RESUMEN

OBJECTIVE: To evaluate the diagnostic performance of surgical indications of the revised International Association of Pancreatology (IAP) 2023 guidelines compared to the IAP 2017 and European 2018 guidelines. SUMMARY BACKGROUND DATA: The revised IAP guidelines for surgical indications for branch duct (BD) intraductal papillary mucinous neoplasms (IPMN) include the presence of at least two worrisome features without mandatory endoscopic ultrasound. METHODS: Among 663 patients who underwent resection for pathologically confirmed IPMN in a tertiary hospital between 2013 and 2023, 556 patients with BD or mixed-type IPMN were retrospectively reviewed. Diagnostic performances of the three guidelines for predicting high-grade dysplasia or IPMN with invasive carcinoma were compared. The primary outcome was the malignancy rate. Clinicopathological and radiological imaging data were analyzed. RESULTS: A total of 540, 451, and 490 patients met the surgical indications of the IAP, 2017, 2023, and European guidelines, respectively. Malignant IPMN was observed in 229 (41.2%) patients (high-grade dysplasia, n=99; invasive carcinoma, n=130). Surgical indication by the IAP 2023 guidelines showed higher specificity (29.1 vs. 4.9%, P<0.001), positive predictive value (48.6 vs. 42.4%, P=0.031), and accuracy (55.5 vs. 44.1%, P<0.001) than the IAP 2017 guidelines. It also had higher specificity than the European guidelines (18.7%, P=0.024). The IAP 2023 guidelines showed a superior AUC of surgical indication (0.623 vs. 0.582 for the European guidelines, P<0.001; and 0.524 for the IAP guidelines, P=0.008). CONCLUSIONS: The IAP 2023 guidelines showed better malignancy prediction than the IAP 2017 and European guidelines, potentially reducing unnecessary surgeries.

RESUMEN

Despite several screening levels for NDMA reported in water, soil, air, and drugs, the human risk assessment using biomonitoring concentrations has not been performed. In this study, gender-specific exposure guidance values were determined in humans, then biomonitoring measurements in healthy Korean subjects (32 men and 40 women) were compared to the exposure guidance values to evaluate the current exposure level to NDMA. For the human risk assessment of NDMA, the gender-specific physiologically based pharmacokinetic (PBPK) model was developed in humans using proper physiological parameters, partition coefficients, and biochemical parameters. Using the PBPK model, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty on the single model predictions. The PBPK modeling and Monte Carlo simulation allowed the estimation of the relationship between external dose and blood concentration for the risk assessment. The procedure for the human risk assessment was summarized as follows: (1) estimating a steady-state blood concentration (Cavg) corresponding to the daily no observed adverse effect level (NOAEL) administration in rats; (2) applying uncertainty factors (UFs) for deriving the human Cavg; (3) determining the exposure guidance values as screening criteria; (4) interpreting the human biomonitoring measurements by forward and reverse dosimetry approaches. Using the biomonitoring concentrations, current daily exposures to NDMA were estimated to be 3.95 µg/day/kg for men and 10.60 µg/day/kg for women, respectively. The result of the study could be used as a basis for implementing further risk management and regulatory decision-making for NDMA.

Asunto(s)

Monitoreo Biológico , Dimetilnitrosamina , Modelos Biológicos , Método de Montecarlo , Humanos , Medición de Riesgo , Masculino , Femenino , Monitoreo Biológico/métodos , Dimetilnitrosamina/toxicidad , Dimetilnitrosamina/farmacocinética , Adulto , Nivel sin Efectos Adversos Observados , Factores Sexuales , Animales , Persona de Mediana Edad , Adulto Joven , Ratas , República de Corea , Exposición a Riesgos Ambientales/efectos adversos

RESUMEN

Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.g., steady-state volume of distribution (Vss), clearance (CL), area under the concentration-time curve (AUC), mean residence time (MRT), etc.) of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) were determined by non-compartmental analysis. In addition, one- or two-compartment PK modeling was performed to support inter-species scaling. The PK models appropriately described the blood concentrations of pyronaridine, artesunate, and dihydroartemisinin in all animal species, and the estimated PK parameters in three species were integrated for inter-species allometric scaling to predict human PKs. The simple allometric equation (Y = a × Wb) well explained the relationship between PK parameters and the actual body weight of animal species. The results from the study could be used as a basis for drug repurposing and support determining the effective dosage regimen for new indications based on in vitro/in vivo efficacy data and predicted human PKs in initial clinical trials.

Asunto(s)

Artemisininas , Artesunato , Reposicionamiento de Medicamentos , Naftiridinas , Artesunato/farmacocinética , Artesunato/farmacología , Reposicionamiento de Medicamentos/métodos , Animales , Ratas , Perros , Naftiridinas/farmacocinética , Naftiridinas/farmacología , Artemisininas/farmacocinética , Especificidad de la Especie , Humanos , Modelos Biológicos , Masculino , Antimaláricos/farmacocinética , Antimaláricos/farmacología

RESUMEN

We investigated the relationship between individuals' mental health traits and the characteristics of YouTube videos they watch. The mental health traits considered were stress, depression, anxiety, and self-esteem, which were measured using a survey questionnaire. We considered violence shown in a video, brightness and saturation of a video as video characteristics. We utilized the viewing history log data of the participants and analyzed the videos they watched on YouTube using computer vision techniques based on deep learning algorithms. The results revealed that viewers' consumption of violent videos was positively related to stress, depression, and anxiety, but negatively related to self-esteem. Individuals with higher levels of stress, depression, or anxiety tended to view darker videos than those with lower levels of stress, depression, or anxiety.

RESUMEN

Lipases are important biocatalysts and ubiquitous in plants, animals, and microorganisms. The high growth rates of microorganisms with low production costs have enabled the wide application of microbial lipases in detergent, food, and cosmetic industries. Herein, a novel lipase from Lacticaseibacillus rhamnosus IDCC 3201 (Lac-Rh) was isolated and its activity analyzed under a range of reaction conditions to evaluate its potential industrial application. The isolated Lac-Rh showed a molecular weight of 24 kDa and a maximum activity of 3438.5 ± 1.8 U/mg protein at 60 °C and pH 8. Additionally, Lac-Rh retained activity in alkaline conditions and in 10% v/v concentrations of organic solvents, including glycerol and acetone. Interestingly, after pre-incubation in the presence of multiple commercial detergents, Lac-Rh maintained over 80% of its activity and the stains from cotton were successfully removed under a simulated laundry  setting. Overall, the purified lipase from L. rhamnosus IDCC 3201 has potential for use as a detergent in industrial applications. KEY POINTS: • A novel lipase (Lac-Rh) was isolated from Lacticaseibacillus rhamnosus IDCC 3201 • Purified Lac-Rh exhibited its highest activity at a temperature of 60 °C and a pH of 8, respectively • Lac-Rh remains stable in commercial laundry detergent and enhances washing performance.

Asunto(s)

Detergentes , Estabilidad de Enzimas , Lacticaseibacillus rhamnosus , Lipasa , Lipasa/metabolismo , Lipasa/química , Lipasa/genética , Lacticaseibacillus rhamnosus/enzimología , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/química , Concentración de Iones de Hidrógeno , Detergentes/química , Temperatura , Peso Molecular , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo

RESUMEN

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Fluorouracilo , Leucovorina , MicroARNs , Compuestos Organoplatinos , Enfermedades del Sistema Nervioso Periférico , Humanos , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , MicroARNs/sangre , MicroARNs/genética , Anciano , Hidrocortisona/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Adulto , Catecolaminas/sangre

RESUMEN

This study aimed to investigate sex, age, and species differences of perfluorooctanoic acid (PFOA) using physiologically-based pharmacokinetic (PBPK) models in rats and humans. PBPK models were generally developed as either flow- or permeability-limited models. The flow-limited model is cost-effective and allows for human PK prediction through simple allometric scaling, while the permeability-limited model can incorporate detailed information on the disposition process through in vitro-in vivo extrapolation (IVIVE). PFOA was administered via oral or intravenous administration with 5 mg/kg in male and female rats of different ages and the data was used to develop the PBPK models. Our results showed that both models successfully captured sex differences in rats, while only the flow-limited model with male rats and the permeability-limited model with both male and female rats provided comparable predictions in the human clinical study. More than the flow-limited model, the permeability-limited model effectively explained sex differences in rats and species differences through IVIVE. Additionally, the ontogeny-based mechanistic description of PFOA disposition enabled the interpretation of age- and sex-dependent pharmacokinetics. Although the flow-limited PBPK model lacked mechanistic interpretability compared to the permeability-limited model, it demonstrated reliable human prediction through simple allometric scaling. In conclusion, the permeability PBPK model could interpret age, sex, and species differences and it could improve the accuracy of human prediction.

Asunto(s)

Caprilatos , Fluorocarburos , Modelos Biológicos , Permeabilidad , Especificidad de la Especie , Caprilatos/farmacocinética , Fluorocarburos/farmacocinética , Animales , Masculino , Femenino , Humanos , Ratas , Factores de Edad , Ratas Sprague-Dawley , Factores Sexuales , Administración Oral , Caracteres Sexuales

RESUMEN

Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. Erigeron annuus (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that Erigeron annuus extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used H2O2-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with H2O2 showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.

Asunto(s)

Dermatitis Atópica , Erigeron , Humanos , Animales , Ratones , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Piel/metabolismo , Dinitroclorobenceno/toxicidad , Erigeron/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Dinitrobencenos/efectos adversos , Dinitrobencenos/metabolismo , Hemo-Oxigenasa 1/metabolismo , Peróxido de Hidrógeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratones Endogámicos BALB C , Citocinas/metabolismo

RESUMEN

We elucidate the catalytic graphitization mechanism using in situ analytical approaches. Catalytic graphitization is achieved through a Ni-P electroless plating process at a relatively low temperature of 1600 °C, which allows for a high crystallinity of coke. We also employ an ultrasonic treatment during the Ni-P electroless plating stage to effectively form metal layers on the surface. The impact of the ultrasonic treatment on the Ni-P electroless plating is confirmed by field emission scanning electron microscopy images of the cross-section and an elemental composition analysis using energy dispersive X-ray spectroscopy mapping. Structural analysis of the graphitized cokes via X-ray diffraction (XRD) and Raman spectroscopy shows that Ni-P electroless plating significantly accelerates the graphitization process. Furthermore, we illuminate the graphitization behavior through in situ transmission electron microscopy and XRD analysis. Nickel layers on the coke surface facilitate graphite formation by encouraging the dissolution and precipitation of amorphous carbons, thus resulting in efficient graphitization at a relatively low temperature.

RESUMEN

In addition to regulating cholesterol synthesis, statins have neuroprotective effects. Apoptosis of retinal ganglion cells (RGCs) causes a gradual loss of visual function in glaucoma. This study aimed to investigate the neuroprotective effect of statins on the RGC apoptosis induced by activated Müller glia. Primary Müller cells and RGCs were cultured from the retina of C57BL6 mice. Müller cells were activated with GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and tumor necrosis factor-alpha (TNF-α) released to the medium was measured using an enzyme-linked immunosorbent assay. Cells were pretreated with simvastatin or lovastatin before GSK101. RGCs were treated with conditioned media from Müller glia cultures, and apoptosis was determined using flow cytometry. TRPV4 activation through GSK101 treatment induced gliosis of Müller cells, and the conditioned media from activated Müller cells was potent to induce RGC apoptosis. Statins suppress both gliosis in Müller cells and subsequent RGC apoptosis. TNF-α release to the media was increased in GSK101-treated Müller cells, and TNF-α in the conditioned media was the critical factor causing RGC apoptosis. The increase in TRPV4-mediated TNF-α expression occurred through the nuclear factor kappa-light chain enhancer of activated B cell pathway activation, which was inhibited by statins. Herein, we showed that statins can modulate gliosis and TNF-α expression in Müller cells, protecting RGCs. These data further support the neuroprotective effect of statins, promoting them as a potential treatment for glaucoma.

Asunto(s)

Antineoplásicos , Glaucoma , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Fármacos Neuroprotectores , Animales , Ratones , Antineoplásicos/farmacología , Apoptosis , Medios de Cultivo Condicionados/farmacología , Células Ependimogliales/metabolismo , Glaucoma/tratamiento farmacológico , Glaucoma/patología , Gliosis/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Canales Catiónicos TRPV/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Recent consecutive discoveries of various 2D materials have triggered significant scientific and technological interests owing to their exceptional material properties, originally stemming from 2D confined geometry. Ever-expanding library of 2D materials can provide ideal solutions to critical challenges facing in current technological trend of the fourth industrial revolution. Moreover, chemical modification of 2D materials to customize their physical/chemical properties can satisfy the broad spectrum of different specific requirements across diverse application areas. This review focuses on three particular emerging application areas of 2D materials: smart fibers, soft robotics, and single atom catalysts (SACs), which hold immense potentials for academic and technological advancements in the post-artificial intelligence (AI) era. Smart fibers showcase unconventional functionalities including healthcare/environmental monitoring, energy storage/harvesting, and antipathogenic protection in the forms of wearable fibers and textiles. Soft robotics aligns with future trend to overcome longstanding limitations of hard-material based mechanics by introducing soft actuators and sensors. SACs are widely useful in energy storage/conversion and environmental management, principally contributing to low carbon footprint for sustainable post-AI era. Significance and unique values of 2D materials in these emerging applications are highlighted, where the research group has devoted research efforts for more than a decade.

RESUMEN

N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and histopathology have been well-studied in animal species, there is insufficient data on the blood and tissue exposures that can be correlated with the toxicity of NDMA. The purpose of this study was to evaluate gender-specific pharmacokinetics/toxicokinetics (PKs/TKs), tissue distribution, and excretion after the oral administration of three different doses of NDMA in rats using a physiologically-based pharmacokinetic (PBPK) model. The major target tissues for developing the PBPK model and evaluating dose metrics of NDMA included blood, gastrointestinal (GI) tract, liver, kidney, lung, heart, and brain. The predictive performance of the model was validated using sensitivity analysis, (average) fold error, and visual inspection of observations versus predictions. Then, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty of the single model predictions. The developed PBPK model was applied for the exposure simulation of daily oral NDMA to estimate blood concentration ranges affecting health effects following acute-duration (≤ 14 days), intermediate-duration (15-364 days), and chronic-duration (≥ 365 days) intakes. The results of the study could be used as a scientific basis for interpreting the correlation between in vivo exposures and toxicological effects of NDMA.

Asunto(s)

Carcinógenos , Dimetilnitrosamina , Ratas , Humanos , Animales , Dimetilnitrosamina/toxicidad , Carcinógenos/toxicidad , Distribución Tisular , Pulmón , Hígado , Modelos Biológicos

RESUMEN

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

RESUMEN

Saussurea neoserrata Nakai offers a reliable and efficient source of antioxidants that can help alleviate adverse skin reactions triggered by air pollutants. Air pollutants, such as particulate matter (PM), have the ability to infiltrate the skin and contribute to the higher occurrence of cardiovascular, cerebrovascular, and respiratory ailments. Individuals with compromised skin barriers are particularly susceptible to the impact of PM since it can be absorbed more readily through the skin. This study investigated the impact of protocatechuic acid and syringin, obtained from the n-BuOH extract of S. neoserrata Nakai, on the release of PGE2 and PGD2 induced by PM10. Additionally, it examined the gene expression of the synthesis of PGE2 and PGD2 in human keratinocytes. The findings of this research highlight the potential of utilizing safe and efficient plant-derived antioxidants in dermatological and cosmetic applications to mitigate the negative skin reactions caused by exposure to air pollution.

RESUMEN

BACKGROUND: Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets. METHODS: In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients. RESULTS: The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein-protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3). CONCLUSIONS: This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC.

Asunto(s)

MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Fosfatidilinositol 3-Quinasas/genética , Perfilación de la Expresión Génica , MicroARNs/metabolismo , Biomarcadores

RESUMEN

Various substances, including collagen (Naticol®) and ascorbic acid, that inhibit and prevent skin aging have been studied. Collagen prevents skin aging, has anti-inflammatory effects, and assists in normal wound healing. Ascorbic acid is a representative antioxidant that plays a role in collagen synthesis. To achieve a synergistic effect of collagen and ascorbic acid on all skin types, we prepared a product named "TEENIALL." In addition, we used a container to separate ascorbic acid and collagen to prevent the oxidation of ascorbic acid. To confirm the effects of TEENIALL, we first confirmed its penetrability in fibroblasts, keratinocytes, melanocyte, and human skin tissues. Thereafter, we confirmed the collagen synthesis ability in normal human fibroblasts. Based on the results of in vitro tests, we conducted a clinical trial (KCT0006916) on female volunteers, aged 40 to 59 years, with skin wrinkles and hyperpigmentation, to evaluate the effects of the product in improving skin wrinkles, skin lifting, and pigmentation areas before using the product, and after 2 and 4 weeks of using the product. The values of nine wrinkle parameters that were evaluated decreased and those for skin sagging, pigmentation, dermal density, and mechanical imprint (pressure) relief were improved. Skin wrinkle and pigmentation were evaluated to ensure that the improvement effect was maintained even after 1 week of discontinuing the product use. The evaluation confirmed that the effects were sustained compared to those after 4 weeks of using the product. Additionally, skin wrinkles, skin lifting, radiance, and moisture content in the skin improved immediately after using the product once. Based on the results of in vitro and ex vivo experiments and the clinical trial, we show that the product containing ascorbic acid and collagen was effective in alleviating skin aging.

Asunto(s)

Ácido Ascórbico , Envejecimiento de la Piel , Femenino , Humanos , Ácido Ascórbico/farmacología , Colágeno/farmacología , Piel , Fibroblastos

RESUMEN

BACKGROUND: Eosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL-1ß overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro-autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy-enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL-1ß production in ECRS pathogenesis. METHODS: We investigated the therapeutic effects of trehalose and saccharin on macrophage IL-1ß production and eosinophilia in the mouse model of ECRS with myeloid cell-specific autophagy-related gene 7 (Atg7) deletion. The mechanisms underlying their anti-inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors. RESULTS: Unexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy-independent effect was associated with reduced macrophage IL-1ß expression. Various sugars recapitulated the anti-inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL-1ß production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin. CONCLUSION: Our results revealed a previously unappreciated anti-inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment.

Asunto(s)

Eosinofilia , Sinusitis , Animales , Antiinflamatorios , Autofagia , Eosinofilia/complicaciones , Eosinofilia/tratamiento farmacológico , Eosinofilia/metabolismo , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Macrófagos/metabolismo , Ratones , Sacarina/farmacología , Sinusitis/complicaciones , Sinusitis/metabolismo , Gusto , Trehalosa/farmacología

RESUMEN

Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.

Asunto(s)

Antineoplásicos , MicroARN Circulante , MicroARNs , Enfermedades del Sistema Nervioso Periférico , Neoplasias Gástricas , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Capecitabina/efectos adversos , MicroARN Circulante/genética , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Oxaloacetatos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética

RESUMEN

We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the gliosis caused by glaucomatous stimulation. To induce Müller gliosis in MIO-M1 cells, GSK101 was used to activate TRPV4, and Müller gliosis was evaluated by analyzing vimentin, nestin, and glial fibrillary acidic protein (GFAP) expression. The expression level of TNF-α was determined by ELISA. To evaluate the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death.

Asunto(s)

Glaucoma , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Células Ependimogliales/metabolismo , Glaucoma/metabolismo , Gliosis/metabolismo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidor NF-kappaB alfa/metabolismo , Nestina/metabolismo , Canales Catiónicos TRPV/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vimentina/metabolismo