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OBJECTIVES: Antioxidant diets are considered to be protective factors against stroke. However, comprehensive measurement and evaluation of antioxidant diets are lacking. This study aimed to investigate the correlation between the Composite Dietary Antioxidant Index (CDAI) and stroke in adults. MATERIALS AND METHODS: In this study, based on the National Health and Nutrition Examination Survey (NHANES) 2011-2020 data, multivariate logistic regression, smoothing curve fitting, and threshold effect analysis were used to explore the relationship between CDAI and stroke. Subgroup analyses and interaction tests were conducted to assess the stability of this association within the population. RESULTS: Among 12,922 U.S. adults, there was a significant negative correlation between CDAI and the prevalence of stroke. In the fully adjusted model, the risk of stroke was reduced by 4 % for each 1-unit increase in CDAI (OR [95% CI] = 0.96 [0.93, 0.99]). Participants in the highest quartile of the CDAI had a 37 % lower risk of stroke than those in the lowest quartile (OR [95% CI] = 0.63 [0.47, 0.84]). This negative correlation remained stable across subgroups. Furthermore, the study revealed an L-shaped association between CDAI and stroke through smoothing curve fitting. The threshold effect analysis further identified the inflection point as -1.55. CONCLUSIONS: This study revealed an L-shaped relationship between CDAI and stroke. Keeping CDAI in the proper range may help prevent stroke in the general population.
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Antioxidantes , Accidente Cerebrovascular , Humanos , Adulto , Encuestas Nutricionales , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Dieta , Factores ProtectoresRESUMEN
Efforts to explore the macrolevel determinants of police-involved homicides have expanded in recent years due in part to increased scrutiny and media attention to such events, and increased data availability of these events through crowdsourced databases. However, little empirical research has examined the spatial determinants of such events. The present study extends the extant macrolevel research on police-involved homicides by employing an underutilized spatial econometric model, the spatial Durbin model (SDM), to assess the direct and indirect county effects of racial threat, economic threat, social disorganization, and community violence on police killings within and between US counties from 2013 through 2020. Results indicate a direct inverse relationship between racial threat and police-involved homicides, no support for economic threat, and a direct positive association with two measures of social disorganization. Additionally, we find firearm availability exhibits significant direct and indirect spatial dependence on focal county police-involved homicides, reflecting spatial spillover processes. In essence, as firearm availability in neighboring counties increases, police-involved homicides within a focal county increase. The implications of these findings for racial threat, economic threat, social disorganization, and community violence are discussed.
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Homicidio , Policia , Humanos , Anomia (Social) , ViolenciaRESUMEN
Although circular RNAs (circRNAs) are found to play important roles in many pathophysiological processes, the canonical theory that they act as microRNA sponges is now more and more challenged, given that most circRNAs only have few binding sites in a particular microRNA. Our previous study revealed that some up-regulated circRNAs play protective roles in bisphenol A (BPA)-induced toxicity in GC-2 germ cells. Here by CCK-8 assay, apoptosis assay, qRT-PCR and western blot analysis, we further discover that circRNAs (represented by circDcbld2, circMapk1 and circTbcld20) can cooperatively sponge miR-214-3p and then up-regulate AKT1 in ameliorating BPA-induced reproductive toxicity. They share binding sites with miR-214-3p and collectively reinforce the sponging effects. In addition, the upstream regulation mechanism, proven by bioinformatics analysis and in vitro gain- and loss-of-function study, shows that down-regulation of RNA binding protein QKI5 after BPA exposure can increase the expressions of these protective circRNAs, and thus activate the cell protective process. The QKI5-circDcbld2/circMapk1/circTblcd20-miR-214-3p-AKT1 axis ameliorates the toxic effect of BPA on GC-2 cells. Many other circRNAs up-regulated upon BPA treatment and QKI5 down-regulation also show binding sites with miR-214-3p. Thus the above axis may also be extrapolated to other circRNAs. Our results enrich the context of circRNA sponge mode and may provide new ideas in future multiple nucleic acid therapy.
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MicroARNs , ARN Circular , Compuestos de Bencidrilo/toxicidad , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Fenoles , ARN Circular/genéticaRESUMEN
Photodynamic therapy (PDT) has significant advantages in the treatment of malignant tumors, such as high efficiency, minimal invasion and less side effects, and it can preserve the integrity and quality of the organs. The power density, irradiation time and photosensitizer (PS) concentration are three main parameters that play important roles in killing tumor cells. However, until now, the underlying relationships among them for PDT outcomes have been unclear. In this study, human malignant glioblastoma U-118MG and melanoma A375 cells were selected, and the product of the power density, irradiation time and PS concentration was defined as the total photodynamic parameter (TPP), in order to investigate the mechanisms of PS sinoporphyrin sodium (DVDMS)-mediated PDT (DVDMS-PDT). The results showed that the survival rates of the U-118MG and A375 cells were negatively correlated with the TPP value in the curve, and the correlation exactly filed an e-exponential function. Moreover, according to the formula, we realized controllable killing effects of the tumor cells by randomly adjusting the three parameters, and we finally verified the accuracy and repeatability of the formula. In conclusion, the establishment and implementation of a newly functional relationship among the PDT parameters are essential for predicting PDT outcomes and providing personalized precise treatment, and they are contributive to the development of PDT dosimetry.
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Fotoquimioterapia , Porfirinas , Línea Celular Tumoral , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/farmacología , Porfirinas/uso terapéuticoRESUMEN
Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in-depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR-125a-5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR-125a-5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR-125a-5p expression by testosterone. Androgen response element in the promoter of miR-125a-5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl-protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR-125a-5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR-125a-5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR-125a-5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH.
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Hipogonadismo/enzimología , Lipoilación , MicroARNs/metabolismo , Procesamiento Proteico-Postraduccional , Testosterona/deficiencia , Tioléster Hidrolasas/metabolismo , Factores de Edad , Anciano , Animales , Estudios de Casos y Controles , Castración , Modelos Animales de Enfermedad , Células HEK293 , Terapia de Reemplazo de Hormonas , Humanos , Hipogonadismo/sangre , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/genética , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Persona de Mediana Edad , Células PC12 , Regiones Promotoras Genéticas , Ratas , Elementos de Respuesta , Testosterona/sangre , Testosterona/uso terapéutico , Tioléster Hidrolasas/genéticaRESUMEN
STUDY OBJECTIVES: In this study, we conducted a cross-sectional analysis of the sleep characteristics in the elderly Chinese people to comprehensively investigate the association between sleep and cognitive function in the elderly people. We aimed to evaluate the most important demographic factors, conventional physiological indices and living habits that may influence sleep. METHODS: We surveyed 2901 elderly people (age ≥60 years old) face-to-face from 1 July to 31 December 2017, who were recruited from 17 communities of the Pudong New Area (Shanghai, China) by probability proportional to size. The Pittsburgh sleep quality index (PSQI) scale was used to describe the sleep features of each participant. Cognitive assessment was performed using the mini-mental state examination (MMSE) scale, Montreal cognitive assessment (MoCA) and the clinical dementia rating (CDR) scale. Those factors which potentially influence sleep and consequentially may impact cognition in the elderly people were evaluated, and the correlations of sleep characteristics and cognitive function were explored by the linear regression analysis. RESULTS: Altogether, there were 1287 (44.4%) people taking part in the investigation. Sleep quality was significantly correlated with MMSE and MoCA total scores. Healthy sleep (especially enough sleep) was correlated with better cognitive functions. Besides recognised relative factors (such as age, sex and living alone), the number of children was found to be a strong risk factor of poor sleep. Anxiety before sleep and light/noise interference significantly damaged sleep while an exercise routine was associated with better sleep. Moderate levels of reading, watching TV and household work were correlated with superior sleep quality. CONCLUSION: In conclusion, sleep characteristics correlate with cognitive decline in the elderly people, and they can be influenced by multiple demographic factors and living habits. To improve sleep quality, it may be important to change sleep environment, to be relax, to increase physical exercise and recreational activities moderately.
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Disfunción Cognitiva , Anciano , Niño , China/epidemiología , Disfunción Cognitiva/epidemiología , Estudios Transversales , Humanos , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , SueñoRESUMEN
Glucocorticoids (GCs) are frequently used to treat chronic disorders in children, including inflammation and cancer. Prolonged treatment with GCs is well known to impair bone growth, an effect linked to increased apoptosis and suppressed proliferation in growth plate chondrocytes. We hypothesized that the endogenous antiapoptotic protein humanin (HN) may prevent these effects. Interestingly, GC-induced bone growth impairment and chondrocyte apoptosis was prevented in HN overexpressing mice, HN-treated wild-type mice, and in HN-treated cultured rat metatarsal bones. GC-induced suppression of chondrocyte proliferation was also prevented by HN. Furthermore, GC treatment reduced Indian Hedgehog expression in growth plates of wild-type mice but not in HN overexpressing mice or HN-treated wild-type animals. A Hedgehog (Hh) antagonist, vismodegib, was found to suppress the growth of cultured rat metatarsal bones, and this effect was also prevented by HN. Importantly, HN did not interfere with the desired anti-inflammatory effects of GCs. We conclude that HN is a novel regulator of Hh signaling preventing GC-induced bone growth impairment without interfering with desired effects of GCs. Our data may open for clinical studies exploring a new possible strategy to prevent GC-induced bone growth impairment by cotreating with HN.-Zaman, F., Zhao, Y., Celvin, B., Mehta, H. H., Wan, J., Chrysis, D., Ohlsson, C., Fadeel, B., Cohen, P., Sävendahl, L. Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid-induced bone growth impairment.
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Desarrollo Óseo/efectos de los fármacos , Glucocorticoides/farmacología , Proteínas Hedgehog/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Citocinas/metabolismo , Fragmentación del ADN/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Proteínas Hedgehog/genética , Inmunohistoquímica , Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Transducción de Señal/fisiologíaRESUMEN
Previous research on segregation and health has been criticized for overlooking the fact that segregation is a multi-dimensional concept (i.e., evenness, exposure, concentration, centralization, and clustering) and recent evidence drawn from non-black minorities challenges the conventional belief that residential segregation widens racial health disparities. Combining a survey data (n = 18,752) from Philadelphia with the 2010 Census tract (n = 925) data, we examine two theoretical frameworks to understand why the association of segregation with health may differ by race/ethnicity. Specifically, we investigate how each dimension of segregation contributed to racial disparities in self-rated health. We found (1) high levels of white/black concentration could exacerbate the white/black health disparities up to 25 percent, (2) the white/Hispanic health disparities was narrowed by increasing the level of white/Hispanic centralization, and (3) no single dimension of segregation statistically outperforms others. Our findings supported that segregation is bad for blacks but may be beneficial for Hispanics.
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Negro o Afroamericano , Disparidades en el Estado de Salud , Hispánicos o Latinos , Vivienda , Características de la Residencia , Segregación Social , Población Blanca , Adulto , Anciano , Censos , Autoevaluación Diagnóstica , Etnicidad , Humanos , Persona de Mediana Edad , Grupos Minoritarios , Philadelphia , Grupos Raciales , Racismo , Factores Socioeconómicos , Encuestas y Cuestionarios , Población Urbana , Adulto JovenRESUMEN
OBJECTIVES: This study examined patients' satisfaction with services provided by different oral health providers, their intent to return for additional care, and associations with patients' demographics and service characteristics. METHODS: Descriptive analyses and multivariable ordinal logistic regressions were conducted using survey data from 898 patients who received care at Apple Tree Dental (ATD) in Minnesota during 2021. The questionnaire included 12 statements on patient satisfaction with the clinician's ability to explain the dental diagnosis and treatment options, to be considerate of the patient's needs and dental anxiety, and to provide technically competent services. RESULTS: In general, patients reported high satisfaction with dental care and a strong intent to return to ATD for future services. No significant differences in patient satisfaction were observed by provider type. Patients' intent to return was higher among non-White respondents (OR = 1.76; 95% CI = 1.06-2.92) and patients who were more satisfied with their providers' technical competence/treatment (OR = 1.47; 95% CI = 1.37-1.57). The association between intent to return and patient satisfaction with providers' information/communication was stronger for patients treated by dental hygienists. The association between intent to return and patient satisfaction with providers' technical competence/treatment was also stronger for patients who were more satisfied with providers' information/communication and understanding/acceptance, and for those treated by their desired or usual provider. CONCLUSIONS: The study underscores the benefits of introducing dental therapists to the oral healthcare team, showing that this can be achieved without sacrificing either the quality of patient care or patient satisfaction.
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Objective: Non-suicidal self-injury (NSSI) has become a common clinical problem that severely threatens the mental and physical health of Chinese adolescents. This study explores the mediation effects of NSSI functions on the relationship between anxiety and NSSI frequency among depressed Chinese adolescents as well as the sex differences in the mediating effects. Methods: In this study, a cross-sectional survey method was used to obtain data of 1773 adolescent patients with major depressive disorders from over 20 specialized psychiatric hospitals across multiple provinces in China. A self-designed questionnaire for demographic information, the Chinese version of Functional Assessment of Self- Mutilation (C-FASM), and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were employed to investigate demographic data, NSSI frequency, NSSI functions, and anxiety and to analyze the mediating effects of NSSI functions on the association between anxiety and NSSI frequency among adolescents of different sexes. Results: A total of 316 male patients and 1457 female patients were investigated. Female patients had a higher NSSI frequency (Z=3.195, P=0.001) and higher anxiety scores than did male patients (Z=2.714, P=0.007). Anxiety had a stronger positive predictive effect on the NSSI frequency in females (OR = 1.090) than in males (OR = 1.064). For male patients, the emotion regulation function in NSSI motivation played a full mediating role in the association between anxiety and NSSI frequency. For female patients, the emotion regulation and social avoidance functions in NSSI functions played a partial mediating role between anxiety and NSSI frequency. Conclusions: There are sex differences in the mediating role of NSSI functions of depressed adolescents in the association between anxiety and NSSI frequency. When experiencing anxiety, both males and females may engage in NSSI behaviors as a means to regulate their emotions. For females, anxiety can directly predict NSSI frequency, and they may attempt NSSI to achieve the purpose of rejecting others. In the face of anxiety among depressed adolescents of different sexes, developing different emotional regulation methods and behavioral regulation strategies may be critical in preventing their NSSI behaviors.
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Background: Antioxidant diets are considered to be protective factors for cognitive function. However, comprehensive measures of antioxidant diets are lacking. Objective: To examine the association between the Composite Dietary Antioxidant Index (CDAI) and cognitive function in the elderly. Methods: This cross-sectional study included a total of 2,456 participants (≥60 years old) from NHANES 2011-2014. Calculation of CDAI based on 6 minerals and vitamins (manganese, selenium, zinc, vitamins A, C, and E). Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). We also created a composite cognitive z-score to represent global cognition. The statistical analyses we used included multiple linear regression analyses, subgroup analyses, curve-fitting analyses, and threshold effects analyses. Results: After controlling for demographic characteristics, lifestyle factors, and disease history, multivariate linear regression analyses showed that increased CDAI was positively associated with scores on global cognitive function and each cognitive domain (pâ<â0.05), with subgroup analyses suggesting that this association was more pronounced in stroke patients (p for interactionâ<â0.05). Curve-fitting analyses and threshold effect analyses showed saturation effects between CDAI and CREAD Test, AFT, and composite Z-score, and an inverted U-shaped relationship with DSST, with inflection points of -1.89, 0.79, 1.13, and 1.77, respectively. Conclusions: Our findings support that higher levels of CDAI are correlated with significantly elevated cognitive function. Maintaining CDAI in an appropriate range may contribute to cognitive health in elderly.
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Antioxidantes , Cognición , Animales , Anciano , Humanos , Estudios Transversales , Encuestas Nutricionales , Vitaminas , Envejecimiento , DietaRESUMEN
Objective: Previous studies have not shown an association between IgD-CD24-B-cell absolute count (IgD-CD24-AC) and ischemic stroke (IS). Our study aimed to assess the causal effect of IgD-CD24-AC on IS and to explore the role of ascorbic acid 2-sulfate (AA2S) as a potential mediator. Methods: Our study was based on the largest available genome-wide association study (GWAS). Inverse variance weighting (IVW), MR-Egger, weighted median (WMN), simple mode, and weighted mode methods were used to assess causal effects, with IVW as the primary outcome. Subsequently, we further performed a two-step MR analysis to evaluate whether AA2S mediated this causal effect. In addition, several sensitivity analyses were conducted to evaluate heterogeneity, including Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis. Results: Using the IVW approach, the risk ratio of IgD-CD24-AC to IS was estimated to be 1.216 (95% CI = 1.079-1.371, p = 0.001). This result was supported by the WMN method (OR = 1.204, 95% CI = 1.020-1.421, p = 0.028) and the MR-Egger method (OR = 1.177, 95% CI = 0.962-1.442, p = 0.133). We also observed the same trend with the simple model and weighted model. Furthermore, the proportion of genetically predicted IgD-CD24-AC mediated through AA2S levels was 3.73%. Conclusion: Our study revealed a causal relationship between IgD-CD24-AC and IS, a small part of which was mediated by AA2S. These findings offer critical insights for developing immune-targeted therapies in the future and lay a strong foundation for advancements in precision medicine.
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Background: CDCA5 has been reported as a gene involved in the cell cycle, however current research provides little details. Our goal was to figure out its functions and probable mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and web-based analysis tools were applied to analyze CDCA5's correlations with the gene expression, clinical prognosis, genetic alterations, promoter methylation, alternative splicing, immune checkpoints, tumor microenvironment and enrichment. Realtime PCR, cell clone formation assay, CCK-8 assay, cell proliferation assay, migration assay, invasion assay and apoptosis assay were used to evaluate the effect of CDCA5 silencing on colon cancer cell lines. Results: CDCA5 is highly expressed in most tumors, which has been linked to a poor prognosis. Immune checkpoints analysis revealed that CDCA5 was associated with the immune gene CD276 in various tumors. Single-cell analysis showed that CDCA5 correlated with proliferating T cell infiltration in COAD. Enrichment analysis demonstrated that CDCA5 may modify cell cycle genes to influence p53 signaling. The examination of DLD1 cells revealed that CDCA5 increased the proliferation and blocked cell apoptosis. Conclusion: This study contributes to the knowledge of the role of CDCA5 in carcinogenesis, highlighting the prognostic potential and carcinogenic involvement of CDCA5 in pan-cancer.
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Proinflammatory cytokines are crucial contributors to neuroinflammation in the development of chronic pain. Here, we identified il16, which encodes interleukin-16 (IL-16), as a differentially expressed gene in spinal dorsal horn of a complete Freund's Adjuvant (CFA) inflammatory pain model in mice by RNA sequencing. We further investigated whether and how IL-16 regulates pain transmission in the spinal cord and contributes to the development of inflammatory pain hypersensitivity. RNA sequencing and bioinformatics analysis revealed elevated IL-16 transcript levels in the spinal dorsal horn after CFA injection. This increase was further confirmed by qPCR, immunofluorescence, and western blotting. Knockdown of IL-16 by intrathecal injection of IL-16 siRNA not only attenuated CFA-induced mechanical and thermal pain hypersensitivity, but also inhibited enhanced c-fos expression and glial activation in the spinal dorsal horn in male mice injected with CFA. Moreover, exogenous IL-16 induced nociceptive responses and increased c-fos expression and glial activation in spinal dorsal horn. This effect was largely impaired when CD4, the binding receptor for IL-16, was inhibited. In addition, CD4 expression was upregulated in the spinal dorsal horn after CFA injection and CD4 was present in microglia and in contact with astrocytes and activated spinal neurons. Taken together, these results suggest that enhanced IL-16-CD4 signaling triggers pain and activates microglia and astrocytes in the spinal dorsal horn, thus contributing to inflammatory pain. IL-16 may serve as a promising target for the treatment of inflammatory pain.
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Hiperalgesia , Interleucina-16 , Ratones , Masculino , Animales , Interleucina-16/genética , Interleucina-16/metabolismo , Interleucina-16/farmacología , Hiperalgesia/metabolismo , Dolor/inducido químicamente , Asta Dorsal de la Médula Espinal/metabolismo , Médula Espinal , Neuronas , Adyuvante de Freund , Inflamación/metabolismoRESUMEN
Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.
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Astrocitos , Complejo CD3 , Interleucina-16 , Neuralgia , Transducción de Señal , Animales , Femenino , Ratones , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Complejo CD3/metabolismo , Antígenos CD4/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Hiperalgesia/metabolismo , Interleucina-16/metabolismo , Ratones Endogámicos C57BL , Neuralgia/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Colon adenocarcinoma (COAD) is the most common malignancy of the digestive tract, which is characterized by a dismal prognosis. No effective treatment has been established presently, thus there is an urgent need to understand the mechanisms driving COAD progression in order to develop effective therapeutic approaches and enhance clinical outcomes. In this study, we found that KLF7 is overexpressed in COAD tissues and correlated with clinicopathological features of COAD. Both gain-of-function and loss-of-function experiments have unequivocally demonstrated that overexpression of KLF7 promotes the growth and metastasis of COAD in vitro and in vivo, while KLF7 knockdown attenuated these effects. Mechanistically, our findings reveal that KLF7 can specifically bind to the promoter region of PDGFB (TGGGTGGAG), thus promoting the transcription of PDGFB and increasing its secretion. Subsequently, secreted PDGFB facilitates the progression of COAD by activating MAPK/ERK, PI3K/AKT, and JAK/STAT3 signaling pathways through PDGFRß. Additionally, we found that sunitinib can block PDGFB signaling and inhibit COAD progression, offering a promising therapeutic strategy for COAD treatment.
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Adenocarcinoma , Neoplasias del Colon , Humanos , Neoplasias del Colon/metabolismo , Proteínas Proto-Oncogénicas c-sis/metabolismo , Adenocarcinoma/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/genética , Becaplermina , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismoRESUMEN
PURPOSE: The purpose of this study was to identify barriers to oral health services experienced by children and evaluate variation across demographic and socioeconomic population groups. METHODS: The data were collected from 1,745 parents/legal guardians who responded to a web-based survey regarding their children's access to health services in 2019. Descriptive statistics and binary and multinomial logistic models were used to examine barriers to needed dental care and factors contributing to differential experiences with those barriers. RESULTS: A quarter of children of responding parents experienced at least one barrier to oral health care, most commonly cost-related barriers. Child-guardian relationship type, having a pre-existing health condition, and dental insurance type increased the risk of encountering certain barriers two-to four-fold. Children with a diagnosed emotional, developmental, or behavioral condition (odds ratio [OR] equals 1.77, dental anxiety; OR equals 4.09, unavailability of needed services) and those with a Hispanic parent/guardian (OR equals 2.44, lack of insurance; OR equals 3.03, insurance not paying for needed services) were more likely to encounter various barriers than other children. The number of siblings, parent/guardian's age, education level, and oral health literacy were also associated with different barriers. The likelihood of encountering multiple barriers was over three times higher for children with a pre-existing health condition (OR equals 3.56; 95 percent confidence interval equals 2.30 to 5.50). CONCLUSIONS: This study highlighted the significance of cost-related barriers to oral health care and suggested disparities in access among children with disparate personal and family backgrounds.
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Accesibilidad a los Servicios de Salud , Salud Bucal , Niño , Humanos , Hispánicos o Latinos , Modelos Logísticos , Padres , Seguro de SaludRESUMEN
Objective: Children with inflammatory bowel disease (IBD) often suffer from poor bone growth and impaired bone health. Humanin is a cytoprotective factor expressed in bone and other tissues and we hypothesized that humanin levels are suppressed in conditions of chronic inflammation. To address this, humanin levels were analyzed in serum samples from IBD patients and in ex vivo cultured human growth plate tissue specimens exposed to IBD serum or TNF alone. Methods: Humanin levels were measured by ELISA in serum from 40 children with IBD and 40 age-matched healthy controls. Growth plate specimens obtained from children undergoing epiphysiodesis surgery were cultured ex vivo for 48 hours while being exposed to IBD serum or TNF alone. The growth plate samples were then processed for immunohistochemistry staining for humanin, PCNA, SOX9 and TRAF2 expression. Dose-response effect of TNF was studied in the human chondrocytic cell line HCS-2/8. Ex vivo cultured fetal rat metatarsal bones were used to investigate the therapeutic effect of humanin. Results: Serum humanin levels were significantly decreased in children with IBD compared to healthy controls. When human growth plate specimens were cultured with IBD serum, humanin expression was significantly suppressed in the growth plate cartilage. When cultured with TNF alone, the expression of humanin, PCNA, SOX9, and TRAF2 were all significantly decreased in the growth plate cartilage. Interestingly, treatment with the humanin analog HNG prevented TNF-induced bone growth impairment in cultured metatarsal bones. Conclusion: Our data showing suppressed serum humanin levels in IBD children with poor bone health provides the first evidence for a potential link between chronic inflammation and humanin regulation. Such a link is further supported by the novel finding that serum from IBD patients suppressed humanin expression in ex vivo cultured human growth plates.
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Inflamación , Enfermedades Inflamatorias del Intestino , Péptidos y Proteínas de Señalización Intracelular , Niño , Ratas , Humanos , Animales , Antígeno Nuclear de Célula en Proliferación , Factor 2 Asociado a Receptor de TNFRESUMEN
BACKGROUND: Hepcidin antimicrobial peptide (HAMP) is a key factor in maintaining iron metabolism, which may induce ferroptosis when upregulated. However, its prognostic value and relation to immune infiltrating cells remains unclear. METHODS: This study analyzed the expression levels of HAMP in the Oncomine, Timer and Ualcan databases, and examined its prognostic potential in KIRC with R programming. The Timer and GEPIA databases were used to estimate the correlations between HAMP and immune infiltration and the markers of immune cells. The intersection genes and the co-expression PPI network were constructed via STRING, R programming and GeneMANIA, and the hub genes were selected with Cytoscape. In addition, we analyzed the gene set enrichment and GO/KEGG pathways by GSEA. RESULTS: Our study revealed higher HAMP expression levels in tumor tissues including KIRC, which were related to poor prognosis in terms of OS, DSS and PFI. The expression of HAMP was positively related to the immune infiltration level of macrophages, Tregs, etc., corresponding with the immune biomarkers. Based on the intersection genes, we constructed the PPI network and used the 10 top hub genes. Further, we performed a pathway enrichment analysis of the gene sets, including Huntington's disease, the JAK-STAT signaling pathway, ammonium ion metabolic process, and so on. CONCLUSION: In summary, our study gave an insight into the potential prognosis of HAMP, which may act as a diagnostic biomarker and therapeutic target related to immune infiltration in KIRC.
Asunto(s)
Carcinoma de Células Renales , Ferroptosis , Enfermedad de Huntington , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Ferroptosis/genética , Bases de Datos Factuales , Neoplasias Renales/genética , Biomarcadores de Tumor/genética , Hepcidinas/genéticaRESUMEN
Recently, organic long persistent luminescence (OLPL) has attracted widespread attention as a new luminescence pathway initiated by the exciplex. However, the low quantum yield, few alternative molecules and high fabrication cost seriously slow down the development of OLPL materials. Herein, a series of simple multi-guest/host OLPL materials with a high quantum yield are reported by doping four phenothiazine derivative guest molecules into 9H-xanthen-9-one host matrices. The F-substituted phenothiazine derivative doping system displays highly efficient emission with 46.3% quantum yield in air. Meanwhile, these OLPL materials provide broad opportunities for further application in the field of heat resistance due to their highly efficient luminescence at high temperatures.