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1.
Sci Rep ; 14(1): 23173, 2024 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369030

RESUMO

Gastric cancer (GC) is a malignant disease worldwide. Angiopoietin-like protein 4 (ANGPTL4) plays a role in pathophysiological processes, including metabolic reprogramming, angiogenesis, proliferation, and metastasis. Current evidence shows conflicting findings regarding the role of ANGPTL4 in the progression of GC. ANGPTL4 in GC was confirmed through bioinformatic analysis and immunofluorescence staining. The impact of ANGPTL4 was subsequently validated in GC cell lines using various assays, including 5-ethynyl-2-deoxyuridine (EdU), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow Cytometry (FCM), wound healing, transwell, tube formation, chorioallantoic membrane model, and nude mouse model assays. RNA-seq analysis, polymerase chain reaction (PCR), western blotting (WB), immunofluorescence (IF) and coimmunoprecipitation (co-IP) were conducted to determine the potential downstream mechanism of ANGPTL4. In SNU5 and MKN7 cells, ANGPTL4 was found to augment proliferation, migration, invasion, evasion of apoptosis, and angiogenesis. Conversely, in the AGS cell line, ANGPTL4 was observed to suppress these processes. Notably, the overexpression of ANGPTL4 in AGS cells led to the upregulation of LGALS7, which has emerged as a pivotal factor contributing to the manifestation of an anticancer phenotype induced by ANGPTL4. LGALS7, which is involved in the regulation of the hedgehog pathway and subsequent promotion of GC progression through various processes, such as proliferation, migration, apoptosis evasion, angiogenesis, and lymphangiogenesis, was found to contribute to the contradictory effects of ANGPTL4.


Assuntos
Proteína 4 Semelhante a Angiopoietina , Proliferação de Células , Proteínas Hedgehog , Transdução de Sinais , Neoplasias Gástricas , Proteína 4 Semelhante a Angiopoietina/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Animais , Camundongos , Linhagem Celular Tumoral , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Camundongos Nus , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Apoptose , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Proteína 7 Semelhante a Angiopoietina/metabolismo , Masculino , Proteínas Semelhantes a Angiopoietina
2.
Front Immunol ; 15: 1431261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39386202

RESUMO

Background: Recent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear. Objective: To elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis. Methods: Applying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype. Results: This study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma. In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a mediator of the negative association of X-18922(unknown metabolite) levels with diffuse large B-cell lymphoma, with a mediation proportion of -8.940% (95% CI=-0.063-(-17.800) %, P=4.84 × 10-2). CD25 on IgD- CD24- B cell was the mediator of the positive association between X-24531(unknown metabolite) levels and diffuse large B-cell lymphoma, with a mediation proportion of 13.200% (95% CI=-0.156-26.200%, P=4.73 × 10-2). Conclusion: In the present study, we identified a causal relationship between metabolites and lymphoma, in which immunocyte phenotypes as mediators are involved in only a minor part. The mediators by which most metabolites affect the risk of lymphoma development remain unclear and require further exploration in the future.


Assuntos
Estudo de Associação Genômica Ampla , Linfoma , Análise da Randomização Mendeliana , Fenótipo , Humanos , Linfoma/imunologia , Linfoma/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Metaboloma
3.
Oncol Rep ; 52(5)2024 11.
Artigo em Inglês | MEDLINE | ID: mdl-39219268

RESUMO

Acute myeloid leukemia (AML) is a predominant form of leukemia. Central nervous system (CNS) involvement complicates its diagnosis due to limited diagnostic tools, as well as its treatment due to inadequate therapeutic methodologies and poor prognosis. Furthermore, its incidence rate is unclear. The mechanisms of AML cell mobilization from the bone marrow (BM) to the CNS are not fully elucidated, and the molecular factors contributing to CNS infiltration are insufficiently recognized. The present review aimed to enhance the understanding of CNS involvement of AML and its impact on CNS. The latest research on the pathways and mechanisms facilitating AML cells to escape the BM and infiltrate the CNS was reviewed. Additionally, novel therapeutic strategies targeting specific molecules and genes for treating CNS involvement in AML were examined.


Assuntos
Neoplasias do Sistema Nervoso Central , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/terapia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/metabolismo , Medula Óssea/patologia , Medula Óssea/metabolismo
4.
Acta Pharmacol Sin ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187678

RESUMO

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

5.
Inorg Chem ; 63(31): 14794-14803, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39037615

RESUMO

Ethylene glycol (EG) is one of the most attractive platform molecules derived from biomass and waste plastics. Thus, the selective electrooxidation of ethylene glycol (EGOR) into value-added chemicals (especially glycolic acid (GA)) can promote its recycling and upgrading. However, the understanding of the EG-to-GA process on Pt-group metal (PGM) electrodes is far limited now. It has been shown that the Pt and Pd electrodes could show considerable EGOR activity but not Rh and Ir electrodes. Meanwhile, EGOR mainly produces the glycolate, oxalate, and formate on Pt and Pd electrodes, whereas it can obtain minute amounts of glycolate and oxalate on Rh and Ir electrodes. Impressively, the selectivity of glycolate on Pt and Pd electrodes can be over 85% (apparent Faradaic efficiency) in alkaline media, although the stability should be further improved through interfacial tuning and/or engineering. This work might deepen the fundamental understanding of the EGOR process on the nature of PGM electrodes.

6.
Biomaterials ; 311: 122679, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38943823

RESUMO

The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health.


Assuntos
Desenvolvimento Embrionário , Histonas , Óxido de Zinco , Animais , Óxido de Zinco/química , Óxido de Zinco/toxicidade , Camundongos , Histonas/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Nanopartículas/química , Nanopartículas/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade
7.
Drug Des Devel Ther ; 18: 1907-1915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828026

RESUMO

Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.


Assuntos
Sonhos , Endoscopia Gastrointestinal , Propofol , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anestesia , Anestésicos Intravenosos/administração & dosagem , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Método Duplo-Cego , Sonhos/efeitos dos fármacos , Propofol/administração & dosagem , Estudos Prospectivos
8.
Bioorg Chem ; 150: 107555, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38885548

RESUMO

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp2-iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and ß-glucosidase isoenzymes. The most effective derivative reached over a 103-fold higher inhibitory potency towards human ß-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and ß-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach.


Assuntos
Compostos Azo , Inibidores Enzimáticos , Glicosídeo Hidrolases , Glicosídeos , Imino Açúcares , Humanos , Compostos Azo/química , Compostos Azo/farmacologia , Compostos Azo/síntese química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/metabolismo , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/síntese química , Imino Açúcares/química , Imino Açúcares/farmacologia , Imino Açúcares/síntese química , Luz , Estrutura Molecular , Relação Estrutura-Atividade , Glucosilceramidase/química , Glucosilceramidase/metabolismo , Glucosilceramidase/farmacologia
9.
J Cancer ; 15(11): 3418-3426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817854

RESUMO

Background: The patients of cervical cancer have more negative emotions and lower quality of life. The aim of this study was to explore the relationships between existential well-being (EWB), social support, resilience, negative emotions in patients with cervical cancer, and to examine whether resilience mediates the associations between EWB or social support and negative emotions. Material and methods: This study enrolled patients with cervical cancer who were treated at the Tianjin Medical University Cancer Institute and Hospital in China during 2012-2019. The Hospital Anxiety and Depression Scale (HADS), the Resilience Scale of 14 items (RS-14) and the McGill Quality of Life Questionnaire (MQOL) were utilized to assess patient's anxiety, depression, resilience, social support and EWB via telephone. Spearman's correlation analyses were used to assess bivariate correlations, and mediation analyses were applied to examine whether resilience mediated the relationship between social support or EWB and negative emotions. Results: A total of 150 (92.0%) out of 163 eligible patients completed the questionnaires. EWB and social support were negatively correlated with anxiety (r=-0.560 and r=-0.561) and depression (r=-0.508 and r=-0.526), and positively correlated with resilience (r=0.691 and r=0.652). Resilience was negatively associated with anxiety (r=-0.545) and depression (r=-0.505). Negative direct effects of social support on anxiety and EWB on anxiety and depression were statistically significant (P<0.05). Resilience played a partial mediating role in the relationship between EWB and depression (ß=-0.085, 95%CI: -0.150 to -0.020), accounting for 37.12% of the total effect. It also served as a partial mediator in the association between EWB and anxiety (ß=-0.061, 95%CI: -0.107 to -0.015), explaining 34.46% of the overall effect. Additionally, resilience partially mediated the connection between social support and depression (ß=-0.173, 95%CI: -0.312 to -0.053), explicating 57.48% of the total effect. Conclusions: A combination of existential, supportive and resilient interventions may help reduce psychological distress and improve quality of life among cervical cancer patients, thereby promoting both physical and psychological health.

10.
Clin Transl Oncol ; 26(8): 1836-1843, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38575837

RESUMO

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.


Assuntos
Criopreservação , Preservação da Fertilidade , Neoplasias Hematológicas , Humanos , Preservação da Fertilidade/métodos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Criopreservação/métodos , Feminino , Masculino , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico
11.
J Occup Environ Med ; 66(7): e266-e271, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38595272

RESUMO

OBJECTIVE: To assess regulatory effect of Mediterranean diet for occupational noise exposure and hearing loss. Methods: This cross-sectional study included 4757 individuals. Weighted logistic regression model was adopted to explore the association of occupational noise exposure and Mediterranean diet with hearing loss, and regulatory effects of the Mediterranean diet for the relationship of occupational noise exposure and hearing loss. Results: Occupational noise exposure was associated with an increased odds of hearing loss. Under low adherence to the Mediterranean diet, the occupational noise exposure group was related to increased odds of hearing loss. Under high adherence to the Mediterranean diet, no significant difference was observed between occupational noise exposure and hearing loss, and adjusted effect size was reduced accordingly. Conclusion: Mediterranean diet may moderate this relationship of occupational noise exposure and hearing loss to some degree.


Assuntos
Dieta Mediterrânea , Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Exposição Ocupacional , Humanos , Ruído Ocupacional/efeitos adversos , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Perda Auditiva Provocada por Ruído/prevenção & controle , Perda Auditiva Provocada por Ruído/etiologia , Exposição Ocupacional/efeitos adversos , Modelos Logísticos , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Doenças Profissionais/epidemiologia
12.
J Transcult Nurs ; 35(4): 263-270, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634631

RESUMO

INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.


Assuntos
Histerectomia , Pesquisa Qualitativa , Qualidade de Vida , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/cirurgia , Pessoa de Meia-Idade , Adulto , Histerectomia/psicologia , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Qualidade de Vida/psicologia , China , Entrevistas como Assunto/métodos , Idoso , Adaptação Psicológica
13.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623681

RESUMO

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Orbitárias , Neoplasias Cutâneas , Masculino , Humanos , Adulto , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/complicações , Neoplasias Orbitárias/patologia , Células Dendríticas , Transplante Autólogo , Neoplasias Cutâneas/patologia , Neoplasias Hematológicas/diagnóstico , Leucemia Mieloide Aguda/complicações
14.
Front Endocrinol (Lausanne) ; 15: 1354577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577568

RESUMO

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Adulto , Humanos , Feminino , Densidade Óssea , Estudos Transversais , Cádmio , Inquéritos Nutricionais
15.
Psychooncology ; 33(3): e6319, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497821

RESUMO

OBJECTIVES: Unmet supportive care needs are associated with psychological symptoms such as depression and anxiety. However, so far, few studies have explored the protective psychological factors of unmet needs. Therefore, this study intends to explore the protective effect of self-compassion on unmet needs of Chinese cancer patients and to examine the predictive role of self-compassion on these needs during treatment. METHODS: A longitudinal study was performed at Shaanxi Provincial Cancer Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and end (T3) of medical treatment. Hierarchical linear regression analyses were used to examine the research questions. RESULTS: Cross-sectional regression analyses showed that self-compassion at T1 was significantly related to psychological needs at T1. Negative self-compassion at T1 was significantly related to total unmet needs, psychological needs, health system, and information and sexual needs. Longitudinal regression analyses showed that self-compassion at T1 significantly predicted total unmet needs; health system and information (HSI) needs at T2, psychological needs at T3, and negative self-compassion at T1 significantly predicted total unmet needs, HSI needs, physical needs, and patient care needs at T2 when controlling for unmet needs at T1. Positive self-compassion was not a predictor of unmet needs. CONCLUSIONS: Self-compassion can be a protective factor of unmet needs in cancer patients. Future intervention studies should focus on improving the overall level of self-compassion and reducing the level of negative self-compassion in cancer patients to reduce patients' unmet needs.


Assuntos
Neoplasias , Autocompaixão , Humanos , Estudos Transversais , Estudos Longitudinais , Ansiedade , Neoplasias/terapia
16.
Cell Mol Life Sci ; 81(1): 113, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436697

RESUMO

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Neoplasias Ovarianas , Grânulos de Estresse , Proteína 1 de Ligação a Y-Box , Feminino , Humanos , Endodesoxirribonucleases , Neoplasias Ovarianas/genética , Fosforilação , Grânulos de Estresse/metabolismo , Proteína 1 de Ligação a Y-Box/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo
17.
Arthritis Res Ther ; 26(1): 64, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459604

RESUMO

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients. METHODS: In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN. RESULTS: Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo. CONCLUSION: In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Camundongos , Animais , Nefrite Lúpica/metabolismo , Vitamina K 3 , Camundongos Endogâmicos MRL lpr , Rim/patologia , Lúpus Eritematoso Sistêmico/patologia , Fibrose , Proteínas Serina-Treonina Quinases , Proteínas Supressoras de Tumor
18.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469766

RESUMO

BACKGROUND: Pseudothrombocytopenia (PTCP) is a relatively rare phenomenon in vitro, the mechanism is not completely clear, and there is no unified solution for it. How to identify and solve PTCP accurately is a challenge for laboratory personnel. METHODS: According to the patient's clinical manifestations, thrombocytopenia caused by hypersplenism was excluded. PTCP was confirmed by platelet volume histograms, scattergrams and platelet clumps on the blood smears. Commonly used alternative anticoagulants such as sodium citrate or heparin were used for platelet counting. The corrective effect of the platelet count was not good, so non-anticoagulant blood was collected and tested immediately, and blood smears were used to count platelets manually. RESULTS: The PTCP of the patient could not be solved using sodium citrate and heparin anticoagulation. By collecting non-anticoagulant blood and testing immediately, the platelet count returned to normal (180 x 109/L), which is consistent with the results of manual counting on the patient's blood smears (175 x 109/L). CONCLUSIONS: When PTCP is confirmed, commonly used alternative anticoagulants can be used. If these do not work, non-anticoagulant blood can be collected and tested immediately, and blood smears can be used to count platelets manually.


Assuntos
Carcinoma , Hiperesplenismo , Trombocitopenia , Humanos , Citrato de Sódio/farmacologia , Ácido Edético/farmacologia , Hiperesplenismo/diagnóstico , Agregação Plaquetária , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoagulantes/farmacologia , Heparina/uso terapêutico , Heparina/farmacologia , Fígado
19.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469787

RESUMO

BACKGROUND: Treatment-related acute myeloid leukemia (t-AML) is often secondary to some cytotoxic drugs or occurs after radiotherapy and immunosuppression therapy. As commonly used drugs in colorectal cancer chemotherapy, oxaliplatin and capecitabine have obvious cytotoxicity, which may also be an important factor causing t-AML. METHODS: In this study, we report the development of treatment-related acute myeloid leukemia in a pT4NIMO colorectal cancer patient after an approximate 16-month latency period following treatment with 6 cycles of oxali-platin (190 mg on Day 1) plus capecitabine (1.5 g orally twice daily on Days 1 - 14) in combination with recombinant human granulocyte-colony stimulating factor treatment. The patient developed severe anemia with thrombocytopenia after treatment. After a peripheral blood smear and bone marrow biopsy, the diagnosis of AML-M2a was confirmed. RESULTS: The patient was diagnosed with t-AML approximately 16 months after treatment. Our case illustrates the possibility of some cytotoxic drugs inducing t-AML after colorectal cancer treatment. CONCLUSIONS: We suggest that clinicians conduct long-term epidemiological follow-up and epidemiological investigations on patients treated with oxaliplatin and capecitabine. In addition, clinicians should carefully check the complete blood cell count on routine follow-ups and observe the morphological changes of white blood cells in peripheral blood smears, even for asymptomatic patients who have undergone chemotherapy. In this way, we can observe the possibility of its development into secondary leukemia.


Assuntos
Neoplasias Colorretais , Leucemia Mieloide Aguda , Humanos , Capecitabina/efeitos adversos , Oxaliplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia
20.
Medicine (Baltimore) ; 103(9): e37200, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428848

RESUMO

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.


Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Resultado do Tratamento , Erros de Diagnóstico , Diarreia/complicações
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