Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.5% genomes), and performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed rare diseases from 6,004 families. We established a collaborative, two-level expert review infrastructure that allowed a genetic diagnosis in 506 (8.4%) families. Of 552 disease-causing variants identified, 464 (84.1%) were single-nucleotide variants or short insertions/deletions. These variants were either located in recently published novel disease genes (n = 67), recently reclassified in ClinVar (n = 187) or reclassified by consensus expert decision within Solve-RD (n = 210). Bespoke bioinformatics analyses identified the remaining 15.9% of causative variants (n = 88). Ad hoc expert review, parallel to the systematic reanalysis, diagnosed 249 (4.1%) additional families for an overall diagnostic yield of 12.6%. The infrastructure and collaborative networks set up by Solve-RD can serve as a blueprint for future further scalable international efforts. The resource is open to the global rare-disease community, allowing phenotype, variant and gene queries, as well as genome-wide discoveries.

• MeSH
• databáze genetické MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• genomika * metody   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• rodokmen MeSH
• výpočetní biologie MeSH
• vzácné nemoci * genetika   diagnóza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

• Publikační typ
• tisková chyba MeSH

We collected O- and A-horizon soil samples in 26 Chinese mountainous forests to investigate the content, spatial pattern, and potential sources of polychlorinated naphthalenes (PCNs). Spatial patterns were influenced mainly by the approximation to sources and soil organic contents. High concentrations often occurred close to populated or industrialized areas. Combustion-related activities contributed to PCN pollution. Relatively high proportions of CN-73 in northern China may be attributed to coke consumption, while CN-51 could be an indicator of biomass burning in Southwest China. There are evidences that PCNs may largely derived from unintentional production. If uncontrolled, UP-PCN (unintentionally produced PCNs) emissions could increase with industrial development. The abnormally high concentrations at Gongga and Changbai Mountains appear to be associated with the high efficient of forest filter of atmospheric contaminants at these densely forested sites. We question whether this is caused by ecotones between forests, and raise additional questions for future analyses.

• Klíčová slova
• Chinese forest soil, Combustion-related sources, Ecotone, PCNs, SOC,
• MeSH
• látky znečišťující půdu chemie   MeSH
• látky znečišťující vzduch chemie   MeSH
• naftaleny chemie   MeSH
• půda chemie   MeSH
• spontánní samovznícení MeSH
• znečištění životního prostředí analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Čína MeSH
• Názvy látek
• látky znečišťující půdu MeSH
• látky znečišťující vzduch MeSH
• naftaleny MeSH
• půda MeSH

Inflammasomes function as immune-signaling platforms that were assembled following detection of pathogens. NLRP1 and CARD8 are related inflammasomes that use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA domain to initiate the inflammasome. At rest, dipeptidyl peptidases 8 and 9 (DPP8/9) inhibit inflammatory CT by interacting with the function-to-find domain (FIIND) of NLRP1/CARD8 and forming an inhibitory NLRP1/CARD8-DPP9 ternary complex consisting of DPP9, full-length NLRP1/CARD8, and NLRP1/CARD8 CT. However, the specific triggers of NLRP1 and CARD8 have not yet been fully identified. Here, we report that a tick-borne bunyavirus SFTSV infection activates the NLRP1 inflammasome in primary keratinocytes and the CARD8 inflammasome in macrophages in a similar manner by targeting the ternary inhibitory complex, respectively. Mechanistically, SFTSV NSs interact with NLRP1 and CARD8 via their FIIND domains, suggesting that DPP8/9 are likely to compete for binding; on the other hand, NSs promote the degradation of DPP8 and DPP9. Both contribute to more efficient destabilization of the DPP8/9 ternary complex and release the activated CT. Moreover, CARD8 deletion promotes SFTSV replication. In conclusion, we found a novel mechanism of viral protein activation of NLRP1 and CARD8 by disrupting the DPP9-binding checkpoint.

• MeSH
• adaptorové proteiny signální transdukční * metabolismus   imunologie   MeSH
• dipeptidasy * metabolismus   MeSH
• dipeptidylpeptidasy a tripeptidylpeptidasy * metabolismus   MeSH
• inflamasomy * metabolismus   imunologie   MeSH
• keratinocyty virologie   metabolismus   imunologie   MeSH
• lidé MeSH
• makrofágy virologie   metabolismus   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové proteiny MeSH
• NLR proteiny metabolismus   MeSH
• proteiny regulující apoptózu * metabolismus   imunologie   MeSH
• signální adaptorové proteiny CARD * metabolismus   imunologie   MeSH
• virové nestrukturální proteiny * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční * MeSH
• CARD8 protein, human MeSH Prohlížeč
• dipeptidasy * MeSH
• dipeptidyl peptidase 9, mouse MeSH Prohlížeč
• dipeptidylpeptidasy a tripeptidylpeptidasy * MeSH
• DPP9 protein, human MeSH Prohlížeč
• inflamasomy * MeSH
• nádorové proteiny MeSH
• NALP1 protein, mouse MeSH Prohlížeč
• NLR proteiny MeSH
• NLRP1 protein, human MeSH Prohlížeč
• proteiny regulující apoptózu * MeSH
• signální adaptorové proteiny CARD * MeSH
• virové nestrukturální proteiny * MeSH

Mangiferin is a kind of polyphenol chemical compound separated from these herbal medicines of Mangifera indica L., Anemarrhena asphodeloides Bge. and Belamcanda chinensis L., which has anti-inflammatory, anti-virus, and other physiological activities without toxic effects. Osteoarthritis (OA) is a chronic disease that is also a kind of arthritis disease in which articular cartilage or bones under the joint is damaged. In addition, artificial replacements are required in severe cases. At present, there are not too much researches on the potential biological activities of mangiferin that plays a protective role in the treatment of OA. In this study, we evaluated the protective effect of mangiferin on osteoarthritis (OA) in vitro and in vivo. First, the effect of different concentrations of mangiferin on rat chondrocytes was determined by MTT assay. Second, the effects of mangiferin on the expression levels of matrix metalloproteinase (MMP)-13, TNF alpha, Collagen II, Caspase-3, and cystatin-C in interleukin-1beta (IL-1beta)-induced rat chondrocytes were examined by the real-time polymerase chain reaction in vitro, meanwhile the effects of mangiferin on the nuclear factor kappa-B (NF-kappaB) signaling pathway were also investigated by Western Blot. Finally, the anti-osteoarthritic protective effect of mangiferin was evaluated in the rat model by anterior cruciate ligament transection (ACLT) combined with bilateral ovariectomy-induced OA in vivo. The results showed that the mangiferin was found to inhibit the expression of MMP-13, TNF-alpha, and Caspase-3 which also increased the expression of Collagen II and cystatin-C in IL 1beta induced rat chondrocytes. In addition, IL-1beta-induced activation of nuclear factor kappa-B (NF-kappaB) and the degradation of inhibitor of kappaB (IkappaB)-alpha were suppressed by mangiferin. For the in vivo study in a rat model of OA, 100 microl of mangiferin was administered by intra-articular injections for rats, the results showed that the cartilage degradation was suppressed by mangiferin through Micro CT and Histological Examination. According to both in vitro and in vivo results, mangiferin has a protective effect in the treatment of OA which may be a promising therapeutic agent for OA.

• MeSH
• chondrocyty MeSH
• interleukin-1beta MeSH
• kloubní chrupavka * metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• NF-kappa B metabolismus   MeSH
• osteoartróza * farmakoterapie   metabolismus   patologie   MeSH
• xantony * metabolismus   farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-1beta MeSH
• mangiferin MeSH Prohlížeč
• NF-kappa B MeSH
• xantony * MeSH

Infiltrated and activated M1 macrophages play a role in kidney injury and fibrosis during chronic kidney disease (CKD) progression. However, the specific ways that M1 macrophage polarization contributes to renal fibrosis are not fully understood. The study seeks to investigate how miR-92a-3p regulates M1 macrophage polarization and its connection to renal fibrosis in the development of CKD. Our results revealed that miR-92a-3p overexpression increased M1-macrophage activation, iNOS, IL-6, and TNF-alpha expression in RAW264.7 upon LPS stimulation. LIN28A overexpression reversed these effects. Moreover, miR-92a-3p overexpression in RAW264.7 exacerbated NRK-52E cell apoptosis induced by LPS, but LIN28A overexpression counteracted this effect. MiR-92a-3p knockout in unilateral ureteral obstruction (UUO) C57BL/6 mice led to reduced renal infiltration and fibrosis, accompanied by decreased iNOS, alpha-SMA, IL-6, TNF-alpha, and increased LIN28A. In summary, our findings suggest that miR-92a-3p may play a role in promoting renal injury and fibrosis both in vitro and in vivo. This effect is potentially achieved by facilitating M1 macrophage polarization through the targeting of LIN28A.

• MeSH
• aktivace makrofágů MeSH
• fibróza * MeSH
• ledviny patologie   metabolismus   MeSH
• makrofágy * metabolismus   patologie   MeSH
• mikro RNA * metabolismus   genetika   MeSH
• myši inbrední C57BL * MeSH
• myši knockoutované MeSH
• myši MeSH
• proteiny vázající RNA * metabolismus   genetika   MeSH
• RAW 264.7 buňky MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Lin-28 protein, mouse MeSH Prohlížeč
• mikro RNA * MeSH
• Mirn92 microRNA, mouse MeSH Prohlížeč
• proteiny vázající RNA * MeSH

Autophagy is one of the basic cellular mechanism during preimplantation development of mammalian embryos, and it plays crucial role in several physiological processes. It is induced by interleukin (IL)-1β in mammalian cells. Our present study shows that IL-1β is important for autophagy activation in embryo development. Our in vitro culture system analysis shows effect of IL-1β in medium on the development of mouse embryos and it was found to be concentration dependent. A preimplantation embryo culture using medium containing IL-1β did not improve cleavage and blastocyst development rates of mouse embryos; however, blastocyst quality was significantly improved by increasing total cell number, especially in supplementary 20 ng/mL IL-1β. Furthermore, autophagy activation mainly occurs in 2 to 4 cell embryo and blastocyst, 20 ng/mL IL-1β into culture medium can effectively enhance levels of messenger RNA and protein of autophagy-related-factors in 2 to 4 cell embryos and blastocyst, while these factors reduce in VGX-1027 (IL-1β inhibitor) groups that also reduce the quality of blastocyst. Effects of IL-1β on the development of embryo reduced in 20 ng/mL IL-1β supplemented group when 5 mM 3-methyladenine (3-MA) was also added, which used to inhibit autophagy activation in endogenous PtdIns3Ks signal pathway. Our current results show that exogenous IL-1β can effectively induce autophagy in mouse embryos at stages of 2 to 8 cell and blastocyst, that also help to improve the quality of blastocyst.

• Klíčová slova
• IL-1β, assisted reproduction, autophagy, blastocyst quality, cytokine,
• MeSH
• autofagie * MeSH
• blastocysta účinky léků   patologie   MeSH
• embryo savčí účinky léků   patologie   MeSH
• embryonální vývoj účinky léků   MeSH
• interleukin-1beta farmakologie   MeSH
• kultivace embrya MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-1beta MeSH

In the study, high internal phase emulsions (HIPEs) prepared from Antarctic krill oil (AKO) were added into surimi and the effects on gel properties, lipid quality and stability were investigated. It is found that HIPEs-added groups exhibited higher gel strength and lower cooking loss than Oil-added counterparts. HIPEs-added groups had higher proportion of capillary water, and microstructure of HIPEs-added gels showed fewer large voids and small size droplets. HIPEs-added groups also showed less pronounced myosin heavy chain band. HIPEs- and Oil-added gels showed > 3500 mg/kg EPA + DHA and 0.4-0.8 mg/kg astaxanthin, and most HIPEs-added groups had higher levels of them but lower TBARS values. Results suggest AKO-HIPEs could reduce the intervention by lipids on myosin crosslinking during gelation, and protect fatty acids and asxtanthin from oxidation due to oxygen-isolation led by their high accumulation. Thus, AKO-HIPEs can be applied to fortify ω-3 PUFA and maintain good gel properties in surimi product.

• Klíčová slova
• Antarctic krill oil, High internal phase emulsion, Surimi, TBARS, ω-3 PUFA,
• MeSH
• emulze chemie   MeSH
• Euphausiacea * chemie   MeSH
• gely MeSH
• mastné kyseliny chemie   MeSH
• omega-3 mastné kyseliny * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• emulze MeSH
• gely MeSH
• mastné kyseliny MeSH
• omega-3 mastné kyseliny * MeSH

Acute myocardial infarction (AMI) represents the acute manifestation of coronary artery disease. In recent years, microRNAs (miRNAs) have been extensively studied in AMI. This study focused on the role of miR-431-5p in AMI and its effect on cardiomyocyte apoptosis after AMI. The expression of miR-431-5p was analyzed by quantitative real-time PCR (qRT-PCR). By interfering with miR-431-5p in hypoxia-reoxygenation (H/R)-induced HL-1 cardiomyocytes, the effect of miR-431-5p on cardiomyocyte apoptosis after AMI was examined. The interaction between miR-431-5p and selenoprotein T (SELT) mRNA was verified by dual-luciferase reporter assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. Cell viability was examined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The results of qRT-PCR showed that the expression of miR-431-5p in AMI myocardial tissues and H/R-induced HL-1 cardiomyocytes was significantly increased. After interfering with miR-431-5p, the expression of SELT in HL-1 cells was up-regulated, cell apoptosis was decreased, cell viability was increased, and lactate dehydrogenase (LDH) activity was decreased. The dual-luciferase reporter assay confirmed the targeting relationship between miR-431-5p and SELT1 3' untranslated region (UTR). In H/R-induced HL-1 cells, the simultaneous silencing of SELT and miR-431-5p resulted in a decrease of Bcl-2 expression, an increase of Bax expression, and an increase of cleaved-caspase 3 expression compared with silencing miR-431-5p alone. Also, cell viability was decreased, while LDH activity was increased by the simultaneous silencing of SELT and miR-431-5p. Interfering miR-431-5p protected cardiomyocytes from AMI injury via restoring the expression of SELT, providing new ideas for the treatment of AMI.

• MeSH
• apoptóza * genetika   MeSH
• infarkt myokardu * genetika   metabolismus   MeSH
• kardiomyocyty metabolismus   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• myši MeSH
• reperfuzní poškození myokardu * metabolismus   MeSH
• selenoproteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN431 microRNA, human MeSH Prohlížeč
• MIRN431 microRNA, mouse MeSH Prohlížeč
• selenoprotein T, mouse MeSH Prohlížeč
• selenoproteiny MeSH

Porcine deltacoronavirus (PDCoV) is a recently discovered RNA virus that belongs to the family Coronaviridae and genus Deltacoronavirus. This virus causes enteric disease in piglets that is characterized by enteritis and diarrhoea. In our present investigation, 189 diarrhoeic samples were collected between July 2016 and May 2017 from Tibetan pigs inhabiting in three different provinces surrounding the Qinghai-Tibet Plateau of China. We then applied the molecular-based method of reverse transcription polymerase chain reactions (RT-PCRs) to detect the presence of PDCoV in collected samples, and RT-PCR indicated that the prevalence of PDCoV was 3.70% (7/189) in Tibetan pigs. Four of 7 PDCoV-positive pigs were monoinfections of PDCoV, three samples were co-infections of PDCoV with porcine epidemic diarrhoea virus (PEDV), and 52 (27.51%) samples were positive for PEDV. Four strains with different full-length genomes were identified (CHN/GS/2016/1, CHN/GS/2016/2, CHN/GS-/2017/1 and CHN/QH/2017/1), and their genomes were used to analyse the characteristics of PDCoV currently prevalent in Tibetan pigs. We found a 3-nt insertion in the spike gene in four strains in Tibetan pigs. Phylogenetic analysis of the complete genome and spike and nucleocapsid gene sequences revealed that these strains shared ancestors with the strain CHN-AH-2004, which was found in pigs from the Anhui province of China mainland. However, PDCoV strains from Tibetan pigs formed different branches within the same cluster, implying continuous evolution in the field. Our present findings highlight the importance of epidemiologic surveillance to limit the spread of PDCoV in livestock at high altitudes in China.

• Klíčová slova
• China, Qinghai-Tibet Plateau, Tibetan pigs, porcine deltacoronavirus,
• MeSH
• Coronavirus genetika   izolace a purifikace   MeSH
• feces virologie   MeSH
• fylogeneze MeSH
• genom virový genetika   MeSH
• koronavirové infekce diagnóza   epidemiologie   veterinární   virologie   MeSH
• kvantitativní polymerázová řetězová reakce veterinární   MeSH
• nemoci prasat diagnóza   epidemiologie   virologie   MeSH
• prasata virologie   MeSH
• prevalence MeSH
• průjem veterinární   virologie   MeSH
• sekvenční analýza DNA MeSH
• virové proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Tibet epidemiologie   MeSH
• Názvy látek
• virové proteiny MeSH