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1.
Heliyon ; 8(12): e12286, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36582688

RESUMO

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.

2.
J Mol Histol ; 53(2): 173-186, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35034206

RESUMO

Gastric cancer (GC) remains a major cause of cancer-related deaths. Increasing studies suggest that cancer development is accompanied by the deregulation of circular RNAs. We investigated the function of circ_0003159 in GC. The expression levels of circ_0003159, miR-221-3p/miR-222-3p and leukemia inhibitory factor receptor (LIFR) mRNA were measured by real-time quantitative polymerase chain reaction. Cell colony formation ability was assessed by colony formation assay, and cell viability was assessed by cell counting kit-8 assay. Cell apoptosis was assessed by flow cytometry assay and caspase3 activity. Cell migration and invasion were assessed by transwell assay. Glycolysis energy metabolism was assessed by 5'-triphosphate production, glucose uptake and lactate production. The protein levels of related marker proteins and LIFR were detected by western blot. The relationship between circ_0003159 and miR-221-3p/miR-222-3p, or LIFR and miR-221-3p/miR-222-3p was obtained from bioinformatics tools and verified by dual-luciferase reporter assay. A cancer tumorogenicity xenograft experiment in nude mice was conducted to determine the role of circ_0003159 in tumor growth by AGS cells. Our results showed that circ_0003159 expression was decreased in GC tissues and cells. Circ_0003159 overexpression sequestered GC cell viability, migration, invasion and glycolysis and induced cell apoptosis. MiR-221-3p and miR-222-3p were targets of circ_0003159, and the inhibition of miR-221-3p and miR-222-3p also blocked GC cell viability, migration, invasion and glycolysis and promoted cell apoptosis. LIFR was a common target of miR-221-3p and miR-222-3p. Interestingly, LIFR knockdown reversed the effects of circ_0003159 overexpression on GC cell behaviors. Circ_0003159 increased the expression level of LIFR by targeting miR-221-3p and miR-222-3p. The tumorigenicity assay showed that circ_0003159 overexpression inhibited tumor growth in vivo. In conclusion, circ_0003159 inhibited GC development in vitro and in vivo by enriching the level of LIFR via direct binding to miR-221-3p/miR-222-3p.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Proliferação de Células/genética , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores de OSM-LIF , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
3.
J Zhejiang Univ Sci B ; 21(7): 581-589, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32633112

RESUMO

OBJECTIVE: To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett's esophagus (BE). METHODS: Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out. RESULTS: The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH. CONCLUSIONS: In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.


Assuntos
Esôfago de Barrett/etiologia , Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/metabolismo , Período Pós-Prandial/fisiologia , Adulto , Idoso , Feminino , Determinação da Acidez Gástrica , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade
4.
Med Sci Monit ; 24: 170-176, 2018 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-29309401

RESUMO

BACKGROUND Postprandial proximal gastric acid pocket (PPGAP) plays important roles in gastroesophageal reflux disease (GERD). In this study, we analyzed the characteristics of PPGAP in GERD. MATERIAL AND METHODS There were 17 normal participants and 20 GERD patients who completed a gastroesophageal reflux disease questionnaire (GerdQ) and underwent a gastroscopy, a high-resolution manometry, an esophageal 24-hour pH monitoring, and a station pull-through pH monitoring to assess their symptomatic degree, endoscopic change, acid exposure, and PPGAP. RESULTS PPGAP was present in all participants. Compared with normal participants, the PPGAP in GERD patients was significantly different, thus the disappearing time was significantly later (p<0.001), the lasting time was significantly longer (p<0.001), the length was significantly longer (p<0.001), and the lowest pH and the mean pH were significantly lower (p<0.001). The length of PPGAP in GERD patients was positively correlated with GerdQ score (p<0.05). The disappearing time, the lasting time, and the length of PPGAP in GERD patients was positively correlated with the DeMeester score (p<0.01). The lowest pH and the mean pH of PPGAP in GERD patients was negatively correlated with the DeMeester score (p<0.001). CONCLUSIONS PPGAP was generally present. PPGAP in GERD patients had characteristics of long time period, long length, and high acidity. Its length was positively correlated with subjective symptomatic degree. Its period, length, and acidity were positively correlated with the objective acid exposure. PPGAP seems to be the originator of acid reflux events and plays important roles in GERD.


Assuntos
Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/metabolismo , Período Pós-Prandial , Adulto , Estudos de Casos e Controles , Demografia , Jejum , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
5.
World J Gastroenterol ; 23(42): 7594-7608, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29204059

RESUMO

AIM: To establish a rat model of anxiety-like gastric hypersensitivity (GHS) of functional dyspepsia (FD) induced by novel sequential stress. METHODS: Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood (8 wk) at which point the anxiety-like behaviors and visceromotor responses to gastric distention (20-100 mmHg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1A receptor (5-HT1AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined. RESULTS: Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequential-stress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT (51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA (2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF (304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1 (1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT (47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF (257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it (1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT (41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF (226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site (1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC (Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB (0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01) (n = 8 in each group). CONCLUSION: Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.


Assuntos
Ansiedade/complicações , Modelos Animais de Doenças , Dispepsia/etiologia , Privação Materna , Estresse Psicológico/complicações , Animais , Dispepsia/sangue , Dispepsia/psicologia , Masculino , Ratos Sprague-Dawley
6.
Inflammation ; 40(3): 818-831, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28197857

RESUMO

Barrett's esophagus (BE) is generally accepted as the only precursor to esophageal adenocarcinoma (EAC). Deoxycholic acid (DCA)-induced inflammation and apoptotic resistance play an important role in the carcinogenesis and progression from BE to EAC. Diallyl disulfide (DADS) is a garlic-derived natural organosulfur compound. This study investigated whether DADS has chemopreventive effects against BE and the potentially related signaling pathway. BAR-T cells were treated with DCA in the presence or absence of DADS. An MTT assay was used to detect the viability of the cells. The apoptosis rate of the cells was measured by light microscopy and flow cytometry. ROS levels were determined by fluorescence microscopy and flow cytometry. Real-time PCR and ELISA were used to detect mRNA and protein levels, respectively. The levels of target proteins were also determined by western blot analysis. DADS did not inhibit cell viability in a certain concentration range. DADS, similar to the NF-κB inhibitor PDTC, inhibited the DCA-induced ROS production, inflammatory factors, IκBα phosphorylation, and expression of p50 in the nucleus in a dose-dependent manner. DADS also increased the cell apoptosis rate through down-regulating the level of Bcl-2. DADS has low cytotoxicity in BAR-T cells. It has an anti-inflammatory effect in BAR-T cells through inhibiting ROS and the NF-κB signaling pathway. Further, it abolishes the apoptotic resistance induced by DCA in an NF-κB/Bcl-2 dependent manner. DADS may be a good candidate for BE and EAC chemical prevention and therapy.


Assuntos
Compostos Alílicos/farmacologia , Apoptose/efeitos dos fármacos , Dissulfetos/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Compostos Alílicos/uso terapêutico , Anti-Hipertensivos/farmacologia , Ácido Desoxicólico/farmacologia , Dissulfetos/uso terapêutico , Células Epiteliais/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
PLoS One ; 10(11): e0142377, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26545111

RESUMO

The dysregulation of miR-137 plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of gastric cancer patients remains unknown. This study was designed to investigate the expression and prognostic significance of miR-137 in gastric cancer patients after radical gastrectomy. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression of miR-137 in human gastric cancer cell lines and tissues in patients with gastric adenocarcinoma. Results were assessed for association with clinical factors and overall survival by using Kaplan-Meier analysis. Prognostic values of miR-137 expression and clinical outcomes were evaluated by Cox regression analysis. The results exhibited that the expression level of miR-137 was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-137 was associated with tumor cell differentiation, N stage, and TNM stage. Decreased miR-137 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients. Further multivariate Cox regression analysis suggested that miR-137 expression was an independent prognostic indicator for gastric cancer except for TNM stage. Applying the prognostic value of miR-137 expression to TNM stage III group showed a better risk stratification for overall survival. In conclusion, the results reinforced the critical role for the down-regulated miR-137 expression in gastric cancer and suggested that miR-137 expression could be a prognostic indicator for this disease. In addition, these patients with TNM stage III gastric cancer and low miR-137 expression might need more aggressive postoperative treatment and closer follow-up.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Gastrectomia , MicroRNAs/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia
8.
J Zhejiang Univ Sci B ; 16(9): 805-10, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26365123

RESUMO

OBJECTIVE: To analyze reflux parameters by means of combined multichannel intraluminal impedance and pH (MII-pH) monitoring in patients with gastroesophageal reflux disease (GERD) symptoms off medication, and to find the reflux characteristics of Chinese GERD patients and the influences of gender, age, body posture, and body mass index (BMI) on gastroesophageal reflux (GER). METHODS: Between Dec. 2008 and May 2014, 125 patients with typical GERD symptoms were subjected to 24-h MII-pH monitoring. Twelve patients with normal MII-pH profiles were not considered for analysis. The reflux parameters of 113 GERD patients with abnormal MII-pH results were analyzed. RESULTS: (1) DeMeester scores were above the normal range in 46.90% (53/113) of GERD patients. Weakly acidic refluxes were prevalent in GERD patients, and the frequency of abnormal weakly acidic reflux was 75.22% (85/113). The frequencies of abnormal symptom index (SI) and symptom association probability (SAP) were 19.47% (22/113) and 14.16% (16/113), respectively. (2) The frequencies of DeMeester scores, the %time at pH<4, and the numbers of reflux episodes and of long reflux episodes >5 min were significantly higher in male patients than in female patients. (3) The %time at pH<4 was much higher during upright periods than during supine periods. During supine periods, 31.86% (36/113) of GERD patients had delayed bolus clearance time, compared with 19.47% (22/113) during upright periods. (4) The number of abnormal DeMeester scores, %time at pH<4, and the number of acid refluxes during upright periods were significantly higher in obese GERD patients than in GERD patients with a normal BMI. Overweight GERD patients also had many more acid refluxes during upright periods than GERD patients with a normal BMI. CONCLUSIONS: Weakly acidic refluxes were prevalent in Chinese GERD patients. The factors male, gender, upright position, obesity (BMI≥25), but not age, may increase the frequency and severity of GER.


Assuntos
Monitoramento do pH Esofágico/estatística & dados numéricos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Incidência , Masculino , Pessoa de Meia-Idade , Postura , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Adulto Jovem
9.
BMC Cancer ; 15: 306, 2015 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-25928665

RESUMO

BACKGROUND: Esophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet. METHODS: Firstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo. RESULTS: Dual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells. CONCLUSION: Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.


Assuntos
Neoplasias Esofágicas/genética , MicroRNAs/genética , Interferência de RNA , Fator de Transcrição STAT3/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Fator de Transcrição STAT3/metabolismo , Carga Tumoral
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