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1.
Eur Rev Med Pharmacol Sci ; 28(5): 1797-1811, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497863

RESUMO

OBJECTIVE: Perioperative anxiety and depression syndrome (PADS) is a common clinical concern among women with systemic tumors. Esketamine has been considered for its potential to alleviate anxiety and depressive symptoms. However, its specific application and effectiveness in PADS among women with systemic tumors remain unclear. This study aimed to analyze the utility of Machine Learning (ML) algorithms based on electroencephalogram (EEG) signals in evaluating perioperative anxiety and depression in women with systemic tumors treated with Esketamine, utilizing a large-scale medical data background. PATIENTS AND METHODS: A single-center, randomized, placebo-controlled (SC-RPC) trial design was adopted. A total of 112 female patients with systemic tumors and PADS who received Esketamine treatment were included as study participants. A moderate dose (0.7 mg/kg) of Esketamine was administered through intravenous infusion over a duration of 60 minutes. EEG signals were collected from all patients, and the EEG signal features of individuals with depression were compared to those without depression. In this study, a Support Vector Machine (SVM)-K-Nearest Neighbour (KNN) hybrid classifier was constructed based on SVM and KNN algorithms. Using the EEG signals, the classifier was utilized to assess the anxiety and depression status of the patients. The predictive performance of the classifier was evaluated using accuracy, sensitivity, and specificity measures. RESULTS: The C2 correntropy feature of the delta rhythm in the left-brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). Moreover, the C2 correntropy feature of the Alpha, Beta, and Gamma rhythms in the left-brain EEG signal was significantly lower in individuals with depression compared to those without depression (p<0.05). In the right brain EEG signal, the C2 correntropy feature of the delta rhythm was significantly higher in individuals with depression (p<0.05), while the C2 correntropy feature of the alpha and gamma rhythms was significantly lower in individuals with depression compared to those without depression (p<0.05). Additionally, the C1 correntropy feature of the Gamma rhythm in the right brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). The SVM classifier achieved accuracy, sensitivity, and specificity of 98.23%, 98.10%, and 98.56%, respectively, in recognizing the left-brain EEG signals, with a correlation coefficient of 0.95. In recognizing the right brain EEG signals, the SVM classifier achieved accuracy, sensitivity, and specificity of 98.74%, 98.43%, and 99.03%, respectively, with a correlation coefficient of 0.96. The improved SVM-KNN approach yielded an accuracy, recall, precision, F-score, area over the curve (AOC), and Receiver Operation Characteristics (ROC) of 0.829, 0.811, 0.791, 0.853, 0.787, and 0.877, respectively, in predicting anxiety. For predicting depression, the accuracy, recall, precision, F-score, AOC, and ROC were 0.869, 0.842, 0.831, 0.893, 0.827, and 0.917, respectively. CONCLUSIONS: Significant differences were observed in the brain EEG signals between individuals with depression and those without depression. The improved SVM-KNN algorithm developed in this study demonstrates good predictive capability for anxiety and depression.


Assuntos
Big Data , Ketamina , Neoplasias , Feminino , Humanos , Depressão/diagnóstico , Depressão/tratamento farmacológico , Ritmo Gama , Ansiedade/diagnóstico , Ansiedade/tratamento farmacológico , Síndrome
2.
Actas Urol Esp (Engl Ed) ; 48(4): 295-303, 2024 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38160794

RESUMO

OBJECTIVE: Tislelizumab, a monoclonal antibody against programed death protein-1 (PD-1), has shown encouraging antitumor activity in urothelial cancer. This study was designed to assess the efficacy and safety of tislelizumab in urotelial cancer in a real-world setting. METHODS: The study was a real-world retrospective study undertaken at Liaoning Cancer Hospital & Institute, China. Eligible patients were ≥18 years. Patients received 200-mg tislelizumab monotherapy intravenously every 3 weeks until the disease progressed to intolerable toxicity. Outcomes included an objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Between March 2020 and December 2022, 33 patients were enrolled. The median follow-up was 10.17 (IQR 5.73-12.47) months. Of all 33 patients, ORR and DCR were 30.30% (95% CI 15.6%-48.7%) and 42.42% (95% CI 25.48%-60.78%), respectively. The median PFS was 5.73 (95% CI 3.27-13.00) months, with a 12-month PFS rate of 31.90% (95% CI 19.20%-53.00%). The median OS was 17.7 (95% CI 12.80-not reach) months, with a 12-month OS rate of 67.50% (95% CI 52.70%-86.40%). Eleven (33.33%) and 8 (24.24%) experienced ≥grade 3 treatment-related adverse events (TRAEs) and immune-related Aes, respectively. No treatment-related deaths occurred. CONCLUSION: The excellent efficacy and controllable safety of tislelizumab in locally advanced or metastatic urothelial cancer suggest that it may be a promising therapeutic option for this population.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Neoplasias Urológicas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso de 80 Anos ou mais
3.
ESMO Open ; 8(4): 101565, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37348348

RESUMO

BACKGROUND: Despite the prolonged median disease-free survival (DFS) by adjuvant targeted therapy in non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the relationship between the treatment duration and the survival benefits in patients remains unknown. PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase II trial, eligible patients aged 18-75 years with EGFR-mutant, stage II-IIIA lung adenocarcinoma and who had not received adjuvant chemotherapy after complete tumor resection were enrolled from eight centers in China. Patients were randomly assigned (1 : 1) to receive either 1-year or 2-year icotinib (125 mg thrice daily). The primary endpoint was DFS assessed by investigator. The secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT01929200). RESULTS: Between September 2013 and October 2018, 109 patients were enrolled (1-year group, n = 55; 2-year group, n = 54). Median DFS was 48.9 months [95% confidence interval (CI) 33.1-70.1 months] in the 2-year group and 32.9 months (95% CI 26.6-44.8 months) in the 1-year group [hazard ratio (HR) 0.51; 95% CI 0.28-0.94; P = 0.0290]. Median OS for patients was 75.8 months [95% CI 64.4 months-not evaluable (NE)] in the 2-year group and NE (95% CI 66.3 months-NE) in the 1-year group (HR 0.34; 95% CI 0.13-0.95; P = 0.0317). Treatment-related adverse events (TRAEs) were observed in 41 of 55 (75%) patients in the 1-year group and in 36 of 54 (67%) patients in the 2-year group. Grade 3-4 TRAEs occurred in 4 of 55 (7%) patients in the 1-year group and in 3 of 54 (6%) patients in the 2-year group. No treatment-related deaths or interstitial lung disease was reported. CONCLUSIONS: Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Duração da Terapia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética
4.
J Bone Miner Metab ; 41(2): 163-170, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36847866

RESUMO

INTRODUCTION: Mouse skeletal stem cells (mSSCs, CD45-Ter119-Tie2-CD51+Thy-6C3-CD105-CD200+population) are identified in growth plates (GP) and play important roles in bone regeneration. However, the role of mSSCs in osteoporosis remains unclear. MATERIALS AND METHODS: The GP were stained by HE staining, and the mSSC lineage was analyzed by flow cytometry at postnatal of 14 days and 30 days in wild-type mice. The mice (8 weeks) were either sham operated or ovariectomy (OVX) and then sacrificed at 2, 4 and 8 w. The GP were stained by Movat staining, and mSSC lineage was analyzed. Then, mSSCs were sorted by fluorescence-activated cell sorting (FACS); the clonal ability, chondrogenic differentiation and osteogenic differentiation were evaluated, and the changed genes were analyzed by RNA-seq. RESULTS: The percentage of mSSCs were decreased with the narrow GP. Heights of GP were decreased significantly in 8w-ovx mice compared with 8w-sham mice. We found the percentage of mSSCs were decreased in mice at 2w after ovx, but the cell numbers were not changed. Further, the percentage and cell numbers of mSSCs were not changed at 4w and 8w after ovx. Importantly, the clonal ability, chondrogenic differentiation and osteogenic differentiation of mSSCs were impaired at 8w after ovx. We found 114 genes were down-regulated in mSSCs, including skeletal developmental genes such as Col10a1, Col2a1, Mef2c, Sparc, Matn1, Scube2 and Dlx5. On the contrary, 526 genes were up-regulated, including pro-inflammatory genes such as Csf1, Nfkbla, Nfatc2, Nfkb1 and Nfkb2. CONCLUSION: Function of mSSCs was impaired by up-regulating pro-inflammatory genes in ovx-induced osteoporosis.


Assuntos
Osteogênese , Osteoporose , Humanos , Feminino , Camundongos , Animais , Osteogênese/genética , Lâmina de Crescimento , Células-Tronco , Diferenciação Celular , Ovariectomia , Proteínas de Ligação ao Cálcio , Proteínas Adaptadoras de Transdução de Sinal
5.
J Eur Acad Dermatol Venereol ; 36(8): 1382-1388, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35442543

RESUMO

BACKGROUND: Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging-associated epidermal dysfunction has been connected to elevations in circulating cytokines. OBJECTIVE: We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. METHODS: This randomized, open-label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient-treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice-daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. RESULTS: Over the three-year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). CONCLUSIONS: These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.


Assuntos
Disfunção Cognitiva , Emolientes , Administração Tópica , Idoso , Disfunção Cognitiva/tratamento farmacológico , Emolientes/uso terapêutico , Epiderme , Humanos , Projetos Piloto
6.
Clin. transl. oncol. (Print) ; 24(2): 305-318, febrero 2022.
Artigo em Inglês | IBECS | ID: ibc-203436

RESUMO

IntroductionIntestinal tumor is one of the most common tumors that seriously threaten the health of residents all over the world. Studies suggest that the imbalance of intestinal flora is associated with tumorgenesis; meanwhile, long-term regular aerobic exercise can improve the occurrence and development of tumors. However, moderate aerobic exercise affecting the development of intestinal tumors and their related flora has not been explored. Thus, the purpose of our study is to explore the effects of aerobic exercise on intestinal tumor growth and flora changes in ApcMin/+ mice, and try to answer whether there is a correlation between them after exercise intervention.MethodsIn this study, 18 required ApcMin/+ mice were randomly divided into Model group (n = 6), Exercise group (n = 6), and Aspirin group (positive control, n = 6), while C57BL/6 J wild-type mice were used as the blank control group. Each group is given corresponding intervention. Weight monitoring, tumor counts, hematoxylin–eosin staining, TdT-mediated dUTP nick-end labeling (TUNEL) fluorescence assay, immunohistochemistry (IHC), fecal sampling and grouping, and bacterial 16S rDNA gene analysis were completed after 12 weeks’ intervention for each group of mice.ResultsAs a result, we were able to show significant improvements in mice’ body weight changing rates (Exercise group 8.6% higher than Model control group), tumor numbers (Exercise group 4.33 ± 0.94 vs. Model control group 7.33 ± 2.49.


Assuntos
Animais , Ciências da Saúde , Exercício Físico , Neoplasias Intestinais , Flora , Microbioma Gastrointestinal , Carcinogênese , Estudos Clínicos como Assunto , Genes de RNAr
7.
Clin. transl. oncol. (Print) ; 24(1): 93-103, enero 2022.
Artigo em Inglês | IBECS | ID: ibc-203418

RESUMO

PurposeElongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study.MethodsBioinformatic analysis was performed to find differential expressed genes and related pathways. Western blotting and quantitative PCR assays were used to verify the EFTUD2 expression in HCC cell lines and tumor tissues of liver cancer patients. Transfection of shRNAs in SKHEP1 and Huh7 cell lines was conducted to explore the mechanisms of EFTUD2 in HCC. CCK-8 method, colony formation, and cell cycle detection kit were used to detect the proliferation. A tumor model in nude mice was used to explore the role of EFTUD2 in liver cancer in vivo.ResultsBased on the tumor tissues and para-tumor tissues in our HCC patients, we identified EFTUD2 as highly expressed in HCC tissues (P < 0.001). Bioinformatic analysis from the TCGA database also supported this biological phenomenon (P = 1.911e−17). Furtherly, the results of clinical specimens and TCGA data suggested that higher EFTUD2 expression levels correlated with high histologic grades, high pathological grades, and poor survival prognoses in HCC patients. And knockdown of EFTUD2 suppressed cell proliferation and colony formation in vitro. In vivo, knockdown of EFTUD2 constrained the tumor growing and expansion derived from SKHEP1 cells and induced a decrease in the tumor volume and tumor weight resected from nude mice. Furthermore, RNA sequencing based on EFTUD2 knockdown revealed that EFTUD2 affected target genes concerned with the cell cycle. Flow cytometric analyses in the SKHEP1 cell model revealed that knockdown significantly suppressed cell cycle course and caused cell cycle arrest in the G1 phase. CyclinD1 proteins were also inhibited by knocking down of EFTUD2.


Assuntos
Humanos , Ciências da Saúde , Carcinoma Hepatocelular , Ribonucleoproteínas , Carga Tumoral , Neoplasias , Estudos Clínicos como Assunto , Proliferação de Células
8.
Br J Dermatol ; 186(2): 307-317, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34498260

RESUMO

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.


Assuntos
Predisposição Genética para Doença , Psoríase , Predisposição Genética para Doença/genética , Antígenos HLA-C/genética , Humanos , Subunidade p40 da Interleucina-12/genética , Complexo Principal de Histocompatibilidade , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética
9.
Z Rheumatol ; 81(2): 164-173, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33320289

RESUMO

OBJECTIVE: To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis. METHODS: A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1 mg/kg, PTX 1.5 mg/kg, PTX 2.5 mg/kg, PTX 3.5 mg/kg, and MTX 1 mg/kg + PTX 3.5 mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1ß and IL­6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and p­NF-κBp65 protein expression in synovial tissue and the changes of serum IL­1ß, IL­6, IL­12, MMP­3, and TNFα protein factors were detected by western blot and ELISA, respectively. RESULTS: PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5 mg/kg group was more than that of the PTX + MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL­6 and IL­1ß and downregulate TLR4 and p­NF-κBp65 protein expression. Furthermore, TLR4 and p­NF-κBp65 reduced the concentration of MMP­3, IL­12, IL­6, IL1­ß, and TNFα. CONCLUSION: Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5 mg/kg every other day was the optimal dose observed in this study.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Metotrexato/uso terapêutico , Paclitaxel , Ratos , Membrana Sinovial
10.
Biol Trace Elem Res ; 200(3): 1020-1031, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33929694

RESUMO

Currently, the removal of iodized salt is carried out in high water iodine regions. The present situation of iodine nutrition and the prevalence of thyroid diseases in such regions have not been clearly elucidated. This study aimed to figure out these problems to help render effective measures for cases of abnormal iodine nutrition status. A cross-sectional study was carried out in four areas of Jining and Heze, Shandong Province, China, with different water iodine concentrations (WIC). In total, 1344 adults were enrolled in this study, and data related to their iodine nutrition, thyroid function, and thyroid ultrasonography were collected. Subjects were grouped according to WIC, urine iodine concentration (UIC), serum iodine concentration (SIC), and combined UIC and SIC for analysis. Iodine levels were in excess in the 100 µg/L ≤ WIC < 300 µg/L and WIC ≥ 300 µg/L areas. Compared with the control WIC group (10-100 µg/L), the WIC ≥ 300 µg/L group had a higher prevalence of thyroid autoimmunity (TAI, 21.25% vs. 13.19%, P <0.05), subclinical hypothyroidism (SH, 20.20% vs. 11.96%, P < 0.05), thyroid nodules (TN, 31.75% vs. 18.71%, P < 0.05), and thyroid dysfunction (23.62% vs. 12.26%, P < 0.05). Compared with the UIC control group (100-300 µg/L), high UIC group (≥ 800 µg/L) had a higher prevalence of TN (33.75% vs. 21.14%, P < 0.05) and thyroid dysfunction (25% vs. 14.47%, P < 0.05). Next, compared with the control SIC group (50-110 µg/L), high SIC group (≥ 110 µg/L) had a higher prevalence of TAI (33.80% vs. 14.47%, P < 0.05), SH (23.94% vs. 14.30%, P < 0.05), and thyroid dysfunction (33.80% vs. 15.29%, P < 0.05). Finally, subjects with the highest UIC and the highest SIC also had a higher prevalence of TAI (25.92% vs. 10.97%, P < 0.05), SH (23.45% vs. 10.97%, P < 0.05), TN (34.56% vs. 15.85%, P < 0.05), and thyroid dysfunction (27.16% vs. 13.41%, P < 0.05) than subjects with middle iodine levels. The iodine nutrition of subjects in the WIC ≥ 300 µg/L areas was still in excess after removing iodized salt from their diets. High levels of iodine also increased the prevalence of TAI, SH, TN, and thyroid dysfunction in those areas. Simply removing iodized salt may not be sufficient for high water iodine regions.


Assuntos
Iodo , Estado Nutricional , Adulto , China/epidemiologia , Estudos Transversais , Humanos , Iodo/análise , Cloreto de Sódio na Dieta/análise , Água
11.
Clin Transl Oncol ; 24(2): 305-318, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34436759

RESUMO

INTRODUCTION: Intestinal tumor is one of the most common tumors that seriously threaten the health of residents all over the world. Studies suggest that the imbalance of intestinal flora is associated with tumorgenesis; meanwhile, long-term regular aerobic exercise can improve the occurrence and development of tumors. However, moderate aerobic exercise affecting the development of intestinal tumors and their related flora has not been explored. Thus, the purpose of our study is to explore the effects of aerobic exercise on intestinal tumor growth and flora changes in ApcMin/+ mice, and try to answer whether there is a correlation between them after exercise intervention. METHODS: In this study, 18 required ApcMin/+ mice were randomly divided into Model group (n = 6), Exercise group (n = 6), and Aspirin group (positive control, n = 6), while C57BL/6 J wild-type mice were used as the blank control group. Each group is given corresponding intervention. Weight monitoring, tumor counts, hematoxylin-eosin staining, TdT-mediated dUTP nick-end labeling (TUNEL) fluorescence assay, immunohistochemistry (IHC), fecal sampling and grouping, and bacterial 16S rDNA gene analysis were completed after 12 weeks' intervention for each group of mice. RESULTS: As a result, we were able to show significant improvements in mice' body weight changing rates (Exercise group 8.6% higher than Model control group), tumor numbers (Exercise group 4.33 ± 0.94 vs. Model control group 7.33 ± 2.49, Then put the slides into xylenewith tumor inhibition rate 40.93%), tumor pathological staging (Exercise group mainly low-grade tumorous adenomas vs. Model group mainly high-grade adenomas), and TUNEL staining (Exercise group 8.59% higher positive rate of apoptotic cells in tumors than Model group). The 16s rRNA sequencing analysis results showed that aerobic exercise could regulate the abundance of some genus (16/149, P < 0.01), and the number of intestinal tumors correlates with changes in the abundance of some bacteria in the intestinal flora (positive correlation with probiotics abundance and negative correlation with conditioned pathogens). DISCUSSION: Changes in flora abundance may be one of the reasons for aerobic exercise to reduce the number of intestinal tumors, probably mediated by cell apoptosis. Future studies should focus on the potential mechanism of aerobic exercise in preventing intestinal tumorgenesis, especially the molecular mechanism through intestinal flora. CONCLUSION: Aerobic exercise has a preventive effect on intestinal tumors in ApcMin/+ mice, and can regulate the abundance of intestinal flora.


Assuntos
Microbioma Gastrointestinal , Neoplasias Intestinais/microbiologia , Condicionamento Físico Animal , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
12.
Clin Transl Oncol ; 24(1): 93-103, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34282556

RESUMO

PURPOSE: Elongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study. METHODS: Bioinformatic analysis was performed to find differential expressed genes and related pathways. Western blotting and quantitative PCR assays were used to verify the EFTUD2 expression in HCC cell lines and tumor tissues of liver cancer patients. Transfection of shRNAs in SKHEP1 and Huh7 cell lines was conducted to explore the mechanisms of EFTUD2 in HCC. CCK-8 method, colony formation, and cell cycle detection kit were used to detect the proliferation. A tumor model in nude mice was used to explore the role of EFTUD2 in liver cancer in vivo. RESULTS: Based on the tumor tissues and para-tumor tissues in our HCC patients, we identified EFTUD2 as highly expressed in HCC tissues (P < 0.001). Bioinformatic analysis from the TCGA database also supported this biological phenomenon (P = 1.911e-17). Furtherly, the results of clinical specimens and TCGA data suggested that higher EFTUD2 expression levels correlated with high histologic grades, high pathological grades, and poor survival prognoses in HCC patients. And knockdown of EFTUD2 suppressed cell proliferation and colony formation in vitro. In vivo, knockdown of EFTUD2 constrained the tumor growing and expansion derived from SKHEP1 cells and induced a decrease in the tumor volume and tumor weight resected from nude mice. Furthermore, RNA sequencing based on EFTUD2 knockdown revealed that EFTUD2 affected target genes concerned with the cell cycle. Flow cytometric analyses in the SKHEP1 cell model revealed that knockdown significantly suppressed cell cycle course and caused cell cycle arrest in the G1 phase. CyclinD1 proteins were also inhibited by knocking down of EFTUD2. CONCLUSION: EFTUD2 is markedly overexpressed in HCC tumor tissues. High EFTUD2 expression in HCC patients is associated with clinical features. Moreover, we confirmed that EFTUD2 shows a pivotal role in HCC cell proliferation and cell cycle course and could be a possible therapeutic avenue in HCC through disturbing EFTUD2.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Fatores de Alongamento de Peptídeos/fisiologia , Ribonucleoproteína Nuclear Pequena U5/fisiologia , Animais , Células Cultivadas , Correlação de Dados , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Taxa de Sobrevida
14.
Cancer Radiother ; 25(4): 323-329, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33446419

RESUMO

PURPOSE: To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients. PATIENTS AND METHODS: We reviewed 82 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP. RESULTS: A total of 22(26.8%) patients developed grade 2 RP and 5(6.1%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.213;95%CI,1.099-1.339; P<0.001) and V20(OR,1.435;95%CI,1.166-1.765; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V5>23% (AUC=0.819, sensitivity:0.701, specificity:0.832) and V20>8% (AUC=0.812, sensitivity:0.683, specificity:0.811). Additionally, grade≥3 RP did not occur when V5<30%, V20<13% and MLD<751.2cGy, respectively. CONCLUSIONS: Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV5<30%, V20<13% and MLD<751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/etiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Nomogramas , Pneumonectomia , Cuidados Pós-Operatórios , Curva ROC , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/patologia , Análise de Regressão , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga Tumoral
15.
Eur Rev Med Pharmacol Sci ; 24(22): 11658-11665, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275233

RESUMO

OBJECTIVE: To explore whether plasmacytoma variant translocation 1 (PVT1) could regulate glioblastoma multiforme (GBM) progression via microRNA-1301-3p (miR-1301-3p) and transmembrane BAX inhibitor motif containing 6 (TMBIM6) axis. MATERIALS AND METHODS: Expression patterns of PVT1 and RMBIM6 in GBM patients were analyzed using GEPIA, an online gene expression analysis tool. Levels of PVT1 in GBM cells and normal cells were analyzed with quantitative real-time PCR method. Cell Counting Kit-8 (CCK-8), transwell invasion assay, and flow cytometry assay were applied to detect cell viability and apoptosis. Connections of PVT1 or TMBIM6 with miR-1301-3p were validated with bioinformatic tool and luciferase activity reporter assay. RESULTS: PVT1 was significantly expressed in GBM tissues and cells. PVT1 promotes GBM cell proliferation and invasion but inhibits apoptosis in vitro. TMBIM6 was significantly expressed in GBM tissues. The knockdown of TMBIM6 reversed the stimulation effects of PVT1 on GBM cell malignancy behaviors with miR-1301-3p as a bridge. CONCLUSIONS: Collectively, we showed PVT1 elevated TMBIM6 expression mediated by miR-1301-3p and thus to promote GBM progression.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias do Sistema Nervoso Central/metabolismo , Glioblastoma/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Neoplasias do Sistema Nervoso Central/patologia , Glioblastoma/patologia , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , RNA Longo não Codificante/genética
17.
Eur Rev Med Pharmacol Sci ; 24(20): 10383-10390, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33155194

RESUMO

OBJECTIVE: To reveal the anti-tumor effect of micro ribonucleic acid (miR)-127-3p on epithelial ovarian cancer (EOC). PATIENTS AND METHODS: The expression of miR-127-3p in 7 kinds of EOC cell lines and 10 cases of clinical samples of EOC patients was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). OVCAR-3 and Caov-3 cell lines were transfected with lentiviruses to overexpress endogenous miR-127-3p. Then, the anti-tumor effect of miR-127-3p on EOC cells was explored through the in vitro cell proliferation assay, bufalin sensitivity assay, wound healing assay, and invasion assay. In addition, whether the mitogen-activated protein kinase 4 (MAPK4) gene is a downstream target of miR-127-3p in EOC was verified via Dual-Luciferase reporter assay and qRT-PCR. The involvement of MAPK4 in regulating phenotypes of OVCAR-3 and Caov-3 cells was finally explored. RESULTS: MiR-127-3p was downregulated in both EOC cell lines and EOC tissues (p<0.05). After lentivirus-mediated overexpression of miR-127-3p, in vitro proliferation and invasion of EOC cells were inhibited, and the sensitivity to bufalin was enhanced (p<0.05). MiR-127-3p directly regulated MAPK4 gene in EOC. Moreover, the upregulation of MAPK4 inhibited the anti-tumor effect of miR-127-3p on EOC, manifested as the remarkably enhanced cell proliferation and migration (p<0.05), and the weakened sensitivity to bufalin (p<0.01). CONCLUSIONS: MiR-127-3p exerts an inhibitory effect on EOC cells via regulating MAPK4 level.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Regulação para Baixo , MicroRNAs/metabolismo , Neoplasias Ovarianas/metabolismo , RNA Helicases/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/patologia , RNA Helicases/genética
18.
Eur Rev Med Pharmacol Sci ; 24(14): 7561, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32744666

RESUMO

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/ß-catenin, by T. Liao, S.-L.-M. Maierdan, C. Lv, published in Eur Rev Med Pharmacol Sci 2019; 23 (3 Suppl): 217-223-DOI: 10.26355/eurrev_201908_18650-PMID: 31389604" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18650.

19.
J Eur Acad Dermatol Venereol ; 34(9): 2059-2065, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32271961

RESUMO

BACKGROUND: Methotrexate (MTX) is the first-line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients. OBJECTIVE: The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population. METHODS: In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5-15 mg/week for at least 8 weeks. Patients were stratified as responders and non-responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher's exact test, the chi-square test, Mann-Whitney tests and ANOVA analyses were used for statistical analysis. RESULTS: Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP-binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non-responders (P = 0.017), especially in moderate-to-severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment. CONCLUSION: We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.


Assuntos
Artrite Psoriásica , Psoríase , Adulto , Idoso , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/genética , Povo Asiático/genética , China , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/genética , Resultado do Tratamento , Adulto Jovem
20.
Eur Rev Med Pharmacol Sci ; 23(22): 9907-9914, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31799659

RESUMO

OBJECTIVE: To explore the effect of micro-ribonucleic acid (miR)-187 on cisplatin (DDP) resistance of gastric cancer cells by regulating the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. MATERIALS AND METHODS: DDP-sensitivities in GES-1, SGC7901, and SGC7901/DDP cells were detected via Cell Counting Kit-8 (CCK-8) assay. The differential expression of miR-187 of these cell lines was detected by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). DDP-resistant gastric cancer cells SGC7901/DDP were divided into control group (blank control), miR-187 inhibitor group (SGC7901/DDP cells transfected with miR-187 inhibitor), and miR-187 mimic group (SGC7901/DDP cells transfected with miR-187 mimic). The protein expressions of miR-187, TGF-ß1, p-Smad4, excision repair cross-complementation group 3 (ERCC3), and ERCC4 were determined through RT-qPCR, immunohistochemistry, and Western blotting. The apoptosis in each group was detected by flow cytometry. RESULTS: MiR-187 level had a negative correlation with DDP-resistance of GES-1, SGC7901, and SGC7901/DDP cells, and among them, the GES-1 cells had the lowest DDP-resistance and the highest expression of miR-187. CCK-8 assay revealed that compared with that in the control group, DDP-resistance significantly declined in the miR-187 mimic group, while it was significantly enhanced in miR-187 inhibitor group (p<0.01). According to the results of flow cytometry, after treatment with 100 nM DDP for 12 h, the apoptotic rate in miR-187 mimic group enhanced, while it was markedly reduced in the miR-187 inhibitor group (p<0.01). Western blotting and immunohistochemistry results showed that expressions of TGF-ß1 and p-Smad4 were significantly downregulated in the miR-187 mimic group, while they were upregulated in the miR-187 inhibitor group (p<0.01). Besides, compared with the control group, ERCC3 and ERCC4 were downregulated in the miR-187 mimic group, while upregulated in miR-187 inhibitor group (p<0.01). CONCLUSIONS: The overexpression of miR-187 alleviates DDP-resistance in gastric cancer cells by inhibiting the TGF-ß/Smad signaling pathway.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Fosforilação , Proteínas Smad/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Fator de Crescimento Transformador beta/metabolismo
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