RESUMEN
Epoxides are important bulk chemicals, playing irreplaceable role in the chemical industry, but facing serious pollution and low productivity in the production process. Therefore, the development of green and efficient epoxidation of olefins by stable catalysts with low prices is of great significance. In this study, a Mo-MATP catalyst was prepared by modifying Mo(CO)6 on attapulgite through Si-O bonding. Mo-MATP exhibits excellent performance (99% yield of cyclooctane oxide, CYCO) and stability (80% selectivity of CYCO after 17 cycles), highly tert-butyl hydroperoxide (TBHP) utilization, and extensive substrate scalability. Furthermore, the in-situ Fourier Transform Infrared Spectroscopy (FT-IR), Electron Spin-resonance Spectroscopy (ESR) and High Resolution Mass Spectrometry (HRMS) spectra suggest that TBHP would be activated by Mo-MATP to generate peroxyl radicals, which then oxidize alkenes to their corresponding epoxides. In this study, the stable loading of Mo would largely solve the problem of Mo loss during the catalytic process, thus providing a stable and dispersed Mo active center, enabling the catalyst to possess high catalytic performance and recycling stability.
RESUMEN
INTRODUCTION: People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities recorded among individuals with a likely alcohol withdrawal syndrome within prison in New South Wales, Australia. METHODS: For this clinical case series review, electronic medical data were used to identify 50 people entering custody between August and November 2018 who likely had a treated alcohol withdrawal syndrome. We aimed for a 3:2 ratio of men and women, and a 1:1 ratio of Aboriginal and non-Aboriginal individuals. Data were extracted using a purposefully designed tool which included current alcohol withdrawal management, comorbidities and alcohol relapse prevention approaches used or recommended. RESULTS: Thirty-eight men and 12 women, of whom 22 were Aboriginal, were included. Twenty-nine individuals (58%) reported a history of medical comorbidities. Thirty-five (70%) reported using other substances and over half (60%) had a diagnosis of mental health disorders. Fourteen (28%) individuals had a record of receiving brief intervention and five (10%) of motivational interviewing. Twenty-three individuals (46%) were referred to and seen by drug and alcohol clinicians. Only seven (14%) of the sample had pre-release community care plans. DISCUSSION AND CONCLUSIONS: Individuals treated for an alcohol withdrawal syndrome in New South Wales prisons have a high prevalence of medical comorbidities and other substance use. Clinical interventions focused on alcohol withdrawal management, and relapse prevention interventions were not recorded for most individuals. Service innovation and expansion are needed to increase the provision of post-withdrawal management.
Asunto(s)
Alcoholismo , Síndrome de Abstinencia a Sustancias , Femenino , Humanos , Masculino , Alcoholismo/epidemiología , Alcoholismo/terapia , Australia/epidemiología , Atención a la Salud , Nueva Gales del Sur/epidemiología , Prisiones , Prevención SecundariaRESUMEN
The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.
Asunto(s)
Neoplasias Colorrectales , Proteínas Cullin , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Regulación hacia Abajo , Movimiento Celular/genética , Transducción de Señal , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
BACKGROUND: Since Heald proposed the total mesorectal excision (TME) procedure, the prognosis of patients with rectal cancer has been significantly improved. But Heald did not specifically describe the anterior surgical plane in female patients. And the surgical plane for mobilizing the anterior rectal wall during TME surgery in female patients remains controversial. AIM: To investigate the anatomy of the female pelvis and identify the optimal plane for mobilizing the anterior rectal wall. METHODS: We retrospectively collected surgical procedure videos and clinical data of female patients diagnosed with middle or low rectal cancer who underwent the TME procedure between January 2020 and October 2022 across six hospitals. The patients were divided into two groups based on the surgical approach used to mobilize the anterior rectal wall: The experimental group was to open the peritoneum at the lowest point of the peritonea reflection and enter the plane for mobilizing, while the control group was cut at 0.5-1 cm above the peritoneal reflection and enter another plan. Then, we compared the preoperative and postoperative information between the two groups. We also dissected and observed ten adult female pelvises to analyze the anatomic structure and compare the entry plane between the two approaches. Finally, we researched the pathological structure between the rectum and the vagina. RESULTS: Finally, 77 cases that met the criteria were included in our study. Our observations revealed that the experimental group underwent a smooth procedure, entering the plane amidst the mesorectal fascia and adventitia of the vagina, whereas the control group entered the plane between the vaginal adventitia and muscle layers. Compared to the control group, the experimental group showed a significant decrease in intraoperative bleeding [22.5 (19.5-50) mL vs 17 (5-20) mL, P = 0.01], as well as a shorter duration of hospitalization [9 (7-11.25) d vs 7 (6-10) d, P = 0.03]. Through the examination of surgical videos and cadaveric studies, we discovered that Denonvilliers' fascia is absent in females. Additionally, pathological sections further revealed the absence of Denonvilliers' fascia in females, with only loose connective tissue present between the mesorectal fascia and adventitia of the vagina. CONCLUSION: The plane amidst the mesorectal fascia and vaginal adventitia is the optimal surgical plane to mobilize the anterior rectal wall for female patients undergoing the TME procedure.
Asunto(s)
Laparoscopía , Neoplasias del Recto , Adulto , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Recto/cirugía , Recto/patología , Pelvis/anatomía & histología , Pelvis/patología , Peritoneo/patología , Laparoscopía/métodosRESUMEN
Most bowel endometriotic lesions are ill-defined serosal and subserosal nodules, and no case of cystic bowel endometriosis has been reported in the literature. This is the first report of an unexpected presentation of bowel endometriosis as a primary cyst located inside the posterior rectal wall. The patient was a 26-year-old nulliparous woman with progressive lower abdominal pain for 6 days and difficult defecation for 1 day. Colorectal surgeons recommended bowel resection owing to the giant rectal mass. However, the patient refused to undergo surgery. Ultrasound-guided aspiration of the rectal endometriotic cyst followed by gonadotropin-releasing hormone agonist injection was individually scheduled, which finally brought significant improvement both in symptoms and in the size of the rectal endometriotic lesion.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Endometriosis , Enfermedades del Recto , Femenino , Humanos , Adulto , Endometriosis/complicaciones , Endometriosis/diagnóstico por imagen , Endometriosis/cirugía , Recto/patología , Enfermedades del Recto/complicaciones , Enfermedades del Recto/diagnóstico por imagen , Enfermedades del Recto/cirugía , Ultrasonografía IntervencionalRESUMEN
MORC family CW-type zinc finger 4 (MORC4) possessing nuclear matrix binding domains has been observed to be involved in multiple cancer development. By digging three gene expression omnibus (GEO) gene microarrays (GSE110223, GSE110224 and GSE24514), we found that MORC4 was overexpressed in colorectal cancer (CRC) samples (log2 Fold change >1, p < 0.05). We aimed to investigate the role of MORC4 in CRC malignant behaviors, with an emphasis on polycomb group ring finger 1 (PCGF1)/cyclin-dependent kinase inhibitor 1A (CDKN1A) axis. Firstly, we confirmed MORC4 as an upregulated gene in 60 pairs of frozen CRC and adjacent normal samples. MORC4 overexpression increased proliferation and metastasis, and decreased apoptosis in SW480 and HT29 cells, which was diminished by the knockdown of PCGF1, a transcriptional repressor of CDKN1A (a potent cyclin-dependent kinase inhibitor). MORC4 was further identified as a novel molecule that interacted with PCGF1 via coimmunoprecipitation. MORC4 itself did not substantially suppress CDKN1A transcriptional activity, but it augmented PCGF1's effect on CDKN1A. Additionally, MORC4 acted as the substrate of HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2 (HECW2) and was degraded through ubiquitin-proteasome system. Collectively, our work suggested that MORC4 accelerated CRC progression via governing PCGF1/CDKN1A signaling.
Asunto(s)
Neoplasias Colorrectales , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Neoplasias Colorrectales/genética , Quinasas Ciclina-Dependientes , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Complejo Represivo Polycomb 1/genética , Proteínas Nucleares/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
In this paper, 2D and 3D plasma photonic crystals (PPCs) were constructed using argon-mercury glow discharge tubes. Firstly, the collisional radiative model (CRM) was established for the glow discharge process, the average electron density of plasma in the discharge tube was calculated, and the average electron density was experimentally diagnosed by microwave diagnosis. By comparing the calculated and experimental results, the variation range of the average electron density in the tube was given. Secondly, according to the analysis results of the average electron density, a layered model of the discharge tube was established, and the transmission characteristics of the 2D and 3D PPC were calculated and measured. Finally, to analyze the cause of the photonic bandgap (PBG) in the transmission spectra, the band structures of 2D and 3D PPC were calculated using the plane wave expansion (PWE) method and the symplectic finite difference time domain (SFDTD) method. The results show that: the layered model is a valid discharge tube model; for 2D PPC, the formation of Localized Surface Plasmons (LSPs) under TE polarization is the main cause of PBG generation, and the number of LSP bandgap increases as the electron density rises; The existence of cutoff bandgap under TM polarization is due to the cutoff effect of plasma on electromagnetic waves. For 3D PPC, both cutoff bandgap and LSP bandgap exist in the transmission spectra, and the cutoff bandgap is shifted to lower frequencies due to the presence of Fano mode. The results of the study can be used as a reference for communication, microwave device fabrication, and military target stealth.
RESUMEN
Under the background of carbon dioxide emission reduction, how to realize the treatment and the high value-added conversion of typical olefin volatile organic compounds (olefin-VOCs), such as styrene, is a big challenge. In this contribution, the ceria-supported coinage metal catalysts (M/CeO2, M = Au, Ag, and Cu) are successfully synthesized by a dry mechanochemical method, and their catalytic performance for styrene-VOC epoxidation with tert-butyl hydrogen peroxide (TBHP) as an oxidant to prepare high-value styrene oxide (SO) is investigated. The oxygen vacancies of ceria play a key role in the anchoring of metal nanoparticles. After ball milling, Au(III) is partially reduced and coexists on ceria in two valence states (Au3+ and Au0), and the reactive oxygen species of the as-prepared catalyst are enhanced. The catalytic behaviors, including solvents effect, substrate concentration, oxidant ratio, catalyst dosage, reaction time, and temperature, are systematically investigated. Au/CeO2 exhibits good styrene epoxidation performance with a total styrene conversion of 94% and a SO yield of 63%, along with good reusability and substrate scalability. Thermodynamics and kinetics show that Au/CeO2 was more favorable for styrene epoxidation and this reaction is dominated by the rate of intrinsic chemical reactions on the surface of the catalyst. Based on experimental discussions and a set of characterizations (XPS, XRD, in-situ FT-IR, ESR, ESI-HSMS, etc.), the mechanism is revealed as the synergistic catalysis between the reactive oxygen species of Au/CeO2 and the peroxide radicals generated by the homolysis of TBHP.
RESUMEN
Hepatocellular carcinoma (HCC) is a familiar malignant tumor, and cepharanthine (CEP) was proven to prevent the malignant activity of multiple cancer cells, including HCC. However, there are few reports on the regulatory role of CEP in HCC. After treatment with CEP or/and JAK2/Stat3 inhibitor (AG490), the associative functions were assessed by MTT, wound healing, Trans well, and Hochest33342-PI double staining in HCC cells. Then the levels of CDK4, MMP-9, Bcl-2, p-JAK2/JAK2, and p-Stat3/Stat3 were monitored via western blot. Besides, the HCC xenograft model was constructed to verify the effects of CEP on tumor growth and the JAK/Stat3 pathway. CEP could restrain proliferation and metastasis and facilitate apoptosis in HCC cells. CEP also reduced Bcl-2 (anti-apoptosis), CDK4 (proliferation), and MMP-9 (invasion) expressions, and inhibited JAK2 and Stat3 phosphorylation. Besides, CEP suppressed HCC progression by JAK2/Stat3 pathway. Moreover, CEP inhibited the growth of subcutaneous HCC xenografts and reduced p-JAK2 and p-Stat3 in tumor tissues. CEP could suppress HCC progression by attenuating the JAK2/Stat3 pathway, indicating that CEP might be a therapeutic drug for HCC patients.
Asunto(s)
Benzodioxoles , Bencilisoquinolinas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias Hepáticas/patología , Janus Quinasa 2/metabolismo , Apoptosis , Proliferación Celular , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción STAT3/metabolismo , Línea Celular TumoralRESUMEN
A broadband frequency selective rasorber (FSR) based on spoofsurface plasmon polaritons (SSPP) is proposed. The FSR is composed of a multi-layer structure comprising frequency selective surface (FSS)-polyresin (PR)-indium tin oxide (ITO)-PR-FSS and placed vertically on a metal base plate. A periodic square cavity structure is formed. The transmission characteristics of the FSR are studied by full-wave simulation and equivalent circuit method. The simulation results demonstrate that under normal incidence, the absorption rate of the structure remains 95% in the 5-30 GHz band, and the absorption rate is also 80% in the 3.5-5 GHz band. As the incident angle of the electromagnetic wave increases to 40°, the absorption rate in the 15-20 GHz band decreases to 70% in the transverse electric (TE) mode, and the absorption rate in the transverse magnetic (TM) mode is almost the same as that of vertical incidence. The transmission response of the structure is measured in an anechoic chamber. The measurement results agree well with the simulation results, proving the reliability of the design and fabrication. The structure is less sensitive to the incident angle of magnetic waves and has a better broadband absorbing ability.
RESUMEN
Our study aimed to develop a prediction model to predict the short-term mortality of hepatocellular carcinoma (HCC) patients with lung metastasis. The retrospective data of HCC patients with lung metastasis was from the Surveillance, Epidemiology, and End Results registration database between 2010 and 2015. 1905 patients were randomly divided into training set (nâ =â 1333) and validation set (nâ =â 572). There were 1092 patients extracted from the Surveillance, Epidemiology, and End Results database 2015 to 2019 as the validation set. The variable importance was calculated to screen predictors. The constructed prediction models of logistic regression, random forest, broad learning system, deep neural network, support vector machine, and naïve Bayes were compared through the predictive performance. The mortality of HCC patients with lung metastasis was 51.65% within 1 month. The screened prognostic factors (age, N stage, T stage, tumor size, surgery, grade, radiation, and chemotherapy) and gender were used to construct prediction models. The area under curve (0.853 vs. 0.771) of random forest model was more optimized than that of logistic regression model in the training set. But, there were no significant differences in testing and validation sets between random forest and logistic regression models. The value of area under curve in the logistic regression model was significantly higher than that of the broad learning system model (0.763 vs. 0.745), support vector machine model (0.763 vs. 0.689) in the validation set, and higher than that of the naïve Bayes model (0.775 vs. 0.744) in the testing model. We further chose the logistic regression prediction model and built the prognostic nomogram. We have developed a prediction model for predicting short-term mortality with 9 easily acquired predictors of HCC patients with lung metastasis, which performed well in the internal and external validation. It could assist clinicians to adjust treatment strategies in time to improve the prognosis.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/secundario , Estudios Retrospectivos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Teorema de Bayes , PronósticoRESUMEN
Pancreatic cancer remains to have a high mortality, which is partly due to the lack of effective treatment strategies. In this study, genes with potential associations with immunophenotyping of pancreatic cancer were screened through bioinformatics analysis and the correlation between immune-related genes and the prognosis of pancreatic cancer patients was assessed. Firstly, differentially expressed immune genes were extracted from the pancreatic cancer-related datasets obtained for purposes of this study. The samples were processed by the "Consensus Cluster Plus" R package to determine the number of immune subtypes. Then, the pancreatic cancer immunophenotyping-related gene modules were determined. Differential analysis of immune gene modules was performed, and the function of genes related to pancreatic cancer immune subtypes was identified. The number of immune cells in the samples was calculated, followed by the differential expression analysis of immune cell numbers in each immune subtype of pancreatic cancer. The immune infiltration score was also estimated, and the correlation between the immune infiltration score and the patient prognosis with different immune subtypes was determined. Gene differences between each immune subtype were identified by differential expression analysis, and key immune genes affecting immunophenotyping were obtained. Following the analysis, 426 immune-related genes were identified to have potential involvement in the occurrence and development of pancreatic cancer, of which CD19 may be the most critical gene affecting the immunophenotyping of pancreatic cancer. CD19 played a significant role in the occurrence and development of IS2 and IS3 immune subtypes of pancreatic cancer through its action on B cells and T cells. Moreover, the expression of CD19 was increased in the collected pancreatic cancer tissues. Overall, our findings uncovered the critical role of CD19 in the prognosis of pancreatic cancer patients.
RESUMEN
The karyopherin α2 subunit gene (KPNA2), an oncogene, is involved in metabolic reprogramming in cancer. This study aimed to explore the function of KPNα2 in the growth and glycolysis in colon cancer (CC) cells. Genes from the Oncomine database that were differentially expressed in multiple CC types were screened. Bioinformatics analysis suggested that KPNA2 was highly expressed in CC, and consequently, high expression of KPNA2 was detected in the CC cell lines. Down-regulation of KPNA2 reduced viability and DNA-replication ability, and increased apoptosis of HCT116 and LoVo cells. It also reduced glucose consumption, extracellular acidification rate, and the ATP production in cells. Centromere protein A (CENPA) was confirmed as an upstream transcription activator of KPNA2. There was significant H3K27ac modification in the promoter region of KPNA2. CENPA primarily recruited histone acetyltransferase general control of amino acid synthesis (GCN)-5 to the promoter region of KPNA2 to induce transcription activation. Overexpression of either CENPA or GCN-5 blocked the role of short hairpin KPNα2 and restored growth and glycolysis in CC cells. To conclude, the findings from this study suggest that CENPA recruits GCN-5 to the promoter region of KPNA2 to induce KPNα2 activation, which strengthens growth and glycolysis in, and augments the development of, CC.
Asunto(s)
Proteína A Centromérica/fisiología , Neoplasias del Colon/genética , alfa Carioferinas/genética , Animales , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Metabolismo Energético/genética , Células HCT116 , Células HEK293 , Humanos , Redes y Vías Metabólicas/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Activación Transcripcional , Células Tumorales Cultivadas , alfa Carioferinas/metabolismoRESUMEN
PURPOSE: The inflammatory response plays a crucial role in the occurrence and development of colon cancer. In this study, we aimed to explore a novel prognostic model for patients with colon cancer (COAD) based on inflammatory response-related genes. METHODS: Inflammatory response-related genes were obtained from Molecular Signatures database. Univariate and multivariate Cox regression analyses were used for model construction based on TCGA dataset. GSE39582 dataset and qRT-PCR dataset were used for validation. Gene set variation analysis and gene set enrichment analysis were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT. Immunohistochemistry analysis and experiments were used to explore the function of genes in model. RESULTS: In this study, a novel prognostic signature was identified using stepwise Cox proportional hazards regression analysis based on TCGA dataset. The results were subsequently validated in 562 patients from GSE39582 and a qRT-PCR data set from 70 tumor samples. Functional analysis indicated that the tumor microenvironment and immune cell infiltrate were different between high- and low-risk groups. Additionally, IHC results showed that the protein levels of prognostic genes were significantly different between COAD tissues and adjacent non-tumorous tissues, and prognostic genes could regulate the malignant phenotype of COAD cells. CONCLUSION: Overall, the inflammation-related gene signature can be used for prognostic prediction in patients with COAD.
RESUMEN
PURPOSE: To investigate the clinicopathological characteristics of stage I-III colorectal cancer (CRC) patients with deficient mismatch repair (dMMR) protein. PATIENTS AND METHODS: A retrospective analysis of 61 patients with stage I-III CRC confirmed by immunohistochemistry as dMMR after radical resection at Shenjing Hospital of China Medical University from May 2017 to June 2019 was performed. A total of 183 stage I-III CRC patients with proficient mismatch repair (pMMR) protein from the same period were randomly selected as a control group. The clinicopathological data of the two groups were investigated. RESULTS: There were significant differences between the two groups in age, sex, site of onset, maximum diameter of tumor, T stage, tumor differentiation, and histological type (P < 0.05). No significant difference was detected in nerve vessel invasion, cancer nodules, the N stage or the TNM stage. In the dMMR group, 41 patients (66.13%) showed PMS2/MLH1 deletion, and the number of MSH2/MSH6 deletion is 21 patients (33.87%). Among them, 34 patients (54.84%) had PMS2 and MLH1 deficiency. In total, 16 patients (25.81%) had MSH2 and MSH6 deficiency. A total of 5 patients (8.06%) showed simply PMS2 deletion and 5 patients (8.06%) showed simply MSH6 deletion. In total, 2 patients (3.23%) showed concurrent loss of PMS2, MLH1 and MSH2. No significant difference were found (P > 0.05) in the above factors among dMMR CRC patients with different MMR proteins deletions. CONCLUSION: Our results show that dMMR status may be more likely exist in female and younger (≤55 years) patients with a greater tumor burden (>5cm), right colon, T4 stage disease, poor differentiation and mucinous adenocarcinoma. Loss of PMS2 and MLH1 is the most common pattern of MMR protein expression deficiency, followed by concurrent deletion of MSH2 and MSH6.
RESUMEN
Cancer stem cells play crucial roles in the development of colon cancer (COAD). This study tried to explore new markers for predicting the prognosis of colon cancer based on stem cell-related genes. In our study, 424 COAD samples from TCGA were divided into three subtypes based on 412 stem cell-related genes; there were significant differences in prognosis, clinical characteristics, and immune scores between these subtypes. 694 genes were screened between subgroups. Subsequently a six-gene signature (DYDC2, MS4A15, MAGEA1, WNT7A, APOD, and SERPINE1) was established. This model had strong robustness and stable predictive performance in cohorts of different platforms. Taken together, the six-gene signature constructed in this study could be used as a novel prognostic marker for COAD patients.
RESUMEN
Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.
Asunto(s)
Acuaporina 3/genética , Estreñimiento/tratamiento farmacológico , Flavanonas/administración & dosificación , Proteínas Proto-Oncogénicas c-kit/genética , Factor de Células Madre/genética , Animales , Estreñimiento/sangre , Estreñimiento/inducido químicamente , Estreñimiento/genética , Endotelinas/sangre , Gastrinas/sangre , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Intersticiales de Cajal/efectos de los fármacos , Laxativos/administración & dosificación , Loperamida/toxicidad , Ratones , Motilina/sangreRESUMEN
PURPOSE: B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior. METHODS: BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression. RESULTS: BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data. CONCLUSIONS: BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Proteínas/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Técnicas de Silenciamiento del Gen , Células HCT116 , Células HT29 , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Proteínas/genética , Transducción de Señal , Células Tumorales CultivadasRESUMEN
Colorectal cancer is one of the most common cancers in the world. Protein phosphatase magnesium-dependent 1 d (PPM1D) is aberrantly upregulated in many human carcinoma cells, and recent research has suggested that it could be a potential therapeutic target of cancer. However, the function of PPM1D in colorectal carcinoma cells is not well studied. To investigate the function of PPM1D in colorectal carcinoma, we used lentivirus-based RNA silencing to knock down the expression of PPM1D in RKO cells. We found that the lentivirus-mediated RNAi system efficiently decreased the expression level of endogenous PPM1D. Inhibiting PPM1D expression efficiently inhibited the proliferation and colony formation of RKO cells. Moreover, we found that PPM1D silencing led to G0/G1 cell-cycle arrest and the accumulation of cells at the sub-G1 phase. Furthermore, we found that PPM1D knockdown reduced the expression level of cyclinB1, inhibited ERK phosphorylation and activated the AKT signaling pathway. We found that PPM1D plays a crucial role in colorectal carcinoma cell proliferation and colony formation. Our work provides strong evidence suggesting that PPM1D is a potential therapeutic target of human colorectal cancers. Lentivirus-mediated PPM1D silencing is a promising gene therapeutic method to treat colorectal cancers.
Asunto(s)
Proliferación Celular , Fosfoproteínas Fosfatasas/genética , Interferencia de ARN , Línea Celular Tumoral , Neoplasias Colorrectales , Puntos de Control de la Fase G1 del Ciclo Celular , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Proteína Fosfatasa 2C , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND: Somatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle. METHODS: In order to understand the role of somatic mutations in human colorectal cancers, we characterized the mutation spectrum in two colorectal tumor tissues and their matched normal tissues, by analyzing deep-sequenced transcriptome data. RESULTS: We found a higher mutation rate of somatic variants in tumor tissues in comparison with normal tissues, but no trend was observed for mutation properties. By applying a series of stringent filters, we identified 418 genes with tumor specific disruptive somatic variants. Of these genes, three genes in mucin protein family (MUC2, MUC4, and MU12) are of particular interests. It has been reported that the expression of mucin proteins was correlated with the progression of colorectal cancer therefore somatic variants within those genes can interrupt their normal expression and thus contribute to the tumorigenesis. CONCLUSIONS: Our findings provide evidence of the utility of RNA-Seq in mutation screening in cancer studies, and suggest a list of candidate genes for future colorectal cancer diagnosis and treatment.