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1.
Front Pharmacol ; 15: 1437479, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144624

RESUMEN

Background: It is unclear whether patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are allowed variable low levels of alcohol. This study aimed to evaluate the effect of mild-moderate alcohol consumption on the biochemical and histological characteristics of patients with MASLD. Methods: Alcohol consumption was assessed in 713 patients with steatotic liver disease (SLD) who underwent liver biopsy. Non-drinking, mild-moderate drinking, and excessive drinking were defined as 0 g/day, 1-<20 g/day, and >20 g/day for women and 0 g/day, 1-<30 g/day, and >30 g/day for men, respectively. Liver biopsies were scored according to the NASH CRN system. Results: A total of 713 participants (median age 39.0 years and 77.1% male) with biopsy-proven SLD were enrolled, including 239 nondrinkers, 269 mild-moderate drinkers and 205 excessive drinkers. Excessive drinking was associated with increased risks for lobular inflammation and liver fibrosis compared to nondrinkers and mild-moderate drinkers. Compared with non-drinkers, mild-moderate drinkers had significantly lower odds for steatosis (OR = 0.60, 95% CI = 0.38-0.93, p = 0.025), hepatocellular ballooning (OR = 0.52, 95% CI = 0.29-0.91, p = 0.020) and fibrosis (OR = 0.50, 95% CI = 0.31-0.81, p = 0.005). However, in non-excessive drinkers with type 2 diabetes mellitus (T2DM), there was no association between mild-moderate alcohol consumption and liver fibrosis (OR = 0.562, 95% CI = 0.207-1.530, p = 0.257). Conclusions: Mild-moderate alcohol consumption might be protective against liver fibrosis in MASLD patients, which is modified by the presence of T2DM. However, further longitudinal studies are needed to determine the effect of ongoing alcohol consumption on disease severity.

2.
Sci Rep ; 14(1): 7078, 2024 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528192

RESUMEN

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.


Asunto(s)
Corteza Auditiva , Cuerpos Geniculados , Ratones , Animales , Cuerpos Geniculados/fisiología , Corteza Auditiva/fisiología , Neuronas , Neuritas , Vías Auditivas/fisiología , Tálamo/fisiología
3.
Hepatol Int ; 18(1): 225-237, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37208493

RESUMEN

BACKGROUND: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. METHODS: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. RESULTS: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). CONCLUSIONS: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.


Asunto(s)
Fallo Hepático Agudo , Humanos , Estudios Retrospectivos , Pronóstico , Fallo Hepático Agudo/etiología , Nomogramas , Factores de Riesgo
4.
Clin Transl Oncol ; 26(2): 363-374, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38103120

RESUMEN

INTRODUCTION: The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. METHODS: Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. RESULTS: We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. CONCLUSION: Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.


Asunto(s)
Tumores del Estroma Gastrointestinal , Linfoma , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Proliferación Celular , ARN Interferente Pequeño/farmacología , Línea Celular Tumoral , Apoptosis
5.
Hepatol Commun ; 7(5)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37141513

RESUMEN

BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.


Asunto(s)
Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Humanos , Estudios de Cohortes , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/complicaciones , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Endoscopía Gastrointestinal
6.
Lancet Gastroenterol Hepatol ; 8(5): 432-445, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36931287

RESUMEN

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/epidemiología , Estudios Prospectivos , China/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Unión Esofagogástrica/patología , Aprendizaje Automático , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiología
7.
Dig Dis ; 41(2): 325-334, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36063790

RESUMEN

BACKGROUND AND AIMS: Choledochoscopic gallbladder-preserving surgery (CGPS) has the advantage of treating benign gallbladder diseases on the premise of gallbladder preservation. However, it has no reliable preoperative diagnosis if the gallbladder is benign. Probe-based confocal laser endomicroscopy (pCLE) can obtain real-time and clear endoscopic images at the cell level in vivo. It is widely used in the diagnosis of digestive system diseases, but not in gallbladder diseases yet. We applied these two technologies in a complementary way into the diagnosis of gallbladder diseases and thereby lifted the reliability of CGPS. METHODS: We retrospectively analyzed the total 28 patients with the indication of CGPS with intraoperative pCLE scan referred to the Second Affiliated Hospital of Baotou Medical College between October 2019 and July 2020. The intraoperative pCLE results were compared with the postoperative pathology in various gallbladder diseases. RESULTS: We compared the intraoperative pCLE diagnosis with the postoperative pathological diagnosis and found a complete match without exception in both sensitivity and specificity. CONCLUSIONS: Based on our investigation, pCLE can provide the same accuracy as the traditional pathology in the diagnosis of gallbladder diseases with the additional advantages like noninvasive, real time, and instancy. This study serves to validate the correlation between CLE and histology. It holds a broad prospect in the application of pCLE as an intraoperative diagnosis in CGPS.


Asunto(s)
Enfermedades de la Vesícula Biliar , Laparoscopía , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Microscopía Confocal/métodos , Rayos Láser
8.
Heliyon ; 8(12): e12286, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36582688

RESUMEN

Excessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the efficacy of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active fraction of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction <10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active fraction of RJ in this action is <10kDa in water-soluble form.

9.
J Hematol Oncol ; 15(1): 162, 2022 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-36333749

RESUMEN

No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Estudios Prospectivos , Factores de Riesgo
10.
Cell Signal ; 96: 110374, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35654297

RESUMEN

Esophageal cancer is commonly seen as either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC), two very different cancers. CCN1 is a matricellular protein that induces apoptosis in EAC cells through upregulation of DR5, a death receptor, while its role in ESCC is unclear. DR6 is another death receptor, which has been reported to induce apoptosis, necroptosis, or pyroptosis in various cell systems with or without the engagement of its putative ligand amyloid precursor protein (APP). In this study, we found that CCN1 and DR6 were both highly expressed in ESCC but downregulated in EAC. Overexpression of CCN1 in ESCC cells inhibited cell proliferation through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not affect cell growth or cell death whatsoever.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Precursor de Proteína beta-Amiloide/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/metabolismo , Humanos , Receptores de Muerte Celular
11.
Front Med (Lausanne) ; 9: 872881, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35572990

RESUMEN

Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

13.
Arch Biochem Biophys ; 722: 109192, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35367194

RESUMEN

TNF, CCN1, and peptidoglycan recognition protein 1 (PGLYRP1) are often found together in the inflammatory tissue. While TNF and CCN1 promote tissue regeneration, PGLYRP1 protects it from bacterial infection. In fibroblasts, CCN1 was reported to support TNF in apoptosis induction while PGLYRP1 was found to compete with TNF for binding to TNFR1. When PGLYRP1 binds to TNFR1 by itself, it silences the receptor, but if HSP70 joins them, it leads to cell death. In cancer cells, however, CCN1 was found to antagonize TNF signaling by increasing the extracellular pool of TNFR1. In this study, we assessed their relationship in the esophageal cancer cells and found a more complex liaison among them. At first, TNF highly upregulated PGLYRP1 expression but downregulated CCN1. Secondly, PGLYRP1 bound TNFR1 and HSP70 both intracellularly and extracellularly, but TNF only promoted their extracellular interaction. Lastly, the knockdown of PGLYRP1 impaired TNF signaling. Taken together, this study shows that CCN1 interrupts TNF signaling by increasing the extracellular TNFR1 species while TNF fights back by upregulating PGLYRP1 to absorb them.


Asunto(s)
Citocinas/metabolismo , Neoplasias Esofágicas , Receptores Tipo I de Factores de Necrosis Tumoral , Proteínas Portadoras , Amigos , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo
14.
Cancer Control ; 29: 10732748221074734, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35291889

RESUMEN

Background: Esophageal cancer is one of the most common and deadliest cancers in the world, particularly esophageal adenocarcinoma. There has never been a special drug to treat it.Purpose: This article summarizes the work that we have done in our laboratory about the role of CCN1 in esophageal cancer and gives a new perspective of CCN1 biology.Research Design: This is a review article. Study Sample: The work was done using validated cell lines and fixed human tissue slides.Data Collection and Analysis: This is a review article, therefore, no data collection or analysis was involved.Results: CCN1 is a matricellular protein supporting adhesion, migration, and survival in normal cells, but in the esophageal cancer cells, it induces TRAIL-mediated apoptosis. CCN1 promotes TRAIL and its death receptor expression but downregulates the decoy receptors and survivin in a p53-dependant manner. It was thought that CCN1 relies on TNF to induce apoptosis, but our study found that these two molecules antagonize each other. CCN1 promotes TNFR1 cleavage and uses the soluble product to block TNF signaling, while TNF upregulates PGLYRP1 to overcome this obstacle because PGLYRP1 is a secreted protein that competes with TNF for TNFR1 binding. As a result, when CCN1 and TNF are present together in the vicinity of esophageal tumors, they cancel each other out.Conclusions: Based on our laboratory study, CCN1 has much potential to be a candidate for the treatment of esophageal cancer.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/patología , Apoptosis/fisiología , Proteína 61 Rica en Cisteína/metabolismo , Neoplasias Esofágicas/patología , Humanos , Transducción de Señal
15.
APL Mater ; 10(4)2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36861033

RESUMEN

Ultrasoft magnetorheological elastomers (MREs) offer convenient real-time magnetic field control of mechanical properties that provides a means to mimic mechanical cues and regulators of cells in vitro. Here, we systematically investigate the effect of polymer stiffness on magnetization reversal of MREs using a combination of magnetometry measurements and computational modeling. Poly-dimethylsiloxane-based MREs with Young's moduli that range over two orders of magnitude were synthesized using commercial polymers Sylgard™ 527, Sylgard 184, and carbonyl iron powder. The magnetic hysteresis loops of the softer MREs exhibit a characteristic pinched loop shape with almost zero remanence and loop widening at intermediate fields that monotonically decreases with increasing polymer stiffness. A simple two-dipole model that incorporates magneto-mechanical coupling not only confirms that micrometer-scale particle motion along the applied magnetic field direction plays a defining role in the magnetic hysteresis of ultrasoft MREs but also reproduces the observed loop shapes and widening trends for MREs with varying polymer stiffnesses.

16.
Cytokine ; 149: 155728, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34634651

RESUMEN

TNF signaling mostly supports cell growth by activating NFκB and only induces cell death when NFκB activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NFκB signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.


Asunto(s)
Adenocarcinoma/genética , Apoptosis/genética , Proteína 61 Rica en Cisteína/genética , Neoplasias Esofágicas/genética , Factores de Necrosis Tumoral/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación de la Expresión Génica/genética , Humanos , FN-kappa B/genética , Transducción de Señal/genética , Regulación hacia Arriba/genética
17.
Cancer Control ; 28: 10732748211066311, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34913371

RESUMEN

DNA mutation is a common event in the human body, but in most situations, it is fixed right away by the DNA damage response program. In case the damage is too severe to repair, the programmed cell death system will be activated to get rid of the cell. However, if the damage affects some critical components of this system, the genetic scars are kept and multiply through mitosis, possibly leading to cancer someday. There are many forms of programmed cell death, but apoptosis and necroptosis represent the default and backup strategy, respectively, in the maintenance of optimal cell population as well as in cancer prevention. For the same reason, the ideal approach for cancer treatment is to induce apoptosis in the cancer cells because it proceeds 20 times faster than tumor cell proliferation and leaves no mess behind. Induction of necroptosis can be the second choice in case apoptosis becomes hard to achieve, however, necroptosis finishes the job at a cost-inflammation.


Asunto(s)
Apoptosis/fisiología , Necroptosis/fisiología , Neoplasias/fisiopatología , Proliferación Celular/fisiología , Reparación del ADN/fisiología , Humanos , Inflamación
18.
Saudi J Gastroenterol ; 27(6): 376-382, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34341248

RESUMEN

BACKGROUND: Only a small proportion of patients with compensated advanced chronic liver disease (cACLD) had varices needing treatment (VNT) after recommended esophagogastroduodenoscopy (EGD) screening. We aimed to create a non-invasive nomogram based on routine tests to detect VNT in cACLD patients. METHODS: The training cohort included 162 cACLD patients undergoing EGD in a university hospital, between January 2014 and September 2019. A nomogram was developed based on the independent predictors of VNT, selected using a multivariate logistic regression analysis. Thirty-three patients from eight university hospitals were prospectively enrolled as validation cohort between December 2018 and December 2019. RESULTS: The prevalence of VNT was 32.7% (53/162) and 39.4% (13/33) in training and validation cohorts, respectively. The univariate analysis identified six risk factors for VNT. On the multivariate analysis, four of them, i.e., gallbladder wall thickness (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 0.98-1.56), spleen diameter (OR: 1.02; 95% CI: 1.00-1.04), platelet count (OR: 0.98; 95% CI: 0.97-0.99), and international normalized ratio (OR: 0.58; 95% CI: 0.06-5.84) were independently associated with VNT. Thus, a nomogram based on the four above - mentioned variables was developed, and showed a favorable performance for detecting VNT, with an area under receiver operating characteristic curve of 0.848 (95% CI: 0.769-0.927) in training cohort. By applying a cut-off value of 105 in validation cohort, 31.0% of EGD were safely spared with 3.4% of missed VNT. CONCLUSION: A nomogram based on routine clinical parameters was developed for detecting VNT and avoiding unnecessary EGD in cACLD patients.


Asunto(s)
Várices Esofágicas y Gástricas , Hepatopatías , Várices , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/epidemiología , Várices Esofágicas y Gástricas/terapia , Humanos , Nomogramas , Recuento de Plaquetas
19.
Chemosphere ; 285: 131392, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34242988

RESUMEN

A field experiment was conducted in a modern municipal solid waste (MSW) incineration power plant to explore the feasibility of using chemical agglomeration agent anionic polyacrylamide (PAM) to reduce the atmospheric emission of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Spraying PAM solution into the cooling tower caused an obvious decrease in the volume fraction of ultrafine and fine particles with diameter of 0.3-30 µm in BF fly ash, and a significant reduction in dust content in stack gas. The increased agglomeration of particles promoted the removal of particle-phase PCDD/Fs by BF, and thus resulted in a lower atmospheric emission of PCDD/Fs. The calculated removal efficiency of PCDD/Fs by BF was almost positively proportional to the concentration of PAM solution, while inversely proportional to the average content of dusk in stack gas. Compared with the control treatment, the spraying of 0.1 g/L PAM solution enhanced the removal efficiency of total tetra-to octa-CDD/Fs (∑PCDD/Fs) from 93.8% to 97.8% by BF, and resulted in a decrease of 47.0% in the concentration of international toxicity equivalent (I-TEQ) in stack gas. During the experiment of 2 d, the spraying of PAM solution did not induce a significant change in the differential pressure of BF, and did not essentially affect the partitioning behaviors of PCDD/F homologues between flue gas and BF fly ash. In view of technical safety and low cost, PAM application is recommended for reducing the atmospheric emission of PCDD/Fs from MSW incineration system.


Asunto(s)
Contaminantes Atmosféricos , Benzofuranos , Dioxinas , Dibenzodioxinas Policloradas , Resinas Acrílicas , Contaminantes Atmosféricos/análisis , Benzofuranos/análisis , Ceniza del Carbón , Dibenzofuranos , Dibenzofuranos Policlorados , Dioxinas/análisis , Incineración , Dibenzodioxinas Policloradas/análisis , Residuos Sólidos
20.
Lancet Reg Health West Pac ; 6: 100072, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34327406

RESUMEN

BACKGROUND: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference. METHODS: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience. FINDINGS: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD (p < 0•0001, d = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred. INTERPRETATION: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction. FUNDING: A full list of funding can be found in the Funding Support section.

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