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1.
Arch Dermatol Res ; 316(8): 553, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172247

RESUMO

Prior evidence suggests that altered energy metabolism plays a crucial role in the development of fibrotic diseases. Recent research indicates that systemic sclerosis (SSc) patients have potentially benefited from energy management, implying that basal metabolic rate (BMR), a vital energy metabolic parameter, may be related to SSc. However, the causal effect of BMR on SSc remains unknown. Thus, we aimed to elucidate the causal links between BMR and SSc. Based on summary statistics from the genome-wide association studies (GWAS) database, two-sample Mendelian randomization (MR) was applied to explore causality between BMR and SSc. The causal relationships were assessed employing inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods. Meanwhile, several sensitivity analyses were carried out to ensure the robustness of the findings. There was an underlying genetic association of BMR on SSc (OR = 0.505, 95% CI: 0.272-0.936, P = 0.030). Moreover, no significant causal effect between SSc and BMR was observed in the reverse MR analysis (OR = 0.999, 95% CI: 0.997-1.001, P = 0.292). According to the sensitivity analysis, the presence of heterogeneity and genetic pleiotropy was not detected. Our findings, derived from a genetic perspective, provide robust evidence of a causal connection between BMR and SSc. To verify these results and clarify the potential mechanisms, further research is warranted.


Assuntos
Metabolismo Basal , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico , Humanos , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/epidemiologia , Metabolismo Basal/genética
2.
Small ; : e2403882, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39194489

RESUMO

Lithium-sulfur batteries (LSBs) are considered as promising candidates in the next generation of high energy density devices. However, the serious shuttle effect, irreversible dendrite growth of Li metal anode, and the potential safety hazard impede the practical application of LSBs. Herein, a novel homogeneous Janus membrane based on functionalized MOFs crosslinked by aramid nanofibers is designed and synthesized to simultaneously solve the above challenges in quasi-solid-state LSBs. The aramid nanofibers with good mechanical properties and thermal stability act as a homogeneous scaffold to crosslink the MOF particles with different ligands on both sides and this Janus membrane upgrades the stability and safety on both the cathode and anode. Specifically, the amino ligand-decorated MOFs contribute to homogenize Li-ion flux and stabilize the lithium anode, and the sulfonic ligand-decorated MOFs effectively suppress the shuttle effect by the dual effects of chemical adsorption and electrostatic repulsion. The quasi-solid-state LSBs assembled with this homogeneous Janus membrane deliver excellent rate performance and cycling stability. Moreover, it exhibits a high initial capacity of 923.4 mAh g-1 at 1 C at 70 °C, and 697.3 mAh g-1 is retained after 100 cycles, indicating great potential for its application in high-safety LSBs.

3.
Eur J Pharmacol ; 979: 176862, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068974

RESUMO

We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.


Assuntos
Exossomos , Lúpus Eritematoso Sistêmico , Células-Tronco Mesenquimais , MicroRNAs , Linfócitos T Reguladores , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Exossomos/metabolismo , Exossomos/genética , Exossomos/imunologia , Exossomos/transplante , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Humanos , Animais , Feminino , Diferenciação Celular , Camundongos , Transplante de Células-Tronco Mesenquimais , Adulto , Regulação para Cima , Masculino
4.
Biol Direct ; 19(1): 51, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956687

RESUMO

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear. MATERIALS AND METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics. RESULT: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes. CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/genética , Masculino , Feminino , Neoplasias Gástricas/genética , Pessoa de Meia-Idade , Idoso , Genômica , Sequenciamento Completo do Genoma , China/epidemiologia , Adenocarcinoma/genética , Adulto
5.
Front Public Health ; 12: 1411688, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952733

RESUMO

Background: Occupational stress and job satisfaction significantly impact the well-being and performance of healthcare professionals, including radiologists. Understanding the complex interplay between these factors through network analysis can provide valuable insights into intervention strategies to enhance workplace satisfaction and productivity. Method: In this study, a convenience sampling method was used to recruit 312 radiologists for participation. Data on socio-demographic characteristics, job satisfaction measured by the Minnesota job satisfaction questionnaire revised short version (MJSQ-RSV), and occupational stress assessed using the occupational stress scale. Network analysis was employed to analyze the data in this study. Results: The network analysis revealed intricate patterns of associations between occupational stress and job satisfaction symptoms among radiologists. Organizational management and occupational interests emerged as crucial nodes in the network, indicating strong relationships within these domains. Additionally, intrinsic satisfaction was identified as a central symptom with high connectivity in the network structure. The stability analysis demonstrated robustness in the network edges and centrality metrics, supporting the reliability of the findings. Conclusion: This study sheds light on the complex relationships between occupational stress and job satisfaction in radiologists, offering valuable insights for targeted interventions and support strategies to promote well-being and job satisfaction in healthcare settings.


Assuntos
Satisfação no Emprego , Estresse Ocupacional , Radiologistas , Humanos , Feminino , Masculino , Adulto , Inquéritos e Questionários , Estresse Ocupacional/psicologia , Pessoa de Meia-Idade , Radiologistas/psicologia , Radiologistas/estatística & dados numéricos , Local de Trabalho/psicologia
6.
Am J Clin Nutr ; 120(2): 398-406, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914226

RESUMO

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Receptores de Calcitriol , Vitamina D , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Infecções/epidemiologia , Infecções/sangue , Fatores de Risco , Reino Unido/epidemiologia , Estudos de Coortes , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/epidemiologia , Polimorfismo Genético , Adulto , Polimorfismo de Nucleotídeo Único
7.
Int Immunopharmacol ; 138: 112562, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38936057

RESUMO

Rheumatoid arthritis (RA) is a complex autoimmune disease featuring invasive and infiltrative fibroblast-like synoviocytes (FLS) that lead to joint damage. While current RA pathological mechanisms remain incompletely defined, exosomes have been implicated as having the potential to drive disease progression due to their ability to deliver different types of biomolecules to tissues effected by RA. One potentially disease exacerbating molecule type found in exosomes are Circular RNAs (circRNAs), which are highly stable and have been previously implicated in RA pathogenesis. Here, we examine hsa_circ_0003914, a circRNA found in exosomes located in blood plasma, for a role in RA. Plasma exosomes were isolated and injected into collagen-induced arthritis (CIA) mice, followed by functional experiments to analyze the influence of exosomes on FLS formation. Sequencing revealed the presence of hsa_circ_0003914 in exosomes, so we examined its association with clinical markers in RA. Finally, the role for hsa_circ_0003914 in RA was directly confirmed through in vivo and in vitro experiments. We found that plasma exosomes isolated from RA patients could aggravate the disease of CIA mice, compared to exosomes isolated from healthy control patients. Hsa_circ_0003914 was highly enriched in the exosomes of RA patients. Mechanistically, Hsa_circ_0003914 promoted abnormal cell proliferation, migration, invasion and stimulated the secretion of inflammatory cytokines in FLSs through targeting NF-κB/p65 signaling pathway. Interestingly, knockdown of hsa_circ_0003914 rescued disease phenotypes in CIA mice. Taken together, these data implicate hsa_circ_0003914 as a potential therapeutic target for the prevention and management of RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Biomarcadores , Exossomos , Camundongos Endogâmicos DBA , RNA Circular , Sinoviócitos , Exossomos/metabolismo , Animais , Artrite Reumatoide/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , RNA Circular/genética , Humanos , Biomarcadores/sangue , Sinoviócitos/metabolismo , Artrite Experimental/imunologia , Artrite Experimental/sangue , Artrite Experimental/genética , Masculino , Camundongos , Feminino , Proliferação de Células , Células Cultivadas , Movimento Celular , Pessoa de Meia-Idade
8.
Int Immunopharmacol ; 133: 112074, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615383

RESUMO

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.


Assuntos
Antígeno B7-H1 , Neoplasias Encefálicas , Glioma , Microglia , Receptor de Morte Celular Programada 1 , Animais , Humanos , Masculino , Camundongos , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Glioma/metabolismo , Glioma/patologia , Glioma/imunologia , Microglia/metabolismo , Microglia/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral/imunologia
9.
Arch Gynecol Obstet ; 309(4): 1629-1641, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38315199

RESUMO

PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.


Assuntos
Blastocisto , Nascido Vivo , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Taxa de Gravidez , Transferência Embrionária , Criopreservação , Vitrificação
10.
J Chem Inf Model ; 64(5): 1704-1718, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38411104

RESUMO

The proline biosynthetic enzyme Δ1-pyrroline-5-carboxylate (P5C) reductase 1 (PYCR1) is one of the most consistently upregulated enzymes across multiple cancer types and central to the metabolic rewiring of cancer cells. Herein, we describe a fragment-based, structure-first approach to the discovery of PYCR1 inhibitors. Thirty-seven fragment-like carboxylic acids in the molecular weight range of 143-289 Da were selected from docking and then screened using X-ray crystallography as the primary assay. Strong electron density was observed for eight compounds, corresponding to a crystallographic hit rate of 22%. The fragments are novel compared to existing proline analog inhibitors in that they block both the P5C substrate pocket and the NAD(P)H binding site. Four hits showed inhibition of PYCR1 in kinetic assays, and one has lower apparent IC50 than the current best proline analog inhibitor. These results show proof-of-concept for our inhibitor discovery approach and provide a basis for fragment-to-lead optimization.


Assuntos
Pirrolina Carboxilato Redutases , delta-1-Pirrolina-5-Carboxilato Redutase , Pirrolina Carboxilato Redutases/química , Pirrolina Carboxilato Redutases/metabolismo , Cristalografia por Raios X , Sítios de Ligação , Prolina
11.
Ren Fail ; 46(1): 2312533, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38391179

RESUMO

OBJECTIVES: Currently, there is no consensus on the optimal timing for the initiation of peritoneal dialysis (PD) after catheter placement. DESIGN: Systematic review and meta-analysis. EXACT DATE OF DATA COLLECTION: From inception till July 31, 2023. MAIN OUTCOME MEASURES: To assess the outcomes and safety of unplanned PD initiation (<14/7 days after catheter insertion) in cohort studies. RESULTS: Fifteen studies involving 3054 participants were included. (1) The risk of unplanned initiation of leakage and Obstruction was no difference in both the break-in period (BI) <14 and BI < 7 groups. (2) Catheter displacement was more likely to occur in the emergency initiation group with BI < 7. (3) No significant differences were observed between the two groups regarding infectious complications. (4) There was no difference in transition to HD between patients with BI < 7 and BI < 14 d. CONCLUSION: Infectious complications of unplanned initiation of peritoneal dialysis did not differ from planned initiation. Emergency initiation in the BI < 7 group had higher catheter displacement, but heterogeneity was higher. There were no differences in leakage or obstruction in either group. Catheter survival was the same for emergency initiation of peritoneal dialysis compared with planned initiation of peritoneal dialysis and did not increase the risk of conversion to hemodialysis. REGISTRATION: This meta-analysis was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023431369).


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Humanos , Estudos de Coortes , Falência Renal Crônica/terapia , Prognóstico , Diálise Renal
12.
J Nutr ; 154(1): 252-260, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38035998

RESUMO

BACKGROUND: It remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype. OBJECTIVES: We aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE ε4 allele could modify this association. METHODS: The study included 16,736 participants from the Singapore Chinese Health Study. The PHD score was calculated using data from a validated 165-item food frequency questionnaire at baseline (1993-1998), with higher scores indicating greater adherence to the PHD. Cognitive function was assessed by the Singapore-modified Mini-Mental State Examination at follow-up 3 visits (2014-2016). A subset of 9313 participants had APOE genotype data. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders. RESULTS: We identified 2397 (14.3%) cases of poor cognitive function. In the total population, OR (95% CI) of poor cognitive function for each one-SD increment in the PHD score was 0.89 (0.85, 0.93). Carriers of APOE ε4 allele had increased risk of poor cognitive function (OR: 1.36, 95% CI: 1.15, 1.61). There was a significant interaction between the PHD score and the APOE ε4 allele (P-interaction = 0.042). Each one-SD increment in the PHD score was significantly associated with lower risk of poor cognitive function (OR: 0.89; 95% CI: 0.83, 0.96) in non-carriers of APOE ε4 allele, but not in APOE ε4 allele carriers (OR: 1.04, 95% CI: 0.89, 1.23). CONCLUSIONS: Midlife adherence to the PHD was associated with reduced risk of poor cognitive function in later life. However, this was not observed in carriers of APOE ε4 allele who had higher risk of poor cognitive function.


Assuntos
Apolipoproteína E4 , Dieta Saudável , Adulto , Humanos , Apolipoproteína E4/genética , Singapura , Testes Neuropsicológicos , Apolipoproteínas E/genética , Cognição , Genótipo , Alelos
13.
J Biophotonics ; 17(4): e202300287, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38040667

RESUMO

Given the significant therapeutic efficacy of anti-HER-2 treatment, the HER-2 status is a crucial piece of information that must be obtained in breast cancer patients. Currently, as per guidelines, HER-2 status is typically acquired from breast tissue of patients. However, there is growing interest in obtaining HER-2 status from serum and other samples due to the convenience and potential for dynamic monitoring. In this study, we have developed a serum Raman spectroscopy technique that allows for the rapid acquisition of HER-2 status in a convenient manner. The established HER-2 negative and positive classification model achieved an area under the curve of 0.8334. To further validate the reliability of our method, we replicated the process using immunohistochemistry and in situ hybridization. The results demonstrate that serum Raman spectroscopy, coupled with artificial intelligence algorithms, is an effective technical approach for obtaining HER-2 status.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Inteligência Artificial , Reprodutibilidade dos Testes , Análise Espectral Raman , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapêutico , Hibridização In Situ
14.
Arthritis Rheumatol ; 76(4): 599-613, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37946666

RESUMO

OBJECTIVE: The peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown. METHODS: We performed single-cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified patients with SLE into two groups: early B cell (Pro-B and Pre-B) normal (EBnor) and EB defective/low (EBlo) groups. RESULTS: The SLE-EBlo group exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE-EBnor group. Moreover, in one patient with SLE who was initially classified in the SLE-EBlo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase. CONCLUSION: In summary, this study suggests that early B cell loss in BM defines a unique pathological state in a subset of patients with SLE that may play an active role in the dysregulated autoimmune responses.


Assuntos
Medula Óssea , Lúpus Eritematoso Sistêmico , Humanos , Criança , Medula Óssea/patologia , Deficiências do Desenvolvimento/metabolismo , Deficiências do Desenvolvimento/patologia , Linfócitos B , Transdução de Sinais
15.
Z Rheumatol ; 83(Suppl 1): 40-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37079036

RESUMO

OBJECTIVE: To assess the effects of exercise intervention on depression in rheumatic diseases by means of a meta-analysis. METHODS: The Cochrane Library, Embase, Medline, PubMed, and relevant records were searched. The qualities of randomized controlled trials were evaluated. Meta-analysis of the obtained related data was completed using RevMan 5.3. Heterogeneity was also evaluated with χ2 test and I2. RESULTS: Twelve RCTs were reviewed. Compared with baseline, the meta-analysis results showed that there was significant difference in the improvement of depression assessed by HADs, BDI, CES­D, and AIMS in patients with rheumatic diseases (post exercise vs. baseline, -0.73 [-1.05, -0.4], P < 0.0001, I2 = 0%). In subgroup analysis, although none of these trends in BDI and CES­D subgroups were significant at P < 0.05, there were clear trends towards improvement in depression. CONCLUSION: As an alternative or supplementary treatment, the effect of exercise on rheumatism is obvious. Rheumatologists can consider exercise as an integral part of the treatment of patients with rheumatism.


Assuntos
Depressão , Doenças Reumáticas , Humanos , Depressão/diagnóstico , Depressão/terapia , Exercício Físico , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/terapia
16.
J Magn Reson Imaging ; 59(4): 1206-1217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37526043

RESUMO

BACKGROUND: Tertiary lymphoid structures (TLSs) are potential prognostic indicators. Radiomics may help reduce unnecessary invasive operations. PURPOSE: To analyze the association between TLSs and prognosis, and to establish a nomogram model to evaluate the expression of TLSs in breast cancer (BC) patients. STUDY TYPE: Retrospective. POPULATION: Two hundred forty-two patients with localized primary BC (confirmed by surgery) were divided into BC + TLS group (N = 122) and BC - TLS group (N = 120). FIELD STRENGTH/SEQUENCE: 3.0T; Caipirinha-Dixon-TWIST-volume interpolated breath-hold sequence for dynamic contrast-enhanced (DCE) MRI and inversion-recovery turbo spin echo sequence for T2-weighted imaging (T2WI). ASSESSMENT: Three models for differentiating BC + TLS and BC - TLS were developed: 1) a clinical model, 2) a radiomics signature model, and 3) a combined clinical and radiomics (nomogram) model. The overall survival (OS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were compared to evaluate the prognostic value of TLSs. STATISTICAL TESTS: LASSO algorithm and ANOVA were used to select highly correlated features. Clinical relevant variables were identified by multivariable logistic regression. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), and through decision curve analysis (DCA). The Kaplan-Meier method was used to calculate the survival rate. RESULTS: The radiomics signature model (training: AUC 0.766; test: AUC 0.749) and the nomogram model (training: AUC 0.820; test: AUC 0.749) showed better validation performance than the clinical model. DCA showed that the nomogram model had a higher net benefit than the other models. The median follow-up time was 52 months. While there was no significant difference in 3-year OS (P = 0.22) between BC + TLS and BC - TLS patients, there were significant differences in 3-year DFS and 3-year DMFS between the two groups. DATA CONCLUSION: The nomogram model performs well in distinguishing the presence or absence of TLS. BC + TLS patients had higher long-term disease control rates and better prognoses than those without TLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.


Assuntos
Neoplasias da Mama , Estruturas Linfoides Terciárias , Humanos , Feminino , Prognóstico , Neoplasias da Mama/diagnóstico por imagem , Radiômica , Estudos Retrospectivos , Imageamento por Ressonância Magnética
17.
Bioorg Chem ; 142: 106955, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924754

RESUMO

Three new ergosterol derivatives brassisterol A-C (1-3) and two new epimeric bicycle-lactones brassictones A and B (4 and 5), were isolated from the co-cultivation of Alternaria brassicicola and Penicillium granulatum. The absolute configurations of these isolates were confirmed by extensive NMR spectra, TD-DFT ECD calculation, and the single crystal XRD data analysis. Amongst the metabolites, compound 1 exhibited potential anti-Parkinson's disease activity in both MPTP-induced zebrafish and MPP+-induced SH-SY5Y cells. Molecular mechanism studies in vitro showed that 1 attenuated the increase of α-synuclein, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and GSDMD expression in the MPP+ induced PD model. Molecular docking in silico simulations exhibited that 1 was well accommodated to one of the binding pockets of NLRP3 8ETR in an appropriate conformation via forming typical hydrogen bonds as well as possessing a high negative binding affinity (-8.97 kcal/mol). Thus, our work suggested that 1 protected dopaminergic cell from neuroinflammation via targeting NLRP3/caspase-1/GSDMD signaling pathway.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Neuroblastoma , Animais , Humanos , Caspase 1/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Simulação de Acoplamento Molecular , Peixe-Zebra/metabolismo , Fungos/metabolismo , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros
18.
Photodiagnosis Photodyn Ther ; 45: 103954, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145772

RESUMO

Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment.


Assuntos
Arthrodermataceae , Fotoquimioterapia , Tinha do Couro Cabeludo , Adulto , Humanos , Antifúngicos/uso terapêutico , Ácido Aminolevulínico/uso terapêutico , Úlcera , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
19.
Int J Rheum Dis ; 26(12): 2419-2429, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37849430

RESUMO

OBJECTIVE: This study aims to explore the status and influencing factors of fertility intention in women of childbearing age with systemic lupus erythematosus (SLE). METHODS: A total of 158 SLE patients admitted to the Affiliated Hospital of Nantong University from February 2021 to February 2022 were selected for a cross-sectional study. The dependent variable in this study was the fertility intention of lupus women of childbearing age, so the questionnaire was selected: "In view of your disease, do you plan to have children? Yes/no" as the measurement statement. Lupus patients were divided into fertility intention groups and non-fertility intention groups. The questionnaire survey comprises following scales: Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), and others. Independent t-test, one-way ANOVA, Mann-Whitney U test, and binary logistic regression were used for analysis. RESULTS: The results showed that 20.9% of lupus patients in this study had a fertility intention. The fertility intention was associated with age, reproductive history, reproductive concerns, sexual distress, fatigue, family function, social support, depression, and sleep. Binary logistic regression showed that physical fatigue (OR 3.56, 95% CI 1.048-12.07) and personal health (OR 2.50, 95% CI 1.065-5.853) had significant predictors of fertility intention. CONCLUSION: Our study identified a lower fertility intention in SLE patients who had reproductive concerns, sexual distress, family dysfunction, and fatigue. We encourage healthcare institutions to provide counseling services to all the SLE patients who have fertility intention and focus more on those who have requirements for fertility.


Assuntos
Intenção , Lúpus Eritematoso Sistêmico , Criança , Humanos , Feminino , Estudos Transversais , Qualidade de Vida , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Fadiga/psicologia , Fertilidade
20.
JAMA Netw Open ; 6(10): e2339468, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37874563

RESUMO

Importance: Although the EAT-Lancet Commission has recently proposed a planetary health diet (PHD) to promote human and environmental health, little is known about how PHD affects environment and mortality risk among an Asian population. Objective: To investigate whether a PHD score is associated with environmental impacts and mortality outcomes in a Chinese cohort living in Singapore. Design, Setting, and Participants: This cohort study used data from the Singapore Chinese Health Study. Eligible participants were without known cardiovascular disease and cancer at baseline; they were recruited between 1993 and 1998 and followed up using record linkage data until 2020. Data were analyzed from September 2022 to April 2023. Exposures: PHD score was calculated based on the reference consumption of 14 dietary components in PHD and individual energy intake assessed using a validated food frequency questionnaire in this cohort. Main Outcomes and Measures: Diet-related environmental impacts were estimated using a food frequency questionnaire. Mortality outcomes (all-cause, cardiovascular disease, cancer, and respiratory disease) were identified via linkage with a nationwide registry. Results: A total of 57 078 participants were included in this study (mean [SD] age, 56.1 (7.9) years; 31 958 women [56.0%]). During a median (IQR) follow-up of 23.4 (18.7-26.2) years, 22 599 deaths occurred. Comparing the highest and lowest quintiles, higher PHD scores were associated with lower greenhouse gas emissions (ß = -0.13 kg CO2 equivalent; 95% CI, -0.14 to -0.12 kg CO2 equivalent), but with higher total water footprint (ß = 0.12 m3; 95% CI, 0.11-0.13 m3) and land use (ß = 0.29 m2; 95% CI, 0.28-0.31 m2). In the adjusted multivariable model, compared with the lowest quintile, participants in the highest quintile of PHD score had lower risk of all-cause mortality (hazard ratio [HR], 0.85; 95% CI, 0.81-0.89), cardiovascular disease mortality (HR, 0.79; 95% CI, 0.73-0.85), cancer mortality (HR, 0.93; 95% CI, 0.86-1.00), and respiratory disease mortality (HR, 0.81; 95% CI, 0.74-0.89). Conclusions and Relevance: In this study of Singapore Chinese adults, higher adherence to PHD was associated with reduced risk of chronic disease mortality. However, environmental impacts were uncertain, as higher adherence was associated with lower greenhouse gas emissions but higher total water footprint and land use.


Assuntos
Doenças Cardiovasculares , Gases de Efeito Estufa , Neoplasias , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Dióxido de Carbono , Estudos Prospectivos , Dieta , Meio Ambiente , Água
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