115) had significantly increased breastfeeding rates (83% versus 71%, p = 0.030), breastfeeding time (31 days versus 19 days, p &lt; 0.001), enteral nutrition time (50 days versus 34 days, p &lt; 0.001), weight gain (29 g/day versus 23 g/day, p = 0.002), and significantly lower respiratory support time (16 days versus 25 days, p &lt; 0.001). Oxygen Exposure Time decreased but not significant (39 days versus 41 days p = 0.393). Parents hospital expenses in local Chinese RMB currency was not significant (84 K versus 88 K, p = 0.391). Conclusion: The results of our study suggests that FIC is feasible in two Chinese NICUs and might improve clinical outcomes of preterm infants with BPD. Further research is needed to include all infants admitted to NICUs and should include parent reported outcome measures. Our study may help other NICUs with limited parental access to implement FIC to enhance parental empowerment and involvement in the care of their infant

Altered expression of miRNAs and mRNAs reveals the potential regulatory role of miRNAs in the developmental process of early weaned goats.

MicroRNAs (miRNAs) play pivotal roles in growth, development, and stress responses. However, the regulatory function of miRNAs in early weaned goats remains unclear. Deep sequencing comparison of mRNA and miRNA expression profiles showed that 18 miRNAs and 373 genes were differentially expressed in pre- and post-weaning Chongming white goats. Bioinformatics analysis indicated that these differentially expressed genes are involved in cellular processes, developmental processes, and growth in terms of biological process analysis. KEGG analysis showed that downregulated genes were enriched in salivary secretion, bile secretion, vascular smooth muscle contraction, and calcium signaling pathways. Additionally, a miRNA-mRNA co-expression network of the 18 dysregulated miRNAs and their 107 target mRNAs was constructed using a combination of Pearson's correlation analysis and prediction by miRanda software. Among the downregulated miRNAs, two (chi-miR-206 and chi-miR-133a/b) were muscle development-related and the others were cell proliferation associated. Further RT-qPCR analysis confirmed that downregulated miRNAs (chi-miR-99b-3p, chi-miR-224, and chi-miR-10b-5p) were highly expressed in muscle tissues (heart, spleen, or kidney) of the rapid growth period (7-month old) in Chongming white goats. The results of the present study suggested that weaning induced cell proliferation repression in post-weaning goats, providing new insight into the mechanism of muscle development of goats, although additional details remain to be elucidated in the future

Enhancing the Anticancer Efficacy of Immunotherapy through Combination with Histone Modification Inhibitors

In the nucleus of each cell, the DNA is wrapped around histone octamers, forming the so-called &#8220;nucleosomal core particles&#8222;. The histones undergo various modifications that influence chromatin structure and function, including methylation, acetylation, ubiquitination, phosphorylation, and SUMOylation. These modifications, known as epigenetic modifications (defined as heritable molecular determinants of phenotype that are independent of the DNA sequence), result in alterations of gene expression and changes in cell behavior. Recent work has shown that epigenetic drugs targeting histone deacetylation or methylation modulate the immune response and overcome acquired resistance to immunotherapy. A number of combination therapies involving immunotherapy and epigenetic drugs, which target histone deacetylation or methylation, are currently under various clinical/pre-clinical investigations and have shown promising anticancer efficacy. These combination therapies may provide a new strategy for achieving sustained anticancer efficacy and overcoming resistance

Optimization of the Process of Compound Enzymatic Hydrolysis of Soluble Protease Preparation

soluble protease preparations, including trypsin, papain and other preparations, are widely used in various fields, such as medicine, agriculture, industry and so on. Based on this, this paper takes the soluble protease as the main research object, and uses the experimental method of compound enzymolysis to observe and analyze the utilization of egg membrane protein, so as to improve the utilization rate of egg membrane protein

chi-miR-99b-3p Regulates the Proliferation of Goat Skeletal Muscle Satellite Cells In Vitro by Targeting <i>Caspase</i>-<i>3</i> and <i>NCOR1</i>

We previously found that chi-miR-99b-3p was highly expressed in the skeletal muscle of 7-month-old (rapid growth period) goats and speculated that it may be associated with muscle development. To further investigate the role of chi-miR-99b-3p in goats, we found that chi-miR-99b-3p acted as a myogenic miRNA in the regulation of skeletal muscle development. Dual-luciferase reporter assays, qRT-PCR, and Western blot results confirmed that Caspase-3 and nuclear receptor corepressor 1 were direct targets for chi-miR-99b-3p as their expression was inhibited by this miR. Cell proliferation and qRT-PCR assays showed that chi-miR-99b-3p promoted proliferation through relevant targets and intrinsic apoptosis-related genes in goat skeletal muscle satellite cells (SMSCs), whereas inhibition of chi-miR-99b-3p had the opposite effect. Furthermore, integrative transcriptomic analysis revealed that overexpression of chi-miR-99b-3p induced various differentially expressed (DE) genes mainly associated with the cell cycle, relaxin signaling pathway, DNA replication, and protein digestion and absorption. Notably, most of the cell-cycle-related genes were downregulated in SMSCs after miR-99b-3p upregulation, including the pro-apoptosis-related gene BCL2. In addition, 47 DE miRNAs (16 upregulated and 31 downregulated) were determined by Small RNA-sequencing in SMSCs after chi-miR-99b-3p overexpression. Based on the KEGG enrichment analysis, we found that these DE miRNAs were involved in the biological pathways associated with the DE genes. Our study demonstrated that chi-miR-99b-3p was an effective facilitator of goat SMSCs and provided new insights into the mechanisms by which miRNAs regulate skeletal muscle growth in goats

Using Lidar technology to assess regional air pollution and improve estimates of PM2.5 transport in the North China Plain

Air pollutants seriously impact climate change and human health. In this study, the gridpoint statistical interpolation (GSI) three-dimensional variational data assimilation system was extended from ground data to vertical profile data, which reduced the simulation error of the model in the vertical layer. The coupled GSI-Lidar-WRF-Chem system was used to improve the accuracy of fine particulate matter (PM _2.5 ) simulation during a wintertime heavy pollution event in the North China Plain in late November 2017. In this experiment, two vehicle-mounted Lidar instruments were utilized to make synchronous observations around the 6th Ring Road of Beijing, and five ground-based Lidars were used for long-term network observations on the North China Plain. Data assimilation was then performed using the PM _2.5 vertical profile retrieved from the seven Lidars. Compared with the model results, the correlation of assimilation increased from 0.74–0.86, and the root-mean-square error decreased by 36.6%. Meanwhile, the transport flux and transport flux intensity of the PM _2.5 were analyzed, which revealed that the PM _2.5 around the 6th Ring Road of Beijing was mainly concentrated below 1.8 km, and there were obvious double layers of particles. Particulates in the southwest were mainly input, while those in the northeast were mainly output. Both the input and output heights were around 1 km, although the input intensity was higher than the output intensity. The GSI-Lidar-WRF-Chem system has great potential for air quality simulation and forecasting