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1.
Res Aging ; : 1640275241259463, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874463

RESUMO

Drawing from theories of affect, role strain and stress processes, we studied the impact of raising grandchildren on older mothers' relationships with the adult offspring whose children they raised, with particular attention to how these patterns differ by race and ethnicity. We used mixed-methods data collected from 531 older mothers regarding their relationships with 1935 of their adult children as part of the Within-Family Differences Study. Multilevel regression analyses showed that raising grandchildren was associated with greater mother-adult child closeness in Black families; however, in White families, raising grandchildren was associated with greater mother-adult child conflict. Qualitative analyses revealed that these differences could be explained by the tendency of Black grandmothers to emphasize positive aspects of raising grandchildren, compared to White grandmothers, who viewed raising grandchildren as demanding and who described their exchanges with their adult children as unequal. Overall, our findings reflect racial and ethnic differences in intergenerational solidarity.

2.
Aging (Albany NY) ; 16(10): 8998-9022, 2024 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-38796789

RESUMO

The discovery of RNA methylation alterations associated with cancer holds promise for their utilization as potential biomarkers in cancer diagnosis, prognosis, and prediction. RNA methylation has been found to impact the immunological microenvironment of tumors, but the specific role of methylation-related genes (MRGs), particularly in breast cancer (BC), the most common cancer among women globally, within the tumor microenvironment remains unknown. In this study, we obtained data from TCGA and GEO databases to investigate the expression patterns of MRGs in both genomic and transcriptional domains in BC. By analyzing the data, we identified two distinct genetic groupings that were correlated with clinicopathological characteristics, prognosis, degree of TME cell infiltration, and other abnormalities in MRGs among patients. Subsequently, an MRG model was developed to predict overall survival (OS) and its accuracy was evaluated in BC patients. Additionally, a highly precise nomogram was created to enhance the practical usability of the MRG model. In low-risk groups, we observed lower TBM values and higher TIDE scores. We further explored how MRGs influence a patient's prognosis, clinically significant characteristics, response to therapy, and the TME. These risk signatures have the potential to improve treatment strategies for BC patients and could be applied in future clinical settings. Moreover, they may also be utilized to determine prognosis and biological features in these patients.


Assuntos
Neoplasias da Mama , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Metilação de DNA , Bases de Dados Genéticas , Nomogramas
3.
Phytomedicine ; 130: 155544, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38810554

RESUMO

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease that affects the quality of life and mental health of approximately 150 million people worldwide. Ze-Qi-Tang (ZQT) is a classic compound used in China for lung disease; however, its mechanism of action in psoriasis remains unclear. This study aimed to investigate the therapeutic effect of the ZQT formula on psoriasis and explore the underlying molecular mechanisms. METHODS: Peripheral blood samples were collected from patients with psoriasis and healthy individuals. Flow cytometry was used to detect changes in the proportions of myeloid-derived suppressor cells (MDSCs) and other immune cells. Psoriasis was induced in mice by the daily application of imiquimod. ZQT was administered separately or in combination with anti-Gr1 antibody to deplete MDSC. The glycolysis levels of the MDSCs were detected using a Seahorse analyzer. The p21/Hif1α/Glut1 pathway was identified and validated by mRNA sequence, RT-qPCR, WB, IF, and the application of p21 inhibitor UC2288. RESULTS: The number of MDSCs was significantly increased in patients with psoriasis, with the increased expression of p21, Hif1α, and Glut1 in MDSCs. ZQT significantly alleviated psoriasis-like skin lesions in mice. ZQT formula significantly reduced the number of MDSCs in psoriatic-like mice and enhanced their suppressive capacity for T cells. The efficacy of ZQT in alleviating psoriatic dermatitis is compromised by MDSC depletion. ZQT decreased the expressions of p21, Hif1α, and Glut1-induced glycolysis in MDSCs, thereby inhibiting Th17 cell differentiation. CONCLUSION: These suggest that ZQT alleviates IMQ-induced psoriatic dermatitis, by inhibiting p21/Hif1α/Glut1-induced glycolysis in MDSCs.


Assuntos
Regulação para Baixo , Medicamentos de Ervas Chinesas , Transportador de Glucose Tipo 1 , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células Supressoras Mieloides , Psoríase , Animais , Psoríase/tratamento farmacológico , Transportador de Glucose Tipo 1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Glicólise/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Camundongos , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/metabolismo , Masculino , Regulação para Baixo/efeitos dos fármacos , Feminino , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Modelos Animais de Doenças , Adulto , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Imiquimode , Pessoa de Meia-Idade
4.
J Exp Clin Cancer Res ; 43(1): 129, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38685125

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. METHODS: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation-qPCR (MeRIP-qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. RESULTS: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. CONCLUSION: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.


Assuntos
Biomarcadores Tumorais , Células Neoplásicas Circulantes , Neoplasias Gástricas , Vimentina , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Vimentina/metabolismo
5.
Nat Commun ; 15(1): 2183, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472217

RESUMO

The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155-147 Myr ago (~1.5° Myr-1), immediately followed by an ~ 10° northward displacement between 147-141 Myr ago (~1.6° Myr-1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic-Cretaceous extinction and endemism.

7.
J Gerontol B Psychol Sci Soc Sci ; 78(12): 2102-2110, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37749827

RESUMO

OBJECTIVES: Parental differential treatment of children, particularly disfavoritism, has been found to detrimentally affect adult children's psychological well-being in the United States. However, no study has investigated the long-reaching influence of parental disfavoritism in China, where there is an absence of equal treatment norms. Drawing from theories of social comparison, life course, and gender dynamics in China, we tested how perceptions of childhood parental disfavoritism affect midlife and older Chinese adults' depressive symptoms, and how the effects differ by own and parent's gender. METHODS: Random-intercept models were used based on a sample of 17,682 midlife and older Chinese adults, drawn from 5 waves of China Health and Retirement Longitudinal Study. RESULTS: Recollections of childhood parental disfavoritism were associated with higher depressive symptoms among Chinese adults. Perceptions of paternal disfavoritism predicted both men's and women's depressive symptoms, whereas perceptions of maternal disfavoritism predicted women's depressive symptoms only. Paternal disfavoritism was more detrimental than maternal disfavoritism, but only for men. Maternal disfavoritism was more detrimental for women than men. DISCUSSION: These findings shed light on the universality of the long-reaching detrimental effect of perceptions of parental disfavoritism across cultures as well as the unique gendered patterns in China shaped by patriarchy. Findings suggest that the implementation of Three-Child Policy in China should be accompanied with parental education programs involving fathers on equal treatment of children.


Assuntos
População do Leste Asiático , Bem-Estar Psicológico , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Pais , Identidade de Gênero , Depressão/epidemiologia
8.
Int Immunopharmacol ; 123: 110710, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37531829

RESUMO

BACKGROUND: Psoriasis is a chronic and incurable skin disorder that causes inflammation. There is an urgent clinical need for new treatments. We identified the natural compound indirubin as a potential potent agent for the treatment of psoriasis, but it's therapeutic effect and underlying mechanisms were not well understood. METHODS: Peripheral blood and skin tissues from psoriasis patients and healthy individuals were collected. Bioinformatics analysis was performed to investigate LAT1 expression and associated signal pathways in psoriasis skin lesions. A mouse model of psoriasis was established. Indirubin was administered separately or in combination with MDSCs depletion or adoptively transferred MDSCs. JPH203, rapamycin, siRNA, and NV5138 were further used to investigate the potential mechanism by which indirubin regulates MDSCs. RESULTS: Psoriasis patients had increased numbers of MDSCs in their blood and skin lesions, with high expression of Lat1. The upregulation of LAT1 expression and the arginine synthesis pathway was observed in psoriasis skin lesions. The number of MDSCs was increased, while their inhibitory effect on psoriatic T cells was decreased. Indirubin decreased Lat1 expression on the surface of MDSCs, inhibited mTOR pathway activation, upregulated Arg1 expression in MDSCs, and enhanced the immunosuppressive activity of MDSCs while inhibiting CD4+CCR6+ T cells. CONCLUSION: This study demonstrates indirubin's pharmacological and therapeutic effects, providing a basis for future clinical application in treating psoriasis.


Assuntos
Células Supressoras Mieloides , Psoríase , Camundongos , Animais , Humanos , Células Supressoras Mieloides/metabolismo , Regulação para Cima , Psoríase/patologia , Pele/patologia , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Imunossupressores/metabolismo
9.
Arch Oral Biol ; 154: 105759, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37422997

RESUMO

OBJECTIVE: Variants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO. DESIGN: Clinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO. RESULTS: We found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients. CONCLUSIONS: Our results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.


Assuntos
Anodontia , Anormalidades Dentárias , Humanos , Anodontia/genética , Anodontia/epidemiologia , Anormalidades Dentárias/genética , Fenótipo , Mutação , Linhagem , Proteínas Wnt/genética
10.
Int J Mol Sci ; 24(8)2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37108518

RESUMO

The selectivity of drugs for G protein-coupled receptor (GPCR) signaling pathways is crucial for their therapeutic efficacy. Different agonists can cause receptors to recruit effector proteins at varying levels, thus inducing different signaling responses, called signaling bias. Although several GPCR-biased drugs are currently being developed, only a limited number of biased ligands have been identified regarding their signaling bias for the M1 muscarinic acetylcholine receptor (M1mAChR), and the mechanism is not yet well understood. In this study, we utilized bioluminescence resonance energy transfer (BRET) assays to compare the efficacy of six agonists in inducing Gαq and ß-arrestin2 binding to M1mAChR. Our findings reveal notable variations in agonist efficacy in the recruitment of Gαq and ß-arrestin2. Pilocarpine preferentially promoted the recruitment of ß-arrestin2 (∆∆RAi = -0.5), while McN-A-343 (∆∆RAi = 1.5), Xanomeline (∆∆RAi = 0.6), and Iperoxo (∆∆RAi = 0.3) exhibited a preference for the recruitment of Gαq. We also used commercial methods to verify the agonists and obtained consistent results. Molecular docking revealed that certain residues (e.g., Y404, located in TM7 of M1mAChR) could play crucial roles in Gαq signaling bias by interacting with McN-A-343, Xanomeline, and Iperoxo, whereas other residues (e.g., W378 and Y381, located in TM6) contributed to ß-arrestin recruitment by interacting with Pilocarpine. The preference of activated M1mAChR for different effectors may be due to significant conformational changes induced by biased agonists. By characterizing bias towards Gαq and ß-arrestin2 recruitment, our study provides insights into M1mAChR signaling bias.


Assuntos
Acetilcolina , Receptor Muscarínico M1 , Humanos , beta-Arrestinas/metabolismo , Simulação de Acoplamento Molecular , Receptor Muscarínico M1/metabolismo , Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio , Pilocarpina/farmacologia , Proteínas de Ligação ao GTP/metabolismo , beta-Arrestina 2/metabolismo , beta-Arrestina 1/metabolismo , Transferência de Energia , Células HEK293
11.
J Ethnopharmacol ; 313: 116491, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37072091

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.


Assuntos
Neoplasias Pulmonares , Células Supressoras Mieloides , Camundongos , Animais , Camundongos Nus , NF-kappa B/metabolismo , Qualidade de Vida , Camundongos Endogâmicos C57BL , Neoplasias Pulmonares/metabolismo , Imunossupressores/farmacologia , Microambiente Tumoral
12.
J Marriage Fam ; 85(2): 539-555, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36936541

RESUMO

Objective: This article examines the transmission of older women's relationship quality with their mothers and fathers to their relationship quality with their own adult children in midlife. We also investigate how the transmission is moderated by the dimension of relationship quality (closeness vs. strain) and the gender of both the older women's parents and their adult children. Background: Prior research has primarily examined parents' transmission of relationship quality to young children with little attention to whether and when this pattern occurs in later-life families. Method: We conducted multilevel analyses using data collected from 249 older women and 643 of their adult children as part of the Within-Family Differences Study-I. Results: We found evidence for transmission of older women's reported closeness and tension with their mothers and fathers to their reported closeness and tension with their adult children. Adult children's reports also revealed that older women's closeness with their own mothers was transmitted to their adult children's reported closeness with the older women themselves. Mother-child closeness was transmitted more strongly than mother-child tension, and mother-child closeness was transmitted more strongly to daughters than sons, based on adult children's reports. Conclusion: This study demonstrates the continuity of intergenerational influence in later-life families and highlights the essential roles that selective social learning and social structural position (i.e., gender) play in conditioning the socialization process.

13.
Int J Biol Sci ; 18(7): 2759-2774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541911

RESUMO

The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer. However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear. After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells. Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc). Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer. In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect. Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future.


Assuntos
NF-kappa B , Neoplasias Pancreáticas , Antraquinonas , Apoptose , Linhagem Celular Tumoral , Humanos , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pancreáticas
14.
J Gerontol B Psychol Sci Soc Sci ; 77(1): 224-236, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34192301

RESUMO

OBJECTIVES: Our goal was to extend research on within-family differences in mother-child relations in later life by focusing on 2 social structural characteristics of mothers and offspring that may play important roles in shaping the impact of maternal favoritism on adult children's depressive symptoms-mother's marital status and child's gender. METHODS: Mixed-methods data were collected as part of the Within-Family Differences Study from 641 adult children nested within 273 families in which: (a) there were at least 2 living adult siblings, and (b) mothers were married or widowed. RESULTS: Multilevel analyses indicated that perceiving oneself as the child to whom one's mother was most emotionally close was a strong predictor of higher depressive symptoms among daughters of widowed mothers; in contrast, perceptions of favoritism did not predict depressive symptoms among sons of either widowed or married mothers, or daughters of married mothers. Qualitative analyses revealed that daughters, but not sons, of widowed mothers tended to attribute their greater closeness with their mothers to their roles as their mothers' "emotional caregivers," particularly solo caregivers, during times when mothers faced negative life events that neither they nor their children could control or ameliorate. DISCUSSION: The quantitative and qualitative findings we present underscore how social structural positions-in this case, mother's marital status and child's gender-combine with social psychological processes to shape how parent-child relations affect children's well-being in adulthood.


Assuntos
Filhos Adultos/psicologia , Casamento/psicologia , Relações Mãe-Filho/psicologia , Satisfação Pessoal , Viuvez/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Fatores Sexuais , Estados Unidos
15.
Res Aging ; 44(2): 215-226, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34002650

RESUMO

As Chinese households are becoming smaller with increasing numbers of adult children and older parents living apart, the extent to which patterns of parental support reflect traditional gender dynamics is under debate. Integrating theories of sibling compensation with ceremonial giving, we tested whether helping non-coresident parents in China is affected by sibship size and how these patterns depend on own and sibling(s)' gender using a sample of 4,359 non-coresident parent-child dyads nesting within 3,285 focal adult children from China Health and Retirement Longitudinal Study 2013. Opposite to patterns in the United States and Europe, we found substitutions of daughters with sons-having more brothers was associated with daughters' reduced probabilities and hours of helping. Sons' patterns of helping were independent of number of brothers and sisters in the family, consistent with the theory of ceremonial giving. These findings reflect the dominance of traditional family dynamics despite changes in family structure.


Assuntos
Pais , Irmãos , Filhos Adultos , China , Humanos , Estudos Longitudinais , Masculino
16.
Mediators Inflamm ; 2021: 8856326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867859

RESUMO

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Granulócitos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Células Supressoras Mieloides/efeitos dos fármacos , Animais , Calgranulina B/fisiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/fisiologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/uso terapêutico , Granulócitos/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/patologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral
17.
Cancer Lett ; 493: 167-177, 2020 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-32829007

RESUMO

Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer with high incidence and mortality. Accumulating studies have shown that traditional Chinese medicine (TCM) and its active ingredients have good anti-tumor activity. However, the anti-tumor effect of Thevebioside (THB), an active ingredient from TCM, is still unknown in NSCLC. In this study, to our best knowledge, it was the first time to report the underlying mechanism of its tumor-suppressive activity in NSCLC based on our previous high-throughput screening data. We further demonstrated that THB effectively inhibited the proliferation of NSCLC cells (A549 and H460) by inducing cellular apoptosis rather than cell cycle arrest. Notably, it was demonstrated that SRC-3 was significantly down-regulated after THB treatment dependent on ubiquitin-proteasome-mediated degradation, which subsequently inhibited the IGF-1R-PI3K-AKT signaling pathway and promoted apoptosis via both in vivo and in vitro experiments. Collectively, THB exerted inhibitory effect on tumor growth of NSCLC through inhibiting SRC-3 mediated IGF-1R-PI3K-AKT signaling by ubiquitination to induce cellular apoptosis with minimal toxicity no matter in vitro or vivo.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Glicosídeos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Coativador 3 de Receptor Nuclear/química , Thevetia/química , Ubiquitina/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Coativador 3 de Receptor Nuclear/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Pharm Biol ; 58(1): 357-366, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32356467

RESUMO

Context: Natural killer (NK) cells can eliminate malignant cells and play a vital role in immunosurveillance. Administration of natural compounds represents a promising approach for antitumor immunotherapy, which may enhance the NK cell activity via multiple mechanisms.Objective: Establishing approaches to evaluate the effect of select natural products on NK cell-mediated cytotoxicity.Materials and methods: We selected a natural product library containing 2880 pure compounds, which was provided by the National Centre for Drug Screening of China. 0.1% DMSO was employed as a negative control, and 100 U/mL human recombinant IL-2 was employed as a positive control. To evaluate the % of tumour cells which were killed by NK cells, expanded NK cells were co-cultured with tumour cells and then treated with natural products at the concentration of 10 µM. After 24-h co-incubation, luminescent signal was detected and percent lysis was calculated.Results: We report on the results of a three-round high-throughput screening effort that identified 20-deoxyingenol 3-angelate (DI3A) and its analogue ingenol 3-angelate (I3A) as immuno enhancers which boosts NK cell-mediated killing of non-small cell lung cancer cells (NSCLCs). Biophotonic cytotoxicity assay and calcein release assay were used as two well-established NK cell cytotoxicity detection assays to validate the immuno-enhancing effects of DI3A and I3A, which was achieved by increasing degranulation and interferon-gamma secretion of NK cells.Conclusions: Our newly established ATP-based method was a valuable and information-rich screening tool to investigate the biological effects of natural products on both NK cells and tumour cells.


Assuntos
Produtos Biológicos/toxicidade , Ensaios de Triagem em Larga Escala/métodos , Células Matadoras Naturais/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Humanos , Interleucina-2/imunologia , Interleucina-2/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo
19.
Netw Sci (Camb Univ Press) ; 8(2): 271-289, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33777395

RESUMO

It is well documented that intergenerational ties play important roles in adults' well-being. However, most studies focus on the impact of individuals' own perceptions of their ties without considering whether family members' assessments of these ties affect well-being. We address this question using data from 296 adult children nested within 95 later-life families in which all offspring were interviewed. Applying a mixed-method within-family approach, we explored whether the effect of perceived maternal favoritism on depressive symptoms was increased when siblings shared ego's perceptions. Multilevel regression analyses revealed that ego's own perceptions predicted depressive symptoms, but only among daughters. Siblings' perceptions that egos were most close to mothers did not affect the well-being of daughters or sons. Qualitative analyses suggested that differential effects of perceived favoritism by gender reflected differences in the meaning sons and daughters associated with being favored children. Favored daughters were more likely than favored sons to report that they were emotional caregivers to their mothers; this pattern was especially strong when siblings reinforced egos' perceptions of being "best suited" for this role. These findings emphasize the salience of egos' own perceptions, relative to those of family network members, in shaping role embracement and psychological well-being, especially among women.

20.
Front Neurosci ; 14: 596780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33633527

RESUMO

BACKGROUND AND PURPOSE: Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4+ T lymphocyte-ß-endorphin axis. METHODS: After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4+ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and ß-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested. RESULTS: The pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of ß-endorphin was up-regulated with the up-regulation of IL-17A in CD4+ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of ß-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted. CONCLUSION: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4+ T lymphocyte-ß-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.

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