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The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVNVGlut2::MC4R and LCVGlut2::MC4R regulation of body weight, and axonal projections of LCVGlut2 neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LCVGlut2 circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LCVGlut2 neurons. The PVN â LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.
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Núcleo Hipotalámico Paraventricular , Receptor de Melanocortina Tipo 4 , Ratones , Animales , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/metabolismo , Peso Corporal , Núcleo Hipotalámico Paraventricular/metabolismo , Neuronas/metabolismo , Aumento de PesoRESUMEN
BACKGROUND: Mastery may shape the way individuals cope with life challenges and influence cognitive function in later life. Mastery grows out of traumatic experience and could change over the life course. This study examined the within-person and between-person associations of mastery and cognitive function, and if these associations were moderated by age in the United States. METHOD: Data were derived from three time points (2006-2008, 2010-2012, and 2014-2016) of the Health and Retirement Study, with 14,461 adults (aged 51 or above). Cognitive function was measured through a 27-point Telephone Interview Cognitive Screen (TICS). Mastery was measured by a modified Pearlin Mastery Scale. Multilevel modeling was employed to analyze the data. RESULTS: Both within-person ( ß =0.124, SE = 0.023, p < 0.001) and between-person ( ß =0.089, SE = 0.029, p = 0.002) mastery were significantly associated with cognitive function. Older adults with higher between-person mastery tended to have slower cognitive decline ( ß =0.063, SE = 0.021, p < 0.001). Moreover, age moderated the within-person ( ß =0.013, SE = 0.003, p < 0.001) associations between mastery and cognition with a stronger association observed among individuals with older age. CONCLUSIONS: The current study provides evidence for within-person and between-person associations between mastery and global cognition in the United States as well as the moderating role of age. The design of the current study did not directly assess the causal direction between mastery and cognitive function. Future studies could test the directionality of associations between mastery and cognitive function.
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Cognición , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Cognición/fisiología , Anciano de 80 o más Años , Factores de Edad , Estados Unidos/epidemiología , Envejecimiento/psicología , Envejecimiento/fisiología , Disfunción Cognitiva/psicología , Disfunción Cognitiva/epidemiología , Adaptación Psicológica/fisiologíaRESUMEN
OBJECTIVES: This study explored the longitudinal association between overall and individual sources of social support and global cognitive function in older adults.Methods:Data were drawn from three waves (2006, 2010 and 2014) of the Health and Retirement Study (HRS). The analytic sample included participants aged 65 and above who were married and had at least one child (N = 1319). Global cognitive function was measured through a 35-point Telephone Interview Cognitive Screen (TICS). Perceived social support was measured via questions across four sources of support (spouse, child, other family members, and friends). Analyses were conducted using Hierarchical Linear Modeling (HLM) with the addition of a cross-lagged panel model (CLPM). RESULTS: There was no significant association between perceived overall social support and global cognitive function over time (ß=-0.02, p=0.19). However, changes in perceived support from children were positively associated with changes in global cognition (ß=0.05,p<0.01). In contrast, changes in perceived support from other family members were negatively associated with changes in cognitive function (ß=-0.07,p<0.01). CONCLUSIONS: Our findings highlight the importance of examining perceived social support from specific elements of one's social networks, rather than in an aggregated variable. Although the positive effect of perceived support from children may be small to moderate, the findings could provide a target for interventions to protect the cognitive function of older adults.
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Objective: Amylin acts on the lateral dorsal tegmental nucleus (LDT), resulting in anorexic and weight-loss effects and activates thermogenesis in the interscapular brown adipose tissue (IBAT). In addition, it induces neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT)-mediated feeding. However, the influence of the intact sympathetic nervous system (SNS) in mediating amylin's effects has not been fully characterised. We investigated whether extracellular signal-regulated kinase (ERK), nNOS, and ChAT activities in the LDT are responsible for amylin's anorexigenic effects and whether this requires an intact SNS.Methods: C57BL/6J mice [wild-type (WT), sham, and sympathetic denervation of IBAT] were used. Food consumption, body weight, and distribution of pERK, nNOS, and ChAT positive neurons in the brain were examined following acute and chronic amylin administration.Results: Food intake was significantly decreased in WT and sham animals following acute amylin injection, but not in the denervated mice. Chronic amylin reduced body weight and serum glucose levels after 6 weeks, but increased insulin levels; no changes were observed in the denervated mice. Acute amylin increased the expression of nNOS, ChAT, and uncoupling protein-1 in the IBAT of WT and sham mice, while no changes were observed in the denervated mice and pERK from the above effect.Conclusions: Intact SNS of IBAT influences amylin-induced suppression of food intake and body weight, thus affecting nNOS and ChAT signalling in the LDT and locus coeruleus.
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Tejido Adiposo Pardo , Polipéptido Amiloide de los Islotes Pancreáticos , Tejido Adiposo Pardo/metabolismo , Animales , Peso Corporal , Ingestión de Alimentos , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/farmacología , Ratones , Ratones Endogámicos C57BL , Sistema Nervioso SimpáticoRESUMEN
Ghrelin is an orexigenic agonist that acts directly on neurons in the hypothalamus, controlling appetite and energy balance. Although its role in appetite-associated neurons has been described, the relationship between peripheral ghrelin stimulation and oxytocin expression in the paraventricular nucleus is not fully understood. We evaluated the suppressive function of ghrelin in oxytocin-positive paraventricular nucleus neurons in ovariectomized C57BL/6 mice 2 h after ghrelin injection. The results showed that, in intact mice, peripheral ghrelin stimulation activated estrogen receptor alpha-expressing neurons during the estrous cycle and that agouti-related peptide mRNA expression was remarkably increased. Agouti-related peptide neuron axons co-localized with oxytocin neurons in the paraventricular nucleus. Moreover, the response of oxytocin-positive paraventricular nucleus neurons to ghrelin was suppressed in the proestrus period, while ghrelin decreased the serum concentration of estradiol in the proestrus phase. These data suggest that ghrelin may suppress oxytocin-positive neuron expression via the arcuate nucleus agouti-related peptide circuit, with the possible influence of estradiol in the murine estrous cycle. Unraveling the mechanism of ghrelin-induced oxytocin expression in the hypothalamus paraventricular nucleus broadens the horizon for ghrelin-related appetite research.
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Proteína Relacionada con Agouti/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Estradiol/sangre , Receptor alfa de Estrógeno/metabolismo , Ciclo Estral/metabolismo , Ghrelina/metabolismo , Neuronas/metabolismo , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Animales , Femenino , Ghrelina/farmacología , Ratones , Ratones Endogámicos C57BL , OvariectomíaRESUMEN
Plasminogen activator, tissue type (PLAT) and its inhibitor serpin family E member 1 (SERPINE1) cooperatively regulate PLAT activity in various reproductive processes. However, it is unknown whether this includes bovine oocyte maturation. We addressed this question in the present study by evaluating PLAT and SERPINE1 protein localization in immature cumulus-oocyte complexes (COCs), as well as PLAT mRNA and protein expression in cultured COCs after 0, 8, 16, and 24 h of in vitro maturation (IVM). We also examined the effects of PLAT and SERPINE1 on germinal vesicle breakdown (GVBD) and oocyte cyclic 3' 5' adenosine monophosphate (cAMP) levels, cumulus expansion index, and expansion-related gene expression in oocytes derived from bovine COCs cultured for 4, 8, and 12 h and in COCs cultured for 16 h. Both PLAT and SERPINE1 localized in cumulus cells but only the latter was detected in oocytes. PLAT and SERPINE1 transcript levels increased during IVM; however, from 8 to 16 h, the levels of PLAT remained stable whereas those of SERPINE1 increased, resulting in a decline in PLAT concentration. Additionally, PLAT delayed GVBD, increased oocyte cAMP levels, and blocked cumulus expansion and associated gene expression, which was reversed by SERPINE1 supplemented. Thus, PLAT delays bovine oocyte GVBD by enhancing oocyte cAMP levels during the first 8 h of IVM; suppression of PLAT activity via accumulation of SERPINE1 in COCs results in cumulus expansion from 8 to 16 h of IVM. These findings provide novel insights into the molecular mechanisms underlying in vitro bovine oocyte maturation.
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Proliferación Celular , Células del Cúmulo/fisiología , Oocitos/fisiología , Oogénesis/fisiología , Activador de Tejido Plasminógeno/fisiología , Animales , Bovinos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Células del Cúmulo/citología , Femenino , Técnicas de Maduración In Vitro de los Oocitos , Oocitos/citología , Oocitos/efectos de los fármacos , Oogénesis/genética , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/farmacología , Inhibidor 1 de Activador Plasminogénico/fisiología , Activador de Tejido Plasminógeno/genética , Activador de Tejido Plasminógeno/farmacología , TranscriptomaRESUMEN
AIMS: Amylin, a pancreatic hormone cosecreted with insulin, exerts important anorexic and weight-loss effects. Melanocortin 4 receptor (MC4R) signalling plays a critical role in energy homeostasis; however, its role on amylin-dependent regulation of food intake and adaptive thermogenesis of interscapular brown adipose tissue (IBAT) are unclear. In this study, we examined the effects of amylin on food intake and thermogenesis on IBAT via the MC4R pathway in mice. MATERIALS AND METHODS: Acute food consumption and thermogenesis in IBAT were measured in male wild-type (WT) and MC4R-deficient mice following intraperitoneal injection of amylin and SHU9119, an MC3R/4R antagonist, to determine the role of the central melanocortin system on the hypothalamus and IBAT. RESULTS: Amylin (50 µg/kg) suppressed feeding and stimulated thermogenesis on IBAT via activation of the MC4R system in mice. Pharmacological blockade of MC4R using SHU9119 (50 µg/kg) attenuated amylin-induced inhibition of feeding and stimulation of thermogenesis in IBAT. No changes were observed when SHU9119 was injected alone. Moreover, amylin significantly increased MC4R expression and c-Fos neuronal signals in the arcuate nucleus and significantly increased acetyl-CoA carboxylase (ACC) phosphorylation in the hypothalamus and IBAT and uncoupling protein-1 (UCP1) expression in the IBAT of WT mice via the MC4R pathway. CONCLUSION: The melanocortin system was involved in amylin-induced suppression of food intake and activation of thermogenesis in both the hypothalamus and IBAT via modulation of ACC phosphorylation and UCP1 expression.
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Ingestión de Alimentos , Polipéptido Amiloide de los Islotes Pancreáticos/farmacología , Receptor de Melanocortina Tipo 4/fisiología , Termogénesis/efectos de los fármacos , Termogénesis/genética , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Animales , Regulación del Apetito/efectos de los fármacos , Regulación del Apetito/genética , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Melanocortina Tipo 4/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMEN
BACKGROUND: The ovine rumen is involved in host defense responses and acts as the immune interface with the environment. The ruminal mucosal epithelium plays an important role in innate immunity and secretes antimicrobial innate immune molecules that have bactericidal activity against a variety of pathogens. Defensins are cationic peptides that are produced by the mucosal epithelia and have broad-spectrum antimicrobial activity. Sheep ß-defensin-1 (SBD-1) is one of the most important antibacterial peptides in the rumen. The expression of SBD-1 is regulated by the probiotic, Saccharomyces cerevisiae (S.c); however, the regulatory mechanism has not yet been elucidated. In the current study, the effects of S.c on the expression and secretion of SBD-1 in ovine ruminal epithelial cells were investigated using quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, specific inhibitors were used to block the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), p38, JNK, and ERK1/2 signalling pathways separately or simultaneously, to determine the regulatory mechanism(s) governing S.c-induced SBD-1 upregulation. RESULTS: Incubation with S.c induced release of SBD-1 by ovine ruminal epithelial cells, with SBD-1 expression peaking after 12 h of incubation. The highest SBD-1 expression levels were achieved after treatment with 5.2 × 107 CFUâmL- 1 S.c. Treatment with S.c resulted in significantly increased NF-κB, p38, JNK, ERK1/2, TLR2, and MyD88 mRNA expression. Whereas inhibition of mitogen-activated protein kinases (MAPKs) and NF-κB gene expression led to a decrease in SBD-1 expression. CONCLUSIONS: S.c was induced SBD-1 expression and the S.c-induced up-regulation of SBD-1 expression may be related to TLR2 and MyD88 in ovine ruminal epithelial cells. This is likely simultaneously regulated by the MAPKs and NF-κB pathways with the p38 axis of the MAPKs pathway acting as the primary regulator. Thus, the pathways regulating S.c-induced SBD-1 expression may be related to TLR2-MyD88-NF-κB/MAPKs, with the TLR2-MyD88-p38 component of the TLR2-MyD88-MAPKs signalling acting as the main pathway.
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Mucosa Gástrica/microbiología , Rumen/microbiología , Saccharomyces cerevisiae/metabolismo , beta-Defensinas/metabolismo , Animales , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Rumen/citología , Rumen/metabolismo , OvinosRESUMEN
PURPOSE: Early post-operative exercise and weight-bearing activities are found to improve the functional recovery of patients with displaced intra-articular calcaneal fractures (DIACFs). We hypothesized that early functional exercise after surgery might have a secondary reduction effect on the subtalar joint, in particular the smaller fracture fragments that were not fixed firmly. A prospective study was conducted to verify this hypothesis. METHODS: From December 2012 to September 2013, patients with unilateral DIACFs were enrolled and received a treatment consisting of percutaneous leverage and minimally invasive fixation. After surgery, patients in the study group started exercising on days two to three, using partial weight bearing starting week three, and full weight bearing starting week 12. Patients in the control group followed a conventional post-operative protocol of partial weight bearing after week six and full weight bearing after the bone healed. Computed tomography (CT) scanning was performed at post-operative day one, week four, week eight, and week 12 to reconstruct coronal, sagittal, and axial images, on which the maximal residual displacements of the fractures were measured. Function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring scale at the 12th post-operative month. RESULTS: Twenty-eight patients in the study group and 32 in the control group were followed up for more than 12 months; their data were collected and used for the final analysis. Repeated-measures analysis of variance (ANOVA) of the maximal residual displacements of the fracture measured on CT images revealed significant differences between the study and the control groups. There were interaction effects between group and time point. Except for the first time point, the differences between the groups at all studied time points were significant. In the study group, the differences between all studied time points were significant. Strong correlations were observed between the AOFAS score at post-operative month 12 and the maximal residual displacement of the fractures on the CT images at postoperative week 12. CONCLUSIONS: Early functional exercise and weight bearing activity can smooth and shape the subtalar joint and reduce the residual displacement of the articular surface, improving functional recovery of the affected foot. Therefore, early rehabilitation functional exercise can be recommended in clinical practice.
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Fracturas de Tobillo/rehabilitación , Calcáneo/lesiones , Fractura-Luxación/rehabilitación , Fracturas Intraarticulares/rehabilitación , Entrenamiento de Fuerza/métodos , Adulto , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Femenino , Estudios de Seguimiento , Fractura-Luxación/diagnóstico por imagen , Fractura-Luxación/cirugía , Fijación de Fractura/métodos , Fijación de Fractura/rehabilitación , Fijación Interna de Fracturas/métodos , Humanos , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Articulación Talocalcánea/diagnóstico por imagen , Articulación Talocalcánea/fisiopatología , Articulación Talocalcánea/cirugía , Tomografía Computarizada por Rayos X/métodosRESUMEN
Periosteal osteosarcoma is a rare subtype of osteosarcoma. Wide surgical removal is the commonly used treatment-method algorithm. However, the limb-salvage procedure of periosteal osteosarcoma in the distal tibia is a technical challenge to orthopedic surgeons because of the scarcity of soft tissue and subcutaneous nature in the anteromedial aspect. We encountered a 16-year-old female patient with periosteal osteosarcoma in the distal half of the left tibia diagnosed preoperatively based upon the CT images and a needle biopsy. A unique identical surgical technique was applied in the case, including marginal resection of the periosteal osteosarcoma with part of the tibia retained at the same level of bone defect and reconstruction using the autologous fibula graft. A combination of cisplatin and doxorubicin was received as chemotherapy after the operation. Postoperative incisional biopsy was performed, and the hematoxylin-eosin-stained results confirmed the diagnosis of periosteal osteosarcoma. The patient was followed up for 11 years. Radiological and clinical evaluation was performed at each follow-up. The retained tibia incorporated well with the fibula autograft, and excellent limb functional recovery was achieved. The patient was free from neoplastic disease at the latest follow-up. In conclusion, young patients with periosteal osteosarcoma without intramedullary involvement can be treated by marginal resection of the lesion with part of the tibia retained at the level of bone defect and reconstructed using a long autologous fibula graft. Subsequent chemotherapy with administration of cisplatin and doxorubicin is recommended.
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Neoplasias Óseas/cirugía , Peroné/trasplante , Osteosarcoma/cirugía , Periostio/cirugía , Procedimientos de Cirugía Plástica/métodos , Tibia/cirugía , Adolescente , Femenino , Humanos , Trasplante AutólogoRESUMEN
Objective: The current longitudinal study examined how (1) cognitive measures, including episodic memory, executive function, and global cognition, predict later healthcare access and how (2) healthcare access predicts later cognition. Methods: Drawing a sample (n = 9920) from the Health and Retirement Study dataset, we created a cross-lagged panel model to examine the longitudinal association between cognitive measures and healthcare access from 2012 to 2018. Results: Results revealed that cognitive measures significantly predict later healthcare access, with effects increasing across waves. However, within sub-domains, memory was more predictive of later healthcare access over time compared to executive function. Discussions: Our study suggested an increased link between cognition and healthcare access during aging. Even outside of the context of AD, there are likely both policy-based and practical implications to ensure those experiencing cognitive decline continue to maintain access to care.
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Cognición , Disfunción Cognitiva , Accesibilidad a los Servicios de Salud , Humanos , Estudios Longitudinales , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Función Ejecutiva , Memoria Episódica , Envejecimiento/psicología , Persona de Mediana EdadRESUMEN
OBJECTIVES: Although education and social engagement are considered cognitive reserves, the pathway of both reserves on cognitive function has been rarely studied. This study aimed to examine the underlying mechanism between education, social engagement, and cognitive function. METHODS: This study used 2-wave data (2010 and 2014) from Health and Retirement Study in the United States (N = 3,201). Education was measured by years of schooling. Social engagement was evaluated by 20 items including volunteering, physical activities, social activities, and cognitive activities. Cognitive function was assessed by a modified Telephone Interview for Cognitive Status. A cross-lagged panel model was fitted to test the mediating mechanism between education, social engagement, and cognitive function. RESULTS: Controlling for covariates, higher education in early life was associated with better cognitive function in old age (b = 0.211, 95% confidence interval [CI] = [0.163, 0.259], p < .01). Late-life social engagement partially mediated the association between education and cognitive function (indirect effect = 0.021, 95% CI = [0.010, 0.033], p < .01). The indirect path between education and social engagement via cognition also existed (b = 0.009, 95% CI = [0.005, 0.012], p < .001). DISCUSSION: Education in earlier life stage may exert a lifelong effect on cognitive function as well as an indirect effect via enhancing late-life cognitive reserve such as social engagement. The cross-lagged effect of social engagement on cognitive function is significant and vice versa. Future research may explore other cognitive reserves over the life course and its underlying mechanism to achieve healthy cognitive aging.
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Reserva Cognitiva , Participación Social , Humanos , Participación Social/psicología , Cognición , Escolaridad , Jubilación/psicología , Estudios LongitudinalesRESUMEN
BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) created a "perfect storm" for financial fraud targeting older adults. Guided by the Contextual Theory of Elder Abuse, we focused on individual and systemic contexts to examine how older adults became prey to financial fraud. RESEARCH DESIGN AND METHODS: In July 2020, 998 adults who were 60-98 years of age (93% White; 64% female) completed an online survey about experiences with financial fraud. Participants were recruited from gerontology research registries at Florida State University, University of Pittsburg, Virginia Tech, and Wayne State University. RESULTS: Over half (65.9%) of the respondents experienced a COVID-19-related scam attempt, with charity contributions (49%) and COVID-19 treatments (42%) being the most common. Perpetrators commonly contacted older adults electronically (47%) two or more times (64%). Although most respondents ignored the request (i.e., hung up the phone and deleted text/e-mail), 11.3% sent a requested payment, and 5.3% provided personal information. Predictors of vulnerability included contentment with financial situation, concern about finances in the aftermath of the pandemic, and wishing to talk to someone about financial decisions. Respondents targeted for a non-COVID-19 scam attempt were less likely to be targets of a COVID-19-related scam. DISCUSSION AND IMPLICATIONS: Older adults who were financially secure, worried about their financial situation, or wished they could speak with someone about their financial decisions appeared susceptible to falling victim to a fraud attempt. The high number of attempts indicates a need for a measurable and concerted effort to prevent the financial fraud of older adults.
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COVID-19 , Abuso de Ancianos , Humanos , Femenino , Anciano , Masculino , Pandemias , COVID-19/epidemiología , Fraude , FloridaRESUMEN
BACKGROUND: Mucosal epithelia, including those of the oviduct, secrete antimicrobial innate immune molecules (AIIMS). These have bactericidal/bacteriostatic functions against a variety of pathogens. Among the AIIMs, sheep ß-defensin-1 (SBD-1) is one of the most potent. Even though the SBD-1 is an important AIIM and it is regulated closely by estrogenic hormone, the regulation mechanism of 17ß-estradiol has not been clearly established. We investigated the effects of E2 and agonist or inhibitor on ovine oviduct epithelial cells in regard to SBD-1 expression using reverse transcription quantitative PCR (RT-qPCR). In addition, three different pathways were inhibited separately or simultaneously to confirm the effect of different inhibitors in the regulation mechanism. RESULTS: 17beta-estradiol (E2) induced release of SBD-1 in ovine oviduct epithelial cells. SBD-1 expression was mediated through G-protein-coupled receptor 30 (GPR30) and Estrogen Receptors (ERs) activation in ovine oviduct epithelial cell. Inhibition of gene expression of protein kinase A (PKA), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) led to a decreased SBD-1 expression. CONCLUSIONS: Taken together, E2-induced up-regulation of SBD-1 expressions were GPR30-dependent during prophase and ERs-dependent during later-stage in ovine oviduct epithelial cells, and we assume that the effect was completed by the PKA, PKC, and NF-κB pathways simultaneous.
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Células Epiteliales/metabolismo , Estradiol/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Oviductos/citología , beta-Defensinas/metabolismo , Animales , Células Cultivadas , Femenino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Ovinos , Regulación hacia Arriba , beta-Defensinas/genéticaRESUMEN
OBJECTIVE: To explore the value of serum miR-144 and miR-221 in diagnosing atherosclerosis (AS). METHODS: The clinical data of 52 AS patients treated in the department of cardiovascular medicine of our hospital from August 2019 to August 2020 were retrospectively analyzed, and 53 healthy persons were selected from the physical examination center at the same period as the control group. By measuring the indicators including the serum vascular endothelial growth factor (VEGF), superoxide dismutase (SOD), miR-144, and miR-221 in patients of both groups, their value of diagnosing AS was analyzed. RESULTS: Compared with the control group, the AS group obtained significantly higher serum miR-221 and miR-144 expression levels (P < 0.001), significantly higher mean serum homocysteine (Hcy) level value (P < 0.001), lower mean serum SOD level (P < 0.001), and significantly higher level values of serum VEGF, nuclear factor-kappaB (NF-kB), and transforming growth factor-ß (TGF-ß) (P < 0.001), and the area under ROC curve, sensitivity, and specificity of combining miR-221 with miR-144 were significantly higher than those of single diagnosis. CONCLUSION: Serum miR-221 and miR-144 expression levels are increased in AS patients, and combining the two indicators in diagnosis is more accurate and can provide an accurate basis for diagnosis and condition assessment of AS.
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Aterosclerosis , MicroARNs , Aterosclerosis/diagnóstico , Humanos , Estudios Retrospectivos , Superóxido Dismutasa , Factor A de Crecimiento Endotelial VascularRESUMEN
Background: Tonifying-Qi-and-Detoxification Decoction (TQDD) is a Chinese medicine compound. This research probed the possible protective effects of TQDD on injuries of the colon and lung tissues in ulcerative colitis (UC) rat model. Methods: UC rat model was established by colon mucosal tissue sensitization combined with TNBS-ethanol. Ninety-six rats were randomly divided into normal control (NC), model, sulfasalazine (SASP), and TQDD (low, middle, and high dosages) groups. After 4 weeks intervention, all rats were sacrificed. The microstructure of lung tissue was observed using hematoxylin-eosin (HE) staining. Transmission electron microscope (TEM) was utilized to assess the ultrastructure change of alveolar epithelial type II cells (AEC-II). The mRNA expressions of Bax, Caspase 3, nuclear factor kappa B (NF-κB) and NF-κB inhibitor α (IKBα) in tissues were measured via quantitative reverse transcription PCR (qRT-PCR) assay. Western blotting and immunohistochemistry (IHC) were used to test p38MAPK, activating transcription factor 2 (ATF2), c-jun and c-fos expressions in tissues. Results: TQDD alleviated microstructure change of lung tissues, lung cell apoptosis and ultrastructure alterations of AEC-II in UC rat model. Moreover, TQDD suppressed activation of NF-κB pathway in colon and lung tissues. Besides, TQDD inhibited p38MAPK pathway in colon and lung tissues, as well as reduced ATF2, c-jun, and c-fos expressions in colon and lung tissues. Conclusions: This research confirmed the beneficial effect of TQDD on injuries of colon and lung tissues in UC rat model. TQDD attenuated injuries of lung and colon tissues in colon mucosal tissue sensitization combined with TNBS-ethanol-caused UC model via regulating NF-κB and p38MAPK pathways.
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Amylin is a peripheral satiation signal polypeptide co-secreted with insulin by pancreatic ß-cells in response to nutrient ingestion. Amylin participates in the eating-inhibitory effect and regulates energy metabolism by acting on the central nervous system (CNS). However, the role of amylin in regulating the biosynthesis of steroid hormones, such as testosterone, through the hypothalamic-pituitary-gonadal axis (HPG) remains unexplored. However, only limited evidence is available on the involvement of amylin in steroid synthesis, we hypothesize that amylin regulates testosterone levels via steroidogenesis-related enzymes in the CNS. In this study, we elucidated the effect of intraperitoneal injection of amylin on the protein expression of steroidogenesis-related enzymes, including 3ß-hydroxysteroid dehydrogenase (3ß-HSD), cytochrome P450 17A1 (CYP17A1), and steroidogenic acute regulatory protein (StAR), and phospho-extracellular signal-regulated kinase (pERK). Additionally, the effect of amylin on testosterone levels in male mice was examined. Our results suggested that 3ß-HSD and CYP17A1 neurons were widely expressed in the CNS of male mice, whereas StAR neurons were mainly expressed in the zona incerta (ZI) and locus coeruleus (LC) regions. Intraperitoneal injection of amylin significantly reduced (p < 0.01) the expression of 3ß-HSD, CYP17A1, and StAR in ZI and other areas near the third ventricle (3 V) but increased (p < 0.01) pERK expression, brain testosterone levels, serum FSH, serum LH, and decreased (p < 0.01) serum testosterone levels in mice. In conclusion, amylin regulates testosterone levels via steroidogenesis-related enzymes in the central nervous system of male mice.
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Polipéptido Amiloide de los Islotes Pancreáticos , Hormonas Peptídicas , Animales , Ratones , Masculino , Testosterona , Esteroides , Sistema Nervioso CentralRESUMEN
Cross-lingual sentiment classification (CLSC) aims to leverage rich-labeled resources in the source language to improve prediction models of a resource-scarce domain in the target language. Existing feature representation learning-based approaches try to minimize the difference of latent features between different domains by exact alignment, which is achieved by either one-to-one topic alignment or matrix projection. Exact alignment, however, restricts the representation flexibility and further degrades the model performances on CLSC tasks if the distribution difference between two language domains is large. On the other hand, most previous studies proposed document-level models or ignored sentiment polarities of topics that might lead to insufficient learning of latent features. To solve the abovementioned problems, we propose a coarse alignment mechanism to enhance the model's representation by a group-to-group topic alignment into an aspect-level fine-grained model. First, we propose an unsupervised aspect, opinion, and sentiment unification model (AOS), which trimodels aspects, opinions, and sentiments of reviews from different domains and helps capture more accurate latent feature representation by a coarse alignment mechanism. To further boost AOS, we propose ps-AOS, a partial supervised AOS model, in which labeled source language data help minimize the difference of feature representations between two language domains with the help of logistics regression. Finally, an expectation-maximization framework with Gibbs sampling is then proposed to optimize our model. Extensive experiments on various multilingual product review data sets show that ps-AOS significantly outperforms various kinds of state-of-the-art baselines.
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In July 2018, the United States Department of Housing and Urban Development (HUD) implemented a mandatory smoke-free rule in public housing. This study assessed administrator and resident perceptions of rule implementation during its initial year in the District of Columbia Housing Authority (DCHA). Assessment included nine focus groups (n = 69) with residents and in-depth interviews with administrators (n = 7) and residents (n = 26) from 14 DCHA communities (family = 7 and senior/disabled = 7). Semi-structured discussion guides based on the multi-level socio-ecological framework captured dialogue that was recorded, transcribed verbatim, and coded inductively. Emerging major themes for each socio-ecological framework level included: (1) Individual: the rule was supported due to perceived health benefits, with stronger support among non-smokers; (2) Interpersonal: limiting secondhand smoke exposure was perceived as a positive for vulnerable residents; (3) Organizational: communication, signage, and cessation support was perceived as a need; (4) Community: residents perceived mobility, disability, weather, and safety-related issues as barriers; and (5) Public Policy: lease amendments were perceived as enablers of rule implementation but expressed confusion about violations and enforcement. A majority of administrators and residents reported favorable implications of the mandated HUD rule. The novel application of a socio-ecological framework, however, detected implementation nuances that required improvements on multiple levels, including more signage, cessation support, clarification of enforcement roles, and addressing safety concerns.
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Política para Fumadores , Contaminación por Humo de Tabaco , Vivienda , Percepción , Vivienda Popular , Contaminación por Humo de Tabaco/análisis , Estados Unidos , Remodelación UrbanaRESUMEN
Immunohistochemical staining is the important method for the identification of protein expression in mammal ovaries, in particular in the follicles with the potential to develop into cumulus-oocyte complexes (COCs), which are able to support oocyte maturation regardless of in vivo or in vitro. Here, we reported an advanced immunohistochemical method based on an artificial structure gathering multiple COCs by paraffin embedding for rapid and highly sensitive detection of co-expressed proteins in ovine COCs rather than ovaries. Compared with the conventional immunohistochemistry on ovine ovaries, the advanced COC paraffin sectioning technique showed the better immunostaining effect and featured the higher generation rate for COCs, the distincter cumulus layers, and the more simplified procedures. These results indicate that the COC paraffin sectioning technique is highly effectively applied for identification of protein expression in ovine COC.