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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 530-534, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812426

RESUMO

OBJECTIVE: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. METHODS: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. RESULTS: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, ß2-MG, Hcy, low-level Hb, and ALB was significantly shortened (all P<0.05). The results of multivariate survival analysis showed that old age, high levels of bone marrow plasma cells, Cr, ß2-MG, low levels of Hb, and ALB were the independent risk factors shorting the overall survival (OS) time of newly diagnosed MM patients (all P<0.05), while Hcy showed no independent relation for the OS of patients (P>0.05). The Hb level of the patients in high Hcy group was significantly lower than those in low-Hcy group, while the LDH level was significantly higher than those in low Hcy group (all P<0.05). Pearson test results showed that serum Hcy and Hb showed negative correlation (r=-0.813, P<0.05), but it shows positive correlation with LDH (r=0.726, P<0.05). CONCLUSION: Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.


Assuntos
Mieloma Múltiplo , Células da Medula Óssea , Homocisteína , Humanos , Prognóstico , Fatores de Risco
4.
Life Sci ; 273: 119298, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667519

RESUMO

The rapid renewal of intestinal epithelium during homeostasis requires balanced proliferation and differentiation of intestinal stem cells (ISCs) at the base of crypt. Upon intestinal inflammation, the vigorous expansion of surviving ISCs is responsible for epithelial repair. However, it is not well depicted how ISCs adapt to the inflammatory conditions within intestinal tissue and support epithelial repair. In the intestinal inflammation, niche cells around ISCs along with their secreted niche factors can facilitate the regeneration of ISCs via niche signals. Additionally, the growth of ISCs can respond to inflammatory cells, inflammatory cytokines, and inflammatory signals. Understanding the adaptive mechanism of ISCs in supporting intestinal epithelial regeneration during inflammation is a focus on the treatment for patients with intestinal inflammation. Here, we aim to present an overview of how ISCs adapt to the acute inflammation to support intestinal repair, with a focus on the roles and interaction of niche signals.

5.
Front Cell Infect Microbiol ; 11: 619354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763383

RESUMO

Parkinson's disease (PD) is the most common movement disorder in the world, affecting 1-2 per 1,000 of the population. The main pathological changes of PD are damage of dopaminergic neurons in substantia nigra of the central nervous system and formation of Lewy bodies. These pathological changes also occur in the intestinal tract and are strongly associated with changes in intestinal flora. By reviewing the research progress in PD and its association with intestinal flora in recent years, this review expounded the mechanism of action between intestinal flora and PD as well as the transmission mode of α - synuclein in neurons. In clinical studies, ß diversity of intestinal flora in PD patients was found to change significantly, with Lactobacillusaceae and Verrucomicrobiaceae being significantly increased and Lachnospiraceae and Prevotellaceae being significantly decreased. In addition, a longer PD course was associated with fewer bacteria and probiotics producing short chain fatty acids, but more pathogenic bacteria. Moreover, the motor symptoms of PD patients may be related to Enterobacteriaceae and bacteria. Most importantly, catechol-O-methyltransferase inhibitors and anticholinergic drugs could change the intestinal flora of PD patients and increase the harmful flora, whereas other anti-PD drugs such as levodopa, dopamine agonist, monoamine oxidase inhibitors, and amantadine did not have these effects. Probiotics, prebiotics, and synbiotics treatment had some potential values in improving the constipation of PD patients, promoting the growth of probiotics, and improving the level of intestinal inflammation. At present, there were only a few case studies and small sample studies which have found certain clinical efficacy of fecal microbiome transplants. Further studies are necessary to elaborate the relationship of PD with microbes.

7.
Chin J Integr Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709239

RESUMO

OBJECTIVE: To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke. METHODS: The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot. RESULTS: Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01). CONCLUSION: EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.

8.
Anticancer Drugs ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675611

RESUMO

Lung squamous carcinoma (LUSC) is the second most frequent subtype of non-small cell lung cancer. Rarely gene alterations are identified in LUSC. Therefore, identifying LUSC-related genes to explain the relevant molecular mechanism is urgently needed. A potential biomarker, calcium-activated nucleotidase 1 (CANT1), was elevated in tissues of LUSC patients relative to normal cases based on the TCGA and/or GTEx database. CCK-8 and transwell tests were then implemented to measure the proliferative, invasive and migratory capacities, and showed that knockdown of CANT1 blocked LUSC cells proliferation. miR-607, predicted as an upstream factor for CANT1, was declined in LUSC using TargetScan analysis and luciferase activity test. Low miR-607 expression was related with unfavorable outcomes of LUSC patients. Moreover, miR-607 downregulation elevated cell viability, invasion and migration in LUSC cells, which was antagonized by si-CANT1. GEPIA website was accessed to estimate the relevance between CANT1 and epithelial-mesenchymal transition (EMT)-related positive factors. The protein levels of Fibronectin, Vimentin, Snail and ß-catenin were altered due to the abnormal CANT1 and miR-607 expression. Together, these data unveiled that miR-607/CANT1 pair may exert a vital role in the progression of LUSC through mediating EMT process, which would furnish an available therapeutic therapy for LUSC.

9.
Zhongguo Zhong Yao Za Zhi ; 46(3): 620-629, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645028

RESUMO

In this study, the antioxidant property changes in fermented Ziziphi Spinosae Semen(FZSS) with Poria cocos were analyzed by DPPH, ABTS and FRAP methods. Then the content determination of active ingredients and ~1H nuclear magnetic resonance(~1H-NMR) spectroscopy were also used to investigate the mechanism of FZSS with P. cocos in enhancing the antioxidant activity. The results showed that the content of active ingredients such as total phenols, total saponins and total polysaccharides were significantly increased during the fermentation time. The results of ~1H-NMR metabonomics showed that the contents of amino acids such as leucine, lysine, valine and alanine, nitrogen compounds such as creatine, creatinine, and betaine, and secondary metabolites, for instance, jujuboside A and spinosin were higher after fermentation, and above components showed positive correlation with antioxidant capacity in Pearson correlation analysis. Therefore, it was inferred that the enhancement of antioxidant activity of FZSS may be the result of the joint action of various chemical components. This study preliminarily clarified the mechanism of FZSS in enhancing the antioxidant activity, and provided new research ideas for the product development and utilization of FZSS.


Assuntos
Medicamentos de Ervas Chinesas , Poria , Wolfiporia , Ziziphus , Antioxidantes , Cromatografia Líquida de Alta Pressão , Sêmen
11.
Signal Transduct Target Ther ; 6(1): 123, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723219

RESUMO

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.


Assuntos
Imunidade Inata , Proteínas de Membrana/imunologia , Nucleotidiltransferases/imunologia , RNA Viral/imunologia , Transdução de Sinais/imunologia , Proteínas Virais/imunologia , Células A549 , Animais , Galinhas , Células HEK293 , Células HeLa , Humanos , Ligases/imunologia , Camundongos
12.
J Hazard Mater ; 415: 125594, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33740722

RESUMO

Inefficiency, high cost, and complex operation have emerged as shackles for large-scale separate oil-in-water emulsion. Herein, a low-cost and eco-friendly separation layer with a rough structure and rich anionic groups was fabricated from rice straw (RS) via a simple acid-base treatment and slight squeeze process. The separation layer's morphology, composition, and wettability were investigated. It was then employed to separate oil-in-water emulsion. The RS after acid and alkali treatment (A1A2-RS) exhibited a clear fiber structure and abundant humps, which made the separation layer superwettable and highly electronegative (-26.55 mV). The overlapped and intertwined A1A2-RS layer structure owned a superior performance for hexadecyl-trimethyl-ammonium-bromide (CTAB) adsorption and tiny oil interception. As a result, the separation layer had stable fluxes (>500 LMH) for multiple CTAB-stabilized emulsions and the obtained filtrates performed low total organic carbon (TOC) contents (<30 mg/L). In addition, the A1A2-RS layer had excellent renewability (10 cycles/ 200 mL) and the flux could be substantially recovered merely by aqueous wash. Moreover, filtrate analysis showed that the A1A2-RS layer had a good effect on actual emulsion treatment with a TOC removal rate of 89.56%.

13.
World J Gastroenterol ; 27(9): 835-853, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33727773

RESUMO

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.


Assuntos
/complicações , Hepatopatias/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , /fisiopatologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
14.
J Sep Sci ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784419

RESUMO

Fructus Aurantii is a traditional medicated diet in East Asia. To determine the underlying chemical markers responsible for the quality and efficacy of Fructus Aurantii, a sensitive metabolomic method was applied to distinguish Fructus Aurantii in Jiangxi Province from other two geographical locations (Hunan Province and Chongqi City) in China. In the present study, multivariate analyses were adopted to compare chemical compositions in 21 batches of Fructus Aurantii samples. Among three geographical origins, 23 differential compounds were structurally identified. Serum pharmacochemistry exhibited that 22 components could be detected in rat serum. Six differential and absorbed components were selected as six potential markers. Statistical analysis of the effects of six potential markers on the quality of Fructus Aurantii revealed that the content of markers varied widely in three origins. Six differential and absorbed components were evaluated further biological activity. Neohesperidin, naringin and meranzin showed inhibitory effect on acetylcholinesterase that regulates gastrointestinal motility in vitro and in silico, suggesting that these three components may be determined as the active biomarkers of Fructus Aurantii. These findings demonstrate the potential of biomarkers for identification and quality control of Fructus Aurantii. This article is protected by copyright. All rights reserved.

15.
Food Chem ; 355: 129411, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33770620

RESUMO

Metal-organic frameworks (MOFs), a sort of dispersive solid-phase extraction (d-SPE) material, has shown considerable prospects in the pretreatment of food, biological and other complex samples. Herein, we developed a method for compounding MOFs for d-SPE and trace determination of tetracyclines (TCs) in honey. When the compounding ratio of MIL-101 (Cr), MIL-100 (Fe) and MIL-53 (Al) was 7:1:2, adsorption-extraction was effective. Followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), the limits of detection were 0.073-0.435 ng/g and the limits of quantitation ranged from 0.239 to 1.449 ng/g for oxytetracycline, tetracycline, chlortetracycline and doxycycline. The method was applied to four kinds of honey samples with recoveries from 88.1% to 126.2%. The compounding of MOFs provides a strategy for purification and multi-target extraction from complex food matrices by d-SPE.

16.
Medicine (Baltimore) ; 100(10): e25124, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725911

RESUMO

ABSTRACT: Although some studies have reported the expression and clinical significance of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in breast cancer tissues, it is still controversial whether p-STAT3 play a role in promoting or suppressing cancer. Here, we used immunohistochemistry analysis to explore expression of p-STAT3 in 407 cases of breast cancer, and analyzed the relationship between p-STAT3 expression and the clinicopathological characteristics and prognosis of breast cancer patients. Positive p-STAT3 expression was seen in 112 cases (27.5%) of breast cancer. p-STAT3 expression was negatively correlated with tumor size, tumor stage and human epidermal growth factor receptor 2 (HER2) status, and the positive rate of p-STAT3 was lowest in HER2-enriched subtype breast cancer (15.3%), while other subtypes were luminal B (23.0%), luminal A (30.2%), and triple-negative breast cancer (TNBC) (37.5%). Logistic regression model multivariate analysis showed that the independent correlation factor of p-STAT3 expression in breast cancer was tumor size (OR = 0.187, 95% CI = 0.042-0.839, P = .029) and HER2 status (OR = 0.392, 95% CI = 0.216-0.710, P = .002). In this study, no clear relationship was observed between patients' prognosis and expression of p-STAT3. Therefore, we suggest that p-STAT3 expression in breast cancer is negatively correlated with tumor size and HER2 status, but appears to have no effect on survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Receptor ErbB-2/análise , Fator de Transcrição STAT3/análise , Análise Serial de Tecidos , Carga Tumoral
17.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1197-1204, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787115

RESUMO

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 µg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/ß-actin after treatment of AFC(100 µg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 µg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.


Assuntos
Neoplasias do Colo , Syzygium , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Células HCT116 , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
18.
Cancer Commun (Lond) ; 41(3): 258-272, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33570246

RESUMO

BACKGROUND: Insulin gene enhancer protein 1, (ISL1), a LIM-homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis. METHODS: We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction (PCR). Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown. RNA-sequencing was performed to identify differentially expressed genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) to reveal key signaling pathways likely regulated by ISL1 in GC. Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) and by detecting glucose consumption and lactate production. The expression of glucose transporter 4 (GLUT4) and ISL1 was assessed by Western blotting, immunohistochemistry, and immunofluorescent microscopy. The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4. RESULTS: High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients. ISL1 knockdown inhibited cell proliferation both in vitro and in vivo. KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown, which was validated by reduced glucose uptake and lactate production, decreased ECAR, and increased OCR. Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter. CONCLUSION: ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.

19.
Mol Med Rep ; 23(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33576443

RESUMO

Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, anti­inflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPS­induced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPS­mediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit­8, JC­1 fluorescence, Hoechst 33258 staining assays, respectively. IL­1ß, IL­6 and TNF­α mRNA expression and protein levels were measured by performing reverse transcription­quantitative PCR and ELISAs, respectively. Bcl­2, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9, phosphorylated (p)­IκB­α, p­IκB­ß, p­NF­κB­p65 and total NF­κB p65 protein expression levels were determined via western blotting. NF­κB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPS­induced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL­1ß, IL­6, TNF­α, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9 and p­NF­κB­p65, but upregulated the expression levels of Bcl­2, p­IκB­α and p­IκB­ß in LPS­induced HUVECs. Moreover, PB2 markedly inhibited LPS­induced NF­κB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl­2 and NF­κB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.

20.
J Vasc Res ; : 1-5, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556943

RESUMO

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.

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