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Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.
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Regeneración Ósea , Supervivencia Celular , Vidrio , Fosfatos , Estroncio , Titanio , Estroncio/química , Estroncio/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Ratones , Fosfatos/química , Fosfatos/farmacología , Vidrio/química , Titanio/química , Supervivencia Celular/efectos de los fármacos , Ensayo de Materiales , Zinc/química , Línea Celular , Osteoblastos/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Microtomografía por Rayos XRESUMEN
BACKGROUND: This study explored dental students' and dentists' perceptions and attitudes toward artificial intelligence (AI) and analyzed differences according to professional seniority. METHODS: In September to November 2022, online surveys using Google Forms were conducted at 2 dental colleges and on 2 dental websites. The questionnaire consisted of general information (8 or 10 items) and participants' perceptions, confidence, predictions, and perceived future prospects regarding AI (17 items). A multivariate logistic regression analysis was performed on 4 questions representing perceptions and attitudes toward AI to identify highly influential factors according to position, age, sex, residence, and self-reported knowledge level about AI of respondents. Participants were reclassified into 2 subgroups based on students' years in school and 4 subgroups based on dentists' years of experience. The chi-square test or Fisher's exact test was used to determine differences between dental students and dentists and between subgroups for all 17 questions. RESULTS: The study included 120 dental students and 96 dentists. Participants with high level of AI knowledge were more likely to be interested in AI compared to those with moderate or low level (adjusted OR 24.345, p < 0.001). Most dental students (60.8%) and dentists (67.7%) predicted that dental AI would complement human limitations. Dental students responded that they would actively use AI in almost all cases (40.8%), while dentists responded that they would use AI only when necessary (44.8%). Dentists with 11-20 years of experience were the most likely to disagree that AI could outperform skilled dentists (50.0%), and respondents with longer careers had higher response rates regarding the need for AI education in schools. CONCLUSIONS: Knowledge level about AI emerged as the factor influencing perceptions and attitudes toward AI, with both dental students and dentists showing similar views on recognizing the potential of AI as an auxiliary tool. However, students' and dentists' willingness to use AI differed. Although dentists differed in their confidence in the abilities of AI, all dentists recognized the need for education on AI. AI adoption is becoming a reality in dentistry, which requires proper awareness, proper use, and comprehensive AI education.
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Inteligencia Artificial , Actitud del Personal de Salud , Odontólogos , Estudiantes de Odontología , Humanos , Estudiantes de Odontología/psicología , Masculino , Femenino , República de Corea , Odontólogos/psicología , Adulto , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: This study evaluated the performance of four large language model (LLM)-based chatbots by comparing their test results with those of dental students on an oral and maxillofacial radiology examination. METHODS: ChatGPT, ChatGPT Plus, Bard, and Bing Chat were tested on 52 questions from regular dental college examinations. These questions were categorized into three educational content areas: basic knowledge, imaging and equipment, and image interpretation. They were also classified as multiple-choice questions (MCQs) and short-answer questions (SAQs). The accuracy rates of the chatbots were compared with the performance of students, and further analysis was conducted based on the educational content and question type. RESULTS: The students' overall accuracy rate was 81.2%, while that of the chatbots varied: 50.0% for ChatGPT, 65.4% for ChatGPT Plus, 50.0% for Bard, and 63.5% for Bing Chat. ChatGPT Plus achieved a higher accuracy rate for basic knowledge than the students (93.8% vs. 78.7%). However, all chatbots performed poorly in image interpretation, with accuracy rates below 35.0%. All chatbots scored less than 60.0% on MCQs, but performed better on SAQs. CONCLUSIONS: The performance of chatbots in oral and maxillofacial radiology was unsatisfactory. Further training using specific, relevant data derived solely from reliable sources is required. Additionally, the validity of these chatbots' responses must be meticulously verified.
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Educación en Odontología , Evaluación Educacional , Radiología , Humanos , Radiología/educación , Evaluación Educacional/métodos , Educación en Odontología/métodos , Lenguaje , Radiografía Dental/métodosRESUMEN
While literature suggests that youth physical activity (PA) behaviors are affected by network influences, less is known about network influences on perceived skill competency, a component of physical literacy and self-efficacy. This study aims to provide an understanding of potential network characteristics which are associated with youth PA skill competency. Youth (n = 158) between the ages of 8 and 12 years recruited from two summer care programs (i.e., Boys & Girls Clubs) participated in researcher-administered surveys. Youth self-reported their age, sex, involvement in team sports, weekly PA, and skill competency assessed using a version of the PLAYself measure. Youth were also asked to report up to five people in the summer program and five out of the program with whom they interacted the most. Linear regression was used to evaluate associations between skill competency and demographics, PA, and social network characteristics. Skill competency was significantly associated (R2 = .17) with age (ß = -.06, p = .01), sex (ß = -.06, p = .01), sports team involvement (ß = .16, p < .001), and weekly PA (ß = -.20, p < .001). Skill competency was also significantly associated with the number of connections with whom the youth played frequently (ß = .09, p < .001), the number of connections that helped the youth to be active (ß = .18, p < .001), and the heterogeneity of the type of relationships within the youth's network (ß = .11, p < .001). Skill competency scores were significantly associated with both individual variables and social network composition. In addition, youth with networks comprising several types of relationships (heterogeneity) reported a significantly high skill competency. PA interventions can be most effective when considering the reinforcing aspects of networks and skill competency.
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The transcriptional regulator YAP, which plays important roles in the development, regeneration, and tumorigenesis, is activated when released from inhibition by the Hippo kinase cascade. The regulatory mechanism of YAP in Hippo-low contexts is poorly understood. Here, we performed a genome-wide RNA interference screen to identify genes whose loss of function in a Hippo-null background affects YAP activity. We discovered that the coatomer protein complex I (COPI) is required for YAP nuclear enrichment and that COPI dependency of YAP confers an intrinsic vulnerability to COPI disruption in YAP-driven cancer cells. We identified MAP2K3 as a YAP regulator involved in inhibitory YAP phosphorylation induced by COPI subunit depletion. The endoplasmic reticulum stress response pathway activated by COPI malfunction appears to connect COPI and MAP2K3. In addition, we provide evidence that YAP inhibition by COPI disruption may contribute to transcriptional up-regulation of PTGS2 and proinflammatory cytokines. Our study offers a resource for investigating Hippo-independent YAP regulation as a therapeutic target for cancers and suggests a link between YAP and COPI-associated inflammatory diseases.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína Coat de Complejo I/metabolismo , MAP Quinasa Quinasa 3/metabolismo , Neoplasias/metabolismo , Interferencia de ARN , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Línea Celular Tumoral , Proteína Coat de Complejo I/genética , Regulación Neoplásica de la Expresión Génica , Genoma , Vía de Señalización Hippo , Humanos , MAP Quinasa Quinasa 3/genética , Ratones , Neoplasias/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Factores de Transcripción/genética , Proteínas Señalizadoras YAPRESUMEN
EML4-ALK is an oncogenic fusion present in â¼5% of non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants of EML4-ALK with different patient outcomes. Here, we show that, in cell models, EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. EML4-ALK V3 also recruits the NEK9 and NEK7 kinases to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4, as well as constitutive activation of NEK9, also perturbs cell morphology and accelerates migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but does not require ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7, leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/genética , Microtúbulos , Quinasas Relacionadas con NIMA/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas ReceptorasRESUMEN
KEY MESSAGE: Overexpression of acdS in petunia negatively affects seed germination by suppression of ethylene biosynthesis and signaling genes and induction of abscisic acid biosynthesis genes in the seeds. The acdS gene, which encodes 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, has been overexpressed in horticultural crops to improve their tolerance to abiotic stress. However, the role of acdS in the germination of crop seeds has not been investigated, despite its suppression of ethylene production. In this study, acdS overexpression significantly reduced seed weight and germination rate in transgenic petunia cv. Merage Rose (T5, T7, and T12) relative to wild type via the suppression of ethylene biosynthesis and signaling genes and induction of abscisic acid (ABA) biosynthesis genes. The germination rate of T7 was significantly lower than those of T5 and T12, which was linked to higher expression of acdS in the former than the latter. The addition of exogenous ACC and gibberellic acid (GA3) to the germination medium improved the germination rate of T5 seeds and GA3 promoted the germination rate of T12 seeds. However, neither ACC nor GA3 promoted the germination rate of T7 seeds. The improved germination rates in T5 and T12 were associated with the transcriptional regulation of ethylene biosynthesis genes, particularly that of the ACO1 gene, signaling genes, and ABA biosynthesis genes. In this study, we discovered a negative role of acdS in seed germination in petunia. Thus, we highlight the need to consider the negative effect of acdS on seed germination when overexpressing the gene in horticultural crops to improve tolerance to abiotic stress.
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Germinación , Petunia , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Petunia/genética , Petunia/metabolismo , Semillas/metabolismo , Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
Food consumption remains the commonest pathway through which humans ingest higher levels of mercury (Hg). Long-term exposure to Hg through Hg-contaminated food may result in acute or chronic Hg toxicity. Incessant discharge of Hg waste from ASGM facilities into nearby farms contaminates food crops. Ingestion of such food crops by residents may lead to detrimental human health effects. The human health risks upon exposure to total mercury (THg) and methylmercury (MeHg) in farmland soils and plantains from farms sited near ASGM facilities were studied in four communities around Obuasi, Ghana. The human health risk assessment was evaluated using hazard quotient (HQ), estimated average daily intake (e AvDI), hazard index (HI) and Hg elimination and retention kinetics. Tweapease, Nyamebekyere and Ahansonyewodea had HQ, e AvDI and HI for THg of plantains for both adults and children below the recommended USEPA limit of 1, 3 × 10-4 mg/kg/day and 1, respectively. Odumase had HQ, e AvDI and HI for THg of plantains for both adults and children, higher than the guideline values. This meant that only Odumase may cause non-carcinogenic human health effects upon repeated exposure. The HQ, e AvDI and HI values of MeHg for all the study areas were far below guideline values, hence may not pose any non-carcinogenic human health risks to residents even upon repeated exposure. Retention and elimination kinetics of Hg also showed that only plantains from Odumase may pose significant non-carcinogenic human health risks to residents because the final amount of inorganic mercury exceeded the extrapolated USEPA guideline value of 0.393 µg/kg/year.
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Exposición a Riesgos Ambientales/efectos adversos , Mercurio/toxicidad , Minería , Plantago/química , Medición de Riesgo , Contaminantes del Suelo/toxicidad , Suelo/química , Granjas , Ghana , Oro , HumanosRESUMEN
BACKGROUND: The Gretchen Hagen 3 (GH3) genes encode acyl acid amido synthetases, many of which have been shown to modulate the amount of active plant hormones or their precursors. GH3 genes, especially Group III subgroup 6 GH3 genes, and their expression patterns in economically important B. oleracea var. oleracea have not been systematically identified. RESULTS: As a first step to understand regulation and molecular functions of Group III subgroup 6 GH3 genes, 34 GH3 genes including four subgroup 6 genes were identified in B. oleracea var. oleracea. Synteny found around subgroup 6 GH3 genes in B. oleracea var. oleracea and Arabidopsis thaliana indicated that these genes are evolutionarily related. Although expression of four subgroup 6 GH3 genes in B. oleracea var. oleracea is not induced by auxin, gibberellic acid, or jasmonic acid, the genes show different organ-dependent expression patterns. Among subgroup 6 GH3 genes in B. oleracea var. oleracea, only BoGH3.13-1 is expressed in anthers when microspores, polarized microspores, and bicellular pollens are present, similar to two out of four syntenic A. thaliana subgroup 6 GH3 genes. Detailed analyses of promoter activities further showed that BoGH3.13-1 is expressed in tapetal cells and pollens in anther, and also expressed in leaf primordia and floral abscission zones. CONCLUSIONS: Sixty-two base pairs (bp) region (- 340 ~ - 279 bp upstream from start codon) and about 450 bp region (- 1489 to - 1017 bp) in BoGH3.13-1 promoter are important for expressions in anther and expressions in leaf primordia and floral abscission zones, respectively. The identified anther-specific promoter region can be used to develop male sterile transgenic Brassica plants.
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Arabidopsis , Brassica , Arabidopsis/genética , Arabidopsis/metabolismo , Brassica/genética , Brassica/metabolismo , Regulación de la Expresión Génica de las Plantas , Masculino , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas , SinteníaRESUMEN
In the peripheral nervous system (PNS), proper development of Schwann cells (SCs) contributing to axonal myelination is critical for neuronal function. Impairments of SCs or neuronal axons give rise to several myelin-related disorders, including dysmyelinating and demyelinating diseases. Pathological mechanisms, however, have been understood at the elementary level and targeted therapeutics has remained undeveloped. Here, we identify Fibulin 5 (FBLN5), an extracellular matrix (ECM) protein, as a key paracrine factor of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) to control the development of SCs. We show that co-culture with WJ-MSCs or treatment of recombinant FBLN5 promotes the proliferation of SCs through ERK activation, whereas FBLN5-depleted WJ-MSCs do not. We further reveal that during myelination of SCs, FBLN5 binds to Integrin and modulates actin remodeling, such as the formation of lamellipodia and filopodia, through RAC1 activity. Finally, we show that FBLN5 effectively restores the myelination defects of SCs in the zebrafish model of Charcot-Marie-Tooth (CMT) type 1, a representative demyelinating disease. Overall, our data propose human WJ-MSCs or FBLN5 protein as a potential treatment for myelin-related diseases, including CMT.
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BACKGROUND: Nurses frequently encounter ethically challenging situations in everyday practice. In these situations, nurses often know an appropriate course of action to take but are unable to do so. Many studies have examined the ethically challenging situations faced by nurses, but how nurses cope with these situations is not well understood. Therefore, this study aims to explore the coping strategies used or adopted in ethically challenging situations by expert nurses in South Korea. METHODS: Participants were recruited via purposive sampling. Small group interviews were conducted with 26 expert registered nurses in a general hospital in South Korea. The data were analyzed using Giorgi's descriptive phenomenological method. RESULTS: The essential theme of nurses' experience of coping with ethically challenging situations was "being faithful to the nature of caring." This essential theme comprised three themes: self-monitoring of ethical insensitivity, maintaining honesty, and actively acting as an advocate. CONCLUSIONS: The findings of this study suggest that the coping strategies of expert nurses are mostly consistent with the attributes of ethical competence as previously defined in healthcare, and expert nurses can address ethically challenging situations in an effective and ethical manner by faithfully adhering to the spirit of caring. System-wide early counseling and interventions should be considered for nurses who have experienced ethical difficulties.
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The electrochemical reduction of carbon dioxide (CO2 ) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO2 to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO2 to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO2 in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions.
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The electrochemical reduction of carbon dioxide (CO2 ) to value-added products is a promising approach to reducing excess CO2 in the atmosphere. However, the development of electrocatalysts for highly selective and efficient electrochemical CO2 reduction has been challenging because protons are usually easier to reduce than CO2 in an aqueous electrolyte. Recently, single-atom catalysts (SACs) have been suggested as candidate CO2 reduction catalysts due to their unique catalytic properties. To prepare single-atom metal active sites, the stabilization of metal atoms over conductive supports such as graphene sheets to prevent metal aggregation is crucial. To address this issue, a facile method was developed to prepare single-atom nickel active sites on reduced graphene oxide (RGO) sheets for the selective production of carbon monoxide (CO) from CO2 . The tris(2-benzimidazolylmethyl)amine (NTB) ligand was introduced as a linker that can homogeneously disperse nickel atoms on the graphene oxide (GO) sheets. Because the NTB ligands form strong interactions with the GO sheets by π-π interactions and with nickel ions by ligation, they can effectively stabilize nickel ions on GO sheets by forming Ni(NTB)-GO complexes. High-temperature annealing of Ni(NTB)-GO under inert atmosphere produces nickel- and nitrogen-doped reduced graphene oxide sheets (Ni-N-RGO) with single-atom Ni-N4 active sites. Ni-N-RGO shows high CO2 reduction selectivity in the reduction of CO2 to CO with 97 % faradaic efficiency at -0.8â V vs. RHE (reversible hydrogen electrode).
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BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein-Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS. METHODS: The study included 58 patients with GCLS (29 EBV+ and 29 EBV-) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal™), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections. RESULTS: The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P = 0.002), TIL density (4548 vs. 2631/mm2, P < 0.001), and intra-tumoral CD8+ T-cell density (2650 vs. 1060/mm2, P < 0.001) were significantly higher in EBV+ than in EBV- GCLS. In addition, CD8+/CD3+ T-cell ratio was higher in EBV+ than in EBV- GCLS (55.3 vs. 35.8%, P < 0.001). Lower TIL density, defined as < 1350/mm2, was a significant negative factor of survival. CONCLUSIONS: Despite histopathological similarity, quantitative multispectral imaging revealed differences in the tumor immune micro-environment between EBV+ and EBV- GCLS, indicating that the underlying pathogenesis differs in these two disease entities. TIL density may be a prognostic marker in patients with GCLS.
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Infecciones por Virus de Epstein-Barr/patología , Tejido Linfoide/patología , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/virología , Adulto , Anciano , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/metabolismo , Complejo CD3/metabolismo , Linfocitos T CD8-positivos/patología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/patogenicidad , Humanos , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Microambiente Tumoral/inmunologíaRESUMEN
[Purpose] The purpose of this research was to examine the effectiveness of modified constraint-induced movement therapy (mCIMT) on the upper extremity function and occupational performance of stroke patients. [Participants and Methods] An experimental study was carried out on two groups of 7 participants selected by a specific criterion. The experimental group received the mCIMT as well as the conventional rehabilitation therapy (CRT) for 5 days per week over a 2 week period. The control group received only the CRT. Outcome measures included the Manual Function Test (MFT), Motor Activity Log (MAL), and Canadian Occupational Performance Measure (COPM). [Results] Average amount of changes in the MAL and COPM is different in statistical analysis between the mCIMT and the CRT groups before and after the intervention. The mCIMT group showed significant improvements on MFT, MAL, and COPM before and after the intervention. [Conclusion] We suggest that the mCIMT improves the upper extremity function and occupational performance of stroke patients better than the CRT alone.
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As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Cav3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Cav3.2 currents (>90% inhibition) at 10µM concentration and exhibited cytotoxic effect (IC50=5.9µM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S. Furthermore, 8h showed approximately a 2-fold increase in liver metabolic stability in rat and human species compared to KYS05090S. Based on these overall results, 8h (KCP10068F) may therefore represent a good backup compound for KYS05090S for further biological investigations as novel cytotoxic agent. In addition, compound 8g (KCP10067F) was found to partially protect from inflammatory pain via a blockade of Cav3.2 channels.
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Analgésicos/síntesis química , Bloqueadores de los Canales de Calcio/síntesis química , Quinazolinas/química , Quinidina/análogos & derivados , Células A549 , Analgésicos/química , Analgésicos/toxicidad , Animales , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/toxicidad , Canales de Calcio Tipo T/química , Canales de Calcio Tipo T/genética , Canales de Calcio Tipo T/metabolismo , Supervivencia Celular/efectos de los fármacos , Estabilidad de Medicamentos , Flúor/química , Células HEK293 , Humanos , Concentración 50 Inhibidora , Microsomas Hepáticos/metabolismo , Técnicas de Placa-Clamp , Quinazolinas/síntesis química , Quinazolinas/toxicidad , Quinidina/síntesis química , Quinidina/química , Quinidina/toxicidad , RatasRESUMEN
In our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE2 levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a-7c) and the other regioisomer corresponds to a thermodynamic product (8a-8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2 assay studies showed that the kinetic product (7a and 7b; IC50=0.69 and 0.55µM against PGE2) is generally more potent than the thermodynamic product (8a and 8b; IC50=>10 and 0.79µM against PGE2). A molecular docking study also exhibited that the kinetic product (7a) has a higher MolDock Score (-147.4) than that of 8a (-142.4), which is consistent with the PGE2 assay results. A new potent phenylsulfonyl hydrazide (7d; IC50=0.06µM against PGE2) without affecting COX-1 and COX-2 enzyme activities was identified based on these overall results.
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Antiinflamatorios/farmacología , Hidrazinas/síntesis química , Hidrazinas/farmacología , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/farmacología , Animales , Línea Celular , Cristalografía por Rayos X , Dinoprostona/antagonistas & inhibidores , Hidrazinas/química , Ratones , Simulación de Dinámica Molecular , Estructura Molecular , Espectroscopía de Protones por Resonancia Magnética , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/químicaRESUMEN
In concert with advances in surgical reconstruction techniques and improved survival after breast cancer, both the aesthetic and functional outcomes, especially sensory recovery, of breast reconstruction have been addressed. Most studies on sensory recovery in reconstructed breasts have utilized patients' subjective responses to touch, pain, temperature, and pressure. In contrast, this report describes a case of herpes zoster that developed in a free transverse rectus abdominis myocutaneous flap, which provides objective evidence of spontaneous reinnervation after breast reconstruction.
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Colgajos Tisulares Libres/virología , Herpes Zóster/etiología , Mamoplastia , Colgajo Miocutáneo/virología , Regeneración Nerviosa , Complicaciones Posoperatorias/etiología , Recto del Abdomen/virología , Neoplasias de la Mama/cirugía , Femenino , Colgajos Tisulares Libres/inervación , Colgajos Tisulares Libres/trasplante , Herpes Zóster/diagnóstico , Humanos , Mamoplastia/métodos , Persona de Mediana Edad , Colgajo Miocutáneo/inervación , Colgajo Miocutáneo/trasplante , Complicaciones Posoperatorias/diagnóstico , Recto del Abdomen/inervación , Recto del Abdomen/trasplanteRESUMEN
The development of a water oxidation catalyst has been a demanding challenge for the realization of overall water-splitting systems. Although intensive studies have explored the role of Mn element in water oxidation catalysis, it has been difficult to understand whether the catalytic capability originates mainly from either the Mn arrangement or the Mn valency. In this study, to decouple these two factors and to investigate the role of Mn valency on catalysis, we selected a new pyrophosphate-based Mn compound (Li2MnP2O7), which has not been utilized for water oxidation catalysis to date, as a model system. Due to the monophasic behavior of Li2MnP2O7 with delithiation, the Mn valency of Li(2-x)MnP2O7 (x = 0.3, 0.5, 1) can be controlled with negligible change in the crystal framework (e.g., volume change ~1%). Moreover, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, ex-situ X-ray absorption near-edge structure, galvanostatic charging-discharging, and cyclic voltammetry analysis indicate that Li(2-x)MnP2O7 (x = 0.3, 0.5, 1) exhibits high catalytic stability without additional delithiation or phase transformation. Notably, we observed that, as the averaged oxidation state of Mn in Li(2-x)MnP2O7 increases from 2 to 3, the catalytic performance is enhanced in the series Li2MnP2O7 < Li(1.7)MnP2O7 < Li(1.5)MnP2O7 < LiMnP2O7. Moreover, Li2MnP2O7 itself exhibits superior catalytic performance compared with MnO or MnO2. Our study provides valuable guidelines for developing an efficient Mn-based catalyst under neutral conditions with controlled Mn valency and atomic arrangement.
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Porous microspherical carriers have great promise for cell culture and tissue engineering. Dynamic cultures enable more uniform cell population and effective differentiation than static cultures. Here we applied dynamic spinner flask culture for the loading and multiplication of cells onto porous biopolymer microcarriers. The abilities of the microcarriers to populate cells and to induce osteogenic differentiation were examined and the feasibility of in vivo delivery of the constructs was addressed. Over time, the porous microcarriers enabled cell adhesion and expansion under proper dynamic culture conditions. Osteogenic markers were substantially expressed by the dynamic cell cultures. The cell-cultured microcarriers implanted in the mouse subcutaneous tissue for 4 weeks showed excellent tissue compatibility, with minimal inflammatory signs and significant induction of bone tissues. This first report on dynamic culture of porous biopolymer microcarriers providing an effective tool for bone tissue engineering.