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1.
Brain ; 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39445466

RESUMEN

The role of radiosurgery in preventing haemorrhage in brainstem cavernous malformations remains a subject of debate. This study aims to evaluate whether radiosurgery provides a protective benefit against haemorrhage in these patients. This multicentre, prospective observational study was conducted in 17 centres and enrolled eligible patients with brainstem cavernous malformations consecutively. Data collected included clinical baseline information, radiosurgery planning details, periodic follow-up evaluations, and any adverse radiation effects. The primary outcome of the study was the incidence of first prospective haemorrhage, while the secondary outcome was the development of new or worsening neurological dysfunctions. The impact of radiosurgery was assessed using multivariate Cox regression analysis. From March 2016 to August 2018, the study enrolled 377 patients: 280 in the observation group receiving standard care alone and 97 in the radiosurgery group receiving both radiosurgery and standard care. The overall cohort consisted of 173 females (45.9%) with a mean age of 40.5 years (range, 18-68 years), and there were no significant differences in baseline characteristics between the two groups. After a median follow-up period of 70 months, haemorrhage occurred in 25.0% (n = 70) of patients in the observation group and 10.3% (n = 10) of patients in the radiosurgery group. Multivariate Cox regression analysis identified radiosurgery as an independent protective factor against haemorrhage (hazard ratio 0.379, 95% confidence interval 0.195-0.738, P = 0.004). Following 1:2 propensity score matching, the incidence of prospective haemorrhage were 24.9% (45/181) in the observation group compared to 10.3% (10/97) in the radiosurgery group (hazard ratio 0.379, 95% confidence interval 0.190-0.755, P = 0.006). Adverse radiation effects were observed in 12 patients (12.4%), with none were permanent. Additionally, new or worsening neurological dysfunctions were significantly more common in the observation group (28.9%) compared to the radiosurgery group (16.5%) (P = 0.016). These results suggest that radiosurgery is associated with a low rate of haemorrhage in patients with brainstem cavernous malformations and could provide a benefit in selected patients. However, further research is required to confirm these findings.

2.
Genes (Basel) ; 15(10)2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39457429

RESUMEN

BACKGROUND/OBJECTIVES: This systematic review aims to explore the role of PERM1 across different organisms, tissues, and cellular functions, with a particular focus on its involvement in regulating skeletal muscle mitochondrial biogenesis. METHODS: This systematic review follows The PRISMA 2020 Statement. We used the Covidence systematic review software for abstract/title screening, full-text review, and data extraction. The review included studies that examined PERM1 expression or activity in skeletal muscle, heart, and adipose tissue and/or cells, from mice, rats, and humans, and involved exercise or disease models. Risk of bias was assessed using the Cochrane Collaboration tool, and the data were extracted and synthesized qualitatively, with bioinformatic analyses performed using the MetaMEx database. RESULTS: Twenty-one studies were included in our data extraction process, where 10 studies involved humans, 21 involved mice, four involved rats, and 11 involved cells. CONCLUSIONS: PERM1 in skeletal muscle increases with endurance exercise, affecting muscle function and oxidative metabolism, but its role in humans is not well understood. In cardiac tissue, PERM1 is vital for function and mitochondrial biogenesis purposes, but decreases with disease and pressure overload. Our review synthesizes the current understanding of PERM1's function, raises awareness of its role in mitochondrial regulation, and identifies key areas for future research in the field.


Asunto(s)
Músculo Esquelético , Biogénesis de Organelos , Animales , Humanos , Músculo Esquelético/metabolismo , Ratones , Ratas , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/genética , Mitocondrias/metabolismo , Mitocondrias/genética
3.
J Transl Med ; 22(1): 914, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39380010

RESUMEN

The heterogeneous nuclear ribonucleoprotein C (HNRNPC) plays a crucial role in tumorigenesis, yet its role in papillary thyroid carcinoma (PTC) remains elusive. Herein, we elucidated the function and molecular mechanism of HNRNPC in PTC tumorigenesis and progression. Our study unveiled a significant upregulation of HNRNPC in PTC, and knockdown of HNRNPC markedly inhibited the proliferation, invasion, and metastasis of BCPAP cells. Furthermore, HNRNPC modulated PKM alternative splicing in BCPAP cells primarily through m6A modification. Additionally, by upregulating PKM2 expression, HNRNPC promoted aerobic glycolysis in BCPAP cells, thereby facilitating malignant progression in PTC. In summary, our findings demonstrate that HNRNPC regulates PKM alternative splicing through m6A methylation modification and promotes the proliferation, invasion and metastasis of PTC through glucose metabolism pathways mediated by PKM2. These discoveries provide new biomarkers for screening and diagnosing PTC patients and offer novel therapeutic targets for personalized treatment strategies.


Asunto(s)
Empalme Alternativo , Proteínas Portadoras , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Glucólisis , Ribonucleoproteína Heterogénea-Nuclear Grupo C , Proteínas de la Membrana , Cáncer Papilar Tiroideo , Proteínas de Unión a Hormona Tiroide , Hormonas Tiroideas , Neoplasias de la Tiroides , Regulación hacia Arriba , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Regulación hacia Arriba/genética , Línea Celular Tumoral , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Empalme Alternativo/genética , Hormonas Tiroideas/metabolismo , Glucólisis/genética , Metilación , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Animales , Invasividad Neoplásica , Metástasis de la Neoplasia , Piruvato Quinasa/metabolismo , Piruvato Quinasa/genética , Ratones Desnudos , Adenosina/análogos & derivados , Adenosina/metabolismo
4.
BMC Med Educ ; 24(1): 1069, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350226

RESUMEN

BACKGROUND: Simulation-Based Learning (SBL) is increasingly adopted in medical education across various specialties, employing realistic simulations to significantly enhance learning experiences. However, a comprehensive evaluation of its effectiveness specifically in endocrinology has not yet been conducted. The study aims to systematically review and meta-analyze the impact of SBL versus Non-Simulation-Based Learning (NSBL) on knowledge acquisition, skills, satisfaction, and interest in learning among endocrinology trainees. METHODS: This systematic review and meta-analysis adhered to the PRISMA guidelines, searching PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Weipu, and Chinese Biomedical Database (CBM) until March 2024. We included randomized controlled trials comparing SBL to NSBL in endocrinology education. The quality evaluation relied on the Cochrane risk-of-bias assessment tool. The main results included evaluations from both theoretical and practical assessments. Additional measures consisted of assessing satisfaction and interest in learning. RESULTS: We identified 22 studies suitable for systematic review and 21 for meta-analysis, involving a total of 2517 participants. SBL greatly enhanced theoretical knowledge [standardized mean difference (SMD) = 1.00, 95% confidence interval (CI): 0.68-1.32, P < 0.00001, I2 = 89%] and practical skills (SMD = 1.56, 95% CI: 1.11-2.01, P < 0.00001, I2 = 93%) compared to NSBL. Additionally, SBL was associated with higher satisfaction and greater interest in learning. No significant publication bias was detected, and sensitivity analysis confirmed the stability of these findings. CONCLUSIONS: SBL significantly enhances knowledge, skills, satisfaction, and interest in learning within endocrinology education compared to NSBL. These findings support the integration of high-quality SBL into endocrinology curricula to improve educational outcomes. Future research should explore the lasting effects of SBL on knowledge retention and clinical practice, as well as to evaluate its cost-effectiveness and compatibility with various educational tools in diverse settings.


Asunto(s)
Competencia Clínica , Endocrinología , Entrenamiento Simulado , Endocrinología/educación , Humanos , Educación Médica/métodos
5.
Anal Chim Acta ; 1329: 343234, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39396297

RESUMEN

Exosomes are extracellular vesicles of 30-200 nm in diameter that inherit molecular markers from their parent cells, including proteins, lipids, nucleic acids, and glycoconjugates. The detection and protein profiling of exosome could provide noninvasive access to disease diagnosis and treatment. In recent years, it has been found that Zr-MOFs can capture exosomes by forming Zr-O-P bonds through the phospholipid bilayer of exosomes. In addition, gold nanoparticles with optical response are used for colorimetric biological analysis, such as proteins, peptides, DNA. In this work, we proposed an aptasensor for exosome capture and sensitive colorimetric detection. The Zr-MOF (PCN-224) is innovatively used to capture exosome by Zr-O-P bond, and sodium tripolyphosphate (STPP) is used to block the non-specific adsorption of DNA aptamers on the surface of PCN-224 by site occupying effect. The aptamer binds to exosome immunity, and the remaining aptamer binds to Au NPs, resulting in an increase in steric hindrance and electrostatic repulsion, which makes the dispersion of Au NPs better and avoids the aggregation of Au NPs induced by dopamine (DA). The ratio of absorbance A650/A520 represents the aggregate degree of Au NPs, which correlates with the concentration of exosomes, and achieves sensitive colorimetric detection of exosomes with a linear range of 1.0 × 105-1.0 × 107 particles/mL. Further studies reveal that our work has excellent selectivity and anti-interference, breast cancer patients and healthy individuals can be distinguished by analyzing the differences in the expression of CD63 protein on exosome. The proposed biosensor integrates the capture and detection of exosomes, the multiple colors of Au NPs changed significantly from red to gray, which was conducive to the naked-eye identification of exosome detection.


Asunto(s)
Aptámeros de Nucleótidos , Colorimetría , Dopamina , Exosomas , Oro , Nanopartículas del Metal , Estructuras Metalorgánicas , Aptámeros de Nucleótidos/química , Oro/química , Exosomas/química , Exosomas/metabolismo , Humanos , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Dopamina/análisis , Límite de Detección , Técnicas Biosensibles
6.
Sci Rep ; 14(1): 20304, 2024 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218910

RESUMEN

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively.


Asunto(s)
Trasplante de Hígado , Sodio , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Sodio/sangre , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto , Donantes de Tejidos , Hiponatremia/sangre , Nitrógeno de la Urea Sanguínea , Receptores de Trasplantes , Bilirrubina/sangre , Periodo Preoperatorio , Anciano , Creatinina/sangre
7.
Brain Sci ; 14(9)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39335357

RESUMEN

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO4), (3) Parkinson's disease (PD), and (4) Parkinson's disease with magnesium sulfate (PD/MgSO4). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats' anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO4 group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO4 group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO4 group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients.

8.
Ann Thorac Surg ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39313087

RESUMEN

BACKGROUND: The characteristics of early-onset lung adenocarcinoma (EOLA) have not been extensively studied. Our research aimed to comprehensively assess the clinical and genetic features of EOLA. METHODS: We conducted a retrospective analysis of surgically resected lung adenocarcinoma patients, categorizing them into the EOLA group (aged <40 years) and the late-onset lung adenocarcinoma (LOLA) group (aged >60 years). A comparative investigation of clinical, germline, and genomic features was conducted. Propensity score matching was used to balance baseline characteristics for gene mutation analysis. RESULTS: We enrolled 487 EOLA and 2507 LOLA patients. EOLA patients exhibited a higher female-to-male ratio (2.55 vs 1.19) and a higher proportion of family history of lung cancer in the ground-grass opacity subgroup (12.7% vs 8.9%). The EOLA group exhibited higher rates of earlier stage in the ground-grass opacity subgroup and solid subgroup. Preinvasive adenocarcinoma was the dominant histologic subtype in the EOLA group within the ground-glass opacity subgroup (73.8% vs 25.6%). After propensity score matching, we analyzed 241 stage 0/I patients with available genetic test results. Significant disparities in gene mutation rates emerged between the EOLA and LOLA patients, including Erb-B2 receptor tyrosine kinase 2 (ERBB2; 38.0% vs 2.8%), epidermal growth factor receptor (EGFR; 36.0% vs 64.5%), MET (0.0% vs 7.1%), neurofibromin 1 (NF1; 0.0% vs. 5.7%), and anaplastic lymphoma kinase (ALK) fusion (10.0% vs 1.4%). CONCLUSIONS: EOLA patients exhibited distinct clinical and genetic characteristics compared with LOLA patients.

9.
Heliyon ; 10(17): e36597, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286126

RESUMEN

Gliomas are the most common malignant intracranial tumors, with no effective treatments. Better understanding and identification of novel targets are urgently warranted. Actin-binding Rho activating C-terminal like (ABRACL) has been reported as an oncogene in several cancer types. However, the potential roles of ABRACL in the tumorigenesis of malignant glioma remain unknown. We discovered that ABRACL is highly expressed in different sub-types of gliomas in both CGGA and TCGA databases, which was further validated in glioblastoma cell lines and normal human astrocyte lines. RT-qPCR, Western blotting and immunohistochemistry demonstrated that ABRACL expression in glioma tissues was upregulated along with the increasing WHO grades. Further survival analysis of glioma patients also revealed that the overall survival of patients in the ABRACL high expression level group were significantly shorter than those in the low expression level group. Knockdown of ABRACL inhibited the proliferation, cell migration, invasion and cytodynamics behaviors in glioma cell lines via activating STAT3 signaling, which also induced apoptosis and cell cycle arrest. Conversely, overexpressing ABRACL promoted cell renewing and migration, enabled more flexible cell deformation, supporting ABRACL being a bona fide oncogene. Intracranial orthotopic xenograft experiment further confirmed that ABRACL downregulation significantly suppressed glioma growth. These results have demonstrated that the tumorigenic effect of ABRACL is partly mediated by STAT3, whose expression also correlates with clinical prognosis. ABRACL facilitates glioma malignancy phenotype through regulating the cytoskeleton by activating STAT3 pathway, suggesting that it may represent a potential therapeutic target for glioblastoma.

10.
Opt Lett ; 49(18): 5099-5102, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39270239

RESUMEN

We realize the observation of near-unity nonreciprocal polarized transmission via the bound states in the continuum (BICs) in a double-layer grating structure. By introducing out-of-plane perturbations and topological defects that break the mirror symmetry between the upper and lower layers, the far-field polarization states in momentum space are inverted vertically and horizontally, showing mirrored polarization characteristics for incident channels from different upper and lower ports. During the process of introducing mirror perturbations in the upper and lower layers, a π/2 phase inversion occurs in the Г-M direction, making chirality possible. Utilizing this bidirectionally tunable nonreciprocal spatiotemporal phase transition enables multiple modulations of polarization states and opens up more possibilities for asymmetric light manipulation in chiral optical effects.

11.
Sports Med ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160296

RESUMEN

BACKGROUND: Although numerous attempts to demonstrate inter-individual differences in trainability across various outcomes have been unsuccessful, the investigation of maximal oxygen consumption (VO2max) trainability warrants further study. OBJECTIVE: Our objective was to conduct the first systematic review and meta-analysis to evaluate inter-individual differences in VO2max trainability across aerobic exercise training protocols utilizing non-exercising comparator groups. METHODS: We conducted a literature search across three databases: EMBASE, PubMed and SCOPUS. The search strategy incorporated two main concepts: aerobic exercise training and VO2max. Studies were included if they used human participants, employed standardized and supervised exercise training, reported absolute or relative VO2max, included a non-exercise comparator group, reported VO2max change scores for non-exercise and exercise groups and provided the standard deviation (SD) of change for all groups. We calculated the SD of individual response (SDIR) to estimate the presence of inter-individual differences in trainability across all studies. RESULTS: The literature search generated 32,968 studies, 24 of which were included in the final analysis. Our findings indicated that (1) the majority of variation in observed change scores following an intervention is due to measurement error, (2) calculating SDIR within a single study would not yield sufficient accuracy of SDIR due to generally small sample sizes and (3) meta-analysis of SD IR 2 across studies does not provide strong evidence for a positive value. CONCLUSION: Overall, our meta-analysis demonstrated that there is not strong evidence supporting the existence of VO2max trainability across single interventions. As such, it appears unlikely that clinically relevant predictors of VO2max response will be discovered. Registration can be found online ( https://doi.org/10.17605/OSF.IO/X9VU3 ).

12.
ACS Appl Mater Interfaces ; 16(30): 39035-39050, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39026394

RESUMEN

Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.


Asunto(s)
Alginatos , Antibacterianos , Quitosano , Hidrogeles , Cráneo , Hidrogeles/química , Hidrogeles/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Animales , Alginatos/química , Cráneo/efectos de los fármacos , Cráneo/patología , Cráneo/diagnóstico por imagen , Cráneo/lesiones , Óxido de Magnesio/química , Óxido de Magnesio/farmacología , Regeneración Ósea/efectos de los fármacos , Dopamina/química , Dopamina/farmacología , Durapatita/química , Durapatita/farmacología , Ratones , Proliferación Celular/efectos de los fármacos , Calcio/metabolismo , Calcio/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Osteogénesis/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos
13.
Opt Lett ; 49(11): 3030-3033, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824320

RESUMEN

We achieve dynamically tunable dual quasi-bound states in the continuum (quasi-BICs) by implementing them in a silicon-graphene multilayer composite structure and utilize the quasi-BIC modes to achieve ultra-large group delays (velocity of light slows down 105 times), showing 2-3 orders of magnitude higher than the group delays of previous electromagnetically induced transparency modes. The double-layer graphene holds great tuning capability and leads to the dramatically reduced group delay from 1929.82 to 1.58 ps with only 100 meV. In addition, the log-linear variation rule of group delay with Fermi level (Ef) in the range of 0-10 meV is analyzed in detail, and the double-logarithmic function relationship between the group delay and quality factor (Q-factor) is theoretically verified. Finally, the quantitative modulation of the optical storage is further realized in this basis. Our research provides ideas for the reform and upgrading of slow optical devices.

14.
Adv Sci (Weinh) ; 11(30): e2403148, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38874408

RESUMEN

Astaxanthin (ASX) is an oxygen-containing non-vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA). Mass cytometry and single-cell RNA sequencing (scRNA-seq) are used to analyze the potential role of ASX in regulating the immune microenvironment of AIH. ASX treatment effectively alleviated liver damage induced by ConA and downregulated pro-inflammatory cytokines production in mice. Mass cytometry and scRNA-seq analyses revealed a significant increase in the number of CD8+ T cells following ASX treatment. Functional markers of CD8+ T cells, such as CD69, MHC II, and PD-1, are significantly downregulated. Additionally, specific CD8+ T cell subclusters (subclusters 4, 13, 24, and 27) are identified, each displaying distinct changes in marker gene expression after ASX treatment. This finding suggests a modulation of CD8+ T cell function by ASX. Finally, the key transcription factors for four subclusters of CD8+ T cells are predicted and constructed a cell-to-cell communication network based on receptor-ligand interactions probability. In conclusion, ASX holds the potential to ameliorate liver damage by regulating the number and function of CD8+ T cells.


Asunto(s)
Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Hepatitis Autoinmune , Xantófilas , Animales , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones , Xantófilas/farmacología , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Citometría de Flujo/métodos , Ratones Endogámicos C57BL
15.
J Cancer Res Clin Oncol ; 150(5): 248, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724804

RESUMEN

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC. METHODS: We reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people. RESULTS: In the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan-Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments. CONCLUSION: ESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Humanos , Masculino , Femenino , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Resección Endoscópica de la Mucosa/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Esofagectomía/métodos , Complicaciones Posoperatorias/epidemiología , Tasa de Supervivencia
16.
Int Immunopharmacol ; 135: 112299, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38776853

RESUMEN

OBJECTIVE: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches. METHODS: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components. RESULTS: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 µg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 µg/ mL, 10 µg/ mL, and 100 µg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 µg/mL. Network pharmacology results revealed the network relationship between Cd's components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds. CONCLUSION: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.


Asunto(s)
Remodelación Ósea , Cistanche , Farmacología en Red , Osteogénesis , Periodontitis , Cistanche/química , Animales , Ratones , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Periodontitis/microbiología , Remodelación Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Simulación de Dinámica Molecular , Mapas de Interacción de Proteínas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Simulación del Acoplamiento Molecular , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular
17.
Int J Biol Macromol ; 267(Pt 1): 131473, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614185

RESUMEN

Actinoplanes utahensis deacylase (AAC)-catalyzed deacylation of echinocandin B (ECB) is a promising method for the synthesis of anidulafungin, the newest of the echinocandin antifungal agents. However, the low activity of AAC significantly limits its practical application. In this work, we have devised a multi-dimensional rational design strategy for AAC, conducting separate analyses on the substrate-binding pocket's volume, curvature, and length. Furthermore, we quantitatively analyzed substrate properties, particularly on hydrophilic and hydrophobic. Accordingly, we tailored the linoleic acid-binding pocket of AAC to accommodate the extended long lipid chain of ECB. By fine-tuning the key residues, the resulting AAC mutants can accommodate the ECB lipid chain with a lower curvature binding pocket. The D53A/I55F/G57M/F154L/Q661L mutant (MT) displayed 331 % higher catalytic efficiency than the wild-type (WT) enzyme. The MT product conversion was 94.6 %, reaching the highest reported level. Utilizing a multi-dimensional rational design for a customized mutation strategy of the substrate-binding pocket is an effective approach to enhance the catalytic efficiency of enzymes in handling complicated substrates.


Asunto(s)
Equinocandinas , Proteínas Fúngicas , Interacciones Hidrofóbicas e Hidrofílicas , Equinocandinas/química , Especificidad por Sustrato , Sitios de Unión , Mutación , Modelos Moleculares , Amidohidrolasas/química , Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Unión Proteica
18.
J Inflamm Res ; 17: 2023-2037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577691

RESUMEN

Background: Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice. Methods: Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated. Results: Selenium yeast lowered IL-1ß, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P<0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P<0.05), and butyric acid (P<0.05). Conclusion: Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.

19.
ACS Appl Mater Interfaces ; 16(15): 19205-19213, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38591860

RESUMEN

An artificial nociceptor, as a critical and special bionic receptor, plays a key role in a bioelectronic device that detects stimuli and provides warnings. However, fully exploiting bioelectronic applications remains a major challenge due to the lack of the methods of implementing basic nociceptor functions and nociceptive blockade in a single device. In this work, we developed a Pt/LiSiOx/TiN artificial nociceptor. It had excellent stability under the 104 endurance test with pulse stimuli and exhibited a significant threshold current of 1 mA with 1 V pulse stimuli. Other functions such as relaxation, inadaptation, and sensitization were all realized in a single device. Also, the pain blockade function was first achieved in this nociceptor with over a 25% blocking degree, suggesting a self-protection function. More importantly, an obvious depression was activated by a stimulus over 1.6 V due to the cooperative effects of both lithium ions and oxygen ions in LiSiOx and the dramatic accumulation of Joule heat. The conducting channel ruptured partially under sequential potentiation, thus achieving nociceptive blockade, besides basic functions in one single nociceptor, which was rarely reported. These results provided important guidelines for constructing high-performance memristor-based artificial nociceptors and opened up an alternative approach to the realization of bioelectronic systems for artificial intelligence.


Asunto(s)
Inteligencia Artificial , Nociceptores , Humanos , Nociceptores/fisiología , Dolor , Biónica , Iones/farmacología
20.
PLoS One ; 19(4): e0298404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38598496

RESUMEN

AIM: Dental erosion is a chemical-mechanical process that leads to the loss of dental hard tissues. This study aimed to investigate the effect of pomegranate juice on the enamel. METHODS: Enamel blocks were randomly divided into three groups: deionized water, cola, and pomegranate juice. The blocks were immersed in the solutions four times a day for 14 days, and stored in artificial saliva for the remaining period. The surface hardness was measured on days 7 and 14. The surface structures of the demineralized blocks were observed via scanning electron microscopy (SEM), and the depth of demineralization was observed via confocal laser scanning microscopy (CLSM). The pH, calcium, and phosphorus levels of the three solutions were analyzed. RESULTS: The microhardness values of the blocks in the pomegranate juice and cola groups decreased with the increase in the demineralization time. The blocks in the pomegranate juice group exhibited large fractures in the enamel column, whereas those in the cola group had pitted enamels with destruction of the interstitial enamel column. Compared with cola group, fluorescent penetration increased in pomegranate juice (P < 0.01). The pH of cola (2.32 ± 0.09) was lower than that of pomegranate juice (3.16 ± 0.16). Furthermore, the calcium content in pomegranate juice was significantly higher than that in cola (P < 0.01). Alternatively, the concentration of phosphorous in cola was significantly higher than that in pomegranate juice (P < 0.01). CONCLUSION: These findings indicate that pomegranate juice can cause enamel demineralization with an erosive potential comparable to that of cola.


Asunto(s)
Granada (Fruta) , Erosión de los Dientes , Humanos , Calcio , Concentración de Iones de Hidrógeno , Erosión de los Dientes/inducido químicamente , Dureza , Cola , Esmalte Dental
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