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Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.
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Comunicación Autocrina , Fibroblastos Asociados al Cáncer , Movimiento Celular , Quimiocina CXCL12 , Neoplasias Colorrectales , Células Madre Neoplásicas , Comunicación Paracrina , Receptores CXCR4 , Transducción de Señal , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Animales , Invasividad Neoplásica , Ratones , Microambiente Tumoral , Línea Celular Tumoral , Células HCT116 , Masculino , Femenino , Células HT29RESUMEN
STATEMENT OF PROBLEM: Limited data exist regarding the effects of postprocessing on the flexural strength of vat-polymerized additively manufactured (AM) interim fixed dental prostheses. PURPOSE: The purpose of this systematic review was to determine how the postprocessing workflow affects the mechanical properties of vat-polymerized additively manufactured interim fixed dental prostheses and to establish clinical guidelines. MATERIAL AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The population, intervention, comparison, and outcome (PICO) question was "For vat-polymerized additively manufactured interim fixed dental prostheses (P), does varying the postprocessing workflow/ protocol (I and C) affect mechanical properties/physical properties/flexural strength (O)?" Searches were conducted in 3 databases: PubMed/Medline, EMBASE, and Web of Science, with 2 investigators performing the title and abstract screening and setting the inclusion and exclusion criteria to identify publications. The risk of bias was evaluated by applying the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies (nonrandomized experimental studies). The reported independent variables of rinse solution, rinse time, and polymerization time on the flexural strength results were extracted for qualitative review. RESULTS: The initial search identified 149 records, with 12 in vitro studies meeting the inclusion criteria. Significant heterogeneity was observed in the manufacturing process and materials. Eleven of 12 included studies reported flexural strength above 100 MPa when following the manufacturer's recommendation. Postprocessing rinsing ranged from 5 seconds to 90 minutes, with potentially reduced flexural strength with extended rinsing. A rinse of 5 to 10 minutes was recommended for optimal mechanical properties, degree of conversion, and biocompatibility. Isopropyl alcohol (IPA) and tripropylene glycol monomethyl ether (TPM) were the most investigated rising solutions, while experimental solutions including 99.5% acetone and 100% bio-ethyl alcohol reportedly decreased flexural strength. Polymerization time and intensity correlated positively with the flexural strength, whereas an artificial aging process reduced the flexural strength. CONCLUSIONS: Heterogeneity existed in the reported postprocessing protocols for AM interim fixed prostheses, including manufacturer materials, methods, and study outcomes. While polymerization time and intensity correlated with greater strength, consistent patterns regarding rinsing solution or time were lacking. Rinsing solution, extended rinsing time, and artificial aging may reduce flexural strength. Further investigation is indicated.
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BACKGROUND AND PURPOSE: Radiomics offers little explainability. This study aims to develop a radiomics model (Rad-Score) using diffusion-weighted imaging (DWI) to predict high-risk patients for nodal metastasis or recurrence in endometrial cancer (EC) and corroborate with choline metabolism. MATERIALS AND METHODS: From August 2015 to July 2018, 356 EC patients were enrolled. Rad-Score was developed using LASSO regression in a training cohort (n = 287) and validated in an independent test cohort (n = 69). MR spectroscopy (MRS) was also used in 230 patients. Nuclear MRS measured choline metabolites in 70 tissue samples. The performance was compared against European Society for Medical Oncology (ESMO) risk groups. A P < .05 denoted statistical significance. RESULTS: Rad-Score achieved 71.1% accuracy in the training and 71.0% in the testing cohorts. Incorporating clinical parameters of age, tumor type, size, and grade, Rad-Signature reached accuracies of 73.2% in training and 75.4% in testing cohorts, closely matching the performance to the post-operatively based ESMO's 70.7% and 78.3%. Rad-Score was significantly associated with increased total choline levels on MRS (P = .034) and tissue levels (P = .019). CONCLUSIONS: Development of a preoperative radiomics risk score, comparable to ESMO clinical standard and associated with altered choline metabolism, shows translational relevance for radiomics in high-risk EC patients. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov on 2015-08-01 with Identifier NCT02528864.
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Colina , Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Colina/metabolismo , Persona de Mediana Edad , Anciano , Medición de Riesgo/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/metabolismo , Adulto , Espectroscopía de Resonancia Magnética/métodos , Metástasis Linfática/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , RadiómicaRESUMEN
ABSTRACT: Chen, P-T, Lin, Y-C, Chang, H-Y, Chiu, C-H, Chen, C-Y, Chen, P, and Lin, Y-H. Effects of shoulder corrective training program on pitching loads and sonographic morphology in elbow joint in youth baseball players. J Strength Cond Res 38(8): e440-e447, 2024-We assessed the effects of a 12-week shoulder corrective training program for shoulder flexibility and strengthening on pitching loads and sonographic morphology of the elbow joints in youth baseball players. Seventeen subjects were recruited and underwent evaluations before and after the training program. We found that following training, subjects demonstrated significantly increased ranges of shoulder internal rotation (38.9 ± 12.9° vs. 69.2 ± 10.8°, p < 0.001), external rotation (91.2 ± 14.6° vs. 107.3 ± 9.5°, p = 0.004), and horizontal adduction (21.5 ± 8.0° vs. 32.7 ± 7.3°, p = 0.002); improved strength in the shoulder internal rotators (8.7 ± 1.6 kg vs. 9.8 ± 2.1 kg, p = 0.04), external rotators (6.5 ± 1.9 kg vs. 7.5 ± 2.8 kg, p = 0.04), middle trapezius (12.7 ± 2.1 kg vs. 14.3 ± 2.4 kg, p = 0.04), and middle deltoid muscles (10.8 ± 3.3 kg vs. 14.8 ± 3.2 kg, p = 0.001); and decreased thickness of the ulnar collateral ligament (6.1 ± 0.6 mm vs. 4.8 ± 0.7 mm, p = 0.002). Although there was no substantial change in elbow torque and arm speed, significantly increased ball speed (51.2 ± 4.6 mph vs. 54.1 ± 4.5 mph, p < 0.001) and decreased arm slot (63.8 ± 11.9° vs. 53.0 ± 12.7°, p = 0.02) were observed. We suggest that adequate corrective training should be performed regularly to minimize or mitigate adverse soft tissue changes at the elbow in youth baseball players. Balanced shoulder strength and flexibility may decrease medial elbow stress during pitching. Future studies should consider the kinetic and kinematic effects of other corrective training programs on the shoulder or elbow joint during pitching.
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Béisbol , Articulación del Codo , Rango del Movimiento Articular , Ultrasonografía , Humanos , Béisbol/fisiología , Articulación del Codo/fisiología , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/anatomía & histología , Adolescente , Masculino , Rango del Movimiento Articular/fisiología , Articulación del Hombro/fisiología , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/anatomía & histología , Fuerza Muscular/fisiología , Rotación , Hombro/fisiología , Hombro/diagnóstico por imagen , Hombro/anatomía & histología , NiñoRESUMEN
Purpose: This study aimed to investigate differences in cervical lymph node image quality on dual-energy computed tomography (CT) scan with datasets reconstructed using filter back projection (FBP), hybrid iterative reconstruction (IR), and deep learning-based image reconstruction (DLIR) in patients with head and neck cancer. Method: Seventy patients with head and neck cancer underwent follow-up contrast-enhanced dual-energy CT examinations. All datasets were reconstructed using FBP, hybrid IR with 30 % adaptive statistical IR (ASiR-V), and DLIR with three selectable levels (low, medium, and high) at 2.5- and 0.625-mm slice thicknesses. Herein, signal, image noise, signal-to-noise ratio, and contrast-to-noise ratio of lymph nodes and overall image quality, artifact, and noise of selected regions of interest were evaluated by two radiologists. Next, cervical lymph node sharpness was evaluated using full width at half maximum. Results: DLIR exhibited significantly reduced noise, ranging from 3.8 % to 35.9 % with improved signal-to-noise ratio (11.5-105.6 %) and contrast-to-noise ratio (10.5-107.5 %) compared with FBP and ASiR-V, for cervical lymph nodes (p < 0.001). Further, 0.625-mm-thick images reconstructed using DLIR-medium and DLIR-high had a lower noise than 2.5-mm-thick images reconstructed using FBP and ASiR-V. The lymph node margins and vessels on DLIR-medium and DLIR-high were sharper than those on FBP and ASiR-V (p < 0.05). Both readers agreed that DLIR had a better image quality than the conventional reconstruction algorithms. Conclusion: DLIR-medium and -high provided superior cervical lymph node image quality in head and neck CT. Improved image quality affords thin-slice DLIR images for dose-reduction protocols in the future.
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Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.
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Adenocarcinoma del Pulmón , Transición Epitelial-Mesenquimal , Interleucina-8 , Neoplasias Pulmonares , Derrame Pleural Maligno , Receptores de Interleucina-8A , Transducción de Señal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/complicaciones , Línea Celular Tumoral , Movimiento Celular , Progresión de la Enfermedad , Interleucina-8/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Derrame Pleural Maligno/patología , Derrame Pleural Maligno/metabolismo , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8A/genética , Microambiente TumoralRESUMEN
Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.
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Proteínas de Ciclo Celular , Centriolos , Centrosoma , Microtúbulos , Humanos , Centrosoma/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Microtúbulos/metabolismo , Centriolos/metabolismo , Centriolos/genética , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Mutación , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Unión Proteica , Proteínas NuclearesRESUMEN
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.
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Cloruro de Cadmio , Senescencia Celular , Degradación Asociada con el Retículo Endoplásmico , Neuronas , Receptores sigma , Animales , Senescencia Celular/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Cloruro de Cadmio/toxicidad , Receptores sigma/metabolismo , Degradación Asociada con el Retículo Endoplásmico/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Ratones , Proteínas tau/metabolismo , Masculino , Enfermedad de Alzheimer/metabolismo , Humanos , Melatonina/farmacología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.
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This article presents a novel bonding method for chip packaging applications in the semiconductor industry, with a focus on downsizing high-density and 3D-stacked interconnections to improve efficiency and performance. Microfluidic electroless interconnections have been identified as a potential solution for bonding pillar joints at low temperatures and pressures. However, the complex and time-consuming nature of their production process hinders their suitability for mass production. To overcome these challenges, we propose a tailored plating solution using an enhanced copper concentration and plating rate. By eliminating the need for fluid motion and reducing the process time, this method can be used for mass production. The Taguchi approach is first used to optimize the copper-quadrol complex solution with the plating rate and decomposition time. This solution exhibits a copper concentration that is over five times higher than that of conventional solutions, a plating rate of 22.2 µm/h, and a decomposition time of 8 min on a Cu layer substrate. This technique enables Cu pillars to be successfully bonded within 7 min at 35 °C. Planarizing the pillar surface yields a high bonding percentage of 99%. Mechanical shear testing shows a significant fracture strength of 76 MPa.
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PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.
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Proteínas Adaptadoras Transductoras de Señales , Enfermedad de Charcot-Marie-Tooth , Proteínas del Citoesqueleto , Mutación Missense , Animales , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/patología , Modelos Animales de Enfermedad , Drosophila/genética , Proteínas Nucleares , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/patología , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMEN
Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.
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Aflatoxina B1 , Vesículas Extracelulares , Células Estrelladas Hepáticas , Hepatocitos , Cirrosis Hepática , Mitofagia , Proteína p53 Supresora de Tumor , Ubiquitina-Proteína Ligasas , Aflatoxina B1/toxicidad , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Mitofagia/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Animales , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ratones , Masculino , Humanos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacosRESUMEN
Cells generate a highly diverse microtubule network to carry out different activities. This network is comprised of distinct tubulin isotypes, tubulins with different post-translational modifications, and many microtubule-based structures. Defects in this complex system cause numerous human disorders. However, how different microtubule subtypes in this network regulate cellular architectures and activities remains largely unexplored. Emerging tools such as photosensitive pharmaceuticals, chemogenetics, and optogenetics enable the spatiotemporal manipulation of structures, dynamics, post-translational modifications, and cross-linking with actin filaments in target microtubule subtypes. This review summarizes the design rationale and applications of these new approaches and aims to provide a roadmap for researchers navigating the intricacies of microtubule dynamics and their post-translational modifications in cellular contexts, thereby opening new avenues for therapeutic interventions.
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Microtúbulos , Microtúbulos/metabolismo , Microtúbulos/química , Humanos , Animales , Procesamiento Proteico-Postraduccional , Optogenética , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/químicaRESUMEN
The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.
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Colitis , Modelos Animales de Enfermedad , Fermentación , Mucosa Intestinal , Limosilactobacillus reuteri , Probióticos , Destete , Animales , Probióticos/farmacología , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/microbiología , Humanos , Ratones , Porcinos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Células CACO-2 , Ligilactobacillus salivarius , Lactobacillus gasseri , Sulfato de Dextran , Masculino , Proliferación Celular/efectos de los fármacosRESUMEN
A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).
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Background and Objectives: The claim that political group attendance is associated with poor mental health among older adults may be conditioned on geographic conditions. This study examined the geographical context in which political group participation may be associated with depression. Research Design and Methods: The 11-year follow-up data from the Taiwan Longitudinal Study on Aging, covering 5,334 persons aged ≥50 years, were analyzed using random-effects panel logit models. Depression was assessed using 10 items on the Centre for Epidemiologic Studies Depression scale. Participants were asked to indicate whether they belonged to different social groups. We modeled depression as a function of political group participation (the independent variable) and geographical region (moderators), adjusting for individual-level characteristics. Results: Respondents in political groups were more likely to report depression than those in nonpolitical groups (adjusted odds ratio [AOR]â =â 1.90, 95% confidence interval [CI]â =â 1.34-2.68). Between urban and rural settlements, there were no statistically significant differences in mental health outcomes among older adults engaged in political groups (AORâ =â 1.72, 95% CIâ =â 0.81-3.67). For those who remained politically engaged, living in areas with lower levels of electoral competition was associated with a lower likelihood of depression (AORâ =â 0.92, 95% CIâ =â 0.86-0.98); this conditional effect was not prevalent among those who were solely engaged in nonpolitical groups (AORâ =â 1.02, 95% CIâ =â 0.99-1.03). Discussion and Implications: Political group participation is associated with poor mental health among older adults living in politically competitive regions.
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Frailty is a common geriatric syndrome. However, there is little information about the relationship between dietary sodium restriction (DSR) and frailty in later life. This study aimed to elucidate the relationship between DSR and frailty in middle-aged and older adults. The 8-year follow-up data from the Taiwan Longitudinal Study on Aging, including 5131 individuals aged ≥50 years, were analyzed using random-effects panel logit models. DSR was evaluated by assessing whether the participants were told by a physician to reduce or avoid sodium intake from food. Three indices were used to measure frailty: the Study of Osteoporotic Fractures (SOF) index, the Fried index, and the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) index. Individuals with DSR were more likely to report frailty compared with those with non-DSR (SOF: adjusted odds ratio [AOR] = 1.82, 95% confidence interval [CI] = 1.46-2.27; Fried: AOR = 2.55, 95% CI = 1.64-3.98; FRAIL: AOR = 2.66, 95% CI = 1.89-3.74). DSR was associated with a higher likelihood of SBF (AOR = 2.61, 95% CI = 1.61-4.22). We identified a temporal trajectory in our study, noting significant participant reactions to both short- and mid-term DSR. Future research should address the balance between frailty risk and cardiovascular risk related to DSR.
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Fragilidad , Fracturas Osteoporóticas , Sodio en la Dieta , Anciano , Persona de Mediana Edad , Humanos , Estudios Longitudinales , Anciano Frágil , Sodio , Evaluación GeriátricaRESUMEN
BACKGROUND: Observational studies and meta-analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis. METHODS AND MATERIALS: Our analyses were performed using individual data from the Taiwan Biobank and summary statistics from the Asian Genetic Epidemiology Network (AGEN). The causal estimates between all genetic variants, exposures of interest and asthma were calculated using an inverse-variance weighted method based on Taiwan Biobank data from 24,853 participants (mean age, 48.8 years; 49.8% women). Sensitivity analyses, including the weighted median, MR Egger regression, MR-PRESSO, mode-based estimate, contamination mixture methods, and leave-one-out analysis, were applied to validate the results and detect pleiotropy. RESULTS: In the inverse-variance weighted (IVW) analyses, we found evidence of a significant causal effect of an increased level of low-density lipoprotein cholesterol on asthma risk (ßIVW = 1.338, p = 0.001). A genetically decreased level of high-density lipoprotein cholesterol was also associated with asthma risk (ßIVW = -0.338, p = 0.01). We also found that an increased level of total cholesterol was associated with an increased risk of asthma (ßIVW = 1.343, p = 0.001). Several sensitivity analyses generated consistent findings. We did not find evidence to support the causality between asthma and blood lipid profiles in either direction. CONCLUSION: Our results supported the causal relationship between higher levels of LDL cholesterol and total cholesterol and lower levels of HDL cholesterol with an increased risk of asthma.
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Asma , Análisis de la Aleatorización Mendeliana , Humanos , Asma/genética , Asma/sangre , Asma/epidemiología , Femenino , Masculino , Persona de Mediana Edad , HDL-Colesterol/sangre , HDL-Colesterol/genética , Lípidos/sangre , LDL-Colesterol/sangre , Polimorfismo de Nucleótido Simple , Adulto , Taiwán/epidemiología , Factores de Riesgo , Predisposición Genética a la EnfermedadRESUMEN
Electrochemical performances can be effectively improved by introducing metal-organic units (MOUs) into polyoxometalates (POMs). However, regulating the bonding strength between POMs and MOUs at the molecular level to improve the electrochemical performance is a challenging task. Three new POM-based metal-organic complexes (MOCs), namely H{Zn2(Hpytty)2(H2O)8[CrMo6(OH)6O18]}·2H2O (1), H{Zn2(Hpyttz)2(H2O)6[CrMo6(OH)6O18]}·8H2O (2), and {(µ2-OH)2Zn6(pyttz)2(H2O)10[TeMo6O24]}·2H2O (3) (H2pytty = 3-(pyrazin-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl, H2pyttz = 3-(pyrid-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl), were obtained. Single-crystal X-ray diffraction shows that the bonding strength (from the hydrogen bond to the coordination bond) between Zn-bistriazole-pyrazine/pyridine units and diverse Anderson-type POMs gradually increases from complexes 1 to 3. Glassy carbon electrodes modified with complex 3 (3-GCE) has the highest specific capacitance, which is 930 F g-1 at 1 A g-1. Moreover, carbon paste electrodes (1-3-CPEs) modified with complexes 1-3 are used as electrochemical sensors for detecting Cr(VI) ions, with limits of detection well below the World Health Organization (WHO) maximum level in drinking water.