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1.
Sci Total Environ ; 783: 147014, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34088129

RESUMEN

Nickel (Ni) is a heavy metal that is both an environmental pollutant and a threat to human health. However, the effects of Ni on the central nervous system in susceptible populations have not been well established. In the present study, the neurotoxicity of Ni and its underlying mechanism were investigated in vivo and in vitro. Ni exposure through drinking water (10 mg Ni/L, 12 weeks) caused learning and memory impairment in mice. Reduced dendrite complexity was observed in both Ni-exposed mouse hippocampi and Ni-treated (200 µM, 72 h) primary cultured hippocampal neurons. The levels of histone acetylation, especially at histone H3 lysine 9 (H3K9ac), were reduced in Ni-exposed mouse hippocampi and cultured neurons. RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing analyses revealed that H3K9ac-modulated gene expression were downregulated. Treatment with sodium butyrate, a histone deacetylase inhibitor, attenuated Ni-induced H3K9 hypoacetylation, neural gene downregulation and dendrite complexity reduction in cultured neurons. Sodium butyrate also restored Ni-induced memory impairment in mice. These results indicate that Ni-induced H3K9 hypoacetylation may be a contributor to the neurotoxicity of Ni. The finding that Ni disturbs histone acetylation in the nervous system may provide new insight into the health risk of chronic Ni exposure.


Asunto(s)
Histonas , Níquel , Acetilación , Animales , Regulación hacia Abajo , Histonas/metabolismo , Ratones , Níquel/toxicidad , Procesamiento Proteico-Postraduccional
2.
Acta Biochim Pol ; 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34106567

RESUMEN

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Our data showed that USP28 mRNA and protein expressions were enhanced in colorectal cancer tissues and cells. Functional assays demonstrated that overexpression of USP28 promoted cell proliferation and aerobic glycolysis of colorectal cancer, while USP28 inhibition could reverse these effects. Protein expression of Forkhead Box C1 (FOXC1) was increased by USP28 over-expression, whereas knockdown of USP28 aggravated cycloheximide (CHX; protein synthesis inhibitor) stimulated decrease of FOXC1. Moreover, proteasome inhibitor, MG132, could rescue USP28 silence-induced degradation of FOXC1. Overexpression of FOXC1 counteracted the suppressive effects of USP28 interference on colorectal cancer cell viability and aerobic glycolysis. In conclusion, USP28 enhanced cell viability and aerobic glycolysis of colorectal cancer by stabilizing FOXC1, suggesting that USP28-FOXC1 might be a novel therapeutic avenue for colorectal cancer.

3.
BMC Public Health ; 21(1): 1114, 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34112122

RESUMEN

BACKGROUND: Health-Related Quality of Life (HRQoL) of hypertensive patients is not only affected by the disease itself but also by some subjective factors. Low health literacy is prevalent among ethnic minorities. Considering the Kazakh-Chinese people have the highest prevalence of hypertension in Xinjiang, and the High Blood Pressure-Health Literacy (HBP-HL) has not been included in the study of HRQoL. The synergistic effects and the potential mechanism HBP-HL, self-management behavior, therapeutic adherence, self-efficacy, social support on HRQoL remain unclear. This study aimed to introduce the HBP-HL, and develop a structural equation model (SEM) to identify the factors influencing of the HRQoL among Kazakh hypertensive patients. METHODS: The data was obtained by questionnaire survey and physical examination in 2015. Patients with hypertension were recruited through random cluster sampling in Kazakh settlements in Xinjiang. Firstly, the blood pressure was measured. Then the one-for-one household interviews were conducted by Kazakh investigators. The questionnaires regarding HBP-HL, HRQoL, self-management behavior, therapeutic adherence, self-efficacy, and social support were used to collect data. Finally, SEM was constructed, and p ≤ 0.05 was taken as significant. RESULTS: The data was analysed by SPSS18.0 and AMOS18.0 software. 516 Kazakh hypertension patients were recruited, and 94.4% of them had a relatively low HBP-HL score. The mean standardized scores of HRQoL, self-management, therapeutic adherence were poor; they were 63.5, 66.2, and 64.4, respectively. But 96.1% and 98.3% of the participants had high levels of self-efficacy and social support. The SEM of the HRQoL had a good overall fit (χ2/df = 2.078, AGFI = 0.944, GFI = 0.968, CFI = 0.947, IFI = 0.949, RMSEA = 0.046). The model indicated that the HBP-HL has the highest correlation with HRQoL, following with self-management behavior, social support, and self-efficacy. CONCLUSIONS: Low HBP-HL is a major influenced factor of HRQoL among Kazakh hypertensive patients. Future programs should consider HBP-HL as the breakthrough point when designing targeting intervention strategies.

4.
BMC Musculoskelet Disord ; 22(1): 534, 2021 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-34118911

RESUMEN

BACKGROUND: To explore the prevalence of bone loss among patients with rheumatoid arthritis (RA) and healthy controls (HC) and further explored the risk factors for osteopenia and osteoporosis of RA patients. METHODS: A cross-sectional survey was undertaken in four hospitals in different districts in South China to reveal the prevalence of bone loss in patients. Case records, laboratory tests, and bone mineral density (BMD) results of patients were collected. Traditional multivariable logistic regression analysis and two machine learning methods, including least absolute shrinkage selection operator (LASSO) and random forest (RF) were for exploring the risk factors for osteopenia or osteoporosis in RA patients. RESULTS: Four hundred five patients with RA and 198 HC were included. RA patients had lower BMD in almost BMD measurement sites than healthy controls; the decline of lumbar spine BMD was earlier than HC. RA patients were more likely to comorbid with osteopenia and osteoporosis (p for trend < 0.001) in the lumbar spine than HC. Higher serum 25-hydroxyvitamin D3 level and using tumor necrosis factor inhibitor in the last year were protective factors; aging, lower body mass index, and increased serum uric acid might be risk factors for bone loss. CONCLUSIONS: RA patients were more prone and earlier to have bone loss than HC. More attention should be paid to measuring BMD in RA patients aging with lower BMI or hyperuricemia. Besides, serum vitamin D and all three measurement sites are recommended to check routinely. TNFi usage in the last year might benefit bone mass.


Asunto(s)
Artritis Reumatoide , Enfermedades Óseas Metabólicas , Absorciometría de Fotón , Artritis Reumatoide/epidemiología , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/epidemiología , China/epidemiología , Estudios Transversales , Humanos , Prevalencia , Factores de Riesgo , Ácido Úrico
5.
Lung Cancer ; 158: 47-54, 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34119932

RESUMEN

OBJECTIVES: As a poor prognostic factor, visceral pleural invasion (VPI) was incorporated into non-small cell lung cancer (NSCLC) staging system. For modifying the T description of NSCLC, the prognostic value of VPI was assessed. MATERIALS AND METHODS: From 2010-2015, data on stage pT2N0M0 NSCLC patients with tumor size (TS) from 3.1 cm to 5.0 cm who received surgery from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled retrospectively. Propensity score matching was utilized to balance the baseline factors according to different TS intervals. Overall survival (OS) was assessed by the Kaplan-Meier method and log-rank test. Univariate and multivariate analysis were applied to identify the prognostic factors. The risk factors of VPI were calculated by logistic regression model. RESULT: The sum of 4005 resected stage pT2N0M0 NSCLC patients with TS from 3.1 cm to 5.0 cm were recruited, which had 1084 patients with VPI and 2921 patients without VPI respectively. As TS interval of 3.1-4.0 cm, the 5-year OS of patients without VPI was significantly better than those with VPI (62.6 % vs 58.7 %, P = 0.015), while the 5-year OS of patients with VPI and TS interval of 3.1-4.0 cm had no significant difference compared with patients whose TS interval of 4.1-5.0 cm (58.7 % vs 58.8 %, P = 0.918). Logistic regressive analysis manifested that older age, female, worse differentiation grade and larger TS had higher incidence of VPI (OR = 1.01, 1.25, 1.25, 1.16, respectively; P < 0.05 for all). CONCLUSION: This study underlined the prognostic effect of VPI and suggested that early-stage NSCLC with VPI and TS interval of 3.1-4.0 cm could be appropriately upstaged from pT2a (stage pIB) to pT2b (modified stage pIIA).

6.
J Hazard Mater ; 418: 126285, 2021 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-34119973

RESUMEN

Marine phycotoxins severely threaten ecosystem health and mariculture. This study investigates the spatial distribution and source of diverse phycotoxins in the South China Sea (SCS), during four 2019/2020 cruises. Saxitoxin (STX) and okadaic acid (OA) -groups, azaspiracids, cyclic imines, pectenotoxins (PTX), yessotoxins, and domoic acid (DA) toxins were analyzed in microalgal samples. PTX2 occurred with the highest (93.5%) detection rate (DR) during all cruises, especially in the Pearl River Estuary (PRE) in June 2019. Homo-yessotoxin (hYTX) and DA were found during three cruises in August 2020, and high DR of hYTX (67.7%, 29.3%) and DA (29.0%, 29.3%) in the PRE and Guangdong coast, respectively, in June 2019 and 2020, peaking at concentrations of 777 pg hYTX L-1 and 38514 pg DA L-1. The phycotoxin distribution demonstrated that DA-producing microalgae gathered close to the PRE and Guangdong coast, while hYTX-producing microalgae distributed relatively far offshore. Microalgae producing PTX2- and STX-group toxins were more widely living in the SCS. High-throughput sequencing results suggested that Alexandrium pacificum and Gonyaulax spinifera were responsible for STX-group toxins and hYTX, respectively, while Pseudo-nitzschia cuspidata was the main source of DA. Widely distributed PTX2, hYTX, and DA were reported for the first time in the SCS.

7.
J Hazard Mater ; 418: 126271, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34119981

RESUMEN

UiO-66-NH2@eosin Y composite was obtained by confining eosin Y (EY) into the cavities of Zr-MOF and could emit two fluorescence peaks at 453 and 543 nm at an excitation wavelength of 355 nm. This multi-responsive and multifunctional ratiometric fluorescent nanoprobe not only enable directly distinct detection of F-/Cr2O72- with ultra-high selectivity and sensitivity, but also could indirectly monitor the concentration of urea based on unique enzymatic hydrolysis reaction. The multifunctional probe was utilized for fluorescence labeling F-/Cr2O72- in sweat latent fingerprint through an environmentally friendly powder strategy and exhibited obvious luminescence visualization changes. Notably, the corresponding portable on-line test strips of probe for detection of F- and Cr2O72- were made for monitoring the levels of F- and Cr2O72-. Furthermore, the probe was applied to evaluate the degrees of F-/Cr2O72- in HepG-2 cell and urea in serum with superior results,which indicate the potential application of the as-synthesized UiO-66-NH2@EY as multifunctional probe for the detection of F-, Cr2O72- and urea in biological samples. Finally, in order to extend the device-based applications of probe, an AND-OR-coupled molecular logic gate was put on agenda.

8.
Artículo en Inglés | MEDLINE | ID: mdl-34129508

RESUMEN

Automatic vessel segmentation in the fundus images plays an important role in the screening, diagnosis, treatment, and evaluation of various cardiovascular and ophthalmologic diseases. However, due to the limited well-annotated data, varying size of vessels, and intricate vessel structures, retinal vessel segmentation has become a long-standing challenge. In this paper, a novel deep learning model called AACA-MLA-D-UNet is proposed to fully utilize the low-level detailed information and the complementary information encoded in different layers to accurately distinguish the vessels from the background with low model complexity. The architecture of the proposed model is based on U-Net, and the dropout dense block is proposed to preserve maximum vessel information between convolution layers and mitigate the over-fitting problem. The adaptive atrous channel attention module is embedded in the contracting path to sort the importance of each feature channel automatically. After that, the multi-level attention module is proposed to integrate the multi-level features extracted from the expanding path, and use them to refine the features at each individual layer via attention mechanism. The proposed method has been validated on the three publicly available databases, i.e. the DRIVE, STARE, and CHASE DB1. The experimental results demonstrate that the proposed method can achieve better or comparable performance on retinal vessel segmentation with lower model complexity. Furthermore, the proposed method can also deal with some challenging cases and has strong generalization ability.

9.
J Cell Mol Med ; 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34132026

RESUMEN

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.

10.
Artículo en Inglés | MEDLINE | ID: mdl-34132184

RESUMEN

BACKGROUND: Santacruzamate A (SCA) is a natural product isolated from a marine cyanobacterium. Activity test results revealed that SCA is a highly potent HDAC2 inhibitor with an IC50 value of 0.112 nM. The IC50 of SCA in inhibiting cancer cell proliferation is 28.3 µM and 1.3µM on HCT116 and HuT-78 cells, respectively. OBJECTIVE: To develop HDAC inhibitors with improved activity, SCA analogs were synthesized for the structure-activity relationship (SAR) studies. METHOD: Various substituted groups were introduced into the zinc binging group, linker, and cap regions of SCA by various chemical synthetic methods. RESULT: Compared with SCA, the derivatives of SCA did not exhibit improved HDAC2 inhibitory activity. Nevertheless, several molecules such as III-32, III-33, IV-4b, and IV-11 showed improved activity in inhibiting cell proliferation on HCT116 and HuT-78 cells. CONCLUSION: Collectively, a potent HDAC2 inhibitor SCA was discovered as a lead compound for further development of selective HDAC inhibitors.

11.
Phys Chem Chem Phys ; 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34132301

RESUMEN

SARS-CoV-2 has recently caused an epidemic in humans and poses a huge threat to global public health. As a primary receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) exists in different hosts that are in close contact with humans, especially cats and dogs. However, the underlying mechanism of how the spike receptor binding domain (RBD) of SARS-CoV-2 cooperates with human ACE2 (hACE2), cat ACE2 (cACE2) and dog ACE2 (dACE2) and the variation in binding remains largely unsolved. Therefore, we explored the binding behavior of the spike RBD with cACE2, dACE2 and hACE2 via all-atom molecular dynamics simulations. In accordance with the binding free energies and residue interactions, the spike RBD has respective binding specificities with cACE2, dACE2 and hACE2, and the binding affinities decrease in the order of hACE2, cACE2, dACE2, mainly due to changes in the amino acids Q24L, H34Y, and M82T in cACE2 or dACE2. Furthermore, alanine scanning analysis results validated some key residues of the spike RBD interact with ACE2 and provided clues to the variation of amino acid that could influence the transmissibility or immune responses of SARS-CoV-2. Decreasing dynamic correlations strengths of ACE2 with the RBD were found in all hACE2-RBD, cACE2-RBD and dACE2-RBD systems. The ACE2 protein shows variable motion modes across the zinc metallopeptidase domain, which induces different interactions between ACE2 and the RBD. Our studies reveal that the motion pattern of the zinc metallopeptidase domain is critical to the binding behavior of RBD with ACE2. These findings could aid our understanding of selective recognition involving various ACE2 with the SARS-CoV-2 spike and shed further light on the binding mechanisms.

12.
Soft Matter ; 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34132309

RESUMEN

To investigate the effect of the number of propylene oxide (PO) units on the wettability of surfactants, the wettability of isomeric dodecyl(polyoxyisopropyl)7 sulfate (S-C12PO7S) and isomeric dodecyl(polyoxyisopropyl)13 sulfate (S-C12PO13S) on the surface of polymethylmethacrylate (PMMA) was investigated. The adsorption behavior on the PMMA surface was analyzed by measuring the surface tension and the contact angle. It is found that the PO group may form hydrogen bonds with the PMMA surface, thus facilitating the hydrophobic tails pointing to the aqueous phase. Moreover, the steric effect of the PO group benefits the formation of semi-micelles above the critical micelle concentration (CMC). Surfactant molecules adsorb on the PMMA surface by polar adsorption below the CMC with hydrophobic tails towards the water. Therefore, the PMMA surface is modified to be more hydrophobic. However, the sodium dodecyl sulfate (SDS) surfactant with no PO unit does not have hydrophobic modification ability on the PMMA surface. Below the CMC, the adsorption amounts of the S-C12PO7S and S-C12PO13S surfactants at the solid-liquid interface were approximately 1/3 of those at the air-liquid interface. Interestingly, the adsorption behavior changes when the concentration of the surfactants is around the CMC. The hydrophilic heads of the surfactant molecules will point to water, and the surfactant molecules will form semi-micellar aggregates on the PMMA surface. Therefore, the PMMA surface is modified to be hydrophilic above the CMC. What's more, both the hydrophilic modification ability and hydrophobic modification ability of the S-C12PO13S surfactant are stronger than those of the S-C12PO7S surfactant. This means that the number of PO units will affect the wettability ability of the surfactants. Therefore, the S-C12PO13S surfactant possesses smaller contact angles than the S-C12PO7S surfactant at high concentrations.

13.
Hum Mol Genet ; 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34132789

RESUMEN

Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies (GWASs) summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression (LDSC) reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, p = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asiany. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, p = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, p = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, p = 4.14E-05) and fracture risk (OR = 1.036, and p = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, p = 1.04E-03) as well as antibodies against citrullinated proteins (ACPA)-positive RA (OR = 1.083, p = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.

14.
Waste Manag ; 130: 127-135, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34082398

RESUMEN

In this study, the effect of leachate seepage on the strength properties of a landfill temporary cover material: sewage sludge solidified with soda residue, ground granulated blast furnace slag, and quicklime, was investigated using small-scale column tests. The strength of the solidified sludge was reflected by penetration resistance with a micro penetrometer. The results showed that the penetration resistance increased at first, but then decreased with the increase in duration. The peak value for penetration resistance appeared at around the 75th day under the effect of leachate seepage. In contrast, without leachate seepage, penetration resistance increased at first as duration increased and then remained stable. The main hydration products were calcium silicate hydrate, ettringite and hydrocalumite. Some pollutants, such as copper, chromium, and arsenic, were also stabilized by the solidified sludge. The nuclear magnetic resonance results showed that the sample with highest penetration resistance had a reduced pore volume, especially macropore volume. Furthermore, leachate corrosion and the removal of some substances contributed to the decrease in penetration resistance after long-term seepage. The strength performance of temporary cover in laboratory short-term seepage and leachate soaking environments might be different from that in a landfill leachate seepage environment. This study improves understanding about the performance of temporary cover materials in landfill.

15.
Ecotoxicol Environ Saf ; 220: 112408, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34111662

RESUMEN

BACKGROUND: Epidemiologic evidence suggests that PM2.5 exposure aggravates asthma, but the molecular mechanisms are not fully discovered. METHODS: Ovalbumin (OVA)-induced mice exposed to PM2.5 were constructed. Pathological staining and immunofluorescence were performed in in vivo study. Gene set enrichment analysis (GSEA) was performed to identify the pathway involved in asthma severity by using U-BIOPRED data (human bronchial biopsies) and RNA-seq data (Beas-2B cells treated with PM2.5). Lentiviruses transfection, Real-time qPCR, immunofluorescence staining and trans-epithelial electrical resistance (TEER) measurement were performed for mechanism exploration in vitro. RESULTS: PM2.5 exposure aggravated airway inflammation and mucus secretion in OVA-induced mice. Based on transcriptome analysis of mild-to-severe asthma from human bronchial biopsies, gene set enrichment analysis (GSEA) showed that up-regulated reactive oxygen species (ROS) pathway gene set and down-regulated apical junction gene set correlated with asthma severity. Consistent with the analysis of mild-to-severe asthma, after PM2.5 exposure, the ROS pathway in Beas-2B cells was up-regulated with the down-regulation of apical junction. The expression levels of genes involved in the specific gene sets were validated by using qPCR. The mRNA levels of junction genes, ZO-1, E-cadherin and Occludin, were significantly decreased in cells exposed to PM2.5. Moreover, it confirmed that inhibition of ROS recovered the expression levels of E-cadherin, Occludin and ZO-1, and ameliorated inflammation and mucus secretion in airway in OVA-induced mice exposed to PM2.5. Meanwhile, ROS level was elevated by PM2.5. By checking trans-epithelial electrical resistance (TEER) value, we also found that epithelial barrier was damaged after PM2.5 exposure. Importantly, Stanniocalcin 2 (STC2) was identified as a key gene in regulation of epithelial barrier. It showed that STC2 expression was up-regulated by PM2.5, which was recovered by NAC as well. Over-expression of STC2 could decrease the expression levels of ZO-1, Occludin and E-cadherin. Contrarily, suppression of STC2 could increase the expression levels of ZO-1, Occludin and E-cadherin reduced by PM2.5. CONCLUSIONS: By using transcriptome analysis, we revealed that STC2 played a key role in PM2.5 aggravated airway dysfunction through regulation of epithelial barrier in OVA-induced mice.

16.
Clin Res Hepatol Gastroenterol ; : 101695, 2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34147661

RESUMEN

BACKGROUND: Preoperative serum carbohydrate antigen 125 (CA125) is used to judge the diagnosis and prognosis of various tumors. However, the relationship between preoperative serum CA125 and prognosis of hilar cholangiocarcinoma (HCCA) has not been proven. This study aims to evaluate preoperative serum CA125 in predicting the prognosis of HCCA after resection. METHODS: A total of 233 patients after radical resection of HCCA were included. The associations between the levels of preoperative serum CA125 and the clinicopathological characteristics of patients were analyzed. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify independent risk factors associated with recurrence-free survival (RFS) and overall survival (OS). RESULTS: Among 233 patients, 198 (84.97%) with normal CA125 levels (≤35 U/mL) had better OS and RFS than 35 (15.02%) patients with higher CA125 levels (>35 U/mL). Preoperative serum CA125 was significantly correlated with tumor size, Bismuth-Corlette classification, microvascular invasion and carcinoembryonic antigen (CEA) (p<0.001, p=0.040, p=0.019 and p=0.042, respectively). The results of multivariable Cox regression showed that preoperative serum CA125 >35 U/mL (p=0.002, HR=1.910 for OS; p=0.006, HR=1.755 for RFS), tumor classification (p<0.001, HR=2.110 for OS; p=0.006, HR=1.730 for RFS), lymph node metastasis (p<0.001, HR=1.795 for OS; p<0.001, HR=1.842 for RFS) and major vascular invasion (p=0.002, HR=1.639 for OS; p=0.005, HR=1.547 for RFS) were independent risk factors for both OS and RFS. CONCLUSIONS: Preoperative serum CA125 is a good tumor marker for predicting prognosis after radical surgery for HCCA.

17.
Med Oncol ; 38(7): 85, 2021 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-34148185

RESUMEN

Hepatocellular carcinoma (HCC) is among the primary causes of cancer deaths globally. Despite efforts to understand liver cancer, its high morbidity and mortality remain high. Herein, we constructed two nomograms based on competing endogenous RNA (ceRNA) networks and invading immune cells to describe the molecular mechanisms along with the clinical prognosis of HCC patients. RNA maps of tumors and normal samples were downloaded from The Cancer Genome Atlas database. HTseq counts and fragments per megapons per thousand bases were read from 421 samples, including 371 tumor samples and 50 normal samples. We established a ceRNA network based on differential gene expression in normal versus tumor subjects. CIBERSORT was employed to differentiate 22 immune cell types according to tumor transcriptomes. Kaplan-Meier along with Cox proportional hazard analyses were employed to determine the prognosis-linked factors. Nomograms were constructed based on prognostic immune cells and ceRNAs. We employed Receiver operating characteristic (ROC) and calibration curve analyses to estimate these nomogram. The difference analysis found 2028 messenger RNAs (mRNAs), 128 micro RNAs (miRNAs), and 136 long non-coding RNAs (lncRNAs) to be significantly differentially expressed in tumor samples relative to normal samples. We set up a ceRNA network containing 21 protein-coding mRNAs, 12 miRNAs, and 3 lncRNAs. In Kaplan-Meier analysis, 21 of the 36 ceRNAs were considered significant. Of the 22 cell types, resting dendritic cell levels were markedly different in tumor samples versus normal controls. Calibration and ROC curve analysis of the ceRNA network, as well as immune infiltration of tumor showed restful accuracy (3-year survival area under curve (AUC): 0.691, 5-year survival AUC: 0.700; 3-year survival AUC: 0.674, 5-year survival AUC: 0.694). Our data suggest that Tregs, CD4 T cells, mast cells, SNHG1, HMMR and hsa-miR-421 are associated with HCC based on ceRNA immune cells co-expression patterns. On the basis of ceRNA network modeling and immune cell infiltration analysis, our study offers an effective bioinformatics strategy for studying HCC molecular mechanisms and prognosis.

18.
FASEB J ; 35(7): e21699, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34151459

RESUMEN

FUT2, a protein that uses l-fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l-fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l-fucose on the restoration of epithelial barrier function in both the DSS-induced colitis mouse model and LPS-stimulated Caco-2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS-induced colitis was significantly reduced by l-fucose. Restoration of epithelial barrier function by l-fucose was detected. Direct l-fucose-mediated protection of tight junctions was observed in Caco-2 cells. Moreover, exogenous l-fucose promoted the exogenous metabolic pathway of l-fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l-fucose on barrier function. The severity of colitis was not improved by l-fucose in Fut2 knockout mice. Therefore we conclude that exogenous l-fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.

19.
Small ; : e2100323, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34151517

RESUMEN

Carbon dioxide (CO2 ) emission has caused greenhouse gas pollution worldwide. Hence, strengthening CO2 recycling is necessary. CO2 electroreduction reaction (CRR) is recognized as a promising approach to utilize waste CO2 . Electrocatalysts in the CRR process play a critical role in determining the selectivity and activity of CRR. Different types of electrocatalysts are introduced in this review: noble metals and their derived compounds, transition metals and their derived compounds, organic polymer, and carbon-based materials, as well as their major products, Faradaic efficiency, current density, and onset potential. Furthermore, this paper overviews the recent progress of the following two major applications of CRR according to the different energy conversion methods: electricity generation and formation of valuable carbonaceous products. Considering electricity generation devices, the electrochemical properties of metal-CO2 batteries, including Li-CO2 , Na-CO2 , Al-CO2 , and Zn-CO2 batteries, are mainly summarized. Finally, different pathways of CO2 electroreduction to carbon-based fuels is presented, and their reaction mechanisms are illustrated. This review provides a clear and innovative insight into the entire reaction process of CRR, guiding the new electrocatalysts design, state-of-the-art analysis technique application, and reaction system innovation.

20.
Bioengineered ; 12(1): 2723-2733, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34151717

RESUMEN

To probe into the impact of Bupivacaine on colorectal cancer (CRC) proliferation, apoptosis, and autophagy through regulating the NF-κB signaling pathway. Our work treated CRC cells with Bupivacaine, detected cell vitality through MTT assay, apoptosis through flow cytometry, cell migration through wound healing assay, NF-κB activity through immunofluorescence, inflammatory factor level, including TNF-α, IL-1ß as well as IL-6 through ESLIA, apoptosis factor mRNA expression, including Bcl-2, Bax and caspase-3q through qRT-PCR, and protein expression linking with NF-κB signaling pathway as well as autophagy-related proteins via western blot. In in vivo experiments, we explored the impact of Bupivacaine on tumor volume, tumor and NF-κB expression. The results showed that 1 mM Bupivacaine was available to signally inhibit CRC cell vitality, promoted apoptosis rate and apoptosis gene expression, like Bax, and caspase-3, inhibited Bcl-2 expression, inhibited cancer cell migration, promoted autophagy-related protein LC3B II/LC3B I ratio and beclin-1 expression, and inhibited p62 expression. Additionally, it could elevate inflammatory factor level and induce IKK and IκB phosphorylation as well as NF-κB proteins. In in vivo experiments, Bupivacaine inhibited tumor volume and tumor, as well as NF-κB expression. In short, bupivacaine is available to inhibit CRC proliferation through regulating NF-κB signaling pathway, promote apoptosis and autophagy, and can be used as a potential drug to treat CRC in the future.

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