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1.
J Voice ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39138041

RESUMO

OBJECTIVE: This study aims to clarify the clinical characteristics of pediatric voice disorders. METHODS: The clinical data of 1782 pediatric patients presenting with voice disorders were retrospectively analyzed. These cases were categorized into four age-based cohorts: 0-3, 4-7, 8-11, and 12-15years. Variables such as gender disparities, laryngoscopic manifestation, disease types, and acoustic parameters were thoroughly examined. RESULTS: A total of 1782 children with acoustic hoarseness were included in this study, comprising 1325 males and 457 females. When the sex ratio among the children in each group was compared, males were found to outnumber females. A notable male predominance was observed across all age groups. Laryngoscopic results revealed that the most prevalent condition was vocal cord nodules (1363 cases, 76.48%), followed by vocal cord polyps (271 cases, 15.20%). Other diseases included laryngeal papillomas, vocal fold movement impairment, vocal cord cysts, functional dysphonia, leukoplakia of the vocal cords, and benign laryngeal tumors such as laryngeal amyloidosis and subglottic granular cell tumors. Among these, adenoid hypertrophy was presented in 382 children (21.44%). Additionally, the Reflux Finding Score (RFS) was conducted, and 799 cases (44.83%) were found to have a score above 7. The distribution of various diseases across different age groups indicated that children with vocal cord nodules (637 cases, 46.74%), vocal cord polyps (109 cases, 40.22%), and laryngeal papillomas (35, 36.84%) were predominantly found in the 4-7 years age group. Pediatric acute laryngitis (three cases, 75%) and vocal fold movement impairment (eight cases, 36.36%) were more common in the 0-3 years age group. Functional dysphonia (four cases, 66.67%) and vocal cord leukoplakia (four cases, 80%) were mainly observed in the 12-15 years age group, while vocal cord cysts were predominantly seen in the 8-11 years age group (four cases, 57.14%). A comparative analysis of acoustic parameters among 153 children showed statistically significant differences in jitter, fundamental frequency (F0), voice handicap index (VHI), reflux symptom index (RSI), and RFS across different pathologies. CONCLUSION: This study highlighted that vocal cord nodules, vocal cord polyps, and laryngeal papillomas were the primary causes of pediatric hoarseness, although the possibility of tumors and rare diseases cannot be disregarded. There was a noticeable gender bias towards males, and functional dysphonia was significantly more prevalent in older children.

2.
Diagnostics (Basel) ; 14(15)2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39125563

RESUMO

The severity of periodontitis can be analyzed by calculating the loss of alveolar crest (ALC) level and the level of bone loss between the tooth's bone and the cemento-enamel junction (CEJ). However, dentists need to manually mark symptoms on periapical radiographs (PAs) to assess bone loss, a process that is both time-consuming and prone to errors. This study proposes the following new method that contributes to the evaluation of disease and reduces errors. Firstly, innovative periodontitis image enhancement methods are employed to improve PA image quality. Subsequently, single teeth can be accurately extracted from PA images by object detection with a maximum accuracy of 97.01%. An instance segmentation developed in this study accurately extracts regions of interest, enabling the generation of masks for tooth bone and tooth crown with accuracies of 93.48% and 96.95%. Finally, a novel detection algorithm is proposed to automatically mark the CEJ and ALC of symptomatic teeth, facilitating faster accurate assessment of bone loss severity by dentists. The PA image database used in this study, with the IRB number 02002030B0 provided by Chang Gung Medical Center, Taiwan, significantly reduces the time required for dental diagnosis and enhances healthcare quality through the techniques developed in this research.

3.
Cancer Lett ; 600: 217179, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39154704

RESUMO

Acquired resistance to endocrine treatments remains a major clinical challenge. In this study, we found that desmoglein-2 (DSG2) plays a major role in acquired endocrine resistance and cellular plasticity in ER+ breast cancer (BC). By analysing the well-established fulvestrant-resistant ER+ BC model using single-cell RNA-seq, we revealed that ER inhibition leads to a specific increase in DSG2 in cancer cell populations, which in turn enhances desmosome formation in vitro and in vivo and cell phenotypic plasticity that promotes resistance to treatment. DSG2 depletion reduced tumorigenesis and metastasis in fulvestrant-resistant xenograft models and promoted fulvestrant efficiency. Mechanistically, DSG2 forms a desmosome complex with JUP and Vimentin and triggers Wnt/PCP signalling. We showed that elevated DSG2 levels, along with reduced ER levels and an activated Wnt/PCP pathway, predicted poor survival, suggesting that a DSG2high signature could be exploited for therapeutic interventions. Our analysis highlighted the critical role of DSG2-mediated desmosomal junctions following antiestrogen treatment.


Assuntos
Neoplasias da Mama , Desmogleína 2 , Desmossomos , Resistencia a Medicamentos Antineoplásicos , Via de Sinalização Wnt , Desmogleína 2/metabolismo , Desmogleína 2/genética , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Feminino , Animais , Desmossomos/metabolismo , Camundongos , Fulvestranto/farmacologia , Antineoplásicos Hormonais/farmacologia , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Fenótipo , Placofilinas/metabolismo , Placofilinas/genética , Plasticidade Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Células MCF-7 , Regulação Neoplásica da Expressão Gênica , gama Catenina
4.
Exp Eye Res ; 246: 110014, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39074653

RESUMO

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450 µm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.


Assuntos
Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia , Fundo de Olho , Camundongos Endogâmicos C57BL , Miopia , Refração Ocular , Retina , Tomografia de Coerência Óptica , Animais , Camundongos , Tomografia de Coerência Óptica/métodos , Miopia/fisiopatologia , Miopia/etiologia , Refração Ocular/fisiologia , Retina/fisiopatologia , Angiofluoresceinografia/métodos , Corioide/irrigação sanguínea , Estimulação Luminosa , Luz , Comprimento Axial do Olho , Masculino
5.
Front Public Health ; 12: 1352417, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957205

RESUMO

Background: In 2017, China launched a comprehensive reform of public hospitals and eliminated drug markups, aiming to solve the problem of expensive medical treatment and allow poor and low-income people to enjoy basic health opportunities. This study attempts to evaluate the policy impact of public hospital reform on the health inequality of Chinese residents and analyze its micro-level mechanism from the perspective of household consumption structure. Studying the inherent causal connection between public hospital reform and health inequality is of paramount significance for strengthening China's healthcare policies, system design, raising the average health level of Chinese residents, and achieving the goal of ensuring a healthy life for individuals of all age groups. Methods: Based on the five waves of data from the China Family Panel Studies (CFPS) conducted in 2012-2020, We incorporates macro-level statistical indicators such as the time of public hospital reforms, health insurance surplus, and aging, generating 121,447 unbalanced panel data covering 27 provinces in China for five periods. This data was used to explore the impact of public hospital reform on health inequality. Logical and empirical tests were conducted to determine whether the reform, by altering family medical care and healthy leisure consumption expenditures, affects the micro-pathways of health inequality improvement. We constructed a two-way fixed model based on the re-centralized influence function (RIF_CI_OLS) and a chained mediation effects model to verify the hypotheses mentioned above. Results: Public hospital reform can effectively improve the health inequality situation among Chinese residents. The reform significantly reduces household medical expenses, increases healthy leisure consumption, promotes the upgrading of family health consumption structure, and lowers the health inequality index. In terms of indirect effects, the contribution of the increase in healthy leisure consumption is relatively greater. Conclusion: Public hospital reform significantly alleviates health inequality in China, with household health consumption serving as an effective intermediary pathway in the aforementioned impact. In the dual context of global digitization and exacerbated population aging, enhancing higher education levels and vigorously developing the health industry may be two key factors contributing to this effect.


Assuntos
Reforma dos Serviços de Saúde , Hospitais Públicos , Humanos , China , Hospitais Públicos/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Saúde da Família , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
6.
Lab Invest ; 104(8): 102104, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945481

RESUMO

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis patients, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in fine needle aspiration (FNA) washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) was computed to evaluate HA's clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than those in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC = 0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in FNA washouts from PTC patients were significantly higher than those in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than those in nonmetastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from nonmetastatic LNs. HA levels in serum and FNA washout exhibited a potential significance for PTC diagnosis and an indicator for LN metastasis in patients with PTC.


Assuntos
Carcinoma Papilar , Ácido Hialurônico , Metástase Linfática , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Ácido Hialurônico/sangue , Ácido Hialurônico/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/diagnóstico , Adulto , Carcinoma Papilar/metabolismo , Carcinoma Papilar/diagnóstico , Linhagem Celular Tumoral , Carcinoma/metabolismo , Carcinoma/diagnóstico , Carcinoma/patologia , Linfonodos/patologia , Linfonodos/metabolismo , Doença de Hashimoto/metabolismo , Doença de Hashimoto/sangue , Doença de Hashimoto/patologia , Doença de Hashimoto/diagnóstico , Biópsia por Agulha Fina , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/sangue , Proliferação de Células
7.
Behav Sci (Basel) ; 14(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38785906

RESUMO

This study aimed to investigate the relationship between parental autonomy support and children's self-concept, and to explore the role of basic psychological needs in Chinese primary schools from the perspective of self-determination theory. A total of 3109 children aged 6-13 years participated in eastern China. The results indicated a significant correlation between parental autonomy support, basic psychological needs, and children's self-concept. Basic psychological needs play a partial mediating role between parental autonomy support and children's self-concept. Specifically, autonomy support varied by need types whereas parental control steadily played a negative predictive role. Parental autonomy support and control predicted children's self-concept differently through three basic psychological needs, with differences across gender and grades. Boys and elder children had stronger relationships to competence needs, while girls were sensitive to autonomy needs; in addition, both of them were sensitive to relatedness needs. The mediating effects model and cross-group analyses revealed the complex predictive role of parental autonomy support on children's self-concept in China, providing an effective entry point for cross-cultural research and family education to improve children's psychological well-being.

8.
J Food Sci ; 89(6): 3577-3590, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38720591

RESUMO

This study investigated preheated (25-100°C) black soybean protein isolate (BSPI) conjugated with syringic acid (SA) (25 and 50 µmol/g protein) under alkaline conditions, focusing on the structure, functional properties, and storage stability. The results revealed that the SA binding equivalent and binding rate on BSPI increased continuously as the preheat temperature increased. Additionally, preheating positively impacted the surface hydrophobicity (H0) of BSPI, with further enhancement observed upon SA binding. Preheating and SA binding altered the secondary and tertiary structure of BSPI, resulting in protein unfolding and increased molecular flexibility. The improvement in BSPI functional properties was closely associated with both preheating temperature and SA binding. Specifically, preheating decreased the solubility of BSPI but enhanced the emulsifying activity index (EAI) and foaming capacity (FC) of BSPI. Conversely, SA binding increased the solubility of BSPI with an accompanying increase in EAI, FC, foaming stability, and antioxidant activity. Notably, the BSPI100-SA50 exhibited the most significant improvement in functional properties, particularly in solubility, emulsifying, and foaming attributes. Moreover, the BSPI-SA conjugates demonstrated good stability of SA during storage, which positively correlated with the preheating temperature. This study proposes a novel BSPI-SA conjugate with enhanced essential functional properties, underscoring the potential of preheated BSPI-SA conjugates to improve SA storage stability. PRACTICAL APPLICATION: Preheated BSPI-SA conjugates can be used as functional ingredients in food or health products. In addition, preheated BSPI shows potential as a candidate for encapsulating and delivering hydrophobic bioactive compounds.


Assuntos
Ácido Gálico , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Proteínas de Soja , Proteínas de Soja/química , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Glycine max/química , Antioxidantes/química , Estabilidade Proteica
9.
PLoS One ; 19(5): e0303683, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38776313

RESUMO

OBJECTIVE: To develop a scale to assess the excessive behavior of superfans in celebrity worship and to test its reliability and validity in China. METHODS: The scale was developed based on the netnography and interviews of celebrity fans and the existing problematic Internet usage scales. Sample 1 (n = 465) was used for exploratory factor analysis, and Sample 2 (n = 804) was used for confirmatory factor analysis, reliability test, criterion validity, and discriminative validity test. RESULTS: There were 36 items in the final scale, including nine factors: impaired social functioning, replacement of real to virtual social relationships, sleep and eating problems, withdrawal, mood alteration, salience, excessive buying, increased craving, and escape from real life. The factor loadings ranged from 0.565 to 0.803. Confirmatory factor analysis showed that the scale was well structured. The reliability of the scale and each factor were satisfactory. The scale showed good discriminant validity in reflecting celebrity worship behavior. In terms of scores, mood alteration was the highest, excessive buying was the lowest, and there were certain gender and age differences. CONCLUSION: This study initially identified the main characteristics of excessive celebrity worship behavior among young fans on social media. The developed Chinese scale has good reliability and validity and can be used as a measurement tool.


Assuntos
Pessoas Famosas , Psicometria , Comportamento Social , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , China , População do Leste Asiático , Análise Fatorial , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
PLoS One ; 19(2): e0296910, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38381720

RESUMO

BACKGROUND: With the evolution of China's social structure and values, there has been a shift in attitudes towards marriage and fertility, with an increasing number of women holding diverse perspectives on these matters. In order to better comprehend the fundamental reasons behind these attitude changes and to provide a basis for targeted policymaking, this study employs natural language processing techniques to analyze the discourse of Chinese women. METHODS: The study focused on analyzing 3,200 comments from Weibo, concentrating on six prominent topics linked to women's marriage and fertility. These topics were treated as research cases. The research employed natural language processing techniques, such as sentiment orientation analysis, Word2Vec, and TextRank. RESULTS: Firstly, the overall sentiment orientation of Chinese women toward marriage and fertility was largely pessimistic. Secondly, the factors contributing to this negative sentiment were categorized into four dimensions: social policies and rights protection, concerns related to parenting, values and beliefs associated with marriage and fertility, and family and societal culture. CONCLUSION: Based on these outcomes, the study proposed a range of mechanisms and pathways to enhance women's sentiment orientation towards marriage and fertility. These mechanisms encompass safeguarding women and children's rights, promoting parenting education, providing positive guidance on social media, and cultivating a diverse and inclusive social and cultural environment. The objective is to offer precise and comprehensive reference points for the formulation of policies that align more effectively with practical needs.


Assuntos
Casamento , Processamento de Linguagem Natural , Criança , Feminino , Humanos , Fatores Socioeconômicos , Dinâmica Populacional , Direitos da Mulher , Fertilidade , Atitude , China
11.
FEBS J ; 291(8): 1719-1731, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38275079

RESUMO

Trastuzumab is widely used in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) therapy, but ubiquitous resistance limits its clinical application. In this study, we first showed that CD44 antigen is a significant predictor of overall survival for patients with HER2-positive GC. Next, we found that CD44 could be co-immunoprecipitated and co-localized with HER2 on the membrane of GC cells. By analyzing the interaction between CD44 and HER2, we identified that CD44 could upregulate HER2 protein by inhibiting its proteasome degradation. Notably, the overexpression of CD44 could decrease the sensitivity of HER2-positive GC cells to trastuzumab. Further mechanistic study showed that CD44 upregulation could induce its ligand, hyaluronan (HA), to deposit on the cancer cell surface, resulting in covering up the binding sites of trastuzumab to HER2. Removing the HA glycocalyx restored sensitivity of the cells to trastuzumab. Collectively, our findings suggested a role for CD44 in regulating trastuzumab sensitivity and provided novel insights into HER2-targeted therapy.


Assuntos
Ácido Hialurônico , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Glicocálix/metabolismo , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/farmacologia
12.
Heliyon ; 10(1): e23715, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192755

RESUMO

Background: China's societal and cultural significance placed on female fertility and the changing roles of women can lead to fertility anxiety in both married and unmarried women. This anxiety is shaped by factors such as social media use, intergroup emotions, fertility risk perceptions, and national policies. This study examines the interplay of these factors in understanding fertility anxiety among Chinese women. Methods: This study surveyed 607 young Chinese women using the Fertility Anxiety Scale developed by Zhang and Zhao. Mplus software was used for latent class analysis of respondents' fertility anxiety. A three-step approach with multinomial logistic regression was used to explore factors influencing fertility anxiety among married and unmarried women. Results: The latent class analysis supported a two-category model: "high fertility anxiety" (65.70 % married, 53.70 % unmarried) and "low fertility anxiety" (34.30 % married, 46.30 % unmarried). Multinomial logistic regression showed that increased social media usage intensity and perception of health-family risks correlated with higher fertility anxiety in both married and unmarried women. Among unmarried women, intergroup emotions and perceptions of occupational-economic risks also influenced fertility anxiety. Attention to national policies did not significantly impact fertility anxiety among young women. Conclusion: This study sheds light on the complex interplay of societal and individual factors in shaping fertility anxiety among young Chinese women. It underscores the enduring cultural significance placed on female fertility and the evolving roles of women in modern China. Regardless of their marital status, both married and unmarried women experience fertility anxiety, highlighting the pervasiveness of this concern.

13.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2281-2296, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37815607

RESUMO

To examine the effects of clomiphene citrate (CC) on follicular fluid metabolites and related metabolic pathways in rats with polycystic ovary syndrome (PCOS) using non-targeted metabolomics and determine how CC treats ovulation disorder in PCOS. The Sprague Dawley rats were randomly divided into control, model, and CC groups. A PCOS model was established with letrozole. Body weight, ovarian weight, estrus cycles, serum hormone levels, and ovary histopathology of the rats were collected for further evaluation. Moreover, through ultra-performance liquid chromatography-mass spectrometry, the study of follicular fluid metabolites revealed the mechanism of action of CC. CC reduced ovarian weight and regulated estrous cycles and serum hormone levels in PCOS rats but did not affect their body weight. Moreover, the metabolomic results showed that CC adjusted 153 metabolites, among which 16 cross metabolites like testosterone, androstenedione, 17α-hydroxyprogesterone, and cholic acid were considered as potential biomarkers for CC to improve ovulation disorders in PCOS rats. Kyoto Encyclopedia of Genes and Genomes pathway enrichment also showed that the CC group mainly engaged in tryptophan metabolism and steroid hormone biosynthesis. CC can improve ovulation disorders in rats, and its mechanism is related to the regulation of the secretion of serum hormone and follicular fluid metabolites and the amelioration of multi-metabolic pathways.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Ratos , Animais , Síndrome do Ovário Policístico/metabolismo , Fármacos para a Fertilidade Feminina/farmacologia , Líquido Folicular/metabolismo , Indução da Ovulação/métodos , Ratos Sprague-Dawley , Clomifeno/farmacologia , Ovulação , Hormônios/farmacologia , Peso Corporal
14.
Front Cell Dev Biol ; 11: 1224827, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842093

RESUMO

Some cancer cells migration and metastasis are characterized by the outgrowth of lamellipodia protrusions in which the underlying mechanism remains unclear. Evidence has confirmed that lamellipodia formation could be regulated by various adhesion molecules, such as CD44, and we previously reported that lamellipodia at the leading edge of luminal type breast cancer (BrCa) were enriched with high expression of CD44. In this study, we found that the overexpression of CD44s could promote lamellipodia formation in BrCa cells through inducing tissue type plasminogen activator (tPA) upregulation, which was achieved by PI3K/Akt signaling pathway activation. Moreover, we revealed that tPA could interact with LDL receptor related protein 1 (LRP1) to activate the downstream NFκB signaling pathway, which in turn facilitate lamellipodia formation. Notably, inhibition of the tPA/LRP1-NFkB signaling cascade could attenuate the CD44s-induced lamellipodia formation. Thus, our findings uncover a novel role of CD44s in driving lamellipodia outgrowth through tPA/LRP1-NFkB axis in luminal BrCa cells that may be helpful for seeking potential therapeutic targets.

15.
Front Immunol ; 14: 1177968, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465687

RESUMO

Background: NETosis is a new form of cell death, marked by DNA chromatin release from dead neutrophils. While it aids in microbe defense, it may worsen inflammation in autoimmune diseases, causing tissue harm. The impact of NETosis on Anti-neutrophil Cytoplasmic Antibody-associated Glomerulonephritis (ANCA-GN) remains unexplored and requires investigation. Methods: First, a weighted gene co-expression network analysis (WGCNA) was conducted to uncover differential expression of neutrophil extranuclear trap-associated genes (DE-NETs) in ANCA-GN. The NETosisScore model was established through the single sample gene set enrichment analysis (ssGSEA), which categorized all patients into high-risk and low-risk groups. The accuracy of model was assessed by ROC curve. The biological function of various subgroups was explored through Gene Set Variation Analysis (GSVA), while the abundance of immune cell infiltration was measured with CIBERSORT. Furthermore, the key NETosis-related genes (NRGs) were identified using three machine learning algorithms, and their relationship with renal function was analyzed through the NephroseqV5 database. Through the application of qPCR and immunohistochemical staining techniques, the mRNA and protein expression levels of NRGs were determined in patients with ANCA-GN and control. Results: A NETosisScore model was developed from 18 DE-NETs using the ssGSEA algorithm. The model's ability to predict ANCA-GN patients with a ROC AUC of 0.921. The high-risk group in ANCA-GN showed enrichment of immune-related pathways and greater infiltration of immune cells, as revealed by KEGG enrichment analysis and CIBERSORT. Using three machine learning algorithms, we identified six NRGs. Significant positive correlations were found between NRGs and CCR, macrophages, T-cell co-inhibition, and TIL. Further KEGG analysis revealed that the functions of NRGs may be closely related to the toll-like receptor signaling pathway. The levels of NRGs increased as kidney function declined and were positively correlated with Scr (serum creatinine) and negatively correlated with GFR (glomerular filtration rate), qPCR analysis showed increased expression of most NRGs in ANCA-GN patients. Furthermore, immunohistochemical staining confirmed higher expression of all NRGs in ANCA-GN patients. Conclusion: NETosisScore model accurately predicts high-risk patients in ANCA-GN with enriched immune pathways, 6 NRGs identified as potential biomarkers.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Biomarcadores , Neutrófilos
16.
Psychol Res Behav Manag ; 16: 2469-2480, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426388

RESUMO

Background: As the elderly increasingly engage with new media, particularly short video platforms, concerns are arising about the formation of "information cocoons" that limit exposure to diverse perspectives. While the impact of these cocoons on society has been investigated, their effects on the mental well-being of the elderly remain understudied. Given the prevalence of depression among the elderly, it is crucial to understand the potential link between information cocoons and depression among older adults. Methods: The study examined the relationships between information cocoons and depression, loneliness, and family emotional support among 400 Chinese elderly people. The statistical software package SPSS was used to establish a moderated mediation model between information cocoons and depression. Results: Information cocoons directly predicted depression among the elderly participants. Family emotional support moderated the first half and the second half of the mediation process, whereby information cocoons affected the depression of the elderly through loneliness. Specifically, in the first half of the mediation process, when the level of information cocoons was lower, the role of family emotional support was more prominent. In the second half of the process, when the level of family emotional support was higher, such support played a more protective role in the impact of loneliness on depression. Discussion: The findings of this study have practical implications for addressing depression among the elderly population. Understanding the influence of information cocoons on depression can inform interventions aimed at promoting diverse information access and reducing social isolation. These results will contribute to the development of targeted strategies to improve the mental well-being of older adults in the context of evolving media landscapes.

17.
BMC Ophthalmol ; 23(1): 173, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095450

RESUMO

AIM: To evaluate association between pretreatment serum metrics and best corrected visual acuity ( BCVA) of patients with macular edema secondary to retinal vein occlusion and its subtypes after intravitreal ranibizumab or conbercept implant. METHODS: This prospective research included 201 patients(201 eyes) who were diagnosed with macular edema secondary to retinal vein occlusion at Heibei Eye Hospital between January 2020 and January 2021, who all received intravitreal anti- vascular endothelial growth factor treatment. Serum metrics were measured before the first treatment, and correlations between BCVA and each of four parameters- platelets, neutrophil- to- lymphocyte ratio(NLR), platelet- to- lymphocyte ratio(PLR) and monocyte- to- lymphocyte ratio(MLR)- were analyzed to identify predictors of effective intravitreal injection treatment outcomes. RESULTS: The mean platelets was significantly different in the effective and ineffective group for RVO-ME (273.02 ± 41.49 × 109/L,214.54 ± 44.08 × 109/L P < 0.01),BRVO-ME (269.43 ± 49.52 × 109/L,214.72 ± 40.42 × 109/L P < 0.01), and CRVO-ME (262.32 ± 32.41 × 109/L,209.27 ± 42 0.91 × 109/L P < 0.01). The cutoff value of the platelets was 266.500, the area under the curve was 0.857,and the sensitivity and specificity were 59.8% and 93.6%, respectively. The mean PLR was significantly different in the effective and ineffective group for RVO-ME (154.66 ± 49.60, 122.77± 44.63 P < 0.01),BRVO-ME (152.24 ± 54.99, 124.72 ± 41.46 P = 0.003), and CRVO-ME (152.06±44.23, 118.67 ± 41.80 P = 0.001). The cutoff value of the platelets was 126.734, the area under the curve was 0.699, and the sensitivity and specificity were 70.7% and 63.3%, respectively. There were no statistical differencies between the effective and ineffective group(RVO- ME and its subtypes) in NLR and MLR. CONCLUSION: Higher pretreatment platelets and PLR were associated with BCVA in patients with RVO- ME and its subtypes who were treated with anti- VEGF drugs. The platelets and PLR may be used as predictive and prognostic tools for effective intravitreal injection treatment outcomes.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/tratamento farmacológico , Edema Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Dexametasona , Glucocorticoides , Estudos Prospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêutico
18.
Front Pharmacol ; 13: 1031487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386154

RESUMO

The development of endocrine resistance is a major clinical problem in estrogen receptor-positive (ER+) breast cancer (BrCa) treatment, in which how cancer cells acquire resistance remains obscure. Hyaluronan synthase 2 (HAS2) is the most critical synthase in producing hyaluronan and is well known for its involvement in cancer growth, metabolism and metastasis. Recent evidence has proved that HAS2 is involved in cellular acquired resistance to drug therapy in BrCa. In this work, we first observed that HAS2 expression was decreased in the endocrine-resistant ER+ BrCa cells. Further knocking-out experiments confirmed that the loss of HAS2 in parental ER+ BrCa cells resulted in a following antiestrogen resistance. Next, we found that the HAS2-loss could induce an upregulation of Ezrin, a member of the membrane cytoskeletal protein family who plays key roles in cellular signal transduction. Notably, we identified that the increase of Ezrin induced by HAS2-loss could inhibit the ERα expression and augment antiestrogen resistance, suggesting that a HAS2-Ezrin-ER axis may be associated with the acquirement of endocrine resistance in ER+ BrCa cells. Finally, knockdown or inhibition of Ezrin could restore the sensitivity of endocrine-resistant cells to antiestrogens treatment by activating ERα signaling. Taken together, our findings unraveled a novel HAS2-Ezrin-ER route in regulating the sensitivity of ER+ BrCa cells to antiestrogens, in which Ezrin may be a potential target in endocrine therapy.

19.
J Biol Chem ; 298(11): 102588, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36243113

RESUMO

Cell adhesion molecule CD44v8-10 is associated with tumor ste0mness and malignancy; however, whether CD44v10 alone confers these properties is unknown. Here, we demonstrated that CD44v10 promotes stemness and chemoresistance of triple-negative breast cancers (TNBCs) individually. Next, we identified that genes differentially expressed in response to ectopic expression of CD44v10 are mostly related to glycolysis. Further, we showed that CD44v10 upregulates glucose transporter 1 to facilitate glycolysis by activating the MAPK/ERK and PI3K/AKT signaling pathways. This glycolytic reprogramming induced by CD44v10 contributes to the stem-like properties of TNBC cells and confers resistance to paclitaxel treatment. Notably, we determined that the knockdown of glucose transporter 1 could attenuate the enhanced effects of CD44v10 on glycolysis, stemness, and paclitaxel resistance. Collectively, our findings provide novel insights into the function of CD44v10 in TNBCs and suggest that targeting CD44v10 may contribute to future clinical therapy.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Paclitaxel/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
20.
PLoS One ; 17(10): e0275872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36223420

RESUMO

Difficulties in collecting, processing, and identifying massive data have slowed research on cutting-edge science and technology hotspots. Promoting these technologies will not be successful without an effective data-driven method to identify cutting-edge technologies. This paper proposes a data-driven model for identifying global cutting-edge science technologies based on SpaCy. In this model, we collected data released by 17 well-known American technology media websites from July 2019 to July 2020 using web crawling with Python. We combine graph-based neural network learning with active learning as the research method in this paper. Next, we introduced a ten-fold cross-check to train the model through machine learning with repeated experiments. The experimental results show that this model performed very well in entity recognition tasks with an F value of 98.11%. The model provides an information source for cutting-edge technology identification. It can promote innovations in cutting-edge technologies through its effective identification and tracking and explore more efficient scientific and technological research work modes.


Assuntos
Redes Neurais de Computação , Tecnologia , Aprendizado de Máquina
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