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1.
bioRxiv ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38979247

RESUMEN

Previous characterization of the genome and transcriptome of glioblastoma (GBM) has revealed molecular alterations that potentially drive GBM pathogenesis and heterogeneity 1-6 . These open-resources are evolving, such as The Cancer Genome Atlas (TCGA) and The Cancer Imaging Atlas (TCIA) at the National Institute of Health comprising a large cohort of molecular and MRI data. Yet, no report deciphers the link between molecular signatures and MRI-classified GBM. The necessity to re-form molecular and imaging data motivated our computational approach to integrate TCIA and TCGA datasets derived from GBM. We uncovered common and distinct molecular signatures across GBM patients and specific to tumor locations, respectively. Despite heterogeneity in GBM, the top 12 genes from our analysis highlights that the dysregulation of a subset of neurotransmitter receptor or transporter and synaptic activity is common across GBM patients. The coherent layer of imaging and molecular information would help us stratify precision neuro-oncology and treatment options in ways that are not possible through MRI or genomic data alone. Our findings provide molecular targets in the disrupted neurocircuit of GBM, suggesting imbalanced excitation and inhibition. Given the fact that GBM patients exhibit similar symptoms resembling patients with neurodegenerative diseases and seizures, our results supported the hypothesis-GBM in the context of neurological disorders beyond a solely cancerous disease.

2.
Molecules ; 29(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930915

RESUMEN

Organic arsenic compounds such as p-aminophenylarsine oxide (p-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/ß anomers, the strategy of 2-acetyl's neighboring group participation was used to lock the configuration of 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra-O-acetyl-ß-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 µM vs. 1.82 ± 0.07 µM) to human embryonic kidney 293T cells (1.38 ± 0.01 µM vs. 1.22 ± 0.06 µM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.


Asunto(s)
Antineoplásicos , Diseño de Fármacos , Tiourea , Humanos , Tiourea/química , Tiourea/farmacología , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Glucosa/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células HCT116 , Estructura Molecular , Arsenicales/química , Arsenicales/farmacología , Arsenicales/síntesis química , Relación Estructura-Actividad
3.
Adv Sci (Weinh) ; : e2404456, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38894569

RESUMEN

Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2-hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two-step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re-epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual-enhanced cell and tissue penetration and multistep interventions.

4.
Immun Inflamm Dis ; 12(6): e1278, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38860750

RESUMEN

BACKGROUND: The current study aims to explore the relationship between tumor necrosis factor-α (TNF-α) polymorphism and the risk of primary nephrotic syndrome (PNS). METHODS: A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF-α polymorphism were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. In addition, a meta-analysis was conducted to analyze previously published literature on this topic. RESULTS: No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta-analysis results revealed a positive association between TNF-α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). CONCLUSIONS: TNF-α rs1800629 polymorphism does not appear to confer any increased risk for PNS.


Asunto(s)
Predisposición Genética a la Enfermedad , Síndrome Nefrótico , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa , Síndrome Nefrótico/genética , Humanos , Factor de Necrosis Tumoral alfa/genética , Estudios de Casos y Controles , Masculino , Femenino , Frecuencia de los Genes , Adulto , Genotipo , Alelos , Persona de Mediana Edad , Factores de Riesgo
6.
Chin J Cancer Res ; 36(2): 138-150, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38751439

RESUMEN

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer (NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment (TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

7.
Nat Med ; 30(5): 1471-1480, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38740996

RESUMEN

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.


Asunto(s)
Inteligencia Artificial , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Cinemagnética/métodos , Tamizaje Masivo/métodos , Anciano , Adulto
8.
Cell Biochem Funct ; 42(3): e3994, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38566355

RESUMEN

This study aimed to investigate the expression pattern and mechanisms of Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 1 (PDP1) in the progression of breast cancer (BC). PDP1, known for its involvement in cell energy metabolism, was found to be overexpressed in BC tissues. Notably, low PDP1 expression aligns with improved overall survival (OS) in BC patients. In this study, we found that PDP1 was overexpressed among BC tissues and low PDP1 expression showed a better prognosis for the patients with BC. PDP1 knockdown suppressed cell amplification and migration and triggered cell apoptosis in BC cells. In vivo assessments through a xenograft model unveiled the pivotal role and underlying mechanisms of PDP1 knockdown. RNA sequencing and kyoto encyclopedia of genes and genomes analysis of RNAs from PDP1 knockdown and normal MCF7 cells revealed 1440 differentially expressed genes, spotlighting the involvement of the JAK/STAT3 signaling pathway in BC progression. Western blot results implied that PDP1 knockdown led to a loss of p-STAT3, whereas overexpression of PDP1 induced the p-STAT3 expression. Cell counting kit-8 assay showed that PDP1 overexpression significantly raised MDA-MB-231 and MCF7 cell viability while STAT3 inhibitor S3I-201 recovered the cell growth to normal level. To summarize, PDP1 promotes the progression of BC through STAT3 pathway by regulating p-STAT3. The findings contribute to understanding the molecular mechanisms underlying BC progression, and opening avenues for targeted therapeutic approaches.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Secuencia de Bases , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Células MCF-7 , Transducción de Señal , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
9.
J Clin Gastroenterol ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38648497

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.

10.
Medicine (Baltimore) ; 103(16): e37824, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38640298

RESUMEN

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.


Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Metabolismo de los Lípidos , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Ácidos Grasos , Pronóstico , Microambiente Tumoral/genética
11.
Heliyon ; 10(5): e26875, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38434329

RESUMEN

Background: Bariatric surgeries, including the sleeve gastrectomy, have been recognized as the most effectively treatment strategy for severe obesity. Magnetic devices have been successfully used in bariatric surgeries. Here, we intended to evaluate the safety and efficiency of magnetic anchoring device assisted-laparoscopic sleeve gastrectomy (MLSG), and to make a comparison of the short-term results between conventional laparoscopic sleeve gastrectomy (CLSG) and MLSG. Methods: The retrospective cohort study was carried out by analyzing and summarizing the data from a database of routinely collected data. The cohort included the patients who underwent either CLSG (n = 120) or MLSG (n = 115) at a single center between January 2018 and December 2020 with a two-year follow-up. The effects of these two surgeries on the weight loss, resolution of comorbidities and quality of life (QOL) were analyzed. Results: The two groups were similar in gender, age, body mass index, abdominal girth, as well as the type and proportion of comorbidities. And the cases in MLSG group had a markedly shorter time of operation (MLSG, 72.59 min vs. CLSG, 76.67 min; P = 0.003). Length of stay in hospital was significantly shorter in the MLSG group than that in the CLSG group (MLSG, 5.59 days vs. CLSG, 5.96 days; P = 0.016). Neither fatal event nor conversion to open surgery happened among all cases. There were no differences in terms of the postoperative complications between the two groups. Magnetic device-related mild hepatic lacerations occurred and were handled by hemostatic treatments in 3 cases. The QOL of patients in MLSG was better at 6-month after surgery, but there was no significant difference between the two groups at 1-year or 2-year after surgery. Conclusion: Both MLSG and CLSG prove safe and effective, and the patients underwent MLSG have a shorter length of stay in hospital, and a better QOL during 6 months after surgery.

12.
Cell Rep ; 43(4): 113972, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38517892

RESUMEN

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.


Asunto(s)
Proteínas de Unión al ADN , Factor 1 Inducible por Hipoxia , Ubiquitina-Proteína Ligasas , Humanos , Hipoxia de la Célula , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Histonas/metabolismo , Factor 1 Inducible por Hipoxia/metabolismo , Células MCF-7 , Unión Proteica , Elementos de Respuesta , Factores de Transcripción/metabolismo , Activación Transcripcional , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación
13.
Adv Mater ; 36(21): e2308126, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38533956

RESUMEN

The behavior of tissue resident cells can be influenced by the spatial arrangement of cellular interactions. Therefore, it is of significance to precisely control the spatial organization of various cells within multicellular constructs. It remains challenging to construct a versatile multicellular scaffold with ordered spatial organization of multiple cell types. Herein, a modular multicellular tissue engineering scaffold with ordered spatial distribution of different cell types is constructed by assembling varying cell-laden modules. Interestingly, the modular scaffolds can be disassembled into individual modules to evaluate the specific contribution of each cell type in the system. Through assembling cell-laden modules, the macrophage-mesenchymal stem cell (MSC), endothelial cell-MSC, and chondrocyte-MSC co-culture models are successfully established. The in vitro results indicate that the intercellular cross-talk can promote the proliferation and differentiation of each cell type in the system. Moreover, MSCs in the modular scaffolds may regulate the behavior of chondrocytes through the nuclear factor of activated T-Cells (NFAT) signaling pathway. Furthermore, the modular scaffolds loaded with co-cultured chondrocyte-MSC exhibit enhanced regeneration ability of osteochondral tissue, compared with other groups. Overall, this work offers a promising strategy to construct a multicellular tissue engineering scaffold for the systematic investigation of intercellular cross-talk and complex tissue engineering.


Asunto(s)
Diferenciación Celular , Condrocitos , Técnicas de Cocultivo , Células Madre Mesenquimatosas , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Condrocitos/citología , Condrocitos/metabolismo , Animales , Ratones , Proliferación Celular , Humanos , Factores de Transcripción NFATC/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Células RAW 264.7 , Transducción de Señal
14.
Quant Imaging Med Surg ; 14(3): 2627-2639, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38545037

RESUMEN

Background: In type 2 diabetes mellitus (T2DM) patients, left ventricular systolic dyssynchrony (LVSD) with normal left ventricular ejection fraction (LVEF) and normal myocardial perfusion could referred to as subclinical myocardial damage, which is difficult to diagnose at an early stage. Epicardial adipose tissue, a distinctive heart-specific visceral fat, is closely related to various cardiovascular diseases. The objective of this study was to investigate the correlation between epicardial fat volume (EFV) and subclinical myocardial damage in T2DM patients. Methods: This retrospective cross-sectional study included 117 T2DM patients with normal myocardial perfusion by single photon emission computed tomography-computed tomography (SPECT-CT) and normal LVEF by echocardiography. The study was conducted from January 2018 to December 2022. Patient data were collected through electronic medical records including basic patient information, medical history, laboratory tests, and medication data. The EFV was quantified through a non-contrast CT scan. Quantitative indicators of LVSD including phase standard deviation (PSD) and phase histogram bandwidth (PBW) were obtained through phase analysis of the gated rest myocardial perfusion imaging (MPI). Additionally, 83 healthy individuals at the same time were selected to gain the reference threshold of LVSD indicators (13.1° for PSD and 37.6° for PBW). Univariate and multivariable logistic regression models were performed to analyze factors influencing LVSD. A generalized additive model (GAM) was applied to explore the relationship between EFV and LVSD. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of EFV for LVSD. Results: Among all patients, 32 (27.4%) patients had LVSD. Compared with the non-LVSD group, the body mass index (BMI) and EFV were higher in the LVSD group (25.83±2.66 vs. 23.94±3.13 kg/m2; 142.41±44.17 vs. 108.01±38.24 cm3, respectively, both P<0.05). Multivariate regression analysis revealed that EFV was independently associated with LVSD [odds ratio (OR) =1.19; 95% confidence interval (CI): 1.06-1.34; P=0.003]. Age, BMI, incidence of hypertension, and LVSD were increased with tertiles of EFV (all P<0.05). The GAM indicated a linear association between EFV and LVSD. The ROC curve analysis concluded that the area under the curve (AUC) of EFV for predicting subclinical myocardial damage in T2DM patients was 0.732 (95% CI: 0.633-0.831, P<0.001), with the optimal threshold of 122.26 cm3, sensitivity of 71.9%, and specificity of 69.4%. Conclusions: EFV is an independent risk factor for LVSD in T2DM patients with normal LVEF and normal MPI, which could potentially serve as a novel imaging marker and a potential therapeutic target for subclinical myocardial damage.

15.
J Stroke Cerebrovasc Dis ; : 107636, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38346661

RESUMEN

PURPOSE: To explore possible mechanism(s) underlying beneficial effects of acupuncture treatment for alleviating focal cerebral infarction-induced neuronal injury, mitochondrial biogenesis, energy metabolism, oxidative stress and dendrite regeneration were evaluated in rats with experimentally induced cerebral ischemia and dendron reperfusion. MATERIALS AND METHODS: Rats were randomly assigned to three groups (sham-operated, operated group without acupuncture, operated group with acupuncture). RT-PCR and Western blotting were used to assess variations of hippocampal cell mitochondrial DNA (mtDNA) copy number and mRNA and protein expression levels associated with key mitochondrial biogenesis proteins, namely peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiration factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). To evaluate mitochondrial oxidative phosphorylation and respiratory function in ischemic tissues, oxidative phosphorylation protein complex expression levels were assessed via Western blot analysis, mitochondrial membrane potential (MMP) was assessed via confocal microscopy and flow cytometry and adenosine triphosphate (ATP) concentration was assessed using an enzymatic fluorescence-based assay. Immunofluorescence staining was used to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2). Additionally, oxidative stress levels were assessed based on superoxide dismutase (SOD) activity, lipid oxidation levels (malondialdehyde, MDA) and glutathione (GSH) levels. Meanwhile, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, transmission electron microscopy observation and neuro behavioral status were used to determine cerebral infarction volume and extent of brain injury. RESULTS: Acupuncture treatment effectively stimulated mRNA-level and protein-level expression associated with PGC-1α, NRF-1 and TFAM and increased levels of electron transport chain complexes I, IV and V, thereby increasing the ATP concentration, maintaining mitochondrial membrane potential, and promoting dendron regeneration levels. Meanwhile, in hippocampal neurons SOD activity and the glutathione/glutathione disulfide (GSH/GSSG) ratio increased and MDA level decreased. CONCLUSION: Acupuncture treatment after ischemic injury promoted mitochondrial biogenesis, as reflected by beneficially increased mitochondrial oxidative phosphorylation complex protein levels and brain tissue energy supply, while preventing oxidative stress injury. These results should guide future explorations to elucidate acupuncture-based mechanisms for alleviating neuronal injury triggered by acute cerebral ischemia.

16.
Oncol Lett ; 27(3): 122, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38348387

RESUMEN

Spread Through Air Spaces (STAS) is involved in lung adenocarcinoma (LUAD) recurrence, where cancer cells spread into adjacent lung tissue, impacting surgical planning and prognosis assessment. Radiomics-based models show promise in predicting STAS preoperatively, enhancing surgical precision and prognostic evaluations. The present study performed network meta-analysis to assess the predictive efficacy of imaging models for STAS in LUAD. Data were systematically sourced from PubMed, Embase, Scopus, Wiley and Web of Science, according to the Cochrane Handbook for Systematic Reviews of Interventions) and A Measurement Tool to Assess systematic Reviews 2. Using Stata software v17.0 for meta-analysis, surface under the cumulative ranking area (SUCRA) was applied to identify the most effective diagnostic method. Quality assessments were performed using Cochrane Collaboration's risk-of-bias tool and publication bias was assessed using Deeks' funnel plot. The analysis encompassed 14 articles, involving 3,734 patients, and assessed 17 predictive models for STAS in LUAD. According to comprehensive analysis of SUCRA, the machine learning (ML)_Peri_tumour model had the highest accuracy (56.5), the Features_computed tomography (CT) model had the highest sensitivity (51.9) and the positron emission tomography (pet)_CT model had the highest specificity (53.9). ML_Peri_tumour model had the highest predictive performance. The accuracy was as follows: ML_Peri_tumour vs. Features_CT [relative risk (RR)=1.14; 95% confidence interval (CI), 0.99-1.32]; ML_Peri_tumour vs. ML_Tumour (RR=1.04; 95% CI, 0.83-1.30) and ML_Peri_tumour vs. pet_CT (RR=1.04; 95% CI, 0.84-1.29). Comparative analyses revealed heightened predictive accuracy of the ML_Peri_tumour compared with other models. Nonetheless, the field of radiological feature analysis for STAS prediction remains nascent, necessitating improvements in technical reproducibility and comprehensive model evaluation.

17.
Clin Oral Investig ; 28(2): 140, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38334890

RESUMEN

OBJECTIVE: To dynamically compare the longitudinal (time axis) and transverse (between groups) differences of the salivary cytokines during thalidomide maintenance treatment of recurrent aphthous stomatitis. METHODS: A randomized, controlled, clinical trial was performed. After the initial prednisone treatment, thalidomide (50 mg/d vs. 25 mg/d) was used as a maintenance drug for 4 or 8 weeks. The salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ were dynamically detected with a cytometric bead array. RESULTS: Overall, the level of six elevated salivary cytokines after prednisone treatment was significantly downregulated, remained low during thalidomide maintenance, and rebounded at recurrence. The effect of 50 mg/d thalidomide on the salivary cytokines was not superior to 25 mg/d medication. The relapse-free period following drug withdrawal was the longest in the subgroup using 25 mg/d thalidomide for 8 weeks. The order of magnitude of IL-6 was the most obvious, and at week 8, only the level of IL-6 in the group (25 mg/d thalidomide for 8 weeks) continued to decline compared with the other groups. CONCLUSION: Thalidomide maintenance treatment can effectively sustain low levels of salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ of recurrent aphthous stomatitis patients. IL-6 displayed a good correlation with the disease and is expected to become an index for diagnosis and follow-up. CLINICAL RELEVANCE: Low-dose long-term thalidomide maintenance treatment was supported for recurrent aphthous stomatitis. TRIAL REGISTRATION: Trial registration number of ChiCTR-IPR-16009759 at http://www.chictr.org/index.aspx .


Asunto(s)
Estomatitis Aftosa , Talidomida , Humanos , Talidomida/uso terapéutico , Estomatitis Aftosa/tratamiento farmacológico , Factor de Necrosis Tumoral alfa , Interleucina-4 , Interleucina-6 , Prednisona/uso terapéutico , Recurrencia
18.
World J Gastrointest Surg ; 16(1): 196-204, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38328336

RESUMEN

BACKGROUND: Transarterial chemoembolization (TACE) combined with microwave ablation (MWA) is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis. However, it may cause severe postoperative pain and inflammatory responses. The paravertebral block (PVB) is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions. AIM: To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis. METHODS: Sixty patients were randomly divided into PVB and control groups. The PVB group received ultrasound-guided PVB with 0.375% ropivacaine preoperatively, whereas the control group received intravenous analgesia with sufentanil. The primary outcome was the visual analog scale (VAS) score for pain at 6 h, 12 h, 24 h, and 48 h after the procedure. Secondary outcomes were the dose of sufentanil used, incidence of adverse events, and levels of inflammatory markers (white blood cell count, neutrophil percentage, C-reactive protein, and procalcitonin) before and after the procedure. RESULTS: The PVB group had significantly lower VAS scores at 6 h, 12 h, 24 h, and 48 h after the procedure compared with the control group (P < 0.05). The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea, vomiting, and respiratory depression than did the control group (P < 0.05). Compared with the control group, the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure (P < 0.05). CONCLUSION: PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

19.
Brain Res ; 1831: 148820, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38417653

RESUMEN

Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified human astrocyte-specific genes and found 131 of these genes significantly differentially expressed in human temporal lobe epilepsy (TLE) datasets. Multiple astrocytic functions, such as cell adhesion, cell morphogenesis, actin filament-based process, apoptotic cell clearance and response to oxidative stress, were found to be promoted. Moreover, multiple altered astrocyte-specific genes were enriched in phagocytosis, perisynaptic astrocyte processes (PAPs), plasticity, and synaptic functions. Nine hub genes (ERBB2, GFAP, NOTCH2, ITGAV, ABCA1, AQP4, LRP1, GJA1, and YAP1) were identified by protein-protein interaction (PPI) network analysis. The correlation between the expression of these hub genes and seizure frequency, as well as epilepsy-related factors, including inflammatory mediators, complement factors, glutamate excitotoxicity and astrocyte reactivity, were analyzed. Additionally, upstream transcription factors of the hub genes were predicted. Finally, astrogliosis and the expression of the hub genes were validated in an epileptic rat model. Our findings reveal the various changes in astrocyte function associated with epilepsy and provide candidate astrocyte-specific genes that could be potential antiepileptogenic targets.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Ratas , Humanos , Animales , Epilepsia del Lóbulo Temporal/metabolismo , Astrocitos/metabolismo , Gliosis/metabolismo , Convulsiones/metabolismo , Epilepsia/metabolismo
20.
Int J Biol Macromol ; 262(Pt 2): 130138, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38354930

RESUMEN

Functional materials with under-liquid dual superlyophobicity have generated a great deal of concern from researchers due to their switchable separation ability oil-water mixtures and emulsions. Conceptually, under-liquid dual superlyophobicity is a Cassie state achievable under-liquid through the synergy of an under-liquid double lyophobic surface and the construction of a highly rough surface. However, obtaining an under-liquid dual superlyophobic surface remains difficult due to its thermodynamic contradiction and complex surface composition. Herein, we successfully prepared a functional coating by modifying the mixture of cellulose nanocrystals (CNCs) and nano-TiO2 with perfluorooctanoic acid (PFOA) via a simple method, then obtained a polyester fiber membrane with under-liquid dual superlyophobicity by roll coating method. The surface wettability of the polyester (PET) membrane was altered, transforming it from the original under-water oleophobic/under-oil superhydrophilic state to the under-water superoleophobic/under-oil superhydrophobic state after coated. The resulting membrane was applied to separate oil and water on-demand. The coated PET membrane exhibited high separation efficiency (>99 %) and high separation flux, effectively separating immiscible oil-water systems as well as oil-in-water and water-in-oil emulsions. The coated PET membrane also demonstrated the ability to perform alternate separation of oil-water mixtures through wetting, washing, and rewetting cycles, with repeated processes up to 10 times without significant reduction in separation efficiency. Furthermore, compared with the previous works, our approach offers a simpler and more convenient method for constructing under-liquid dual superlyophobic surface, making it more suitable for continuous corporate production. This study may provide inspiration for the production and application in large-scale of under-liquid dual superlyophobic membranes.


Asunto(s)
Fabaceae , Nanopartículas , Celulosa , Poliésteres , Termodinámica
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