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1.
Sensors (Basel) ; 24(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931766

RESUMO

Currently, complex scene classification strategies are limited to high-definition image scene sets, and low-quality scene sets are overlooked. Although a few studies have focused on artificially noisy images or specific image sets, none have involved actual low-resolution scene images. Therefore, designing classification models around practicality is of paramount importance. To solve the above problems, this paper proposes a two-stage classification optimization algorithm model based on MPSO, thus achieving high-precision classification of low-quality scene images. Firstly, to verify the rationality of the proposed model, three groups of internationally recognized scene datasets were used to conduct comparative experiments with the proposed model and 21 existing methods. It was found that the proposed model performs better, especially in the 15-scene dataset, with 1.54% higher accuracy than the best existing method ResNet-ELM. Secondly, to prove the necessity of the pre-reconstruction stage of the proposed model, the same classification architecture was used to conduct comparative experiments between the proposed reconstruction method and six existing preprocessing methods on the seven self-built low-quality news scene frames. The results show that the proposed model has a higher improvement rate for outdoor scenes. Finally, to test the application potential of the proposed model in outdoor environments, an adaptive test experiment was conducted on the two self-built scene sets affected by lighting and weather. The results indicate that the proposed model is suitable for weather-affected scene classification, with an average accuracy improvement of 1.42%.

2.
Inorg Chem ; 62(16): 6510-6517, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37027781

RESUMO

A simple template strategy was applied to prepare a Fe, N co-doped hollow carbon (Fe-NHC) nanoreactor for the oxygen reduction reaction (ORR) by coating Fe nanoparticles (Fe-NPs) with polydopamine (PDA), followed by high temperature pyrolysis and acid-leaching. With this method, Fe-NPs were used as both the template and the metal precursor, so that the nanoreactors can preserve the original spherical morphology and embed Fe single atoms on the inner walls. The carbonized PDA contained abundant N content, offering an ideal coordination environment for Fe atoms. By regulating the mass ratio of Fe-NPs and PDA, an optimal sample with a carbon layer thickness of 12 nm (Fe-NHC-3) was obtained. The hollow spherical structure of the nanoreactors and the atomically dispersed Fe were verified by various physical characterizations. As a result, Fe-NHC-3 performed well in ORR tests under alkaline conditions, with high catalytic activity, durability, and methanol resistance, demonstrating that the as-fabricated materials have the potential to be applied in the cathodic catalysis of fuel cells.

3.
Biol Chem ; 403(10): 917-928, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35357096

RESUMO

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas Cromossômicas não Histona/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Metástase Neoplásica , Neovascularização Patológica , Fator de Transcrição PAX2/metabolismo
4.
Gastroenterology ; 152(4): 851-866.e24, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27876571

RESUMO

BACKGROUND & AIMS: Nearly 20% of the global cancer burden can be linked to infectious agents. Fusobacterium nucleatum promotes tumor formation by epithelial cells via unclear mechanisms. We aimed to identify microRNAs (miRNAs) induced by F nucleatum and evaluate their ability to promote colorectal carcinogenesis in mice. METHODS: Colorectal cancer (CRC) cell lines were incubated with F nucleatum or control reagents and analyzed in proliferation and would healing assays. HCT116, HT29, LoVo, and SW480 CRC cell lines were incubated with F nucleatum or phosphate-buffered saline (PBS [control]) and analyzed for miRNA expression patterns and in chromatin immunoprecipitation assays. Cells were incubated with miRNAs mimics, control sequences, or small interfering RNAs; expression of reporter constructs was measured in luciferase assays. CRC cells were incubated with F nucleatum or PBS and injected into BALB/C nude mice; growth of xenograft tumors was measured. C57BL adenomatous polyposis colimin/+, C57BL miR21a-/-, and C57BL mice with full-length miR21a (controls) were given F nucleatum by gavage; some mice were given azoxymethane and dextran sodium sulfate to induce colitis and colon tumors. Intestinal tissues were collected and tumors were counted. Serum samples from mice were analyzed for cytokine levels by enzyme-linked immunosorbent assay. We performed in situ hybridization analyses to detect enrichment of F nucleatum in CRC cells. Fusobacterium nucleatum DNA in 90 tumor and matched nontumor tissues from patients in China were explored for the expression correlation analysis; levels in 125 tumor tissues from patients in Japan were compared with their survival times. RESULTS: Fusobacterium nucleatum increased proliferation and invasive activities of CRC cell lines compared with control cells. CRC cell lines infected with F nucleatum formed larger tumors, more rapidly, in nude mice than uninfected cells. Adenomatous polyposis colimin/+ mice gavaged with F nucleatum developed significantly more colorectal tumors than mice given PBS and had shorter survival times. We found several inflammatory factors to be significantly increased in serum from mice given F nucleatum (interleukin 17F, interleukin 21, and interleukin 22, and MIP3A). We found 50 miRNAs to be significantly up-regulated and 52 miRNAs to be significantly down-regulated in CRCs incubated with F nucleatum vs PBS; levels of miR21 increased by the greatest amount (>4-fold). Inhibitors of miR21 prevented F nucleatum from inducing cell proliferation and invasion in culture. miR21a-/- mice had a later appearance of fecal blood and diarrhea after administration of azoxymethane and dextran sodium sulfate, and had longer survival times compared with control mice. The colorectum of miR21a-/- mice had fewer tumors, of smaller size, and the miR21a-/- mice survived longer than control mice. We found RASA1, which encodes an RAS GTPase, to be one of the target genes consistently down-regulated in cells that overexpressed miR21 and up-regulated in cells exposed to miR21 inhibitors. Infection of cells with F nucleatum increased expression of miR21 by activating Toll-like receptor 4 signaling to MYD88, leading to activation of the nuclear factor-κB. Levels of F nucleatum DNA and miR21 were increased in tumor tissues (and even more so in advanced tumor tissues) compared with non-tumor colon tissues from patients. Patients whose tumors had high amounts of F nucleatum DNA and miR21 had shorter survival times than patients whose tumors had lower amounts. CONCLUSIONS: We found infection of CRC cells with F nucleatum to increase their proliferation, invasive activity, and ability to form xenograft tumors in mice. Fusobacterium nucleatum activates Toll-like receptor 4 signaling to MYD88, leading to activation of the nuclear factor-κB and increased expression of miR21; this miRNA reduces levels of the RAS GTPase RASA1. Patients with both high amount of tissue F nucleatum DNA and miR21 demonstrated a higher risk for poor outcomes.


Assuntos
Neoplasias do Colo/microbiologia , DNA Bacteriano/análise , Infecções por Fusobacterium/genética , Fusobacterium nucleatum , MicroRNAs/genética , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteína da Polipose Adenomatosa do Colo/genética , Idoso , Animais , Azoximetano , Carcinogênese , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Neoplasias do Colo/química , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Sulfato de Dextrana , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/antagonistas & inibidores , Prognóstico , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Receptor 4 Toll-Like/genética , Regulação para Cima , Proteína p120 Ativadora de GTPase/genética
5.
Cryobiology ; 70(2): 164-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25578982

RESUMO

The correlation between the 90 kDa heat-shock protein (HSP90) and sperm quality following the process of freezing-thawing in bulls has not been studied clearly. Therefore, the objective of the present was to clarify the relationship between HSP90 level and semen parameters during the process of cryopreservation in bulls. Semen samples from 5 Holstein bulls were obtained by artificial vagina. Characteristics of these semen at three stages (fresh, after equilibration and frozen-thawed), including motility, plasma membrane integrity and acrosome integrity were evaluated. The mRNA expression level of HSP90 at the three stages was evaluated by using quantitative Real-Time PCR. Meanwhile, the protein level of HSP90 expression at the three stages was detected according to Western blot. The results showed that sperm parameters evaluated in fresh semen was the highest in the three groups. Sperm parameters in semen after equilibration were lower than those in fresh semen (P>0.05) and higher than those in post-thawed semen (P<0.05). Sperm parameters in frozen-thawed semen were the lowest among the three groups (P<0.05). This study indicated that HSP90 expression is proportional to sperm quality. HSP90 expression level in fresh semen was significantly higher than that in frozen-thawed semen (P<0.05). Although no significant differences in HSP90 expression were observed between fresh semen and semen after equilibration (P>0.05). Results in this study suggest that HSP90 level in bull spermatozoa was gradually declined following the process of freezing-thawing, and might be associated with sperm motility, plasma membrane integrity and acrosome integrity.


Assuntos
Criopreservação/métodos , Proteínas de Choque Térmico HSP90/metabolismo , Análise do Sêmen , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides/fisiologia , Acrossomo/fisiologia , Animais , Bovinos , Membrana Celular/fisiologia , Criopreservação/veterinária , Congelamento , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Sêmen/fisiologia , Preservação do Sêmen/veterinária , Espermatozoides/fisiologia
6.
J Colloid Interface Sci ; 663: 53-60, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38387186

RESUMO

FeNC single atom catalysts (SACs) have attracted great interest due to their highly active FeN4 sites. However, the pyrolysis treatment often leads to inevitable metal migration and aggregation, which reduces the catalytic activity. Moreover, due to the Fenton reaction caused by FeNC in alkaline and acidic solutions, the presence of Fe and peroxide in electrodes may generate free radicals, resulting in serious degradation of the organic ionomer and the membrane. Herein, we report an original strategy of introducing Co single atoms into FeNC catalysts, forming atomically dispersed bimetallic active sites (FeCoNC) and improving the activity and stability of the catalyst. Benefiting from this strategy, FeCoNC catalyst exhibits excellent oxygen reduction reaction (ORR) activity in alkaline media (E1/2 = 0.88 V) and in acidic media (E1/2 = 0.77 V). As the cathode of Zn-air battery (ZAB), FeCoNC shows an excellent peak power density of 142.8 mW cm-2 and a specific capacity of 806.6 mAh/gZn. This work provides a novel avenue to optimize and enhance the ORR performance of atomic dispersed FeNC catalysts.

7.
Biochem Biophys Res Commun ; 434(4): 746-52, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23583411

RESUMO

Although epithelial barrier dysfunction in the gut has been extensively reported in ulcerative colitis (UC), the pathogenesis of this disease is not completely understood. In the present study, we investigated the role of miR-21 in regulating intestinal epithelial barrier function in UC. Colonic biopsies were obtained from 30 chronic UC patients and 30 healthy controls. Using real-time quantitative polymerase chain reaction (qRT-PCR), we found that both the mucosal and serum levels of miR-21 were upregulated in UC. In situ hybridization (ISH) analysis confirmed the accumulation of miR-21 in UC epithelia cells in vivo. Immunohistochemistry, Western Blot, qRT-PCR, and ultrastructural analyses further demonstrated that the overexpression of miR-21 in UC mucosa and Caco-2 cells impaired the integrity of the tight junctions, resulted in a decrease of the transepithelial electrical resistance (TER) and an increase of the inulin permeability. Furthermore, miR-21 induced the degradation of RhoB mRNA, which led to the depletion of RhoB and the impairment of tight junctions in intestinal epithelial cells.


Assuntos
Colite Ulcerativa/genética , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , MicroRNAs/genética , Proteína rhoB de Ligação ao GTP/genética , Adulto , Idoso , Western Blotting , Células CACO-2 , Colite Ulcerativa/metabolismo , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , MicroRNAs/metabolismo , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Permeabilidade , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Junções Íntimas/metabolismo , Junções Íntimas/ultraestrutura , Adulto Jovem , Proteína rhoB de Ligação ao GTP/metabolismo
8.
Tumour Biol ; 34(3): 1285-300, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23397545

RESUMO

The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 10(13)-10(14) microorganisms in the colon. These microorganisms are essential to a host's well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.


Assuntos
Neoplasias Colorretais/patologia , Trato Gastrointestinal/microbiologia , Animais , Neoplasias Colorretais/etiologia , Humanos , Fatores de Risco
9.
Nanomaterials (Basel) ; 12(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36234434

RESUMO

The rareness and weak durability of Pt-based electrocatalysts for oxygen reduction reactions (ORRs) have hindered the large-scale application of fuel cells. Here, we developed an efficient metal-free catalyst consisting of N, S co-doped graphene nanoribbons (N, S-GNR-2s) for ORRs. GNRs were firstly synthesized via the chemical unzipping of carbon nanotubes, and then N, S co-doping was conducted using urea as the primary and sulfourea as the secondary heteroatom sources. The successful incorporation of nitrogen and sulfur was confirmed by elemental mapping analysis as well as X-ray photoelectron spectroscopy. Electrochemical testing revealed that N, S-GNR-2s exhibited an Eonset of 0.89 V, E1/2 of 0.79 V and an average electron transfer number of 3.72, as well as good stability and methanol tolerance. As a result, N, S-GNR-2s displayed better ORR property than either N-GNRs or N, S-GNRs, the control samples prepared with only a primary heteroatom source, strongly clarifying the significance of secondary-heteroatom-doping on enhancing the catalytic activity of carbon-based nanomaterials.

10.
Zhonghua Zhong Liu Za Zhi ; 33(5): 388-90, 2011 May.
Artigo em Zh | MEDLINE | ID: mdl-21875473

RESUMO

OBJECTIVE: To observe the efficacy and side effects of the combination therapy of oxaliplatin and S-1 in treating postoperative colorectal cancer patients. METHODS: 54 postoperative colorectal cancer patients received the combination therapy of oxaliplatin and S-1 regimen, repeated every 3 weeks, and evaluate the efficacy after 3 cycles. RESULTS: All of the 54 patients but 2 (changed the chemotherapy regimen after the first cycle because of economic reason) finished 6 cycles of the chemotherapy treatment. There were 6 cases (11.5%) with complete response (CR), 28 cases (53.8%) with partial response (PR), and the overall response rate was 65.4%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. There were no chemotherapy-related deaths. CONCLUSIONS: Oxaliplatin combined with S-1 is an effective and better tolerated chemotherapy treatment for postoperative colorectal cancer patients, with no serious side effects for liver and kidney. Therefore, it can be used as an alternative chemotherapy regimen for postoperative colorectal cancer patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/cirurgia , Diarreia/induzido quimicamente , Feminino , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Período Pós-Operatório , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Neoplasias Retais/cirurgia , Indução de Remissão , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Vômito/induzido quimicamente
11.
Surg Radiol Anat ; 33(10): 851-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21986989

RESUMO

PURPOSE: The term Waldeyer's fascia has caused confusion in surgery for rectal cancer. We have therefore dissected endopelvic fasciae to clarify the structure and location of Waldeyer's fascia, and to determine its anatomical relationships with adjacent fasciae. METHODS: Twenty cadavers (13 males and 7 females) were dissected. Each specimen was sectioned in the sagittal plane and both hemipelvises were examined. RESULTS: Waldeyer's fascia was observed in all specimens originating from the presacral fascia at the S2-S4 level and fusing with the posterior leaf of the mesorectal parietal fascia. Waldeyer's fascia divided the retrorectal space (RRS) into inferior and superior compartments, with the upper leaf constituting the floor of the superior compartment and the lower leaf constituting the dome of the inferior compartment. There were no nerves, blood vessels or lymphatic vessels within the two leaves. CONCLUSION: Waldeyer's fascia was located between the mesorectal parietal and presacral fasciae. Waldeyer's fascia included two leaves, which jointly divided the RRS into inferior and superior compartments. Waldeyer's fascia is a pivotal anatomical structure in the surgical treatment of rectal cancer.


Assuntos
Fáscia/anatomia & histologia , Pelve/anatomia & histologia , Reto/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Ying Yong Sheng Tai Xue Bao ; 31(8): 2491-2499, 2020 Aug.
Artigo em Zh | MEDLINE | ID: mdl-34494769

RESUMO

In this study, we examined the characteristics and influence mechanism of soil extracellular enzyme activity (EEA) and enzymatic stoichiometry in different soils in forests at different altitudes (750-1420 m) in Aokelidui Mountains in the north of the Greater Khingan Mountains. The results showed that altitude, season and their interactions significantly affected the activities of ß-glucosidase (BG), ß-1,4-N-acetylglucosaminidase (NAG), L-leucine aminopeptidase (LAP), and acid phosphatase (AP). In May, BG and NAG activities gradually increased with increasing altitude, while AP activities increased first and then decreased with increasing altitude. In July, NAG activity increased with altitude, while AP activity increased first and then decreased. In September, NAG activity changed significantly in different altitudes, with the highest activity at 1420 m (124.22 nmol·h-1·g-1). With the increases of altitude, ln(BG): ln(NAG+LAP) showed a decreasing trend. Except for the altitude of 830 m, stoichiometric ratio in all altitudes was the highest in July. The ratio of logarithmic conversion of soil C, N, and P invertase activity was 1:1.25:0.82. Altitude and soil temperature were the main factors affecting soil extracellular enzyme activities. There was a significant positive correlation between soil temperature and BG, NAG, and AP. Enzymatic stoichiometry ln(BG):ln(NAG+LAP) and ln(NAG+LAP):ln(AP) showed significant positive and negative correlations with soil pH, and had a negative and positive relationship with DOC. The ratio of ln(BG):ln(AP) was greatly affected by soil bulk density.


Assuntos
Altitude , Solo , China , Florestas , Nitrogênio/análise , Estações do Ano , Microbiologia do Solo
13.
Onco Targets Ther ; 13: 31-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021252

RESUMO

PURPOSE: Dioscin is a natural product isolated from traditional Chinese medicines and is reported to have antitumor activities against several cancers. In the present study, we aimed to investigate its potency against colorectal cancers, especially the effects on tumor glycolysis, and to elaborate related molecular mechanisms. METHODS: The antitumor activities of dioscin were evaluated by cell proliferation assays and colony formation assays in vitro and the mouse xenograft models in vivo. The effects of dioscin on tumor glycolysis were determined by measuring glucose absorption and lactate generation. Cell apoptosis was detected by cleaved PARP and the activity of caspase-3. Protein overexpression or gene knockdown was conducted to illustrate molecular mechanisms. Immunoprecipitation experiments were applied to identify the interaction between different proteins. RESULTS: Dioscin substantially inhibited colorectal cancer cell proliferation in vitro and suppressed the xenograft growth in nude mice. After dioscin treatment, with the suppression of hexokinase-2, the tumor glycolysis was significantly decreased. Dioscin substantially impaired the interaction between hexokinase-2 and VDAC-1, and induced cell apoptosis. Exogenous overexpression of hexokinase-2 significantly antagonized the glycolysis suppression and apoptosis induction by dioscin. Through enhancing the binding of E3 ligase FBW7 to c-myc, dioscin promoted the ubiquitination of c-myc and gave rise to c-myc degradation, which contributed to the inhibition of hexokinase-2. CONCLUSION: Our studies revealed a novel mechanism by which dioscin exerted its antitumor activity in colorectal cancer, and verified that dioscin or its analog might have potentials for colorectal cancer therapy.

14.
Biomed Pharmacother ; 95: 1574-1579, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28950657

RESUMO

Colorectal cancer (CRC) cells undergo apoptosis in the presence of the small-molecule inhibitor ABT-263 by up-regulating antiapoptotic Bcl-2 family members. However, the resistance to ABT-263 gradually developed in most solid tumors due to its low affinity to Mcl-1. Here, we found the BET-Bromodomain inhibitor JQ1, when combined with ABT-263, synergistically reduced Mcl-1 protein level, induced apoptosis, and decreased cell viability in the CRC HCT-15, HT-29 and SW620 cells. The subsequent mechanism study revealed that a pathway of c-Myc/miR-1271-5p/Noxa/Mcl-1 underlies the synergistic effect of such combination treatment. We discovered that miR-1271-5p, the key mediator for the synergistic effect, is transcriptionally activated by c-Myc, and binds to the 3'-UTR of noxa to inhibit its protein production. The combination treatment of JQ1 and ABT-263 inhibited c-Myc protein level and also c-Myc-driven expression of miR-1271-5p, subsequently increased the protein level of Noxa, and finally promotes the degradation of Mcl-1. Our findings provide an alternative strategy to resolve the resistance during treatment of CRC by JQ1, and also discovered a novel miR-1271-5p-dependent regulatory mechanism for gene expression of noxa.


Assuntos
Compostos de Anilina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Sulfonamidas/uso terapêutico , Compostos de Anilina/farmacologia , Apoptose/efeitos dos fármacos , Azepinas/farmacologia , Sequência de Bases , Linhagem Celular Tumoral , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfonamidas/farmacologia , Triazóis/farmacologia
15.
Oncotarget ; 7(15): 19680-92, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-26967242

RESUMO

Zinc-finger protein X-linked (ZFX) was recently identified as a novel oncoprotein in several human malignancies. In this study, we examined the correlation between ZFX expression and the clinical characteristics of stage II/III CRC patients, as well as the molecular mechanism by which ZFX apparently contributes to CRC tumor progression. Using immunohistochemistry, we detected expression of ZFX in CRC tissues collected from stage II/III patients and determined that its expression correlated with tumor differentiation and stage. Survival analysis indicated that patients with high ZFX expression had poorer overall and disease-free survival. ZFX knockdown in SW620 and SW480 CRC cells significantly inhibited cell proliferation and colony formation, enhanced apoptosis and induced cell cycle arrest. It also enhanced the sensitivity of CRC cells to 5-Fu. In a xenograft model, ZFX knockdown suppressed in vivo CRC tumor growth. Microarray analysis revealed the primary target of ZFX to be DUSP5. Whereas ZFX knockdown increased DUSP5 expression, DUSP5 knockdown rescued ZFX-mediated cell proliferation in ZFX knockdown cells. These findings demonstrate that ZFX promotes CRC progression by suppressing DUSP5 expression and suggest that ZFX is a novel prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Kruppel-Like/biossíntese , Fatores de Transcrição Kruppel-Like/genética , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Células CACO-2 , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/metabolismo , Fluoruracila/farmacologia , Perfilação da Expressão Gênica/métodos , Células HCT116 , Células HT29 , Humanos , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , Transplante Heterólogo
16.
Front Microbiol ; 6: 20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25699023

RESUMO

The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals differed significantly. Firmicutes and Fusobacteria were over-represented whereas Proteobacteria was under-represented in CRC patients. In addition, Lactococcus and Fusobacterium exhibited a relatively higher abundance while Pseudomonas and Escherichia-Shigella was reduced in cancerous tissues compared to adjacent non-cancerous tissues. Meanwhile, the overall microbial structures of proximal and distal colon cancerous tissues were similar; but certain potential pro-oncogenic pathogens were different. These results suggested that the mucosa-associated microbiota is dynamically associated with CRC, which may provide evidences for microbiota-associated diagnostic, prognostic, preventive, and therapeutic strategies for CRC.

17.
World J Gastroenterol ; 21(21): 6550-60, 2015 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-26074693

RESUMO

AIM: To investigate alternative splicing in vascular endothelial growth factor A (VEGFA), amyloid beta precursor protein (APP), and Numb homolog (NUMB) in colorectal cancer (CRC). METHODS: Real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and PCR-restriction fragment length polymorphism analyses were performed to detect the expression of VEGFA, APP, and NUMB mRNA in 20 CRC tissues and matched adjacent normal tissues, as well as their alternative splicing variants. RESULTS: qRT-PCR analysis revealed that the expression of APP, NUMB, and VEGFA165b mRNA were significantly downregulated, while VEGFA mRNA was upregulated, in CRC tissues (all P < 0.05). PCR-restriction fragment length polymorphism analysis revealed that the expression of VEGFA165a/b in CRC tissues was significantly higher than in adjacent normal tissues (P < 0.05). Compared with adjacent normal tissues, the expression of NUMB-PRR(S) in CRC tissues was significantly decreased (P < 0.05), and the expression of NUMB-PRR(L) was increased (P < 0.05). CONCLUSION: Alternative splicing of VEGFA, APP, and NUMB may regulate the development of CRC, and represent new targets for its diagnosis, prognosis, and treatment.


Assuntos
Adenocarcinoma/genética , Processamento Alternativo , Precursor de Proteína beta-Amiloide/genética , Neoplasias Colorretais/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adenocarcinoma/patologia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Mol Med Rep ; 12(4): 6119-27, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26238090

RESUMO

Studies using animal models have demonstrated that probiotics may have a beneficial role in the prevention of colorectal cancer (CRC); however, the underlying mechanism of the beneficial effects of interventional probiotic treatment on gut microbiota has remained elusive. In the present study, pyrosequencing of the V3 region of the 16S rRNA genes was conducted in order to determine the extent to which probiotics alter the microbiota. The observations of the present study indicated that the microbial structure of cancerous tissue differed significantly from that of healthy individuals and that the CRC microbiota exhibited lower diversity. It was indicated that interventional treatment with probiotics increased the density and diversity of mucosal microbes, and altered the mucosa­associated microbiota. Pyrosequencing demonstrated that probiotics significantly reduced (5­fold) the abundance of a bacterial taxon assigned to the genus Fusobacterium, which had been previously suggested to be a contributing factor to increase tumorigenesis. Accordingly, interventional probiotic therapy is suggested to be able to improve the composition of the mucosal microbial flora and significantly reduce the abundance of mucosa-associated pathogens in patients with CRC.


Assuntos
Neoplasias Colorretais/terapia , Microbioma Gastrointestinal , Mucosa Intestinal/microbiologia , Probióticos/administração & dosagem , Adulto , Idoso , Índice de Massa Corporal , Neoplasias Colorretais/microbiologia , DNA Bacteriano/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
World J Gastroenterol ; 20(3): 738-44, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24574747

RESUMO

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differentiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS.


Assuntos
Doenças Retais/diagnóstico , Doenças Retais/terapia , Reto , Úlcera/diagnóstico , Úlcera/terapia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Doenças Retais/complicações , Doenças Retais/fisiopatologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/fisiopatologia , Reto/cirurgia , Síndrome , Resultado do Tratamento , Úlcera/complicações , Úlcera/fisiopatologia
20.
PLoS One ; 9(6): e90849, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603888

RESUMO

Recent reports have suggested that multiple factors such as host genetics, environment and diet can promote the progression of healthy mucosa towards sporadic colorectal carcinoma. Accumulating evidence has additionally associated intestinal bacteria with disease initiation and progression. In order to examine and analyze the composition of gut microbiota in the absence of confounding influences, we have established an animal model of 1, 2-dimethylhydrazine (DMH)-induced colon cancer. Using this model, we have performed pyrosequencing of the V3 region of the 16S rRNA genes in this study to determine the diversity and breadth of the intestinal microbial species. Our findings indicate that the microbial composition of the intestinal lumen differs significantly between control and tumor groups. The abundance of Firmicutes was elevated whereas the abundance of Bacteroidetes and Spirochetes was reduced in the lumen of CRC rats. Fusobacteria was not detected in any of the healthy rats and there was no significant difference in observed Proteobacteria species when comparing the bacterial communities between our two groups. Interestingly, the abundance of Proteobacteria was higher in CRC rats. At the genus level, Bacteroides exhibited a relatively higher abundance in CRC rats compared to controls (14.92% vs. 9.22%, p<0.001). Meanwhile, Prevotella (55.22% vs. 26.19%), Lactobacillus (3.71% vs. 2.32%) and Treponema (3.04% vs. 2.43%), were found to be significantly more abundant in healthy rats than CRC rats (p<0.001, respectively). We also demonstrate a significant reduction of butyrate-producing bacteria such as Roseburia and Eubacterium in the gut microbiota of CRC rats. Furthermore, a significant increase in Desulfovibrio, Erysipelotrichaceae and Fusobacterium was also observed in the tumor group. A decrease in probiotic species such as Ruminococcus and Lactobacillus was likewise observed in the tumor group. Collectively, we can conclude that a significant difference in intestinal bacterial flora exists between healthy rats and CRC rats.


Assuntos
Colo/microbiologia , Neoplasias Colorretais/microbiologia , Microbiota , Animais , Bacteroides/genética , Neoplasias Colorretais/induzido quimicamente , Genes Bacterianos , Lactobacillus , Masculino , Microbiota/genética , Tipagem Molecular , Prevotella/genética , Proteobactérias/genética , Ratos Wistar , Análise de Sequência de DNA , Treponema/genética
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