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1.
Langmuir ; 40(29): 15196-15204, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39007690

RESUMEN

Micro/nanostructured metal surfaces fabricated by laser direct writing (LDW) have been widely used in wettability-related fields. Previous studies focused on the effects of surface structural patterns or chemical composition on wettability, while the coupling mechanism and respective contributions of the two are not distinct. This paper reveals the coupling effect of micro/nanoscale characteristics on the wettability of LDW aluminum surfaces and elucidates the transition mechanism between wetting states on the surfaces with linear laser energy density. Through the contact angle experiments, a wetting state transition of the LDW surface is found from a more hydrophilic than pristine rose petal effect to lotus effect. Based on the bionic analysis method of the superhydrophobicity factors of lotus leaves, the contributions to the wettability of LDW surfaces are divided into the micro/nanoscale characteristics. The theoretical model for identifying the wetting state of a rough surface is proposed. Based on this model, the average Young's contact angle, θ̅Y, is calculated, which indicates the contribution of the nanoscale characteristics. During the transition process from rose petal effect to lotus effect, θ̅Y > 90° is a necessary condition for detachment from the rose petal effect, which is contributed by the high specific surface organic adsorption at the nanoscale. What is more, the wetting state determined by the microscale characteristics further enhances its hydrophobicity, leading to the lotus effect. Based on the wetting state identification model and the Cassie-Baxter equation, the change of micro/nanoscale characteristics on aluminum surfaces after LDW treatment is presented, and the influence of micro/nanoscale characteristics on the wetting state is decoupled and quantified. This research helps to coordinate the effects of surface structure and chemical composition on wettability in the design of specific wettability functional surfaces and can also be applied to other high heat density surface processing fields.

2.
Gut Microbes ; 16(1): 2363020, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841892

RESUMEN

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1-/- mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.


Asunto(s)
Butiratos , Colitis , Microbioma Gastrointestinal , Granzimas , Interleucina-10 , Ratones Endogámicos C57BL , Células TH1 , Animales , Interleucina-10/metabolismo , Interleucina-10/genética , Interleucina-10/inmunología , Células TH1/inmunología , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Butiratos/metabolismo , Butiratos/farmacología , Granzimas/metabolismo , Colitis/inmunología , Colitis/microbiología , Colitis/metabolismo , Ratones Noqueados , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Tolerancia Inmunológica , Proteínas de Homeodominio
3.
Biochem Biophys Res Commun ; 726: 150264, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-38905784

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.


Asunto(s)
Regulación hacia Abajo , Gastrectomía , N-Metiltransferasa de Histona-Lisina , Activación de Macrófagos , Macrófagos , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/etiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Masculino , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Metabolismo de los Lípidos
4.
Zhongguo Gu Shang ; 37(5): 445-50, 2024 May 25.
Artículo en Chino | MEDLINE | ID: mdl-38778526

RESUMEN

OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Anciano , Fracturas Óseas/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Fijación Interna de Fracturas/métodos
5.
Int J Surg ; 110(6): 3307-3325, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573134

RESUMEN

BACKGROUND: Sleeve gastrectomy (SG) is known to alleviate non-alcoholic fatty liver disease (NAFLD) and restore liver function; however, its underlying mechanism remains unclear. MATERIALS AND METHODS: We investigated the effect of SG on the metabolic phenotype of diet-induced obese (DIO) mice. Postoperative stained liver images were analyzed to determine the hepatocyte proliferation phenotype. Single-cell RNA sequencing was used to characterize the regeneration signals of the liver after SG in DIO mice, and real-time quantitative reverse transcription PCR was performed to verify the above results. We employed Olink proteomics to capture serum element changes and investigated the role of Yes1 protein in liver regeneration and carcinogenesis through the Hippo-YAP pathway. DIO mice were treated with YAP inhibitor verteporfin after SG mice to clarify whether SG-induced liver regeneration is related to the YAP signaling pathway. RESULTS: SG significantly reduced NAFLD-associated dysfunction in hepatocytes and replaced them with fully functional hepatocytes, which have a high regenerative capacity across the entire liver. SG also enhanced the hepatic regenerative capacity, as demonstrated by SG combined with hepatic lobectomy in healthy mice. Yes1 protein was identified as the signaling molecule most closely related to classical regeneration signals. Our study showed that SG-enhanced proliferation and improved metabolism did not depend on YAP signaling. CONCLUSION: SG can enhance hepatic regenerative capacity and improve liver metabolism. This study provides a better understanding of the mechanisms underlying SG-induced metabolic improvements.


Asunto(s)
Modelos Animales de Enfermedad , Gastrectomía , Hepatocitos , Regeneración Hepática , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/cirugía , Regeneración Hepática/fisiología , Ratones , Hepatocitos/metabolismo , Gastrectomía/métodos , Masculino , Ratones Endogámicos C57BL , Proliferación Celular , Transducción de Señal
6.
BMC Musculoskelet Disord ; 25(1): 250, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561697

RESUMEN

BACKGROUND: Ankle fractures are prevalent injuries that necessitate precise diagnostic tools. Traditional diagnostic methods have limitations that can be addressed using machine learning techniques, with the potential to improve accuracy and expedite diagnoses. METHODS: We trained various deep learning architectures, notably the Adapted ResNet50 with SENet capabilities, to identify ankle fractures using a curated dataset of radiographic images. Model performance was evaluated using common metrics like accuracy, precision, and recall. Additionally, Grad-CAM visualizations were employed to interpret model decisions. RESULTS: The Adapted ResNet50 with SENet capabilities consistently outperformed other models, achieving an accuracy of 93%, AUC of 95%, and recall of 92%. Grad-CAM visualizations provided insights into areas of the radiographs that the model deemed significant in its decisions. CONCLUSIONS: The Adapted ResNet50 model enhanced with SENet capabilities demonstrated superior performance in detecting ankle fractures, offering a promising tool to complement traditional diagnostic methods. However, continuous refinement and expert validation are essential to ensure optimal application in clinical settings.


Asunto(s)
Fracturas de Tobillo , Humanos , Fracturas de Tobillo/diagnóstico por imagen , Benchmarking , Aprendizaje Automático
7.
World J Gastroenterol ; 30(13): 1887-1898, 2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38659480

RESUMEN

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.


Asunto(s)
Gastrectomía , Pérdida de Peso , Humanos , Masculino , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/cirugía , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Comorbilidad , Obesidad/cirugía , Obesidad/diagnóstico , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Cirugía Bariátrica/métodos , Puntaje de Propensión , Enfermedad del Hígado Graso no Alcohólico/cirugía , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Incidencia
8.
iScience ; 27(2): 108843, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38303702

RESUMEN

This study was designed to explore the roles of CREB3L4 in the pathogenesis and drug resistance of hepatocellular carcinoma (HCC). The proliferation of HCC lines was determined in the presence of CREB3L4 over-expression and silencing. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay were performed to screen the potential target of CREB3L4 on mTORC1. Xenografted tumor model was established to define the regulatory effects of CREB3L4 in the tumorigenesis. Then we evaluated the roles of CREB3L4 in chemosensitivity to sorafenib treatment. CREB3L4 significantly induced the HCC cell proliferation by modulating the activation of mTROC1-S6K1 signaling pathway via binding with RHEB promoter. Moreover, CREB3L4 dramatically inhibited the chemosensitivity to sorafenib treatment via up-regulating RHEB-mTORC1 signaling. CREB3L4 promoted HCC progression and decreased its chemosensitivity to sorafenib through up-regulating RHEB-mTORC1 signaling pathway, indicating a potential treatment strategy for HCC through targeting CREB3L4.

9.
Cell Mol Gastroenterol Hepatol ; 17(5): 703-711, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38246590

RESUMEN

Intestinal inflammatory fibrosis is a severe consequence of inflammatory bowel diseases (IBDs). There is currently no cure for the treatment of intestinal fibrosis in IBD. Although inflammation is necessary for triggering fibrosis, the anti-inflammatory agents used to treat IBD are ineffective in preventing the progression of intestinal fibrosis and stricture formation once initiated, suggesting that inflammatory signals are not the sole drivers of fibrosis progression once it is established. Among multiple mechanisms involved in the initiation and progression of intestinal fibrosis in IBD, stromal cells play critical roles in mediating the process. In this review, we summarize recent progress on how stromal cells regulate intestinal fibrosis in IBD and how they are regulated by focusing on immune regulation and gut microbiota. We also outline the challenges moving forward in the field.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/patología , Intestinos/patología , Inflamación/patología , Fibrosis
10.
J Orthop Surg Res ; 18(1): 957, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38087344

RESUMEN

BACKGROUND: Posterior malleolus fractures are known to be associated with ankle instability. The complexities involved in obtaining precise laboratory-based spatial pressure measurements of the ankle highlight the significance of exploring the biomechanical implications of these fractures. METHODS: Finite element analysis was utilized to examine the stress distribution across the contact surface of the ankle joint, both in its natural state and under varied sagittal fracture line angles. The study aimed to identify stress concentration zones and understand the influence of sagittal angles on stress distribution. RESULTS: Three distinct stress concentration zones were identified on the ankle's contact surface: the anterolateral tibia, the anteromedial tibia, and the fracture line. The most significant stress was observed at the fracture line when a fracture occurs. Stress at the fracture line notably spikes as the sagittal angle decreases, which can potentially compromise ankle stability. Larger sagittal angles exhibited only minor stress variations at the contact surface's three vertices. It was inferred that sagittal angles below 60° might pose risks to ankle stability. CONCLUSIONS: The research underscores the potential implications of fractures on the stress profile of the ankle joint, emphasizing the role of the contact surface in ensuring stability. The identification of three zones of stress concentration and the influence of sagittal angles on stress distribution offers a valuable reference for therapeutic decision-making. Further, the study reinforces the importance of evaluating sagittal fracture angles, suggesting that angles below 60° may compromise ankle stability.


Asunto(s)
Fracturas de Tobillo , Inestabilidad de la Articulación , Humanos , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/complicaciones , Tobillo , Análisis de Elementos Finitos , Articulación del Tobillo , Fijación Interna de Fracturas
11.
Sensors (Basel) ; 23(15)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37571615

RESUMEN

Rapid and accurate identification of precipitation clouds from satellite observations is essential for the research of quantitative precipitation estimation and precipitation nowcasting. In this study, we proposed a novel Convolutional Neural Network (CNN)-based algorithm for precipitation cloud identification (PCINet) in the daytime, nighttime, and nychthemeron. High spatiotemporal and multi-spectral information from the Fengyun-4A (FY-4A) satellite is utilized as the inputs, and a multi-scale structure and skip connection constraint strategy are presented in the framework of the algorithm to improve the precipitation cloud identification. Moreover, the effectiveness of visible/near-infrared spectral information in improving daytime precipitation cloud identification is explored. To evaluate this algorithm, we compare it with five other deep learning models used for image segmentation and perform qualitative and quantitative analyses of long-time series using data from 2021. In addition, two heavy precipitation events are selected to analyze the spatial distribution of precipitation cloud identification. Statistics and visualization of the experiment results show that the proposed model outperforms the baseline models in this task, and adding visible/near-infrared spectral information in the daytime can effectively improve model performance. More importantly, the proposed model can provide accurate and near-real-time results, which has important application in observing precipitation clouds.

12.
Gut Microbes ; 15(1): 2190311, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36927391

RESUMEN

G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and Gpr120-/- mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120-/- mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120-/- mice showed altered microbiota composition. Gpr120-/- mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli O83:H1 isolated from a Crohn's disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.


Asunto(s)
Infecciones por Enterobacteriaceae , Microbioma Gastrointestinal , Ratones , Animales , Neutrófilos , Especies Reactivas de Oxígeno , ARN Ribosómico 16S , Bacterias/genética , Escherichia coli
13.
Cell Mol Gastroenterol Hepatol ; 15(5): 1161-1179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36736893

RESUMEN

BACKGROUND & AIMS: T helper 1 (Th1) effector cells are implicated in inflammatory bowel disease. The stimulator of interferon genes (STING), an intracellular DNA sensor, has been shown to regulate infection and various cancers. However, whether and how intrinsic STING signaling in Th1 cells regulates colitis is still unknown. METHODS: Dextran sodium sulfate-induced colitis and wild-type/STING-deficient CD4+T cell adoptive transfer models were used to analyze the role of STING in regulating colitis. The effect of STING on Th1 cells was determined by flow cytometry, RNA sequencing, metabolic assays, and mitochondrial functions. 16S ribosomal RNA sequencing and germ-free mice were used to investigate whether the microbiota were involved. The in vivo effect of STING agonist in murine colitis was determined. The expression and role of STING in human T cells were also determined. RESULTS: Activation of STING transformed proinflammatory IFNγ+Th1 cells into IL-10+IFNγ+Th1 cells, which were dramatically less pathogenic in inducing colitis. STING promoted Th1 interleukin (IL)-10 production by inducing STAT3 translocation into nuclear and mitochondria, which promoted Blimp1 expression and mitochondrial oxidation, respectively. Blockade of glucose or glutamine-derived oxidation, but not lipid-derived oxidation, suppressed STING induction of IL-10. Gut microbiota were changed in STING-/- mice, but the altered microbiota did not mediate STING effects on intestinal CD4+T cell production of IL-10. Translationally, STING agonists suppressed both acute and chronic colitis. Intestinal STING+ CD4+T cells were increased in inflammatory bowel disease patients, and STING agonists upregulated IL-10 production in human CD4+T cells. CONCLUSIONS: These findings establish a crucial role of T cell-intrinsic STING in switching off the pathogenic programs of Th1 cells in intestinal inflammation.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Humanos , Ratones , Colitis/patología , Interleucina-10 , Intestinos/patología , Células TH1
14.
Inflamm Bowel Dis ; 29(6): 946-959, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36661414

RESUMEN

BACKGROUND: Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood. We further investigated whether and how STING affects intestinal IgA response. METHODS: Intestinal IgA was determined between wild-type (WT) mice and Sting-/- mice in steady conditions and upon enteric Citrobacter rodentium infection. STING agonists were used to stimulating B cells or dendritic cells in vitro. Gut microbiota composition was examined by 16S ribosomal RNA gene sequencing. Bacteria metabolomics functional analyses was performed by PICRUSt2. Fecal short-chain fatty acid (SCFA) was determined by Mass spectrometry and Cedex Bio Analyzer. Gut bacteria from WT mice and Sting-/- mice were transferred into germ-free mice and antibiotic-pretreated mice. RESULTS: Intestinal IgA response was impaired in Sting-/- mice. However, STING agonists did not directly stimulate B cells or dendritic cells to induce IgA. Interestingly, Sting-/- mice displayed altered gut microbiota composition with decreased SCFA-producing bacteria and downregulated SCFA fermentation pathways. Transfer of fecal bacteria from Sting-/- mice induced less IgA than that from WT mice in germ-free mice and antibiotic-pretreated mice, which is mediated by GPR43. Acetate, the dominant SCFA, was decreased in Sting-/- mice, and supplementation of acetate restored intestinal IgA production in Sting-/- mice. CONCLUSIONS: STING promotes intestinal IgA by regulating acetate-producing gut bacteria.


STING pathway contributes to maintaining a group of acetate-producing bacteria. STING regulates through these bacteria in a GPR43-dependent manner.


Asunto(s)
Inmunoglobulina A , Microbiota , Ratones , Animales , Inmunoglobulina A/metabolismo , Simbiosis , Acetatos/metabolismo , Ácidos Grasos Volátiles/metabolismo , Factores Inmunológicos , Bacterias , Antibacterianos , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo
15.
Orthop Surg ; 15(1): 214-222, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36419316

RESUMEN

OBJECTIVE: Valgus-impacted femoral neck fractures with or without posterior tilt of the femoral head are very common and full of pitfalls in clinical practice, which may lead to femoral neck shortening (FNS) and avascular necrosis (AVN). The study tries to introduce a novel technical trick aiming at anatomical reduction of valgus-impacted femoral neck fracture with minimally invasive procedure, and summarize the clinical prognosis in case series. METHODS: In this retrospective study, 24 patients (seven men and 17 women) with valgus-impacted femoral neck fractures between May 2017 and July 2020 were managed by "in-out-in" percutaneous reduction technique (percutaneous reduction group). Another 24 cases (10 men and 14 women) suffering the fractures underwent in situ fixation were enrolled as control group for function comparison (in situ fixation group). All patients were followed up for 24-42 months. The clinical outcomes included complications after operations (χ2 test) and Harris Hip Score (HHS) for hip function (unpaired t test) in the two groups. The radiographic outcomes were evaluated by collodiaphyseal angle, posterior tilt angle, and FNS before the operation and during the follow-up in the percutaneous reduction group (unpaired t test). RESULTS: Patients' preoperative data, including age, sex, affected side, fracture types, and medical history, were similar between the two groups, respectively (p > 0.05). After surgery, the mean HHS at 6, 12, and 24 months were all better in the percutaneous reduction group (76 ± 6.72, 85.34 ± 6.33 and 90.54 ± 5.81) than that in the in situ fixation group (70.86 ± 6.91, 80 ± 6.11 and 84.1 ± 7.82), respectively (p < 0.05). One patient suffered fixation failure with screws retreat and one patient suffered AVN in the percutaneous reduction group. In the in situ fixation group, AVN occurred in two patients at last follow-up. There was no significant difference in complication amounts between the two groups (p > 0.05). In the percutaneous reduction group, collodiaphyseal angle, posterior tilt angle, and amount of FNS were significantly different between preoperative cases and immediately postoperative cases (p < 0.05). However, there was no statistical difference of the measurements among postoperative cases at different time points (within 24 h, 6 months, and 2 years postoperatively) (p > 0.05). CONCLUSIONS: Our experience of the technique and the case series show that "in-out-in" percutaneous reduction technique for treatment of valgus-impacted femoral neck fracture with or without posterior tilt of the femoral head is safe and effective for achieving successful bone union and satisfactory function.


Asunto(s)
Fracturas del Cuello Femoral , Osteonecrosis , Masculino , Humanos , Femenino , Estudios Retrospectivos , Resultado del Tratamiento , Fijación Interna de Fracturas/métodos , Fracturas del Cuello Femoral/cirugía
16.
Gastroenterology ; 164(1): 89-102, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36113570

RESUMEN

BACKGROUND & AIMS: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood. METHODS: In this study, T-cell transfer model with wild-type (WT) and Areg-/- Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg-/- mice were used. CD4+ T-cell expression of AREG was determined by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of AREG on proliferation/migration/collagen expression in human intestinal myofibroblasts was determined. AREG expression was assessed in healthy controls and patients with CD with or without intestinal fibrosis. RESULTS: Although Th1 and Th17 cells induced intestinal inflammation at similar levels when transferred into Tcrßxδ-/- mice, Th17 cells induced more severe intestinal fibrosis. Th17 cells expressed higher levels of AREG than Th1 cells. Areg-/- mice developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg-/- Th17 cells induced less severe fibrosis in Tcrßxδ-/- mice compared with WT Th17 cells. Interleukin (IL)6 and IL21 promoted AREG expression in Th17 cells by activating Stat3. Stat3 inhibitor suppressed Th17-induced intestinal fibrosis. AREG promoted human intestinal myofibroblast proliferation, motility, and collagen I expression, which was mediated by activating mammalian target of rapamycin and MEK. AREG expression was increased in intestinal CD4+ T cells in fibrotic sites compared with nonfibrotic sites from patients with CD. CONCLUSIONS: These findings reveal that Th17-derived AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD. Thereby, AREG might serve as a potential therapeutic target for fibrosis in CD.


Asunto(s)
Colitis , Enfermedad de Crohn , Animales , Humanos , Ratones , Anfirregulina/genética , Anfirregulina/metabolismo , Colitis/metabolismo , Colágeno/metabolismo , Enfermedad de Crohn/patología , Sulfato de Dextran/efectos adversos , Fibrosis , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Miofibroblastos/patología , Células Th17/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
17.
Sci Rep ; 12(1): 19090, 2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36351978

RESUMEN

An open jet wind tunnel has low-frequency pressure pulsation in common wind speed range due to its unique structural form, which seriously damages the quality of flow field in the test section. The low-frequency pressure fluctuation performance and control mechanism of Jilin University open jet and return flow wind tunnel are investigated by experiments and numerical simulation. The results show that the low-frequency pressure fluctuation is a narrow pulse phenomenon that only occurs in certain intervals, and several velocity intervals may be found in the same wind tunnel. The reliability of the numerical simulation is verified by comparing the peak frequency and amplitude of pressure fluctuation in numerical simulation and wind tunnel tests. A simplified model similar to and amplifying the phenomenon is established. The flow structure and vortex evolution are analyzed via detached eddy simulation. In the test section, large-scale shedding vortices are formed at the nozzle exit, introducing periodic pulsating instantaneous velocity and acting with the collector to form an edge-feedback. This acoustic feedback forms resonance with the pipeline circuit, resulting in poor flow field quality. In accordance with the mechanism of nozzle jet, two methods of controlling pulsation are proposed: spoiler and flow-follow device. The study shows that the effects of two methods are abrupt, and the frequency of pressure pulsation is changed. The spoiler destroys the complete structure of vortex ring in free jet and develops into a complementary double vortex ring structure, which is highly sensitive to size factors. The flow-follow device supplements the velocity loss of the free jet at the nozzle and develops into a double vortex ring with master-slave structure in the middle of the test section. Its vibration reduction effect is greatly affected by the flow velocity. It takes effect in an appropriate range where the flow velocity is higher than the nozzle velocity. If the follow velocity is extremely low, the flow-follow device cannot change the original jet structure. If the follow velocity is extremely high, the momentum of the fan will be greatly reduced, the flow field will be unstable, and another order of pulsation may be induced. This work lays a solid foundation for further understanding the aerodynamic characteristics and optimization mechanism of open jet wind tunnel.

18.
Orthop Surg ; 14(10): 2553-2562, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36056570

RESUMEN

OBJECTIVE: Surgical treatment for Schatzker type II tibial plateau fractures remains challenging and requires high-quality research. The aim of the study is to compare the "windowing" and "open book" techniques for the treatment of Schatzker type II tibial plateau fractures. METHODS: In this prospective study, all patients with Schatzker type II tibial plateau fractures between January 2014 and December 2017 were managed by open reduction and internal fixation using an anterolateral incision approach. "Windowing" group included 78 patients (53 men and 25 women), with an average age of 57.7 ± 13.5 years, who underwent the "windowing" technique, in which the procedure was performed through a small cortical window against the depressed zone of the lateral plateau. The "open book" group included 80 patients (56 men and 24 women), with an average age of 54.8 ± 12.4 years, who underwent the technique. The clinical outcomes included the Rasmussen classification of knee function and grading of post-traumatic arthritis. The radiographic outcome (x-ray and computed tomography [CT]) was the reduction quality of the lateral plateau based on the modified Rasmussen radiological assessment. The patient-reported outcome was visual analogue scale (VAS) scores. RESULTS: The mean follow-up time for the158 patients was 32 months (range, 24-42 months). The time elapsed from injury to surgery in "windowing" group and "open book" group were 3.7 ± 1.2 (range, 1-10 days) and 3.5 ± 1.4 days (range, 1-11 days), respectively, with no significant difference between the groups (P > 0.05). The operation times did not differ significantly between the "windowing" group (61.0 ± 8.3 min, range, 45-120 min) and the "open book" group (61.2 ± 10.4 min, range, 40-123 min) (P > 0.05). After surgery, CT revealed five (6.4%) and 15 (18.8%) cases of articular depression in the "windowing" and "open book" groups, respectively. Significant differences were observed in the articular depression of tibial plateau fractures between the groups (P < 0.05). However, condylar widening or valgus/varus did not differ significantly between the groups. Furthermore, no significant differences in knee function were observed during follow-up (P > 0.05). VAS scores were similar between the groups at 24 months after surgery (P > 0.05). There were significant differences in the number of severe post-traumatic arthritis (grades 2 and 3) cases between the groups (P < 0.05). CONCLUSIONS: The "windowing" and "open book" techniques are both effective for the treatment of Schatzker type II tibial plateau fractures. However, the "windowing" technique provides better reduction quality, leading to a satisfactory prognosis.


Asunto(s)
Artritis , Fracturas de la Tibia , Adulto , Anciano , Femenino , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Persona de Mediana Edad , Reducción Abierta/métodos , Estudios Prospectivos , Estudios Retrospectivos , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Resultado del Tratamiento
19.
iScience ; 25(9): 105004, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36093065

RESUMEN

Glucose, the critical energy source in the human body, is considered a potential risk factor in various autoimmune diseases when consumed in high amounts. However, the roles of glucose at moderate doses in the regulation of autoimmune inflammatory diseases and CD4+ T cell responses are controversial. Here, we show that while glucose at a high concentration (20% w/v) promotes intestinal inflammation, it suppresses colitis at a moderate dose (6% w/v), which increases the proportion of intestinal regulatory T (Treg) cells but does not affect effector CD4+ T cells. Glucose treatment promotes Treg cell differentiation but it does not affect Treg stability. Feeding glucose alters gut microbiota compositions, which are not involved in the glucose induction of Treg cells. Glucose promotes aryl hydrocarbon receptor (AhR) activation to induce Treg polarization. These findings reveal the different effects of glucose at different doses on the intestinal immune response.

20.
Zhongguo Gu Shang ; 35(9): 878-82, 2022 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-36124461

RESUMEN

OBJECTIVE: To explore clinical efficacy of staged surgery in treating complex closed Pilon fracture. METHODS: From June 2019 to January 2021, 29 patients with complex closed Pilon fracture were treated by staging surgery, including 18 males and 11 females, aged ranged from 31 to 68 years old with an average of (43.50±6.62) years old;7 cases were typeⅡand 22 cases were type Ⅲ according to Ruedi-Allgower classification. All patients had fresh closed fractures without talus and calcaneal fractures. The time from injury to closed reduction and external fixation, the interval between two stages of surgery, fracture healing time and complications were recorded. American Orthopedic Foot and Ankle Society(AOFAS) was used to assess clinical effects. Burwell-Charnley system was used to evaluate radiological reduction. RESULTS: All 29 patients were followed up from 13 to 30 months with an aver age of (15.43±5.31) months. All fractures healed well from 2 to 6 months with an average of (3.77±1.22) months. No internal fixation fracture, screw loosening, infection, internal fixation irritation, ankle stiffness occurred. The time from injury to closed reduction and cross-ankle fixation ranged from 1.22 to 7.34 h with an average of(2.31±3.52) h, the interval between two stages ranged from 5 to 9 days with an average of (5.98±2.11) days. AOFAS score was improved from 34.11±6.89 before operation to 90.10±10.11 after oepration at 12 months(P<0.05). According to AOFAS grading, 16 patients got excellent result, 9 good and 4 moderate. Fifteen patients got anatomic reduction, 12 patients were good reduction, and 2 cases were poor reduction according to Burwell-Charnley system. CONCLUSION: Staged surgery for complex closed Pilon fracture has advantages of less complications, statisfied reduction, stable fixation, which could obtain good recovery of ankle joint.


Asunto(s)
Fracturas de Tobillo , Traumatismos del Tobillo , Fracturas de la Tibia , Adulto , Anciano , Fracturas de Tobillo/cirugía , Traumatismos del Tobillo/cirugía , Femenino , Fijación Interna de Fracturas , Curación de Fractura , Humanos , Lactante , Masculino , Persona de Mediana Edad , Fracturas de la Tibia/cirugía
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