RESUMO
Long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in tumor progression. Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. This research aimed to investigate the roles and mechanisms of LEF1-AS1 in colorectal cancer (CRC). We firstly showed that LEF1-AS1 expression was upregulated in human CRC tissues and cell lines. LEF1-AS1 upregulation was demonstrated to be induced by CREB1. Clinical study revealed that high LEF1-AS1 expression was positively associated with histological grade, lymph nodes metastasis, and decreased survivals of CRC patients. Functionally, down-regulation of LEF1-AS1 using si-LEF1-AS1 decreased cell growth, migration and invasion, as well as increased apoptosis in CRC cells. Mechanically, LEF1-AS1 functioned as competing endogenous RNA (ceRNA) for miR-489 to positively recover DIAPH1, thus playing an oncogenic role in CRC pathogenesis. Overall, our observations identified a novel CRC-related lncRNA LEF1-AS1 and discovered a critical role for this lncRNA as a ceRNA in CRC pathogenesis, suggesting that it may serve as a novel biomarker for prognosis and act as a therapeutic target for CRC treatment.
Assuntos
Neoplasias Colorretais/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Forminas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Progressão da Doença , HumanosRESUMO
Peroral endoscopic myotomy (POEM) is a new technique to treat achalasia, but the effects on esophageal motor function and structure are still unclear. This study aimed to examine the esophageal function and anatomical changes of patients with achalasia treated with POEM. This was a retrospective study of 43 patients with achalasia treated with POEM between January 2013 and January 2016 at the Second Affiliated Hospital of Xi'an Jiaotong University. The patients were grouped as previous treatments for achalasia (n = 19) versus no previous treatment (n = 24). Surgical success (defined as Eckardt score ≤3 points or decreased by >3 points compared with baseline), recurrence, and reintervention were analyzed. Three patients (7.0%) were Eckardt grade I, 16 (37.2%) were grade II, and 24 (55.8%) were grade III. Operation time was 35 to 150 (median = 49) minutes. Both groups showed improvements in the Eckardt score after surgery (both P < .001), without a difference between the 2 groups (P = .749). The maximal mean diameter of the esophagus was reduced, and the lower esophageal sphincter pressure was improved after surgery (both groups, all P < .001), without difference between the 2 groups (all P > .05). One case of failure was probably due to the presence of an esophageal stent. POEM has a high success rate and is possibly unaffected by previous treatments, except maybe stent implantation. Clinical symptoms of achalasia are significantly relieved by POEM; the function of the esophageal sphincter and the esophagus structure are improved. Previous esophageal stent implantation could increase failure likelihood, but this will have to be confirmed.
Assuntos
Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Acalasia Esofágica/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Esofagoscopia , Humanos , Manometria , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The purpose of the present study is to investigate the effect of L-cysteine on colonic motility and the underlying mechanism. Immunohistochemical staining and Western blot were used to detect the localization of the H2S-generating enzymes cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). Organ bath system was used to observe the muscle contractile activities. Whole-cell patch-clamp technique was applied to record ionic channels currents in colonic smooth muscle cells. The results showed that both CBS and CSE were localized in mucosa, longitudinal and circular muscle and enteric neurons. L-cysteine had a dual effect on colonic contraction, and the excitatory effect was blocked by pretreatment with CBS inhibitor aminooxyacetate acid (AOAA) and CSE inhibitor propargylglycine (PAG); L-cysteine concentration-dependently inhibited L-type calcium channel current (ICa,L) without changing the characteristic of L-type calcium channel (P < 0.01); In contrast, the exogenous H2S donor NaHS increased ICa,L at concentration of 100 µmol/L, but inhibited ICa,L and modified the channel characteristics at concentration of 300 µmol/L (P < 0.05); Furthermore, L-cysteine had no effect on large conductance calcium channel current (IBKCa), but NaHS significantly inhibited IBKCa (P < 0.05). These results suggest that L-cysteine has a potential dual effect on colonic smooth muscle and the inhibitory effect might be directly mediated by L-type calcium channel while the excitatory effect might be mediated by endogenous H2S.
Assuntos
Cisteína/farmacologia , Sulfeto de Hidrogênio , Cistationina beta-Sintase , Cistationina gama-Liase , Músculo LisoRESUMO
BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM: To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS: We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS: HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION: Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.
Assuntos
Ressecção Endoscópica de Mucosa , Mucosa Gástrica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Mucosa Gástrica/diagnóstico por imagem , Idoso , Resultado do Tratamento , Prognóstico , Adulto , Carcinoma in Situ/cirurgia , Carcinoma in Situ/patologia , Diferenciação Celular , Gradação de Tumores , Gastroscopia/efeitos adversos , Gastroscopia/métodos , Fatores de Tempo , Estadiamento de Neoplasias , SeguimentosRESUMO
OBJECTIVES: To compare the migrating motor complex (MMC) in irritable bowel syndrome (IBS) patients with that in healthy controls. To explore whether discrete clustered contractions (DCC) are connected with abdominal pain in IBS patients. To improve the method of measuring gastroenteric motility (esp. jejunum). METHODS: By using 16-channel water-perfused catheter and manometry instruments, MMC in 16 cases of IBS with constipation (IBS-C), 18 cases of IBS with diarrhea (IBS-D) and 18 cases of healthy controls were monitored. RESULTS: The MMC durations of IBS-C and IBS-D patients were (127.5 +/- 25.5) min and (74.5 +/- 18.7) min, respectively. Comparision with those in the control group [(87.5 +/- 24.2) min] showed significant differences (P < 0.001). The contraction amplitudes of stage III in different sites of IBS-C patients decreased significantly as compared with those in the controls [jejunum, (39.8 +/- 11.7) mm Hg vs. (61.1 +/- 14.1) mm Hg, P < 0.001, 1 mm Hg = 0.133 kPa]. The propagation velocities of stage III in different sites of IBS-C patients also decreased significantly as compared with those in the controls [jejunum, (1.8 +/- 0.9) cm/min vs. (2.6 +/- 0.8) cm/min, P < 0.01]. The contraction amplitudes of stage III in different sites of IBS-D patients increased significantly as compared with those in the controls [jejunum, (69.7 +/- 20.5) mm Hg vs. (61.1 +/- 14.1) mm Hg, P < 0.01]. The propagation velocities of stage III in different sites of IBS-D patients also increased significantly as compared with those in the controls [jejunum, (4.1 +/- 2.5) cm/min vs. (2.6 +/- 0.8) cm/min, P < 0.01]. DCC incidences of IBS-C and IBS-D were 87.5% and 88.8%, respectively. Comparision with those in the normal group (83.3%) did not show significant difference (P > 0.05). The prevalences of abnormal stage III contractions (include disturbances and interferences of stage III contractions) in IBS-C and IBS-D patients were 68.8% and 66.7%, respectively; there were no significant differences between the two groups (P > 0.05). However abnormal stage III contractions did not exist in healthy controls. CONCLUSIONS: (1) The MMC of IBS-C and IBS-D patients are changed, as compared with that in healthy people; this implies that small intestinal motility dysfunction is one of the pathogenetic factors of IBS. The abnormal stage III contractions in jejunum may be a predominant change in IBS gastroenteric motility. (2) No apparent connection is found between DCC and pain in IBS. (3) By using 16-channel water-perfused catheter, we first carried out the method of monitoring jejunum contractions in China. Parameters of MMC in Chinese healthy people were investigated, esp. those of jejunum.
Assuntos
Intestino Delgado/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Complexo Mioelétrico Migratório , Adulto , Estudos de Casos e Controles , Feminino , Motilidade Gastrointestinal , Humanos , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To explore the effect of ghrelin on the duodenal myoelectrical activity during the feeding state and the fasting state in rats. METHODS: One pair of bipolar silver electrodes were chronically implanted in the duodenal serosa of rats for electromyography. The myoelectrical activity was recorded when ghrelin was injected intravenously into rats during the feeding state or the fasting state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, and (D-Lys3)GHRP-6 respectively to explore the mechanism of ghrelin. RESULTS: Duodenal migrating myoelectrical complex (MMC) could be induced by ghrelin in the feeding state. Ghrelin could shorten the length of duodenal MMC cycle and increase the amplitude and frequency of phase III during the fasting state. The percentage of phase III in the MMC cycle did not change. These effects were inhibited by atropine and L-arginine (D-Lys3)GHRP-6, but not by propranolol and phentolamine. CONCLUSION: Ghrelin seems to be closely related to the duodenal motility. The excitatory effect of ghrelin on duodenal MMC might rely on the cholinergic pathway, and have a close relationship with NO. The receptor of ghrelin can regulate its activity.
Assuntos
Duodeno/efeitos dos fármacos , Grelina/farmacologia , Músculo Liso/fisiologia , Complexo Mioelétrico Migratório/efeitos dos fármacos , Animais , Duodeno/fisiologia , Eletromiografia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. METHODS: A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. RESULTS: The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P < 0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P < 0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P < 0.05). Real time-PCR results showed that the expression level of the 5-HT(7) receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P < 0.05). The expression level of 5-HT(7) receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P < 0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P < 0.01 and P < 0.05). The cAMP accumulation in the IBS-C group was higher than that in the control group in the proximal and distal colon (P < 0.05). CONCLUSIONS: The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.
Assuntos
Encéfalo/metabolismo , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/etiologia , Receptores de Serotonina/fisiologia , Animais , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Síndrome do Intestino Irritável/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/análise , Receptores de Serotonina/genética , Serotonina/análiseRESUMO
OBJECTIVE: To study the effect and mechanism of mexican tea herb and pilular adina herb (abbreviated to MP) on concrescence of gastric mucosa in experimental gastric ulcer rats by observing the changes of epidermal growth factor (EGF), nitrogen monoxidum (NO) and expression of epidermal growth factor receptor (EGFR). METHODS: The rat ulcer model was established by 100% glacial acetic injection into the subserosa. The ulcer index (UI) was measured by sliding caliper. The levels of NO and EGF in tissue and serum were measured by the nitrate reductase method and enzyme-linked immunosorbent assay, respectively. The expression of EGFR in the mucosa around the ulcer was detected by the immunohistochemical assay and microimage analysis system. RESULTS: (1) Compared with the model group, UI of MP groups (10, 15 and 20 mg.kg(-1).d(-1)) and ranitidine group was lower (P<0.05 or P<0.01), the levels of NO and EGF in the tissue and serum were higher (P<0.05), the thickness of regenerated mucous membrane increased, and the width loss of lamina muscularis mucosa decreased (all P<0.05). (2) The expression of EGFR is weakly positive in gastric mucosa cells in the normal group, mainly in the cytoplasm and cytomembrane. In the model group, the expression of EGFR was mainly in epithelial cells in cervical part and basilar part of gastric gland around the ulcer margin, and the number of cells with EGFR weakly positive expression was more than that in the normal group. Compared with that in the normal and model groups, the number of cells with EGFR positive in MP groups and ranitidine group increased (all P<0.05), with weakly positive expression. CONCLUSION: MP can protect gastric mucosa, cure gastric ulcer, restrain the secretion of gastric acid, and boost multiplication, differentiation, migration and repair of the endothelial cell by promoting the secretion of NO and EGF, and increasing the expression of EGFR of gastric mucosa epithelial cells.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Chá , Animais , Fator de Crescimento Epidérmico/análise , Receptores ErbB/análise , Feminino , Mucosa Gástrica/química , Mucosa Gástrica/patologia , Imuno-Histoquímica , Masculino , Óxido Nítrico/análise , Ratos , Ratos Sprague-Dawley , Regeneração , Úlcera Gástrica/patologiaRESUMO
RATIONALE: A solitary Peutz-Jeghers-type polyp is a hamartomatous polyp which without either mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome (PJS). It can occur in all of the gastrointestinal tract, but it is extremely rare in the stomach. PATIENT CONCERNS: A 53-year-old man was admitted to the local hospital with left upper abdominal pain lasting 2 weeks. A gastroscopy showed a giant and extensive bulging lesion on the greater curvature and posterior and anterior walls of the gastric antrum, involving three-quarters of the gastric wall. Endoscopic ultrasonography showed a muscularis mucosa lesion. DIAGNOSES: A solitary Peutz-Jeghers-type polyp in the antrum of stomach. INTERVENTIONS: The patient underwent an endoscopic submucosal dissection (ESD). OUTCOMES: The patient recovered quickly, without any complications. LESSONS: This is the second largest gastric solitary Peutz-Jeghers-polyp reported until now, and the largest gastric solitary Peutz-Jeghers type-polyp treated by endoscope.
Assuntos
Hamartoma/diagnóstico por imagem , Síndrome de Peutz-Jeghers/diagnóstico por imagem , Pólipos/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Hamartoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/patologia , Pólipos/patologia , Antro Pilórico/diagnóstico por imagem , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To investigate the effects of serum containing Chinese medicine (CM) Sanpi Pingwei (, SPPW) formula on the proliferation and apoptosis of human SGC-7901 cells and the possible mechanism. METHODS: Serum containing CM SPPW formula (SPPW serum) was prepared by a serum pharmacology method. Human SGC-7901 cells were incubated with SPPW serum at three different concentrations and with the anticancer drug 5-fluorouracil (5-FU), respectively. Cell proliferation was assessed by MTT assay, and cell apoptosis was detected by flow cytometry assay. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot assay were employed to confirm the expressions of Bcl-2, Bax and p53 in SGC-7901 cells at mRNA and protein levels, respectively. RESULTS: SPPW serum suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. The colony forming rate of negative control was 48.2%, while those in the three SPPW serum groups and the 5-FU group decreased significantly (P<0.01). The number of colony forming units in the SPPW high dosage group was significantly smaller than that in the 5-FU group (P<0.01). MTT assay showed that SPPW serum restrained the proliferation of SGC-7901 cells, and the inhibition rate increased significantly in a dose-dependent manner. Annexin V/PI Assay suggested that SPPW serum induced the apoptosis of SGC-7901 cells significantly. RT-PCR and western blot assay indicated that SPPW serum upregulated the protein and mRNA expression levels of Bax and p53 in SGC-7901 cells, but downregulated the protein and mRNA expressions of Bcl-2. CONCLUSIONS: SPPW formula inhibits the proliferation of SGC-7901 cells in vitro and induces the cell apoptosis. It plays an anticancer role by regulating the expressions of Bax, p53 and Bcl-2 in SGC-7901 cells.
Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Soro/química , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Ensaio Tumoral de Célula-Tronco , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To evaluate and compare the health-related quality of life (HRQOL) on patients with irritable bowel syndrome (IBS). METHODS: Following the Rome III Criteria, 411 IBS patients and 430 healthy people were selected as subjects,who were outpatients in Department of Gastroenterology, 2nd Hospital of Xi' an Jiaotong University and Shaanxi Provincial People's Hospital from July 2006 to April 2007. Using the 36-Item Short-Form Health Survey (SF-36). This study compared the SF-36 scale scores of IBS patients with the healthy people. RESULTS: On all of the 8 SF-36 scales, patients with IBS scored significantly lower than healthy people (P < 0.001). Decrements in HRQOL were most predominant in general health perception and role limitations caused by emotional health problem, with scores of 33.5 + 16.9, 40.8 +/- 25.1 respectively. The emotional well-being and energy/fatigue scale scores were also quite low (42.2 +/- 19.3,43.1 +/- 20.2,respectively). They also scored significantly lower on both physical summary. and mental summary scores (P < 0.001). IBS patients were classified into IBS with constipation,IBS with diarrhea, mixed IBS and unsubtyped IBS subgroups, with percentages as 25.3%, 50.1%, 11.2% and 13.4% respectively. CONCLUSION: IBS patients experienced great impairment in HRQOL. These data offered further insight into the impact of IBS on patient functional status and well-being.