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1.
Environ Geochem Health ; 45(11): 8153-8168, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37548847

RESUMO

A screening survey has been carried out to measure the radon concentration in drinking water at various locations of Ajodhya hill and surrounding areas in Purulia district of West Bengal, India, using AlphaGUARD radon monitor. The obtained 222Rn concentration in ground water varies from 5.71 ± 0.29 to 579.47 ± 23.18 Bq/l with an average of 110.00 ± 6.61 Bq/l. Comparison between our results with the internationally recommended reference levels reveals that drinking of water from the majority of these tube-wells can pose significant health risks to the local people. Correlation study indicates that tube-well depth has significant influence on the radon level in water samples. Using 60 l/yr and 1642.50 l/yr water consumption estimated annual effective radon doses for most of the samples (almost 70% and 96%, respectively) are high compared to the World Health Organization (WHO) and the European Union (EU) Commission prescribed reference dose limit of 100 µSv/yr. Also, the evaluated Excess Lifetime Cancer Risk (ELCR) values associated with the tube-wells are showing serious threat to the health of the locals.The primary goal of this work is to develop a radon profile map of this area and to find out the possible reasons behind the elevated radon level in ground water. This type of work may play a very crucial role to aware the locals in perspective of human exposure to radon. The local health officials and the water quality regulators of India are requested to take necessary steps for protecting the local people from water radon hazard.


Assuntos
Água Potável , Monitoramento de Radiação , Radônio , Poluentes Radioativos da Água , Humanos , Radônio/toxicidade , Radônio/análise , Monitoramento de Radiação/métodos , Poluentes Radioativos da Água/análise , Estômago/química , Pulmão/química , Índia
2.
Int J Mol Sci ; 24(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37108221

RESUMO

The lectin TFF2 belongs to the trefoil factor family (TFF). This polypeptide is typically co-secreted with the mucin MUC6 from gastric mucous neck cells, antral gland cells, and duodenal Brunner glands. Here, TFF2 fulfills a protective function by forming a high-molecular-mass complex with the MUC6, physically stabilizing the mucus barrier. In pigs and mice, and slightly in humans, TFF2 is also synthesized in the pancreas. Here, we investigated the murine stomach, pancreas, and duodenum by fast protein liquid chromatography (FPLC) and proteomics and identified different forms of Tff2. In both the stomach and duodenum, the predominant form is a high-molecular-mass complex with Muc6, whereas, in the pancreas, only low-molecular-mass monomeric Tff2 was detectable. We also investigated the expression of Tff2 and other selected genes in the stomach, pancreas, and the proximal, medial, and distal duodenum (RT-PCR analysis). The absence of the Tff2/Muc6 complex in the pancreas is due to a lack of Muc6. Based on its known motogenic, anti-apoptotic, and anti-inflammatory effects, we propose a protective receptor-mediated function of monomeric Tff2 for the pancreatic ductal epithelium. This view is supported by a report that a loss of Tff2 promotes the formation of pancreatic intraductal mucinous neoplasms.


Assuntos
Lectinas , Estômago , Fator Trefoil-2 , Animais , Humanos , Camundongos , Mucinas/genética , Mucinas/metabolismo , Pâncreas/metabolismo , Peptídeos/química , Estômago/química , Suínos , Fator Trefoil-2/metabolismo
3.
Sci Total Environ ; 878: 162942, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36940749

RESUMO

The spatial distribution and pollution level of heavy metal(loid)s in soil (0-6 m) from a typical industrial region in Jiangmen City, Southeast China was investigated. Their bioaccessibility, health risk, and human gastric cytotoxicity in topsoil were also evaluated using an in vitro digestion/human cell model. The average concentrations of Cd (87.52 mg/kg), Co (106.9 mg/kg), and Ni (1007 mg/kg) exceeded the risk screening values. The distribution profiles of metal(loid)s showed a downward migration trend to reach a depth of 2 m. The highest contamination was found in topsoil (0-0.5 m), with the concentrations of As, Cd, Co, and Ni being 46.98, 348.28, 317.44, and 2395.60 mg/kg, respectively, while Cd showed the highest bioaccessibility in the gastric phase (72.80 %), followed by Co (21.08 %), Ni (18.27 %), and As (5.26 %) and unacceptable carcinogenic risk. Moreover, the gastric digesta of topsoil suppressed the cell viability and triggered cell apoptosis, evidenced by disruption of mitochondrial transmembrane potential and increase of Cytochrome c (Cyt c) and Caspases 3/9 mRNA expression. Bioaccessible Cd in topsoil was responsible for those adverse effects. Our data suggest the importance to reduce Cd in the soil to decrease its adverse impacts on the human stomach.


Assuntos
Metais Pesados , Poluentes do Solo , Humanos , Cádmio/toxicidade , Monitoramento Ambiental , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Medição de Risco , Metais Pesados/análise , China , Solo , Estômago/química
4.
Biol Trace Elem Res ; 201(3): 1065-1079, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35460466

RESUMO

The infection caused by Helicobacter pylori (H. pylori) disrupts the metabolism and absorption of essential trace elements. Stomach disorders are related to changes in essential trace element metabolism caused by increased toxic metal exposure and H. pylori infection. The aim of the work is to link the development of stomach-related illnesses to an imbalance of essential trace and toxic metals. We have investigated the variations in essential trace elements such zinc (Zn), iron (Fe), and copper and toxic metals like lead (Pb) and cadmium (Cd) in biological (scalp hair, blood) samples of glass and cement workers. The study participants are further divided into smokers and nonsmokers, as well as diseased (gastric ulcer, irritable bowel syndrome, and chronic ulcer) and exposed referents (non-diseased industrial workers). Biological samples of age-matched (40-60 years) male subjects living in non-industrial areas were gathered for comparative purposes. After a pre-concentration method, the drinking water of industrial and domestic areas was analysed for both toxic metals. Microwave-aided acid digestion was used to oxidise the matrices of biological samples before atomic absorption spectrometer analysis of selected metals. Toxic metal levels in both industries' drinking water were much higher than those found in domestically treated water (p < 0.01). Industrial workers suffering different types of stomach disorders have two to three times higher Pb and Cd concentrations than age-matched referents. Toxic metals are found in higher concentrations in smoker referents and diseased patients' biological samples than in nonsmoker subjects. The findings of this study suggested that Pb and Cd toxicity's immunological effects may be associated to an increased vulnerability to chronic infections.


Assuntos
Água Potável , Oligoelementos , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Oligoelementos/análise , Cádmio/análise , Água Potável/análise , Chumbo/análise , Fumar , Estômago/química , Espectrofotometria Atômica/métodos
5.
J Clin Lab Anal ; 36(2): e24189, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953081

RESUMO

BACKGROUND: Gastric cancer is the third leading cause of cancer-related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6-phosphogluconolactonase (PGLS) in gastric cancer. METHODS: The protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8-plex) reagents, and followed by LC-ESI-MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan-Meier plotter database. RESULTS: The present study found that PGLS was significantly up-regulated in gastric cancer by using iTRAQ-based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post-progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e-05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her-2 (-). CONCLUSIONS: These findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post-progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow-up monitoring for gastric cancer.


Assuntos
Biomarcadores Tumorais/análise , Hidrolases de Éster Carboxílico/análise , Detecção Precoce de Câncer/métodos , Proteoma/análise , Neoplasias Gástricas/diagnóstico , Estômago/química , Biomarcadores Tumorais/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteômica , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
6.
Braz. j. biol ; 82: 1-7, 2022. tab, ilus, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468429

RESUMO

This work aimed to obtain aspartic proteases of industrial and biotechnological interest from the stomach of the crevalle jack fish (Caranx hippos). In order to do so, a crude extract (CE) of the stomach was obtained and subjected to a partial purification by salting-out, which resulted in the enzyme extract (EE) obtainment. EE proteases were characterized physicochemically and by means of zymogram. In addition, the effect of chemical agents on their activity was also assessed. By means of salting-out it was possible to obtain a purification of 1.6 times with a yield of 49.4%. Two acid proteases present in the EE were observed in zymogram. The optimum temperature and thermal stability for EE acidic proteases were 55 ºC and 45 °C, respectively. The optimum pH and pH stability found for these enzymes were pH 1.5 and 7.0, respectively. Total inhibition of EE acid proteolytic activity was observed in the presence of pepstatin A. dithiothreitol (DTT) and Ca2+ did not promote a significant effect on enzyme activity. In the presence of heavy metals, such as Al3+, Cd2+ and Hg2+, EE acidic proteases showed more than 70% of their enzymatic activity. The results show that it is possible to obtain, from the stomach of C. hippos, aspartic proteases with high proteolytic activity and characteristics that demonstrate potential for industrial and biotechnological applications.


Este trabalho objetivou obter proteases aspárticas de interesse industrial e biotecnológico a partir do estômago do peixe xaréu (Caranx hippos). Para isso, foi obtido um extrato bruto do estômago, o qual foi submetido a uma purificação parcial por salting-out onde se obteve o extrato enzimático (EE). As proteases do EE foram caracterizadas físico-quimicamente e através de zimograma. Além disso, o efeito de agentes químicos sobre sua atividade também foi avaliado. Através de salting-out foi possível obter uma purificação de 1,6 vezes com rendimento de 49,4%. Foram observadas duas proteases ácidas presentes no EE através de zimograma. A temperatura ótima e a estabilidade térmica para as proteases ácidas do EE foram de 55 ºC e 45 °C, respectivamente. O pH ótimo e a estabilidade ao pH encontrados para estas enzimas foram o pH 1,5 e 7,0, respectivamente. Observou-se a inibição total da atividade proteolítica ácida do EE na presença de pepstatina A. O ditiotreitol (DTT) e o Ca2+ não promoveram efeito significativo na atividade enzimática. Na presença de metais pesados, como Al3+, Cd2+ e Hg2+, o EE manteve mais de 70% de atividade enzimática do EE. Os resultados mostram que é possível obter, a partir do estômago de C. hippos, proteases aspárticas com alta atividade proteolítica e características que demonstram potencial para aplicações industriais e biotecnológicas.


Assuntos
Animais , Estômago/enzimologia , Estômago/química , Peixes , Ácido Aspártico Proteases/análise , Ácido Aspártico Proteases/economia
7.
Aging (Albany NY) ; 13(21): 24349-24359, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751670

RESUMO

AIMS: In cancer research, normal tissues adjacent to the tumor are usually defined as controls to compare with tumor samples, in order to screen out cancer-related genes. Although there is no obvious difference in pathology between normal tissues adjacent to the tumor and healthy tissues, there are significant changes at the molecular level. We aim to explore more potential tumor biomarkers using healthy tissues as controls rather than normal tissues adjacent to the tumor. METHODS: Here we combine the Genotype-Tissue Expression project and The Cancer Genome Atlas for differential gene analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied in order to predict the biological effects of related lncRNAs. RESULTS: We established a 5-lncRNA prognosis model with an AUC value of 0.815. Pathway analysis indicated that 5-lncRNA mainly affected tissue carcinogenesis through PI3K-AKT signaling pathway, Focal adhesion, MAPK signaling pathway. CONCLUSION: The 5-lncRNA prognostic model we set up is more conducive to assess the overall survival time of gastric cancer patients.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Estômago/química , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estômago/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Transcriptoma/genética
8.
PLoS One ; 16(8): e0256487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34449790

RESUMO

BACKGROUND: Hypochlorhydria (gastric pH >4) increases susceptibility to diarrhoea, iron deficiency, and gastric cancer. We sought to clarify the prevalence of this condition and its predisposing factors in Zambia by pooling data from previous studies conducted in hospital and community settings. METHODS: Gastric pH was measured in participants from five separate studies by collecting gastric aspirate from fasted adults and children under 3 years of age undergoing gastroscopy. Gastric pH was correlated with serological testing for Human Immunodeficiency Virus (HIV) and Helicobacter pylori (H. pylori) infections. RESULTS: We studied 597 individuals (487 adults and 110 children). Hypochlorhydria was present in 53% of adults and 31% of children. HIV infection was detected in 41% of adults and 11% of children. H. pylori serology was available for 366 individuals: 93% of adults and 6% of children were seropositive. In univariate analysis, hypochlorhydria was significantly associated with HIV seropositivity (OR 1.7; 95% CI 1.2-2.4; p = 0.004) and H. pylori antibody seropositivity (OR 4.9; 95% CI 2.8-8.6; p<0.0001), and with advancing age in HIV negative individuals (p = 0.0001). In multivariable analysis, only H. pylori was associated with hypochlorhydria (OR 4.0; 95% CI 2.2-7.2; p<0.0001) while excluding possible exposure to proton pump inhibitors. CONCLUSIONS: Hypochlorhydria is common in our population, with H. pylori being the dominant factor. Only young HIV seronegative individuals had a low prevalence of hypochlorhydria. This may have implications for the risk of other health conditions including gastric cancer.


Assuntos
Acloridria/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/patogenicidade , Estômago/química , Acloridria/microbiologia , Acloridria/patologia , Adulto , Idoso , Criança , Pré-Escolar , Endoscopia , Feminino , Gastroscopia , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estômago/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virologia
9.
Am J Surg Pathol ; 45(5): 672-679, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534221

RESUMO

Historic and current pathology society guidelines recommend using visual gestalt to identify substantial inflammatory cell infiltrate in Helicobacter pylori gastritis, but these scales were subjectively designed. This study aims to objectively investigate the density of inflammation that justifies additional workup for H. pylori infection. We retrospectively identified 2 patient cohorts who had undergone endoscopy with gastric biopsies; 1 with H. pylori infection (n=66), confirmed with a positive stool antigen test and/or Campylobacter-like organism test, and 1 without infection (n=81). Antral and body biopsies were selected from each case, if available, and stained with MUM-1 to highlight mucosal plasma cells. Digital analysis was performed to calculate the number of plasma cells/mm2, termed the "inflammatory score" (IS). Patients with H. pylori infection had an average of 1289 plasma cells/mm2 in the antrum and 835 plasma cells/mm2 in the body, compared with 346 plasma cells/mm2 in the antrum and 178 plasma cells/mm2 in the body in patients without infection. IS cut-off values for a positive infection were 714 plasma cells/mm2 in the antrum and 316 plasma cells/mm2 in the body, with high sensitivities and specificities in both the antrum (92%, 92%) and body (85%, 84%), respectively. A visual analog scale was created to provide a histologic correlate of the observed IS ranges and cut-offs. This practical and objective scale is associated with a high sensitivity and specificity for diagnosing H. pylori infection and justifies moving away from upfront universal H. pylori testing in routine clinical practice.


Assuntos
Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Plasmócitos/patologia , Estômago/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Criança , Pré-Escolar , Feminino , Gastrite/metabolismo , Gastrite/microbiologia , Gastroscopia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Humanos , Imuno-Histoquímica , Fatores Reguladores de Interferon/análise , Masculino , Pessoa de Meia-Idade , Plasmócitos/química , Plasmócitos/microbiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estômago/química , Estômago/microbiologia , Adulto Jovem
10.
Forensic Sci Int ; 318: 110613, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33254094

RESUMO

We report here detection of helium in specimens derived from a burn autopsy case. A male was found in a burnt bedroom. Part of a heat-denatured plastic bag, sealing tape, and flexible tubing remained on his head and neck. In addition, five helium tanks were found near him. His history in conjunction with the discovery conditions suggested a suicide attempt by inhalation of helium. The body had extensive first to fourth degree burns caused by heat. A small amount of soot was deposited in the respiratory tract. Except for the thermal burns, no other injuries were found. Toxicologically, the blood carboxyhemoglobin saturation levels were less than 6%, while combustion-derived volatile hydrocarbons such as benzene or toluene were detected in the blood. In addition, tracheal gas, gastric gas, headspace gas of lung tissue, brain, and heart blood were collected during autopsy for detection of helium. Analysis was performed using headspace gas chromatography with a thermal conductivity detector. Helium was detected in all of the samples tested. Etizolam at a low limit of therapeutic concentration or less was detected in the blood. Neither ethanol nor other drugs of abuse were detected in his blood or urine. Autopsy findings and experiments suggest that the victim inhaled helium and was still alive when a fire broke out. The cause of his death was diagnosed as death from fire and flames. The present result suggests that helium may remain in a burned body and that investigation of helium in cases of fire-related deaths is informative for determination of the cause of death or confirmation of the ante mortem involvement of helium.


Assuntos
Incêndios , Hélio/análise , Administração por Inalação , Química Encefálica , Queimaduras/etiologia , Carboxihemoglobina/análise , Cromatografia Gasosa , Patologia Legal , Toxicologia Forense , Humanos , Hidrocarbonetos/sangue , Pulmão/química , Pulmão/patologia , Masculino , Fuligem/análise , Estômago/química , Tentativa de Suicídio , Traqueia/química , Traqueia/patologia
11.
Environ Pollut ; 268(Pt A): 115830, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33162217

RESUMO

Oral bioaccessibility (BAc) is a surrogate for the bioavailability (BAv) of a broad range of substances, reflecting the value that the approach offers for assessing oral exposure and risk. BAc is generally considered to have been validated as a proxy for oral BAv for the important soil contaminants Pb, Cd, and As. Here, using literature data for Ni BAc and BAv, we confirmed that Ni BAc (gastric only, with HCl mimicking stomach conditions) is a conservative measure of BAv for the oral exposure pathway. Measured oral BAv of Ni in soil was shown to be 50-100 times less than the simplest oral BAc estimates (%BAv = 0.012(%BAc) - 0.023 (r = 0.701, 95%CI [0.456, 0.847], n = 30)) in rats, demonstrating a significant conservatism for exposure assessment. The relationship between the oral BAv and BAc of nickel sulfate hexahydrate (NSHH) was comparable to that of soil, with measured oral BAv of NSHH (1.94%) being a small fraction of NSHH gastric BAc (91.1%). BAc and BAv reflect the underlying Ni speciation of the sample, with the bioaccessible leaching limits being represented by the highly soluble Ni salts and the poorly soluble Ni monoxide, and the environmental (e.g. soil properties) or gastric (e.g. food present) conditions. BAc has potential utility for chemical classification purposes because pure Ni substances can be grouped by %BAc values(using standardized methodologies for the relevant exposure routes), these groupings reflecting the underlying chemistry and speciation of the samples of substances tested here, with 0.008% %BAc for alloys (SS304, SS316, Inconel, Monel), <1% in green NiO and Ni metal massives, 0.9-23.6% for Ni powders, 9.8-22.7% for Ni sulfides, 26.3-29.6% for black oxidic Ni, and 82-91% for the soluble Ni salts. Oral BAc provides realistic yet conservative estimates of BAv for the hazard classification and risk assessment of Ni substances.


Assuntos
Níquel , Poluentes do Solo , Ligas , Animais , Disponibilidade Biológica , Monitoramento Ambiental , Níquel/análise , Ratos , Solo , Poluentes do Solo/análise , Estômago/química
12.
J Clin Lab Anal ; 34(12): e23555, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32951272

RESUMO

OBJECTIVE: Our research group was aim to explore the molecular mechanism of Talin-1 protein affecting gastric cancer progression through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis. METHODS: 12 cases of patients with gastric cancer in this hospital from 2018 to 2019 were collected. Immunohistochemistry assay and Western blotting were used to detect the expression of Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 protein in gastric cancer tissue. Cell migration and invasion were measured by Transwell. RESULTS: The results showed that the expression levels of protein Talin-1, PXN and MAPK1 in gastric cancer tissues were significantly higher than that in normal tissue. The number of cell adhesion in the model group was significantly lower than that in the normal group. However, the cell adhesion number in ov-TLN1 was the highest. Transwell results showed that TLN1 could accelerate the migration and invasion abilities of gastric cancer MKN-45 cells. Moreover, Western blotting showed that protein Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 in model group all increased compared with normal group. CONCLUSION: It indicated that talin-1 protein influenced the development of gastric cancer through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias Gástricas , Talina , Antígenos CD/metabolismo , Caderinas/metabolismo , Calpaína/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Quinase 1 de Adesão Focal/metabolismo , Humanos , Imuno-Histoquímica , Paxilina/metabolismo , Estômago/química , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Talina/análise , Talina/metabolismo , Vinculina/metabolismo
13.
Proc Natl Acad Sci U S A ; 117(36): 22390-22401, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32848063

RESUMO

Targeted cancer therapy aims to achieve specific elimination of cancerous but not normal cells. Recently, PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, have emerged as promising candidates for targeted cancer therapy. PPD proteins are essential for small noncoding RNA pathways. The Argonaute subfamily partners with microRNA and small interfering RNA, whereas the PIWI subfamily partners with PIWI-interacting RNA (piRNA). Both PIWI proteins and piRNA are mostly expressed in the germline and best known for their function in transposon silencing, with no detectable function in mammalian somatic tissues. However, PIWI proteins become aberrantly expressed in multiple types of somatic cancers, thus gaining interest in targeted therapy. Despite this, little is known about the regulatory mechanism of PIWI proteins in cancer. Here we report that one of the four PIWI proteins in humans, PIWIL1, is highly expressed in gastric cancer tissues and cell lines. Knocking out the PIWIL1 gene (PIWIL1-KO) drastically reduces gastric cancer cell proliferation, migration, metastasis, and tumorigenesis. RNA deep sequencing of gastric cancer cell line SNU-1 reveals that KO significantly changes the transcriptome, causing the up-regulation of most of its associated transcripts. Surprisingly, few bona fide piRNAs exist in gastric cancer cells. Furthermore, abolishing the piRNA-binding activity of PIWIL1 does not affect its oncogenic function. Thus, PIWIL1 function in gastric cancer cells is independent of piRNA. This piRNA-independent regulation involves interaction with the UPF1-mediated nonsense-mediated mRNA decay (NMD) mechanism. Altogether, our findings reveal a piRNA-independent function of PIWIL1 in promoting gastric cancer.


Assuntos
Proteínas Argonautas , RNA Interferente Pequeno , Neoplasias Gástricas , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Linhagem Celular Tumoral , Feminino , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Camundongos Nus , Degradação do RNAm Mediada por Códon sem Sentido/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Estômago/química , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
14.
Biomed Res Int ; 2020: 1049179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626731

RESUMO

BACKGROUND: Acetylsalicylic acid (ASA) is a commonly used anti-inflammatory, antipyretic, and analgesic drug, which has many side effects on the gastric mucosal layer. Despite this, knowledge concerning the influence of ASA on neuronal cells supplying the stomach is very scanty. METHODS: This investigation was performed on ten immature gilts of the Large White Polish race divided into two groups (five animals in each): a control group and animals which were treated with ASA. The retrograde neuronal tracer Fast Blue (FB) was injected into the prepyloric region of the stomach in all animals. ASA was then given orally to the experimental (ASA) group of gilts from the seventh day after FB injection to the 27th day of the experiment. After this period, all animals were euthanized. Immediately after euthanasia, nodose ganglia (NG) were collected and subjected to a standard double-labelling immunofluorescence technique using antibodies directed toward substance P (SP) and other selected neuronal factors, such as galanin (GAL), neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP). Key Results. The obtained results show that SP-LI neurons located in NG supplying the porcine stomach were also immunoreactive to all the above-mentioned neuronal factors. Moreover, ASA administration caused an increase in the degree of colocalization of SP with other neuronal active substances, and the most visible changes concerned the number of neurons simultaneously immunoreactive to SP and CGRP. Conclusions and Inferences. These observations indicate that the population of SP-LI neurons supplying the stomach is not homogeneous and may undergo changes after ASA administration. These changes are probably connected with inflammatory processes and/or neuroprotective reactions although their exact mechanisms remain unknown.


Assuntos
Aspirina/farmacologia , Gânglio Nodoso/efeitos dos fármacos , Estômago/inervação , Substância P/metabolismo , Animais , Aspirina/administração & dosagem , Feminino , Neuropeptídeos/metabolismo , Gânglio Nodoso/química , Estômago/química , Suínos
15.
Biomed Res Int ; 2020: 6590303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626753

RESUMO

OBJECTIVE: Long noncoding RNA (LncRNA) SBF2-AS1 was reportedly to function as an oncogene in several types of cancers, such as hepatocellular carcinoma, nonsmall cell lung cancer, glioma, and colorectal cancer. However, the biological roles and regulatory mechanisms of SBF2-AS1 in gastric cancer (GC) are unknown. METHODS: The expression of SBF2-AS1 and miR-545 were examined in GC tissues and cell lines via real-time quantitative PCR. The relationship of SBF2-AS1 with miR-545 was verified via dual-luciferase reporter gene assay and RNA immunoprecipitation. The influences of SBF2-AS1 on cell proliferation, migration, and invasion were determined using cell counting Kit-8 (CCK-8), wound healing, and transwell invasion assays, respectively. RESULTS: LncRNA SBF2-AS1 expression was upregulated in GC tissues, especially in advanced clinical stage cases. Moreover, increased SBF2-AS1 indicated a poor survival rate. Functionally, the downregulation of SBF2-AS1 by siRNA in GC cells suppressed the proliferation, migration, and invasion. In terms of mechanism, SBF2-AS1 can directly bind to miR-545 and regulate its expression. Moreover, SBF2-AS1 knockdown significantly decreased the expression of EMS1, which was the direct target of miR-545. Importantly, inhibition of miR-545 or overexpression of EMS1 partially reversed SBF2-AS1-depletion-caused suppression on proliferation, migration, and invasion. CONCLUSION: These findings elucidated a crucial role of SBF2-AS1 as a miR-545 sponge in GC cells, suggesting that SBF2-AS1 might be a potential target for GC.


Assuntos
Cortactina , MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Linhagem Celular Tumoral , Cortactina/genética , Cortactina/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estômago/química , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
16.
ScientificWorldJournal ; 2020: 6326452, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549800

RESUMO

The current study has been conducted to evaluate the effect of different processing techniques on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and the gastroprotective potential of Chenopodium quinoa red seeds in acute gastric injury induced by absolute ethanol in rats. Seven groups of female Sprague Dawley rats were assigned to normal and absolute ethanol (absolute EtOH) groups, given distilled water, reference control omeprazole (OMP, 20 mg/kg), pressure-cooked quinoa seeds (QP, 200 mg/kg), first stage-germinated quinoa seeds (QG, 200 mg/kg), Lactobacillus plantarum bacteria-fermented quinoa seeds (QB, 200 mg/kg), and Rhizopus oligosporus fungus-fermented quinoa seeds (QF, 200 mg/kg). One hour after treatment, all groups were given absolute ethanol, except for the normal control rats. All animals were sacrificed after an additional hour, and the stomach tissues were examined for histopathology of hematoxylin and eosin staining, immunohistochemistry of cyclooxygenase 2 (COX-2), and nitric oxide synthase (iNOS). Stomach homogenates were evaluated for oxidative stress parameters and prostaglandin E2 (PGE2). Gene expression was performed for gastric tumor necrosis factor alpha (TNF-α) and nuclear factor kappa of B cells (NF-kB). QB and QG recorded the highest DPPH scavengers compared to QF and QP. The gastroprotective potential of QB was comparable to that of OMP, followed by QF, then QG, and QP as confirmed by the histopathology, immunohistochemistry, and gene expression assessments. In conclusion, differently processed red quinoa seeds revealed variable antioxidant capacity and gastroprotective potential, while the bacterial fermented seeds (QB) showed the highest potential compared to the other processing techniques. These results might offer promising new therapy in the treatment of acute gastric injury.


Assuntos
Chenopodium quinoa/química , Sequestradores de Radicais Livres/farmacologia , Fármacos Gastrointestinais/farmacologia , Sementes/química , Gastropatias/prevenção & controle , Animais , Culinária , Ciclo-Oxigenase 2/metabolismo , Etanol , Feminino , Fermentação , Sequestradores de Radicais Livres/química , Fármacos Gastrointestinais/química , Expressão Gênica/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Estômago/química , Estômago/efeitos dos fármacos , Estômago/patologia , Gastropatias/induzido quimicamente , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Biomed Res Int ; 2020: 2863236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32596290

RESUMO

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p < 0.05) and human gastric cancer cell lines (p < 0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p < 0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p < 0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p < 0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.


Assuntos
Apoptose/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Estômago/química , Estômago/patologia , Neoplasias Gástricas/química , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
18.
Biomed Res Int ; 2020: 6726759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462010

RESUMO

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases' data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.


Assuntos
Proteínas de Ligação a DNA , Transição Epitelial-Mesenquimal/fisiologia , Proteínas Nucleares , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/metabolismo , Fatores de Transcrição , Idoso , Biomarcadores Tumorais , Adesão Celular , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Estômago/química , Estômago/patologia , Neoplasias Gástricas/química , Neoplasias Gástricas/mortalidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Environ Sci Pollut Res Int ; 27(18): 22353-22363, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32314282

RESUMO

Globally, fine particulate matter has been associated with several health problems including cancer. However, most studies focused mainly on lung cancer. Stomach and colorectal cancers play significant roles in increasing public health's cancer globally. This study focused on investigating a possible significant association between exposure to fine particulate matter (PM2.5) and mortality due to stomach and colorectal cancer in Xi'an from 2014 to 2016. Using time-series analysis, the study applied both single and multi-pollutant(s) approaches for investigations; PM2.5 was the pollutant of interest. Generalized additive model (GAM) was the core statistical method used with the addition of distributed lag model (DLM) to observe delayed effects. As a single pollutant, PM2.5 was significantly associated with stomach cancer mortality only RR (95%CI): 1.0003 (1.0001, 1.002). For the multi-pollutant analysis, PM2.5 combinations with NO2 were significantly associated with both stomach and colorectal cancer mortality RR (95%CI): 1.0103 (1.009, 1.021) and 1.054 (1.0324, 1.0667), respectively. Also, PM2.5 combination with O3 was significantly associated with colorectal cancer mortality, RR (95%CI): 1.0151 (1.0091, 1.0172), but no association was noted for combination with SO2. Though this study has reported significant associations, it will be beneficial for the public's health if more studies further investigate the relationship between exposure to PM2.5 and other cancer mortality.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Neoplasias Colorretais , China , Exposição Ambiental/análise , Humanos , Mortalidade , Material Particulado/análise , Estômago/química
20.
J Clin Lab Anal ; 34(8): e23303, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32196751

RESUMO

BACKGROUND: Circular RNAs (circRNAs), proven as single-stranded closed RNA molecules, have been implicated in the onset and development of multiple cancers. This study aimed to summarize existing evidences regarding the clinicopathologic, diagnostic, and prognostic significances of circRNAs in gastric cancer (GC). METHODS: Eligible studies were identified using online databases. The quality of the included studies was judged, and patients' clinical characteristics, diagnostic data, and overall survival (OS) were extracted from the electronic medical record. Fisher's method was adopted to determine P values for clinicopathologic features. The diagnostic and prognostic data from all included studies were merged. RESULTS: Thirty eligible studies were comprised of 2687 GC patients were enrolled in the meta-analyses. Altered expressions of circRNAs in GC tissues were significantly associated with worse clinicopathologic features. Abnormally expressed circRNAs yielded a pooled sensitivity of 0.76 (95% CI: 0.69-0.81) and a specificity of 0.77 (95% CI: 0.70-0.83) in distinguishing GC from noncancerous controls, which corresponded to an area under the curve (AUC) of 0.83. The survival analysis showed that the oncogenic circRNA signature could be an independent risk factor of OS (HR = 2.11, 95% CI: 1.60-2.78, P = .000). Patients with down-regulated circRNAs (tumor suppressor genes) presented a significantly shorter OS time than those with high-level circRNAs (HR = 0.33, 95% CI: 0.27-0.42, P = .000). Stratified analyses based on sample type, control source, circRNA expression status, and cutoff setting also produced robust results. CONCLUSIONS: CircRNAs may play an important role as potential diagnostic and prognostic biomarkers of GC.


Assuntos
RNA Circular , Neoplasias Gástricas , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Humanos , Prognóstico , RNA Circular/análise , RNA Circular/genética , Sensibilidade e Especificidade , Estômago/química , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
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