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BACKGROUND: Improving cancer survival rates highlights post-treatment fertility implications for reproductive-aged women. To provide fertility care for cancer survivors, nurses need instruments to assess and communicate reproductive concerns with cancer survivors and healthcare providers. This study aimed to translate the Reproductive Concerns after Cancer Scale (RCAC) into Korean and examine its psychometric properties in young female cancer survivors in South Korea. METHODS: The RCAC was translated into Korean, involving expert bilingual translators for initial translation and reverse translation for cultural and semantic accuracy. In detail, the RCAC was translated into Korean and evaluated in a preliminary study involving 10 cancer survivors. Subsequently, a revised version of the instrument was administered to 182 cancer survivors and a psychometric evaluation was conducted. The process included verifying content validity, and then assessing construct validity using exploratory factor analysis and criterion validity. The reliability of the instrument was quantified by measuring its internal consistency using Cronbach's alpha. RESULTS: The translated RCAC demonstrated an item-level content validity index of 1.0 and a scale-level index of 1.0. The content was finalized based on preliminary survey findings, which revealed that all participants thought the instrument was clear. The Korean version of the RCAC demonstrated a satisfactory level of validity per exploratory factor analysis, which resulted in a 14-item instrument consisting of three subscales: "fertility potential" (six items), "health problem" (five items), and "acceptance" (three items). The items and subscales explained 57.6% of the variance. Criterion validity was confirmed through an analysis of the correlation between the Korean version of the RCAC and both the FACT-G (r = -0.36, p < .001) and PHQ-9 (r = 0.38, p < .001). Cronbach's alpha coefficient of the Korean version of the RCAC was 0.83. CONCLUSIONS: The Korean version of the RCAC is a valid and reliable instrument for assessing reproductive concerns in female cancer survivors. Thus, this instrument can be used to provide tailored care to female cancer survivors of reproductive age by clarifying and assess their reproductive concerns. This may support the development of guidelines or policies to provide care for those with reproductive concerns who require nursing care.
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BACKGROUND: Digital health technologies are becoming increasingly available to children and young people and their families. However, there are no scoping reviews that provide both an overview of the characteristics of digital interventions for children and young people and potential challenges to be considered when developing and implementing them. OBJECTIVE: This study aimed to systematically review scientific publications to identify the current characteristics and potential complications of digital interventions for children and young people. METHODS: This scoping review was conducted using the framework of Arksey and O'Malley and adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews. A search of 5 databases (PubMed, Scopus, Embase, MEDLINE, and CINAHL) and Google Scholar was performed for eligible clinical trials published between January 1, 2018, and August 19, 2022. RESULTS: The initial search of the 5 databases yielded 3775 citations; duplicates and those not meeting the inclusion criteria were eliminated. In total, 34 articles were included in the final review and relevant information, such as the descriptive characteristics and potential challenges, were classified. Mental health (26/34, 76%) was the most common target for the digital intervention for children and young people, exceeding physical health (8/34, 24%) by more than 3 times. In addition, a substantial number of digital interventions were dedicated solely to children and young people. Digital interventions for children and young people were more likely to be delivered via computers (17/34, 50%) rather than smartphones (13/34, 38%). More than one-third of the studies (13/34, 38%) applied cognitive behavioral theory as the theory of digital interventions. The duration of the digital intervention for children and young people was more likely to vary depending on the target user rather than the target disease. Intervention components were classified into 5 categories: guidance, task and activity, reminder and monitoring, supportive feedback, and reward system. Potential challenges were subcategorized into ethical, interpersonal, and societal challenges. For ethical challenges, the consent of children and young people or caregivers, potential risk of adverse events, and data privacy issues were considered. For interpersonal challenges, the engagement of children and young people was affected by the preference or barrier of caregivers to participate in studies. For societal challenges, restricted ethnicity in recruitment, limited availability of digital technology, differences in internet use patterns between girls and boys, unified clinical settings, and language barriers were described. CONCLUSIONS: We identified potential challenges and provided suggestions about ethical, interpersonal, and societal aspects to consider when developing and deploying digital-based interventions for children and young people. Our findings provide a thorough overview of the published literature and may serve as a comprehensive, informative foundation for the development and implementation of digital-based interventions for children and young people.
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Saúde Mental , Smartphone , Masculino , Feminino , Humanos , Criança , AdolescenteRESUMO
BACKGROUND: We investigated whether the distribution of mechanoreceptors in three sections of the anterior talofibular ligament (ATFL) differed. METHODS: The ATFL was obtained from 29 ankles of 21 fresh-frozen cadavers and divided into fibular attachment, mid-ligament, and talar attachment parts. Histologically, mechanoreceptors were classified as Ruffini (type I), Vater-Pacini (type II), Golgi-Mazzoni (type III), and free nerve ending corpuscles (type IV); the presence of these mechanoreceptors was compared among the three ATFL sections. RESULTS: Type I mechanoreceptors were significantly more numerous than the other receptor types. Comparing the three sections of the ATFL, the number of type I mechanoreceptors differed significantly between the mid-ligament and fibular attachment (p = 0.006), while the number of type III mechanoreceptors differed significantly between the talar and fibular attachments (p = 0.005) and between the mid-ligament and talar attachment (p = 0.011). CONCLUSIONS: The four types of mechanoreceptors were distributed differently among the three sections of the ATFL. Type I mechanoreceptors were more numerous in all sections compared to the other receptors.
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Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3ß oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.
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Adenocarcinoma/tratamento farmacológico , Antígeno Ca-125/genética , Carcinogênese/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Receptores ErbB/genética , Proteínas de Membrana/genética , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Anticorpos Monoclonais/farmacologia , Antígeno Ca-125/imunologia , Carcinogênese/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Camundongos , Metástase Neoplásica , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Transdução de SinaisRESUMO
Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.
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Acetatos/química , Fatores de Transcrição NFATC/metabolismo , Osteogênese/efeitos dos fármacos , Ligante RANK/efeitos dos fármacos , Cogumelos Shiitake/química , Transdução de Sinais/efeitos dos fármacos , Animais , Reabsorção Óssea/metabolismo , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/genética , Proteínas de Neoplasias/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Proteínas Proto-Oncogênicas c-fos , Ligante RANK/genética , Ligante RANK/metabolismo , Fatores de Transcrição/metabolismo , Transcriptoma , Peixe-ZebraRESUMO
By means of electrospinning with the thermal annealing process, we investigate a highly efficient sensing platform driven by a hierarchical hetero-nanostructure for the sensitive detection of biologically relevant molecules, consisting of single crystalline ruthenium dioxide nanorods (RuO2 NRs) directly grown on the surface of electrospun tungsten trioxide nanofibers (WO3 NFs). Electrochemical measurements reveal the enhanced electron transfer kinetics at the prepared RuO2 NRs-WO3 NFs hetero-nanostructures due to the incorporation of conductive RuO2 NRs nanostructures with a high surface area, resulting in improved relevant electrochemical sensing performances for detecting H2O2 and L-ascorbic acid with high sensitivity.
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Ácido Ascórbico/isolamento & purificação , Técnicas Biossensoriais , Técnicas Eletroquímicas , Peróxido de Hidrogênio/isolamento & purificação , Ácido Ascórbico/química , Peróxido de Hidrogênio/química , Nanofibras/química , Nanoestruturas/química , Nanotubos/química , Óxidos/química , Compostos de Rutênio/química , Tungstênio/químicaRESUMO
The bone tissue is a dynamic complex that constitutes of several interdependent systems and is continuously remodeled through the concerted actions of bone cells. Osteoblasts are mononucleated cells, derived from mesenchymal stem cells, responsible for bone formation. Osteoclasts are large multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage and are responsible for bone resorption. The lineage-specific differentiation of bone cells requires an epigenetic regulation of gene expressions involving chromatin dynamics. The key step for understanding gene regulatory networks during bone cell development lies in characterizing the chromatin modifying enzymes responsible for reorganizing and potentiating particular chromatin structure. This review covers the histone-modifying enzymes involved in bone development, discusses the impact of enzymes on gene expression, and provides future directions and clinical significance in this area.
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Remodelação Óssea , Diferenciação Celular , Código das Histonas , Animais , Humanos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , OsteogêneseRESUMO
Osteoporosis is a common disorder of bone remodeling, caused by the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Recently, we reported that matrix metalloproteinase-9 (MMP-9)-dependent histone H3 proteolysis is a key event for proficient osteoclast formation. Although it has been reported that several MMP-9 inhibitors, such as tetracycline and its derivatives, show an inhibitory effect on osteoclastogenesis, the molecular mechanisms for this are not fully understood. Here we show that tetracycline analogs, especially tigecycline and minocycline, inhibit osteoclast formation by blocking MMP-9-mediated histone H3 tail cleavage. Our molecular docking approach found that tigecycline and minocycline are the most potent inhibitors of MMP-9. We also observed that both inhibitors significantly inhibited H3 tail cleavage by MMP-9 in vitro. These compounds inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by blocking the NFATc1 signaling pathway. Furthermore, MMP-9-mediated H3 tail cleavage during osteoclast differentiation was selectively blocked by these compounds. Treatment with both tigecycline and minocycline rescued the osteoporotic phenotype induced by prednisolone in a zebrafish osteoporosis model. Our findings demonstrate that the tetracycline analogs suppress osteoclastogenesis via MMP-9-mediated H3 tail cleavage, and suggest that MMP-9 inhibition could offer a new strategy for the treatment of glucocorticoid-induced osteoporosis.
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Histonas/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Minociclina/farmacologia , Osteogênese/efeitos dos fármacos , Tigeciclina/farmacologia , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Modelos Moleculares , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Peixe-ZebraRESUMO
A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-κB (NF-κB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell-penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-α (TNFα)-induced NF-κB activation. We observed that TAT-A20 was effectively transduced into cells within 30 min, whereas A20 protein without TAT motive was not. TAT-A20 also inhibited NF-κB induction in fibroblasts stimulated with TNFα. These results suggest that increasing intracellular level of A20 can be an effective means to suppress NF-κB activation and treat inflammatory diseases.
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Peptídeos Penetradores de Células/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Escherichia coli/genética , Células HEK293 , Humanos , Espaço Intracelular/metabolismo , Redobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/química , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genéticaRESUMO
NiO/NiCo2O4 nanotubes with a diameter of approximately 100 nm are synthesized using Ni and Co precursors via electro-spinning and subsequent calcination processes. The tubular structure is confirmed via transmission electron microscopy imaging, whereas the structures and elemental compositions of the nanotubes are determined using x-ray diffraction, energy dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. N2 adsorption isotherm data reveal that the surface of the nanotubes consists of micropores, thereby resulting in a significantly higher surface area (â¼20 m2 g-1) than expected for a flat-surface structure (<15 m2 g-1). Herein, we present a study of the catalytic activity of our novel NiO/NiCo2O4 nanotubes for CO and acetaldehyde oxidation. The catalytic activity of NiO/NiCo2O4 is superior to Pt below 100 °C for CO oxidation. For acetaldehyde oxidation, the total oxidation activity of NiO/NiCo2O4 for acetaldehyde is comparable with that of Pt. Coexistence of many under-coordinated Co and Ni active sites in our structure is suggested be related to the high catalytic activity. It is suggested that our novel NiO/NiCo2O4 tubular structures with surface microporosity can be of interest for a variety of applications, including the catalytic oxidation of harmful gases.
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PURPOSE: Obesity is a major public health concern. Despite its multi-factorial etiology, alterations in intestinal microbiota and the immune system are frequently observed. We investigated the effect of Duolac Gold (DG), a probiotic formulation containing 2 Lactobacillus strains (L. acidophilus LA1 and L. rharmnosus LR5), 3 Bifidobacterium (B. bifidum BF3, B. lactis BL3, and B. longum BG7), and Streptococcus thermophilus ST3, on morphometric and metabolic parameters, intestinal microbiota, and intestinal immune responses in a high-fat diet (HFD)-induced obese rat model. METHODS: Rats received either a conventional balanced diet or HFD with or without water containing DG for 8 weeks. HFD-induced adiposity, intestinal microbiota, and changes in inflammatory cytokine, chemokine, and metabolite levels in serum were evaluated. RESULTS: DG administration effectively decreased HFD-induced body weight and modulated morphometric and metabolic parameters. Quantitative analysis of fecal microbiota showed that obese rats given DG exhibited significantly increased levels of Bacteroidetes, Lactobacillus, and Bifidobacterium, with significant decreases in the level of Firmicutes. Serum levels of the inflammatory cytokines and the chemokine were also altered. Serum metabolite analysis revealed that DG administration modulated HFD-induced changes in serum metabolites, including fatty acids (FA), lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylcholine (PC), and triacylglycerol (TAG). CONCLUSIONS: DG administration appears to have the potential to alleviate HDF-induced obesity through the modulation of intestinal microbiota, immune responses, and host metabolism, which supports the use of probiotics to treat obesity.
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Dieta Hiperlipídica , Obesidade/terapia , Probióticos , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Pollen is an important cause of respiratory allergic reactions. As individual sanitation has improved, allergy risk has increased, and this trend is expected to continue due to climate change. Atmospheric pollen concentration is highly influenced by weather conditions. Regression analysis and modeling of the relationships between airborne pollen concentrations and weather conditions were performed to analyze and forecast pollen conditions. Traditionally, daily pollen concentration has been estimated using regression models that describe the relationships between observed pollen concentrations and weather conditions. These models were able to forecast daily concentrations at the sites of observation, but lacked broader spatial applicability beyond those sites. To overcome this limitation, an integrated modeling scheme was developed that is designed to represent the underlying processes of pollen production and distribution. A maximum potential for airborne pollen is first determined using the Weibull probability density function. Then, daily pollen concentration is estimated using multiple regression models. Daily risk grade levels are determined based on the risk criteria used in Korea. The mean percentages of agreement between the observed and estimated levels were 81.4-88.2 % and 92.5-98.5 % for oak and Japanese hop pollens, respectively. The new models estimated daily pollen risk more accurately than the original statistical models because of the newly integrated biological response curves. Although they overestimated seasonal mean concentration, they did not simulate all of the peak concentrations. This issue would be resolved by adding more variables that affect the prevalence and internal maturity of pollens.
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Alérgenos/análise , Modelos Biológicos , Modelos Estatísticos , Pólen , Poluentes Atmosféricos/análise , Previsões , Humulus , Quercus , Análise de Regressão , República da Coreia , RiscoRESUMO
To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify key regulatory genes, we performed an integrated analysis of the transcriptome and metabolome in sprouts germinated from three colored potato cultivars: light-red Hongyoung, dark-purple Jayoung, and white Atlantic. We investigated transcriptional and metabolic changes using statistical analyses and gene-metabolite correlation networks. Transcript and metabolite profiles were generated through high-throughput RNA-sequencing data analysis and ultraperformance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, respectively. The identification and quantification of changes in anthocyanin were performed using molecular formula-based mass accuracy and specific features of their MS(2) spectra. Correlation tests of anthocyanin contents and transcriptional changes showed 823 strong correlations (correlation coefficient, R (2)>0.9) between 22 compounds and 119 transcripts categorized into flavonoid metabolism, hormones, transcriptional regulation, and signaling. The connection network of anthocyanins and genes showed a regulatory system involved in the pigmentation of light-red Hongyoung and dark-purple Jayoung potatoes, suggesting that this systemic approach is powerful for investigations into novel genes that are potential targets for the breeding of new valuable potato cultivars.
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Redes Reguladoras de Genes , Metaboloma/genética , Pigmentação/genética , Solanum tuberosum/genética , Transcriptoma/genética , Antocianinas/metabolismo , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Análise de Componente Principal , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.
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Desdiferenciação Celular , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Meniscos Tibiais/metabolismo , Plasma Rico em Plaquetas/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Animais , Condrócitos/citologia , Colágeno/genética , Colágeno/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Meniscos Tibiais/citologia , CoelhosRESUMO
A substantial proportion of men with prostatic disease have an increased risk of bone loss. In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea (MNU)-induced prostatic hyperplasia. The rats used in this study were categorized into groups of healthy controls, rats treated with MNU, and rats treated with MNU and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which ultrasonography, serum biochemical tests, histopathological examinations, immunohistochemical analysis, and semi-quantitative reverse-transcription polymerase chain reaction analysis were performed. There were no marked differences in body weight gain and the size and weight of the prostate gland between the MNU group and the MNU and RCM group. However, treatment with RCM inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate gland, as observed by histopathological evaluation and by analyzing changes in the levels of bone regulatory factors. In addition, the group treated with MNU and RCM had higher expression levels of cannabinoid receptors-1, -2, and osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM in prostatic hyperplasia is attributable to the cannabinoid receptor-related upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The results of the present study suggest that treatment with RCM may benefit osteoporotic patients with prostatic disease by simultaneously altering the activation of osteoblasts and osteoclasts.
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Osteoporose/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/complicações , Receptores de Canabinoides/metabolismo , Rubus/química , Envelhecimento , Animais , Modelos Animais de Doenças , Masculino , Metilnitrosoureia , Osteoporose/metabolismo , Fitoterapia/efeitos adversos , Próstata/patologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/patologia , RatosRESUMO
In the present study, we determined whether two endocrine-disrupting chemicals (EDCs), triclosan (TCS) and octylphenol (OP), are able to alter the expression of two cell cycle regulators, cyclin D1 and p21, in both in vitro and mouse breast cancer models. In addition, we determined whether the stimulatory effects of OP or TCS on breast cancer progression may be associated with an estrogen receptor (ER)-mediated signaling pathway. Altered expressions of cyclin D1 and p21 were observed in MCF-7 human breast cancer cells treated with TCS and OP, which is linked to the G1/S transition of cell cycle, leading to cell proliferation. In a xenograft mouse model, breast tumor masses were established following exposure to TCS and OP for 8 weeks. In these animals, the tumor cells with BrdU-positive nuclei were increased by treatment with 17ß-estradiol (E2), OP, and TCS compared to that of a control (corn oil), suggesting that TCS and OP increase DNA synthesis during the S phase in tumor cells. Increased level of cyclin D1 protein by TCS and OP was also observed in vivo, implying that the effects of these EDCs possessing estrogenic activity alter the expression of genes related to cancer progression. It was of interest that the effects of TCS and OP were reversed by ICI 182,780, an ER antagonist, indicating that EDC-induced activities are mediated by an ER-dependent signaling pathway. Taken together, these results suggest that TCS and OP may promote breast cancer progression, via an ER-mediated signaling cascade.
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Neoplasias da Mama/patologia , Mama/patologia , Disruptores Endócrinos/efeitos adversos , Fenóis/efeitos adversos , Receptores de Estrogênio/metabolismo , Triclosan/efeitos adversos , Animais , Mama/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacosRESUMO
Anastomotic stricture is a typical complication of esophageal atresia surgery. Remote ischemic conditioning (RIC) has demonstrated multiorgan benefits, however, its efficacy in the esophagus remains unclear. This study aimed to investigate whether applying RIC after esophageal resection and anastomosis in rats could attenuate esophageal stricture and improve inflammation. Sixty-five male Sprague-Dawley rats were categorized into the following groups: controls with no surgery, resection and anastomosis only, resection and anastomosis with RIC once, and resection and anastomosis with RIC twice. RIC included three cycles of hind-limb ischemia followed by reperfusion. Inflammatory markers associated with the interleukin 6/Janus kinase/ signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) and tumor necrosis factor-alpha/nuclear factor-κB (TNF-α/NF-kB) signaling pathways were evaluated with RNA and protein works. The RIC groups showed significantly lower stricture rates, lower inflammatory markers levels than the resection and anastomosis-only group. The RIC groups had significantly lower IL-6 and TNFa levels than the resection and anastomosis-only group, confirming the inhibitory role of remote ischemic conditioning in the IL-6/JAK/STAT3 and TNF-α/NF-kB signaling pathways. RIC after esophageal resection and anastomosis can reduce the inflammatory response, improving strictures at the esophageal anastomosis site, to be a novel noninvasive intervention for reducing esophageal anastomotic strictures.
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Anastomose Cirúrgica , Modelos Animais de Doenças , Estenose Esofágica , Precondicionamento Isquêmico , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Animais , Masculino , Ratos , Precondicionamento Isquêmico/métodos , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Fator de Transcrição STAT3/metabolismo , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangue , Transdução de Sinais , Esôfago/cirurgia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/sangue , Janus Quinases/metabolismoRESUMO
BACKGROUND: User engagement is crucial for digital therapeutics (DTx) effectiveness; due to variations in the conceptualization of engagement and intervention design, assessment and retention of engagement remain challenging. OBJECTIVE: We investigated the influence of the perceived acceptability of experimental intervention components and satisfaction with core intervention components in DTx on user engagement, while also identifying potential barriers and facilitators to user engagement. METHODS: We conducted a mixed methods study with a 2 × 2 factorial design, involving 12 outpatients with atopic dermatitis. Participants were randomized into 4 experimental groups based on push notification ("basic" or "advanced") and human coach ("on" or "off") experimental intervention components. All participants engaged in self-monitoring and learning courses as core intervention components within an app-based intervention over 8 weeks. Data were collected through in-app behavioral data, physician- and self-reported questionnaires, and semistructured interviews assessed at baseline, 4 weeks, and 8 weeks. Descriptive statistics and thematic analysis were used to evaluate user engagement, perceived acceptability of experimental intervention components (ie, push notification and human coach), satisfaction with core intervention components (ie, self-monitoring and learning courses), and intervention effectiveness through clinical outcomes. RESULTS: The primary outcome indicated that group 4, provided with "advanced-level push notifications" and a "human coach," showed higher completion rates for self-monitoring forms and learning courses compared to the predetermined threshold of clinical significance. Qualitative data analysis revealed three key themes: (1) perceived acceptability of the experimental intervention components, (2) satisfaction with the core intervention components, and (3) suggestions for improvement in the overall intervention program. Regarding clinical outcomes, the Perceived Stress Scale and Dermatology Life Quality Index scores presented the highest improvement in group 4. CONCLUSIONS: These findings will help refine the intervention and inform the design of a subsequent randomized trial to test its effectiveness. Furthermore, this design may serve as a model for broadly examining and optimizing overall engagement in DTx and for future investigation into the complex relationship between engagement and clinical outcomes. TRIAL REGISTRATION: Clinical Research Information Service KCT0007675; http://tinyurl.com/2m8rjrmv.
RESUMO
Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds present in the environment which can interfere with hormone synthesis and normal physiological functions of male and female reproductive organs. Most EDCs tend to bind to steroid hormone receptors including the oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). As EDCs disrupt the actions of endogenous hormones, they may induce abnormal reproduction, stimulation of cancer growth, dysfunction of neuronal and immune system. Although EDCs represent a significant public health concern, there are no standard methods to determine effect of EDCs on human beings. The mechanisms underlying adverse actions of EDC exposure are not clearly understood. In this review, we highlighted the toxicology of EDCs and its effect on human health, including reproductive development in males and females as shown in in vitro and in vivo models. In addition, this review brings attention to the toxicity of EDCs via interaction of genomic and non-genomic signalling pathways through hormone receptors.
Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Receptores Androgênicos/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Feminino , Regulação da Expressão Gênica , Aptidão Genética/efeitos dos fármacos , Hormônios Esteroides Gonadais/antagonistas & inibidores , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/agonistas , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/agonistas , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/metabolismo , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 µM resveratrol, whereas FERM had no effect on apoptosis induced by TNF-α. We determined that resveratrol at low doses (<20 µM) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production.