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1.
Stem Cell Reports ; 16(4): 868-882, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33798451

RESUMO

Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we investigated the functioning of a cardiomyogenic cell-surface marker, latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, in cardiac differentiation. LPHN2 was selectively expressed in cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cell (PSC) differentiation; cell sorting with an anti-LPHN2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs. Lphn2 knockdown or knockout PSCs did not express cardiac genes. We used the Phospho Explorer Antibody Array, which encompasses nearly all known signaling pathways, to assess molecular mechanisms underlying LPHN2-induced cardiac differentiation. LPHN2-dependent phosphorylation was the strongest for cyclin-dependent kinase 5 (CDK5) at Tyr15. We identified CDK5, Src, and P38MAPK as key downstream molecules of LPHN2 signaling. These findings provide a valuable strategy for isolating CPCs and CMCs from PSCs and insights into the still-unknown cardiac differentiation mechanisms.

2.
Polymers (Basel) ; 13(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810007

RESUMO

A trachea has a structure capable of responding to various movements such as rotation of the neck and relaxation/contraction of the conduit due to the mucous membrane and cartilage tissue. However, current reported tubular implanting structures are difficult to impelement as replacements for original trachea movements. Therefore, in this study, we developed a new trachea implant with similar anatomical structure and mechanical properties to native tissue using 3D printing technology and evaluated its performance. A 250 µm-thick layer composed of polycaprolactone (PCL) nanofibers was fabricated on a rotating beam using electrospinning technology, and a scaffold with C-shaped cartilage grooves that mimics the human airway structure was printed to enable reconstruction of cartilage outside the airway. A cartilage type scaffold had a highest rotational angle (254°) among them and it showed up to 2.8 times compared to human average neck rotation angle. The cartilage type showed a maximum elongation of 8 times higher than that of the bellows type and it showed the elongation of 3 times higher than that of cylinder type. In cartilage type scaffold, gelatin hydrogel printed on the outside of the scaffold was remain 22.2% under the condition where no hydrogel was left in other type scaffolds. In addition, after 2 days of breathing test, the amount of gelatin remaining inside the scaffold was more than twice that of other scaffolds. This novel trachea scaffold with hydrogel inside and outside of the structure was well-preserved under external flow and is expected to be advantageous for soft tissue reconstruction of the trachea.

3.
Cell Death Dis ; 12(3): 238, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664230

RESUMO

The ubiquitin protease pathway plays important role in human bone marrow-derived mesenchymal stem cell (hBMSC) differentiation, including osteogenesis. However, the function of deubiquitinating enzymes in osteogenic differentiation of hBMSCs remains poorly understood. In this study, we aimed to investigate the role of ubiquitin-specific protease 53 (USP53) in the osteogenic differentiation of hBMSCs. Based on re-analysis of the Gene Expression Omnibus database, USP53 was selected as a positive regulator of osteogenic differentiation in hBMSCs. Overexpression of USP53 by lentivirus enhanced osteogenesis in hBMSCs, whereas knockdown of USP53 by lentivirus inhibited osteogenesis in hBMSCs. In addition, USP53 overexpression increased the level of active ß-catenin and enhanced the osteogenic differentiation of hBMSCs. This effect was reversed by the Wnt/ß-catenin inhibitor DKK1. Mass spectrometry showed that USP53 interacted with F-box only protein 31 (FBXO31) to promote proteasomal degradation of ß-catenin. Inhibition of the osteogenic differentiation of hBMSCs by FBXO31 was partially rescued by USP53 overexpression. Animal studies showed that hBMSCs with USP53 overexpression significantly promoted bone regeneration in mice with calvarial defects. These results suggested that USP53 may be a target for gene therapy for bone regeneration.

4.
Clin Mol Hepatol ; 27(2): 257-269, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33751877

RESUMO

There is some dissatisfaction with the term "nonalcoholic fatty liver disease (NAFLD)," which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended "metabolic (dysfunction)-associated fatty liver disease (MAFLD)" as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

5.
J Nat Prod ; 84(3): 562-569, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33667099

RESUMO

Three new guaianolide lactones (1-3) and four new 9-oxonerolidol glucosides (5-8) together with 20 known compounds were isolated from the MeOH extract of the flowers of Chrysanthemum indicum. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data along with acid hydrolysis. Of the isolates, sesquiterpenoids 1-4 and 15 and flavones 17 and 18 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values in the range 0.2-27.0 µM.

6.
Medicine (Baltimore) ; 100(13): e25409, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787651

RESUMO

ABSTRACT: Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.


Assuntos
Alopecia/terapia , Ciclo Celular/fisiologia , Folículo Piloso/fisiologia , Gases em Plasma/uso terapêutico , Alopecia/fisiopatologia , Técnicas de Cultura de Células/métodos , Linhagem Celular , Proliferação de Células/fisiologia , Meios de Cultura , Humanos , Espécies Reativas de Oxigênio/metabolismo
7.
Am J Sports Med ; 49(5): 1220-1226, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661712

RESUMO

BACKGROUND: Arthroscopic bone marrow stimulation (BMS) is considered the first-line treatment for osteochondral lesions of the talus (OLTs). However, the long-term stability of the clinical success of BMS remains unclear. PURPOSE: To investigate the long-term clinical outcomes among patients who underwent BMS for OLT and to identify prognostic factors for the need for revision surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective analysis was performed on 202 ankles (189 patients) that were treated with BMS for OLT and had a minimum follow-up of 10 years. The visual analog scale for pain, American Orthopaedic Foot & Ankle Society ankle-hindfoot score, and the Foot and Ankle Outcome Score (FAOS) were assessed by repeated measures analysis of variance. Prognostic factors associated with revision surgery were evaluated with Cox proportional hazard regression models and log-rank tests. RESULTS: The mean lesion size was 105.32 mm2 (range, 19.75-322.79); 42 ankles (20.8%) had large lesions (≥150 mm2). The mean visual analog scale for pain improved from 7.11 ± 1.73 (mean ± SD) preoperatively to 1.44 ± 1.52, 1.46 ± 1.57, and 1.99 ± 1.67 at 1, 3 to 6, and ≥10 years, respectively, after BMS (P < .001). The mean ankle-hindfoot score also improved, from 58.22 ± 13.57 preoperatively to 86.88 ± 10.61, 86.17 ± 10.23, and 82.76 ± 11.65 at 1, 3 to 6, and ≥10 years after BMS (P < .001). The FAOS at the final follow-up was 82.97 ± 13.95 for pain, 81.81 ± 14.64 for symptoms, 83.49 ± 11.04 for activities of daily living, 79.34 ± 11.61 for sports, and 78.71 ± 12.42 for quality of life. Twelve ankles underwent revision surgery after a mean 53.5 months. Significant prognostic factors associated with revision surgery were the size of the lesion (preoperative magnetic resonance imaging measurement ≥150 mm2; P = .014) and obesity (body mass index ≥25; P = .009). CONCLUSION: BMS for OLT yields satisfactory clinical outcomes at a mean follow-up of 13.9 years. The success of the surgery may depend on the lesion size and body mass index of the patient.

8.
ChemSusChem ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655716

RESUMO

Quinoxaline (Qx) derivatives are promising building units for efficient photovoltaic polymers owing to their strong light absorption and high charge-transport abilities, but they have been used exclusively in the construction of polymer donors. Herein, for the first time, Qx-based polymer acceptors (PA s) were developed by introducing electron-withdrawing cyano (CN) groups into the Qx moiety (QxCN). A series of QxCN-based PA s, P(QxCN-T2), P(QxCN-TVT), and P(QxCN-T3), were synthesized by copolymerizing the QxCN unit with bithiophene, (E)-1,2-di(thiophene-2-yl)ethene, and terthiophene, respectively. All of the PA s exhibited unipolar n-type characteristics with organic field-effect transistor (OFET) mobilities of around 10-2  cm2 V-1 s-1 . In space-charge-limited current devices, P(QxCN-T2) and P(QxCN-TVT) exhibited electron mobilities greater than 1.0×10-4  cm2 V-1 s-1 , due to the well-ordered structure with tight π-π stacking. When the PA s were applied in all-polymer solar cells (all-PSCs), the highest performance of 5.32 % was achieved in the P(QxCN-T2)-based device. These results demonstrate the significant potential of Qx-based PA s for high-performance all-PSCs and OFETs.

9.
J Nat Prod ; 84(2): 503-517, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33565879

RESUMO

Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 < 0.30 µg/mL) and low levels of toxicity against human cells (less than 50% reduction in HepG2 growth at 25 µg/mL). Analysis of the two top-performing extracts from Trichoderma sp. and Hypocrea sp. isolates revealed both contained chemically diverse assemblages of putative peptaibol-like compounds that were responsible for their antiplasmodial actions. Purification and structure determination efforts yielded 30 new peptaibols and lipopeptaibols (1-14 and 28-43), along with 22 known metabolites (15-27 and 44-52). While several compounds displayed promising activity profiles, one of the new metabolites, harzianin NPDG I (14), stood out from the others due to its noteworthy potency (EC50 = 0.10 µM against multi-drug-resistant P. falciparum line Dd2) and absence of gross toxicity toward HepG2 at the highest concentrations tested (HepG2 EC50 > 25 µM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.

10.
Sci Rep ; 11(1): 2878, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536553

RESUMO

We conducted a nationwide population-based cohort study to identify the risk factors associated with failure of total ankle arthroplasty (TAA). We included 2,914 subjects who underwent primary TAA between January 1, 2010, and December 31, 2016, utilizing the database of the Korean National Health Insurance Service. Failure of TAA was defined as revision TAA or arthrodesis procedures. An increased risk of TAA failure was observed in the < 65 age group versus the ≥ 75 age group [adjusted hazard ratios (aHR) 2.273, 95% confidence interval (CI) 1.223-4.226 in the 60-64 age group; aHR 2.697, 95% CI 1.405-5.178 in the 55-59 age group; aHR 2.281, 95% CI 1.145-4.543 in the 50-54 age group; aHR 2.851, 95% CI 1.311-6.203 in the < 50 age group]. Conversely, the ≥ 65 age group displayed no increase in the risk of TAA failure. The risk of TAA failure was increased in the severely obese group with body mass index (BMI) of ≥ 30 kg/m2 versus the normal BMI group (aHR 1.632; 95% CI 1.036-2.570). This population-based longitudinal study demonstrated that age < 65 years and BMI of ≥ 30 kg/m2 were associated with increased risk of TAA failure.

11.
Clin Mol Hepatol ; 27(2): 346-359, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33493393

RESUMO

BACKGROUND/AIMS: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. METHODS: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). RESULTS: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. CONCLUSION: BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

12.
Aliment Pharmacol Ther ; 53(8): 919-927, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33465253

RESUMO

BACKGROUND: The modified PAGE-B (mPAGE-B) and PAGE-B models reliably predict the risk of developing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). AIM(S): To investigate whether the addition of liver stiffness (LS) value, assessed using transient elastography, enhanced the predictive accuracies of these models METHODS: Patients with CHB who started anti-viral therapy (AVT) between 2007 and 2017 were enrolled. The training (Yonsei University Hospital) and validation (seven Korean referral institutes) cohorts contained 1211 and 973 patients, respectively. RESULTS: Based on multivariate analysis, older age (hazard ratio [HR] = 1.051, 95% confidence interval [CI] = 1.031-1.071), male sex (HR = 2.265, 95% CI = 1.463-3.506), lower platelet count (HR = 0.993, 95% CI = 0.989-0.997) and greater LS values (HR = 1.015, 95% CI = 1.002-1.028) were independently associated with an increased risk of HCC development (all P < 0.05). Thus, we developed a modified PAGELS -B model (maximum score 34) that included age, male sex, platelet count and LS value. The integrated area under the curve of the modified PAGELS model was greater than those of the PAGE-B and mPAGE-B models (0.760 vs 0.714 and 0.716, respectively) in the derivation dataset. The cumulative HCC incidence was significantly higher in the high-risk (modified PAGE-BLS score ≥ 24) group than in the intermediate-risk (modified PAGELS -B score 12-24) or low-risk (modified PAGELS -B score < 12) group (all P < 0.001). Similar results were observed in the validation cohort. CONCLUSIONS: The predictive accuracies of the PAGE-B and mPAGE-B models were validated in Korean patients with CHB receiving AVT. However, the modified PAGELS -B model featuring the addition of LS value showed higher predictability than the PAGE-B and mPAGE-B models.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino
13.
J Nat Prod ; 84(2): 230-238, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33476145

RESUMO

Bioactivity-guided isolation of a MeOH extract of Aralia cordata led to the isolation of four new ent-pimarane diterpenoids (1-4) and a diacetylene (5) together with 21 known compounds (6-26). Their structures were established based on the interpretation of one- and two-dimensional NMR and HRESIMS data. The absolute configurations of the new isolates were determined by electronic circular dichroism data analysis, single crystal X-ray diffraction, and Mosher's esterification method. All compounds exhibited inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with IC50 values ranging from 1.1 to 69.4 µM.

14.
BMC Gastroenterol ; 21(1): 40, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509102

RESUMO

BACKGROUND: Gastrointestinal tumor bleeding remains a clinical challenge because it is difficult to treat with conventional endoscopic hemostatic options. Recently, an endoscopic hemostatic powder (UI-EWD) was developed and reported to provide effective control of upper gastrointestinal bleeding. The aim of current study was to evaluate the feasibility and efficacy of this novel hemostatic powder in tumor bleeding. METHODS: A total of 41 consecutive patients with upper gastrointestinal tumor bleeding were included. UI-EWD was applied in all patients as an auxiliary hemostatic method as a salvage therapy or monotherapy during endoscopic treatment. Hemostasis success rates, adverse event related to UI-EWD, and rates of re-bleeding were evaluated. RESULTS: In all cases, UI-EWD application was successful at tumor bleeding sites. Immediate hemostasis occurred in 40/41 (97.5%) patients, and re-bleeding within 28 days occurred in 10 of 40 (22.5%) patients that achieved initial hemostasis. The success rate of immediate hemostasis for UI-EWD monotherapy was 100% (23/23). The re-bleeding rate at 28 days after UI-EWD monotherapy was 26.1% (6/23). No adverse events associated with UI-EWD application were encountered. CONCLUSIONS: The success rate of UI-EWD for immediate hemostasis in cases of GI tumor bleeding was excellent and UI-EWD produced promising results with respect to the prevention of re-bleeding. Based on these results, we suggest that UI-EWD be considered an effective salvage therapy or even monotherapy for GI tumor bleeding.

15.
Arthroscopy ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33276050

RESUMO

PURPOSE: We aimed to compare the results of bone marrow stimulation (BMS) versus autologous osteochondral transfer (AOT) as primary surgical option for large cystic osteochondral lesion of talus (OLT) and to further distinguish factors associated with clinical failures and overall survival. METHODS: We retrospectively analyzed patients with symptomatic large cystic OLT (>300 mm3) who underwent either primary BMS or AOT between January 2001 and January 2016 with minimum follow-up of 36 months. Lesion surface area and volume were measured on magnetic resonance imaging. Clinical outcomes were assessed using pain visual analog scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Foot and Ankle Outcome Score (FAOS). Survival outcomes and factors associated with clinical failures were evaluated using Kaplan-Meier analysis and Cox regression analyses, respectively. RESULTS: Fifty of total 853 patients had large cystic OLTs. Thirty-two patients underwent primary BMS and 18 patients underwent primary AOT. Mean follow-up period was 118 months and average lesion surface area and volume were 152.8 mm2 and 850.7 mm3, respectively. Primary AOT group showed significantly superior improvements in clinical outcomes compared to BMS group at last follow-up (p = 0.001). Fourteen patients in primary BMS group and 2 patients in primary AOT group resulted in clinical failure. Kaplan-Meier analysis showed superior survival rate of primary AOT (p = 0.042). Syndesmosis widening (hazard ratio (HR) 12.361; p = 0.004) and large lesion surface area (HR 1.011; p = 0.014) were significant relative risks of clinical failure in primary BMS group. However, the lesion volume showed no significant relationship with clinical failure. CONCLUSION: Long-term results of primary AOT showed superior clinical improvements and survival rate in treating large cystic OLT. Risk factors for failure in primary BMS group were large lesion surface area and syndesmosis widening. STUDY DESIGN: Retrospective comparative study; Level of evidence, 3.

16.
Orthod Craniofac Res ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237624

RESUMO

OBJECTIVES: Greater advancement of the maxilla can be achieved with skeletal-anchored facemasks (SAFM) using miniplates than with conventional tooth-borne facemasks (TBFM). The purpose of this study was to compare the effects of TBFM and SAFM on midfacial soft tissue and nasal bone up to two years after treatment. SETTINGS AND SAMPLE POPULATION: Sixty-seven growing patients with Class III malocclusions were treated with facemasks. They were divided into a SAFM group with 31 subjects (average age 11.1 years) and a TBFM group with 36 subjects (average age 11.0 years). MATERIALS AND METHODS: Cephalometric analysis was conducted using linear and angular midfacial measurements. Lateral cephalograms were taken initially (T0), after treatment (T1) and at two years post-treatment (T2). Significance was assessed between the two groups. RESULTS: Comparing changes in the midfacial area between the SAFM and TBFM groups during the traction period (T0-T1), angular measurements such as SNOr (1.34°), nasolabial angle (4.20°), nasal angles 1 and 2 (1.23°, 2.14°) and linear measurements such as Prn, Sn, A' distance (approximately 2 mm) increased significantly more in the SAFM group. Over the entire treatment period (T0-T2), the changes in SNOr (1.33°), nasolabial angle (6.54°), nasal angles 1 and 2 (1.45°, 2.99°) and Prn, Sn, A' distance (approximately 2 mm) remained significant (P < .05). CONCLUSIONS: In the treatment of growing patients with Class III malocclusions with maxillary deficiency, it was possible to achieve significantly greater advancement in the midfacial area with SAFM treatment than with TBFM treatment. This significant difference was well maintained at two years post-treatment.

17.
Mol Ther ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33160074

RESUMO

Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3-7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction.

19.
Sensors (Basel) ; 20(20)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33076533

RESUMO

The main objectives of this study are to investigate the spectral responses of a fire-damaged concrete slab using Impact-echo (IE) testing, and to develop a simplified model for interpreting the frequency shift due to heat-induced concrete damage after the fire. For these purposes, a reinforced concrete slab specimen (1000 mm (width) by 5000 mm (length) by 210 mm (thickness)) was fabricated in the laboratory. Heat damage in the concrete slab specimen was induced by exposing the bottom of the specimen to the temperatures corresponding to the standard fire curve described in the ASTM E 119 for 3 h. Impact-echo testing was performed on the bottom surface of the concrete slab specimen before and after inducing the fire damage. It was observed that the spectral responses of the fire-damaged concrete were dominated by several non-propagating waves, which resulted in main peak frequencies around 4500 Hz and 5100 Hz. A discrete layered concrete damage model developed in this study was used to reconstruct the variation of the P-wave velocity with the depth of the fire-damaged concrete. It was demonstrated that the predicted P-wave velocity profile using the simplified model showed a good agreement with the measured values from the five core samples, which measured 100 mm (diameter) by 200 mm (height) cylinders, using ultrasonic pulse velocity (UPV) measurements at eight different depths. In addition, the peak frequencies predicted by the simplified model were consistent with the measured peak frequencies. The experimental results in this study demonstrated that IE testing is effective for evaluating the post-fire damage of reinforced concrete slabs. Particularly, the simplified model in this study can be effective for better interpreting the spectral responses of fire-damaged concrete slabs by IE testing.

20.
Biomol Ther (Seoul) ; 28(6): 542-548, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32938818

RESUMO

Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diosmetin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.

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