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1.
Huan Jing Ke Xue ; 44(7): 3872-3880, 2023 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-37438286

RESUMO

In order to explore the impact of different anthropogenic disturbances on the ecological environment of natural rivers, the bacterial community in the channel sediments of the Jialing River was taken as the research object, and the high-throughput sequencing technique was used to analyze the community composition and functional changes of bacteria in the channel sediments of rivers with engineering disturbance, tributary disturbance, sand mining disturbance, reclamation disturbance, and undisturbed section. The results showed that there were significant differences in the physical and chemical properties of channel sediments and bacterial community diversity in different disturbance sections of the Jialing River (P<0.05). The undisturbed section had the highest bacterial community diversity, whereas the sand mining disturbance and undisturbed section had the highest bacterial community uniformity, and tributary disturbance and reclamation disturbance both resulted in a decrease in bacterial community diversity and uniformity. The effect of engineering disturbance on bacterial community composition was significantly different from that of the other four disturbance sections. The dominant bacterial phyla were Proteobacteria, Actinobacteriota, Acidobacteriota, and Chloroflexi, and the dominant bacterial classes were γ-Proteobacteria, α-Proteobacteria, and Vicinamibacteria. Sand mining disturbance led to the increase in Actinobacteria, and engineering disturbance promoted the increase in Acidobacteria. Moisture content, total organic carbon, total nitrogen, and total phosphorus were the main environmental factors affecting the changes in sediment microbial communities. The bacterial communities mainly involved four categories of primary metabolic functions, including metabolism, genetic information processing, environmental information processing, and cellular processes, and 18 categories of secondary metabolic functions, such as global and overview maps, carbohydrate metabolism, amino acid metabolism, cofactor and vitamin metabolism, and energy metabolism. Human interference led to significant changes in energy metabolism, cofactor and vitamin metabolism, nucleotide metabolism, replication and repair, and translation (P<0.05). In conclusion, anthropogenic disturbance led to the mutation of bacterial community diversity and function, which destroyed the stability of the microbial community structure in Jialing River sediments.


Assuntos
Rios , Areia , Humanos , Bactérias/genética , Acidobacteria , Vitaminas
2.
Int J Oncol ; 63(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37203411

RESUMO

The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co­expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit­8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca­109 and KYSE­150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription­quantitative PCR, co­immunoprecipitation and fluorescence co­localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl­CoA synthetase long­chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca­109 and KYSE­150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca­109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis­associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Proteína Supressora de Tumor p53/genética
3.
Pharmacology ; 108(3): 286-300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37023725

RESUMO

INTRODUCTION: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. METHODS: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. RESULTS: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1ß and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. CONCLUSION: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.


Assuntos
Enteropatias , Microbiota , Ratos , Animais , Indometacina/toxicidade , Intestino Delgado , Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mucosa Intestinal , Enteropatias/induzido quimicamente
4.
Int J Biol Macromol ; 236: 123862, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36870625

RESUMO

The gut mucosa of human is covered by mucus, functioning as a crucial defense line for the intestine against external stimuli and pathogens. Mucin2 (MUC2) is a subtype of secretory mucins generated by goblet cells and is the major macromolecular component of mucus. Currently, there is an increasing interest on the investigations of MUC2, noting that its function is far beyond a maintainer of the mucus barrier. Moreover, numerous gut diseases are associated with dysregulated MUC2 production. Appropriate production level of MUC2 and mucus contributes to gut barrier function and homeostasis. The production of MUC2 is regulated by a series of physiological processes, which are orchestrated by various bioactive molecules, signaling pathways and gut microbiota, etc., forming a complex regulatory network. Incorporating the latest findings, this review provided a comprehensive summary of MUC2, including its structure, significance and secretory process. Furthermore, we also summarized the molecular mechanisms of the regulation of MUC2 production aiming to provide developmental directions for future researches on MUC2, which can act as a potential prognostic indicator and targeted therapeutic manipulation for diseases. Collectively, we elucidated the micro-level mechanisms underlying MUC2-related phenotypes, hoping to offer some constructive guidance for intestinal and overall health of mankind.


Assuntos
Células Caliciformes , Mucosa Intestinal , Humanos , Mucosa Intestinal/metabolismo , Células Caliciformes/metabolismo , Mucinas/metabolismo , Muco/metabolismo , Homeostase , Mucina-2/genética , Mucina-2/metabolismo
6.
Microb Ecol ; 85(4): 1308-1322, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35419656

RESUMO

Nonpoint source pollution (NPSP) from human production and life activities causes severe destruction in river basin environments. In this study, three types of sediment samples (A, NPSP tributary samples; B, non-NPSP mainstream samples; C, NPSP mainstream samples) were collected at the estuary of the NPSP tributaries of the Jialing River. High-throughput sequencing of the fungal-specific internal transcribed spacer (ITS) gene region was used to identify fungal taxa. The impact of NPSP on the aquatic environment of the Jialing River was revealed by analysing the community structure, community diversity, and functions of sediment fungi. The results showed that the dominant phylum of sediment fungi was Rozellomycota, followed by Ascomycota and Basidiomycota (relative abundance > 5%). NPSP caused a significant increase in the relative abundances of Exosporium, Phialosimplex, Candida, Inocybe, Tausonia, and Slooffia, and caused a significant decrease in the relative abundances of Cercospora, Cladosporium, Dokmaia, Setophaeosphaeria, Paraphoma, Neosetophoma, Periconia, Plectosphaerella, Claviceps, Botrytis, and Papiliotrema. These fungal communities therefore have a certain indicator role. In addition, NPSP caused significant changes in the physicochemical properties of Jialing River sediments, such as pH and available nitrogen (AN), which significantly increased the species richness of fungi and caused significant changes in the fungal community ß-diversity (P < 0.05). pH, total phosphorus (TP), and AN were the main environmental factors affecting fungal communities in sediments of Jialing River. The functions of sediment fungi mainly involved three types of nutrient metabolism (symbiotrophic, pathotrophic, and saprotrophic) and 75 metabolic circulation pathways. NPSP significantly improved the pentose phosphate pathway, pentose phosphate pathway, and fatty acid beta-oxidation V metabolic circulation pathway functions (P < 0.05) and inhibited the chitin degradation to ethanol, super pathway of heme biosynthesis from glycine, and adenine and adenosine salvage III metabolic circulation pathway functions (P < 0.05). Hence, NPSP causes changes in the community structure and functions of sediment fungi in Jialing River and has adversely affected for the stability of the Jialing River Basin ecosystem.


Assuntos
Ascomicetos , Basidiomycota , Micobioma , Poluição Difusa , Humanos , Rios/microbiologia , Ecossistema , Sedimentos Geológicos/microbiologia , China , Basidiomycota/genética , Ascomicetos/genética
7.
Scand J Gastroenterol ; 57(10): 1264-1271, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35576559

RESUMO

BACKGROUND AND AIM: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors. METHODS: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2). RESULT: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, p < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period. CONCLUSION: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.


Assuntos
Neoplasias Esofágicas , Tumor de Células Granulares , Adulto , Endoscopia , Endossonografia/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Feminino , Tumor de Células Granulares/diagnóstico por imagem , Tumor de Células Granulares/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Huan Jing Ke Xue ; 43(3): 1620-1629, 2022 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-35258226

RESUMO

The purpose of this study was to clarify the differences in soil bacterial community diversity in different land uses in the coastal zone of the Jialing River and to provide theoretical reference for reasonable land development and resource protection of the Jialing River basin. Based on second generation high-throughput sequencing technology, the diversity, structural composition, functional types, and influencing factors of soil bacterial communities in different land use types were analyzed. The results showed that:① there were some differences in soil physical and chemical properties among different land uses. The nutritional indexes of agricultural land and soil wetland were significantly higher than those of natural forest land and sandy soil wetland (P<0.05). ②The Ace, Shannon, and Chao indexes of sandy soil wetland and soil wetland were significantly higher than those of natural forest land and agricultural land (P<0.05). The Simpson index of soil bacteria in different land use types was significantly different (P<0.05). ③ The dominant phyla of soil bacteria in the coastal zone of the Jialing River were Proteobacteria, Actinobacteriata, Acidobacteriata, and Chloroflexi, and the relative abundance accounted for more than 65%. The community structure of sandy soil wetland was similar to that of soil wetland and was significantly different from that of other land use types (P<0.05). ④ Primary functional metabolism was the core function of the bacterial community, accounting for more than 75%. Agricultural activities had the greatest impact on the community function, which significantly improved the metabolism of amino acids and carbohydrates, enhanced the utilization of nitrogen and phosphorus, reduced the metabolism of energy and coenzyme vitamins, and weakened the resistance of bacterial community to environmental impact (P<0.05). ⑤ Total phosphorus (TP) was the key influencing factor of the soil bacterial community. In conclusion, the construction of the wetland habitat in the Jialing River coastal zone is most conducive to the development of underground ecological diversity and the stability of the soil ecosystem.


Assuntos
Microbiologia do Solo , Solo , Bactérias/genética , China , Ecossistema , Rios , Solo/química
10.
Front Immunol ; 12: 777665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899735

RESUMO

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.


Assuntos
Colite Ulcerativa/prevenção & controle , Colo/microbiologia , Microbioma Gastrointestinal , Ácido Láctico/metabolismo , Macrófagos/microbiologia , Probióticos , Piroptose , Saccharomyces cerevisiae/metabolismo , Animais , Caspase 1/metabolismo , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Ácidos Graxos Voláteis/metabolismo , Inflamassomos/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Simportadores/metabolismo
11.
Front Oncol ; 11: 709486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552870

RESUMO

OBJECTIVE: This article investigates the role of Transgelin (TAGLN) in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers. METHODS: Tissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin. RESULTS: The expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P < 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P < 0.05). CONCLUSION: Transgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.

13.
J Cell Mol Med ; 25(12): 5707-5720, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34002930

RESUMO

To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H2 O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Colite Ulcerativa/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Quinolizinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Adulto , Animais , Estudos de Casos e Controles , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
15.
Digestion ; 102(3): 342-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32570246

RESUMO

BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated clinicopathological condition characterized by esophageal infiltration with eosinophils resulting in chronic inflammation and stricture. SUMMARY: The recent increase in the incidence of EoE and the characteristic presentation of symptoms with difficulty swallowing and food bolus impaction has raised key concerns of clinicians as well as researchers. EoE often presents with dysphagia, food impaction, nausea, regurgitation or vomiting, and decreased appetite. It is more common in males, affecting both adults and children. The causative manner of this condition is complex and multifactorial. Throughout recent years, researchers have made a significant contribution to understanding the pathogenesis of EoE, genetic background, natural history, work on allergy, and standardization in the evaluation of disease activity. There is relatively high prevalence of EoE among the population, emphasizing the importance of this disease. Key messages: Esophageal involvement with eosinophils may be manifested as isolated or with coexisting conditions and should be taken into consideration in the differential diagnosis. This study aimed to provide gastroenterologists with novel insights into the evaluation of esophageal involvement with eosinophils and to pay special attention to the etiological factors, coexisting clinical diseases, and complications.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Adulto , Criança , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/epidemiologia , Eosinófilos , Humanos , Masculino , Náusea
16.
World J Clin Cases ; 8(19): 4565-4571, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083419

RESUMO

BACKGROUND: Angiosarcoma is a rare disease with a poor prognosis. Its occurrence in the small intestine is low, and gastrointestinal bleeding caused by small intestinal angiosarcoma is unusual. CASE SUMMARY: Here, we report the case of a 57-year-old man who presented with hematochezia for 1 mo. The patient had a medical history of chronic viral hepatitis B for 15 years. The causes of gastrointestinal bleeding were initially diagnosed as esophagogastric variceal bleeding or portal hypertensive gastropathy before endoscopy. However, after a complicated diagnostic and therapeutic process, including gastroendoscopy, colonoscopy, contrast-enhanced computed tomographic (CT), positron emission computed tomography/CT, capsule endoscopy, and pathological and immunohistochemical examinations, small intestinal angiosarcoma was diagnosed. Arrest of bleeding was achieved after surgical treatment. Furthermore, the patient had lung cancer with bone and adrenal metastases. At the follow-up 10 mo after the operation, the patient was alive. CONCLUSION: Gastroenterologists should maintain strong vigilance to small intestinal angiosarcoma, which is necessary for the early identification of this infrequent but fatal disease.

17.
Theranostics ; 10(19): 8790-8806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754278

RESUMO

Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum, was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.


Assuntos
Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Flavonoides/farmacologia , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Animais , Proteína de Matriz Oligomérica de Cartilagem/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Proteínas dos Microfilamentos/química , Simulação de Acoplamento Molecular , Proteínas Musculares/química , Transplante de Neoplasias , Ligação Proteica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
18.
Scand J Gastroenterol ; 55(7): 834-842, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32649237

RESUMO

AIM: To investigate whether endoscopic treatment is applicable to American patients and explores the predictors of lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Patients with EGC confined to either mucosa (T1a, n = 1799) and submucosa (T1b, n = 1689) were identified from the Surveillance, Epidemiology, and End Result database. Multivariate logistic regression, Kaplan-Meier method, and univariate/multivariate Cox regression were used to assess the correlation between invasion depth and LNM or prognosis. A nomogram for predicting LNM was constructed and internally validated. RESULTS: EGC limited to T1a exhibited a 2.4% incidence of LNM, which increased to 11.1% when the depth invaded T1b.LNM was present at 1.4%, 5.2%, and 5.0% for sizes ≤2, 2-5, and >5cm of low-grade T1a EGC, respectively, (p = .019) and at 4.8%, 12.4%, and 28.6% of T1b EGC, respectively (p < .001).The multivariate logistic model revealed that older age, T1b invasion, larger tumor size, and high-grade lesions were associated with a higher risk of LNM. Moreover, the T1a EGC patients had better cancer-specific survival (OS) and overall survival(CSS) compared with the T1b EGC patients (5-year OS: 77.2% versus 67.4%, p < .001; 5-year CSS: 90.6% versus 81.4%, p < .001). The discrimination of the prediction model was 0.745. CONCLUSIONS: Endoscopic treatment may only be suitable for patients in the US population who have low-grade T1a lesions of less than 2 cm in size. Patients with T1a lesions of greater than 2 cm in size, lesions with high-grade, and all T1b lesions may benefit from radical surgical resection with lymphadenectomy.


Assuntos
Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/patologia , Ressecção Endoscópica de Mucosa , Feminino , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Carga Tumoral , Estados Unidos/epidemiologia , Adulto Jovem
19.
Gastroenterol Res Pract ; 2020: 6591341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32587613

RESUMO

BACKGROUND: To assess the role of endoscopic ultrasound (EUS) in the diagnosis of upper gastrointestinal subepithelial lesions (SELs) and to investigate EUS combined with a grayscale histogram analysis for the differentiation of leiomyomas and gastrointestinal stromal tumors (GISTs). METHODS: A retrospective study of 709 patients with upper gastrointestinal SELs was conducted by EUS before endoscopic resection. The EUS findings of SELs and pathological results after endoscopic resection were compared. The EUS images of SELs, particularly, leiomyoma and GIST, were further analyzed via a grayscale histogram to differentiate between the two tumors. RESULTS: Of the 709 patients, 47 cases were pathologically undetermined. The diagnostic consistency of EUS with endoscopic resection was 88.2% (584/662), including 185 muscularis mucosa, 61 submucosa, and 338 muscularis propria, respectively. The diagnostic consistency of EUS with pathology was 80.1% (530/662). The gray value of GISTs was significantly higher than that of leiomyomas (58.9 ± 8.3 vs. 39.5 ± 5.9, t = 57.0, P < 0.0001). The standard deviation of leiomyomas was significantly lower than that of GISTs (20.6 ± 7.0 vs. 39.8 ± 9.3, t = 23.7, P < 0.0001). The grayscale histogram analysis of GISTs showed higher echo ultrasound, and the echo of leiomyoma was more uniform. CONCLUSION: EUS is the preferred procedure for the evaluation of upper gastrointestinal SELs. EUS combined with a grayscale histogram analysis is an effective method for the differentiation of leiomyomas and GISTs.

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