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OBJECTIVE: The study aimed to examine the relationship between preoperative nutritional status, symptom burden, and the occurrence of postoperative atrial fibrillation in Esophageal Squamous Cell Carcinoma patients. METHODS: The study, conducted in the Department of Thoracic Surgery at the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, applied the NRS 2002, SGA and MSAS scoring systems as measures of nutritional status and symptom occurrence in patients diagnosed with ESCC. Univariate and multivariate logistic regression analysis were performed to evaluate the association between nutritional scores, symptom scores, and postoperative complications. RESULTS: The research found a significant correlation between high MSAS scores and postoperative atrial fibrillation. Patients with high symptom burden also tended to have nutritional risk or malnutrition according to the NRS2002 and SGA scores. CONCLUSION: There is a need for healthcare providers to pay attention to ESCC patients' physical and psychological symptoms. Close monitoring of nutritional status and timely nutritional interventions should be integrated into these patients' care plans as they have been found to be related to postoperative complications such as atrial fibrillation.
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Fibrilação Atrial , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Estado Nutricional , Complicações Pós-Operatórias , Humanos , Fibrilação Atrial/etiologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Neoplasias Esofágicas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/complicações , Idoso , Avaliação de Sintomas , Avaliação Nutricional , Período Pré-Operatório , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/epidemiologia , Esofagectomia/efeitos adversos , Carcinoma de Células Escamosas/cirurgiaRESUMO
Circular RNAs (circRNAs) are non-coding RNAs that exert vital function in many human diseases, including preeclampsia (PE). Circ_0015382 is considered to be a key regulator of PE progression, so more molecular mechanisms need to be further studied. Real-time quantitative PCR was used to detect the mRNA levels of circ_0015382, miR-942-5p, and N-myc downstream regulated 1 (NDRG1). Western blot analysis was conducted to assess the protein levels. MTT and EdU assays were used to assess cell proliferation. Cell invasion was analyzed by transwell assay. Tube formation assay was conducted to detect cell angiogenesis. Dual-luciferase reporter assay and RNA immunoprecipitation were used to analyze the target relationship between miR-942-5p and circ_0015382 or NDRG1. Our data showed that circ_0015382 and NDRG1 were up-regulated, while miR-942-5p was down-regulated in the placental tissues of PE patients. Trophoblast cell proliferation, invasion, and angiogenesis were promoted by knockdown of circ_0015382. Circ_0015382 could sponge miR-942-5p, and NDRG1 was a target of miR-942-5p. MiR-942-5p inhibitor could reverse the promoting effects of si-circ_0015382 on trophoblast cell functions. Besides, the enhancing effects of miR-942-5p mimic on trophoblast cell proliferation, invasion, and angiogenesis could be eliminated by NDRG1 overexpression. In conclusion, our data showed that circ_0015382 inhibited trophoblast cell proliferation, invasion, and angiogenesis through regulating miR-942-5p/NDRG1 axis, providing a new mechanism for the regulation of PE progression.
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PURPOSE: To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). METHODS: The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. RESULTS: There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p < 0.05). In addition, the ROC curve revealed that the blue area ratio, MEAN, and skewness had significant diagnostic value (the area under the curve > 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. CONCLUSION: Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. CLINICAL TRIAL NUMBER: Not applicable.
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Técnicas de Imagem por Elasticidade , Insuficiência Renal Crônica , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Feminino , Insuficiência Renal Crônica/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Idoso , Diagnóstico Precoce , Rim/diagnóstico por imagem , Rim/irrigação sanguínea , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Esophageal cancer is one of the most common malignant tumors. The three-dimensional quality structure model is a quality assessment theory that includes three dimensions: Structure, process, and results. AIM: To investigate the effects of nursing interventions with three-dimensional quality assessment on the efficacy and disease management ability of patients undergoing esophageal cancer surgery. METHODS: In this prospective study, the control group received routine nursing, and the intervention group additionally received a three-dimensional quality assessment intervention based on the above routine care. Self-efficacy and patient disease management abilities were evaluated using the General Self-Efficacy Scale (GSES) and Exercise of Self-Care Agency scale, respectively. IBM SPSS Statistics for Windows, version 17.0, was used for the data processing. RESULTS: This study recruited 112 patients who were assigned to the control and experimental groups (n = 56 per group). Before the intervention, there was no significant difference in GSES scores between the two groups (P > 0.05). After the intervention, the GSES scores of both groups increased, with the experimental group showing higher values (P < 0.05). At the time of discharge and three months after discharge, the scores for positive attitudes, self-stress reduction, and total score of health promotion in the experimental group were higher than those in the control group (P < 0.05). CONCLUSION: The implementation of a three-dimensional quality structure model for postoperative patients with esophageal cancer can effectively improve their self-management ability and self-efficacy of postoperative patients.
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People readily change their behavior to comply with others. However, to which extent they will internalize the social influence remains elusive. In this preregistered electroencephalogram (EEG) study, we investigated how learning from one's in-group or out-group members about facial attractiveness would change explicit attractiveness ratings and spontaneous neural representations of facial attractiveness. Specifically, we quantified the neural representational similarities of learned faces with prototypical attractive faces during a face perception task without overt social influence and intentional evaluation. We found that participants changed their explicit attractiveness ratings to both in-group and out-group influences. Moreover, social conformity updated spontaneous neural representation of facial attractiveness, an effect particularly evident when participants learned from their in-group members and among those who perceived tighter social norms. These findings offer insights into how group affiliations and individual differences in perceived social norms modulate the internalization of social influence.
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Beleza , Eletroencefalografia , Conformidade Social , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Reconhecimento Facial/fisiologia , Face/fisiologia , Percepção SocialRESUMO
OBJECTIVE: Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI. METHODS: Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained. RESULTS: There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05). CONCLUSION: First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso , Resultado do TratamentoRESUMO
BACKGROUND: Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy. OBJECTIVE: To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes. STUDY DESIGN: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes. RESULTS: Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group. CONCLUSION: This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.
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Physalis pubescens and Physalis alkekengi, members of the Physalis genus, are valued for their delicious and medicinal fruits as well as their different ripened fruit colors-golden for P. pubescens and scarlet for P. alkekengi. This study aimed to elucidate the pigment composition and genetic mechanisms during fruit maturation in these species. Fruit samples were collected at four development stages, analyzed using spectrophotometry and high-performance liquid chromatography (HPLC), and complemented with transcriptome sequencing to assess gene expression related to pigment biosynthesis. ß-carotene was identified as the dominant pigment in P. pubescens, contrasting with P. alkekengi, which contained both lycopene and ß-carotene. The carotenoid biosynthesis pathway was central to fruit pigmentation in both species. Key genes pf02G043370 and pf06G178980 in P. pubescens, and TRINITY_DN20150_c1_g3, TRINITY_DN10183_c0_g1, and TRINITY_DN23805_c0_g3 in P. alkekengi were associated with carotenoid production. Notably, the MYB-related and bHLH transcription factors (TFs) regulated zeta-carotene isomerase and ß-hydroxylase activities in P. pubescens with the MYB-related TF showing dual regulatory roles. In P. alkekengi, six TF families-bHLH, HSF, WRKY, M-type MADS, AP2, and NAC-were implicated in controlling carotenoid synthesis enzymes. Our findings highlight the intricate regulatory network governing pigmentation and provide insights into Physalis germplasm's genetic improvement and conservation.
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Carotenoides , Frutas , Regulação da Expressão Gênica de Plantas , Physalis , Physalis/genética , Physalis/metabolismo , Physalis/crescimento & desenvolvimento , Frutas/genética , Frutas/metabolismo , Frutas/crescimento & desenvolvimento , Carotenoides/metabolismo , Pigmentação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pigmentos Biológicos/metabolismo , Pigmentos Biológicos/biossíntese , Transcriptoma , beta Caroteno/metabolismo , beta Caroteno/biossíntese , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Perfilação da Expressão Gênica/métodosRESUMO
Individuals' affective experience can be intricate, influenced by various factors including monetary rewards and social factors during social interaction. However, within this array of factors, divergent evidence has been considered as potential contributors to social anxiety. To gain a better understanding of the specific factors associated with anxiety during social interaction, we combined a social interaction task with neurophysiological recordings obtained through an anxiety-elicitation task conducted in a Virtual Reality (VR) environment. Employing inter-subject representational similarity analysis (ISRSA), we explored the potential linkage between individuals' anxiety neural patterns and their affective experiences during social interaction. Our findings suggest that, after controlling for other factors, the influence of the partner's emotional cues on individuals' affective experiences is specifically linked to their neural pattern of anxiety. This indicates that the emergence of anxiety during social interaction may be particularly associated with the emotional cues provided by the social partner, rather than individuals' own reward or prediction errors during social interaction. These results provide further support for the cognitive theory of social anxiety and extend the application of VR in future cognitive and affective studies.
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Ansiedade , Recompensa , Interação Social , Realidade Virtual , Humanos , Masculino , Feminino , Ansiedade/fisiopatologia , Ansiedade/psicologia , Adulto Jovem , Adulto , Eletroencefalografia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Sinais (Psicologia)RESUMO
PURPOSE: Doxorubicin is an antibiotic drug used clinically to treat infectious diseases and tumors. Unfortunately, it is cardiotoxic. Autophagy is a cellular self-decomposition process that is essential for maintaining homeostasis in the internal environment. Accordingly, the present study was proposed to characterize the autophagy-related signatures of doxorubicin-induced cardiotoxicity. METHODS: Datasets related to doxorubicin-induced cardiotoxicity were retrieved by searching the GEO database and differentially expressed genes (DEGs) were identified. DEGs were taken to intersect with autophagy-related genes to obtain autophagy-related signatures, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed on them. Further, construction of miRNA-hub gene networks and identification of target drugs to reveal potential molecular mechanisms and therapeutic strategies. Animal models of doxorubicin-induced cardiotoxicity were constructed to validate differences in gene expression for autophagy-related signatures. RESULTS: PBMC and heart samples from the GSE37260 dataset were selected for analysis. There were 995 and 2357 DEGs in PBMC and heart samples, respectively, and they had 23 intersecting genes with autophagy-related genes. RT-qPCR confirmed the differential expression of 23 intersecting genes in doxorubicin-induced cardiotoxicity animal models in general agreement with the bioinformatics results. An autophagy-related signatures consisting of 23 intersecting genes is involved in mediating processes and pathways such as autophagy, oxidative stress, apoptosis, protein ubiquitination and phosphorylation. Moreover, Akt1, Hif1a and Mapk3 are hub genes in autophagy-associated signatures and their upstream miRNAs are mainly rno-miR-1188-5p, rno-miR-150-3p and rno-miR-326-3p, and their drugs are mainly CHEMBL55802, Carboxyamidotriazole and 3-methyladenine. CONCLUSION: This study identifies for the first-time autophagy-related signatures in doxorubicin's cardiotoxicity, which could provide potential molecular mechanisms and therapeutic strategies for doxorubicin-induced cardiotoxicity.
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Autofagia , Cardiotoxicidade , Doxorrubicina , Doxorrubicina/toxicidade , Autofagia/efeitos dos fármacos , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , Mapas de Interação de Proteínas , Antibióticos Antineoplásicos/toxicidade , Redes Reguladoras de Genes/efeitos dos fármacos , Camundongos , Perfilação da Expressão Gênica/métodos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismoRESUMO
Fluorosis is a worldwide public health problem, in which the heart is an important target organ. However, studies on its toxicological mechanism in embryonic development are limited. This study assessed the toxicity of sodium fluoride (NaF) toward zebrafish embryos. We determined the mortality, hatching rate, phenotypic malformation, heart function, and morphology of zebrafish embryos after exposure to NaF. Subsequently, the molecular mechanism was revealed using high-throughput RNA sequencing analysis. The expression levels of key genes for heart development were detected using quantitative real-time reverse transcription PCR. The 50% lethal concentration (LC50) value of NaF toward zebrafish embryos at 96 h post-fertilization was 335.75 mg/L. When the concentration of NaF was higher than 200 mg/L, severe deformities, such as pericardial edema, yolk sac edema, spine curvature, shortened body length, reduced head area, and eye area, were observed. The heart rate of the embryos exposed to NaF decreased in a dose-dependent fashion. The distance between the sinus venosus and bulbus arteriosus was significantly increased in the NaF-exposed group compared with that in the control group. The stroke volume and cardiac output decreased significantly in the NaF groups. Compared with the control group, the expression levels of Gata4, Tbx5a, Hand2, Tnnt2c, Nppa, and Myh6 were significantly increased in the NaF-treated group. Through transcriptome sequencing, 1354 differentially expressed genes (DEGs) were detected in the NaF (200 mg/L) treated groups, including 1253 upregulated genes and 101 downregulated genes. Gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEGs showed that cardiac-related pathways, such as actin cytoskeleton regulation, Jak-Stat, PI3k-Akt, and Ras, were activated in the NaF-exposed group. This study revealed the underlying mechanism of fluoride-induced cardiac morphological and functional abnormalities and provides clues for the clinical prevention and treatment of fluorosis.
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BACKGROUND: Abnormalities in iron and lipid metabolism are recognized as key contributors to atherosclerosis (AS). Therefore, this study proposes to characterize the biomarker related to iron and lipid metabolism in AS using bioinformatics, animal, and cell experiments. METHODS: The limma package was utilized to identify differentially expressed genes (DEGs) in GSE70126 and GSE70619 datasets, and biomarkers were screened using enrichment analysis and PPI networks. IFIT2 was knocked down using shRNA lentivirus in a high fat diet (HFD)-induced APOE-/- AS model to investigate its effects of IFIT2 on the pathology, iron retention, and lipid accumulation. Iron storage-related and cholesterol efflux-related proteins were evaluated following exogenous modulation of IFIT2 expression in ox-LDL-induced foamy macrophages. RESULTS: Compared to non-foamy macrophages from the aorta, 189 and 4152 DEGs were identified in foamy macrophages within the GSE70126 and GSE70619 datasets, respectively. Moreover, intersecting DEGs may modulate immune responses, cell adhesion, vascular permeability, and oxidative stress through NF-kappa B, Wnt, TNF and HIF-1 signaling pathways. Notably, IFIT2 was significantly upregulated in foamy macrophages and AS models. In vivo, IFIT2 co-localized with foamy macrophages, and its knockdown led to reductions in plasma lipid levels, plaque area, immune infiltration, iron retention, and lipid accumulation. In vitro, IFIT2 knockdown alleviated the ox-LDL-induced increase in iron storage-related proteins (Ferritin-L and Ferritin-H) and iron (Fe2+ and Fe3+) in foamy macrophages. Furthermore, IFIT2 knockdown reduced lipid accumulation and upregulated cholesterol efflux-related proteins (PPARγ, LXRα, ABCA1, and ABCG1) in foamy macrophages. CONCLUSION: IFIT2 knockdown attenuates iron retention and lipid accumulation in AS plaques, and facilitated cholesterol efflux from foamy macrophages via the PPARγ/LXRα/ABCA1-ABCG1 pathway.
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Aterosclerose , Colesterol , Ferro , Aterosclerose/metabolismo , Aterosclerose/genética , Animais , Ferro/metabolismo , Camundongos , Colesterol/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Macrófagos/metabolismo , Macrófagos/imunologia , Dieta Hiperlipídica , Células Espumosas/metabolismo , Metabolismo dos Lipídeos/genética , Lipoproteínas LDL/metabolismo , Modelos Animais de DoençasRESUMO
MIL77-3 is one component of antibody cocktail that is produced in our lab and represents an effective regimen for animals suffering from Zaire Ebolavirus (EBOV) infection. MIL77-3 is engineered to increase its affinity for the FcγRIIIa (CD16a) by deleting the fucose in the framework region. The potential effects of this modification on host immune responses, however, remain largely unknown. Herein, we demonstrated that MIL77-3 recognized secreted glycoproptein (sGP), produced by EBOV, and formed the immunocomplex to potently augment antibody-dependent cytotoxicity of human peripheral blood-derived natural killer cells (pNKs), including CD56dim and CD56bright subpopulations, in contrast to the counterparts (Mab114, rEBOV548, fucosylated MIL77-3). Intriguingly, this effect was not observed when NK92-CD16a cell line was utilized and restored by the addition of beads-coupled or membrane-anchored sGP in combination with MIL77-3. Furthermore, sGP bound to unrecognized receptors on T cells contaminated in pNKs rather than NK92-CD16a cells. Administration of beads-coupled sGP/MIL77-3 complex in mice elicited NK activation. Overall, this work reveals an immune-stimulating function of sGP/MIL77-3 complex by triggering cytotoxic activity of NK cells, highlighting the necessity to evaluate the potential impact of MIL77-3 on host immune reaction in clinical trials. IMPORTANCE: Zaire Ebolavirus (EBOV) is highly lethal and causes sporadic outbreaks. The passive administration of monoclonal antibodies (mAbs) represents a promising treatment regimen against EBOV. Mounting evidence has shown that the efficacy of a subset of therapeutic mAbs in vivo is intimately associated with its capacity to trigger NK activity, supporting glycomodification of Fc region of anti-EBOV mAbs as a putative strategy to enhance Fc-mediated immune effector function as well as protection in vivo. Our work here uncovers the potential harmful influence of this modification on host immune responses, especially for mAbs with cross-reactivity to secreted glycoproptein (sGP) (e.g., MIL77-3), and highlights it is necessary to evaluate the NK-stimulating activity of a fucosylated mAb engaged with sGP when a new candidate is developed.
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Anticorpos Antivirais , Citotoxicidade Celular Dependente de Anticorpos , Ebolavirus , Doença pelo Vírus Ebola , Células Matadoras Naturais , Receptores de IgG , Células Matadoras Naturais/imunologia , Humanos , Animais , Ebolavirus/imunologia , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Camundongos , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Anticorpos Antivirais/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Fucose , Linhagem CelularRESUMO
Background: A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT). Materials and Methods: In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy. Results: MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response. Conclusion: The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.
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Camptotecina , Imunoterapia , Indóis , Camundongos Endogâmicos BALB C , Polímeros , Triptofano , Zeolitas , Animais , Indóis/química , Indóis/farmacologia , Zeolitas/química , Zeolitas/farmacologia , Imunoterapia/métodos , Triptofano/química , Triptofano/farmacologia , Triptofano/análogos & derivados , Camundongos , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Feminino , Polímeros/química , Polímeros/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Nanopartículas/química , Apoptose/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Humanos , Terapia Fototérmica/métodos , Imidazóis/química , Imidazóis/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Terapia CombinadaRESUMO
Sensory and emotional experiences are essential for mental and physical well-being, especially within the realm of psychiatry. This article highlights recent advances in cognitive neuroscience, emphasizing the significance of pain recognition and empathic artificial intelligence (AI) in healthcare. We provide an overview of the recent development process in computational pain recognition and cognitive neuroscience regarding the mechanisms of pain and empathy. Through a comprehensive discussion, the article delves into critical questions such as the methodologies for AI in recognizing pain from diverse sources of information, the necessity for AI to exhibit empathic responses, and the associated advantages and obstacles linked with the development of empathic AI. Moreover, insights into the prospects and challenges are emphasized in relation to fostering artificial empathy. By delineating potential pathways for future research, the article aims to contribute to developing effective assistants equipped with empathic capabilities, thereby introducing safe and meaningful interactions between humans and AI, particularly in the context of mental health and psychiatry.
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BACKGROUND: Several studies have explored the potential link between gut microbiota and breast cancer; nevertheless, the causal relationship between gut microbiota and breast cancer remains unclear. METHODS: We utilized summary statistics from genome-wide association studies (GWAS) of the gut microbiome from the MiBioGen project with summary data from GWAS on breast cancer from the FinnGen consortium and the IEU database, with the IEU data sourced from the Biobank Japan. Preliminary statistical analyses were conducted using inverse variance weighting (IVW), supplemented by various sensitivity analysis methods, including MR-Egger regression, weighted median, weighted mode, simple median, and simple mode, to ensure the robustness of our findings. Heterogeneity and pleiotropy were assessed to avoid misleading conclusions caused by unconsidered confounders or non-specific effects of genetic variants, ensuring that the results reflect a genuine causal relationship. RESULTS: In European populations, four types of gut microbiota were associated with breast cancer. The genus Erysipelatoclostridium was positively associated with the risk of breast cancer, with an odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.083-1.358), false discovery rate (FDR) = 0.0039. The class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae, which belong to the same phylogenetic system, showed a consistent inversely association with breast cancer risk, with an OR of 0.757 (95% CI 0.616-0.930), FDR = 0.0281. In East Asian populations, three types of gut microbiota were related to breast cancer. The Eubacterium ruminantium group was positively associated with breast cancer risk, with an OR of 1.259 (95% CI 1.056-1.499), FDR = 0.0497. The families Porphyromonadaceae and Ruminococcaceae were inversely associated with breast cancer risk, with ORs of 0.304 (95% CI 0.155-0.596), FDR = 0.0005, and 0.674 (95% CI 0.508-0.895), FDR = 0.03173, respectively. However, these two taxa had limited instrumental variables, restricting the statistical power and potentially affecting the interpretation of the results. CONCLUSION: This MR analysis demonstrated a probable causal link between specific gut microbiota and breast cancer. This study, through Mendelian randomization analysis comparing European and East Asian populations, reveals that gut microbiota may influence breast cancer risk differently across populations, providing potential directions for developing targeted prevention and treatment methods.
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Neoplasias da Mama , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/microbiologia , Neoplasias da Mama/epidemiologia , População do Leste Asiático/genética , Microbioma Gastrointestinal/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genéticaRESUMO
In order to analyze the influence of deep learning model on detecting denial-of-service (DoS) attacks, this article first examines the concepts and attack strategies of DoS assaults before looking into the present detection methodologies for DoS attacks. A distributed DoS attack detection system based on deep learning is established in response to the investigation's limitations. This system can quickly and accurately identify the traffic of distributed DoS attacks in the network that needs to be detected and then promptly send an alarm signal to the system. Then, a model called the Improved Conditional Wasserstein Generative Adversarial Network with Inverter (ICWGANInverter) is proposed in response to the characteristics of incomplete network traffic in DoS attacks. This model automatically learns the advanced abstract information of the original data and then employs the method of reconstruction error to identify the best classification label. It is then tested on the intrusion detection dataset NSL-KDD. The findings demonstrate that the mean square error of continuous feature reconstruction in the sub-datasets KDDTest+ and KDDTest-21 steadily increases as the noise factor increases. All of the receiver operating characteristic (ROC) curves are shown at the top of the diagonal, and the overall area under the ROC curve (AUC) values of the macro-average and micro-average are above 0.8, which demonstrates that the ICWGANInverter model has excellent detection performance in both single category attack detection and overall attack detection. This model has a greater detection accuracy than other models, reaching 87.79%. This demonstrates that the approach suggested in this article offers higher benefits for detecting DoS attacks.
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Bodily self-consciousness (BSC), a subject of interdisciplinary interest, refers to the awareness of one's bodily states. Previous studies have noted the existence of individual differences in BSC, while neglecting the underlying factors and neural basis of such individual differences. Considering that BSC relied on integration from both internal and external self-relevant information, we here review previous findings on individual differences in BSC through a three-level-self model, which includes interoceptive, exteroceptive, and mental self-processing. The data show that cross-level factors influenced individual differences in BSC, involving internal bodily signal perceptibility, multisensory processing principles, personal traits shaped by environment, and interaction modes that integrate multiple levels of self-processing. Furthermore, in interoceptive processing, regions like the anterior cingulate cortex and insula show correlations with different perceptions of internal sensations. For exteroception, the parietal lobe integrates sensory inputs, coordinating various BSC responses. Mental self-processing modulates differences in BSC through areas like the medial prefrontal cortex. For interactions between multiple levels of self-processing, regions like the intraparietal sulcus involve individual differences in BSC. We propose that diverse experiences of BSC can be attributed to different levels of self-processing, which moderates one's perception of their body. Overall, considering individual differences in BSC is worth amalgamating diverse methodologies for the diagnosis and treatment of some diseases.