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1.
J Cancer Res Clin Oncol ; 150(6): 306, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879666

RESUMO

BACKGROUND: Metastasis is a main cause of death from ovarian cancer (OC). Identifying key markers involved in OC metastasis can aid in the effective detection of early postoperative metastasis. However, the role of FCGR1A in OC metastasis has yet to be fully established. A genome-wide CRISPR/Cas9-based screening system was used to identify regulatory factors involved in metastasis. METHODS: The expression of FCGR1A and LSP1 in ovarian cancer cell lines was examined by quantitative real-time polymerase chain reaction (qRT‒PCR). The functions of FCGR1A and LSP1 in OC cell migration, invasion and proliferation were determined using wound healing, Transwell invasion and CKK-8 assays. A transcription-activated library was used to identify the potential downstream genes of FCGR1A. FCGR1A expression was detected by immunohistochemistry and the immunity risk score (IRS) scores were calculated. RESULTS: FCGR1A was upregulated in OC cells compared with normal ovarian cells. Downregulation of FCGR1A inhibited metastasis, proliferation and epithelial-mesenchymal transition (EMT) progression in OC cells in vitro and intraperitoneal metastasis in vivo. Moreover, downregulation of FCGR1A was accompanied by decreased LSP1 expression. Overexpression of LSP1 partially reversed the tumor suppressive effect of FCGR1A downregulation. Higher FCGR1A expression was related to metastasis, higher grade, higher stage, and lymph node metastasis in OC. Survival analysis suggested that the group with higher FCGR1A expression had a lower tumor-free survival rate and a lower overall survival rate than did the group with low FCGR1A expression. CONCLUSIONS: FCGR1A enhances OC metastasis by regulating LSP1, and FCGR1A is associated with poor prognosis, suggesting that FCGR1A is a potential predictive factor for detecting early postoperative metastasis.


Assuntos
Sistemas CRISPR-Cas , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Camundongos , Animais , Linhagem Celular Tumoral , Receptores de IgG/genética , Receptores de IgG/metabolismo , Proliferação de Células/genética , Metástase Neoplásica , Camundongos Nus , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Camundongos Endogâmicos BALB C , Proteínas dos Microfilamentos
2.
J Obstet Gynaecol Res ; 50(4): 671-681, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38178729

RESUMO

AIM: To characterize the effects of CO2 laser treatment and estrogen treatment on vaginal microbiota in patients with genitourinary syndrome of menopause (GSM). METHODS: Sixty-four patients with genitourinary syndrome were divided into the estrogen group, the CO2 laser group, and the control group. The control group did not receive any treatment. Vaginal mucosa was collected after 3 and 12 months of treatment. The former was used for 16S rRNA sequencing, and the latter was used for pathological evaluation. Vaginal health and voiding function were assessed using the vaginal health index (VHI) scale and the UDI-6 scale at 3 and 12 months after treatment. RESULTS: The results showed that both treatments reduced alpha diversity in the vaginal flora. Additionally, the abundance of 65 genera differed significantly between the treatment and control groups, with an increase in potentially beneficial bacteria such as Lactobacillus, IheB3_7, Mycoplasma urealyticum, and Streptococcus. In addition, the VHI and UDI-6 scores improved in both treatment groups compared to the control group after 3 months. Whereas VHI and UDI-6 scores were close to baseline in the estrogen group, and remained significantly improved in the CO2 laser group after 12 months. Pathological results showed that both methods improved the vaginal health status of patients with GSM after 12 months of treatment. However, the CO2 group exhibited a more significant increase in type III collagen. CONCLUSIONS: Both CO2 laser and estrogen therapies can regulate the vaginal flora imbalance of GSM and improve the corresponding symptoms. However, the long-term efficacy of CO2 laser therapy is superior compared to estrogen therapy.


Assuntos
Doenças Urogenitais Femininas , Terapia a Laser , Lasers de Gás , Feminino , Humanos , Menopausa , Dióxido de Carbono , RNA Ribossômico 16S , Doenças Urogenitais Femininas/tratamento farmacológico , Vagina/patologia , Estrogênios/farmacologia , Terapia a Laser/métodos , Lasers de Gás/uso terapêutico , Resultado do Tratamento
3.
Anim Biosci ; 37(2): 161-172, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37946437

RESUMO

For sustainable development, better performance, and less gas pollution during rumen fermentation, there is a need to find a green and safe feed additive for ruminants. Cysteamine (CS) is a biological compound naturally produced in mammalian cells. It is widely used as a growth promoter in ruminants because of its ability to control hormone secretions. It mainly controls the circulating concentration of somatostatin and enhances growth hormone production, leading to improved growth performance. CS modulates the rumen fermentation process in a way beneficial for the animals and environment, leading to less methane production and nutrients loss. Another beneficial effect of using CS is that it improves the availability of nutrients to the animals and enhances their absorption. CS also works as an antioxidant and protects the cells from oxidative damage. In addition, CS has no adverse effects on bacterial and fungal alpha diversity in ruminants. Dietary supplementation of CS enhances the population of beneficial microorganisms. Still, no data is available on the use of CS on reproductive performance in ruminants, so there is a need to evaluate the effects of using CS in breeding animals for an extended period. In this review, the action mode of CS was updated according to recently published data to highlight the beneficial effects of using CS in ruminants.

4.
Chem Sci ; 13(42): 12567-12576, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36382282

RESUMO

Nearly 30% of human proteins have tandem repeating sequences. Structural understanding of the terminal repeats is well-established for many repeat proteins with the common α-helix and ß-sheet foldings. By contrast, the sequence-structure interplay of the terminal repeats of the collagen triple-helix remains to be fully explored. As the most abundant human repeat protein and the most prevalent structural component of the extracellular matrix, collagen features a hallmark triple-helix formed by three supercoiled polypeptide chains of long repeating sequences of the Gly-X-Y triplets. Here, with CD characterization of 28 collagen-mimetic peptides (CMPs) featuring various terminal motifs, as well as DSC measurements, crystal structure analysis, and computational simulations, we show that CMPs only differing in terminal repeat may have distinct end structures and stabilities. We reveal that the cross-chain hydrogen bonding mediated by the terminal repeat is key to maintaining the triple-helix's end structure, and that disruption of it with a single amide to carboxylate substitution can lead to destabilization as drastic as 19 °C. We further demonstrate that the terminal repeat also impacts how strong the CMP strands form hybrid triple-helices with unfolded natural collagen chains in tissue. Our findings provide a spatial profile of hydrogen bonding within the CMP triple-helix, marking a critical guideline for future crystallographic or NMR studies of collagen, and algorithms for predicting triple-helix stability, as well as peptide-based collagen assemblies and materials. This study will also inspire new understanding of the sequence-structure relationship of many other complex structural proteins with repeating sequences.

5.
Medicine (Baltimore) ; 101(18): e29074, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35550459

RESUMO

BACKGROUND: There are still controversies about the optimal anesthesia protocol for patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). The aim of this study was to explore the effect of supraglottic airway device (SAD) versus endotracheal intubation (EI) general anesthesia on clinical and angiographic outcomes in patients with AIS undergoing MT. METHODS: One hundred sixteen patients with large-vessel occlusion stroke were randomized to receive either SAD or EI general anesthesia. The primary outcome was the rate of occurrence of >20% fall in mean arterial pressure (MAP). Secondary outcomes included hemodynamics, successful recanalization, time metrics, satisfaction score of neurointerventionalist, number of passes performed, the conversion rate from SAD to EI, the National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score before and 24 hours after surgery, length of stay in the stroke unit and hospital, complications and functional independence at discharge, and 90 days after stroke. RESULTS: Both the lowest systolic blood pressure and lowest diastolic blood pressure were significantly lower in the EI group (P = .001). The consumption of vasoactive agents, the occurrence of >20% reduction in MAP and time spent with >20% fall in MAP were significantly higher in the EI group (P < .05). Compared with the EI group, the time for door-to-puncture was significantly shorter in the SAD group (P = .015). There were no significant differences with respect to puncture-to-reperfusion time, number of passes performed, rates of successful recanalization, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score 24 hours after surgery. The satisfaction score of neurointerventionalist was significantly lower in the EI group (P = .043). Conversion rate from SAD to EI was 7.41%. There were no significant differences with respect to complications, mortality, and mean Modified Rankin Scale scores both at discharge and 90-day after stroke. However, length of stroke unit and hospital stays were significantly shorter in the SAD group (P < .05). CONCLUSION: AIS patients undergoing MT with SAD general anesthesia led to more stable hemodynamics, higher satisfaction score of neurointerventionalist, shorter door-to-puncture time, length of stroke unit, and hospital stay. However, there were no significant differences between the 2 groups on the angiographic and functional outcomes both at discharge and 90 days after stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Anestesia Geral/efeitos adversos , Isquemia Encefálica/complicações , Humanos , Intubação Intratraqueal/efeitos adversos , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
6.
J Healthc Eng ; 2022: 1635446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35388328

RESUMO

Coronary heart disease is a common disease threatening human health. In recent years, the incidence of coronary heart disease in China has only increased. It is the most common type of organ disease caused by coronary atherosclerosis, which is observed in the aorta, carotid artery, and femoral artery. The main clinical treatments for coronary heart disease include coronary artery bypass grafting and drug treatment. To investigate the relationship of serum adipocytokine C1q/tumor necrosis factor-related protein 9 (CTRP9), amyloid A (SAA), and plasma homocysteine (Hcy) with coronary artery plaque characteristics in patients with coronary heart disease. Overall, 143 patients with coronary heart disease admitted to our hospital are selected as research participants. The proportion of plaque necrosis core volume is higher in group A than in group B, and the differences are statistically significant (P < 0.05). In group A, necrotic core volume percentage is negatively correlated with CTRP9 levels and positively correlated with SAA and Hcy levels (P < 0.05). Logistic regression analysis revealed that increased systolic blood pressure, increased number of coronary artery lesions, decreased CTRP9 levels, and increased Hcy levels are independent risk factors for thin fibrous cap atherosclerosis in patients with coronary heart disease (P < 0.05). Decreased CTRP9 levels and increased Hcy levels are independent risk factors for coronary heart disease patients with thin fibrous cap atherosclerosis.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Placa Aterosclerótica , Aterosclerose/metabolismo , Aterosclerose/patologia , Homocisteína , Humanos
7.
Front Med (Lausanne) ; 9: 819239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198576

RESUMO

BACKGROUND: Ultrasound guided-deep serratus anterior plane block (USG-DSAPB) has been used for pain management of patients undergoing modified radical mastectomy (MRM), but evidence supporting their adjuvant analgesic benefits is limited. We explored the efficacy and safety of preemptive use of ropivacaine combined with different doses of dexmedetomidine (DEX) in USG-DSAPB for patients undergoing MRM. METHODS: Ninety-five female patients undergoing unilateral MRM were allocated randomly to two groups. Group RD1 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 0.5 µg·kg-1 DEX in USG-DSAPB. Group RD2 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 1 µg·kg-1 DEX in USG-DSAPB. The primary outcome was sufentanil consumption 72 h after USG-DSAPB. Secondary outcomes were: postoperative pain scores and level of sedation; intraoperative hemodynamics; duration of post-anesthesia care unit (PACU) stay; prevalence of moderate-to-severe pain; one-time puncture success; procedure time of blockade; time to first rescue analgesia; requirement of rescue analgesia; satisfaction scores of patients and surgeons; duration of hospital stay; adverse events; prevalence of chronic pain; quality of postoperative functional recovery. RESULTS: Compared with the RD1 group, the visual analog scale score for coughing was significantly lower at 4, 8, 12 h and sufentanil consumption was significantly lower at 4, 8, 12, 24, and 48 h after surgery in the RD2 group (P < 0.05). The time to first rescue analgesia was significantly longer in the RD2 group (P < 0.05). The requirement for rescue analgesia was significantly higher in the RD1 group (P < 0.05). The prevalence of moderate-to-severe pain, number of patients using vasoactive agents, duration of PACU stay, as well as consumption of propofol, remifentanil, and DEX were significantly lower in the RD2 group (P < 0.05). There were no significant differences between the two groups with respect to one-time puncture success, procedure time of blockade, total dermatomal spread, satisfaction scores of patients and surgeons, postoperative complications, duration of hospital stay, 40-item Quality of Recovery questionnaire (QoR-40) score, or prevalence of chronic pain (P > 0.05). CONCLUSIONS: We discovered that 1 µg·kg-1 (not 0.5 µg·kg-1) DEX combined with 20 mL of 0.5% ropivacaine and 5 mg of dexamethasone in USG-DSAPB could provide superior postoperative analgesia for patients undergoing MRM. However, the quality of postoperative functional recovery and prevalence of chronic pain were similar.Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=54929, identifier: ChiCTR2000033685.

8.
J Hazard Mater ; 423(Pt A): 127018, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34461531

RESUMO

Millions of waste plastic express packaging bags (PEPBs) were generated with the rapid development of the express delivery industry due to the boom of electronic commerce. Waste PEPBs contain polyethylene (PE) material and large number of pollutants such as plasticizers and flame retardants. In this study, two effective and environmental-friendly methods were proposed to produce valuable products and remove pollutants from waste PEPBs by supercritical water degradation (SCWD) and supercritical water partial oxidation (SCWPO) treatments. Both SCWD and SCWPO treatments could effectively obtain valuable products (wax, liquid oil, CaCO3) and remove bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) from waste PEPBs. No obvious difference about the conversion could be found between SCWD and SCWPO treatments. 425 °C, 60 min, solid-to-liquid ratio of 1:20 g/mL, and V(H2O2):V(H2O) ratio of 1:3 mL/mL were the optimal conditions for the conversion of waste PEPBs by SCWD and SCWPO treatments. The maximum conversion could reach 98.13%. The produced wax and liquid oil were easily separated from each other. The produced wax mainly included long-chain olefins or long-chain alkanes, and a small amount of alcohols, ethers and aldehydes. SCWD treatment was favorable for obtaining long-chain alkenes, while SCWPO treatment was favorable for obtaining long-chain alkanes. The main chemical compounds contained in the produced liquid oil were decomposed from DEHP and BPA. DEHP was decomposed to produce 2-ethyl-1-hexanol and acetophenone. BPA was decomposed to produce 4-tert-butylphenol and other alkylated derivatives of benzene and phenol. In comparison with SCWD treatment, DEHP and BPA could be decomposed more thoroughly by SCWPO treatment.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Peróxido de Hidrogênio , Plastificantes/análise , Plásticos , Água
9.
Biomed Eng Online ; 20(1): 83, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399777

RESUMO

BACKGROUND: Ovarian cancer is one of the most common gynecological malignancies with the high morbidity and mortality. This study was aimed to explore the role of non-structure maintenance of chromosomes condensin I complex subunit H (NCAPH) in the progression of ovarian cancer (OC) and the transcription regulatory effects of GATA binding protein 3 (GATA3) on this gene. METHODS: Firstly, NCAPH and GATA3 expression in OC tissues and several human OC cell lines was, respectively, evaluated by TNMplot database and Western blot analysis. Then, NCAPH was silenced to assess the proliferation, migration, and invasion of OC cells in turn using CCK-8, wound healing, and transwell assays. Western blotting was used to determine the expression of epithelial--mesenchymal transition (EMT)-related proteins and PI3K/PDK1/AKT signaling proteins. The potential binding sites of GATA3 on NCAPH promoter were predicated using JASPAR database, which were verified by luciferase reporter assay and chromosomal immunoprecipitation. Subsequently, GATA3 was overexpressed to examine the biological functions of OC cells with NCAPH silencing. RESULTS: NCAPH and GATA3 expression was significantly upregulated in OC tissues and cell lines. NCAPH loss-of-function notably inhibited the proliferation, migration, invasion, and EMT of OC cells. Moreover, the expression of p-PI3K, PDK1, and p-AKT was downregulated after NCAPH knockdown. Furthermore, GATA3 was confirmed to bind to NCAPH promoter. GATA3 overexpression alleviated the inhibitory effects of NCAPH silencing on the proliferation, migration, invasion, EMT, and expression of proteins in PI3K/PDK1/AKT pathway of OC cells. CONCLUSION: To sum up, NCAPH expression transcriptional activation by GATA3 accelerates the progression of OC via upregulating PI3K/PDK1/AKT pathway.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Ovarianas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Humanos , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Fatores de Transcrição
10.
Cancer Manag Res ; 13: 2057-2069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664593

RESUMO

PURPOSE: Sevoflurane (SEV) is a frequently used volatile anesthetic in cancer surgery. Sevoflurane treatment has been shown to suppress the migration and invasion of several human cancer cells. However, the effect of sevoflurane on glioma remains largely unclear. METHODS: Glioma cell lines (U251 and U343) were treated by various concentrations of sevoflurane. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry assay, and transwell assay were performed to detect the cell viability, apoptosis, migration and invasion. Western blot assay was employed to detect the protein levels of ß-catenin, c-Myc, CyclinD1, ß-catenin, N-cadherin, vimentin, and DEK. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the expression level of miR-218-5p. The target interaction between miR-218-5p and DEK was predicted through bioinformatics analysis and verified by dual-luciferase reporter assay system. RESULTS: We found that sevoflurane aberrantly inhibited the abilities on viability, migration, invasion, EMT and ß-catenin signaling and promoted cell apoptosis in U251 and U343 cells in a dose-dependent manner. MiR-218-5p strikingly suppressed the abilities of proliferation, migration, invasion rather than apoptosis and activation of ß-catenin signaling. Sevoflurane could facilitate the miR-218-5p expression, and its suppressing effects on glioma cells were reversed by pre-treatment with miR-218-5p inhibitors or pcDNA3.1/DEK in vitro and in vivo. Silencing of miR-218-5p reverted sh-DEK and sevoflurane-induced repression on proliferation, migration, invasion, and ß-catenin signaling, and promotion on apoptosis in the glioma cells. CONCLUSION: Our data showed that sevoflurane inhibited the proliferation, migration, invasion, and enhanced the apoptosis in glioma cells through regulating miR-218-5p/DEK/ß-catenin axis.

11.
Transl Cancer Res ; 10(1): 162-173, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35116248

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NACT) may help reduce the difficulty of surgery and eliminate tiny tumor metastatic foci. It has been reported that 69.4% to 95% of patients with cervical cancer respond to NACT. The aim of this study was to evaluate the value of microvessel features in the prediction of response of cervical carcinoma to NACT and its association with the prognosis. METHODS: In all, 106 patients (FIGO stage IB2 and IIA2) received NACT followed by radical hysterectomy. Pre-treatment biopsy specimens and post-treatment surgical specimens were stained by immunohistochemistry using CD31 and CD105 antibodies and were counted by quantitative stereology. The correlation between microvessel features [microvessel density (MVD) and volume density (Vv)] and the clinical response and prognosis were determined using the Mann-Whitney U-test and logistic multivariate analysis. RESULTS: Of the 106 patients, 74 (69.4%) responded to NACT. The chemotherapeutic response was more favorable in patients with poor pathological grades and tumors larger than 5 cm (P=0.047, P<0.010). According to the pretreatment tumor size and the pathological grade, the patients were divided into six subgroups. In the subgroup of patients with a pretreatment tumor size ≥5 cm and tumors of moderate pathologic grade, the pre-NACT CD31-Vv was higher in NACT nonresponders than in responders (P=0.028). The area under the ROC curve for CD31-Vv was 0.767. In the logistic multivariate analysis, CD31-Vv was not an independent factor that affected the clinical response. The survival analysis showed that although higher post-treatment CD31-Vv was associated with a worse prognosis, Cox proportional hazards regression analysis did not indicate that microvessel features are prognostic predictors (P>0.05). Both pathological grade and invasive depth were independent predictors of survival. CONCLUSIONS: Pre-treatment CD31-Vv could be a predictor of chemosensitivity in one specific subgroup (pre-treatment tumor size ≥5 cm and moderate pathological grade). Post-treatment CD31-Vv is associated with a worse prognosis but is not an independent factor for overall survival.

12.
Arch Toxicol ; 94(1): 77-87, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31712840

RESUMO

The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of D-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60 mg/L sodium arsenite (NaAsO2) through drinking water from the first day of gestation until the end of lactation. D-serine levels in the hippocampus of mice of postnatal day (PND) 10, 20 and 40 were examined by high-performance liquid chromatography. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine-cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptors (NMDARs) in the hippocampus of mice were measured by Western blot and Real-time RT-PCR. Results showed that arsenic exposure significantly decreased D-serine levels of mice exposed to 60 mg/L NaAsO2. Exposure to 60 mg/L NaAsO2 could inhibit both mRNA and protein expression of SR, whereas increase in the protein expression of DAAO, only enhances the mRNA levels of DAAO of PND 20 mice. In addition, arsenic exposure could upregulate protein expression of asc-1. The mRNA and protein levels of NR1, NR2A and NR2B in the hippocampus of mice were down-regulated by arsenic. Findings from this study suggested that SR might play an important role in the reduction of D-serine levels caused by arsenic exposure, which might further influence the levels of NMDAR subunits especially on PND20, and then might disturb the function of NMDARs and cause the deficits of learning and memory ability of offspring mice.


Assuntos
Arsênio/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Serina/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , D-Aminoácido Oxidase/genética , D-Aminoácido Oxidase/metabolismo , Feminino , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Teste do Labirinto Aquático de Morris , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Racemases e Epimerases/genética , Racemases e Epimerases/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
13.
Exp Ther Med ; 18(6): 4221-4230, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31777532

RESUMO

Brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), vascular endothelial growth factor (VEGF) and CD105 are highly expressed in several types of cancer. The present study aimed to determine whether BDNF, TrkB, VEGF and CD105 are associated with the prognosis and metastasis of patients with cervical squamous cell carcinoma (SCC) at the IB2 stage. A total of 79 patients with IB2-stage SCC were enrolled in the present study. The expression levels of BDNF, TrkB, VEGF and CD105 in IB2-stage cervical cancer tissue were detected by immunohistochemistry and their association with clinicopathological indexes or prognostic factors was statistically analyzed. Reverse transcription quantitative PCR was used to detect whether the expression of VEGF was affected in SiHa cells co-cultured with BDNF. In addition, BDNF-induced SiHa cell migration and invasion were examined. BDNF expression in the cervical cancer samples was significantly associated with positive lymphovascular space invasion (P<0.001) and pelvic lymph node metastasis (P<0.05). In addition, microvessel density was verified as an independent prognostic factor for overall survival (P<0.05). In vitro analysis indicated that BDNF significantly induced cellular migration and invasion of SiHa cells in a dose-dependent manner (P<0.001). BDNF induced the expression of VEGF in SiHa cells, which was inhibited by BDNF antibodies or an inhibitor of TrkB receptor (P<0.05). BDNF may be considered a useful indicator of pelvic metastasis, which is involved in the aggressive spread of IB2-stage SCC. BDNF-induced upregulation of VEGF was revealed to act as a pro-angiogenic factor in SCC (Trial registration no. http://apps.who.int/trialsearch/; ChiCTR1800017778).

14.
Cancer Metastasis Rev ; 38(3): 507-524, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31471691

RESUMO

Matriptase is a type II transmembrane serine protease, which has been suggested to play critical roles in numerous pathways of biological developments. Matriptase is the activator of several oncogenic proteins, including urokinase-type plasminogen activator (uPA), hepatocyte growth factor (HGF) and protease-activated receptor 2 (PAR-2). The activations of these matriptase substrates subsequently lead to the generation of plasmin, matrix metalloproteases (MMPs), and the triggers for many other signaling pathways related to cancer proliferation and metastasis. Accordingly, matriptase is considered an emerging target for the treatments of cancer. Thus far, inhibitors of matriptase have been developed as potential anti-cancer agents, which include small-molecule inhibitors, peptide-based inhibitors, and monoclonal antibodies. This review covers established literature to summarize the chemical and biochemical aspects, especially the inhibitory mechanisms and structure-activity relationships (SARs) of matriptase inhibitors with the goal of proposing the strategies for their future developments in anti-cancer therapy.


Assuntos
Neoplasias/tratamento farmacológico , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/enzimologia , Neoplasias/patologia , Serina Endopeptidases/química , Inibidores de Serina Proteinase/administração & dosagem , Bibliotecas de Moléculas Pequenas/farmacologia
15.
J Cataract Refract Surg ; 44(8): 949-954, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30033112

RESUMO

PURPOSE: To evaluate the visual quality of patients with different angle κ sizes after a trifocal diffractive intraocular lens (IOL) implantation. SETTING: The Affiliated Hospital of Qingdao University, Qingdao, China. DESIGN: Prospective case series. METHODS: Patients who had phacoemulsification with the implantation of the trifocal IOL AT LISA tri 839MP were enrolled in the study. The patients were divided into 3 groups based on the size of the preoperative angle κ. Monocular far, intermediate, and near uncorrected visual acuities were measured during a 3-month follow-up. Other outcome measurements taken were the modulation transfer function (MTF) cutoff, the Strehl ratio, and objective scatter index. All the patients completed a subjective questionnaire survey. RESULTS: The study comprised 89 patients (89 eyes). The 3 groups showed statistically significant differences in the incidence of glare and halo after their surgery. There were no significant differences in the following variables: uncorrected far, intermediate, and near visual acuities, MTF cutoff, Strehl ratio, and spectacle independence. There was a significant difference in the MTF cutoff and Strehl ratio between the patients with the largest and the smallest angle κ. CONCLUSIONS: The patients' postoperative far, intermediate, and near vision was not affected by their angle κ. However, when angle κ was greater than 0.4 mm, the incidence of glare and halo increased and when it was greater than 0.5 mm, patients' visual quality decreased. In clinical work, for patients with a larger angle κ, the choice to implant a trifocal IOL should be carefully evaluated.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Facoemulsificação , Acuidade Visual/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
J Hazard Mater ; 344: 333-342, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29080486

RESUMO

Critical water system used for decomposition and debromination of waste printed circuit board (PCBs) has two disadvantages: low value-added oil phase products and halfway debromination at low temperature condition. In this study, critical water-alcohol composite medium was found to be a promising method to surmount these disadvantages. Critical water-ethanol (CWE) and critical water-methanol (CWM) were selected as the composite medium. The temperature of CWE and CWM had a significant effect on the oil phase composition. At low temperature CWE/CWM of 300°C, 4-(1-methylethyl)-phenol with high concentration could be recovered. CWM of 400°C was beneficial to the generation of ether compounds and high level of anisole could be obtained, while 450°C was beneficial to the generation of high level of multi-alkyl substituted phenol derivatives or benzene derivatives such as p-xylene. Br-free oil phase products could be obtained when the temperature of CWE/CWM ≥300°C. Different oil phase products with high level of chemicals or chemical intermediates could be obtained by controlling the reaction conditions of CWE/CWM. It is believed that the additional value of the oil phase products derived from waste PCBs can be greatly improved by this new process.

17.
Cancer Biol Ther ; 18(12): 990-999, 2017 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-29173024

RESUMO

Ovarian cancer is the third most common cancer in the female reproductive organs and epithelial ovarian cancer has the highest lethality of all gynecological cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of several types of cancer other than ovarian cancer. In this study, we exposed the ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and luteolin). MTT and wound healing assays demonstrated that all three treatments suppressed the proliferation and migration of the ovarian cancer cells. In addition, western blotting and ELISA assays showed that the expression levels of MMP2 and MMP9 gradually decreased after treatment with increasing concentrations of ellagic acid and luteolin. To confirm our findings in the in vitro experiments, we used another ovarian cancer cell line, ES-2, in nude mice experiments. All three treatments inhibited tumor growth without obvious side-effects. Furthermore, compared with the control group, the expression levels of MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a promising candidate for further preclinical testing for treatment of human ovarian cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Ácido Elágico/administração & dosagem , Luteolina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ácido Elágico/química , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Luteolina/química , Lythraceae/química , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Ovarian Res ; 10(1): 49, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28738876

RESUMO

BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. RESULTS: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. CONCLUSION: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.


Assuntos
4-Butirolactona/análogos & derivados , Antineoplásicos/uso terapêutico , Lignanas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Fitoestrógenos/uso terapêutico , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Lignanas/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/patologia , Fitoestrógenos/farmacologia , Carga Tumoral/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
19.
Mol Med Rep ; 7(6): 1826-30, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23588898

RESUMO

Protein phosphatase 2, regulatory subunit A, α (PPP2R1A) and ß (PPP2R1B) are paralogous subunits of the heterotrimeric protein phosphatase 2 (PP2A) holoenzyme that catalyzes the dephosphorylation of target substrate proteins. Subtype­specific PPP2R1A mutations have been frequently observed in ovarian and endometrial cancer. Mutations in the paralogous genes were frequently observed in human malignancies. Thus, the present study aimed to analyze the mutation frequencies of the paralogous PPP2R1A and PPP2R1B genes in patients with primary and secondary ovarian cancer. A total of 251 patients with primary (n=234) and secondary (n=17) ovarian cancer were analyzed for the presence of PPP2R1A and PPP2R1B mutations by direct sequencing. For PPP2R1A, a heterozygous, somatic mutation (c.771G>T, p.W257C) was identified in 1 out of 37 patients (2.7%) with primary ovarian endometrioid carcinoma. The mutant sample was that of a 46­year­old female, who was also diagnosed with ectopic endometriosis in the benign ovary. No PPP2R1A mutations were detected in the remaining 250 patients with ovarian cancer. For PPP2R1B, no mutations were detected in our samples. The results of this study suggested that PPP2R1A mutations are less common in Chinese patients with ovarian cancer when compared with European and American patients. Furthermore, our study also supported previous observations that PPP2R1B mutations were absent in ovarian cancer, suggesting that PPP2R1B mutations are not actively involved in the pathogenesis of ovarian cancer.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Ovarianas/genética , Proteína Fosfatase 2/genética , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/secundário , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/secundário , Análise de Sequência de DNA , Adulto Jovem
20.
Oncol Lett ; 4(5): 925-930, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23162624

RESUMO

We investigated the expression of UDP-glucuronosyltransferase 1A (UGT1A), nuclear factor erythroid-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in normal colonic mucosa, adenoma tissue and adenocarcinoma tissue, to analyze the correlation between their expression and the clinicopathological features of adenocarcinoma and their roles in colonic carcinogenesis. Using immunohistochemical analysis, we investigated the expression of UGT1A, Nrf2 and Keap1 in normal colonic mucosa (n=24), adenoma tissue (n=30) and adenocarcinoma tissue (n=77). We found that the positive rate of UGT1A was 83.3% in normal colonic mucosa, 80.0% in adenoma tissue and significantly lower, 53.2%, in adenocarcinoma tissue (normal colonic vs. adenoma tissue, P=0.071; normal colonic vs. adenocarcinoma tissue, P=0.023; adenoma vs. adenocarcinoma tissue, P=0.019). The expression levels of Nrf2 were high in adenoma and adenocarcinoma tissues, with positive rates of 70.0 and 87.0%, respectively, but were significantly lower in normal colonic tissue, with a positive rate of 41.7% (normal colonic vs. adenoma tissue, P=0.000; normal colonic vs. adenocarcinoma tissue, P=0.000; adenoma vs. adenocarcinoma tissue, P=0.000). The positive rate of Keap1 was 54.2% in normal mucosa, 70.0% in adenoma tissue and 61.0% in adenocarcinoma tissue (normal colonic mucosa vs. adenoma tissue, P=0.200; normal colonic vs. adenocarcinoma tissue, P=0.040; adenoma vs. adenocarcinoma, P=0.002). In addition, there was no correlation between the expression of Nrf2/Keap1 in adenoma and adenocarcinoma tissues (r=0.067, P=0.723; r=0.042, P=0.715, respectively). The results suggest that decreased expression of UGT1A and the dysregulation of the Nrf2/Keap1 system may be related to colonic carcinogenesis.

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