RESUMO
In the investigation of heterotrimeric G protein-mediated signal transduction in planta, their roles in the transmittance of low K+ stimuli remain to be elucidated. Here, we found that the primary root growth of wild-type Arabidopsis was gradually inhibited with the decrease of external K+ concentrations, while the primary root of the mutants for G protein ß subunit AGB1 and γ subunits AGG1, AGG2 and AGG3 could still grow under low K+ conditions (LK). Exogenous NAA application attenuated primary root elongation in agb1 and agg1/2/3 but promoted the growth in wild-type seedlings under LK stress. Using ProDR5:GFP, ProPIN1:PIN1-GFP and ProPIN2:PIN2-GFP reporter lines, a diminishment in auxin concentration at the radicle apex and a reduction in PIN1and PIN2 efflux carrier abundance were observed in wild-type roots under LK, a phenomenon not recorded in the agb1 and agg1/2/3. Further proteolytic and transcriptional assessments revealed an enhanced degradation of PIN1 and a suppressed expression of PIN2 in the wild-type background under LK, contrasting with the stability observed in the agb1 and agg1/2/3 mutants. Our results indicate that the G protein ß and γ subunits play pivotal roles in suppressing of Arabidopsis root growth under LK by modulating auxin redistribution via alterations in PIN1 degradation and PIN2 biosynthesis.
RESUMO
BACKGROUND: A comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB). METHODS: A retrospective review of our institution's local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin. RESULTS: ACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival. CONCLUSION: There may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population.
Assuntos
Neoplasias Ósseas , Condroblastoma , Humanos , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Condroblastoma/diagnóstico , Condroblastoma/cirurgia , Imuno-Histoquímica , Prognóstico , Estudos RetrospectivosRESUMO
Acute transient swelling (ATS) of the thyroid is a rare complication following fine-needle aspiration (FNA) of thyroid nodules. We present 31 cases with 35 nodules encountered at our institute and reported in the literature, to provide further information. The incidence rate in our institute was 0.46%. Of these nodules, 74.3% (26/35) were solid, 65.7% (23/35) exhibited hypervascularity, and 77.2% (27/35) were benign or follicular neoplasms. Although most cases (87.1%, 27/31) occurred within 2 h after FNA, four patients experienced delayed ATS after 7 h to 2 days. Therefore, awareness of this complication, especially its delayed occurrence, should be raised.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina/efeitos adversos , Edema , Humanos , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
BACKGROUND: This study aimed to investigate the effect of enamel-surface modifications on the shear bond strength between ceramic brackets bonded using different adhesive materials and the enamel surface and to identify the most suitable clinical adhesive and bonding method. Whether the non-acid-etching treatment met the clinical bond strength was also determined. METHODS: A total of 108 extracted premolars were divided into nine groups (n = 12) based on the different enamel-surface modification techniques (acid etching, deproteinization, and wetting). Group 1 was bonded with Transbond™ XT adhesive, whereas groups 2-9 were bonded with resin-modified glass ionomer cement (RMGIC). The treatment methods for each group were as follows: groups 1 and 2, acid etching; group 3, acid etching and wetting; group 4, acid etching and deproteinization; group 5, acid etching, deproteinization, and wetting; group 6, deproteinization; group 7, deproteinization and wetting; group 8, without treatment; and group 9, wetting. The samples' shear bond strength was measured using an universal testing machine. Adhesive remnant index (ARI) was examined using a stereomicroscope. The enamel-surface morphology was observed with a scanning electron microscope. One-way ANOVA with Tukey's post-hoc test and chi-square test were used for statistical analysis, and p < 0.05 and α = 0.05 were considered statistically significant. RESULTS: The ARIs of groups 1-5 and 6-9 were statistically significant (p = 0.000). The enamel surface of groups 1-5 was demineralized, and only a tiny amount of protein remained in groups 7 and 8, whereas a thick layer of protein remained in groups 8 and 9. CONCLUSIONS: RMGIC adhesive did not damage the enamel surface and achieved the required clinical bond strength. The enamel surface was better treated with 5.25% sodium hypochlorite preferably under non-acid-etching conditions.
Assuntos
Colagem Dentária , Braquetes Ortodônticos , Condicionamento Ácido do Dente/métodos , Colagem Dentária/métodos , Cimentos Dentários/uso terapêutico , Esmalte Dentário , Análise do Estresse Dentário , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/uso terapêutico , Humanos , Teste de Materiais , Cimentos de Resina/química , Cimentos de Resina/uso terapêutico , Resistência ao Cisalhamento , Propriedades de SuperfícieRESUMO
BACKGROUND: This study aimed to compare the maxillary sinus dimensions and surface area in accordance with skeletal malocclusion, gender and ethnicity factors in a sample of Chinese and Yemeni patients. METHODS: This cross-sectional study analysed 180 maxillary sinuses using 180 lateral cephalometric radiographs. The patients were subdivided into two ethnic groups: Chinese and Yemeni. Each ethnic group comprised 90 patients, and men and women were divided equally. Each ethnic group was classified into three skeletal classes using ANB and Wits appraisal (skeletal Classes I, II and III). Pearson's correlation coefficient was also used to assess the relationship between maxillary sinus dimensions and cephalometric parameters. RESULTS: Men had larger maxillary sinuses than women; skeletal Class II had a higher length and surface area increase than other skeletal classes, although skeletal Classes I and II were almost equal in height. Except for the maxillary sinus length, none of these findings were statistically significant. The maxillary sinuses in Chinese are larger than those in Yemenis (P = 0.000). These variables were positively correlated with SNA, SNB and Co-A. The maxillary sinus length and Co-Gn were positively correlated. The NA-APO and NA-FH angles were also correlated with the maxillary sinus surface area. However, the gonial and GoGn-Sn angles negatively affected the maxillary sinus dimension and surface area. CONCLUSIONS: Men had larger maxillary sinuses than women in both ethnic groups, and Chinese individuals had larger maxillary sinuses than Yemenis. Skeletal Class II malocclusion of both ethnicities had larger maxillary sinus dimensions. Furthermore, the maxillary sinus dimensions correlated with cephalometric parameters.
Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Masculino , Humanos , Feminino , Seio Maxilar/diagnóstico por imagem , Estudos Transversais , População do Leste Asiático , Cefalometria/métodos , Maxila/diagnóstico por imagem , Má Oclusão Classe III de Angle/diagnóstico por imagemRESUMO
In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.
Assuntos
Inflamassomos , MicroRNAs , Animais , Proteínas Hedgehog , Inflamassomos/genética , Inflamassomos/metabolismo , Interleucina-6 , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Medicina Tradicional Chinesa , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de SinaisRESUMO
RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.
Assuntos
Autofagia/fisiologia , Neoplasias Colorretais/genética , Desoxiglucose/administração & dosagem , Lovastatina/administração & dosagem , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Antimetabólitos/administração & dosagem , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cloroquina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Células HCT116 , Células HEK293 , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVES: Biliary perfusion is considered to contribute to biliary diseases, but routine imaging methods are insufficient to show it. This research investigated the ability of contrast-enhanced ultrasound (CEUS) for biliary perfusion in a biliary ischemia model. METHODS: This research consisted of 2 parts. First, to determine whether CEUS enhancement of the tiny biliary wall represents biliary perfusion, a vascular tracer was used as a reference to evaluate the consistency with the enhancement of the biliary wall on CEUS and the staining by the vascular tracer under the conditions of occluded and recovered biliary perfusion. In the second part, the ability of CEUS for biliary ischemia was further evaluated with microvascular density measurement as a reference. The enhancement patterns were assigned CEUS scores, in which higher scores meant more decreased enhancement, and the diagnostic ability of CEUS was assessed by a receiver operating characteristic curve analysis. RESULTS: The biliary wall was unstained by the vascular tracer and nonenhanced on CEUS when biliary perfusion was interrupted and was stained blue and enhanced after recovery. The biliary wall in the ischemia surgery group showed lower microvascular density measurements (P < .001), decreased enhancement levels (P < .001), and higher CEUS scores (P < .001). When a CEUS score of 3 or higher (obvious decrease of the biliary wall to hypoenhancement or nonenhancement in the arterial phase or rapid wash-out to nonenhancement in the portal venous phase) was applied, CEUS had sensitivity of 87.8%, specificity of 98.3%, accuracy of 93.8%, and an area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Contrast enhancement of the biliary wall on CEUS represents biliary perfusion and has reasonably good diagnostic performance for biliary ischemia in an experimental animal setting.
Assuntos
Meios de Contraste , Isquemia , Animais , Humanos , Isquemia/diagnóstico por imagem , Curva ROC , UltrassonografiaRESUMO
The purpose of this letter to the Editor is to report some shortcomings in the statistical analysis and variable grouping in the recent publication of the article "Clinical outcomes of chondroblastoma treated using synthetic bone substitute: risk factors for developing radiographic joint degeneration," and to further explore some of the factors that may affect the clinical prognosis of chondroblastoma patients. We also suggest future prospective controlled studies with large samples to improve the limitations encountered by Outani et al. (World J Surg Oncol. 18(1):47, 2020) due to insufficient statistical power of variables and lack of controls.
Assuntos
Neoplasias Ósseas , Substitutos Ósseos , Condroblastoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Humanos , Prognóstico , Fatores de RiscoAssuntos
Neoplasias Ósseas , Condroblastoma , Fusão Vertebral , Adulto , Condroblastoma/diagnóstico , Condroblastoma/cirurgia , Humanos , CrânioRESUMO
Alzheimer's disease (AD) is one of the common neurodegenerative diseases and amyloid-ß (Aß) is thought to be a key molecule contributing to AD pathology. Recently, curcumin is supposed to be beneficial to AD treatment. This study investigates the inhibitory effects of curcumin on Aß-induced cell damage and death involving NMDA receptor-mediated intracellular Ca(2+) elevation in human neuroblastoma SH-SY5Y cells. Cells were impaired significantly in Aß-damaged group compared with the control group, and cell viability was decreased while the released LDH from the cytosol was increased. Curcumin promotes cell growth and decreases cell impairment induced by Aß. Curcmin attenuates Aß-induced elevation of the ratio of cellular glutamate/γ-aminobutyric acid (GABA) with a concentration-dependent manner. Curcumin inhibits Aß-induced increase of cellular Ca(2+) and depresses Aß-induced phosphorylations of both NMDA receptor and cyclic AMP response element-binding protein (CREB) and activating transcription factor 1 (ATF-1). These results indicated that curcumin inhibits Aß-induced neuronal damage and cell death involving the prevention from intracellular Ca(2+) elevation mediated by the NMDA receptor.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Cálcio/metabolismo , Curcumina/administração & dosagem , Neurônios/metabolismo , Neurônios/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Chordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial. METHODS: We employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma. RESULTS: Previous research by van Oost et al argued that compared with other sarcomas, chordomas typically exhibit an immunologically "hot" microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of "cold" and "hot". Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells. CONCLUSIONS: These findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma.
Assuntos
Cordoma , Microambiente Tumoral , Humanos , Cordoma/imunologia , Cordoma/genética , Cordoma/terapia , Microambiente Tumoral/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Imunoterapia/métodosRESUMO
BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.
Assuntos
Neoplasias Ósseas , Denosumab , Tumor de Células Gigantes do Osso , Microambiente Tumoral , Humanos , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/patologia , Microambiente Tumoral/imunologia , Feminino , Masculino , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/imunologia , Pessoa de Meia-Idade , Estudos de Coortes , Adulto Jovem , Resultado do Tratamento , Prognóstico , Conservadores da Densidade Óssea/uso terapêutico , AdolescenteRESUMO
BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.
Assuntos
Fibroblastos Associados a Câncer , Cordoma , Humanos , Cordoma/genética , Perfilação da Expressão Gênica , RNA-Seq , Estresse do Retículo Endoplasmático , Microambiente TumoralRESUMO
OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.
RESUMO
We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.
Assuntos
Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Medula Espinal , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Animais , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , NF-kappa B/metabolismo , Masculino , Apoptose/fisiologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Sistema Linfático/fisiopatologia , Sistema Linfático/patologia , Edema/patologia , Ducto Torácico/fisiopatologia , Feminino , Micropartículas Derivadas de Células/metabolismoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Polimorfismo de Nucleotídeo Único , Feminino , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Predisposição Genética para Doença , Estudos Transversais , Estudos Prospectivos , Estudos Observacionais como Assunto , Idoso , Estudo de Associação Genômica AmplaRESUMO
Slippery liquid-infused porous surfaces (SLIPS) are self-healing protective coatings that can be made by infiltration of a porous scaffold with a chemically resistant oil. A popular method to apply a SLIPS coating is using electrospinning to deposit a nanofiber mesh onto the intended substrate. However, electrospinning only lightly deposits the nanofibers onto the intended substrate, so the coating detaches easily even when unintended. We report a simple, yet effective, solution to the adhesion problem. Electrospun nanofiber meshes are typically well entangled and cohesive, so they can be detached from the electrospinning target and transferred onto the final target. Using a thin layer of adhesive on the intended surface, the electrospinning mesh can be securely attached and infiltrated with protective oil to yield a more stable SLIPS coating. An adhered coating can be submerged under corrosive solution and repeatedly self-heal from damage to the same spot. With the electrospun nanofiber meshes' flexibility and stretchability, the meshes can be fitted around a wide range of targets including ones that are otherwise difficult to apply a nanofiber mesh on. The use of an adhesive interlayer between the nanofiber mesh and substrate is a simple solution to improve coating stability, and the solution facilitates application of SLIPS onto a broader range of substrates.
RESUMO
Bioleaching is a promising route for electrolytic manganese (Mn) residue (EMR) reutilization due to being eco-friendly and cost-effective. However, microbes with high bioleaching efficiency are scarce. This work aimed to isolate, screen, and characterize a novel fungal strain with high Mn-bioleaching efficiency from EMR, and study the kinetics and mechanism. The novel Penicillium oxalicum strain Z6-5-1 was found to selectively bioleach Mn from EMR. A maximum Mn2+ recovery of 93.3 % was achieved after 7 days and was mainly dependent upon acidolysis of the bio-organic acids, specifically gluconic acid and oxalic acid, as well as mycelial biosorption. This efficiency was the highest reported in the literature for a fungus over such a short time. EMR strongly induced P. oxalicum to produce gluconic acid and oxalic acid. The novel transcription factor PoxCxrE of P. oxalicum controlled the production of bio-organic acids by regulating the expression of rate-limiting enzyme genes involved in the biosynthesis of bio-organic acids. Scanning electron microscopy, laser particle size analysis, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy were employed to analyze EMR changes after bioleaching. This study provides an alternative fungal resource for Mn-bioleaching of EMR, and a novel target for metabiotic engineering to improve bio-organic acid production.