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1.
Plants (Basel) ; 13(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39273911

RESUMO

Cannabis (Cannabis sativa) is a versatile crop belonging to the Cannabaceae family, and is dioecious, typically with separate male and female plants. The flowers of female plants, especially the trichomes, accumulate relatively higher contents of cannabinoids compared with those of male plants. For this reason, to obtain seeds that are genetically female, it is desirable to induce the development of male flowers on a female plant that produces genetically female haploid gametes. Silver thiosulfate (STS) is a highly effective chemical for male flower induction. We investigated male flower induction in three commercial cultivars of female cannabis (Spectrum303, SuperwomanS1, and CBGambit) regarding the treatment frequency, stage of application, and concentration of STS applied as a foliar spray. All three cultivars showed adequate induction of male flowers in response to 1.5 mM STS applied at the early reproductive stage. In particular, SuperwomanS1 was most highly responsive to induction of male flowers, even when treated with 0.3 mM STS at the early reproductive stage. Treatment with three applications of STS was more effective compared with a single application, but a single application of 1.5 mM STS at the early reproductive stage was sufficient for male flower induction. A single STS application during the middle stage of reproductive growth was inadequate for induction of male flowers. However, 6 weeks after three applications of STS, CBGambit exhibited approximately 54% male flower induction at 0.3 mM STS, Spectrum303 showed approximately 56% induction at 3 mM STS, and SuperwomanS1 yielded approximately 26% induction at 1.5 mM (expressed as percentage of total number of individuals with the induced male flowers). Pollen stainability tests using KI-I2 solution and Alexander's staining showed high pollen viability with over 65% at different single STS concentrations, indicating that pollen grains induced by STS have sufficient viability for the self-pollination. This study demonstrated that different cultivars of cannabis respond diversely to different STS concentrations and highlighted the potential benefits of three STS applications during the middle reproductive stage for cannabis breeding.

2.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273248

RESUMO

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.


Assuntos
Colágeno , Peptídeos , Pele , Animais , Humanos , Pele/efeitos dos fármacos , Pele/metabolismo , Colágeno/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Camundongos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ondas Ultrassônicas , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Células HaCaT , Peso Molecular , Melaninas , Monofenol Mono-Oxigenase/metabolismo
3.
BMC Oral Health ; 24(1): 1033, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227885

RESUMO

BACKGROUND: The accuracy of intraoral scanning is critical for computer-aided design/computer-aided manufacturing workflows in dentistry. However, data regarding the scanning accuracy of various adjacent restorative materials and intraoral scanners are lacking. This in vitro study aimed to evaluate the effect of adjacent restorative material type and CEREC's intraoral scanners on the accuracy of intraoral digital impressions for inlay cavities. METHODS: The artificial tooth was prepared with an occlusal cavity depth of 2 mm, a proximal box width at the gingival floor of 1.5 mm, and an equi-gingival margin extended disto-occlusally at the transition line angle on both the lingual and buccal sides for an inlay restoration. The adjacent teeth were veneered with crowns made of gold and zirconia, and an artificial tooth (resin) was utilized as the control group. The inlay cavity and adjacent teeth (Gold, Zirconia, and resin) were scanned 10 times using Chairside Economical Restoration of Esthetic Ceramics (CEREC) Primescan (PS), Omnicam (OC), and Bluecam (BC). A reference scan was obtained using a laboratory scanner (3-shape E3). Scanning was performed according to the manufacturer's instructions, including powder application for the BC group. Standard tesselation language files were analyzed using a three-dimensional analysis software program. Experimental data were analyzed using a two-way analysis of variance and the Tukey's post-hoc comparison test. RESULTS: The restorative materials of the adjacent teeth significantly affected the accuracy of the intraoral digital impressions (p < .05). The zirconia group exhibited the highest trueness deviation, followed by the resin and gold groups, with each demonstrating a statistically significant difference (p < .05). The resin group demonstrated the highest maximum positive deviation and deviation in precision. Gold exhibited the lowest average deviation value for trueness compared with those of the other adjacent restorative materials. Intraoral scanner type significantly influenced the trueness and precision of the scan data (p < .05). The average deviation of trueness according to the intraoral scanner type increased in the following order: BC > PS > OC. The average deviation in precision increased in the following order: PS>OC>BC (p < .05). CONCLUSION: The restorative materials of the adjacent tooth and the type of intraoral scanner affect the accuracy of the intraoral digital impression. The trueness of the digital images of the BC group, obtained by spraying the powder, was comparable to that of the PS group. Among the adjacent restorative materials, zirconia exhibited the lowest trueness. In contrast, PS demonstrated the highest precision among the intraoral scanners, while resin displayed the lowest precision among the adjacent restorative materials.


Assuntos
Desenho Assistido por Computador , Restaurações Intracoronárias , Zircônio , Humanos , Técnica de Moldagem Odontológica , Técnicas In Vitro , Materiais Dentários , Coroas , Cerâmica , Planejamento de Prótese Dentária/métodos , Restauração Dentária Permanente/métodos
4.
J Endod ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033800

RESUMO

INTRODUCTION: The aim of this study was to evaluate the efficacy of different irrigation needles and passive ultrasonic activation in removing Ca(OH)2 from an endodontic model that duplicated a root canal configuration of a human natural tooth. METHODS: An extracted human maxillary premolar was subjected to root canal preparation and scanned with microcomputed tomography. A 3-dimensional reconstruction model of the natural tooth was printed to endodontic models using a polyjet printer. The root canals of the models were filled with Ca(OH)2 paste and divided into 2 groups based on the irrigation protocol: conventional syringe-needle irrigation (conventional group) and passive ultrasonic irrigation (PUI) group. Each group was subdivided into 3 groups (n = 10) according to the type of needle: half-cut, side-vented, and TruNatomy irrigation needle. Microcomputed tomographyimaging was used to assess the percentage of reduction of Ca(OH)2. Data were analyzed using two-way analysis of variance test (α = .05). RESULTS: The side-vented and TruNatomy irrigation needles showed significantly higher percentage reductions than the half-cut needle (P < .05) in the conventional irrigation group. The PUI group showed significantly higher percentage reductions of Ca(OH)2 than the conventional group regardless of the type of needle (P < .05). However, no significant difference was found among the needles in the PUI group. CONCLUSIONS: The type of irrigation needle and the use of PUI influenced the removal efficacy of Ca(OH)2. PUI enhanced the removal of Ca(OH)2 regardless of the type of irrigation needle.

5.
Am J Cancer Res ; 14(6): 3186-3197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005664

RESUMO

This study developed a molecular classification model for cervical cancer using machine learning, integrating prognosis related biomarkers with clinical features. Analyzing 281 specimens, 27 biomarkers were identified, associated with recurrence and treatment response. The model identified four molecular subgroups: group 1 (OALO) with Overexpression of ATP5H and LOw risk; group 2 (LASIM) with low expression of ATP5H and SCP, indicating InterMediate risk; group 3 (LASNIM) characterized by Low expression of ATP5H, SCP, and NANOG, also at InterMediate risk; and group 4 (LASONH), with Low expression of ATP5H, and SCP, Over expression of NANOG, indicating High risk, and potentially aggressive disease. This classification correlated with clinical outcomes such as tumor stage, lymph node metastasis, and response to treatment, demonstrating that combining molecular and clinical factors could significantly enhance the prediction of recurrence and aid in personalized treatment strategies for cervical cancer.

7.
PLoS One ; 19(6): e0305360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38935680

RESUMO

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.


Assuntos
Neoplasias do Endométrio , Miométrio , Gradação de Tumores , Invasividade Neoplásica , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Miométrio/patologia , Miométrio/cirurgia , Pessoa de Meia-Idade , Adulto , República da Coreia/epidemiologia , Estudos Prospectivos , Idoso , Período Pré-Operatório , Imageamento por Ressonância Magnética , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia
8.
Animals (Basel) ; 14(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891758

RESUMO

Despite the precarious state of marine turtles as a highly endangered species, our understanding of their diseases remains limited. This case report presents a detailed pathological investigation of spirorchiidiasis, a blood fluke infection that poses a substantial threat to marine turtles. This retrospective study examined three cases of spirorchiid-infected sea turtles, specifically, green sea turtles stranded on Jeju Island, South Korea. Premortem examination of the three spirorchiid-infected green sea turtles demonstrated nonspecific clinical symptoms; blood analysis revealed dehydration, malnutrition, and anemia. Computed tomography scans provided insights into severe pulmonary and extrapulmonary manifestations, including the mass present in the joint region. Post-mortem examinations consistently indicated severe lung lesions and systemic manifestations, with histopathological examination confirming the presence of spirorchiid ova across various organs. Despite the global prevalence of spirorchiidiasis in sea turtles, disease severity varies regionally. This report provides a detailed demonstration of the pathology of spirorchiidiasis in sea turtles from Northeast Asia.

9.
Adv Ther ; 41(7): 2808-2825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771476

RESUMO

INTRODUCTION: Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. METHODS: A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40 mg in study 1 and 16/5/20 mg in study 2. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CVwr) of Cmax was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90% CI was within the BE range. RESULTS: The GMRs (90% CIs) for the AUClast for candesartan and amlodipine were 0.9612 (0.9158-1.0089)/0.9965 (0.9550-1.0397) and 1.0033 (0.9800-1.0271)/1.0067 (0.9798-1.0344), and the GMRs (90% CIs) for Cmax were 0.9600 (0.8953-1.0294)/0.9851 (0.9368-1.0359) and 1.0198 (0.9950-1.0453)/1.0003 (0.9694-1.0321) in studies 1 and 2, respectively. The extended BE ranges calculated from the CVwr of the Cmax of atorvastatin were 0.7814-1.2797 and 0.7415-1.3485, respectively. The GMRs (90% CIs) for the AUClast of atorvastatin were 1.0532 (1.0082-1.1003)/1.0252 (0.9841-1.0680), and the GMRs (90% CIs) for Cmax were 1.0630 (0.9418-1.1997)/0.9888 (0.8792-1.1120) in studies 1 and 2, respectively. CONCLUSION: The Cmax and AUClast values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40 mg and 16/5/20 mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, study 1: NCT04478097; study 2: NCT04627207.


Assuntos
Anlodipino , Atorvastatina , Benzimidazóis , Compostos de Bifenilo , Estudos Cross-Over , Combinação de Medicamentos , Tetrazóis , Humanos , Compostos de Bifenilo/farmacocinética , Compostos de Bifenilo/administração & dosagem , Anlodipino/farmacocinética , Anlodipino/administração & dosagem , Benzimidazóis/farmacocinética , Benzimidazóis/administração & dosagem , Tetrazóis/farmacocinética , Tetrazóis/administração & dosagem , Masculino , Adulto , Feminino , Atorvastatina/farmacocinética , Atorvastatina/administração & dosagem , Adulto Jovem , Área Sob a Curva , Pessoa de Meia-Idade , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/administração & dosagem , Equivalência Terapêutica , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/administração & dosagem , Ácidos Heptanoicos/farmacocinética , Ácidos Heptanoicos/administração & dosagem , Voluntários Saudáveis
10.
Artigo em Inglês | MEDLINE | ID: mdl-38811187

RESUMO

PURPOSE: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives. METHODS: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination. RESULTS: It was necessary to consider including competency assessments for "emergency rescue skills" and "planning and performing prosthetic treatment." There were no significant differences between current and former examinees in their perceptions of the clinical skill test's objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that "oromaxillofacial cranial nerve examination," "temporomandibular disorder palpation test," and "space management for primary and mixed dentition" were unfeasible evaluation objectives and overlapped with dental specialty areas. CONCLUSION: When revising the Korean Dentist Clinical Skill Test's objectives, it is advisable to consider incorporating competency assessments related to "emergency rescue skills" and "planning and performing prosthetic treatment."


Assuntos
Competência Clínica , Avaliação Educacional , Grupos Focais , Humanos , Competência Clínica/normas , República da Coreia , Avaliação Educacional/métodos , Inquéritos e Questionários , Odontólogos , Educação em Odontologia/métodos , Masculino
11.
Dent Mater J ; 43(3): 469-476, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38719583

RESUMO

This study investigates the effects of dentin's drying time, roughness, and curing modes of resin cement on bond strength. Forty human teeth were divided into eight groups based on three experimental factors: dentin's roughness by 240-or 600-grit SiC paper (coarse or fine), dentin wetness with air-drying time (5-s or 10-s), and Single Bond Universal adhesive's curing mode by co-curing with RelyX Ultimate cement or light-curing separately (co-curing or light-curing). The micro-tensile bond strength of fifteen resin-dentin stikcs per groups was measured. Failure mode and adhesive layers were observed using stereoscopic and confocal laser scanning microscopy, respectively. The curing mode of the adhesive layer affected the bond strength of the dentin-resin cement (p<0.05). In particular, the light-curing mode exhibited a significantly higher bond strength than the co-curing one (p<0.05). The bond strength between the resin cement and dentin was improved in the 5-s drying groups than in the 10-s drying groups.


Assuntos
Colagem Dentária , Adesivos Dentinários , Dentina , Teste de Materiais , Cimentos de Resina , Propriedades de Superfície , Resistência à Tração , Humanos , Cimentos de Resina/química , Colagem Dentária/métodos , Adesivos Dentinários/química , Microscopia Confocal , Bis-Fenol A-Glicidil Metacrilato/química , Análise do Estresse Dentário , Cura Luminosa de Adesivos Dentários , Fatores de Tempo
12.
J Neurosurg ; : 1-8, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788231

RESUMO

OBJECTIVE: Shunt-dependent hydrocephalus is a major complication of aneurysmal subarachnoid hemorrhage (SAH). Despite this, the factors influencing shunt dependency and shunt failure remain unclear. Therefore, the aim of this study was to estimate shunt dependency and failure rates and determine the contributing factors in patients with aneurysmal SAH using the Korean National Health Insurance database over a 13-year period. METHODS: Patients with aneurysmal SAH aged > 18 years who underwent surgical procedures were included. Using the shunt surgery prescription data, the shunt-dependent hydrocephalus rate was evaluated according to sex, age, aneurysm location, and year of admission. Among patients who underwent shunt surgery, the shunt failure rate was estimated using surgical prescription data. RESULTS: A total of 57,030 patients with SAH who underwent aneurysm surgery were included. The overall raw rate of shunt-dependent hydrocephalus was 15.0% (8530/57,030). Age (HR 1.04, 95% CI 1.04-1.04; p < 0.001) and endovascular coiling (vs surgical clipping, HR 0.71, 95% CI 0.67-0.74; p < 0.001) were related to shunt-dependent hydrocephalus in the multivariate logistic regression analysis. Posterior circulation and anterior communicating aneurysms showed a high risk of shunt dependency. Among 8530 patients who underwent shunt surgery, the shunt failure rate was 11.3% (961/8530). Female sex (HR 1.18, 95% CI 1.01-1.39; p = 0.0324), age (HR 0.99, 95% CI 0.98-0.99; p < 0.001), early shunt placement (HR 1.25, 95% CI 1.08-1.47; p = 0.004) and lumboperitoneal shunt placement (HR 2.19, 95% CI 1.65-2.91; p < 0.001) were the risk factors for shunt failure in the multivariate logistic regression analysis. CONCLUSIONS: The rate of shunt-dependent hydrocephalus after aneurysmal SAH was 15.0% in this study using a medical claims database in Korea. The shunt surgery rate was highest in patients in their 60s and 70s. Shunt failure occurred in 11.3% of the patients, and a lumboperitoneal shunt was most related to the need for revision surgery.

13.
BMB Rep ; 57(7): 324-329, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38649146

RESUMO

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma. [BMB Reports 2024; 57(7): 324-329].


Assuntos
Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Colangiocarcinoma , Colangiocarcinoma/metabolismo , Colangiocarcinoma/diagnóstico , Humanos , Biomarcadores Tumorais/metabolismo , Prognóstico , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Transdução de Sinais , Masculino , Proteínas de Membrana/metabolismo
14.
J Gynecol Oncol ; 35(3): e87, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38606827

RESUMO

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Laparoscopia/métodos , Recidiva Local de Neoplasia , Quimioterapia de Manutenção/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/uso terapêutico , Ásia Oriental , População do Leste Asiático
15.
Nat Commun ; 15(1): 2983, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582860

RESUMO

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.


Assuntos
Verrucomicrobia , beta Catenina , Masculino , Camundongos , Animais , beta Catenina/metabolismo , Verrucomicrobia/metabolismo , Intestinos , Caderinas/metabolismo , Akkermansia
16.
Clin Pharmacol Drug Dev ; 13(8): 842-851, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38469999

RESUMO

The combined cilostazol and rosuvastatin therapy is frequently used for coronary artery disease treatment. This open-label, 3 × 3 crossover clinical trial evaluated the pharmacokinetics and safety of a fixed-dose combination (FDC) of cilostazol/rosuvastatin (200 + 20 mg) versus a concurrent administration of the separate components (SCs) under both fasted and fed conditions. Among 48 enrolled healthy adults, 38 completed the study. Participants were administered a single oral dose of cilostazol/rosuvastatin (200 + 20 mg), either as an FDC or SCs in a fasted state, or FDC in a fed state, in each period of the trial. Blood samples were taken up to 48 hours after dosing, and plasma concentrations were analyzed using validated liquid chromatography-tandem mass spectrometry. The geometric mean ratios of FDC to SCs for area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast) and maximum plasma concentration (Cmax) were 0.94/1.05 and 1.06/1.15 for cilostazol and rosuvastatin, respectively (AUClast/Cmax). Compared with that during fasting, fed-state administration increased the AUClast and Cmax for cilostazol by approximately 72% and 160% and decreased these parameters for rosuvastatin by approximately 39% and 43%, respectively. To conclude, the FDC is bioequivalent to the SCs, with notable differences in pharmacokinetics when administered in a fed state. No significant safety differences were observed between the treatments.


Assuntos
Área Sob a Curva , Cilostazol , Estudos Cross-Over , Combinação de Medicamentos , Jejum , Voluntários Saudáveis , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administração & dosagem , Rosuvastatina Cálcica/efeitos adversos , Masculino , Adulto , Cilostazol/administração & dosagem , Cilostazol/farmacocinética , Cilostazol/efeitos adversos , Feminino , Jejum/metabolismo , Adulto Jovem , Administração Oral , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Equivalência Terapêutica , Espectrometria de Massas em Tandem
17.
Heliyon ; 10(3): e25040, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333812

RESUMO

Resin-based composite materials are commonly used for restorations, but their dimensional changes during the polymerization could cause various clinical problems. This study evaluated the influence of a base of different materials and thicknesses on the stress magnitude and distribution in a second maxillary premolar with an MOD resin composite restoration using three-dimensional finite element analysis. A sound tooth without cavity was considered as the control group (ST), and another group was restored with composite resin without applying a base material in a MOD cavity (CR). The other three groups were restored with composite resin along with the following base materials: glass ionomer cement, low-viscosity resin, and tricalcium silicate, respectively (CR-GIC, CR-LR, and CR-TS). These three groups were further divided into two subgroups according to the thickness of the base layer: thin (0.5 mm) and thick (1.0 mm). The stress distribution was compared using the maximum principal stress after polymerization shrinkage and vertical loading with 600 N on the occlusal surface. Group ST showed the lowest stress value, and its stress propagation was confined to outer enamel surfaces only. Group CR demonstrated the highest stress distribution in the tooth-restoration interface with increased failure risk on marginal areas. The thin and thick subgroups of the three groups with a base layer had lower stress levels than Group CR. The base materials reduced the marginal stress caused by polymerization shrinkage of composite resin in MOD cavities. Different base materials and thicknesses did not affect the stress distribution.

18.
Int J Mol Sci ; 25(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38397026

RESUMO

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson's trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration.


Assuntos
Degeneração do Disco Intervertebral , Humanos , Degeneração do Disco Intervertebral/metabolismo , Caspase 3/genética , Proteína Beclina-1/genética , Proteína Beclina-1/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Apoptose , Autofagia
19.
J Gynecol Oncol ; 35(5): e57, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38330380

RESUMO

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.


Assuntos
Quimiorradioterapia , Procedimentos Cirúrgicos de Citorredução , Metástase Linfática , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Quimiorradioterapia/métodos , Linfonodos/patologia , Adulto , Pessoa de Meia-Idade , Excisão de Linfonodo/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso
20.
J Imaging Inform Med ; 37(4): 1683-1690, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38381385

RESUMO

Federated learning, an innovative artificial intelligence training method, offers a secure solution for institutions to collaboratively develop models without sharing raw data. This approach offers immense promise and is particularly advantageous for domains dealing with sensitive information, such as patient data. However, when confronted with a distributed data environment, challenges arise due to data paucity or inherent heterogeneity, potentially impacting the performance of federated learning models. Hence, scrutinizing the efficacy of this method in such intricate settings is indispensable. To address this, we harnessed pathological image datasets of endometrial cancer from four hospitals for training and evaluating the performance of a federated learning model and compared it with a centralized learning model. With optimal processing techniques (data augmentation, color normalization, and adaptive optimizer), federated learning exhibited lower precision but higher recall and Dice similarity coefficient (DSC) than centralized learning. Hence, considering the critical importance of recall in the context of medical image processing, federated learning is demonstrated as a viable and applicable approach in this field, offering advantages in terms of both performance and data security.


Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico por imagem , Aprendizado de Máquina , Processamento de Imagem Assistida por Computador/métodos , Inteligência Artificial
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