RESUMO
This study aimed to investigate the effect and mechanism of 2α, 3α, 24-thrihydroxyurs-12-en-24-ursolic acid (TEOA) alone or in combination with cisplatin on oral cancer. TEOA, a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha, has demonstrated antitumor activity in preclinical experiments. However, its role in oral cancer remains poorly understood. Our findings revealed that a low concentration of TEOA did not exhibit significant cytotoxicity against oral squamous cell carcinoma cells. However, when combined with cisplatin, TEOA showed a significant therapeutic effect. The combined treatments resulted in a significant inhibition of proliferation and migration and a significant increase in apoptosis of squamous cell carcinoma cells. Cisplatin exposure increased autophagy levels, which may contribute to chemoresistance. Of note, the presence of TEOA significantly inhibited cisplatin-induced autophagy, leading to improved chemotherapy efficacy. Our findings indicate that a mild low dosage of TEOA may enhance the cytotoxic effect of cisplatin by downregulating autophagy in oral cancer cells.
Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ácido Ursólico , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia , Apoptose , Resistencia a Medicamentos Antineoplásicos , Proliferação de CélulasRESUMO
OBJECTIVES: To compare the facial asymmetry after bimaxillary surgery between mild craniofacial microsomia (CFM) and non-syndromic class II asymmetry. MATERIALS AND METHODS: Cone-beam computed tomography scans of adults with Pruzansky-Kaban types I and IIA CFM (CFM groups, n = 20), non-syndromic skeletal class II asymmetry (Class II group, n = 20), and normal controls (control group, n = 20) were compared. The area asymmetry of lower face and jaw bones was quantified. Landmark-based method was used to evaluate the lower facial asymmetry regarding midline, cants, and contour. RESULTS: There were no significant postoperative differences in the hemi-facial and hemi-jaw area asymmetry between CFM and Class II groups, both of which were significantly larger than the control group. No significant difference was found in the midline deviation and lip and occlusal cants between CFM and Class II groups. The vertical contour asymmetry in CFM group became significantly larger than Class II group. Compared to the control group, the deviation of pronasale, subnasale, and soft-tissue menton, lip and occlusal cants, and sagittal and vertical contour asymmetry in CFM group were significantly larger, as were the deviation of subnasale and soft-tissue menton and vertical contour asymmetry in Class II group. CONCLUSIONS: The vertical contour asymmetry of mild CFM was significantly larger than non-CFM class II after surgery, while the area asymmetry, midline deviation, cants, and sagittal contour asymmetry of lower face showed no significant difference. CLINICAL RELEVANCE: Be aware that correcting vertical asymmetry of contour, lip, and dentition in CFM is still challenging.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Assimetria Facial , Síndrome de Goldenhar , Má Oclusão Classe II de Angle , Procedimentos Cirúrgicos Ortognáticos , Humanos , Assimetria Facial/cirurgia , Assimetria Facial/diagnóstico por imagem , Masculino , Procedimentos Cirúrgicos Ortognáticos/métodos , Feminino , Má Oclusão Classe II de Angle/cirurgia , Má Oclusão Classe II de Angle/diagnóstico por imagem , Adulto , Síndrome de Goldenhar/diagnóstico por imagem , Síndrome de Goldenhar/cirurgia , Resultado do Tratamento , Pontos de Referência Anatômicos , Adolescente , Estudos de Casos e ControlesRESUMO
OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.
Assuntos
Fenda Labial , Fissura Palatina , Tomografia Computadorizada de Feixe Cônico , Má Oclusão Classe III de Angle , Osteotomia de Le Fort , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Fissura Palatina/cirurgia , Fissura Palatina/diagnóstico por imagem , Fenda Labial/cirurgia , Fenda Labial/diagnóstico por imagem , Estudos Retrospectivos , Osteotomia de Le Fort/métodos , Feminino , Masculino , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Adulto , Resultado do Tratamento , Maxila/cirurgia , Maxila/diagnóstico por imagem , Maxila/anormalidades , Osteotomia Maxilar/métodos , Pontos de Referência Anatômicos , AdolescenteRESUMO
OBJECTIVES: The study aimed (1) to evaluate the site and severity of facial asymmetry in Class III patients before and after bimaxillary surgery, and (2) to identify the influence of initial severity and positional jaw asymmetry on residual facial asymmetry. MATERIALS AND METHODS: Preoperative and postoperative cone-beam computed tomography of 65 patients with Class III facial asymmetry who underwent bimaxillary surgery were evaluated. Five midline and 14 paramedian facial soft tissue landmarks were identified to assess facial asymmetry. The outcomes were compared to a control group consisting of 30 age- and gender-matched Class I subjects. The postoperative positional jaw asymmetry (i.e., shift, roll, yaw) of each osteotomy segment (maxilla, mandible, chin, ramus) was also measured. RESULTS: Before surgery, the asymmetry was more severe at the chin, middle and lower contour. Bimaxillary surgery effectively corrected facial asymmetry, particularly in achieving normalization of chin deviation. However, significant asymmetry persisted postoperatively in the middle and lower contour (p < 0.001 and p < 0.01, respectively), which was affected by the positional ramus asymmetry in the roll and shift. CONCLUSIONS: Deviation of the chin, middle and lower contour contributed significantly to overall facial asymmetry in Class III asymmetry. Despite normalization of the chin deviation after bimaxillary surgery, asymmetry persisted at the middle and lower contour, primarily as the result of insufficient correction of the positional ramus asymmetry. CLINICAL RELEVANCE: Understanding the residual asymmetry after bimaxillary surgery is important for minimizing deviation and optimizing the surgical planning for its correction.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Assimetria Facial , Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Humanos , Assimetria Facial/cirurgia , Assimetria Facial/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Masculino , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Procedimentos Cirúrgicos Ortognáticos/métodos , Resultado do Tratamento , Adulto , Pontos de Referência Anatômicos , Índice de Gravidade de Doença , Adolescente , Osteotomia de Le FortRESUMO
This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.
Assuntos
Traumatismos Cardíacos , Células-Tronco Mesenquimais , Infarto do Miocárdio , Animais , Ratos , Antígeno B7-H1 , Infarto do Miocárdio/terapia , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Espécies Reativas de OxigênioRESUMO
The respiratory system is always exposed to air and is most vulnerable to attack by environmental free radicals. The nuclear factor E2-related factor 2-Kelch-like ECH-associated protein 1-antioxidant response element (Nrf2-Keap1-ARE) pathway and p62 are both involved in the oxidative stress response. However, the interplay between these two systems remains largely unknown. This study shows that treatment of L2 cells with tert-Butylhydroquinone (tBHQ) generates a high-molecular-weight (HMW) form of p62, leading to activation of the Nrf2-Keap1-ARE pathway. The levels of HMW-p62 increased as the tBHQ concentration increased, with concomitant decreases seen in the classical form of p62. Moreover, small interfering RNA targeting p62 increases Keap1 protein levels and inactivates the Nrf2-Keap1-ARE pathway. These results demonstrate that the Nrf2-Keap1 pathway is partially regulated by p62. tBHQ-induced HMW-p62 production may be a novel mechanism in the activation of the Nrf2-Keap1-ARE pathway.
Assuntos
Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Hidroquinonas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteína Sequestossoma-1/metabolismoRESUMO
OBJECTIVES: To compare the characteristics of mandibular asymmetry in patients with unilateral craniofacial microsomia (CFM) and class II asymmetry. MATERIALS AND METHODS: Pretreatment cone-beam computed tomography of consecutive adults with Pruzansky-Kaban type I and IIA CFM (CFM group) was analyzed by 3D cephalometry. Fourteen mandibular landmarks and two dental landmarks were identified. The mandibular size and positional asymmetry were calculated by using landmark-based linear and volumetric measurements, in terms of asymmetry ratios (affected/non-affected side) and absolute differences (affected - non-affected side). Results were compared with non-syndromic class II with matched severity of chin deviation (Class II group). Statistical analyses included independent t test, paired t test, chi-square test, and ANOVA. RESULTS: CFM group (n, 21; mean age, 20.4 ± 2.5 years) showed significantly larger size asymmetry in regions of mandibular body, ramus, and condyle compared to Class II group (n, 21; mean age, 27.8 ± 5.9 years) (p < 0.05). The curvature of mandibular body was asymmetric in CFM. Regarding the positional asymmetry of mandibular body, while a comparable transverse shift and a negligible yaw rotation were found among the two groups, the roll rotation in CFM was significantly greater as well as the occlusal (6.06° vs. 4.17°) and mandibular (7.84° vs. 2.80°) plane cants (p < 0.05). CONCLUSIONS: Mild CFM showed significantly more severe size asymmetry and roll rotation in mandible than non-CFM class II asymmetry. CLINICAL RELEVANCE: To improve the mandibular size and positional asymmetry in CFM, adjunct hard tissue augmentation or reduction in addition to OGS orthodontics with a meticulous roll and yaw planning is compulsory, which is expected to be distinct from treating non-CFM class II asymmetry.
Assuntos
Síndrome de Goldenhar , Adolescente , Adulto , Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Assimetria Facial/diagnóstico por imagem , Síndrome de Goldenhar/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Mandíbula/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: The combination of a prosthetic index with Morse taper connection was developed, with the purpose of making prosthetic procedures more precise. However, the presence of the index may compromise the mechanical performance of the abutment. The aim of this study is to evaluate the effect of prosthetic index on stress distribution in implant-abutment-screw system and peri-implant bone by using the 3D finite element methodology. METHODS: Two commercial dental implant systems with different implant-abutment connections were used: the Morse taper connection with platform switching (MT-PS) implant system and the internal hex connection with platform matching (IH-PM) implant system. Meanwhile, there are two different designs of Morse taper connection abutment, namely, abutments with or without index. Consequently, three different models were developed and evaluated: (1) MT-PS indexed, (2) MT-PS non-indexed, and (3) IH-PM. These models were inserted into a bone block. Vertical and oblique forces of 100 N were applied to each abutment to simulate occlusal loadings. RESULTS: For the MT-PS implant system, the maximum stress was always concentrated in the abutment neck under both vertical and oblique loading. Moreover, the maximum von Mises stress in the neck of the MT-PS abutment with index even exceed the yield strength of titanium alloy under the oblique loading. For the IH-PM implant system, however, the maximum stress was always located at the implant. Additionally, the MT-PS implant system has a significantly higher stress level in the abutment neck and a lower stress level around the peri-implant bone compared to the IH-PM implant system. The combined average maximum stress from vertical and oblique loads is 2.04 times higher in the MT-PS indexed model, and 1.82 times for the MT-PS non-indexed model than that of the IH-PM model. CONCLUSIONS: MT-PS with index will cause higher stress concentration on the abutment neck than that of without index, which is more prone to mechanical complications. Nevertheless, MT-PS decreases stress within cancellous bone and may contribute to limiting crestal bone resorption.
Assuntos
Implantes Dentários , Ligas , Fenômenos Biomecânicos , Análise do Estresse Dentário/métodos , Análise de Elementos Finitos , Humanos , Estresse Mecânico , TitânioRESUMO
PURPOSE: To assess the condylar hypoplasia and its correlation with craniofacial deformities in adults with unilateral craniofacial microsomia (CFM). METHODS: Pretreatment cone-beam computed tomography scans of consecutive adults (mean age: 20.4 ± 3.0 years; range: 17.3 to 31.4 years) with Pruzansky-Kaban type I and IIA CFM were reconstructed in 3D. Both condyles were segmented. Asymmetry ratios (affected side/contralateral side) of condylar volume were calculated to indicate the extent of condylar hypoplasia. 3D cephalometry was performed to quantify the maxillomandibular morphology and facial asymmetry. The correlations in between were assessed by using Pearson's or Spearman's correlation coefficients. RESULTS: Thirty-six subjects were enrolled, consisting of 22 subjects with Pruzansky-Kaban type I and 14 subjects with type IIA. The condyles in type IIA group were significantly more hypoplastic in height (asymmetry ratio: 40.69 vs 59.95%, Pâ¯=â¯.006) and volume (18.16 vs 47.84%, P < .001) compared to type I group. Type IIA group had a significantly smaller SNB value than type I group (72.94° vs 77.41°, Pâ¯=â¯.012), and a significantly greater facial asymmetry (P < .05). The hypoplastic extent of condylar volume and Pruzansky-Kaban types were significantly correlated with SNB (râ¯=â¯0.457 and ρâ¯=â¯-0.411, respectively), upper incisor deviation (râ¯=â¯-0.446 and ρâ¯=â¯0.362), chin deviation (râ¯=â¯-0.477 and ρâ¯=â¯0.527), upper occlusal plane cant (râ¯=â¯-0.672 and ρâ¯=â¯0.631), and mandibular plane cant (râ¯=â¯-0.557 and ρâ¯=â¯0.357, P < .05). CONCLUSION: For unilateral CFM adults, greater condylar hypoplasia in volume along with more severe mandibular retrusion and facial asymmetry objectively indicated a higher scale of Pruzansky-Kaban classification (type IIA). These quantitative distinctions are expected to enhance the diagnostic reliability of CFM.
Assuntos
Síndrome de Goldenhar , Adolescente , Adulto , Tomografia Computadorizada de Feixe Cônico , Assimetria Facial/diagnóstico por imagem , Síndrome de Goldenhar/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Mandíbula , Côndilo Mandibular/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Microcarriers are 100- to 300-micron support matrices that permit the growth of adherent cells in bioreactor systems. They have a larger surface area to volume ratio in comparison to single cell monolayers, enabling cost-effective cell production and expansion. Microcarriers are composed of a solid matrix that must be separated from expanded cells during downstream processing stages. The detachment method is chosen on the basis of several factors like cell type, microcarrier surface chemistry, cell confluency and degree of aggregation. The development of microcarriers with a range of physiochemical properties permit controlled cell and protein associations that hold utility for novel therapeutics. In this review, we provide an overview of the recent advances in microcarrier cell culture technology. We also discuss its significance as an ex vivo research tool and the therapeutic potential of newly designed microcarrier systems in vivo.
Assuntos
Biotecnologia/métodos , Técnicas de Cultura de Células/métodos , Microesferas , Reatores Biológicos , Biotecnologia/tendências , Técnicas de Cultura de Células/tendênciasRESUMO
This study aims to investigate the protective effects of the Bauhinia championii (BC) against ischemia/reperfusion (I/R)-induced injury in an isolated heart model. Langendorff-perfused C57BL/6JNarl mice hearts were performed with 30 minutes ischemia and 60 minutes reperfusion by left anterior descending artery ligation. Before reperfusion, boiling water extracts of BC (10 mg/L) was pretreated for 15 minutes. During reperfusion, BC significantly decreased the occurrence of ventricular arrhythmias by lead II electrocardiogram (ECG). Electrophysiological effect of BC was further determined in isolated ventricular myocytes by whole-cell patch clamp technique. The underlying mechanism may result from its Na+ channel blocking activity characterized with reduced rise slope of action potential and Na+ current density. Moreover, BC dramatically reduced I/R-caused infarct size, which was accessed by 2,3,5-triphenyltetrazolium chloride (TTC) assay. Since BC decreased I/R-induced myoglobin release and oxidation of Ca2+ -calmodulin-dependent protein kinase, inhibition of myocardial necroptosis may account for the protective effects of BC on myocytes lose. This study indicated that BC may prevent I/R induced ventricular arrhythmias and myocyte death by blocking Na+ channels and decreasing necroptosis, respectively. Since most of the available antiarrhythmic remedies have unwanted adverse actions, BC could be a novel candidate for the treatment of myocardial infarction and ventricular arrhythmia.
Assuntos
Bauhinia/química , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Extratos Vegetais/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Animais , Eletrocardiografia , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Necroptose/efeitos dos fármacos , Técnicas de Patch-Clamp , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Bloqueadores dos Canais de Sódio/isolamento & purificação , Canais de Sódio/metabolismoRESUMO
OBJECTIVES: This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky-Kaban classification system. MATERIALS AND METHODS: Cone-beam computed tomography images of 48 adult CFM cases were collected. The asymmetry of the mandibular body and ramus was analyzed with 3D landmarks. The mirrored mandibular model was registered on the original model, yielding a color-coded distance map and an average distance (i.e., asymmetry score) to quantify the overall mandibular asymmetry. RESULTS: The lengths of the mandibular body and ramus were significantly shorter on the affected than the contralateral side (p < 0.001). The ANB (p = 0.009), body and ramal lengths (both p < 0.001), and body and ramal length asymmetry (both p < 0.05) were significantly different between mild (types I/IIA) and severe (types IIB/III) cases. The mandibular asymmetry score correlated with mandibular body length asymmetry (r = 0.296, p = 0.046). CFM mandibles showed high variability in shape asymmetry. CONCLUSIONS: CFM patients showed distinct body and ramal length asymmetries. In severe cases, mandibles were smaller, more retruded, and more asymmetric in length. The mandibular shape asymmetry was highly variable regardless of the Pruzansky-Kaban types, being a determinant in the extent of overall mandibular asymmetry. CLINICAL RELEVANCE: The 3D morphologic analysis provides better insights into real mandibular asymmetry. Although the Pruzansky-Kaban classification was applied, high individual variability of the mandibular morphology still existed within the types. Therefore, individualized analyses and treatment plans for CFM patients are highly recommended.
Assuntos
Síndrome de Goldenhar , Adulto , Tomografia Computadorizada de Feixe Cônico , Assimetria Facial/diagnóstico por imagem , Síndrome de Goldenhar/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Mandíbula/diagnóstico por imagemRESUMO
This study investigates the subjective experiences of terminal cancer patients who expedite their corneal donation decisions. The percentage of cancer patients who donate their corneas postmortem is low in Taiwan. The reasons are complex and needs further exploration. A qualitative design using content analysis was used. A semistructured interview approach was adopted to interview cancer patients recruited from a cancer ward in northern Taiwan. The study findings show that the factors contributing to an aversive preference of cancer patients included the necessity to consider the emotions of family members, traditional perceptions, religious reasons, disease, and no reason at all. Most cancer patients maintain a negative stance toward corneal donation. The results obtained in the present study can be used as a reference for future in-service education and promotional efforts regarding corneal donation. Discussing cornea donation needs to become a routine end-of-life care discussion.
Assuntos
Córnea , Tomada de Decisões , Neoplasias/psicologia , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. METHODS AND RESULTS: The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. CONCLUSIONS: Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.
Assuntos
Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hipertensão/complicações , Miocárdio/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Função do Átrio Esquerdo/efeitos dos fármacos , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Fibrose , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Recuperação de Função Fisiológica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of Class III deformity, there are few reports of the success of this approach for patients with facial asymmetry. Therefore, the purpose of this study was to evaluate the outcome of bimaxillary surgery for asymmetric skeletal Class III deformity using a surgery-first approach. MATERIALS AND METHODS: Sixty-five patients who consecutively underwent at least a combined Le Fort I and a bilateral sagittal split osteotomy for asymmetric skeletal Class III deformity were identified in the authors' patient database. Standardized frontal photographs were used to measure the change in midface, intercommissural line, chin from midface, and chin deviation angles as well as upper, middle, and lower contour deviation angles. The facial midline symmetry index, facial contour symmetry index, and overall facial symmetry index were also calculated. Self-reported questionnaires regarding overall appearance and satisfaction with facial areas were administered at least 1 year post-surgery. RESULTS: Forty-six patients had genioplasty. There was a statistically significant improvement in the deviation angles measured and the facial midline, facial contour, and overall facial symmetry index. Self-reported questionnaires, completed at least 1 year post-surgery, showed that patient satisfaction was high. CONCLUSIONS: These findings demonstrate that the surgical-orthodontic treatment with surgery-first approach can successfully maintain or improve facial symmetry. CLINICAL RELEVANCE: The surgery-first approach for improving facial asymmetry using the guidelines described for setups of the models is a feasible alternative to the classic orthodontic-first approach for bimaxillary orthognathic surgery.
Assuntos
Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Face , Assimetria Facial , Feminino , Mentoplastia , Humanos , Má Oclusão Classe III de Angle/cirurgia , Osteotomia de Le Fort , Osteotomia Sagital do Ramo Mandibular , Resultado do TratamentoRESUMO
OBJECTIVES: Facial asymmetry is one of the main concerns in patients with a dentofacial deformity. The aims of the study were to (1) evaluate the changes in facial asymmetry after bimaxillary surgery for asymmetric skeletal class II deformity and (2) compare preoperative and postoperative facial asymmetry of class II patients with normal controls. MATERIALS AND METHODS: The facial asymmetry was assessed for 30 adults (21 women and 9 men, mean age: 29.3 years) who consecutively underwent bimaxillary surgery for asymmetric skeletal class II deformity using cone-beam computed tomography before and at least 6 months after surgery. Thirty soft tissue and two dental landmarks were identified on each three-dimensional facial image, and the asymmetry index of each landmark was calculated. Results were compared with those of 30 normal control subjects (21 women and 9 men, mean age: 26.2 years) with skeletal class I structure. RESULTS: Six months after surgery, the asymmetric index of the lower face and total face decreased significantly (17.8 ± 29.4 and 16.6 ± 29.5 mm, respectively, both p < 0.01), whereas the asymmetric index of the middle face increased significantly (1.2 ± 2.2 mm, p < 0.01). Postoperatively, 53% of the class II patients had residual chin asymmetry. The postoperative total face asymmetric index was positively correlated with the preoperative asymmetric index (r = 0.37, p < 0.05). CONCLUSIONS: Bimaxillary surgery for patients with asymmetric class II deformity resulted in a significant improvement in lower face asymmetry. However, approximately 50% of the patients still had residual chin asymmetry. The total face postoperative asymmetry was moderately related to the initial severity of asymmetry. CLINICAL RELEVANCE: These findings could help clinicians better understand orthognathic outcomes on different facial regions for patients with asymmetric class II deformity.
Assuntos
Assimetria Facial/cirurgia , Má Oclusão Classe III de Angle/cirurgia , Maxila/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Adulto , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.
RESUMO
The nuclear factor erythroid 2-related factor 2 (Nrf2) is required to combat increases in oxidative stress. The chemical compound tert-butylhydroquinone (tBHQ) can downregulate Kelch-like ECH-associated protein 1 (Keap1), a repressor of Nrf2, thus maintaining the stability of Nrf2. tBHQ can also increase intracellular "free" zinc in human bronchial epithelial (16HBE) cells. We aim to investigate whether the intracellular free zinc change plays a role in Nrf2 activation. tBHQ exposure dose-dependently increases intracellular free zinc concentrations within 30 min in 16HBE cells by mobilizing intracellular zinc pools. Active Nrf2 and the antioxidant enzyme heme oxygenase-1 (HO-1) increase at 3 h after tBHQ treatment. Chelating intracellular free zinc with tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) during tBHQ exposure partially abrogates the tBHQ-induced activation of Nrf2 and HO-1 expression, while Keap1 is further decreased. These results indicate that tBHQ-induced stability of Nrf2 is associated with the intracellular free zinc level. Because the activated Nrf2 is phosphorylated, the serine/threonine protein phosphatase activity, which is known to be inhibited by zinc, is assayed. The results showed that tBHQ treatment can suppress cellular protein phosphatase-2A (PP2A) and protein phosphatase-2C (PP2C) activity, which can be abrogated by adding TPEN. This finding is verified in a cell-free protein extract experiment by supplying zinc or by chelating zinc with TPEN. These results provide a novel mechanistic insight into Nrf2 activation in antioxidant enzyme induction involving zinc signaling. The increase of intracellular free zinc may be one mechanism for Nrf2 activation. The inhibition of PP2A and PP2C activity may be involved in Nrf2 phosphorylation modulation.
Assuntos
Hidroquinonas/metabolismo , Membranas Intracelulares/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteína Fosfatase 2/metabolismo , Zinco/metabolismo , Linhagem Celular , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Hidroquinonas/farmacologia , Membranas Intracelulares/efeitos dos fármacos , Fosfoproteínas Fosfatases/antagonistas & inibidores , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2CRESUMO
This study was conducted to synthesize a series of nanosized BiOI-TiO2 catalysts to photodegrade Bisphenol A solution. The BiOI-TiO2 nanoparticles were synthesized in the reverse microemulsions, consisting of cyclohexane, Triton X-100, n-hexanol, and aqueous salt solutions. The synthesized particles were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analyzer, Fourier transform-infrared spectroscopy (FT-IR), ultraviolet-visible light (UV-Vis) absorption spectra and transmission electron microscope (TEM). The photodegradation of Bisphenol A (BPA) in aqueous suspension under visible light irradiation was investigated to explore the feasibility of using the photocatalytic method to treat BPA wastewater. The effects of different molar ratios of BiOI to TiO2 on the photocatalytic activity were discussed. The experimental results revealed that the photocatalytic effect of the BiOI-TiO2 particles was superior to the commercial P25 TiO2. The BPA degradation could be approached by a pseudo-first-order rate expression. The observed reaction rate constant (kobs) was related to nanoparticles dosage and initial solution pH.
Assuntos
Bismuto/química , Técnicas de Química Sintética/métodos , Nanopartículas Metálicas/química , Fotoquímica/métodos , Titânio/química , Catálise , Emulsões , Difração de Raios X/métodosRESUMO
BACKGROUND: Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of class III deformity, there is no report of the success of this approach for patients with cleft lip and palate. Therefore, the purpose of this study was to evaluate the stability and outcome of bimaxillary surgery for cleft-related dentofacial deformity using a surgery-first approach. METHODS: Forty-one patients with unilateral cleft lip and palate who consecutively underwent Le Fort I and bilateral sagittal split osteotomies for skeletal class III deformity were included. Cone-beam computed tomographic scans before surgery, 1 week after surgery, and after orthodontic treatment were used to measure the surgical and postsurgical changes in jaw position by landmarks, and outcomes of jaw protrusion and relation, incisor angle and occlusion, and menton deviation after treatment. Self-report questionnaires regarding satisfaction with overall appearance of the face and seven facial regions were administered after treatment. RESULTS: A clinically insignificant relapse was found in the maxilla (<1 mm) and mandible (<2 mm). There was a significant improvement in the jaw protrusion and relation, incisor angle and occlusion, and menton deviation. Responses from the self-report questionnaires completed after treatment indicated that patient satisfaction was high. CONCLUSION: These findings demonstrate surgical-orthodontic treatment with a surgery-first approach can successfully improve cleft-related dentofacial deformity in patients with unilateral cleft lip and palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.