RESUMEN
BACKGROUND: Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-mutated non-small-cell lung cancer. Recently, the association between alectinib and red cell morphological abnormalities has been reported in a few case series. This retrospective observational study aims to determine the frequency of occurrence of acanthocytosis in patients taking alectinib and to evaluate the red cell indices, biochemical markers of haemolysis and eosin-5-maleimide (EMA) binding assay results in patients receiving alectinib. METHODS: Patients who were on alectinib and had a complete blood count test performed in Queen Elizabeth Hospital Haematology Laboratory between 1 May 2021 and 31 August 2021 were included in the study. Haematological investigations that had been performed before and after the commencement of alectinib were reviewed. RESULTS: Fifty patients receiving alectinib were evaluated in this analysis. One hundred per cent of patients showed 3+ acanthocytes on the peripheral blood smears. Compared with the test results before starting alectinib, the post-alectinib blood tests showed a significantly lower haemoglobin concentration, red blood cell count and haematocrit; and a significantly higher mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width. All the tested patients showed a marked reduction in EMA mean channel fluorescence compared with normal control. CONCLUSION: Our cohort revealed that alectinib caused significant acanthocytosis in all patients. Alectinib was also associated with changes in red cell indices and biochemical markers of haemolysis, compatible with a spherocytic and anisopoikilocytic morphology with haemolysis. Patients on alectinib had reduced EMA binding.
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Carbazoles , Eritrocitos , Piperidinas , Humanos , Piperidinas/uso terapéutico , Piperidinas/farmacología , Carbazoles/farmacología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Índices de Eritrocitos/efectos de los fármacos , Adulto , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Anciano de 80 o más Años , Pruebas HematológicasRESUMEN
OBJECTIVE: Sleep and circadian disturbance is highly comorbid with a range of psychological disorders, especially major depressive disorder (MDD). In view of the complexity of sleep and circadian problems in MDD, this study aimed to evaluate the efficacy of a group-based transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) for improving depressive symptoms and sleep and circadian functions. METHOD: One hundred fifty-two adults diagnosed with comorbid MDD and sleep and circadian dysfunctions were randomized into TranS-C group treatment (TranS-C; n = 77) or care as usual (CAU; n = 75) control group. The TranS-C group received six weekly 2-hr group sessions of TranS-C, whereas the CAU group continued to receive usual care. Assessments were at baseline, immediate (Week 7), and 12-week (Week 19) posttreatment. Primary and secondary outcomes included depression, anxiety, sleep disturbances, fatigue, quality of life, and functional impairment. RESULTS: The TranS-C group showed significant improvement in depressive symptoms (p < .001, d = 0.84), insomnia severity (p < .001, d = 0.77), sleep disturbances (p < .001, d = 1.15), sleep-related impairment (p < .001, d = 1.22), fatigue (p < .001, d = 1.06), anxiety symptoms (p = .004, d = 0.67), quality of life (p < .001, d = 0.71), and sleep diary-derived parameters (ps < .05, d = 0.12-0.77) relative to the CAU group at immediate posttreatment. These treatment gains remained significant at 12-week follow-up. Significant improvement in functional impairment was also noted at 12-week follow-up. CONCLUSIONS: TranS-C was efficacious and acceptable in alleviating depressive symptoms and sleep and circadian disruptions in adults with MDD. The group format appears to be a low-cost, widely disseminable option to deliver TranS-C. Further research on TranS-C to examine its benefits on other psychiatric disorders is warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Trastorno Depresivo Mayor , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Humanos , Trastorno Depresivo Mayor/psicología , Calidad de Vida , Resultado del Tratamiento , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Fatiga/complicacionesRESUMEN
Given the high death rate caused by high-risk prostate cancer (PCa) (>40%) and the reliability issues associated with traditional prognostic markers, the purpose of this study is to investigate planning computed tomography (pCT)-based radiomics for the long-term prognostication of high-risk localized PCa patients who received whole pelvic radiotherapy (WPRT). This is a retrospective study with methods based on best practice procedures for radiomics research. Sixty-four patients were selected and randomly assigned to training (n = 45) and testing (n = 19) cohorts for radiomics model development with five major steps: pCT image acquisition using a Philips Big Bore CT simulator; multiple manual segmentations of clinical target volume for the prostate (CTVprostate) on the pCT images; feature extraction from the CTVprostate using PyRadiomics; feature selection for overfitting avoidance; and model development with three-fold cross-validation. The radiomics model and signature performances were evaluated based on the area under the receiver operating characteristic curve (AUC) as well as accuracy, sensitivity and specificity. This study's results show that our pCT-based radiomics model was able to predict the six-year progression-free survival of the high-risk localized PCa patients who received the WPRT with highly consistent performances (mean AUC: 0.76 (training) and 0.71 (testing)). These are comparable to findings of other similar studies including those using magnetic resonance imaging (MRI)-based radiomics. The accuracy, sensitivity and specificity of our radiomics signature that consisted of two texture features were 0.778, 0.833 and 0.556 (training) and 0.842, 0.867 and 0.750 (testing), respectively. Since CT is more readily available than MRI and is the standard-of-care modality for PCa WPRT planning, pCT-based radiomics could be used as a routine non-invasive approach to the prognostic prediction of WPRT treatment outcomes in high-risk localized PCa.
RESUMEN
Pt(IV) complexes bearing axial carbonate linkages have drawn much attention recently. A synthetic method behind this allows the hydroxyl group of bioactive ligands to be attached to the available hydroxyl group of Pt(IV) complexes, and the rapid release of free drugs is achieved after the reduction of carbonate-linked Pt(IV) complexes. Further understanding on the properties of Pt(IV) carbonates such as hydrolytic stability and reduction profiles, however, is hindered by limited research. Herein, six mono-carbonated Pt(IV) complexes in which the carbonate axial ligands possess various electron-withdrawing powers were synthesized, and the corresponding mono-carboxylated analogues were also prepared as references to highlight the different properties. The influence of the coordination environment towards the hydrolysis and reduction rate of Pt(IV) carbonates and carboxylates was explored. The mono-carbonated Pt(IV) complexes are both less stable and reduced faster than the corresponding mono-carboxylated ones. Moreover, the hydrolysis and reduction profiles are dependent not only on the electron-withdrawing ability of the carbonates but also on the nature of the opposite axial ligands. Besides, the exploration of the hydrolytic pathway for Pt(IV) carbonates suggests that the process proceeds by an attack of OH- on the carbonyl carbon, followed by elimination, which is different from that of Pt(IV) carboxylates. This study provides some information on the influence of axial carbonate ligands with different electron-withdrawing abilities on the properties of the Pt(IV) center, which may inspire new thoughts on the design of "multi-action" Pt(IV) prodrugs.
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Carbonatos , Platino (Metal)/química , Platino (Metal)/farmacología , Profármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , HidrólisisRESUMEN
BACKGROUND: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. FINDINGS: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. INTERPRETATION: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. FUNDING: Hong Kong Research Grants Council.
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Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2 , Humanos , Nasofaringe/virología , Orofaringe/virología , Faringe/virología , Valor Predictivo de las Pruebas , Saliva/virología , Sensibilidad y Especificidad , Manejo de Especímenes/métodosRESUMEN
OBJECTIVES: The aim of this review is to describe academic advising schemes at the undergraduate level, examine the perspectives of advisors and advisees towards the schemes, and explore the implications of academic advising in undergraduate and nursing education. DESIGN: A systematic review was conducted of the protocol of PRISMA-P. DATA SOURCES: Six electronic databases were searched for journal articles, namely, Academic Search Premier, CINAHL, ERIC, Medline, Teacher Reference Center, and Scopus. REVIEW METHODS: A total of 6189 articles were examined, and 37 empirical studies were included in the final review. The Mixed Methods Appraisal Tool (MMAT) was used to assess the eligibility of studies for inclusion in the review. RESULTS: The review involved summarizing and categorizing the components of existing academic advising schemes, analysing the perspectives of advisors and advisees, and identifying four aspects of the perspectives of advisees: their experiences, preferences, benefits gained from the scheme, and barriers to seeking help from advisors. Six issues relating to academic advising schemes were discussed: insufficient information about the schemes, the means of communication used in the process of advising, the issue of time management for both advisors and advisees, a lack of training for advisors, the evaluation of the outcomes of advising, and the implications for nursing education. CONCLUSIONS: Advisors and advisees held positive views of the scheme. Academic advising benefited students and advisors, even as some barriers were identified. It is suggested that sufficient training, better time management, and the utilization of different tools for communication are needed to increase the effectiveness of academic advising. Further studies should be conducted to investigate the effects of different elements of the scheme on the outcome of advising.
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Comunicación , Bachillerato en Enfermería/métodos , Mentores/psicología , Bachillerato en Enfermería/tendencias , Humanos , Universidades/organización & administraciónRESUMEN
The benzophenone (BP) organic ultraviolet (UV) filters have been measured in seawater at ng/L to µg/L levels, but more data on their effects in non-target marine organisms are needed. Corals can be exposed to BPs due to wastewater discharges and coastal recreational activities. In this study, toxicities and bioaccumulation of BP-1 (2,4-dihydroxybenzophenone), BP-3 (oxybenzone), BP-4 (sulisobenzone) and BP-8 (dioxybenzone) to larvae and adults of two coral species, Pocillopora damicornis and Seriatopora caliendrum, were assessed at concentrations ranging from 0.1-1000⯵g/L. BP-1 and BP-8 exposure caused significant settlement failure, bleaching and mortality of S. caliendrum larvae [lowest observed effect concentration (LOEC): ≥10⯵g/L] compared to the other BPs, while none of the tested compounds and concentrations affected P. damicornis larvae. Nubbins were more sensitive to BP-3, BP-1 and BP-8 than larvae. Overall, BP-1 and BP-8 were more toxic to the two tested species than BP-3 and BP-4, which matches the relative bioaccumulation potential of the four BPs (BP-8â¯>â¯BP-1â¯≈â¯BP-3â¯>â¯BP-4). A conservative risk assessment using the effect concentrations derived from this study showed that BP-3, BP-1 and BP-8 pose high or medium risk to the health of corals in popular recreational areas of Taiwan and Hong Kong. Our study suggests that future ecotoxicological studies of corals should take their sensitivities, life stages and metabolic capacities into consideration.
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Antozoos/efectos de los fármacos , Benzofenonas/toxicidad , Protectores Solares/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Antozoos/crecimiento & desarrollo , Monitoreo del Ambiente , Hong Kong , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Parques Recreativos , TaiwánRESUMEN
Traditional Chinese medicine (TCM) treatments are often prescribed based on individuals' pattern diagnoses. A systematic review of randomized controlled trials in Chinese and English literatures on TCM pattern-based treatment for depression has therefore been conducted. A total of 61 studies, 2504 subjects, and 27 TCM patterns were included. Due to the large variation of TCM pattern among participants, we only analyzed the top four commonly studied TCM patterns: liver qi depression, liver depression and spleen deficiency, dual deficiency of the heart, and spleen and liver depression and qi stagnation. We found that Xiaoyao decoction was the most frequently used herbal formula for the treatment of liver qi depression and liver depression with spleen deficiency, while Chaihu Shugan decoction was often used for liver depression and qi stagnation. Bai Shao (Paeonia lactiflora Pall.) and Chai Hu (Bupleurum chinense DC.) were commonly used across different TCM patterns regardless of the prescribed Chinese herbal formulas. The rationale underlying herb selection was seldom provided. Due to the limited number of studies on TCM pattern-based treatment of depression and their low methodological quality, we are unable to draw any conclusion regarding which herbal formulas have higher efficacy and which TCM patterns respond better to CHM.
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Organic ultraviolet (UV) filters are used widely in various personal care products and their ubiquitous occurrence in the aquatic environment has been reported in recent years. However, data on their fate and potential impacts in marine sediments is limited. This study reports the occurrence and risk assessment of eleven widely used organic UV filters in marine sediment collected in Hong Kong and Tokyo Bay. Seven of the 11 target UV filters were detected in all sediment samples (median concentrations: Asunto(s)
Ecología
, Sedimentos Geológicos/química
, Agua de Mar
, Rayos Ultravioleta
, Hong Kong
, Japón
, Medición de Riesgo
RESUMEN
Chinese herbal medicine (CHM) is one of the commonly used complementary and alternative medicine therapies for major depressive disorder. The objective of this study was to review the efficacy, safety and types of CHM for depression. We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs) and examined 7 systematic reviews for additional articles. Methodological quality was assessed by modified Jadad scale and Cochrane's risk of bias assessment. Only studies with moderate methodological quality, defined as modified Jadad scale score ≥3, were included in meta-analysis for efficacy. Of the 296 RCTs that were assessed in details, 278 (93.9%) had modified Jadad scale score < 3, and only 21 scored ≥ 3. The frequently used formulas were Xiao Yao decoction, Chaihu Shugan decoction and Ganmai Dazao decoction; while Chaihu, Bai Shao and Fu Ling were the frequently used single herb. Meta-analyses showed that CHM monotherapy was better than placebo and as effective as antidepressants in reducing Hamilton Depression Rating Scale (HDRS) score (CHM vs. placebo: mean difference: -7.97, 95% CI: -10.25 to -5.70, P < 0.00001, 2 studies; CHM vs. antidepressants: mean difference: 0.01, 95% CI: -0.28 to 0.30, P = 0.95, 7 studies). CHM were associated with less adverse events than antidepressants, and adding CHM to antidepressants reduced adverse events. Despite the overall positive results, due to the small number of studies with sufficient methodological quality, it is premature to accurately conclude the benefits and risks of CHM for depression.
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Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Medicina Tradicional China/efectos adversos , Preparaciones de Plantas/efectos adversos , Adulto , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Medicina Tradicional China/métodos , Persona de Mediana Edad , Preparaciones de Plantas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ganmai Dazao (GMDZ) decoction is a traditional Chinese herbal formula commonly used for the treatment of depression. The objective of this study was to assess the efficacy and safety of GMDZ, either alone or as co-therapy, for depression. MATERIALS AND METHODS: We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs). The primary outcomes were effective rate and self-rated or clinician-rated severity of depression. The secondary outcome was the occurrence of adverse events. Methodological quality of the RCTs was assessed by the Cochrane׳s risk of bias assessment. RESULTS: Ten RCTs were included. All were written in Chinese and the methodological quality was generally low. Pooled analysis of 5 studies which compared GMDZ with antidepressants showed that GMDZ was significantly more efficacious than antidepressants in effective rate (risk ratio: 1.14, 95% CI: 1.02 to 1.27, P=0.02, I(2)=0%), but comparable in Hamilton Depression Rating Scale (HDRS) score (mean difference: -2.10, 95% CI: -4.62 to -0.41, P=0.10, I(2)=92%). With regard to the other 5 studies which compared GMDZ plus antidepressants with antidepressants alone, there was no significant difference in effective rate (risk ratio: 1.24, 95% CI: 0.99 to 1.55, P=0.07, I(2)=93%), but the end-point HDRS score was significantly lower in GMDZ antidepressants combination (mean difference: -4.25, 95% CI: -6.50 to -2.00, P=0.0002, I(2)=96%). Adverse events were more common with antidepressants than GMDZ (rate ratio: 0.52, 95% CI: 0.32 to 0.82, P=0.005, I(2)=37%) and in antidepressants alone compared to GMDZ antidepressants combination (rate ratio: 0.23, 95% CI: 0.08 to 0.68, P=0.08, I(2)=0%). CONCLUSION: The overall results suggest that GMDZ has few side effects and the potential as an antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants. However, due to the small number of studies and their limitations, further studies with better methodological quality and more comprehensive safety assessment are needed to determine the benefits and risks of GMDZ in the treatment of depression.
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Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Medicina Tradicional China/métodos , Preparaciones de Plantas/uso terapéutico , Antidepresivos/efectos adversos , Trastorno Depresivo/etnología , Trastorno Depresivo/psicología , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/etnología , Humanos , Preparaciones de Plantas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del TratamientoRESUMEN
Recent advance in directed differentiation of pancreatic stem cells offers potential to the development of replacement therapy for diabetic patients. However, the existing differentiation protocols are complex, time-consuming, and costly; thus there is a need for alternative protocols. Given the common developmental origins of liver and pancreas, we sought to develop a novel protocol, devoid of growth factors, by using liver stromal cells (LSCs) derived from human fetal liver. We examined the effects of the LSCs on the differentiation of pancreatic progenitor cells (PPCs) into islet-like cell clusters (ICCs). PPCs and LSCs isolated from 1st to 2nd trimester human fetal tissues underwent co-cultures; differentiation and functionality of ICCs were determined by examining expression of critical markers and secretion of insulin. Co-culture with 2nd but not 1st trimester LSCs enhanced ICC differentiation and functionality without the use of exogenous differentiation 'cocktails'. Differential expression profiles of growth factors from 1st versus 2nd trimester fetal liver were compared. Many morphogenic factors were expressed by LSCs, while insulin-like growth factor 1 (IGF1) was identified as one of the key molecules responsible for the ICC differentiation. This is the first report showing that an LSC-induced microenvironment can enhance ICC differentiation and functionality. Further modifications of the stroma microenvironment may offer an alternative, efficient and cost-effective approach to providing islets for transplantation.
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Diferenciación Celular , Islotes Pancreáticos/citología , Hígado/citología , Células Madre/fisiología , Animales , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/terapia , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Trasplante de Islotes Pancreáticos , Ratones , Ratones Desnudos , Células del Estroma/fisiología , Proteínas de la Superfamilia TGF-beta/genética , Proteínas de la Superfamilia TGF-beta/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The growth and development of pancreatic islet cells are regulated by various morphogens. Vitamin A modulates in vitro differentiation of islet cells and vitamin D affects beta-cell insulin secretion, while both vitamin ligands act through heterodimerization with the retinoid X receptor (RXR). However, their effects in modulating pancreatic development have not been determined. In this study, cultured human pancreatic progenitor cells (PPCs) isolated from human fetal pancreas were stimulated to differentiate into islet-like cell clusters (ICCs). RT-PCR, Western blotting and immunocytochemistry were used to examine the expression and localization of vitamin D receptor (VDR), retinoic acid receptor (RAR), and RXR in PPCs. The effects of added all-trans retinoic acid (atRA, a form of vitamin A), calcitriol (activated vitamin D) and of these ligands together on PPC cell viability, proliferation and apoptosis were assessed by MTT, BrdU and ELISA assays, respectively. Post-treatment neurogenin-3 (NGN3) expression, necessary for islet-cell lineage development, was examined by real-time RT-PCR. Results showed that RAR, RXR and VDR were expressed in PPCs. RAR and RXR were localized in nuclei, and the VDR in nuclei, cytoplasm and plasma membrane. atRA and calcitriol each increased PPC viability and proliferation; atRA additionally decreased PPC apoptosis. Co-addition of atRA and calcitriol had no additive effects on cell viability but did increase ngn3 responses. In conclusion, RAR, RXR and VDR are expressed in human fetal PPCs and PPC proliferation can be promoted by calcitriol, atRA or both together, data valuable for elucidating mechanisms underlying islet development and for developing clinical islet transplantation.
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Feto/citología , Páncreas/citología , Páncreas/embriología , Receptores de Calcitriol/metabolismo , Receptores de Ácido Retinoico/metabolismo , Receptores X Retinoide/metabolismo , Células Madre/metabolismo , Apoptosis/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Calcitriol/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Ligandos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Calcitriol/genética , Receptores de Ácido Retinoico/genética , Ácido Retinoico 4-Hidroxilasa , Receptores X Retinoide/genética , Células Madre/citología , Células Madre/efectos de los fármacos , Esteroide Hidroxilasas/metabolismo , Tretinoina/farmacología , Regulación hacia Arriba/efectos de los fármacos , Vitamina D3 24-HidroxilasaRESUMEN
Hormones like leptin and estrogen have been suggested to increase energy expenditure and modulate estrous cycle. The aim of this study was to investigate the stages of estrous cycle in mouse models with contrasting leptin and estrogen levels. Estrous cycle of wild type (WT), WT ovariectomized (OVX), ob/ob and ob/ob OVX was observed by obtaining vaginal smear and staining with Papanicolaou (PAP) procedure. Quantitative analysis showed cellular morphology and predominance of cellular content across the estrous cycle. Microscopical and quantitative counts showed a 4-5 day regular cycle in WT mouse, WTOVX were acyclic, infertile and hardly showed any cells, ob/ob and ob/ob OVX were both acyclic, infertile and were at persistent estrous or persistent metaestrous phase. Enzyme-Immunometric Assay results showed that leptin levels were about 3 fold higher in WTOVX than WT mouse (p<0.0001) with beta-estradiol values being negligible in WTOVX. The beta-estradiol levels for ob/ob and WT were similar. These results suggest that although leptin and estrogen play an important role in the estrous cycle, they are not the sole factor influencing the cycle. It is probable that in the absence of leptin and decrease in sex steroid hormones with increase in acyclicity, the central nervous system probably interprets the circulation as absence of energy stores and shuts down reproduction indicated by the changes in the estrous cycle.