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Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.
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Aprendizaje Automático , Robótica , Dispositivos Electrónicos Vestibles , Humanos , Robótica/métodos , Piel , Diseño de Equipo , Ingeniería Biomédica/métodosRESUMEN
Material advances in soft bioelectronics, particularly those based on stretchable nanocompositesâfunctional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bondsâhave driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.
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Nanocompuestos , Nanocompuestos/química , Humanos , Prótesis e Implantes , Materiales Biocompatibles/química , Animales , Polímeros/química , ElectrónicaRESUMEN
High dietary fat intake is associated with metabolic dysregulation, but little is known regarding the effects of a high fat diet (HFD) on photoreceptor cell functioning. We explored the intersection of an HFD and the visual cycle adducts that form in photoreceptor cells by nonenzymatic reactions. In black C57BL/6J mice and albino C57BL/6Jc2j mice raised on an HFD until age 3, 6, or 12 months, chromatographically quantified bisretinoids were increased relative to mice on a standard diet. In vivo measurement of fundus autofluorescence, the source of which is bisretinoid, also revealed a significant increase in the HFD mice. Additionally, mice provided with a diet high in fat presented with elevated retinol-binding protein 4, the protein responsible for transporting retinol in plasma. Vitamin A was elevated in plasma although not in ocular tissue. Bisretinoids form in photoreceptor cell outer segments by random reactions of retinaldehyde with phosphatidylethanolamine. We found that the latter phospholipid was significantly increased in mice fed an HFD versus mice on a control diet. In leptin-deficient ob/ob mice, a genetic model of obesity, plasma levels of retinol-binding protein 4 were higher but bisretinoids in retina were not elevated. Photoreceptor cell viability measured as outer nuclear layer thickness was reduced in the ob/ob mice relative to WT. The accelerated formation of bisretinoid we observed in diet-induced obese mice is related to the high fat intake and to increased delivery of vitamin A to the visual cycle.
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Dieta Alta en Grasa , Células Fotorreceptoras , Retinoides , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Leptina/genética , Leptina/metabolismo , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , Proteínas de Unión al Retinol/metabolismo , Vitamina A/metabolismo , Células Fotorreceptoras/citología , Células Fotorreceptoras/fisiología , Supervivencia Celular , Retinoides/metabolismoRESUMEN
Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.
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Degeneración Retiniana , Retinitis Pigmentosa , Animales , Suplementos Dietéticos , Ratones , Mutación , Degeneración Retiniana/genética , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Vitamina ARESUMEN
BACKGROUND: The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). METHODS: This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. RESULTS: After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. CONCLUSIONS: EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.
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The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.
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Electroencefalografía , Epilepsia , Genotipo , Mutación , Fenotipo , Proteínas Activadoras de ras GTPasa , Preescolar , Femenino , Humanos , Masculino , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Discapacidades del Desarrollo/fisiopatología , Epilepsia/genética , Epilepsia/patología , Epilepsia/fisiopatología , Secuenciación del Exoma , Estudios de Asociación Genética , Estudios Longitudinales , Mutación/genética , Proteínas Activadoras de ras GTPasa/genética , Estudios RetrospectivosRESUMEN
BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation. METHODS: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome. RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations. CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.
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Ventilación Unipulmonar , Respiración con Presión Positiva , Humanos , Respiración con Presión Positiva/efectos adversos , Pulmón , Respiración Artificial/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Volumen de Ventilación Pulmonar , Ventilación Unipulmonar/efectos adversosRESUMEN
This study explored the extracellular metabolomic responses of three different Salmonella enterica serotype Typhimurium (S. Typhimurium) strains-ATCC 13311 (STy1), NCCP 16964 (STy4), and NCCP 16958 (STy8)-cultured at refrigeration temperatures. The objective was to identify the survival mechanisms of S. Typhimurium under cold stress by analyzing variations in their metabolomic profiles. Qualitative and quantitative assessments identified significant metabolite alterations on day 6, marking a critical inflection point. Key metabolites such as trehalose, proline, glycerol, and tryptophan were notably upregulated in response to cold stress. Through multivariate analyses, the strains were distinguished using three metabolites-4-aminobutyrate, ethanol, and uridine-as potential biomarkers, underscoring distinct metabolic responses to refrigeration. Specifically, STy1 exhibited unique adaptive capabilities through enhanced metabolism of betaine and 4-aminobutyrate. These findings highlight the variability in adaptive strategies among S. Typhimurium strains, suggesting that certain strains may possess more robust metabolic pathways for enhancing survival in refrigerated conditions.
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BACKGROUND: Whether lateral pelvic node metastasis should be considered as a regional or systemic disease is a long-standing debate. Although previous Japanese studies have considered it to be locoregional disease, Western countries consider it a systemic disease and do not perform lateral pelvic node dissection after preoperative chemoradiotherapy. OBJECTIVE: To evaluate whether lateral pelvic node metastasis is a systemic or regional disease that is amenable to curative resection. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: There were 616 consecutive patients who underwent curative total mesorectal excision alone or with lateral pelvic node dissection after preoperative chemoradiotherapy for locally advanced rectal cancer between 2011 and 2019. MAIN OUTCOME MEASURES: Three-year disease-free and overall survival. RESULTS: A total of 360 patients underwent total mesorectal excision, and 160 patients underwent total mesorectal excision with lateral pelvic node dissection. There was no difference in the 3-year disease-free survival (DFS; p = 0.844) or overall survival rates ( p = 0.921) between the groups. Patients with lateral pelvic node metastasis showed DFS similar to those with perirectal lymph node metastasis in the total mesorectal excision group. In a subgroup analysis, patients with internal iliac pelvic node metastasis showed a disease-free survival comparable to those with perirectal node involvement, and patients with other lateral pelvic node metastasis showed a DFS similar to those with intermediate node involvement. In the lateral pelvic node dissection group, the lateral pelvic node metastatic rate was 32.5%. On multivariate analysis, fewer than 8 of the unilateral harvested lateral pelvic nodes and advanced ypT stage were significantly associated with poor disease-free survival. LIMITATION: The retrospective design. CONCLUSIONS: Lateral lymphatic metastasis showed oncologic outcomes similar to those of upward spread, especially perirectal lymph nodes metastasis. Large cohort studies with long-term follow-up are required to confirm these results. See Video Abstract . LAS METSTASIS LINFTICAS SECUENCIALES LATERALES MUESTRAN RESULTADOS ONCOLGICOS SIMILARES EN LA PROPAGACIN ASCENDENTE DEL CNCER RECTAL AVANZADO DESPUS DE LA RADIOQUIMIOTERAPIA PREOPERATORIA: ANTECEDENTES:Es un debate muy antiguo si las metástasis en los ganglios pélvicos laterales deben considerarse una enfermedad regional o sistémica. Si bien estudios japoneses anteriores las consideran como una enfermedad locorregional, en los países de occidente se las considera como una enfermedad sistémica por la cual no se realiza disección de ganglios pélvicos laterales después de una radioquimioterapia preoperatoria.OBJETIVOS:Evaluar si la metástasis en los ganglios pélvicos laterales se consideran como enfermedad sistémica o enfermedad regional susceptible de resección curativa.DISEÑO:Análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTE:Este estudio se realizó en un centro oncológico terciario.PACIENTES:616 pacientes consecutivos se sometieron a excisión total del mesorrecto curativa sola o con disección de los ganglios pélvicos laterales después de radioquimioterapia preoperatoria en casos de cáncer de recto localmente avanzado entre 2011 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida global y libre de enfermedad a 3 años.RESULTADOS:Un total de 360 pacientes se sometieron a excisión total del mesorrecto y 160 pacientes se sometieron a excisión total del mesorrecto con disección de ganglios pélvicos laterales.No hubo diferencias en la sobrevida libre de enfermedad a 3 años (p = 0,844) ni en las tasas de sobrevida general (p = 0,921) entre los grupos. Los pacientes con metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con metástasis en los ganglios linfáticos perirrectales que se encontraban en el grupo de excisión total del mesorrecto.En el análisis de subgrupos, los pacientes con metástasis en los ganglios pélvicos ilíacos internos mostraron una sobrevida libre de enfermedad comparable a aquellos con afección de los ganglios perirrectales y los pacientes con otras metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con afección de los ganglios intermedios.En el grupo de disección de los ganglios pélvicos laterales, la tasa de metástasis en dichos ganglios fué del 32,5%. En el análisis multivariado, < de 8 ganglios pélvicos laterales resecados unilateralmente y el estadio ypT avanzado se asociaron significativamente con una menor sobrevida libre de enfermedad.LIMITACIÓN:El diseño retrospectivo del estudio.CONCLUSIONES:Las metástasis linfáticas laterales mostraron resultados oncológicos similares a la diseminación ascendente, especialmente las metástasis en los ganglios linfáticos perirrectales. Se requieren grandes estudios de cohortes con seguimiento a largo plazo para confirmar estos resultados. (Traducción-Dr. Xavier Delgadillo ).
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Neoplasias del Recto , Humanos , Metástasis Linfática , Estudios Retrospectivos , Neoplasias del Recto/terapia , Oncología Médica , Quimioradioterapia , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Patients with rectal cancer who underwent lateral pelvic node dissection might be at a higher risk of postoperative complications derived from technical complexity. However, little is known regarding the long-term complications after lateral pelvic node dissection. OBJECTIVES: The study aimed to investigate the long-term complications of preoperative chemoradiotherapy, followed by total mesorectal excision with lateral pelvic node dissection for locally advanced rectal cancers. DESIGN: A retrospective analysis of a prospectively collected database. SETTINGS: This study was conducted in a tertiary cancer center. PATIENTS: Patients with rectal cancer who underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy between 2011 and 2019 were analyzed. All operations were performed via a laparoscopic or robotic approach. MAIN OUTCOME MEASURES: Long-term complications were defined as adverse events that persisted or newly appeared ≥90 days after surgery and could be related to the surgery. RESULTS: A total of 164 patients underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy. Short-term and long-term complication rates were 36.0% and 36.6%, respectively. Lymphocele was the most common long-term complication (17.7% of patients), and 11.6% had anastomotic leakage with chronic sinus. Of the patients with long-term complications, 20.7% of patients needed readmission for treatment. Of the 29 patients with lymphocele, 13 (41.0%) experienced spontaneous absorption and 11 (37.9%) required surgical or percutaneous catheter drainage or antibiotics use. Multivariate analysis showed pathologic pelvic node metastases ( p = 0.008), and a higher number of unilateral harvested pelvic nodes ( p = 0.001) were significantly associated with long-term complications. At the last follow-up (median duration of 43 months), 15.9% of patients had unresolved complications. LIMITATIONS: The retrospective design. CONCLUSIONS: Patients undergoing lateral pelvic node dissection experienced a higher frequency of long-term complications, but half of them had asymptomatic lymphoceles, most of which resolved spontaneously. However, further efforts should be paid to reduce anticipated complications related to lateral pelvic node dissection. See Video Abstract . COMPLICACIONES A LARGO PLAZO DE LA DISECCIN DE LOS GANGLIOS LIFTICOS PLVICOS LATERALES LAPAROSCPICA O ROBTICA DESPUS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA CONTRA EL CNCER DEL RECTO LOCALMENTE AVANZADO: ANTECEDENTES:Los pacientes con cáncer del recto sometidos a disección ganglionar linfática pélvica lateral podrían tener mayor riesgo de complicaciones postoperatorias derivadas de la complejidad técnica. Sin embargo, se sabe poco sobre las complicaciones a largo plazo después de la disección de los ganglios linfáticos pélvicos laterales.OBJETIVOS:Investigar las complicaciones a largo plazo de la quimiorradioterapia preoperatoria, seguida de escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales contra el cáncer de recto localmente avanzado.DISEÑO:Un análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTES:Este estudio se llevó a cabo en un centro oncológico terciario.PACIENTES:Se analizaron pacientes con cáncer de recto que se sometieron a escisión mesorrectal total con disección de ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria entre 2011 y 2019. Todas las operaciones se realizaron mediante abordaje laparoscópico o robótico.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones a largo plazo se definieron como eventos adversos que persistieron o aparecieron recientemente ≥ 90 días después de la cirugía y podrían estar relacionados con la cirugía.RESULTADOS:Un total de 164 pacientes se sometieron a escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria. Las tasas de complicaciones a corto y largo plazo fueron del 36,0% y 36,6%, respectivamente. El linfocele fue la complicación a largo plazo más común (17,7% de los pacientes) y el 11,6% tuvo fuga anastomótica con seno crónico. De los pacientes con complicaciones a largo plazo, el 20,7% de los pacientes necesitaron reingreso para recibir tratamiento. De 29 pacientes con linfocele, 13 (41,0%) experimentaron absorción espontánea y 11 (37,9%) requirieron drenaje quirúrgico o percutáneo con catéter o uso de antibióticos. El análisis multivariado mostró metástasis patológicas en los ganglios linfáticos pélvicos ( p = 0,008) y un mayor número de ganglios pélvicos extraídos unilateralmente ( p = 0,001) se asociaron significativamente con complicaciones a largo plazo. En el último seguimiento (mediana de 43 meses), el 15,9% de los pacientes tuvieron complicaciones no resueltas.LIMITACIÓN:El diseño retrospectivo.CONCLUSIONES:Los pacientes sometidos a disección de ganglios pélvicos linfáticos laterales experimentaron una mayor frecuencia de complicaciones a largo plazo, pero la mitad de ellos tuvieron linfoceles asintomáticos, la mayoría de los cuales se resolvieron espontáneamente. Sin embargo, se deben realizar mayores esfuerzos para reducir las complicaciones previstas relacionadas con la disección de los ganglios linfáticos pélvicos laterales. (Traducción-Dr. Aurian Garcia Gonzalez ).
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Laparoscopía , Linfocele , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Escisión del Ganglio Linfático , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Linfocele/patología , Linfocele/cirugía , Ganglios Linfáticos/patología , Laparoscopía/efectos adversos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Quimioradioterapia/efectos adversos , Resultado del TratamientoRESUMEN
This study used mixed methods to explore the impact of front-of-package health claims and bonus pack messages on consumer evaluations. First, a comprehensive audit of cereal box packages at the world's largest retailer examined how these messages are presented in practice. It was found that negative claims are more frequent and positive claims are less frequent on products with a bonus pack message compared to those without. A subsequent experiment investigated how combinations of health claims and bonus pack messages influence consumer evaluations. It also found that health claims significantly influenced consumer preferences, while bonus pack messages diminished perceptions of food healthiness but increased perceived value. Pairing positive health claims with bonus pack messages, such as "Family Size," improved perceptions of healthiness. Moreover, positive health claims made products seem of lower value, whereas negative health claims did not affect perceived value. Health claims negatively affected value perceptions, even when paired with bonus pack messages like "Large Size." However, the negative effect of health claims on tastiness perceptions was mitigated with "Large Size". The study underscores the complexity of consumer decision-making, and offer insights for food marketers, emphasizing the need of a strategic approach in crafting health-related messaging and promotional strategies for product packaging.
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Conducta de Elección , Comportamiento del Consumidor , Etiquetado de Alimentos , Embalaje de Alimentos , Preferencias Alimentarias , Humanos , Femenino , Masculino , Adulto , Etiquetado de Alimentos/métodos , Preferencias Alimentarias/psicología , Embalaje de Alimentos/métodos , Adulto Joven , Persona de Mediana Edad , Promoción de la Salud/métodos , Percepción , Adolescente , Dieta Saludable/psicología , GustoRESUMEN
Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.
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Antineoplásicos Fitogénicos , Interleucina-6 , Neoplasias Ováricas , Piper , Componentes Aéreos de las Plantas , Extractos Vegetales , Humanos , Interleucina-6/metabolismo , Piper/química , Femenino , Línea Celular Tumoral , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Estructura Molecular , Proliferación Celular/efectos de los fármacosRESUMEN
Based on the fact that substances with a ß-phenyl-α,ß-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.
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Agaricales , Antioxidantes , Inhibidores Enzimáticos , Melaninas , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Agaricales/enzimología , Animales , Antioxidantes/farmacología , Antioxidantes/química , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Melaninas/antagonistas & inhibidores , Melaninas/biosíntesis , Tiazolidinas/química , Tiazolidinas/farmacología , Línea Celular Tumoral , Cinética , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Compuestos de Bencilideno/farmacología , Compuestos de Bencilideno/química , PironasRESUMEN
Efficient delivery of vitamin A to the retinal pigment epithelium is vital to the production of the light-sensitive visual chromophore 11-cis-retinal. Nevertheless, retinol binding protein 4 (RBP4) is the only known carrier of vitamin A in plasma. Here, we present new findings that further characterize the visual cycle in the presence of Rbp4 deficiency. In the face of impaired delivery of retinol in Rbp4-/- mice, we determined that 11-cis-retinaldehyde reached levels that were â¼60% of WT at 4 months of age and all-trans-retinyl ester was 18% of normal yet photoreceptor cell loss was apparent by 8 months of age. The lack of Rbp4 appeared to have a greater impact on scotopic rod-mediated responses than on cone function at early ages. Also, despite severely impaired delivery of retinol, bisretinoid lipofuscin that forms as a byproduct of the visual cycle was measurable by HPLC and by quantitative fundus autofluorescence. In mice carrying an Rpe65 amino acid variant that slows visual cycle kinetics, Rbp4 deficiency had a less pronounced effect on 11-cis-retinal levels. Finally, we found that ocular retinoids were not altered in mice expressing elevated adipose-derived total Rbp4 protein (hRBP4+/+AdiCre+/-). In conclusion, our findings are consistent with a model in which vitamin A can be delivered to the retina by Rbp4-independent pathways.
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Retinaldehído , Vitamina A , Animales , Ratones , Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Retinaldehído/metabolismo , Retinoides/metabolismo , Vitamina A/metabolismo , Proteínas Plasmáticas de Unión al Retinol/genética , Proteínas Plasmáticas de Unión al Retinol/metabolismoRESUMEN
The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.
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OBJECTIVE: To evaluate whether robotic for middle or low rectal cancer produces an improvement in surgical outcomes compared with laparoscopic surgery in a randomized controlled trial (RCT). BACKGROUND: There is a lack of proven clinical benefit of robotic total mesorectal excision (TME) compared with a laparoscopic approach in the setting of multicenter RCTs. METHODS: Between July 2011 and February 2016, patients diagnosed with an adenocarcinoma located <10 cm from the anal verge and clinically rated T1-4aNxM0 were enrolled. The primary outcome was the completeness of TME assessed by a surgeon and a pathologist. RESULTS: The RCT was terminated prematurely because of poor accrual of data. In all, 295 patients were assigned randomly to a robot-assisted TME group (151 in R-TME) or a laparoscopy-assisted TME group (144 in L-TME). The rates of complete TME were not different between groups (80.7% in R-TME, 77.1% in L-TME). Pathologic outcomes including the circumferential resection margin and the numbers of retrieved lymph nodes were not different between groups. In a subanalysis, the positive circumferential resection margin rate was lower in the R-TME group (0% vs 6.1% for L-TME; P =0.031). Among the recovery parameters, the length of opioid use was shorter in the R-TME group ( P =0.028). There was no difference in the postoperative complication rate between the groups (12.0% for R-TME vs 8.3% for L-TME). CONCLUSIONS: In patients with middle or low rectal cancer, robotic-assisted surgery did not significantly improve the TME quality compared with conventional laparoscopic surgery (ClinicalTrial.gov ID: NCT01042743).
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Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Márgenes de Escisión , Resultado del Tratamiento , Estudios Retrospectivos , Laparoscopía/efectos adversos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patologíaRESUMEN
Despite a high vaccination rate, the COVID-19 pandemic continues with immune-evading Omicron variants. The success of additional antigenic stimulation through breakthrough infection (BI) and updated vaccination in overcoming antigenic imprinting needs to be determined. Participants in a long-term follow-up cohort of healthcare worker (HCW) vaccinee were categorized according to their infection/vaccination status. Anti-SARS-CoV-2 spike/nucleocapsid protein antibodies were measured, and plaque reduction neutralization tests (PRNTs) against wild-type (WT), BA.5, BN.1, and XBB.1.5 were conducted. The neutralization activity of intravenous immunoglobulin (IVIG) products was evaluated to assess the immune status of the general population. Ninety-five HCWs were evaluated and categorized into seven groups. The WT PRNT ND50 value was highest regardless of infection/vaccination status, and groups with recent antigenic stimulation showed high PRNT titers overall. Groups with double Omicron stimulation, either by BI plus BA.4/5 bivalent vaccination or repeated BI, exhibited significantly higher BA.5 and BN.1 PRNT to WT PRNT ratios than those with single Omicron stimulation. Overall group immunity was estimated to be boosted in January 2023, reflecting the effect of the BA.4/5 bivalent booster and additional BIs, but slightly declined in June 2023. A substantial increase in the antibody concentrations of IVIG products was noticed in 2022, and recently produced IVIG products exhibited a substantial level of cross-reactive neutralizing activity against emerging variants. Neutralizing activity against emerging variants could be enhanced by repeated antigenic stimulation via BI and/or updated vaccination. Overall group immunity was elevated accordingly, and IVIG products showed substantial activity against circulating strains.
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Anticuerpos Neutralizantes , COVID-19 , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Infección Irruptiva , Pandemias , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Antivirales , VacunaciónRESUMEN
Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.
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COVID-19 , SARS-CoV-2 , Humanos , Pruebas de Neutralización , SARS-CoV-2/genética , COVID-19/diagnóstico , Inmunoensayo , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Disruption of the endothelial glycocalyx (EG) is associated with a poor prognosis in various clinical settings. This study aimed to determine the association between immediate postoperative serum syndecan-1 levels, a representative marker for EG degradation, and major postoperative morbidity and mortality in patients undergoing robot-assisted esophagectomy. METHODS: Patients who underwent robot-assisted esophagectomy between 2018 and 2022 were prospectively enrolled. The primary outcome was the association between immediate postoperative syndecan-1 levels and the occurrence of major postoperative morbidity and mortality within 30 days of surgery. Patients were classified into low and high syndecan-1 groups based on the optimal cut-off value of syndecan-1 for predicting major morbidity and mortality. A multivariable logistic regression analysis was performed to investigate the risk factors for major morbidity and mortality. RESULTS: A total of 207 patients were analyzed. Patients with high syndecan-1 levels (≥48 ng/mL) showed a significantly greater incidence of unexpected returns to the operating room and anastomotic leaks and longer durations of hospital and intensive care unit stays than patients with low syndecan-1 levels (<48 ng/mL). Immediate postoperative syndecan-1 levels ≥48 ng/mL (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.23-4.76), American Society of Anesthesiologists physical status ≥III (OR 3.36, 95% CI 1.56-7.22), and current smoker (OR 4.02, 95% CI 1.52-10.61) were independently associated with major morbidity and mortality within 30 days of esophagectomy. CONCLUSIONS: Immediate postoperative syndecan-1 levels ≥48 ng/mL could be used for the early detection of patients at high risk of complications after robot-assisted esophagectomy.
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Neoplasias Esofágicas , Robótica , Humanos , Sindecano-1 , Esofagectomía/efectos adversos , Neoplasias Esofágicas/cirugía , Incidencia , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM). METHODS: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values. RESULTS: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods. CONCLUSIONS: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes.