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1.
MedComm (2020) ; 5(4): e537, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617434

RESUMO

Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2-like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum-free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum-induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP-ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient-derived xenografts, especially those with wild-type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.

2.
Front Immunol ; 15: 1323209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585267

RESUMO

Introduction: Early detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies. Methods: This retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses. Results: Among the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-ß2 glycoprotein I (-ß2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index - 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]). Conclusions: Disease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE's pathological mechanism.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Autoanticorpos , Anticorpos Antifosfolipídeos , Anticorpos Anticardiolipina
3.
Aging Dis ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377031

RESUMO

In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.

4.
J Affect Disord ; 350: 746-754, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38246287

RESUMO

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.


Assuntos
Doenças Cardiovasculares , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/psicologia , Resultado do Tratamento , Transtornos de Ansiedade , Ansiedade , Depressão
5.
BMC Med Res Methodol ; 24(1): 16, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254038

RESUMO

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Teorema de Bayes , Prognóstico , Calibragem , China/epidemiologia
6.
Environ Pollut ; 342: 123037, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030106

RESUMO

Microplastics (MPs), a pervasive pollutant in aquatic environments, are increasingly recognized for their detrimental effects on aquatic organisms. However, the present understanding of their impact on phytoplankton, particularly freshwater microalgae, remains limited. Furthermore, previous studies have predominantly focused on MP particles, largely overlooking the most prevalent form of MPs in aquatic settings-fibers. In this study, we scrutinized the toxicological implications of microplastic fibers (MFs) spanning four distinct lengths (50 µm, 100 µm, 150 µm, and 200 µm) on the protein-nucleated algae Chlorella pyrenoidosa over a six-day period. The study unequivocally demonstrated that MFs markedly impeded C. pyrenoidosa growth, diminished photosynthetic pigment content, and induced oxidative stress, with all observed effects exhibiting a length-dependent correlation. Electron microscopy further revealed notable damage to algal cell membranes. Cell membrane shrinkage, cytoplasm outflow, and abnormalities in cell division were observed in the 150 µm and 200 µm groups. Furthermore, C. pyrenoidosa clustered around the 200 µm MF were notably denser compared to other groups. The present study demonstrated that MFs had length-dependent toxic effects on C. pyrenoidosa. These findings offer novel insights into the deleterious impact of MFs on aquatic organisms, underscoring the pivotal role of length in influencing their toxicity.


Assuntos
Chlorella , Poluentes Químicos da Água , Microplásticos/metabolismo , Plásticos/metabolismo , Poluentes Químicos da Água/análise , Estresse Oxidativo
7.
J Pathol ; 262(2): 240-253, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38018407

RESUMO

Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal-fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4+ T cells being more observable within the umbilical cord blood, whereas CD8+ T cells became relatively more abundant in fetal membranes. CD4+ and CD8+ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8+ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8+ T but not CD4+ T cells in vivo. Collectively, we showed that CD8+ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Gravidez , Animais , Camundongos , Humanos , Feminino , Recém-Nascido , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/prevenção & controle , Linfócitos T CD8-Positivos , Membranas Extraembrionárias , Fenótipo
8.
BMC Psychiatry ; 23(1): 900, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041038

RESUMO

OBJECTIVE: The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. METHODS: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. RESULTS: The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors' MBI score (r = -0.467, p < .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30 ~ 10.18), and the test information within the range of low-quality relationship was relatively high. CONCLUSION: The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity and thus was appropriate for measuring the DPR in Chinese medical settings.


Assuntos
Esgotamento Profissional , Relações Médico-Paciente , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Esgotamento Psicológico/diagnóstico
9.
JAMA Netw Open ; 6(12): e2347176, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085543

RESUMO

Importance: Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. Objective: To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. Design, Setting, and Participants: This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Exposures: Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Main Outcomes and Measures: Follow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. Results: A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64). Conclusions and Relevance: In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.


Assuntos
Neoplasias Pulmonares , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Tomografia Computadorizada por Raios X/métodos , Pulmão
10.
Aquat Toxicol ; 265: 106755, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944326

RESUMO

Microplastic pollution, especially microfibers (MFs), presents a critical global environmental challenge in natural water bodies. Yet, research on the toxic effects of MFs, particularly during early fish development, is limited. This study aimed to investigate MFs' toxic effects and mechanisms on early-stage zebrafish. Zebrafish embryos were exposed to varying concentrations of polyacrylonitrile microfibers (PanMfs) for 7 days. Results revealed PanMfs adhering to the embryos' surface, with higher concentrations accelerating heart rate and causing pericardial edema in post-hatching larvae. Larvae ingested PanMfs, leading to their accumulation in the intestines and increased levels of reactive oxygen species (ROS) and mitochondrial quantity. Notably, lipid metabolism and calcium ion related signaling pathways underwent significant changes. Low concentration MFs affected glycometabolism pathways, with potential roles for aldob and cacng1a, exhibiting pronounced increases in ROS levels. High concentration of MFs had the most profound impact on signal transduction-related pathways, and possibly triggering micromitophagy and apoptosis in zebrafish intestinal epithelial cells through the Kras/MAPK signaling pathway, with potential roles for kras and mapk9. Although ROS increase was somewhat alleviated, it resulted in decreased survival rates and restricted growth in high concentration of MFs group. These findings highlight the significant threat of MFs to the early survival of fish. MFs pollution prevention and control hold great significance in the conservation of fishery resources.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Embrião não Mamífero , Plásticos , Poluentes Químicos da Água/toxicidade , Larva
11.
BMC Psychiatry ; 23(1): 890, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38031007

RESUMO

BACKGROUND: For better disease management and improved prognosis, early identification of co-morbid depression in diabetic patients is warranted. the WHO-5 well-being index (WHO-5) has been used to screen for depression in diabetic patients, and its Chinese version (WHO-5-C) has been validated. However, its psychometric properties remain to be further validated in the type 2 diabetes patient population. The aim of our study was to examine the reliability and validity of the WHO-5-C in patients with type 2 diabetes mellitus. METHODS: The cross-sectional study was conducted on 200 patients from July 2014 to March 2015. All patients should complete the WHO-5-C, the Patient Health Questionnaire-9 (PHQ-9), the 20-item Problem Areas in Diabetes Scale (PAID-20), the Mini International Neuropsychiatric Interview (M.I.N.I), and Hamilton Rating Scale for Depression (HAM-D). Internal consistency of WHO-5 was revealed by Cronbach's alpha, and constructive validity by confirmatory factor analysis (CFA). Relationship with PHQ-9, HAM-D, and PAID-20 was examined for concurrent validity, and ROC analysis was performed for criterion validity. RESULTS: The WHO-5-C presented satisfactory reliability (Cronbach's alpha = 0.88). CFA confirmed the unidimensional factor structure of WHO-5-C. The WHO-5-C had significant negative correlation with HAM-D (r = -0.610), PHQ-9 (r = -0.694) and PAID-20 (r = -0.466), confirming good concurrent validity. Using M.I.N.I as the gold standard, the cut-off value of WHO-5-C was 42, with a sensitivity of 0.83 and specificity of 0.75. CONCLUSION: The WHO-5-C holds satisfactory reliability and validity that is suitable for depression screening in type 2 diabetes patients as a short and convenient instrument.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Estudos Transversais , Reprodutibilidade dos Testes , Questionário de Saúde do Paciente , Psicometria , Organização Mundial da Saúde , Inquéritos e Questionários , Depressão/complicações , Depressão/diagnóstico
12.
J Genet Genomics ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37923173

RESUMO

The cerebral cortex is a pivotal structure that is integral to advanced brain functions within the mammalian central nervous system. Patterns of DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'- hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in early stages profoundly alters the epigenetic regulation program, which provides new insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

13.
Front Endocrinol (Lausanne) ; 14: 1266183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881500

RESUMO

Introduction: Previous research has revealed a bidirectional relationship between type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). A very limited proportion of patients with T2DM comorbid MDD received adequate psychiatric intervention. This study investigated the help-seeking behaviors of patients with T2DM comorbid with MDD during one-year follow-up. Methods: At a medical center in China, a cohort of outpatients with T2DM were assessed and diagnosed for comorbid depression at baseline and after one year. The Mini International Neuropsychiatric Interview was used to diagnose MDD, while The Patient Health Questionnaire-9 (PHQ-9) and The Hamilton Depression Scale 17-item (HAMD-17) were used for depression assessment. Mental health help-seeking behaviors of patients during follow-up period were also evaluated. Results: Out of the 203 patients with T2DM at baseline, 114 (56.2%) completed the follow-up. The prevalence of MDD in participants with T2DM was 12.8% at baseline and 22.8% at follow-up. Patients who completed the follow-up had a lower baseline PHQ-9 score (test statistic -2.068, p=0.039), HAMD-17 score (test statistic -2.285, p=0.022) than those who did not complete the follow-up. A total of 26 patients had comorbid MDD during the follow-up period, among which 8 patients (30.8%) voluntarily visited psychiatric clinics, while others did not seek assistance. The level of HbA1c at follow-up was higher in patients who sought help than in those who did not (8.1 ± 1.8% vs. 7.0 ± 0.7%), although the difference was not statistically significant. Conclusion: Voluntary psychiatric help-seeking for Chinese patients with comorbid T2DM and MDD is uncommon. It is crucial to increase awareness of depression among patients and healthcare professionals alike.


Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Comorbidade , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , População do Leste Asiático , Seguimentos
14.
Cancer Cell Int ; 23(1): 248, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37865750

RESUMO

BACKGROUND: An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored. METHODS: A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies-namely RNA-sequencing, western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay-were used to reveal the mechanisms of MYBL2 in the OVC microenvironment. RESULTS: We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance. CONCLUSIONS: The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.

15.
Aquat Toxicol ; 263: 106690, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37708703

RESUMO

With the widespread utilization of plastic products, microplastics (MPs) have merged as a newfound environmental contaminant in the United States, and the bulk of these MPs in the environment manifest as fibrous structures. Concerns have also been voiced regarding the potential hazards posed by microplastic fibers (MFs). However, research examining the toxicity of MFs, particularly in relation to planktonic organisms, remains severely limited. Meanwhile, polyester fiber materials find extensive applications across diverse industries. As a result, this investigation delved into the toxicology of polyester microplastic fibers (PET-MFs) with a focus on their impact on Daphnia carinata (D. carinata), a freshwater crustacean. Newly hatched D. carinata were subjected to varying concentrations of PET-MFs (0, 50, and 500 MFs/mL) to scrutinize the accumulation of PET-MFs within these organisms and their resultant toxicity. The outcomes revealed that D. carinata was capable of ingesting PET-MFs, leading to diminished rates of survival and reproduction. These effects were accompanied by mitochondrial impairment, heightened mitochondrial count, apoptosis, escalated generation of reactive oxygen species, augmented activity of antioxidant enzymes, and distinct patterns of gene expression. Interestingly, when comparing the group exposed to 50 MFs/mL with the one exposed to 500 MFs/mL, it was observed that the former triggered a more pronounced degree of mitochondrial damage, apoptosis, and oxidative stress. This phenomenon could be attributed to the fact that brief exposure to 500 MFs/mL resulted in greater mortality, eliminating individuals with lower adaptability. Those that survived managed to regulate elevated in vivo reactive oxygen species levels through an increase in glutathione S-transferase content, thereby establishing an adaptive mechanism. Low concentrations did not induce direct mortality, yet PET-MFs continued to inflict harm within the organism. RNA-seq analysis unveiled significant alterations in 279 and 55 genes in the 50 MFs/mL and 500 MFs/mL exposure groups, respectively. Functional enrichment analysis of the 50 MFs/mL group indicated involvement of the apoptosis pathway and ferroptosis pathway in the toxic effects exerted by PET-MFs on D. carinata. This study imparts valuable insights into the toxicological ramifications of PET-MFs on D. carinata, underscoring their potential risks within aquatic ecosystems.


Assuntos
Ferroptose , Poluentes Químicos da Água , Humanos , Animais , Microplásticos/metabolismo , Plásticos , Daphnia/metabolismo , Poliésteres/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ecossistema , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo , Apoptose
17.
Front Psychiatry ; 14: 1201707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37377470

RESUMO

Objectives: A general expectation measurement of inpatients across wards is needed in the patient safety management systems of general hospitals. This study developed and psychometrically validated a new scale fulfilling the requirements above: the Hospitalized Patients' Expectations for Treatment Scale-Patient version (HOPE-P). Methods: A total of 35 experts and ten inpatients were interviewed during the formulation of the HOPE-P scale, which was initially designed with three dimensions: doctor-patient communication expectations, treatment outcome expectations, and disease management expectancy. We recruited 210 inpatients from a general hospital in China and explored the reliability, validity, and psychometric characteristics of the questionnaire. Item analysis, construct validity, internal consistency and 7-day test-retest reliability analysis were applied. Results: Exploratory and confirmatory analyses supported a 2-dimension (doctor-patient communication expectation and treatment outcome expectation) structure with satisfactory model fit parameters (root mean square residual (RMR) = 0.035, a root-mean-square-error of approximation (RMSEA) = 0.072, comparative fit index (CFI) = 0.984, Tucker-Lewis index (TLI) = 0.970). Item analysis revealed an appropriate item design (r = 0.573-0.820). The scale exhibited good internal consistency, with Cronbach's α of 0.893, 0.761, and 0.919 for the overall scale, the doctor-patient communication expectation subscale, and the treatment outcome expectation subscale, respectively. The 7-day test-retest reliability was 0.782 (p < .001). Conclusion: Our results indicated that the HOPE-P is a reliable and valid assessment tool to measure the expectations of general hospital inpatients, with a strong capacity to recognize patients' expectations regarding doctor-patient communication and treatment outcomes.

18.
Fish Shellfish Immunol ; 137: 108780, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37120086

RESUMO

Scavenger receptor (SRs) are pattern recognition receptors that play important roles in innate immunity. However, studies on SR in Procambarus clarkii are still lacking. In the present study, a novel scavenger receptor B on P. clarkii (PcSRB) was identified. The ORF of PcSRB was 548 bp and encoded 505 amino acid residues. It was a transmembrane protein with two transmembrane domains. The molecular weight was about 57.1 kDa. The tissue analysis by real-time PCR showed that the highest expression level was found in hepatopancreas, while the lowest expression level was found in heart, muscle, nerve and gill. After P. clarkii were infected with Aeromonas hydrophila, the expression of SRB in hemocytes increased rapidly at 12 h, and SRB in hepatopancreas and intestine also increased rapidly at 48 h after infection. The recombinant protein was obtained by prokaryotic expression. The recombinant protein (rPcSRB) could bind to bacteria and different molecular pattern recognition substances. The present study confirmed that SRB may be involved in the immune regulation process and play a certain role in the immune defense of P. clarkii, especially in the recognition and binding of pathogens. Therefore, this study provides theoretical support for further improving and enriching the immune system of P. clarkii.


Assuntos
Astacoidea , Imunidade Inata , Animais , Sequência de Aminoácidos , Imunidade Inata/genética , Receptores de Reconhecimento de Padrão , Proteínas Recombinantes , Proteínas de Artrópodes
19.
Front Psychiatry ; 14: 1117174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873225

RESUMO

Objective: The patient-doctor relationship has been considered as a crucial concept in primary healthcare, while the medical reform launched by the Chinese government in 2009 has brought significant changes to the healthcare system, which made it urgent to introduce reliable measurement instruments for assessing today's doctor-patient relationship in China. This study examined the psychometric properties of the Chinese version of the Patient-Doctor-Relationship Questionnaire-9 item (PDRQ-9) scale among general hospital inpatients in China. Materials and methods: A total of 203 participants responded to the survey, of which 39 completed retest after 7 days. Factor analyses were used to test the construct validity of the scale. Convergent validity was evaluated by the correlation between PDRQ-9 and depressive symptoms measured using PHQ-9 (Patient Health Questionnaire Depression Scale-9 item). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) framework were used to estimate the parameters of each item. Results: The two-factor model of relationship quality and treatment quality was supported (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, RMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). The PDRQ-9 and both subscales showed significant correlation with PHQ-9 (r = -0.196∼-0.309) and good internal consistency (Cronbach's alpha = 0.865∼0.933). ANCOVA analysis adjusted with age revealed significant difference in PDRQ-9 ratings between patients with or without significant depressive symptoms (P = 0.019). The 7-day test-retest reliability of the scale was 0.730. The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.46∼38.46), and the test information within the range of low-quality relationship was relatively high. Conclusion: The Chinese version of PDRQ-9 is a valid and reliable rating scale, which can measure the doctor-patient relationship among Chinese patients.

20.
Front Immunol ; 14: 1084056, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733483

RESUMO

The contribution of bone-marrow derived cells (BMCs) to a newly formed beta-cell population in adults is controversial. Previous studies have only used models of bone marrow transplantation from sex-mismatched donors (or other models of genetic labeling) into recipient animals that had undergone irradiation. This approach suffers from the significant shortcoming of the off-target effects of irradiation. Partial pancreatic duct ligation (PDL) is a mouse model of acute pancreatitis with a modest increase in beta-cell number. However, the possibility that recruited BMCs in the inflamed pancreas may convert into beta-cells has not been examined. Here, we used an irradiation-free model to track the fate of the BMCs from the donor mice. A ROSA-mTmG red fluorescent mouse was surgically joined to an INS1Cre knock-in mouse by parabiosis to establish a mixed circulation. PDL was then performed in the INS1Cre mice 2 weeks after parabiosis, which was one week after establishment of the stable blood chimera. The contribution of red cells from ROSA-mTmG mice to beta-cells in INS1Cre mouse was evaluated based on red fluorescence, while cell fusion was evaluated by the presence of green fluorescence in beta-cells. We did not detect any red or green insulin+ cells in the INS1Cre mice, suggesting that there was no contribution of BMCs to the newly formed beta-cells, either by direct differentiation, or by cell fusion. Thus, the contribution of BMCs to beta-cells in the inflamed pancreas should be minimal, if any.


Assuntos
Medula Óssea , Pancreatite , Camundongos , Animais , Doença Aguda , Células da Medula Óssea , Pâncreas
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