Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 171
Filtrar
1.
Medicine (Baltimore) ; 103(29): e38905, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029047

RESUMO

The assessment of patient satisfaction following cataract surgery is heavily reliant on the evaluation of visual quality, specifically after the placement of diffractive multifocal intraocular lenses (MIOLs) under varying pupil conditions. The objective of this study was to examine the visual and optical clarity following cataract phacoemulsification and the use of Tecnis ZMB00 MIOL for implantation. The study involved 116 individuals (135 eyes) who received cataract phacoemulsification and underwent Tecnis ZMB00 MIOL implantation. Assessments were conducted 1 week and 3 months after the surgery. These assessments involved measuring uncorrected and corrected visual acuity for distant, intermediate, and near vision. Additionally, scatter light values and wavefront aberrations were measured under different aperture settings of 3 and 5 mm. There was no noticeable disparity in visual acuity between 1 week and 3 months after the surgery. After 3 months of surgery, there was a considerable decrease in scatter light values and spherical aberrations compared to the values observed 1 week after surgery, under the setting of a 5 mm aperture. Moreover, the modulation transfer function values showed a significant rise after 3 months following the surgery, particularly under the 5 mm aperture condition. The most substantial increase was observed at the intermediate spatial frequency of 20 cycles per degree (cpd), in comparison to the values obtained 1 week after the operation. The combination of cataract phacoemulsification and Tecnis ZMB00 MIOL implantation yielded favorable visual acuity at various distances for patients. Furthermore, enhancements in the measurements of scattered light, higher-order aberrations, and modulation transfer function values were noted 3 months after the surgical procedure, specifically under the condition of a 5 mm pupil. These findings suggest an increase in visual clarity and night vision to a certain degree.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares Multifocais , Facoemulsificação , Acuidade Visual , Humanos , Facoemulsificação/métodos , Feminino , Masculino , Idoso , Implante de Lente Intraocular/métodos , Pessoa de Meia-Idade , Satisfação do Paciente , Idoso de 80 Anos ou mais
2.
Biochem Biophys Res Commun ; 724: 150221, 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-38865811

RESUMO

MYB is a key regulator of hematopoiesis and erythropoiesis, and dysregulation of MYB is closely involved in the development of leukemia, however the mechanism of MYB regulation remains still unclear so far. Our previous study identified a long noncoding RNA (lncRNA) derived from the -34 kb enhancer of the MYB locus, which can promote MYB expression, the proliferation and migration of human leukemia cells, and is therefore termed MY34UE-AS. Then the interacting partner proteins of MY34UE-AS were identified and studied in the present study. hnRNPA0 was identified as a binding partner of MY34UE-AS through RNA pulldown assay, which was further validated through RNA immunoprecipitation (RIP). hnRNPA0 interacted with MY34UE-AS mainly through its RRM2 domain. hnRNPA0 overexpression upregulated MYB and increased the proliferation and migration of K562 cells, whereas hnRNPA0 knockdown showed opposite effects. Rescue experiments showed MY34UE-AS was required for above mentioned functions of hnRNPA0. These results reveal that hnRNPA0 is involved in leukemia through upregulating MYB expression by interacting with MY34UE-AS, suggesting that the hnRNPA0/MY34UE-AS axis could serve as a potential target for leukemia treatment.


Assuntos
Proliferação de Células , Leucemia , Proteínas Proto-Oncogênicas c-myb , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Elementos Facilitadores Genéticos , Regulação Leucêmica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Células K562 , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
3.
J Chem Phys ; 160(21)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38832737

RESUMO

High voltage power capacitors employ the oil-impregnated polypropylene film as the insulation. The swelling phenomenon might drive the antioxidants and small molecules within the film to migrate into the oil. It is necessary to comprehensively investigate the physical migration mechanism of antioxidants and their impact on the electrical performance of the oil-film combination insulation system and, consequently, formulate the proper selective prescription of antioxidants. Theoretical elucidation of the competitive interaction mechanism between the film and the oil in attracting antioxidant molecules was achieved through the calculation of inter-molecular binding energy, and the migration coefficient ηm was introduced to quantify the migration characteristics of antioxidants. Experimentally, the effects of antioxidants on the space charge distribution of the film, the dielectric properties of the oil, and the breakdown characteristics of both the film and oil were investigated. The experimental conclusions are consistent with theoretical analysis. The lamellar structure antioxidant molecules with ηm > 1 tend to migrate from the film to the oil, which results in increased dielectric loss and decreased breakdown strength of the insulating oil. In addition, the presence of phosphorus atoms in phosphite antioxidants contributes to a reduction in the breakdown strength of the film. For capacitor grade polypropylene film, in addition to the synergistic effect between different types of antioxidants on the thermo-oxidative stability, the structure of the antioxidant molecules and its influence on the electrical performance of the oil-film systems should also be taken into account.

4.
Chemosphere ; 361: 141485, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38438022

RESUMO

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.


Assuntos
Bronquite Crônica , Enfisema , Inflamação , Inquéritos Nutricionais , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/urina , Bronquite Crônica/urina , Bronquite Crônica/epidemiologia , Humanos , Enfisema/urina , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Inflamação/urina , Teorema de Bayes , Idoso , Poluentes Atmosféricos/urina , Poluentes Atmosféricos/análise , Modelos Logísticos , Exposição Ambiental/estatística & dados numéricos
5.
Nephrol Dial Transplant ; 39(10): 1642-1648, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-38373839

RESUMO

BACKGROUND: Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear. METHODS: This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines. RESULTS: The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101-2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135-27.035; P = .034) for the higher levels group. CONCLUSIONS: Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN.


Assuntos
Complemento C4b , Progressão da Doença , Taxa de Filtração Glomerular , Glomerulonefrite por IGA , Fragmentos de Peptídeos , Humanos , Masculino , Feminino , Adulto , Glomerulonefrite por IGA/urina , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/complicações , Complemento C4b/urina , Seguimentos , Fragmentos de Peptídeos/urina , Prognóstico , Estudos de Casos e Controles , Pessoa de Meia-Idade , Imunoglobulina A/urina , Vasculite/urina , Vasculite/etiologia , Vasculite/patologia , Biomarcadores/urina , Glomerulosclerose Segmentar e Focal/urina , Glomerulosclerose Segmentar e Focal/patologia
6.
Eur J Med Res ; 29(1): 73, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268058

RESUMO

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is one of prevalent kidney malignancies with an unfavorable prognosis. There is a need for a robust model to predict ccRCC patient survival and guide treatment decisions. METHODS: RNA-seq data and clinical information of ccRCC were obtained from the TCGA and ICGC databases. Expression profiles of genes related to natural killer (NK) cells were collected from the Immunology Database and Analysis Portal database. Key NK cell-related genes were identified using consensus clustering algorithms to classify patients into distinct clusters. A NK cell-related risk model was then developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to predict ccRCC patient prognosis. The relationship between the NK cell-related risk score and overall survival, clinical features, tumor immune characteristics, as well as response to commonly used immunotherapies and chemotherapy, was explored. Finally, the NK cell-related risk score was validated using decision tree and nomogram analyses. RESULTS: ccRCC patients were stratified into 3 molecular clusters based on expression of NK cell-related genes. Significant differences were observed among the clusters in terms of prognosis, clinical characteristics, immune infiltration, and therapeutic response. Furthermore, six NK cell-related genes (DPYSL3, SLPI, SLC44A4, ZNF521, LIMCH1, and AHR) were identified to construct a prognostic model for ccRCC prediction. The high-risk group exhibited poor survival outcomes, lower immune cell infiltration, and decreased sensitivity to conventional chemotherapies and immunotherapies. Importantly, the quantitative real-time polymerase chain reaction (qRT-PCR) confirmed significantly high DPYSL3 expression and low SLC44A4 expression in ACHN cells. Finally, the decision tree and nomogram consistently show the dramatic prediction performance of the risk score on the survival outcome of the ccRCC patients. CONCLUSIONS: The six-gene model based on NK cell-related gene expression was validated and found to accurately mirror immune microenvironment and predict clinical outcomes, contributing to enhanced risk stratification and therapy response for ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Prognóstico , Nomogramas , Carcinoma de Células Renais/genética , Células Matadoras Naturais , Neoplasias Renais/genética , Microambiente Tumoral/genética
7.
Natl Sci Rev ; 11(2): nwad286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213521

RESUMO

Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG).

8.
Eur J Med Res ; 29(1): 22, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183155

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized as one of the most common types of urological cancer with high degrees of malignancy and mortality. Due to the limited effectiveness of existing traditional therapeutic methods and poor prognosis, the treatment and therapy of advanced ccRCC patients remain challenging. Tryptophan metabolism has been widely investigated because it significantly participates in the malignant traits of multiple cancers. The functions and prognostic values of tryptophan metabolism-related genes (TMR) in ccRCC remain virtually obscure. METHODS: We employed the expression levels of 40 TMR genes to identify the subtypes of ccRCC and explored the clinical characteristics, prognosis, immune features, and immunotherapy response in the subtypes. Then, a model was constructed for the prediction of prognosis based on the differentially expressed genes (DEGs) in the subtypes from the TCGA database and verified using the ICGC database. The prediction performance of this model was confirmed by the receiver operating characteristic (ROC) curves. The relationship of Risk Score with the infiltration of distinct tumor microenvironment cells, the expression profiles of immune checkpoint genes, and the treatment benefits of immunotherapy and chemotherapy drugs were also investigated. RESULTS: The two subtypes revealed dramatic differences in terms of clinical characteristics, prognosis, immune features, and immunotherapy response. The constructed 6-gene-based model showed that the high Risk Score was significantly connected to poor overall survival (OS) and advanced tumor stages. Furthermore, increased expression of CYP1B1, KMO, and TDO2 was observed in ccRCC tissues at the translation levels, and an unfavorable prognosis for these patients was also found. CONCLUSION: We identified 2 molecular subtypes of ccRCC based on the expression of TMR genes and constructed a prognosis-related model that may be used as a powerful tool to guide the prediction of ccRCC prognosis and personalized therapy. In addition, CYP1B1, KMO, and TDO2 can be regarded as the risk prognostic genes for ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Triptofano , Imunoterapia , Neoplasias Renais/genética , Microambiente Tumoral
9.
J Virol ; 98(1): e0167023, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38088561

RESUMO

Lactate, traditionally considered a metabolic by-product, has recently been identified as a substrate for the induction of lactylation, a newly identified epigenetic modification that plays an important role in the regulation of host gene expression. Our previous study showed that lactate levels were significantly elevated in cells infected with the porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has devastated the swine industry worldwide for over 30 years. However, the role of elevated lactate in PRRSV infections remains unknown. In this study, we found that lactate was required for optimal PRRSV proliferation, and PRRSV infection increased cellular lactylation in a dose-dependent manner. Using the Cleavage Under Targets and Tagmentation (CUT&Tag) combined with RNA sequencing (RNA-seq) to screen the downstream genes regulated by lactylation in PRRSV-infected cells, we found that PRRSV-induced lactylation activated the expression of heat shock 70 kDa protein 6 (HSPA6). Follow-up experiments showed that HSPA6 is important for PRRSV proliferation by negatively modulating interferon (IFN)-ß induction. Mechanistically, HSPA6 impeded the interaction between TNF-receptor-associated factor 3 (TRAF3) and inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε), thereby hindering the production of IFN-ß. Taken together, these results indicate that the activated lactate-lactylation-HSPA6 axis promotes viral growth by impairing IFN-ß induction, providing new therapeutic targets for the prevention and control of PRRSV infection. The results presented here also link lactylation to the virus life cycle, improving our understanding of epigenetic regulation in viral infection.IMPORTANCEAs a newly identified epigenetic modification, lactate-induced lactylation has received attentions because it plays important roles in gene expression and contributes to tumorigenesis and the innate immune response. Previous studies showed that many viruses upregulate cellular lactate levels; however, whether virus-elevated lactate induces lactylation and the subsequent biological significance of the modification to viral infection have not been reported. In this study, we demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection induced cellular lactylation, which, in turn, upregulated the expression of HSPA6, an IFN-negative regulator. We also dissected the mechanism by which HSPA6 negatively regulates IFN-ß production. To our knowledge, this is the first report to study virus-induced lactylation and establish the relationship between lactylation and virus infection.


Assuntos
Ácido Láctico , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Epigênese Genética , Expressão Gênica , Ácido Láctico/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Suínos , Replicação Viral
10.
Talanta ; 270: 125521, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091750

RESUMO

As the most common cause of liver diseases, nonalcoholic fatty liver disease (NAFLD) can be classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). While NAFL is generally benign, the transition from NAFL to NASH is a cardinal feature of the non-benign liver disease that leads to cirrhosis and cancer, which indicates that tracking the transformation of NAFL to NASH timely is significant for precision management of liver diseases. Therefore, two fluorescent probes (CNFCl and DRNO) have been developed to visualize this pathological event. α-Fluorochloroacetamide and α-ketoamide was employed as the recognition site for carboxylesterase (CE) in CNFCl and peroxynitrite (ONOO-) in DRNO, respectively. CNFCl (λem = 445 nm) and DRNO (λem = 560 nm) showed high specificity and sensitivity towards CE and ONOO- respectively. By incubating with CE/ONOO- for 0.5 h respectively, both the emission intensity of CNFCl (linear range: 0-0.2 U/mL) and DRNO (linear range: 0-17.5 µM) displayed significant enhancement. As a result, the detection limit of CNFCl and DRNO for CE and ONOO- was calculated as 4.2 mU/L and 0.05 µM respectively. More importantly, the emission spectra of CNFCl and DRNO in the presence of CE and ONOO- respectively were cross-talk free under the two-photon excitation of 720 nm. This greatly facilitated the simultaneous detection of CE and ONOO- at distinctive channel, thus ensuring the high fidelity of the detection. These two probes were combined to image the fluctuation of CE and ONOO- during the conversion of NAFL to NASH in vitro and in vivo. It was found that while CE displayed a tendency to rise and then reduce during the transition from NAFL to NASH, ONOO- increased continuously, confirming that the combined imaging by CNFCl and DRNO might visualize the transformation of NAFL to NASH. The results provide robust visual tool to decipher the relationship between the stage of NAFLD and the level of CE/ONOO-. We anticipate this study may open new avenues to distinguish NASH from NAFL, which may further promote the study of intracellular biological activities of CE and the development of NAFLD diagnostic methods.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Corantes Fluorescentes , Fígado/diagnóstico por imagem , Fígado/patologia , Hidrolases de Éster Carboxílico
11.
ESC Heart Fail ; 11(1): 503-512, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38083998

RESUMO

AIMS: Circulating biomarkers can provide important information for the diagnosis and prognosis of dilated cardiomyopathy (DCM). We explored novel biomarkers for the diagnosis and prognosis of DCM to improve clinical decision-making. METHODS AND RESULTS: A total of 238 DCM patients and 65 control were consecutively enrolled at Zhongshan Hospital between January 2017 and January 2019. In the screening set, four DCM patients and four controls underwent measurements of serum proteomic analysis. Seventy-six differentially expressed circulating proteins were screened by data-independent acquisition proteomics, and three of these proteins (S100A4, S100A8/A9, and S100A12) were validated by multiple-reaction monitoring-mass spectrometry. In the validation set, subsequently, a total of 234 DCM patients and 61 control subjects were evaluated by enzyme-linked immunosorbent assay. Circulating S100A4, S100A8/A9, and S100A12 were significantly increased in DCM patients (P < 0.001). These three proteins were significant positively correlated with other parameters, such as Lg (NT-proBNP), IL-1ß, TGF-ß, CRP, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter, whereas they were negatively correlated with left ventricular ejection fraction, respectively (P < 0.05). The receiver operator characteristic curve showed the combination of S100A4, S100A8/A9, and S100A12 [area under curve (AUC) 0.88, 95% confidence interval (CI) 0.84-0.93] was better than single S100A4 (AUC 0.74, 95% CI 0.68-0.81), S100A8/A9 (AUC 0.82, 95% CI 0.77-0.88), or S100A12 (AUC 0.80, 95% CI 0.72-0.88) in the diagnosis of DCM (P < 0.01). After a median follow-up period of 33.5 months, 110 patients (47.01%) experienced major adverse cardiac events (MACEs), including 46 who had cardiac deaths and 64 who had heart failure rehospitalizations. Kaplan-Meier analysis indicated that the DCM patients with ≥75th percentile level of S100A4 had a significantly higher incidence of MACEs than those with <75th percentile level of S100A4 (61.40% vs. 42.37%, P < 0.05). There were no significant differences of MACE rate among DCM patients with different concentrations of S100A8/A9 and S100A12 (P > 0.05). Cox proportional hazards regression analysis revealed that S100A4 [≥75th percentile vs. <75th percentile: hazard ratio (HR) 1.65; 95% CI 1.11-2.45] remained significant independent predictors for MACEs (P < 0.05); however, S100A8/A9 and S100A12 were not independent factors for predicting MACE (P ≥ 0.05). CONCLUSIONS: S100A4, S100A8/A9, and S100A12 may be additional diagnostic tools for human DCM recognition, and the combination of these three indicators helped to improve the accuracy of a single index to diagnose DCM. Additionally, S100A4 was identified as a significant predictor of prognosis in patients with DCM.


Assuntos
Cardiomiopatia Dilatada , Proteína S100A12 , Humanos , Proteína S100A12/metabolismo , Projetos Piloto , Calgranulina B , Volume Sistólico , Cardiomiopatia Dilatada/diagnóstico , Proteômica , Função Ventricular Esquerda , Calgranulina A , Prognóstico , Biomarcadores , Proteína A4 de Ligação a Cálcio da Família S100
12.
BMC Genomics ; 24(1): 525, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670254

RESUMO

BACKGROUND: The incidence of kidney disease caused by thyroid cancer is rising worldwide. Observational studies cannot recognize whether thyroid cancer is independently associated with kidney disease. We performed the Mendelian randomization (MR) approach to genetically investigate the causality of thyroid cancer on immunoglobulin A nephropathy (IgAN). METHODS AND RESULTS: We explored the causal effect of thyroid cancer on IgAN by MR analysis. Fifty-two genetic loci and single nucleotide polymorphisms were related to thyroid cancer. The primary approach in this MR analysis was the inverse variance weighted (IVW) method, and MR‒Egger was the secondary method. Weighted mode and penalized weighted median were used to analyze the sensitivity. In this study, the random-effect IVW models showed the causal impact of genetically predicted thyroid cancer across the IgAN risk (OR, 1.191; 95% CI, 1.131-1.253, P < 0.001). Similar results were also obtained in the weighted mode method (OR, 1.048; 95% CI, 0.980-1.120, P = 0.179) and penalized weighted median (OR, 1.185; 95% CI, 1.110-1.264, P < 0.001). However, the MR‒Egger method revealed that thyroid cancer decreased the risk of IgAN, but this difference was not significant (OR, 0.948; 95% CI, 0.855-1.051, P = 0.316). The leave-one-out sensitivity analysis did not reveal the driving influence of any individual SNP on the association between thyroid cancer and IgAN. CONCLUSION: The IVW model indicated a significant causality of thyroid cancer with IgAN. However, MR‒Egger had a point estimation in the opposite direction. According to the MR principle, the evidence of this study did not support a stable significant causal association between thyroid cancer and IgAN. The results still need to be confirmed by future studies.


Assuntos
Glomerulonefrite por IGA , Neoplasias da Glândula Tireoide , Humanos , Análise da Randomização Mendeliana , Loci Gênicos , Polimorfismo de Nucleotídeo Único
13.
Free Radic Biol Med ; 208: 430-444, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37660839

RESUMO

Exploring the immune mechanism of coxsackievirus B3 (CVB3)-induced myocarditis may provide a promising therapeutic strategy. Here, we investigated the regulatory role of macrophage CAPN4 in the phenotypic transformation of macrophages and NOD-like receptor protein 3 (NLRP3) inflammasome activation. We found that CAPN4 was the most upregulated subtype of the calpain family in CVB3-infected bone marrow-derived macrophages (BMDMs) and Raw 264.7 cells after CVB3 infection and was upregulated in cardiac macrophages from CVB3-infected mice. Conditional knockout of CAPN4 (CAPN4flox/flox; LYZ2-Cre, CAPN4-cKO mice) ameliorated inflammation and myocardial injury and improved cardiac function and survival after CVB3 infection. Enrichment analysis revealed that macrophage differentiation and the interleukin signaling pathway were the most predominant biological processes in macrophages after CVB3 infection. We further found that CVB3 infection and the overexpression of CAPN4 promoted macrophage M1 polarization and NLRP3 inflammasome activation, while CAPN4 knockdown reversed these changes. Correspondingly, CAPN4-cKO alleviated CVB3-induced M1 macrophage transformation and NLRP3 expression and moderately increased M2 transformation in vivo. The culture supernatant of CAPN4-overexpressing or CVB3-infected macrophages impaired cardiac fibroblast function and viability. Moreover, macrophage CAPN4 could upregulate C/EBP-homologous protein (chop) expression, which increased proinflammatory cytokine release by activating the phosphorylation of transducer of activator of transcription 1 (STAT1) and 3 (STAT3). Overall, these results suggest that CAPN4 increases M1-type and inhibits M2-type macrophage polarization through the chop-STAT1/STAT3 signaling pathway to mediate CVB3-induced myocardial inflammation and injury. CAPN4 may be a novel target for viral myocarditis treatment.


Assuntos
Infecções por Coxsackievirus , Inflamassomos , Miocardite , Animais , Camundongos , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/metabolismo , Enterovirus Humano B/metabolismo , Inflamassomos/metabolismo , Inflamação/genética , Inflamação/metabolismo , Macrófagos/metabolismo , Miocardite/genética , Miocardite/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo
14.
Digit Health ; 9: 20552076231185280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456128

RESUMO

Eliminating the NOx emission after coal combustion is a critical task for thermal power plants to reduce threats to the human body, such as respiratory diseases, heart disease, lung disease and even lung cancer. To this end, various treatments have been taken to optimize, monitor and control the combustion process. However, optimizing the coal composition prior to combustion can further reduce possible NOx emissions. This topic was rarely discussed in the past. To fill this gap, this study proposes a fuzzy big data analytics approach. The proposed methodology combines recursive feature elimination, fuzzy c-means, XG Boost, support vector regression, random forests, decision trees and deep neural networks to predict post-combustion NOx emission based on coal composition and specification. Subsequently, additional treatments can be implemented to optimize boiler configuration and combustion conditions with pollution prevention equipment. In other words, the method proposed in this study is a kind of pretreatment. The proposed methodology has been applied to the real case of a thermal power plant in Taiwan. Experimental results showed that the prediction accuracy using the proposed methodology was significantly better than several existing methods. The forecasting error, measured in terms of root mean square error and mean absolute percentage error, was only 14.55 ppm and 8.9%, respectively.

15.
Molecules ; 28(14)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37513241

RESUMO

Biofilm-associated infections exert more severe and harmful attacks on human health since they can accelerate the generation and development of the antibiotic resistance of the embedded bacteria. Anti-biofilm materials and techniques that can eliminate biofilms effectively are in urgent demand. Therefore, we designed a type I photosensitizer (TTTDM) with an aggregation-induced emission (AIE) property and used F-127 to encapsulate the TTTDM into nanoparticles (F-127 AIE NPs). The NPs exhibit highly efficient ROS generation by enhancing intramolecular D-A interaction and confining molecular non-radiative transitions. Furthermore, the NPs can sufficiently penetrate the biofilm matrix and then detect and eliminate mature bacterial biofilms upon white light irradiation. This strategy holds great promise for the rapid detection and eradication of bacterial biofilms.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fotoquimioterapia/métodos , Luz , Bactérias , Biofilmes , Antibacterianos/farmacologia
16.
Bioorg Med Chem Lett ; 88: 129290, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37080476

RESUMO

A novel benzene sulfonamide compound named IMB16-4 exhibits excellent anti-hepatic fibrosis activity in a recent study. To develop potential anti-hepatic fibrosis agents, a series of benzene sulfonamide derivatives were designed and synthesized based on the scaffold of the lead compound IMB16-4. As it turned out, most of the derivatives displayed potential anti-hepatic fibrosis activity, among which, compounds 11a, 11b, 11d, 13a, 36b, and 47b exhibited inhibition rates of 42.3%, 48.7%, 42.4%, 40.0%, 39.4%, and 49.3%, respectively, which were equivalent to the control IMB16-4 with an inhibition rate of 35.9%, Costunolide with an inhibition rate of 45.4%, and much more potent than that of Epigallocatechin gallate (EGCG) with an inhibition rate of 25.3%. Especially, compounds 46a, 46b, and 46c exhibited excellent anti-hepatic fibrosis activity with inhibition rates of 61.7%, 54.8%, and 60.7%, which were almost 1.5-fold inhibition rates of IMB16-4. In addition, compounds 46a, 46b, and 46c exhibited remarkable inhibitory activity in the gene expression of COL1A1, MMP-2, and the protein expression of COL1A1, FN, α-SMA, and TIMP-1 by inhibiting the JAK1-STAT1/3 pathway. These findings furnished valuable inspiration for the further development of anti-hepatic fibrosis agents.


Assuntos
Antifibróticos , Benzeno , Humanos , Derivados de Benzeno , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Sulfonamidas/farmacologia , Relação Estrutura-Atividade
17.
J Photochem Photobiol B ; 241: 112670, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36841175

RESUMO

BACKGROUND: Antimicrobial blue light (aBL) kills a variety of bacteria, including Porphyromonas gingivalis. However, little is known about the transcriptomic response of P. gingivalis to aBL therapy. This study was designed to evaluate the selective cytotoxicity of aBL against P. gingivalis over human cells and to further investigate the genetic response of P. gingivalis to aBL at the transcriptome level. METHODS: Colony forming unit (CFU) testing, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to investigate the antimicrobial effectiveness of blue light against P. gingivalis. The temperatures of the irradiated targets were measured to prevent overheating. Multiple fluorescent probes were used to quantify reactive oxygen species (ROS) generation after blue-light irradiation. RNA sequencing (RNA-seq) was used to investigate the changes in global gene expression. Following the screening of target genes, real-time quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the regulation of gene expression. RESULTS: A 405 nm aBL at 100 mW/cm2 significantly killed P. gingivalis within 5 min while sparing human gingival fibroblasts (HGFs). No obvious temperature changes were detected in the irradiated surface under our experimental conditions. RNA-seq showed that the transcription of multiple genes was regulated, and RT-qPCR revealed that the expression levels of the genes RgpA and RgpB, which may promote heme uptake, as well as the genes Ftn and FetB, which are related to iron homeostasis, were significantly upregulated. The expression levels of the FeoB-2 and HmuR genes, which are related to hydroxyl radical scavenging, were significantly downregulated. CONCLUSIONS: aBL strengthens the heme uptake and iron export gene pathways while reducing the ROS scavenging pathways in P. gingivalis, thus improving the accumulation of endogenous photosensitizers and enhancing oxidative damage to P. gingivalis.


Assuntos
Cor , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Ferro , Luz , Porfirinas , Porphyromonas gingivalis , Porfirinas/metabolismo , Ferro/metabolismo , Porphyromonas gingivalis/citologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/efeitos da radiação , Transporte Biológico/genética , Transporte Biológico/efeitos da radiação , Humanos , Gengiva/citologia , Fibroblastos/citologia , Fibroblastos/efeitos da radiação , Radical Hidroxila/metabolismo , Heme/metabolismo , Regulação para Cima/efeitos da radiação , Homeostase/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Viabilidade Microbiana/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Aerobiose , Genes Bacterianos/efeitos da radiação , Regulação Bacteriana da Expressão Gênica/genética , Regulação Bacteriana da Expressão Gênica/efeitos da radiação
18.
Acta Psychiatr Scand ; 147(4): 360-372, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36585771

RESUMO

OBJECTIVES: We conducted a comprehensive meta-analysis of all available trials to evaluate the efficacy and safety of estrogen and selective estrogen receptor modulators as adjunctive treatment for women with schizophrenia. METHODS: Multiple databases were searched from the inception until March 2022. Only randomized, double-blind, placebo-controlled studies (randomized controlled trials) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: The meta-analysis included six estradiol versus placebo studies (n = 724) and seven raloxifene versus placebo studies (n = 419), covering a total of 1143 patients. Adjunctive estradiol outperformed the placebo in terms of the Positive and Negative Syndrome Scale (PANSS) total score (MD = -7.29; 95% CI = -10.67 to -3.91; I2  = 59.1%; p < 0.001; k = 9; N = 858), positive symptom score (MD = -1.54; 95% CI = -3.04 to -0.72; I2  = 45.8%; p < 0.001; k = 7; N = 624), negative symptom score (MD = -1.9; 95% CI = -1.77 to -0.34; I2  = 37.6%; p < 0.05; k = 14; N = 1042), and general psychopathology score (MD = -4.27; 95% CI = -7.14 to -1.41; I2  = 76.3%; p < 0.005; k = 7; N = 624). Adjunctive raloxifene outperformed the placebo in terms of the PANSS total score (MD = -6.83; 95% CI = -11.69 to -1.97; I2  = 67.8%; p = 0.006; k = 8; N = 432) and general psychopathology score (MD = -3.82; 95% CI = -6.36 to -1.28; I2  = 65.3%; p < 0.005; k = 8; N = 432). CONCLUSIONS: Our meta-analysis showed that estradiol and raloxifene are effective and safe adjunctive treatments that improve schizophrenia symptoms in women. Moreover, the effects of estradiol and raloxifene differed in terms of timing and dosage. Both are promising adjunctive treatments that merit further study.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Feminino , Cloridrato de Raloxifeno/farmacologia , Cloridrato de Raloxifeno/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/diagnóstico , Estradiol , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Quimioterapia Combinada , Pós-Menopausa , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Bull Entomol Res ; 113(2): 282-291, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36503531

RESUMO

Liriomyza trifolii is a significant pest of vegetable and ornamental crops across the globe. Microwave radiation has been used for controlling pests in stored products; however, there are few reports on the use of microwaves for eradicating agricultural pests such as L. trifolii, and its effects on pests at the molecular level is unclear. In this study, we show that microwave radiation inhibited the emergence of L. trifolii pupae. Transcriptomic studies of L. trifolii indicated significant enrichment of differentially expressed genes (DEGs) in 'post-translational modification, protein turnover, chaperones', 'sensory perception of pain/transcription repressor complex/zinc ion binding' and 'insulin signaling pathway' when analyzed with the Clusters of Orthologous Groups, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases, respectively. The top DEGs were related to reproduction, immunity and development and were significantly expressed after microwave radiation. Interestingly, there was no significant difference in the expression of genes encoding heat shock proteins or antioxidant enzymes in L. trifolii treated with microwave radiation as compared to the untreated control. The expression of DEGs encoding cuticular protein and protein takeout were silenced by RNA interference, and the results showed that knockdown of these two DEGs reduced the survival of L. trifolii exposed to microwave radiation. The results of this study help elucidate the molecular response of L. trifolii exposed to microwave radiation and provide novel ideas for control.


Assuntos
Dípteros , Micro-Ondas , Animais , Pupa/genética , Pupa/metabolismo , Proteínas de Choque Térmico/genética , Verduras
20.
J Affect Disord ; 325: 297-305, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586618

RESUMO

BACKGROUND: Secondhand smoke (SHS) exposure is associated with negative emotions in adolescents, but the association between SHS exposure and negative emotions has been understudied, especially in low- and middle-income countries. Hence, we studied the association between SHS exposure and negative emotions among 12-15-year-old non-smoking adolescents from 63 low- and middle-income countries (LMICs). METHODS: We calculated the pooled prevalence of SHS exposure, loneliness, and anxiety in 12-15-year-old non-smoking adolescents. Multivariable logistic regression was used to evaluate country-specific associations between SHS exposure and negative emotions, after adjusting for important confounders. Meta-analyses were performed to evaluate the overall, regional, and country-income level pooled associations. RESULTS: Of the adolescents included in the analysis, 34.88 % had less than daily SHS exposure and 13.41 % were exposed to SHS daily. The overall prevalence of loneliness and anxiety in the adolescents was 10.51 % and 8.95 %, respectively. Exposure to SHS in the past 7 days was associated with loneliness and anxiety, with odds ratios (95 % confidence intervals) of 1.15 (1.09-1.21) and 1.24 (1.17-1.31), respectively. These positive associations were observed in girls, but not in boys. In addition, there was a positive dose-response relationship between the day of exposure to SHS and loneliness and anxiety. LIMITATIONS: The GSHS data were obtained from a self-report questionnaire and the participants were only adolescents in school. CONCLUSIONS: Our study revealed a positive association between SHS exposure and negative emotions among non-smoking adolescents from LMICs.


Assuntos
Poluição por Fumaça de Tabaco , Masculino , Feminino , Humanos , Adolescente , Criança , Poluição por Fumaça de Tabaco/efeitos adversos , Países em Desenvolvimento , Inquéritos e Questionários , Autorrelato , Emoções , Exposição Ambiental
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA