Early-onset Marfan syndrome with aortic dilatation and giant pulmonary artery aneurysm: A case report.

A 30-year-old woman with ankylosing spondylitis was referred to our clinic with abnormal fetal echocardiography findings, including ascending aortic dilatation, giant main pulmonary artery aneurysm, and aortic and pulmonary valve stenosis at 22 weeks of gestation. The full-term male neonate was born by cesarean section and was transferred to the cardiac intensive care unit soon after delivery for respiratory distress with low percutaneous oxygen saturation. Based on cardiovascular and genetic analysis findings, the patient was diagnosed with Marfan syndrome. Surgery was performed; however, the patient died due to cardiac arrest. In conclusion, main pulmonary artery dilatation and aneurysms are uncommon in Marfan syndrome; therefore, presentation with these findings during the fetal life, as in the present case, is likely a sign of severe Marfan syndrome-related cardiac involvement.

Analysis of the effects of apical backfilling depth on apical sealing of different root canal filling qualities and morphologies.

PURPOSE: The aim of this study was to evaluate the effects of apical backfilling depth on the apical sealing of different root canal filling qualities and morphologies. METHODS: 3D-printed root canals (A: round, B: oval, C: long oval, D: flat) were used and divided into subgroups by root canal filling quality (a: good, b: poor, c: nonfilling) and backfilling depth (3 mm, 5 mm). A glucose microleakage device was used to measure leakage. RESULTS: (1) 3-mm iRoot BP Plus was filled at the apex, and no obvious leakage occurred in the good root canal filling group, which was significantly smaller than that in the poor/nonfilling groups (P < 0.05). Under good root canal filling conditions in groups A, B, C, and D, no obvious leakage was observed. Under poor/nonfilling root canal filling conditions, there was significant leakage; A and B (P > 0.05) and C and D were compared (P < 0.05). (2) Apical backfilling with 5-mm iRoot BP Plus showed no significant leakage in the poor root canal filling groups with the four morphologies. CONCLUSION: 3-mm iRoot BP Plus was filled at the apex, root canal filling was poor, apical sealing was poor, and root canal morphology affected apical sealing. Apical backfilling with 5-mm iRoot BP Plus improved apical sealing under poor root canal filling conditions, and apical sealing was unaffected by root canal morphology.

Aerosol inhalation of Mycobacterium vaccae ameliorates airway structural remodeling in chronic asthma mouse model.

Background: Airway remodeling is accepted to be a determining component within the natural history of asthma. Nebulized inhalation of Mycobacterium vaccae (M. vaccae) has a protective effect on asthmatic mice. However, little is known regarding the effect of M. vaccae on airway structural remodeling in asthmatic mice. The purpose of this study was to explore the effect and the underlying mechanism of M. vaccae aerosol inhalation on airway structural remodeling in an asthma mouse model. Methods: Chronic asthma mouse models were established by ovalbumin induction. The number of inflammatory cells in bronchoalveolar lavage fluid (BALF), pathological alterations in lung tissue, and levels of associated cytokines (IL-5, IL-13, TNF-α, and ovalbumin-specific immunoglobulin E [OVA-sIgE]) were all assessed after M. vaccae therapy. The relative expression of interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and Wnt1-induced signaling protein 1 (WISP1) mRNA were detected. Western blotting and immunohistochemistry detected the expression of Wnt/ß-catenin pathway-related proteins in lung tissue. Results: M. vaccae aerosol inhalation relieved airway inflammation, airway hyper-responsiveness, and airway remodeling. M. vaccae reduced the levels of IL-5, IL-13, TNF-α, and OVA-sIgE in and downregulated the expression of IL-1ß, TNF-α, NF-κB, and WISP1 mRNA in the pulmonary. In addition, M. vaccae inhibited the expression of ß-catenin, WISP1, and Wnt1 protein and upregulated the expression of glycogen synthase kinase-3beta (GSK-3ß). Conclusion: Nebulized inhalation of M. vaccae can reduce airway remodeling during asthma.

Morphological changes of the root apex in anterior teeth with periapical periodontitis: an in-vivo study.

INTRODUCTION: The aim was to analyze the morphological changes of root apex in anterior teeth with periapical periodontitis. METHODS: 32 untreated anterior teeth with periapical periodontitis were enrolled, compared with the healthy contralateral teeth. Two-dimensional measurement of Cone-beam computed tomography was used to determine the location and measure diameter of the apical constriction according to Schell's methods. An open-source software (3D Slicer) was used to reconstruct the teeth. The apical constriction form was analysis according to Schell's topography. The distances of apical constriction to apical foramen and anatomical apex were measured respectively. RESULTS: The difference value between buccolingual and mesiodistal diameter was (0.06 ± 0.09) mm and (0.04 ± 0.04) mm in periapical periodontitis and controls (p < 0.05). The mean distance between apical constriction and anatomical apex was significantly shorter in periapical periodontitis than controls, so was the mean distance of apical constriction to apical foramen. The most common form of apical constriction was flaring (65.6%) in periapical periodontitis. CONCLUSIONS: The anterior teeth with periapical periodontitis had shorter distances of apical constriction to anatomical apex and apical foramen, bigger disparities between the diameters of buccolingual and mesiodistal, and higher proportion of flaring apical constriction.

Transcriptomic Analysis Reveals a Link Between Hippo Signaling Pathway and Macrophages in Lungs of Mice with OVA-Induced Allergic Asthma.

PURPOSE: The Hippo signaling pathway participates in the restriction of cell proliferation and organ growth. Activated macrophages have been implicated in the pathogenesis of allergic asthma. Recent studies have shown that Hippo signaling pathway may also be involved in the regulation of asthma. However, the link between Hippo signaling pathway and macrophages in the context of allergic asthma has not been investigated. The purpose of this study was to explore the link between Hippo signaling pathway and macrophages using a mice model of OVA-induced allergic asthma. METHODS: Mice models of asthma were established. Lung tissues were collected from mice and pooled for mRNA sequencing and bioinformatics analysis. The relative mRNA expression of Hippo signalling pathway-related proteins Yap1, Lef1 and Ctgf was also measured. Double immunofluorescence staining was performed on lung tissues to evaluate macrophage marker F4/80 expression and Yap1/Lef1/Ctgf expression. RESULTS: Results of the RNA-Seq of lung tissues demonstrated that the Hippo signaling pathway was down-regulated in OVA-induced allergic asthma. Using the cytoHubba tool kits in Cytoscape, the following top 10 hub genes of Hippo signalling pathway were identified: Yap1, Lef1, Ctgf, Ccnd1, Axin2, Smad7, Wnt4, Wnt3a, Pard6b, and Wwc1. Using the seq-ImmuCC (http://218.4.234.74:3200/immune/), a negative correlation was found between macrophages and Hippo signaling pathway activity (R2 = 0.93). The mRNA expression levels of pulmonary Yap1, Lef1, and Ctgf were down-regulated in the mice model of OVA-induced allergic asthma. Moreover, double-stained immunofluorescence for F4/80 and Yap1, Lef1, Ctgf in mouse lung sections respectively revealed that macrophage proliferation was correlated with downregulation of the Hippo signaling pathway in the mice model of OVA-induced allergic asthma. CONCLUSION: These results demonstrated that the Hippo signaling pathway was down-regulated in asthma mice, and the proliferation of macrophages was associated with downregulation of the Hippo signaling pathway. These findings reveal novel insights into the pathogenesis and treatment of asthma.

Effects of Mycobacterium vaccae Aerosol Inhalation on Airway Inflammation in Asthma Mouse Model.

Background:Mycobacterium vaccae vaccine, a composition of Mycobacterium proteins, has been known to have bidirectional immunomodulatory functions. Recent studies have shown that M. vaccae has a therapeutic potential for treating asthma. However, little is known regarding the effect of M. vaccae aerosol inhalation during allergen sensitization or challenge on asthma. The purpose of this study was to explore the effect and the underlying mechanism of M. vaccae aerosol inhalation during allergen sensitization or challenge on airway inflammation in an asthma mouse model. Methods: Asthma mouse models were established. Mice received aerosol inhalation with M. vaccae once daily during allergen sensitization or challenge for 5 days successively. Airway responsiveness, bronchoalveolar lavage fluid (BALF) cell count, histology, and cytokine concentrations (IL-4, IFN-γ, IL-10, and IL-17) were measured. The relative mRNA expression of ASC, caspase-1, TNF-α, and IL-1ß was also determined. Expression of pulmonary NLRP3 and nuclear factor kappa B (NF-κB) protein was measured using immunohistochemistry and Western blot. Results:M. vaccae aerosol inhalation suppressed airway hyperresponsiveness and inflammation, reduced levels of IL-4, upregulated expression of IFN-γ and IL-10 in BALF, inhibited mRNA expression of pulmonary ASC, caspase-1, TNF-α, and IL-1ß, and also inhibited expression of pulmonary NLRP3 and NF-κB protein during allergen sensitization or challenge. Conclusion:M. vaccae aerosol inhalation can suppress airway hyperresponsiveness and inflammation during allergen sensitization or challenge, and may be a promising approach for asthma therapy.

Redescription of the Cranium of Jingshanosaurus xinwaensis (Dinosauria: Sauropodomorpha) from the Lower Jurassic Lufeng Formation of Yunnan Province, China.

The Lower Jurassic Lufeng Formation in Yunnan Province of southwestern China has yielded an important and diverse terrestrial vertebrate fauna dominated by basal sauropodomorph dinosaurs. Nevertheless, many of them lack detailed descriptions and/or explicit diagnoses, hampering systematic analyses of their interrelationships and further studies. We present a detailed redescription of the cranial osteology of Jingshanosaurus xinwaensis and amend its diagnosis. Incorporation of the revised anatomical data into a phylogenetic analysis finds Jingshanosaurus to be one of the earliest diverging sauropodiforms. Moreover, the previously reported Chuxiongosaurus lufengensis is considered to be a junior synonym of J. xinwaensis. Jingshanosaurus can be diagnosed by a unique combination of character states, including (1) an inflection at the base of the dorsal premaxillary process; (2) the level of the caudal margin of the external naris being caudal to the mid-length of the maxillary tooth row and the rostral margin of the antorbital fenestra; (3) a ventrally constricted subtriangular orbit; (4) the height-to-length ratio of the dentary being greater than 0.2; and (5) a distally recurved long axis of the premaxillary and rostral maxillary tooth crowns. As the largest taxon (around 9 m long) currently known among Lufeng basal sauropodomorphs and one of the best known basal-most sauropodiforms, a better understanding of Jingshanosaurus will allow for reconstruction of the ecomorphotypic diversity of the Lower Jurassic Lufeng dinosaurs and help to decipher the origin and early evolution of sauropodiforms, the clade ultimately leading to the gigantic sauropods. Anat Rec, 303:759-771, 2020. © 2019 Wiley Periodicals, Inc.

A new sauropodiform dinosaur with a 'sauropodan' skull from the Lower Jurassic Lufeng Formation of Yunnan Province, China.

The Early Jurassic Lufeng Formation of Yunnan Province in southwestern China is one of the best fossil localities in the world for understanding the early radiation of sauropodomorph dinosaurs. It has yielded a rich assemblage of complete and three-dimensionally preserved skeletons of herbivorous dinosaurs that provide crucial morphological information for systematic and evolutionary studies. Here we describe a new taxon, Yizhousaurus sunae gen. et sp. nov., represented by a nearly complete skeleton with an exquisitely preserved skull and mandible. Yizhousaurus is distinguished from other non-sauropodan sauropodomorphs by a unique combination of plesiomorphic and apomorphic features, which increases our understanding of the anatomical variation on the relatively conservative 'prosauropod' cranial plan. Phylogenetic analysis resolves Yizhousaurus as a sauropodiform, showcasing a mosaic character suite combining plesiomorphic states in the postcranial skeleton with some more 'sauropodan'-like features in the skull. Furthermore, Yizhousaurus is placed closer to the base of Sauropoda than other non-sauropodan sauropodomorphs currently known from the Lufeng Formation, adding another taxon to enrich the Lower Jurassic Lufeng dinosaur fauna.

[Effect of Interfering the ADAM10 by Lentivirul Vector-Mediated shRNA on Multiple Myeloma MM.1S Cell Proliferation].

OBJECTIVE: To explore the effect of interfering ADAM10 on proliferation and apoptosis of multiple myeloma MM.1S cells, and its possible mechanism. METHODS: Four pairs of shRNA-coding sequences directed against different sites of ADAM10 mRNA were designed and inserted into lentiviral vector plasimd pLVshRNA-EGFP(2A) Puro for constructing the sh/ADAM10-1, sh/ADAM10-2, sh/ADAM10-3, sh/ADAM10-4 and sh/Con. These plasmids and lentiviral packaging plasmids were co-transfected into the packaging cells 293FT, then the virus particles were collected and the viral titer was assayed after concentration, and these viral particles were transfected to MM.1S cells. The flow cytometry was used to sort GFP+ cells. Real-time quantitative PCR, and Western blot were used to detect the effect of interfering the ADAM10 gene by lentiviral vector mediated shRNA. The proliferation-inhibition curve was plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V and 7-AAD staining, the transcripts of pro-apoptosis gene BAD, BAK, BIK, anti-apoptotic genes BCL-2, c-Myc and Notch1 target gene Hes-1 were detected by real-time PCR. RESULTS: Lentivirus vector was successfully constructed, that could specifically interfere ADAM10 expression. Interfering ADAM10 gene could inhibit the MM.1S cell proliferation and induce apoptosis. After the interferencing ADAM10 gene the mRNA levels of pro-apoptosis gene BAD, BAK and BIK were increased, and the mRNA levels of anti-apoptotic genes BCL-2 and c-Myc were reduced. Q-PCR results showed that the mRNA level of Notch1 were increased, but that of Hes-1 were reduced. CONCLUSION: Down-regulated ADAM10 expression can significantly inhibit multiple myeloma MM.1S cell proliferation and promote the apotosis. Its mechanism may be related to Notch1 signaling pathways.

Change in iron metabolism in rats after renal ischemia/reperfusion injury.

Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1) and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI). In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum creatinine and blood urea nitrogen were found to be time-dependently increased with different degrees of kidney injury. Regular variations in iron metabolism indexes in the blood and kidneys were observed in renal IRI. Renal iron content, serum iron and serum ferritin increased early after reperfusion and then declined. Hepcidin expression in the liver significantly increased early after reperfusion, and its serum concentration increased beginning at 8 h after reperfusion. The splenic iron content decreased significantly in the early stage after reperfusion and then increased time-dependently with increasing reperfusion time, and the hepatic iron content showed a decrease in the early stage after reperfusion. The early decrease of the splenic iron content and hepatic iron content might indicate their contribution to the increase in serum iron in renal IRI. In addition, the duodenal iron content showed time-dependently decreased since 12 h after reperfusion in the IRI groups compared to the control group. Along with the spleen, the duodenum might contribute to the decrease in serum iron in the later stage after reperfusion. The changes in iron metabolism indexes observed in our study demonstrate an iron metabolism disorder in renal IRI, and hepcidin might be involved in maintaining iron homeostasis in renal IRI. These findings might suggest a self-protection mechanism regulating iron homeostasis in IRI and provide a new perspective on iron metabolism in attenuating renal IRI.

Recombinant adeno-associated virus carrying thymosin ß4 suppresses experimental colitis in mice.

AIM: To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin ß4 (AAV-Tß4) on murine colitis via intracolonic administration. METHODS: AAV-Tß4 was prepared and intracolonically used to mediate the secretory expression of Tß4 in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tß4 on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively. RESULTS: Recombinant AAVs efficiently delivered LacZ and Tß4 into the colonic tissues of the mice, and AAV-Tß4 led to a strong expression of Tß4 in mouse colons. In both the DSS and TNBS colitis models, AAV-Tß4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tß4 significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tß4 also modulated colonic TNF-α, IL-1ß and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice. CONCLUSION: Tß4 exerts a protective effect on murine colitis, indicating that AAV-Tß4 could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.

A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice.

Connective tissue growth factor (CTGF) has been recognized as a central mediator and promising therapeutic target in hepatic fibrosis. In this study, we generated a novel virus-like particle (VLP) CTGF vaccine by inserting the 138-159 amino acid (aa) fragment of CTGF into the central c/e1 epitope of C-terminus truncated hepatitis B virus core antigen (HBc, aa 1-149) using a prokaryotic expression system. Immunization of BALB/c mice with the VLP vaccine efficiently elicited the production of anti-CTGF neutralizing antibodies. Vaccination with this CTGF vaccine significantly protected BALB/c mice from carbon tetrachloride (CCl4)-induced hepatic fibrosis, as indicated by decreased hepatic hydroxyproline content and lower fibrotic score. CCl4 intoxication-induced hepatic stellate cell activation was inhibited by the vaccination, as indicated by decreased α-smooth muscle actin expression and Smad2 phosphorylation. Vaccination against CTGF also attenuated the over-expression of some profibrogenic factors, such as CTGF, transforming growth factor-ß1, platelet-derived growth factor-B and tissue inhibitor of metalloproteinase-1 in the fibrotic mouse livers, decreased hepatocyte apoptosis and accelerated hepatocyte proliferation in the fibrotic mouse livers. Our results clearly indicate that vaccination against CTGF inhibits fibrogenesis, alleviates hepatocyte apoptosis and facilitate hepatic regeneration. We suggest that the vaccine should be developed into an effective therapeutic measure for hepatic fibrosis.