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1.
Pharmazie ; 78(6): 86-88, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37537773

RESUMO

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.


Assuntos
Cisteína , Expectorantes , Ratos , Animais , Carragenina/efeitos adversos , Expectorantes/farmacologia , Expectorantes/uso terapêutico , Cisteína/efeitos adversos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico
2.
J Phys Chem Lett ; 14(17): 4011-4018, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37083457

RESUMO

Valence s electrons in alkali- or coinage-metal clusters are conceived to delocalize over the metal frameworks. The electrons occupy so-called superatomic orbitals (SAOs, i.e., 1S, 1P, 1D, 2S, 1F, ...), which provide an essential picture for understanding the size-dependent, unique properties of these metal clusters. While such electronic shells are unambiguously identified in their photoelectron spectra and supported by electronic structure calculations, characterization of SAOs in heteroatom-doped metal clusters has remained elusive as the doping significantly affects its energy levels and even alters the ordering of SAOs. Here, we present a photoelectron imaging study to explore SAOs formed in Sc-doped and undoped silver cluster anions, AgNSc- (N = 15, 16) and AgN- (N = 18, 19). Photoelectron angular distributions from their outermost SAOs are clearly visualized, whose characters are analyzed with the aid of density functional theory calculations. The present methodology enables us to explore not only the quantized energy levels but also the spatial distributions of SAOs formed in various metal cluster anions.

3.
Benef Microbes ; 14(1): 17-30, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36815492

RESUMO

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific ß-lactoglobulin-IgE (sIgE) and ß-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow's milk allergy.


Assuntos
Hipersensibilidade a Leite , Probióticos , Animais , Feminino , Bovinos , Hipersensibilidade a Leite/terapia , Temperatura Alta , Imunoterapia , Imunoglobulina E , Alérgenos , Biomarcadores , Lactoglobulinas
4.
J Dent Res ; 102(2): 197-206, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36366748

RESUMO

We have developed methods to achieve efficient CRISPR-Cas9-mediated gene knockout in ex vivo mouse embryonic salivary epithelial explants. Salivary epithelial explants provide a valuable model for characterizing cell signaling, differentiation, and epithelial morphogenesis, but research has been limited by a paucity of efficient gene perturbation methods. Here, we demonstrate highly efficient gene perturbation by transient transduction of guide RNA-expressing lentiviruses into Cas9-expressing salivary epithelial buds isolated from Cas9 transgenic mice. We first show that salivary epithelial explants can be cultured in low-concentration, nonsolidified Matrigel suspensions in 96-well plates, which greatly increases sample throughput compared to conventional cultures embedded in solidified Matrigel. We further show that salivary epithelial explants can grow and branch with FGF7 alone, while supplementing with insulin, transferrin, and selenium (ITS) enhances growth and branching. We then describe an efficient workflow to produce experiment-ready, high-titer lentiviruses within 1 wk after molecular cloning. To track transduced cells, we designed the lentiviral vector to coexpress a nuclear fluorescent reporter with the guide RNA. We routinely achieved 80% transduction efficiency when antibiotic selection was used. Importantly, we detected robust loss of targeted protein products when testing 9 guide RNAs for 3 different genes. Moreover, targeting the ß1 integrin gene (Itgb1) inhibited branching morphogenesis, which supports the importance of cell-matrix adhesion in driving branching morphogenesis. In summary, we have established a lentivirus-based method that can efficiently perturb genes of interest in salivary epithelial explants, which will greatly facilitate studies of specific gene functions using this system.


Assuntos
Células Epiteliais , Glândulas Salivares , Animais , Camundongos , Técnicas de Inativação de Genes , Camundongos Knockout , Morfogênese/fisiologia , RNA/metabolismo
5.
Nature ; 609(7926): 265-268, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36071186

RESUMO

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

6.
Radiography (Lond) ; 28(3): 725-731, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35428571

RESUMO

INTRODUCTION: Many patients experience anxiety, not limited to claustrophobia, before magnetic resonance imaging (MRI) examination. We performed a non-randomized controlled trial to evaluate whether a patient-friendly audiovisual (AV) system in the MR scanner room reduces patient anxiety. METHODS: We randomly selected 61 participants from outpatients who required brain MRI examination. Patients were informed that they could choose to undergo an MRI examination with a patient-friendly AV system (Ambient Experience, Philips Healthcare, Best, The Netherlands) or the standard system. To complete the MRI examination without affecting clinical practice, all patients who preferred the patient-friendly AV system were assigned to the preferring AV group. Patients who indicated that either system was acceptable were randomly assigned to the no preference but allocated AV group or control (using the standard system) groups. In both groups, state anxiety using the State-Trait Anxiety Inventory (STAI) was assessed before and after the MRI examination (A-State-before and A-State-after MRI, respectively). The changes in A-State-before and A-State-after MRI were categorized as follows: relieved high-state anxiety, no change in high-state anxiety, stable easiness, and intensified anxiety. RESULTS: Among the 61 included patients, 19 were assigned to the preferring AV group, 20 to the no preference but allocated AV group, and 22 to the control group. There were no significant differences between the group. However, in patients with high-state anxiety before MRI, the preferring AV group and the no preference but allocated AV group, which used the patient-friendly AV system, relieved high-state anxiety by 63.6% (7 of 11 patients) and 81.8% (9 of 11 patients), respectively. In contrast, the control group using the standard system relieved high-level anxiety by only 42.9% (three out of seven patients). CONCLUSION: The patient-friendly AV system may reduce anxiety in patients undergoing MRI examinations. IMPLICATIONS FOR PRACTICE: The patient-friendly AV system may reduce anxiety in patients undergoing MRI examination by providing a more patient-centered MRI examination environment. These findings may help ameliorate negative perceptions associated with MRI examination.


Assuntos
Ansiedade , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Países Baixos
7.
Acta Gastroenterol Belg ; 85(1): 7-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35304988

RESUMO

Background and study aims: This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Patients and methods: Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. Results: 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Conclusions: Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.


Assuntos
Varizes Esofágicas e Gástricas , Hemostáticos , Hepatite C Crônica , Neoplasias Hepáticas , Varizes , Antivirais , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Hemostasia , Hemostáticos/uso terapêutico , Hepatite C Crônica/complicações , Humanos
8.
Osteoarthritis Cartilage ; 29(11): 1564-1574, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34425229

RESUMO

OBJECTIVE: Low molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression. DESIGN: High-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system. RESULTS: Colchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1ß and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression. CONCLUSIONS: Colchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca2+ signaling pathway.


Assuntos
Condrócitos/metabolismo , Colchicina/farmacologia , Metaloproteinase 13 da Matriz/efeitos dos fármacos , Fosfolipase C gama/metabolismo , Animais , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Osteoartrite , Fosforilação , RNA Mensageiro/metabolismo , Transdução de Sinais , Membrana Sinovial/patologia
9.
AJNR Am J Neuroradiol ; 42(5): 955-960, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33632737

RESUMO

BACKGROUND AND PURPOSE: The signal intensity of the thyroid in neonates is high on T1WI. It is affected by gestational and postnatal ages. However, the extent of the influence of these ages is unknown. This study investigated the relationship of signal intensities of the infant thyroid with postnatal and gestational ages and anterior pituitary using 3D gradient-echo T1WI. MATERIALS AND METHODS: This retrospective study included 183 T1-weighted images from 181 infants. Using a multiple linear regression analysis, we evaluated the effects of postnatal and gestational ages on the thyroid-muscle signal intensity ratio. The relationship between the thyroid and anterior pituitary signal intensities on T1WI and the age of the infants was evaluated. RESULTS: Multiple linear regression analysis showed that the thyroid signal intensity was affected negatively by postnatal age at examination and positively by gestational age at birth (P < .01 and P = .04, respectively). According to the standardized partial regression coefficients, the influence of postnatal age at examination was stronger than that of gestational age at birth (-0.72 and 0.13, respectively). The thyroid and anterior pituitary signal intensities reached constant values at 12 weeks' postnatal age, and the mean thyroid-anterior pituitary signal intensity ratios were almost 1 throughout the entire period. CONCLUSIONS: The signal intensity of the infant thyroid on T1WI was more strongly influenced by the postnatal age at examination than the gestational age at birth, and it was almost equal to that of the anterior pituitary.


Assuntos
Idade Gestacional , Imageamento por Ressonância Magnética/métodos , Glândula Tireoide/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Recém-Nascido , Masculino , Hipófise/diagnóstico por imagem , Estudos Retrospectivos
10.
J Appl Microbiol ; 130(6): 1972-1980, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33064909

RESUMO

AIM: Aspergillus niger S17-5 produces two alkylitaconic acids, 9-hydroxyhexylitaconic acid (9-HHIA) and 10-hydroxyhexylitaconic acid (10-HHIA), which have cytotoxic and polymer building block properties. In this study, we characterized the production of 9-HHIA and 10-HHIA by addition of their expected precursor, caprylic acid, to a culture of A. niger S17-5, and demonstrated batch fermentation of 9-HHIA and 10-HHIA in a jar fermenter with DO-stat. METHODS AND RESULTS: Production titres of 9-HHIA and 10-HHIA from 3% glucose in a flask after 25 days cultivation were 0·35 and 1·01 g l-1 respectively. Addition of 0·22 g l-1 of caprylic acid to a suspension of resting cells of A. niger S17-5 led to 32% enhancement of total 9-HHIA and 10-HHIA production compared to no addition. No enhancement of the production of 9-HHIA or 10-HHIA by the addition of oxaloacetic acid was observed. Addition of caprylic acid to the culture at mid-growth phase was more suitable for 9-HHIA and 10-HHIA production due to less cell growth inhibition by caprylic acid. DO-stat batch fermentation with 3% glucose and 14·4 g l-1 of caprylic acid in a 1·5 l jar fermenter resulted in the production titres of 9-HHIA and 10-HHIA being 0·48 and 1·54 g l-1 respectively after 10 days of cultivation. CONCLUSIONS: Addition of caprylic acid to the culture of A. niger S17-5 enhances 9-HHIA and 10-HHIA production. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that 9-HHIA and 10-HHIA are synthesized with octanoyl-CoA derived from caprylic acid, and that the supply of octanoyl-CoA is a rate-limiting step in 9-HHIA and 10-HHIA production. To the best of our knowledge, this is the first report regarding the fermentation of naturally occurring itaconic acid derivatives in a jar fermenter.


Assuntos
Aspergillus niger/metabolismo , Caprilatos/metabolismo , Succinatos/metabolismo , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Reatores Biológicos , Caprilatos/análise , Caprilatos/farmacologia , Fermentação , Glucose/análise , Glucose/metabolismo , Succinatos/análise , Succinatos/química
11.
Int Endod J ; 54(2): 255-267, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32961600

RESUMO

AIM: To evaluate the efficacy of a prototype root canal dressing containing surface pre-reacted glass-ionomer (S-PRG) fillers on repairing induced periapical lesions in a rat model. Calcium hydroxide [Ca(OH)2 ] was applied as a comparison in the healing process. METHODOLOGY: The pulp chambers of the maxillary first molars in 64 male Wistar rats aged 16 weeks were opened to induce periapical lesions. After 28 days, the mesial canal of each tooth was prepared, irrigated with 2.5% sodium hypochlorite only (control group: irrigation) or followed by the respective dressing [Ca(OH)2 group, irrigation + Ca(OH)2 ; S-PRG group, irrigation + S-PRG] and restored with composite resin for 3 or 7 days (10/group). Four rats with healthy molars were used as blank controls. Descriptive analysis of the periapical radiographs, haematoxylin and eosin staining and immunohistochemical observation was performed 3 and 7 days after treatment. The periapical grey value, CD68 macrophages and osteoclasts (cathepsin-K) were quantified and statistically analysed with Tukey's honest significant difference test. A significant difference was achieved when P values were <0.05. RESULTS: S-PRG and Ca(OH)2 dressings were associated with increased periapical grey values and inhibited osteoclast activity at 3 and 7 days; a significant difference in radiographic results and the number of osteoclasts was obtained at 3 and 7 days compared with the control group (P < 0.05). Reparative tissue was observed histologically in the space of the periapical resorbed necrotic area after S-PRG and Ca(OH)2 treatment for 3 and 7 days. The number of macrophages was significantly decreased at 3 and 7 days in the S-PRG and Ca(OH)2 specimens when compared with the controls (P < 0.05). CONCLUSIONS: In a rat experimental model, the S-PRG root canal dressing was comparable to Ca(OH)2 in promoting the healing of experimentally induced periapical lesions. S-PRG paste has the potential to be used as an alternative intracanal dressing in teeth with apical periodontitis.


Assuntos
Periodontite Periapical , Materiais Restauradores do Canal Radicular , Animais , Bandagens , Hidróxido de Cálcio , Cavidade Pulpar , Masculino , Periodontite Periapical/terapia , Ratos , Ratos Wistar , Irrigantes do Canal Radicular
12.
Osteoarthritis Cartilage ; 28(11): 1459-1470, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818603

RESUMO

OBJECTIVE: Exostosin-1 (EXT1) and EXT2 are the major genetic etiologies of multiple hereditary exostoses and are essential for heparan sulfate (HS) biosynthesis. Previous studies investigating HS in several mouse models of multiple hereditary exostoses have reported that aberrant bone morphogenetic protein (BMP) signaling promotes osteochondroma formation in Ext1-deficient mice. This study examined the mechanism underlying the effects of HS deficiency on BMP/Smad signaling in articular cartilage in a cartilage-specific Ext-/- mouse model. METHOD: We generated mice with a conditional Ext1 knockout in cartilage tissue (Ext1-cKO mice) using Prg4-Cre transgenic mice. Structural cartilage alterations were histologically evaluated and phospho-Smad1/5/9 (pSmad1/5/9) expression in mouse chondrocytes was analyzed. The effect of pharmacological intervention of BMP signaling using a specific inhibitor was assessed in the articular cartilage of Ext1-cKO mice. RESULTS: Hypertrophic chondrocytes were significantly more abundant (P = 0.021) and cartilage thickness was greater in Ext1-cKO mice at 3 months postnatal than in control littermates (P = 0.036 for femur; and P < 0.001 for tibia). However, osteoarthritis did not spontaneously occur before the 1-year follow-up. matrix metalloproteinase (MMP)-13 and adamalysin-like metalloproteinases with thrombospondin motifs(ADAMTS)-5 were upregulated in hypertrophic chondrocytes of transgenic mice. Immunostaining and western blotting revealed that pSmad1/5/9-positive chondrocytes were more abundant in the articular cartilage of Ext1-cKO mice than in control littermates. Furthermore, the BMP inhibitor significantly decreased the number of hypertrophic chondrocytes in Ext1-cKO mice (P = 0.007). CONCLUSIONS: HS deficiency in articular chondrocytes causes chondrocyte hypertrophy, wherein upregulated BMP/Smad signaling partially contributes to this phenotype. HS might play an important role in maintaining the cartilaginous matrix by regulating BMP signaling.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Heparitina Sulfato/deficiência , Osteoartrite do Joelho/metabolismo , Proteína ADAMTS5/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Cartilagem Articular/citologia , Condrócitos/patologia , Modelos Animais de Doenças , Hipertrofia , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , N-Acetilglucosaminiltransferases/genética , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Proteína Smad8/metabolismo
13.
Osteoporos Int ; 31(12): 2355-2361, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32642853

RESUMO

We analyzed osteoporosis in 20 HME patients. According to the T-score of BMD, 30% and 67.5% of the patients fell in the range of osteopenia in the lumbar spine and femoral neck. Our results indicate HME patients have low bone mass. They do not have abnormal bone metabolism. INTRODUCTION: There are few reports of osteoporosis in hereditary multiple exostoses (HME) patients. Therefore, the purpose of this study was to analyze osteoporosis in HME patients. METHODS: This retrospective cohort study included 20 patients diagnosed with HME. Patients underwent bone mineral density (BMD) measurement of the lumbar spine (n = 20) and femoral neck (n = 40). Bone metabolic parameters, including serum osteocalcin and urinary cross-linked N-telopeptide of type 1 collagen (NTx), were analyzed in all subjects. EXT1 and EXT2 genes were sequenced using genomic DNA. We also examined the correlation between genotype and BMD Z-score and T-score. RESULTS: The mean BMD values of the lumbar spine were 1.085 ± 0.116 g/cm2 (n = 11) in male and 1.108 ± 0.088 g/cm2 (n = 9) in female. The mean BMD values of the femoral neck area were 0.759 ± 0.125 g/cm2 (n = 22) in male and 0.749 ± 0.115 g/cm2 (n = 18) in female. Z-score of most HME patients show < 0, indicating that these patients tend to have low bone mass compared with the age-matched population. According to the T-score of BMD, 30% (6 of 20) and 67.5% (27 of 40) of the patients fell in the range of osteopenia in the lumbar spine and femoral neck areas, respectively. Serum osteocalcin and urinary NTx were in the normal range in most patients. There was no significant correlation between genotypes and Z-score. CONCLUSION: HME patients have low bone mass, especially in the femoral neck area. They do not have abnormal bone metabolism, and there was no correlation between genotypes and Z-score.


Assuntos
Exostose Múltipla Hereditária , Osteoporose , Densidade Óssea , Feminino , Colo do Fêmur , Humanos , Vértebras Lombares , Masculino , Osteoporose/epidemiologia , Osteoporose/etiologia , Estudos Retrospectivos
14.
Tissue Cell ; 63: 101321, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223949

RESUMO

BACKGROUND: We have been trying to produce scaffold-free structures for airway regeneration using a bio-3D-printer with spheroids, to avoid scaffold-associated risks such as infection. Previous studies have shown that human umbilical vein endothelial cells (HUVECs) play an important role in such structures, but HUVECs cannot be isolated from adult humans. The aim of this study was to identify alternatives to HUVECs for use in scaffold-free structures. METHODS: Three types of structure were compared, made of chondrocytes and mesenchymal stem cells with HUVECs, human lung microvascular endothelial cells (HMVEC-Ls), and induced pluripotent stem cell (iPSC)-derived endothelial cells. RESULTS: No significant difference in tensile strength was observed between the three groups. Histologically, some small capillary-like tube formations comprising CD31-positive cells were observed in all groups. The number and diameters of such formations were significantly lower in the iPSC-derived endothelial cell group than in other groups. Glycosaminoglycan content was significantly lower in the iPSC-derived endothelial cell group than in the HUVEC group, while no significant difference was observed between the HUVEC and HMVEC-L groups. CONCLUSIONS: HMVEC-Ls can replace HUVECs as a cell source for scaffold-free trachea-like structures. However, some limitations were associated with iPSC-derived endothelial cells.


Assuntos
Células Endoteliais/ultraestrutura , Pulmão/ultraestrutura , Neovascularização Fisiológica/genética , Impressão Tridimensional , Diferenciação Celular/genética , Proliferação de Células/genética , Condrócitos/citologia , Células Endoteliais da Veia Umbilical Humana/ultraestrutura , Humanos , Pulmão/crescimento & desenvolvimento , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/fisiologia , Alicerces Teciduais , Traqueia/crescimento & desenvolvimento , Traqueia/ultraestrutura
15.
Cancer Gene Ther ; 27(3-4): 266, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31664167

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Science ; 364(6437): 272-275, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890589

RESUMO

The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu's surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.

19.
Science ; 364(6437): 268-272, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890588

RESUMO

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

20.
Science ; 364(6437): 252, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890587

RESUMO

The near-Earth carbonaceous asteroid 162173 Ryugu is thought to have been produced from a parent body that contained water ice and organic molecules. The Hayabusa2 spacecraft has obtained global multicolor images of Ryugu. Geomorphological features present include a circum-equatorial ridge, east-west dichotomy, high boulder abundances across the entire surface, and impact craters. Age estimates from the craters indicate a resurfacing age of [Formula: see text] years for the top 1-meter layer. Ryugu is among the darkest known bodies in the Solar System. The high abundance and spectral properties of boulders are consistent with moderately dehydrated materials, analogous to thermally metamorphosed meteorites found on Earth. The general uniformity in color across Ryugu's surface supports partial dehydration due to internal heating of the asteroid's parent body.

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