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1.
BMC Public Health ; 24(1): 1018, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609940

RESUMO

BACKGROUND: Tour guides' identification and internalization of occupational stigma may exacerbate their career development, perceived professional reputation and status, and mental health. The current study aimed to develop and verify the Tour guides Internalized Occupational Stigma Scale (TIOSS) to provide an effective tool for relevant quantitative research. METHODS: The study developed an initial questionnaire through literature analysis, expert review, and semi-structured surveys. We conducted item analyses and exploratory factor analyses among 326 tour guides, and confirmatory factor analysis and reliability and validity tests among 315 tour guides. RESULTS: The TIOSS consists of 21 items and is formed in three dimensions referring to Stigma Perception (SP), Status Loss (SL), and Career Denial (CD). The correlation coefficient values of the TIOSS total scale and dimension scores with the criterion instruments ranged from 0.17 to 0.68. In addition, the Cronbach's α coefficients for the TIOSS and its dimensions ranged from 0.837 to 0.928, and the split-half reliability coefficients ranged from 0.843 to 0.916. The study also revealed that the TIOSS was consistent across genders. CONCLUSION: The TIOSS performed favorable reliability and validity to be a valid instrument to assess tour guides' internalized occupational stigma.


Assuntos
Saúde Mental , Estigma Social , Humanos , Feminino , Masculino , Reprodutibilidade dos Testes , Análise Fatorial
2.
Cancer Lett ; 592: 216909, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679407

RESUMO

Natural killer (NK) cells exert an indispensable role in innate immune responses against cancer progression, however NK cell dysfunction has been rarely reported in hepatocellular carcinoma (HCC). This study sought to uncover the immunoregulatory mechanisms of tumor-infiltrating NK cells in HCC. A consensus NK cell-based signature (NKS) was constructed using integrative machine learning algorithms based on multi-omics data of HCC patients. HCC tumors had lower numbers of infiltrating NK cells than para-tumor normal liver tissues. Based on the NK cell-associated genes, the NKS was built for HCC prognostic prediction and clinical utilities. Drug targets and novel compounds were then identified for high-NKS groups. RAC1 was confirmed as the hub gene in the NKS genes. RAC1 was upregulated in HCC tumors and positively correlated with shorter survival time. RAC1 overexpression in NK-92 cells facilitated the cancer-killing capacity by the anticancer cytotoxic effectors and the upregulated NKG2D. The survival time of PDX-bearing mice was also prolonged upon NK-92RAC1 cells. Mechanistically, RAC1 interacted with STAT3 and facilitated its activation, thereby enabling its binding to the promoter region of NKG2D and functioning as a transcriptional regulator in NK-92 via molecular docking, Co-IP assay, CHIP and luciferase experiments. Collectively, our study describes a novel function of RAC1 in potentiating NK cell-mediated cytotoxicity against HCC, highlighting the clinical utilities of NKS score and RAC1high NK cell subset in HCC immunotherapy.

3.
Trop Anim Health Prod ; 56(4): 147, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38684622

RESUMO

This study investigates the effect of supplementation of Perilla seeds (PS) on the performance, egg quality, blood biochemical parameters, and egg yolk fatty acids composition in the diet of egg-laying chicken. A total of 1600 Lohmann laying hens were randomly assigned to four different groups with 4 replicates each (100 chickens/replicate) and were subjected to varying PS concentrations (PS0, PS6, PS12, and PS18; 0%, 6%, 12%, and 18%, respectively) for four weeks, including an acclimation period of one week. The results showed no significant differences among the groups for average egg weight (P > 0.005). The laying rate (%), feed conversion ratio (FCR) and average feed intake (AFI) decreased significantly for birds fed on 18% PS as compared to the other treatments (P < 0.005). Haugh unit, albumin height, egg-shape index and eggshell thickness among hens fed PS diets were greater averaging 80.53, 7.00, 1.29, 0.34 compared to 76.84, 6.86, 1.25 and 0.32 from Control hen eggs (P < 0.05). Serum analysis showed a trend towards elevated levels of glucose (Glu), total protein (TP) and aspartate aminotransferase (AST) among treatments. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) decreased for the birds fed on 6% PS. The fatty acid composition of egg yolk showed a substantial reduction for α-linolenic acid and docosahexaenoic acid increased significantly by the incorporating PS in the diet (P < 0.001). PS incorporation in diets resulted in significant improvements in both performance indicators and greater amounts of α-linolenic acid and DHA in egg yolks. These findings indicate that PS at 6% inclusion has the potential to improve fatty acid profiles of egg yolk without any adverse effect on performance of egg quality.


Assuntos
Ração Animal , Galinhas , Dieta , Suplementos Nutricionais , Gema de Ovo , Ácidos Graxos , Sementes , Animais , Galinhas/fisiologia , Gema de Ovo/química , Feminino , Ácidos Graxos/análise , Ração Animal/análise , Dieta/veterinária , Sementes/química , Suplementos Nutricionais/análise , Perilla/química , Distribuição Aleatória , Ovos/análise , Ovos/normas , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38452850

RESUMO

Declining flesh quality has drawn considerable attention in the farmed large yellow croaker (LYC; Larimichthys crocea) industry. Inosine monophosphate (IMP) is the primary flavor substance in aquatic animals. Adenosine monophosphate deaminase 1 (AMPD1) plays a critical role in IMP formation by catalyzing the deamination of AMP to IMP in the purine nucleotide cycle. To further evaluate the correlation between ampd1 mRNA expression levels and IMP content in the LYC muscle tissue, the relevant open reading frame (ORF) of L. crocea (Lcampd1) was cloned, and the IMP content and Lcampd1 mRNA expression in the muscles of LYCs of different sizes were examined. The ORF cDNA of Lcampd1 was 2211 bp in length and encoded a polypeptide of 736 amino acids (AAs). The deduced protein, LcAMPD1, possesses conserved AMPD active regions (SLSTDDP) and shows high homology with AMPD proteins of other teleost fishes. The genomic DNA sequence of Lcampd1 exhibits a high degree of evolutionary conservation in terms of structural organization among species. Phylogenetic analysis of the deduced AA sequence revealed that teleost fish and mammalian AMPD1 were separate from each other and formed a cluster with AMPD3, suggesting that AMPD1 and AMPD3 arose by duplication of a common primordial gene. In healthy LYC, Lcampd1 mRNA was expressed only in the muscle tissue. The IMP content in the muscle of LYCs with different average body weights was measured by high-performance liquid chromatography; the results showed that the IMP content in the muscle of LYCs with greater body weight was significantly higher than that in LYC with lower body weight. Moreover, a similar trend in Lcampd1 expression was observed in these muscle tissues. The Pearson correlation analysis further showed that the Lcampd1 mRNA expression was positively correlated with IMP content in the muscles of different-sized LYCs. These results suggest the potential function of Lcampd1 in determining the IMP content in LYC and provide a theoretical basis for flesh quality improvement, as well as a scientific basis for the development of the molecular breeding of LYC.


Assuntos
Inosina Monofosfato , Perciformes , Animais , Sequência de Bases , Sequência de Aminoácidos , Inosina Monofosfato/metabolismo , Filogenia , Perciformes/genética , Perciformes/metabolismo , Monofosfato de Adenosina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peso Corporal/genética , Proteínas de Peixes/metabolismo , Mamíferos/metabolismo
5.
Cell Signal ; 117: 111072, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38307306

RESUMO

BACKGROUND: Cuproptosis is a novel form of cell death that exhibits close association with mitochondrial respiration and occurs through distinct mechanisms compared to previously characterized forms of cell death. However, the precise impact of cuproptosis-associated genes (CAGs) on prognosis, immune profiles, and treatment efficacy in hepatocellular carcinomas (HCC) remains poorly understood. METHODS: A comprehensive analysis of CAGs in hepatocellular carcinoma (HCC) prognosis was conducted using genomic data from HCC patients. Consensus clustering analysis was performed to determine molecular subtypes related to cuproptosis in HCC. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to quantify the infiltration levels of immune cells, while the "ESTIMATE" package was employed to calculate tumor purity, stromal scores, and immune scores in the tumor microenvironment (TME). Principal component analysis (PCA) algorithm was utilized to construct a risk score related to CAGs. Finally, CCK8, wound healing, Transwell migration/invasion, EDU and xenograft model were employed to explore the potential oncogenic role of MTF1. RESULTS: Three distinct patterns of cuproptosis modification were identified, each associated with unique functional enrichments, clinical characteristics, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), and prognosis. A CAGs-related risk score (Cuscore) was developed to predict prognosis in TCGA and validated in GSE76427 and ICGC datasets. Notably, patients with a low Cuscore had better prognoses and were more likely to benefit from immunotherapy.Additionally, the high Cuscore group in HCC also revealed three potential therapeutic targets (TUBA1B, CDC25B, and CSNK2A1) as well as several therapeutic compounds. Moreover, the experiment measured the expression levels of six prognosis-related CAGs, wherein knockdown of MTF1 exhibited suppression of proliferation, invasion, and migration formation in HCC cell lines. CONCLUSION: The findings have enhanced our comprehension of the cuproptosis characteristics in HCC, and stratification based on CuScore may potentially enhance the prediction of patients' prognosis and facilitate the development of effective and innovative treatment strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Algoritmos , Morte Celular , Linhagem Celular , Microambiente Tumoral/genética , Apoptose
6.
Front Endocrinol (Lausanne) ; 15: 1326684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318292

RESUMO

Background: Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease. Methods: We comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded. Results: We identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD. Conclusion: IAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.


Assuntos
Insuficiência Adrenal , Doenças do Sistema Endócrino , Doenças Genéticas Inatas , Hipoglicemia , Inibidores de Checkpoint Imunológico , Humanos , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Hormônio Adrenocorticotrópico , Inibidores de Checkpoint Imunológico/efeitos adversos
7.
BMC Public Health ; 24(1): 238, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245671

RESUMO

BACKGROUND: The stigma of loneliness exacerbates the negative effect of loneliness, reduces the willingness to seek help, damages interpersonal relationships, and threatens health status. However, there is currently no valid scale for measuring the stigma of loneliness in China. The study aims to translate the Stigma of Loneliness Scale (SLS) and evaluate the reliability and validity of the Chinese version. METHODS: The investigation was conducted in two phases. In the first phase, the SLS was used to conduct a questionnaire survey on 657 college students aged 17 to 24; in the second phase, the SLS, the UCLA Loneliness Scale (ULS-8), the Distress Disclosure Index (DDI), the Revised Cheek and Buss Shyness Scale (RCBS), the Self-Concealment Scale (SCS), the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS), the Kessler Psychological Distress Scale (K10), and the Rosenberg Self-Esteem Scale (RSES) were used to conduct the questionnaire survey on 801 college and graduates students aged 18 to 39. RESULTS: Two dimensions of Self-stigma of Loneliness and Public Stigma of Loneliness were extracted with a cumulative factor interpretation rate of 74.60% when conducting exploratory factor analysis on the first-stage data. The factor loading of each item ranged from 0.585 to 0.890, and the commonality ranged from 0.609 to 0.735. The confirmatory factor analysis and reliability and validity test were carried out on the data gathered in the second phase, indicating that the two-factor model fits well. In addition, the scores of SLS and all dimensions were significantly positively correlated with the total scores of ULS-8, RCBS, SCS, SIAS, SPS, and K10, and negatively correlated with those of DDI and RSES. The Cronbach's alpha coefficients for SLS and SSL and PSL dimensions were 0.957, 0.941, and 0.955. The cross-group invariance test found that the SLS was equivalent for males and females. Meanwhile, males scored significantly higher than females on both the total scores of SLS score and each dimension. CONCLUSIONS: The Chinese version of SLS displayed satisfactory psychometric properties and can be a valid tool to assess the stigma of loneliness among Chinese young people.


Assuntos
Solidão , Estigma Social , Masculino , Feminino , Humanos , Adolescente , Solidão/psicologia , Reprodutibilidade dos Testes , Estudantes , China , Inquéritos e Questionários , Psicometria
8.
BMC Public Health ; 24(1): 273, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263059

RESUMO

BACKGROUND: The present study aimed to examine the relationship between regulatory focus and loneliness stigma, as well as the intergenerational transmission of the two. Specifically, the study analyzed the effects of fathers' and mothers' regulatory focus on their own and their spouses' stigma of loneliness. In addition, a mediation model was constructed to explore how parents' regulatory focus influences their children's stigma of loneliness and the potential mediating mechanisms involved. METHODS: Questionnaires were distributed to 470 college students and their parents, employing the Regulatory Focus Questionnaire (RFQ) and the Stigma of Loneliness Scale (SLS) to collect data. RESULTS: The analysis of intergenerational transmission effects revealed that parents' regulatory focus and loneliness stigma significantly and positively predicted children's regulatory focus and loneliness stigma, respectively. The Actor-Partner Interdependence Model (APIM) elucidated that both fathers' and mothers' promotion focus exerted significant influence on both actor and partner's loneliness stigma. Furthermore, the mediation model analysis indicated that parents' loneliness stigma, along with children's regulatory focus operate as mediators in the influence of parental regulatory focus on loneliness stigma of their college-aged offspring. CONCLUSIONS: From a familial context, this study, investigated the association between regulatory focus and loneliness stigma, along with the mediating roles within parent-child groups and couples. The findings enhanced our comprehension of the interrelation between regulatory focus and loneliness stigma, underpinned by empirical evidence.


Assuntos
Solidão , Pais , Humanos , Feminino , Adulto Jovem , Mães , Cônjuges , Estigma Social
10.
Toxicol In Vitro ; 94: 105709, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37820748

RESUMO

OBJECTIVE: Sepsis-induced acute lung injury (ALI) is a life-threatening disease. Macrophage pyroptosis has been reported to exert function in ALI. We aimed to investigate the mechanisms of ANGPTL4-mediated cell pyroptosis in sepsis-induced ALI, thus providing new insights into the pathogenesis and prevention and treatment measures of sepsis-induced ALI. METHODS: In vivo animal models and in vitro cell models were established by cecal ligation and puncture (CLP) method and lipopolysaccharide-induced macrophages RAW264.7. ANGPTL4 was silenced in CLP mice or macrophages, followed by the determination of ANGPTL4 expression in bronchoalveolar lavage fluid (BALF) or macrophages. Lung histopathology was observed by H&E staining, with pathological injury scores evaluated and lung wet and dry weight ratio recorded. M1/M2 macrophage marker levels (iNOS/CD86/Arg1), inflammatory factor (TNF-α/IL-6/IL-1ß/iNOS) expression in BALF, cell death and pyroptosis, NLRP3 inflammasome, cell pyroptosis-related protein (NLRP3/Cleaved-caspase-1/caspase-1/GSDMD-N) levels, NF-κB pathway activation were assessed by RT-qPCR/ELISA/flow cytometry/Western blot, respectively. RESULTS: ANGPTL4 was highly expressed in mice with sepsis-induced ALI, and ANGPTL4 silencing ameliorated sepsis-induced ALI in mice. In vivo, ANGPTL4 silencing repressed M1 macrophage polarization and macrophage pyroptosis in mice with sepsis-induced ALI. In vitro, ANGPTL4 knockout impeded LPS-induced activation and pyroptosis of M1 macrophages and hindered LPS-induced activation of the NF-κB pathway in macrophages. CONCLUSION: Knockdown of ANGPTL4 blocks the NF-κB pathway activation, hinders macrophage M1 polarization and pyroptosis, thereby suppressing sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Sepse , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Angiopoietinas/toxicidade , Angiopoietinas/metabolismo , Caspases/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Macrófagos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Sepse/complicações , Sepse/metabolismo , Sepse/patologia
11.
Int J Biol Sci ; 19(14): 4571-4587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781039

RESUMO

Tumor-associated angiogenesis positively associates with malignant metastasis of intrahepatic cholangiocarcinoma (ICCA). Cancer cell-derived exosomes carrying microRNAs involves in tumor microenvironment (TME) regulation. We aimed to evaluate exosomal miR-30a-5p in ICCA development. Our data showed that increased miR-30a-5p level was correlated with higher microvascular density (MVD) and worse prognosis. Augmented miR-30a-5p expression was induced by hypoxia induced factor 1α (HIF-1α) in ICCA cell. Further exploration revealed that ICCA-derived miR-30a-5p could be transferred to endothelial and increased endothelial cells recruitment and proliferation, induced angiogenesis and vascular permeability in exosome dependent manner. In addition, circulating exosomal miR-30a-5p was higher in ICCA patients, and correlated with ICCA tissues-expressing miR-30a-5p. Hypoxic stress enhanced the effects of exosomal miR-30a-5p on endothelial-associated phenotypes. Rescued experiments showed that exosomal miR-30a-5p modulated endothelial-associated phenotypes in a way relied on programmed cell death 10 (PDCD10). Moreover, we revealed that the packing of miR-30a-5p into ICCA cells-derived exosomes was mediated by eukaryotic translation initiation factor 4B (EIF4B). More importantly, the combined application of targeting miR-30a-5p and apatinib could synergistically improve antiangiogenic efficacy in ICCA. Combined, ICCA-derived exosomal miR-30a-5p could be an excellent therapeutic and monitoring indicator for ICCA patients.


Assuntos
Colangiocarcinoma , Exossomos , MicroRNAs , Humanos , Proteínas Reguladoras de Apoptose/metabolismo , Permeabilidade Capilar , Linhagem Celular Tumoral , Proliferação de Células/genética , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Células Endoteliais/metabolismo , Exossomos/genética , Exossomos/metabolismo , Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Microambiente Tumoral/genética
12.
Psychol Res Behav Manag ; 16: 4341-4352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905165

RESUMO

Background: Individuals who initiate the concealment of their adverse or distressing thoughts from others can trigger off negative psychological experiences and social isolation, and lead to poorer health. Therefore, this study aimed to analyze the psychometric properties of the Self-Concealment Scale (SCS) in Chinese older adults. Methods: A questionnaire was administered to 1085 elderly people using convenience sampling and snowball sampling. Scales used included the SCS, Distress Disclosure Index (DDI), Revised Cheek and Buss Shyness Scale (RCBS), Social Interaction Anxiety Scale (SIAS), Social Phobia Scale (SPS), UCLA Loneliness Scale (ULS-8), and Kessler Psychological Distress Scale (K10). Results: The SCS consisted of 10 items with a one-dimensional structure, explaining 55.66% of the variance. The factor loading values for each item ranged from 0.68 to 0.75, and the covariance ranged from 0.46 to 0.57. Confirmatory factor analysis showed good model fit (χ2/df=2.829, RMSEA=0.057, CFI=0.981, IFI=0.981, TLI=0.974, PNFI=0.712, PGFI=0.719). The criterion-related validity test found that the SCS was significantly and positively correlated with the RCBS, SIAS, SPS, ULS-8, K10, depression, and anxiety; and the SCS was significantly and negatively correlated with the DDI. The Cronbach's α coefficient value for the scale was 0.923; the split-half reliability coefficient value was 0.923. In addition, the SCS had cross-gender consistency. Conclusion: The SCS has good reliability and validity in older adults and can be used as a valid tool to assess self-concealment among older people.

13.
Oncogene ; 42(45): 3344-3357, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37752233

RESUMO

Spindle assembly checkpoint (SAC) plays an essential part in facilitating normal cell division. However, the clinicopathological and biological significance of mitotic arrest deficient 2 like 1 (MAD2/MAD2L1), a highly conserved member of SAC in cholangiocarcinoma (CCA) remain unclear. We aim to determine the role and mechanism of MAD2 in CCA progression. In the study, we found up-regulated MAD2 facilitated CCA progression and induced lymphatic metastasis dependent on USP44/LIMA1/PI3K/AKT pathway. MAD2 interfered the binding of USP44 to LIMA1 by sequestrating more USP44 in nuclei, causing impaired formation of USP44/LIMA1 complex and enhanced LIMA1 K48 (Lys48)-linked ubiquitination. In therapeutic perspective, the data combined eleven cases of CCA PDTX model showed that high-MAD2 inhibits tumor necrosis and diminishes the inhibition of cell viability after treated with gemcitabine-based regimens. Immunohistochemistry (IHC) analysis of tissue microarray (TMA) for CCA patients revealed that high-MAD2, low-USP44 or low-LIMA1 level are correlated with worse survival for patients. Together, MAD2 activates PI3K/AKT pathway, promotes cancer progression and induces gemcitabine chemo-resistance in CCA. These findings suggest that MAD2 might be an excellent indicator in prognosis analysis and chemotherapy guidance for CCA patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Proteínas do Citoesqueleto , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1 , Ubiquitina Tiolesterase/genética
14.
Biophys J ; 122(21): 4135-4143, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37731243

RESUMO

Lysophospholipids (lysoPLs) are crucial metabolites involved in various physiological and pathological cellular processes. Understanding their binding interactions, particularly with human serum albumin (HSA), is essential due to their role in regulating lysoPLs-induced cytotoxicity. However, the precise mechanism of lysoPLs binding to HSA remains elusive. In this study, we employed fluorescence quenching and optical interferometry assays to demonstrate direct binding between lysophosphatidylcholine (LPC) and HSA (KD = 25 µM). Furthermore, we determined crystal structures of HSA in complex with LPC, both in the absence and the presence of the endogenous fatty acid myristate (14:0). The crystal structure of binary HSA:LPC revealed that six LPC molecules are bound to HSA at the primary fatty acid binding sites. Interestingly, the ternary HSA:Myr:LPC structure demonstrated the continued binding of three LPC molecules to HSA at binding sites 1, 3, and 5 in the presence of myristate. These findings support HSA's role as a carrier protein for lysoPLs in blood plasma and provide valuable insights into the structural basis of their binding mechanisms.


Assuntos
Lisofosfatidilcolinas , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Albumina Sérica/química , Ligação Proteica , Miristatos , Modelos Moleculares , Ácidos Graxos/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-37622693

RESUMO

BACKGROUND AND PURPOSE: There is a lack of a reliable outcome prediction model for patients evaluating the feasibility of postoperative adjuvant transarterial chemoembolization (PA-TACE) therapy. Our goal was to develop an easy-to-use tool specifically for these patients. METHODS: From January 2013 to June 2017, patients with hepatocellular carcinoma from the Liver Center of the First Affiliated Hospital of Chongqing Medical University received postoperative adjuvant Transarterial chemoembolization (TACE) therapy after liver cancer resection. A Cox proportional hazards model was established for these patients, followed by internal validation (enhanced bootstrap resampling technique) to further evaluate the predictive performance and discriminanceevaluate the predictive performance and discriminance, and compare it with other predictive models. The prognostic factors considered included tumour number, maximum tumor diameter, Edmondson-Steiner (ES) grade, Microvascular invasion (MVI) grade, Ki67, age, sex, hepatitis B surface antigen, cirrhosis, Alpha-fetoprotein(AFP), Albumin-bilirubin (ALBI) grade, Child-pugh grade, body mass index (BMI), Neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR). RESULTS: The endpoint of the study was overall survival. The median overall survival was 36 (95%CI: 34.0-38.0 ) months, with 1-year, 2-year and 3-year survival rates being 96.3%, 84.0% and 75.3%, respectively. Tumour number, MVI grade, and BMI was incorporated into the model, which had good differentiation and accuracy. Internal validation (enhanced bootstrap ) suggested that Harrell's C statistic is 0.72. The model consistently outperforms other currently available models. CONCLUSION: This model may be an easy-to-use tool for screening patients suitable for PA-TACE treatment and guiding the selection of clinical protocols. But further research and external validation are required.

16.
Front Oncol ; 13: 1067849, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546388

RESUMO

Introduction: Colorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain. Methods: In this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data. Results: Despite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice. Conclusion: This study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

17.
Plant Cell ; 35(12): 4199-4216, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37647532

RESUMO

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.


Assuntos
Genoma de Planta , Triticum , Estados Unidos , Triticum/genética , Genoma de Planta/genética , Melhoramento Vegetal , Fenótipo , China , Variação Genética
18.
Adv Healthc Mater ; 12(24): e2202707, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37409443

RESUMO

Injectable hydrogels have been extensively used in tissue engineering where high mechanical properties are key for their functionality at sites of high physiological stress. In this study, an injectable, conductive hydrogel is developed exhibiting remarkable mechanical strength that can withstand a pressure of 500 kPa (85% deformation rate) and display good fatigue resistance, electrical conductivity, and tissue adhesion. A stable covalent cross-linked network with a slip-ring structure by threading amino ß-cyclodextrin is formed onto the chain of a four-armed (polyethylene glycol) amino group, and then reacted with the four-armed (polyethylene glycol) maleimide under physiological conditions. The addition of silver nanowires enhances the hydrogel's electrical conductivity, enabling it to act as a good conductor in vivo. The hydrogel is injected into the fascial space, and the results show that the weight and muscle tone of the atrophied gastrocnemius muscle improve, subsequently alleviating muscle atrophy. Overall, this study provides a simple method for the preparation of a conductive hydrogel with high mechanical properties. In addition, the interstitial injection provides a strategy for the use of hydrogels in vivo.


Assuntos
Hidrogéis , Nanofios , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Prata , Polietilenoglicóis/farmacologia , Polietilenoglicóis/química , Condutividade Elétrica , Atrofia Muscular/tratamento farmacológico
19.
World J Psychiatry ; 13(6): 298-318, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37383285

RESUMO

Psychiatrists require frequent contact with and treatment of patients with mental illnesses. Due to the influence of associative stigma, psychiatrists may also be targets of stigma. Occupational stigma warrants special consideration because it significantly affects psychiatrists' career advancement, well-being, and their patients' health. Given that there is no complete summary of this issue, this study reviewed the existing literature on psychiatrists' occupational stigma to clearly synthesize its concepts, measurement tools, and intervention strategies. Herein, we emphasize that psychiatrists' occupational stigma is a multifaceted concept that simultaneously encompasses physically, socially, and morally tainted aspects. Currently, standardized methods to specifically measure psychiatrists' occupational stigma are lacking. Interventions for psychiatrists' occupational stigma may consider the use of protest, contact, education, comprehensive and systematic methods, as well as the use of psychotherapeutic approaches. This review provides a theoretical basis for the development of relevant measurement tools and intervention practices. Overall, this review seeks to raise public awareness of psychiatrists' occupational stigma, thereby promoting psychiatric professionalism and reducing its stigma.

20.
Toxics ; 11(6)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37368639

RESUMO

The study of microplastics and their impact on aquatic ecosystems has received increasing attention in recent years. Drawing from an analysis of 814 papers related to microplastics published between 2013 and 2022 in the Web of Science Core Repository, this paper explores trends, focal points, and national collaborations in freshwater microplastics research, providing valuable insights for future studies. The findings reveal three distinct stages of microplastics: nascent development (2013-2015), slow rise (2016-2018), and rapid development (2019-2022). Over time, the focus of research has shifted from "surface", "effect", "microplastic pollution", and "tributary" to "toxicity", "species", "organism", "threat", "risk", and "ingestion". While international cooperation has become more prevalent, the extent of collaboration remains limited, mostly concentrated among English-speaking countries or English and Spanish/Portuguese-speaking countries. Future research directions should encompass the bi-directional relationship between microplastics and watershed ecosystems, incorporating chemical and toxicological approaches. Long-term monitoring efforts are crucial to assessing the sustained impacts of microplastics.

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