Immunomodulatory roles of metalloproteinases in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, autoimmune pathology characterized by persistent synovial inflammation and gradually advancing bone destruction. Matrix metalloproteinases (MMPs), as a family of zinc-containing enzymes, have been found to play an important role in degradation and remodeling of extracellular matrix (ECM). MMPs participate in processes of cell proliferation, migration, inflammation, and cell metabolism. A growing number of persons have paid attention to their function in inflammatory and immune diseases. In this review, the details of regulation of MMPs expression and its expression in RA are summarized. The role of MMPs in ECM remodeling, angiogenesis, oxidative and nitrosative stress, cell migration and invasion, cytokine and chemokine production, PANoptosis and bone destruction in RA disease are discussed. Additionally, the review summarizes clinical trials targeting MMPs in inflammatory disease and discusses the potential of MMP inhibition in the therapeutic context of RA. MMPs may serve as biomarkers for drug response, pathology stratification, and precision medicine to improve clinical management of rheumatoid arthritis

Viral Aetiology in Adults with Acute Upper Respiratory Tract Infection in Jinan, Northern China

Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n=596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14–25-year-old group than in the 26–65-year-old group. Codetection rates were higher (7.52%) in the 14–25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China

Highly stable gasified straw slag as a novel solid base catalyst for the effective synthesis of biodiesel: Characteristics and performance

A novel solid base catalyst derived from gasified straw slag for producing biodiesel was prepared by simple pulverization and sieving. This catalyst exhibited high stability, low leaching of the catalytic species, and good catalytic activity, caused by high -temperature melting in the biomass gasifier. SiO2, CaO, K2O, MgO, FeO, and A1(2)O(3) were the common constituents (calculated as oxides) as per XRF analysis and EA. XRD and TEM-EDS analysis indicated that the catalyst comprises three crystallites: quartz, leucite, and dkermanite. The catalyst was strongly basic with a basic site concentration of 0.3974 mniol.g(-1), including strongly basic low-coordination oxygen anions, moderately basic OH groups, and metal-oxygen pairs, as identified by CO2-TPD and IR. TGA results indicated that the catalyst is thermally stable up to 400 degrees C, which is greater than the typical reaction temperature. BET analysis results indicated that the slag exhibits a broad pore distribution with pore diameters of 5-15 and 45-75 nm. The catalyst exhibited high catalytic activity and stability, exhibiting a fatty acid methyl ester (FAME) conversion of 95% for transesterification conducted at 200 degrees C for 8 h with a catalyst dose of 20% and a methanol-oil molar ratio of 12:1. The FAME conversion remained greater than 85% even after reusing the catalyst for 33 reactions without any appreciable loss of catalytic activity. Small amounts of K and Mg (<10 ppm) leached into the product from the catalyst. These results indicated that the gasified straw slag catalyst demonstrates promise for producing biodiesel. (C) 2017 Elsevier Ltd. All rights reserved

Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy

Abstract Background Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short‐rib polydactyly syndrome (SRPS)‐like phenotype. Method Karyotyping and NGS‐based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole‐exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. Results No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS‐like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. Conclusion Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling

Characterization and annotation of Babesia orientalis apicoplast genome

Abstract Background Babesia orientalis is an obligate intraerythrocytic protozoan parasite of the buffalo (Bubalus bubalis, Linnaeus, 1758) transmitted by the tick Rhipicephalus heamaphysaloides. It is the causative agent of water buffalo babesiosis, one of the most important pathogens of water buffalo in central and southern China. As a member of the phylum Apicomplexa, B. orientalis possesses a relatively independent and alga originated organelle the apicoplast. Apicoplasts in other apicomplexa parasites are involved in the biosynthesis of haem, fatty acids, iron-sulphur clusters and isoprenoids. Some of these metabolic pathways were shown to be essential for parasite survival, therefore can serve as potential drug targets. Methods 30 pairs of primers were designed based on the full genome sequence of B. orientalis (unpublished data) and by aligning reported apicoplast genomes of Babesia bovis and Theileria parva. Conventional PCRs was performed to obtain overlapped fragments to cover the whole apicoplast genome. Then the apicoplast genome of B.orientalis was sequenced, assembled and aligned with reported apicoplast genomes of B. bovis and T. parva. The obtained apicoplast genome was annotated by using Artemis and comparing with published apicomplexan apicoplast genomes. The SSU and LSU nucleotide sequences generated were used in a phylogenetic analysis using the maximum likelihood implemented in MAGE 6.0. Results We have obtained and analyzed the complete genome sequence of the B. orientalis apicoplast. It consisted of a 33.2 kb circular DNA (78.9 % A + T). The apicoplast genome unidirectionally encodes one large and one small subunit ribosomal RNAs, 24 tRNA genes, 4 DNA-dependent RNA polymerase beta subunits (rpoB, rpoC1, rpoC2a and rpoC2b), 17 ribosomal proteins, one EF-Tu elongation factor, 2 Clp protease chaperones, and 14 hypothetical proteins. In addition, it includes two copies of the clpC gene. The structure and organization of the B. orientalis apicoplast genome are most similar to those of the B. bovis apicoplast. Conclusions This is the first report of the complete sequence of the B. orientalis apicoplast genome. This information should be useful in the development of safe and efficient treatment against buffalo babesiosis

The overexpression of Rps14 in Lgr5+ progenitor cells promotes hair cell regeneration in the postnatal mouse cochlea

Sensory hair cells (HCs) in the cochlea cannot regenerate spontaneously in adult mammals after being damaged by external or genetic factors. However, several genes and signaling pathways are reported to induce cochlear HC regeneration at the early neonatal stage. Rps14 encodes a ribosomal protein that is involved in the regulation of cell differentiation and proliferation in mammals. However, its roles in the cochlea have not been reported in vivo. Here, we specifically overexpressed Rps14 in Lgr5+ progenitor cells in the newborn mouse cochlea and found that Rps14 conditional overexpression (cOE) mice had significantly increased the ectopic HCs, including inner and outer HCs. We further explored the source of these ectopic HCs and found no EdU+ supporting cells observed in the Rps14 cOE mice. The lineage tracing results, on the other hand, revealed that Rps14 cOE mice had significantly more tdTomato+ HCs in their cochleae than control mice. These results indicated that regenerated HCs by cOE of Rps14 are most likely derived from inducing the direct trans-differentiation of Lgr5+ progenitor cells into HCs. Moreover, real-time qPCR results suggested that the transcription factor genes Atoh1 and Gfi1, which are important in regulating HC differentiation, were upregulated in the cochlear basilar membrane of Rps14 cOE mice. In summary, this study provides in vivo evidence that, in the postnatal mouse cochlea, Rps14 is a potential gene that can promote the spontaneous trans-differentiation of Lgr5+ progenitor cells into HCs. This gene may one day be exploited as a therapeutic target for treating hearing loss

Additional file 1: Table S1. of Characterization and annotation of Babesia orientalis apicoplast genome

PCR primers used in sequencing the Babesia orientalis apicoplast genome. (DOC 67 kb

Additional file 1: Table S1. of Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats

Nutritional Composition of Diets. Table S2 Fatty acid Composition of fish oil. (DOCX 13 kb

Additional file 2: Figure S1. of Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats

Chromatogram of fish oil. (JPG 387 kb