RESUMO
Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5-30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult. Here, maleimide-modified resiquimod (R848) prodrug nanoparticles (MAL-NPs) are reported and combined with radiotherapy (RT) and anti-PD1 to enhance ICI therapy. MAL-NPs can promote antigen endocytosis by dendritic cells and are radio-reduced to produce R848. When combined with RT, MAL-NPs can augment the concentration of nanoparticles at tumor sites and be selectively radio-reduced within the tumor, thereby triggering a potent antitumor immune response. The systemic immune response and long-term memory efficacy induced by MAL-NPs + RT + anti-PD1 significantly inhibit the abscopal tumor growth and prevent tumor recurrence. This strategy can achieve systemic therapy through selective training of the tumor immune microenvironment, offering a new approach to overcome the obstacles of ICI therapy.
Assuntos
Nanoestruturas , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Microambiente Tumoral , Linhagem Celular Tumoral , ImunoterapiaRESUMO
BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate bloodâbrain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. FINDINGS: In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = - 0.401, p = 0.031). CONCLUSION: Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Barreira Hematoencefálica , Humanos , Metaloproteinase 9 da Matriz , Microglia , BiomarcadoresRESUMO
Brucellosis is a zoonotic infectious disease caused by Brucella spp, which could cause serious economic losses to animal husbandry and threaten human public health. Ingestion of contaminated animal products is a common way to acquire Brucella infection in humans, while research on effect of oral Brucella infection on host gut microbiota and the gene expression in intestinal tissues is limited. In the present study, 16S rRNA sequencing and RNA sequencing were conducted to explore gut microbiota and expression profiles of mRNAs in the colon of BALB/c mice, which were infected by Brucella abortus 2308. The fecal samples were collected at 7 and 28 days post infection to observe changes in the gut microbiota during Brucella infection. In the alpha diversity analysis, significantly increased Chao 1 index was observed at 28 days after Brucella infection. The Bray-Curtis distancebased principal coordinate analysis indicated that the WT group showed a separation from the Brucella infection groups. In addition, analysis of composition of microbes revealed that Prevotellaceae_NK3B31_group were more abundant in 1 week and 4 week infection groups, while Turicibacter was only more abundant in 4 week infection group. Based on the RNA-seq assay, a total of 45 differentially expressed genes were detected between Brucella abortus infection group and control group. Furthermore, KEGG pathway enrichment analysis showed that protein processing in endoplasmic reticulum, Legionellosis, Spliceosome, Hippo signaling pathway and Influenza A were significantly enriched in response to Brucella abortus infection. Our finding will help to improve the knowledge of the mechanisms underlying Brucella infection and may provide novel targets for future treatment of this pathogen infection.
Assuntos
Brucelose Bovina , Brucelose , Microbioma Gastrointestinal , Animais , Camundongos , Bovinos , Humanos , Brucella abortus/genética , Brucella abortus/metabolismo , Transcriptoma , Camundongos Endogâmicos BALB C , RNA Ribossômico 16S/genéticaRESUMO
Background: To explore the value of a novel ventricular-vascular coupling index (VVI) system in relation to age, gender and body mass index (BMI). Methods: A total of 239 volunteers with single-center and cross-sectional health screening were enrolled in the study. Subjects were divided according to age (young [18-44 years], middle-age [45-59 years], old [60-80 years]), gender (male, female), and BMI (overweight/obese [BMI ≥ 24], control [BMI < 24]). The left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) provided the left ventricular structure index, while the TDI e ' provided the functional index. Also derived from routine echocardiography were the effective arterial elastance (Ea), left ventricular end-systolic elastance (Ees), and VVI. The novel VVI systems were arterial velocity pulse index (AVI), left ventricular global longitudinal strain (LVGLS), and the AVI to LVGLS ratio (AVI/LVGLS). Results: (1) Middle-age and elderly subjects had higher Ea and lower LVGLS compared to young subjects. AVI and AVI/LVGLS increased progressively from young to middle-age to old subjects. (2) Females had higher Ea, Ees and LVGLS than male subjects. No significant differences in AVI and AVI/LVGLS were observed between males and females. (3) No significant differences in Ea, Ees, VVI, AVI, LVGLS and AVI/LVGLS were observed between the overweight/obese and control groups. (4) AVI/LVGLS was negatively correlated with LVEDV and LVESV and with TDI e ' . LVEDV, LVESV and TDI e ' were independent predictors of AVI/LVGLS. (5) The diagnostic performance of AVI/LVGLS was higher than that of VVI in the young and middle-age groups. The diagnostic efficacy of AVI/LVGLS was higher than that of VVI in the young and old groups, and the diagnostic efficacy of AVI was higher than that of Ea. The difference in diagnostic efficacy between LVGLS and Ees was not statistically significant. The differences in diagnostic efficacy between AVI/LVGLS and VVI, AVI and Ea, and LVGLS and Ees were not statistically significant in the middle-age and old groups. Conclusions: The novel index system of ventricular-vascular coupling described here (AVI, LVGLS, and AVI/LVGLS) was more effective than traditional indexes in detecting differences in cardiovascular function between different ages groups. Clinical Trial Registration: The study protocol was registered on the official website of China Clinical Trial Registration Center (ChiCTR2000035937).
RESUMO
The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.
Assuntos
Peptídeo Hidrolases , Animais , Camundongos , Brucella abortus/genética , Endopeptidase Clp/genética , Proteômica , Virulência , Modelos Animais de DoençasRESUMO
Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells lose their characteristics and acquire mesenchymal phenotypes, participates in the pathogenic mechanism of idiopathic pulmonary fibrosis. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) has been introduced as a promising treatment in organ fibrosis. This study aimed to explore the effects as well as the molecular mechanism for hucMSC-Exo in pulmonary fibrosis. The intravenous administration of hucMSC-Exos alleviated bleomycin-induced pulmonary fibrosis in vivo. Moreover, hucMSC-Exos elevated miR-218 expression and restored endothelial properties weakened by TGF-ß in endothelial cells. Knockdown of miR-218 partially abrogated the inhibition effect of hucMSC-Exos on EndMT. Our mechanistic study further demonstrated that MeCP2 was the direct target of miR-218. Overexpressing MeCP2 aggravated EndMT and caused increased CpG islands methylation at BMP2 promoter, which lead to BMP2 post-transcriptional gene silence. Transfection of miR-218 mimic increased BMP2 expression as well, which was downregulated by overexpression of MeCP2. Taken together, these findings indicate exosomal miR-218 derived from hucMSCs may possess anti-fibrotic properties and inhibit EndMT through MeCP2/BMP2 pathway, providing a new avenue of preventive application in pulmonary fibrosis.
Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Células Endoteliais/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fibrose , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismoRESUMO
OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.
Assuntos
COVID-19 , Pneumonia Viral , Rigidez Vascular , Humanos , Pressão Sanguínea , Frequência Cardíaca , Pneumonia Viral/diagnósticoRESUMO
Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding their host immune response, which may limit their clinical efficacy and applications. Here, we find that cisplatin (CDDP)-loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) elicit a strong antitumor CD8+ T cell-mediated immune response in a tumor-bearing mouse model compared to free CDDP. Mechanistically, the sustained retention of CDDP-NPs results in persistent tumor MHC-I overexpression, which promotes the formation of MHC-I-antigen peptide complex (pMHC-I), enhances the interaction between pMHC-I and T cell receptor (TCR), and leads to the activation of TCR signaling pathway and CD8+ T cell-mediated immune response. Furthermore, CDDP-NPs upregulate the costimulatory OX40 on intratumoral CD8+ T cells, and synergize with the agonistic OX40 antibody (aOX40) to suppress tumor growth by 89.2%. Our study provides a basis for the efficacy advantage of CDDP-based nanomedicines and immunotherapy.
Assuntos
Cisplatino , Nanopartículas , Animais , Apresentação de Antígeno , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Camundongos , Receptores de Antígenos de Linfócitos TRESUMO
Soil salinization can affect the ecological environment of soil and alter greenhouse gas (GHG) emissions. Chitooligosaccharides and Arbuscular mycorrhizal fungi (AMF) reduced the GHG fluxes of salinized soil, and this reduction was attributed to an alteration in the rhizosphere microecology, including changes in the activities of ß-glucosidase, acid phosphatase, N-acetyl-ß-D-glucosidase, and Leucine aminopeptidase. Additionally, certain bacteria species such as paracoccus, ensifer, microvirga, and paracyclodium were highly correlated with GHG emissions. Another interesting finding is that foliar spraying of chitooligosaccharides could transport to the soybean root system, and improve soybean tolerance to salt stress. This is achieved by enhancing the activities of antioxidant enzymes, and the changes in amino acid metabolism, lipid metabolism, and membrane transport. Importantly, the Co-application of chitooligosaccharides and Arbuscular mycorrhiza fungi was found to have a greater effect compared to their application alone.
Assuntos
Gases de Efeito Estufa , Micorrizas , Glycine max , Rizosfera , Solo/química , Raízes de Plantas , Fungos , Microbiologia do SoloRESUMO
The Peace of Mind Program is an evidence-based intervention to improve mammography appointment adherence in underserved women. The aim of this study was to assess effectiveness of the intervention and implementation of the intervention in safety net clinics. The intervention was implemented through a non-randomized stepped wedge cluster hybrid study design with 19 Federally Qualified Health Centers and charity care clinics within the Greater Houston area. A multivariable generalized estimating equation logistic regression was conducted to examine mammography appointment adherence. A survey assessing Consolidated Framework for Implementation Research constructs was also conducted with clinic staff prior to adoption and eight weeks post implementation. One-sided t-tests were conducted to analyze mean score changes between the surveys. A total of 4402 women (baseline period = 2078; intervention period = 2324) were included in the final regression analysis. Women in the intervention period were more likely to attend or reschedule their mammography appointment (OR = 1.30; p < 0.01) than those in the baseline period receiving usual care. Women who completed the intervention were more likely to attend or reschedule their mammography appointment than those who did not complete the intervention (OR = 1.62; p < 0.01). The mammography appointment no-show rates for those in the baseline period, in the intervention period, and who completed the intervention were, respectively, 22%, 19%, and 15%. A total of 15 clinics prior to adoption and eight clinics completed the survey at 8 weeks post implementation A statistically significant mean score decrease was observed in Inner Setting and in two Inner Setting CFIR constructs, Culture-Effort, and Implementation Climate. While the intervention improved mammography appointment adherence, there are opportunities to further integrate Consolidated Framework for Implementation Research constructs. Trial registration: Clinical trials registration number: NCT02296177.
Assuntos
Instituições de Assistência Ambulatorial , Provedores de Redes de Segurança , Humanos , Feminino , Mamografia , Projetos de Pesquisa , Medicina Baseada em EvidênciasRESUMO
It is of great importance to better understand how trees regulate nitrogen (N) uptake under N deficiency conditions which severely challenge afforestation practices, yet the underlying molecular mechanisms have not been well elucidated. Here, we functionally characterized PuHox52, a Populus ussuriensis HD-ZIP transcription factor, whose overexpression greatly enhanced nutrient uptake and plant growth under N deficiency. We first conducted an RNA sequencing experiment to obtain root transcriptome using PuHox52-overexpression lines of P. ussuriensis under low N treatment. We then performed multiple genetic and phenotypic analyses to identify key target genes of PuHox52 and validated how they acted against N deficiency under PuHox52 regulation. PuHox52 was specifically induced in roots by N deficiency, and overexpression of PuHox52 promoted N uptake, plant growth, and root development. We demonstrated that several nitrate-responsive genes (PuNRT1.1, PuNRT2.4, PuCLC-b, PuNIA2, PuNIR1, and PuNLP1), phosphate-responsive genes (PuPHL1A and PuPHL1B), and an iron transporter gene (PuIRT1) were substantiated to be direct targets of PuHox52. Among them, PuNRT1.1, PuPHL1A/B, and PuIRT1 were upregulated to relatively higher levels during PuHox52-mediated responses against N deficiency in PuHox52-overexpression lines compared to WT. Our study revealed a novel regulatory mechanism underlying root adaption to N deficiency where PuHox52 modulated a coordinated uptake of nitrate, phosphate, and iron through 'PuHox52-PuNRT1.1', 'PuHox52-PuPHL1A/PuPHL1B', and 'PuHox52-PuIRT1' regulatory relationships in poplar roots.
Assuntos
Ferro , Populus , Nitratos , Populus/genética , Nitrogênio/metabolismo , Fosfatos , Raízes de Plantas/genética , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Temporomandibular joint (TMJ) disc repositioning through open suturing (OSu) is a new disc repositioning method. Its result for adolescents with condylar resorption and dentofacial deformities combined with and without postoperative occlusal splints (POS) has not been well studied. OBJECTIVE: This study was to evaluate and compare the effects of OSu with and without POS in the treatment of TMJ anterior disc displacement without reduction (ADDwoR) in adolescent skeletal Class II malocclusion. METHODS: A total of 60 adolescents with bilateral ADDwoR were enrolled in this study. They were randomly allocated into two groups: OSu with and without POS. Magnetic resonance imaging (MRI) and lateral cephalometric radiographs were used to measure changes in condylar height and the degree of skeletal Class II malocclusion from before operation and at 12 months postoperatively. Changes in these indicators were compared within and between the two groups. RESULTS: After OSu, both groups exhibited significant improvements in condylar height and occlusion at the end of 12 months follow-up (P < 0.05). The group of OSu with POS had significantly more new bone formation (2.83 ± 0.75 mm vs. 1.42 ± 0.81 mm, P < 0.001) and improvement in dentofacial deformity than the group of OSu only (P < 0.05). The new bone height was significantly correlated with POS (P < 0.001), the changes of SNB (P = 0.018), overjet (P = 0.012), and Wits appraisal (P < 0.001). CONCLUSION: These findings indicated that OSu can effectively stimulate condylar regeneration and improve skeletal Class II malocclusion in adolescents with bilateral ADDwoR. The results are better when combined with POS. TRIAL REGISTRATION: This trial was prospectively registered on the chictr.org.cn registry with ID: ChiCTR1900021821 on 11/03/2019.
Assuntos
Luxações Articulares , Má Oclusão Classe II de Angle , Transtornos da Articulação Temporomandibular , Adolescente , Humanos , Oclusão Dentária , Imageamento por Ressonância Magnética/métodos , Má Oclusão Classe II de Angle/terapia , Má Oclusão Classe II de Angle/patologia , Placas Oclusais , Articulação Temporomandibular , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/terapia , Transtornos da Articulação Temporomandibular/patologiaRESUMO
Since the roots are the very organ where plants first sense and respond drought stress, it is of great importance to better understand root responses to drought. Yet the underlying molecular mechanisms governing root responses to drought stress have been poorly understood. Here, we identified and functionally characterized a CCCH type transcription factor, PuC3H35, and its targets, anthocyanin reductase (PuANR) and early Arabidopsis aluminum induced1 (PuEARLI1), which are involved in mediating proanthocyanidin (PA) and lignin biosynthesis in response to drought stress in Populus ussuriensis root. PuC3H35 was root-specifically induced upon drought stress. Overexpressing PuC3H35 promoted PA and lignin biosynthesis and vascular tissue development, resulting in enhanced tolerance to drought stress by the means of anti-oxidation and mechanical supporting. We further demonstrated that PuC3H35 directly bound to the promoters of PuANR and PuEARLI1 and overexpressing PuANR or PuEARLI1 increased root PA or lignin levels, respectively, under drought stress. Taken together, these results revealed a novel regulatory pathway for drought tolerance, in which PuC3H35 mediated PA and lignin biosynthesis by collaboratively regulating 'PuC3H35-PuANR-PA' and 'PuC3H35-PuEARLI1-PuCCRs-lignin' modules in poplar roots.
Assuntos
Populus , Proantocianidinas , Secas , Regulação da Expressão Gênica de Plantas , Lignina , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Populus/genética , Populus/metabolismo , Estresse Fisiológico/genéticaRESUMO
It is widely acknowledged that pseudogenes play important roles in bacterial diversification and evolution and participate in gene regulation and RNA interference (RNAi). However, the function of most pseudogenes in Brucella spp remains poorly understood, warranting further studies.To comprehensively analyze the function of the pseudogenes BMEA_B0173 in Brucella melitensis strain 63/9, a BMEA_B0173 in-frame deleted mutant strain was constructed. Then, the phenotypes of the mutant strain, such as growth characteristics and bacterial virulence, were assessed in mice infection models. Finally, iTRAQ analysis was performed to investigate the gene expression profile affected by the pseudogenes BMEA_B0173. In this study, we found that BMEA_B0173 deletion exhibited increased agglutination with M monospecific sera. In a mouse model of chronic infection, the BMEA_B0173 deletion strain displayed increased colonization in the spleen compared to the wild-type pathogen. The iTRAQ assay revealed that 252 proteins were differentially expressed between the BMEA_B0173 deletion and the wild-type strains. In addition, deletion of BMEA_B0173 significantly increased the expression of proteins involved in the denitrification pathway, iron metabolism, and several transcriptional regulators, which might cause increased virulence of the mutant strain. In conclusion, this study preliminary uncovered the function of the pseudogene BMEA_B0173 in Brucella melitensis 63/9 and provided novel insights for studying the pathogenesis of Brucella strains.
Assuntos
Brucella melitensis , Brucelose , Camundongos , Animais , Brucella melitensis/genética , Brucella melitensis/metabolismo , Virulência/genética , Pseudogenes , Epitopos/metabolismo , Brucelose/microbiologia , Modelos Animais de Doenças , Proteínas de Bactérias/genéticaRESUMO
Multi-level organizational stakeholder engagement plays an important role across the research process in a clinical setting. Stakeholders provide organizational specific adaptions in evidence-based interventions to ensure effective adoption, implementation, and sustainability. Stakeholder engagement strategies involve building mutual trust, providing clear communication, and seeking feedback. Using constructs from the Consolidated Framework for Implementation Research and The International Association for Public Participation spectrum, a conceptual framework was created to guide stakeholder engagement in an evidence-based intervention to increase mammography appointment adherence in underserved and low-income women. A document review was used to explore the alignment of the conceptual framework with intervention activities and stakeholder engagement strategies. The results indicate an alignment with the conceptual framework constructs and a real-world application of stakeholder engagement in a mammography evidence-based intervention. The conceptual framework and stakeholder engagement strategies can be applied across a range of community-based cancer programs and interventions, organizations, and clinical settings.
Assuntos
Participação da Comunidade , Participação dos Interessados , Medicina Baseada em Evidências , Feminino , Humanos , Mamografia , PobrezaRESUMO
PURPOSE: To report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol. MATERIALS AND METHODS: A total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300-500 µm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits. RESULTS: Nine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed. CONCLUSIONS: TASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Embolização Terapêutica , Hemangioma/terapia , Neoplasias Parotídeas/terapia , Propranolol/uso terapêutico , Escleroterapia , Bleomicina/administração & dosagem , Bleomicina/análogos & derivados , Embolização Terapêutica/efeitos adversos , Óleo Etiodado/administração & dosagem , Feminino , Hemangioma/diagnóstico por imagem , Hemangioma/patologia , Humanos , Lactente , Masculino , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Álcool de Polivinil/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Escleroterapia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
Ovarian cancer is a severe malignant tumour of the female genital organs. Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) expression is correlated with the occurrence and progression of multiple cancers. Here, we assessed STEAP1 expression in ovarian cancer and explored the relationship between STEAP1 and ovarian cancer progression. We used immunohistochemistry and public databases to test STEAP1 expression in normal human ovarian tissues, benign ovarian tumours, and ovarian cancer. The expression of STEAP1 and epithelial-to-mesenchymal transition (EMT)-related genes was analysed using immunocytochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting in ovarian cancer cell lines. Lentivirus was used to knockdown and overexpress STEAP1. Invasion, migration, growth, clonogenicity, and apoptosis were assessed using transwell assay, growth curve, plate clone formation assay, and flow cytometry. We used a tumour xenograft to verify the relationship between STEAP1 and in vivo ovarian cancer cell growth. Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) activities were examined using Matrix metalloproteinase zymography assay. STEAP1 was highly expressed in the human ovarian cancer tissues and a highly invasive ovarian cancer cell line. Overexpression of STEAP1 was related to poor prognosis in ovarian cancer patients. Down-regulation of STEAP1 suppressed the invasion, migration, proliferation, clonogenicity, EMT progression in human ovarian cancer cells and xenograft tumour growth in vivo, but it enhanced apoptosis. In human ovarian cancer, the STEAP1 gene is highly expressed, and its function is correlated with human ovarian cancer cell metastasis and growth. STEAP1 may be a possible target for suppressing ovarian cancer metastasis.
Assuntos
Antígenos de Neoplasias/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/secundário , Oxirredutases/genética , Animais , Apoptose , Proliferação de Células , Feminino , Regulação da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Experimentais/secundário , Neoplasias Ovarianas/patologia , Células Tumorais CultivadasRESUMO
Brucella spp. are facultative intracellular pathogens and zoonotic agents which pose a huge threat to human health and animal husbandry. The B. melitensis, B. abortus, and B. suis cause undulant fever and influenza-like symptoms in humans. However, the effects of B. canis have not been extensively studied. The quorum sensing-dependent transcriptional regulator VjbR influences the Brucella virulence in smooth type Brucella strains, such as B. melitensis, B. abortus and rough type Brucella ovis. However, the function of VjbR in the rough-type B. canis is unknown. In the present study, we discovered that deletion of this regulator significantly affected Brucella virulence in macrophage and mice infection models. The expression levels of virB operon and the ftcR gene were significantly altered in the vjbR mutant strain. We further investigated the protective effect of different doses of the vjbR mutant in mice and the results indicated that VjbR conferred protection against the virulent B. canis strain. This study presents the first evidence that the transcriptional regulator VjbR has important function in B. canis. In addition, according to its reduced virulence and the protective immunity it induces in mice, it can be a potential live attenuated vaccine against B. canis.
Assuntos
Proteínas de Bactérias/genética , Brucella canis/fisiologia , Brucelose/microbiologia , Regulação Bacteriana da Expressão Gênica , Mutação , Proteínas Repressoras/genética , Transativadores/genética , Sistemas de Secreção Tipo IV/fisiologia , Animais , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Vacinas Bacterianas/imunologia , Brucelose/imunologia , Brucelose/prevenção & controle , Linhagem Celular , Deleção de Genes , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Percepção de Quorum/genética , Células RAW 264.7 , Proteínas Repressoras/imunologia , Proteínas Repressoras/metabolismo , Transativadores/imunologia , Transativadores/metabolismo , Virulência , Fatores de Virulência/genéticaRESUMO
Purpose: We investigated which obesity-associated parameters can better predict the risk of anastomotic leakage (AL) in rectal cancer patients that underwent anterior resection of the rectum.Method: Patients (n = 589) who underwent anterior resection of the rectum with a primary anastomosis were included in this study, including 44 patients with AL and 545 without AL. Univariate analysis was used to compare demographic characteristics and to select risk factors that were used in one-to-one propensity score matching (PSM). Obesity-associated parameters, including preoperative body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA), VFA/TFA ratio, serum cholesterol, and triglycerides, were compared between the two groups after PSM.Results: Sex, neoadjuvant chemotherapy, operation time, and anastomosis level from the anal verge were risk factors for AL (p < .05). After the PSM, BMI, VFA, SFA, TFA, VFA/TFA, and serum cholesterol showed no significant difference between the two group (p > .05). However, the level of serum triglycerides was an independent risk factor for AL (p = .024, odds ratio = 2.95).Conclusions: Serum triglycerides have potential as a predictive indicator for AL, which may improve the treatment and outcomes of patients with AL.
Assuntos
Fístula Anastomótica/etiologia , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/cirurgia , Triglicerídeos/sangue , Idoso , Canal Anal/cirurgia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/sangue , Fístula Anastomótica/epidemiologia , Índice de Massa Corporal , Feminino , Humanos , Gordura Intra-Abdominal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
In December 2019, an outbreak of coronavirus infection emerged in Wuhan, Hubei Province of China, which is now named Coronavirus Disease 2019 (COVID-19). The outbreak spread rapidly within mainland China and globally. This paper reviews the different imaging modalities used in the diagnosis and treatment process of COVID-19, such as chest radiography, computerized tomography (CT) scan, ultrasound examination, and positron emission tomography (PET/CT) scan. A chest radiograph is not recommended as a first-line imaging modality for COVID-19 infection due to its lack of sensitivity, especially in the early stages of infection. Chest CT imaging is reported to be a more reliable, rapid, and practical method for diagnosis of COVID-19, and it can assess the severity of the disease and follow up the disease time course. Ultrasound, on the other hand, is portable and involves no radiation, and thus can be used in critically ill patients to assess cardiorespiratory function, guide mechanical ventilation, and identify the presence of deep venous thrombosis and secondary pulmonary thromboembolism. Supplementary information can be provided by PET/CT. In the absence of vaccines and treatments for COVID-19, prompt diagnosis and appropriate treatment are essential. Therefore, it is important to exploit the advantages of different imaging modalities in the fight against COVID-19.