Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
1.
J Transl Med ; 22(1): 369, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637862

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Fator de Transcrição STAT3 , Humanos , Camundongos , Animais , Colite Ulcerativa/terapia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ácidos Graxos Voláteis/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Modelos Animais de Doenças , Inflamação , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Colo , Proteína Forkhead Box O3/metabolismo
2.
J Immunother Cancer ; 11(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37597850

RESUMO

BACKGROUND: Immunotherapy, including adoptive cell therapy (ACT) and immune checkpoint inhibitors (ICIs), has a limited effect in most patients with colorectal cancer (CRC), and the efficacy is further limited in patients with liver metastasis. Lack of antitumor lymphocyte infiltration could be a major cause, and there remains an urgent need for more potent and safer therapies for CRC. METHODS: In this study, the antitumoral synergism of low molecular weight heparin (LMWH) combined with immunotherapy in the microsatellite stable (MSS) highly aggressive murine model of CRC was fully evaluated. RESULTS: Dual LMWH and ACT objectively mediated the stagnation of tumor growth and inhibition of liver metastasis, neither LMWH nor ACT alone had any antitumoral activity on them. The combination of LMWH and ACT obviously increased the infiltration of intratumor CD8+ T cells, as revealed by multiplex immunohistochemistry, purified CD8+ T-cell transfer assay, and IVIM in vivo imaging. Mechanistically, evaluation of changes in the tumor microenvironment revealed that LMWH improved tumor vascular normalization and facilitated the trafficking of activated CD8+ T cells into tumors. Similarly, LMWH combined with anti-programmed cell death protein 1 (PD-1) therapy provided superior antitumor activity as compared with the single PD-1 blockade in murine CT26 tumor models. CONCLUSIONS: LMWH could enhance ACT and ICIs-based immunotherapy by increasing lymphocyte infiltration into tumors, especially cytotoxic CD8+ T cells. These results indicate that combining LMWH with an immunotherapy strategy presents a promising and safe approach for CRC treatment, especially in MSS tumors.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias Colorretais/tratamento farmacológico , Microambiente Tumoral
3.
J Gastroenterol Hepatol ; 38(11): 2006-2017, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37608570

RESUMO

BACKGROUND AND AIM: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y-box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. METHODS: We studied the characteristics of UXT-V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT-V1 in the colonic epithelium was investigated using lentivirus-mediated shRNA in vitro and ex vivo. Through endogenous Co-immunoprecipitation and LC-MS/MS, we identified ZONAB as a UXT-V1-interactive protein. RESULTS: Herein, we report that UXT-V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT-V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT-V1 in NCM-460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT-V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT-V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation-related genes, including AML1 and KLF4. CONCLUSION: Taken together, our study reveals a potential role of UXT-V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Mucosa Intestinal/metabolismo , Diferenciação Celular/genética , Células Epiteliais/metabolismo , Isoformas de Proteínas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Chaperonas Moleculares/metabolismo
4.
Plants (Basel) ; 12(14)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37514342

RESUMO

Amendments with activators or microorganisms to enhance phytoremediation in toxic-metal-polluted soils have been widely studied. In this research, the production of indoleacetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase by phosphate-solubilizing bacteria was investigated during a pure culture experiment. Pot experiments were performed using Cd-polluted soil with the following treatments: control (CK, only ultrapure water), orange-peel-based activator (OG), and a combination of phosphate-solubilizing bacteria (Acinetobacter pitti) and OG (APOG). Ryegrass plant height and fresh weight, Cd content in ryegrass, total and available Cd soil content, soil enzyme activity, and soil bacterial diversity were determined in this work. The findings showed that the height of ryegrass in OG and APOG increased by 14.78% and 21.23%. In the APOG group, a decreased ratio of Cd was 3.37 times that of CK, and the bioconcentration factor was 1.28 times that of CK. The neutral phosphatase activity of APOG was 1.33 times that of CK and catalase activity was 1.95 times that of CK. The activity of urease was increased by 35.48%. APOG increased the abundance of beneficial bacteria and Proteobacteria was the dominant bacterium, accounting for 57.38% in APOG. Redundancy analysis (RDA) showed that nutrient elements were conducive to the propagation of the dominant bacteria, the secretion of enzymes, and the extraction rate of Cd in the soil. The possible enhancement mechanism of phytoremediation of cadmium by A. pitti combined with OG was that, on the one hand, APOG increased soil nutrient elements and enzyme activities promoted the growth of ryegrass. On the other hand, APOG activated Cd and boosted the movement of Cd from soil to ryegrass. This research offers insight for the combination of phosphate-solubilizing bacteria with an orange-peel-based activator to improve phytoremediation of Cd-contaminated soils and also provides a new way for the resource utilization of fruit residue.

5.
Discov Nano ; 18(1): 94, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37477789

RESUMO

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.

6.
Bioorg Chem ; 126: 105919, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35667254

RESUMO

As a promising targeted drug delivery system, aptamer-drug conjugates (ApDCs) can specifically bind with cognate molecular targets for improving therapeutic efficacy and reducing drug toxicity. However, current ApDC strategies suffer from problems caused by the complicated synthesis, relatively high cost, low controllability of drug binding sites and loading ratio. To solve these difficulties, we have designed and synthesized an artificial pharmaceutical solid-phase module of Combretastatin A-4 (CA-4), in which an inactive ingredient was selected as bonding moiety to incorporate with solid phase functionalities. Through solid-phase synthesis technology, this module was automatically and efficiently conjugated with an aptamer at predesigned positions. Biological studies revealed that these ApDCs can not only maintain excellent specific recognition ability, but also possess definite cytotoxicity against tumor cells.


Assuntos
Aptâmeros de Nucleotídeos , Aptâmeros de Nucleotídeos/química , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Técnicas de Síntese em Fase Sólida
7.
Altern Ther Health Med ; 28(6): 118-123, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35687706

RESUMO

Context: Early diagnosis and early treatment of cornual pregnancy are very important. Conservative treatment before rupture can greatly reduce the patient's trauma. It's very important to choose a treatment method for cornual pregnancy with a high level of effectiveness, few adverse reactions, and no effects on fertility. Objective: The study intended to compare the clinical efficacy of different treatments for unruptured cornual pregnancy to find a safe, effective, minimally invasive treatment for unruptured cornual pregnancy that has few side effects and doesn't affect fertility. Design: The research team retrospectively collected the clinical data of patients to analyze the benefits of treatments for cornual pregnancy. Setting: The study took place in the Department of Obstetrics and Gynecology at the Wuhan Third Hospital in Wuhan, Hubei Province, China. Participants: Participants were 61 patients with an unruptured cornual pregnancy who had been admitted to the hospital between September 2002 and May 2012. Intervention: Participants were divided into four groups according to the treatment they received: (1) 20 patients who had been orally administered mifepristone combined with misoprostol and received uterine curettage were included in the drug abortion + curettage group (D group); (2) 16 patients who had received ultrasound-guided uterine aspiration were included in the uterine aspiration group (U group); (3) 15 patients who had received methotrexate (MTX) chemotherapy were included in the chemotherapy group (C group); and (4) 10 patients who had received ultrasound-guided hysteroscope operation were included in the hysteroscope operation group (H group). Outcome Measures: Adverse reactions and the decrease in participants' blood ß-HCG were recorded in detail. The participants were followed up for two months. Results: Of the 61 participants, 12 underwent surgery after failed conservative treatment, one in the D group, four in the U group, three in the C group, and four in the H group. No significant difference existed in the baseline data among the four groups. The decline rates of ß-HCG at seven days after treatment and the treatment success rates of participants in the D group were significantly higher than those in the U group, the C group, and the H group (all P < .05). The time at which the ß-HCG turned negative and the average hospital stays weren't significantly different among the four groups. Conclusions: The current study found that oral administration of mifepristone, combined with misoprostol, plus uterine curettage was superior to the other three methods in treatment of unruptured cornual pregnancy. The drug abortion + curettage treatment was found to be a safe, effective, minimally invasive treatment for unruptured cornual pregnancy, which has few side effects and doesn't affect fertility.


Assuntos
Misoprostol , Gravidez Cornual , Tratamento Conservador , Feminino , Humanos , Mifepristona/uso terapêutico , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
8.
Dis Markers ; 2022: 9461444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251378

RESUMO

PURPOSE: In this study, we evaluated the effect of Tiaojing Cuyun Recipe (TJCYR) on embryo implantation dysfunction- (EID-) induced damage of endometrial receptivity in mice and investigated the mechanisms underlying the effect. METHODS: The main compounds of TJCYR were identified by high-performance liquid chromatography (HPLC). One hundred and twenty pregnant mice were randomly divided into six groups: control, EID only, progesterone (Prog)+EID, TJCYR-low-dose+EID, TJCYR-medium-dose+EID, and TJCYR-high-dose+EID. Mifepristone was injected to make the EID model. On the fourth day of pregnancy, serum was obtained to analyze hormone level by radioimmunoassay, the uterus was collected to analyze morphology by hematoxylin and eosin (H&E) and scanning electron microscopy (SEM), and a combination of immunofluorescence and Western blot was used to identify the related proteins. On the eighth day of pregnancy, the mice were sacrificed and the number of uterus-implanted blastocysts was counted. RESULTS: Treatment with TJCYR significantly improved the number of implanted sites, the number of well-developed pinopodes, and microvascular formation in the mice. Moreover, TJCYR significantly activated PI3K/Akt/eNOS signaling pathways to promote angiogenesis, resulting in significantly improved endometrial receptivity and fertility outcomes when compared to the model group. CONCLUSION: These findings demonstrate that TJCYR was able to protect embryo implantation of EID mice due to TJCYR-mediated improvement in endometrial receptivity by promoting endometrial angiogenesis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Implantação do Embrião/efeitos dos fármacos , Endométrio/metabolismo , Resultado da Gravidez , Transdução de Sinais , Animais , Feminino , Camundongos , Mifepristona/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Progesterona/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
BMC Palliat Care ; 21(1): 35, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287635

RESUMO

BACKGROUND: Despite the increasing longevity of the world's population, with an unprecedented rise in the number of people who need palliative care (PC), there has been sparse research regarding palliative care for older people, especially when it comes to comparison of PC between healthcare systems and cultures. The aim of this systematic scoping review was to identify the characteristics of the body of literature and to examine the knowledge gaps concerning PC research for older people (> 60 years) in two healthcare systems and cultures, mainland China and Sweden. METHODS: The guidelines PRISMA (Preferred Reporting Items for Systematic Reviews), and PICOS (Patient/population, Intervention, Comparison/control, and Outcome) were used. Empirical studies on patients 60 years or older, next of kin or staff participating in a palliative care intervention or setting were included. They were conducted in mainland China or in Sweden during 2007-2019, were published in English and were extracted from seven databases: Embase, PubMed, Scopus, Cinahl, PsycInfo, Academic Search Complete and Cochrane Library. Two independent researchers conducted the selection of studies, data extraction and methodological evaluation. Any disagreements were resolved in consultation with a third researcher. The analysis was manifest directed content analysis based on PICOS domains. RESULTS: Of the 15 studies, four were from mainland China and 11 from Sweden. Both countries included older patients with cancer but also other end-stage diseases such as heart failure and dementia. The studies differed in design, method and the content of the interventions. The study in China based on traditional Chinese medicine concerns traditional Chinese folk music. The six qualitative studies from Sweden were evaluations of five interventions. CONCLUSIONS: Despite the high age of the participating patients, there was no focus on an ageing perspective concerning palliative care. To adapt to the changes taking place in most societies, future research should have increased focus on older persons' need for palliative care and should take account of issues concerning research ethics, ethnicity and culture. REGISTERED IN PROSPERO: CRD42020078685 , available from.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Idoso , Idoso de 80 Anos ou mais , China , Humanos , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Suécia
10.
Bioresour Technol ; 345: 126530, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34896534

RESUMO

The succession of bacterial communities and their function, and the core microorganisms for water soluble organic carbon (WSC) and organic matter (OM) changes during agricultural waste composting with addition of iron oxide nanomaterials (FeONPs, Fe2O3 NPs and Fe3O4 NPs) were investigated. Moreover, driving factors for bacterial composition and metabolism were analyzed. Results showed that FeONPs treatments increased the relative abundance of thermophilic microorganisms for OM degradation. Most of the core genera were responsible for decomposition of OM and synthesis of WSC. Additionally, FeONPs promoted the metabolism of amino acids. The most significant factors for dominant genera in control, Fe2O3 NPs and Fe3O4 NPs group were moisture (62.1%), moisture (62.0%) and OM (58.2%), respectively. For metabolism, the most significant factors in control, Fe2O3 NPs and Fe3O4 NPs group were temperature (57.2%), NO3--N (60.5%), NO3--N (62.6%), respectively. The relationships between compost properties, bacterial community and metabolism were changed by FeONPs.


Assuntos
Compostagem , Agricultura , Bactérias , Nanopartículas Magnéticas de Óxido de Ferro , Solo
11.
Horm Metab Res ; 53(11): 738-745, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34740275

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metformin is introduced for treatment of women with PCOS, and the beneficial effects of exercise in women with PCOS are found for a range of outcomes. Our aim is to compare the effects of metformin plus exercise with exercise intervention in PCOS on clinical, anthropometric, metabolic, and psychological parameters. MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. Nine studies were considered eligible for inclusion. The meta-analysis reveals that metformin offers additive benefits to exercise, leading to modest improvements in menstrual cycles, hyperandrogenism, and abdominal fat.


Assuntos
Terapia por Exercício , Exercício Físico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/terapia , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia
12.
Chem Asian J ; 16(18): 2618-2621, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34342941

RESUMO

Visible-light-driven sulfonylation/cyclization of N-methacryloyl-2-phenylbenzoimidazoles has been successfully developed. Using commercially available sulfonyl chloride as sulfonylation reagent, a wide range of sulfonylated benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-ones with potential antitumor activity were provided in acceptable to excellent yields. This method has the advantages of mild reaction conditions and outstanding functional group tolerance, and provides a new strategy for the development of potential antitumor lead compounds.

13.
Medicine (Baltimore) ; 100(22): e26194, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087888

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) can work as microRNA (miRNA) sponges through a competitive endogenous RNA (ceRNA) mechanism. LncRNAs and miRNAs are important components of competitive endogenous binding, and their expression imbalance in hepatocellular carcinoma (HCC) is closely related to tumor development, diagnosis, and prognosis. This study explored the potential impact of the ceRNA regulatory network in HCC on the prognosis of HCC patients. METHODS: We thoroughly researched the differential expression profiles of lncRNAs, miRNAs, and mRNAs from 2 HCC Gene Expression Omnibus datasets (GSE98269 and GSE60502). Then, a dysregulated ceRNA network was constructed by bioinformatics. In addition, hub genes in the ceRNA network were screened by Cytoscape, these hub genes functional analysis was performed by gene set enrichment analysis, and the expression of these hub genes in tumors and their correlation with patient prognosis were verified with Gene Expression Profiling Interactive Analysis. RESULTS: A ceRNA network was successfully constructed in this study including 4 differentially expressed (DE) lncRNAs, 7 DEmiRNAs, and 166 DEmRNAs. Importantly, 4 core genes (CCNA2, CHEK1, FOXM1, and MCM2) that were significantly associated with HCC prognosis were identified. CONCLUSIONS: Our study provides comprehensive and meaningful insights into HCC tumorigenesis and the underlying molecular mechanisms of ceRNA. Furthermore, the specific ceRNAs can be further used as potential therapeutic targets and prognostic biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Adulto , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinoma Hepatocelular/diagnóstico , Quinase 1 do Ponto de Checagem/genética , Ciclina A2/genética , Feminino , Proteína Forkhead Box M1/genética , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Prognóstico , RNA Mensageiro/genética , Motivos de Ligação ao RNA/genética
14.
PLoS One ; 15(10): e0238836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095797

RESUMO

Recently, the Cancer Genome Atlas and Asian Cancer Research Group propose two new classifications system of gastric cancer by using multi-platforms of molecular analyses. However, these highly complicated and cost technologies have not yet been translated into full clinical utility. In addition, the clinicians are expected to gain more guidance of treatment for different molecular subtypes. In this study, we developed a panel of gastric cancer patients in population from Southern China using commercially accessible TMA and immunohistochemical technology. A cohort of 259 GC patients was classified into 4 subtypes on the basis of expression of mismatch repair proteins (PMS2, MLH1, MSH2, and MSH6), E-cadherin and p21 protein. We observed that the subtypes presented distinct prognosis. dMMR-like subtype was associated with the best prognosis, and E-cadherin-a subtype was associated with the worst prognosis. Patients with p21-High and p21-Ligh subtypes had intermediate overall survival. In multivariate analysis, the dMMR-like subtype remained an independent prediction power for overall survival in the model. We described a molecular classification of gastric cancers using clinically applicable assay. The biological relevance of the four subtypes was illustrated by significant differences in prognosis. Our molecular classification provided an effective and inexpensive screening tool for improving prognostic models. Nevertheless, our study should be considered preliminary and carries a limited predictive value as a single-center retrospective study.


Assuntos
Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , China , Estudos de Coortes , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise Serial de Tecidos
15.
Exp Ther Med ; 19(4): 2650-2660, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256746

RESUMO

Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

16.
Cancer Lett ; 481: 15-23, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184145

RESUMO

Chemotherapy failure is a major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. Inhibition of autophagy is a promising strategy to augment the cytotoxicity of chemotherapeutic agents. We identified prodigiosin, a secondary metabolite produced by various bacteria, as a novel autophagy inhibitor that interfered with the autophagic flux in CRC cells by blocking autophagosome-lysosome fusion and lysosomal cathepsin maturation, resulting in the accumulation of LC3B-II and SQSTM. Suppression of autophagy by prodigiosin sensitized the CRC cells to 5-fluorouracil (5-Fu) in vitro, and the combination treatment markedly reduced cancer cell viability partly via caspase-dependent apoptosis. Furthermore, prodigiosin and 5-Fu synergistically inhibited CRC xenograft growth in vivo without any adverse effects. In conclusion, prodigiosin inhibits late stage autophagy and sensitizes tumor cells to 5-Fu, indicating its therapeutic potential in CRC.


Assuntos
Autofagossomos/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/farmacologia , Lisossomos/efeitos dos fármacos , Prodigiosina/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Células HCT116 , Células HT29 , Humanos , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo
17.
Cell Oncol (Dordr) ; 43(3): 409-420, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32166582

RESUMO

PURPOSE: DCBLD2 expression dysregulation has been reported in several types of human cancer. As yet, however, the role of DCBLD2 in colorectal cancer (CRC) is not known. METHODS: CRC tissues were obtained from patients undergoing surgery from February 2009 to May 2014 (n = 90). Tissue microarray construction and immunohistochemistry were carried out to determine DCBLD2 expression. In vivo studies were performed in 4-week-old BALB/c nude mice. In vitro studies were conducted using CRC-derived HT29 and HCT116 cell lines. RESULTS: DCBLD2 expression was found to be significantly increased in CRC tissues compared to adjacent normal tissues (p < 0.001). In addition, we found that DCBLD2 expression was positively correlated with the stage of the disease, the degree of differentiation and vascular invasion. High DCBLD2 expression was significantly associated with a poor overall survival. In vitro, DCBLD2 expression downregulation significantly reduced CRC cell proliferation and invasion. In a mouse xenograft model, DCBLD2 expression downregulation reduced lung metastasis and increased overall survival. Gene set enrichment analysis (GSEA) revealed that DCBLD2 overexpression induces epithelial-mesenchymal transition (EMT) and activates the JAK/STAT3 pathway. CONCLUSIONS: We found that high DCBLD2 expression correlated with a poor clinical outcome, as well as tumorigenesis, invasion and metastasis of CRC cells. DCBLD2 may serve as a prognostic biomarker and a novel therapeutic target for CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Proteínas de Membrana/genética , Regulação para Cima/genética , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Oncogenes , Prognóstico , Transdução de Sinais , Análise de Sobrevida
18.
J Inorg Biochem ; 206: 111022, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32070916

RESUMO

Six novel organotin phosphonate complexes, [(Me3Sn)4(HL1)4]n1, [(Me3Sn)2(HL2)2]n2, [(Me3Sn)2L3(H2O)]n3, [(Ph3Sn)(HL1)]64, [(Ph3Sn)2L2]n5 and [(Ph3Sn)2L3]66, derived from phosphonic acid ligands [NaHL1 = 1-C10H7OPO2(OH)Na, H2L2 = 1-C10H7PO(OH)2, H2L3 = 2-C10H7PO(OH)2], have been synthesized and characterized by elemental analysis, FT-IR, NMR (1H, 13C, 31P and 119Sn) spectroscopy and X-ray crystallography. The structural analysis reveals that complexes 1 and 5 display 1D infinite zig-zag chain structures, and complex 2 shows 1D right-handed helical chain structure, while complex 3 displays 1D left-handed helical chain structure. Complexes 4 and 6 are 24-membered macrocyclic rings interconnected by P, O and Sn atoms. Additionally, the molecules of complexes 1 and 3 are further linked through intermolecular π···π and O-H···O interaction into supramolecular structures, respectively. Furthermore, we preliminarily estimated in vitro cytostatic activity of complexes 1-6 against the human cervix tumor cells (HeLa), human hepatocellular carcinoma cells (HepG-2) and human normal breast cells (HBL-100). Importantly, the anti-proliferative properties and possible pathway of complex 6 are investigated, and the results demonstrate that complex 6 could induce apoptotic cell death via an overload of intracellular reactive oxygen species (ROS) levels and the dysfunctional depolarization of mitochondrial membranes.


Assuntos
Citostáticos/química , Citostáticos/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Ácidos Fosforosos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Citostáticos/síntese química , Feminino , Células HeLa , Humanos , Ligantes , Neoplasias Hepáticas/patologia , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Ácidos Fosforosos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Estanho/química , Neoplasias do Colo do Útero/patologia
19.
J Hazard Mater ; 391: 122057, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32044627

RESUMO

The nano zero-valent iron sludge-based biochar (nZVI-SBC) was prepared in this study to eliminate Sb(III) from aqueous solutions, which was characterized by BET, SEM, XRD, TEM, FTIR, XPS. Our results proved that the incorporated nZVI on SBC matrix could significantly enhance eliminating Sb(III), and the max-adsorption capacity (160.40 mg g-1) can be achieved at pH = 4.8 ± 0.2 and temperature of 298 K. The effect of co-existing anions and natural organic matters on the Sb(III) adsorption efficiencies were systematically investigated. The surface complexation is the possible adsorption mechanisms by FTIR and XPS. Furthermore, mechanistic investigation revealed that •OH and hydroquinone radical (H-SQ•-) could be the primary oxidants for the transformation of Sb(III) under oxic conditions, while 9,10-phenanthrene quinone radical (P-SQ•-) were responsible under anoxic conditions. Thus, the enhanced elimination of Sb(III) from aqueous solution was ascribed to the combined adsorption and oxidation. The potential engineering application of nZVI-SBC can be proved through three actual water matrix experiments, including lake water, river water and acid mine drainage. Our present findings proved that nZVI-SBC could be a potential adsorbent, given the excellent performance in the adsorption processes, as well as the toxicity alleviating ability and economic advantages, especially under sub-surface water.


Assuntos
Antimônio/química , Carvão Vegetal/química , Ferro/química , Nanocompostos/química , Espécies Reativas de Oxigênio/química , Esgotos/química , Poluentes Químicos da Água/química , Adsorção , Resíduos Industriais , Lagos , Mineração , Oxirredução , Rios
20.
J Hazard Mater ; 389: 122091, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31972529

RESUMO

Roxarsone is a phenyl-substituted arsonic acid comprising both arsenate and benzene rings. Few adsorbents are designed for the effective capture of both the organic and inorganic moieties of ROX molecules. Herein, nano zerovalent iron (nZVI) particles were incorporated on the surface of sludge-based biochar (SBC) to fabricate a dual-affinity sorbent that attracts both the arsenate and benzene rings of ROX. The incorporation of nZVI particles significantly increased the binding affinity and sorption capacity for ROX molecules compared to pristine SBC and pure nZVI. The enhanced elimination of ROX molecules was ascribed to synergetic adsorption and degradation reactions, through π-π* electron donor/acceptor interactions, H-bonding, and As-O-Fe coordination. Among these, the predominate adsorption force was As-O-Fe coordination. During the sorption process, some ROX molecules were decomposed into inorganic arsenic and organic metabolites by the reactive oxygen species (ROS) generated during the early stages of the reaction. The degradation pathways of ROX were proposed according to the oxidation intermediates. This work provides a theoretical and experimental basis for the design of adsorbents according to the structure of the target pollutant.


Assuntos
Carvão Vegetal/química , Ferro/química , Nanocompostos/química , Roxarsona/isolamento & purificação , Esgotos/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Recuperação e Remediação Ambiental/métodos , Concentração de Íons de Hidrogênio , Oxirredução , Roxarsona/química , Poluentes do Solo/química , Poluentes do Solo/isolamento & purificação , Poluentes Químicos da Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA