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1.
Exp Cell Res ; 402(2): 112574, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33794264

RESUMO

Congenital anorectal malformations (ARMs) are among the most prominent deformities of the gastrointestinal tract; however, their precise aetiology remains obscure. Immunohistochemistry demonstrated that, in the ARM group, the PPPDE1-positive cells were widely distributed in the hindgut epithelial tissue from GD13 to GD16. Immunofluorescence revealed that most TUNEL-, Bax-, and Cytochrome C (Cyt C)-positive cells overlapped with PPPDE1-positive cells in the urorectal septum (URS). Western blotting and quantitative real-time RT-PCR revealed that PPPDE1 levels were significantly higher in the ARM group from GD13 to GD14 (p < 0.05). IEC-6 cells were transfected with PPPDE1 overexpression plasmid/NC (negative control) or si-PPPDE1/si-NC. Flow cytometry analysis and CCK-8 assay (used to detect apoptosis and proliferation, respectively), as well as western blotting, showed that the levels of PPPDE1 were positively correlated with the pro-apoptotic molecules Bax and Cyt C. Accordingly, aberrantly high expression of PPPDE1 caused a spatiotemporal imbalance in foetal rats with ARMs during hindgut development. Therefore, the upregulation of PPPDE1 may promote epithelial apoptosis and reduce proliferation in the hindgut via the mitochondrial apoptotic pathway. This could affect the fusion of the URS and cloacal membrane, ultimately inhibiting the hindgut development and resulting in ARMs.

2.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1094-1101, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787102

RESUMO

Phylogeography is a research hotspot in the field of the genetic diversity and core germplasm construction of endangered rare plants. Paris polyphylla var. yunnanensis is a rare plant species mainly distributed in China. Wild individuals have been overexploited for the last few decades because of increasing demand for such medicines. Therefore, it is great significance to study the phylogeography of P. poliphylla var. yunnanensis based on chloroplast gene trnL-trnF sequences. In this study, chloroplast genes trnL-trnF were used in the phylogeography analysis of 15 wild and 17 cultivated populations of P. polyphylla var. yunnanensis. This study revealed that based on the results of neutrality tests and mismatch analysis, the rapid expansion of wild population has not been detected in P. polyphylla var. yunnanensis. After aligning and sorting the obtained cpDNA sequences, a total of 15 haplotypes were detected in all 32 populations. One haplotype was unique to the wild population, and 5 haplotypes were unique to the cultivated population. It can be seen that the haplotype richness of cultivated population was higher than that of wild population. The wild populations of P. polyphylla var. yunnanensis were divided into two groups according to evolutionary relationship of haplotypes and distribution map of haplotypes. The haplotype of branch Ⅰ was mainly distributed in Guizhou, and the haplotype of branch Ⅱ was located in Yunnan and Huidong, Sichuan. Therefore, it's speculated that Guizhou and the west Yunnan region may be glacial refuge in the evolutionary history of wild populations of P. polyphylla var. yunnanensis, and in order to protect the wild resources more effectively, wild populations of P. polyphylla var. yunnanensis in these two areas should be included in the protection zone.


Assuntos
Liliaceae , Melanthiaceae , China , Genes de Cloroplastos , Humanos , Liliaceae/genética , Filogeografia
3.
J Clin Lab Anal ; 35(4): e23734, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33660884

RESUMO

BACKGROUND: The aim of this study was to define the performance characteristics of the Mindray chemiluminescence assay for anti-Müllerian hormone (AMH) detection. DESIGNS AND METHODS: Intra-assay and total imprecision, analytical sensitivity, linearity, and interference were compared between the Mindray and Roche assays using pools of human serum according to Clinical and Laboratory Standards Institute protocols. Additionally, male and female reference intervals were established using serum specimens collected from otherwise healthy groups and patients with polycystic ovary syndrome (PCOS). RESULTS: The intra-assay and total imprecision percent coefficients of variation for low and high AMH serum levels were 2.74%/ 3.01% and 5.41%/5.35% respectively. The limits of blank, detection, and quantitation were 0.007, 0.01, and 0.03 ng/ml, respectively. The assay displayed good linearity over the range of 0.01-23 ng/ml. The coefficient of determination (R2 ) of the Mindray versus Roche assays was 0.9713 with 411 samples with AMH concentrations ranging from 0.014 to 22.1 ng/ml. The slope and intercept of the regression equation were 0.9687 and 0.3419, respectively. There was no significant interference from triglycerides (up to 3000 mg/dl), bilirubin (up to 50 mg/dl), hemoglobin (up to 500 mg/dl), or total protein (up to 10 g/dl). Reference intervals showed the expected decrease in serum AMH levels with age in healthy women and increased levels in women with PCOS. CONCLUSION: The Mindray AMH assay demonstrated acceptable analytical performance under routine conditions and is suitable for determining AMH levels in serum samples.

4.
Zhongguo Zhong Yao Za Zhi ; 46(4): 894-901, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645094

RESUMO

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.


Assuntos
Medicamentos de Ervas Chinesas , Eczema , Ephedra sinica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Tecnologia
5.
J Immunother Cancer ; 9(2)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33637599

RESUMO

BACKGROUND: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. METHODS: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. RESULTS: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. CONCLUSIONS: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

6.
Int J Med Sci ; 18(5): 1167-1178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526977

RESUMO

Background: To investigate the efficacy and safety of hirudin plus aspirin therapy compared with warfarin in the secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation (NVAF). Methods: Patients with cardioembolic stroke due to NVAF were prospectively enrolled from 18 collaborating hospitals from Dec 2011 to June 2015. Fourteen days after stroke onset, eligible patients were assigned to the hirudin plus aspirin group (natural hirudin prescribed as the traditional Chinese medicine Maixuekang capsule, 0.75 g, three times daily, combined with aspirin 100 mg, once daily) or the warfarin group (dose-adjusted warfarin targeting international normalized ratio (INR) 2-3, with an initial daily dose of 1.25 mg). Patients were followed up at 1, 2, 3, 6, 9, and 12 months after stroke onset. Time in therapeutic range (TTR) was calculated according to Rosendaal methodology to evaluate the quality of INR management in the warfarin group. The primary efficacy endpoint was the recurrence of stroke within 12 months after stroke onset. Safety was assessed as the occurrence of the composite event "intracranial hemorrhage and other bleeding events, death, and other serious adverse events". The Cox proportional hazard model and Kaplan-Meier curve were used to analyze the efficacy and safety events. Results: A total of 221 patients entered final analysis with 112 patients in the hirudin plus aspirin group and 109 in the warfarin group. Over the whole duration of our study, TTR for patients taking warfarin was 66.5 % ± 21.5%. A significant difference was not observed in the recurrence of stroke between the two groups (3.57% vs. 2.75%; P = 0.728). The occurrence of safety events was significantly lower in the hirudin plus aspirin group (2.68% vs.10.09%; P = 0.024). The risk for efficacy event was similar between the two groups (hazard ratio (HR), 1.30; 95% confidence interval (CI), 0.29-5.80). The safety risk was significantly lower in the hirudin plus aspirin group (HR, 0.27; 95% CI, 0.07-0.95). Kaplan-Meier analysis revealed significant difference in the temporal distribution in safety events (P = 0.023) but not in stroke recurrence (P = 0.726). Conclusion: Significant difference in efficacy was not detected between warfarin group and hirudin plus aspirin group. Compared with warfarin, hirudin plus aspirin therapy had lower safety risk in the secondary prevention of cardioembolic stroke due to NVAF.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(12): 1320-1325, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33328004

RESUMO

A boy, aged 2 years and 4 months, had a sudden onset of blepharoptosis of the right eyelid, accompanied by the mouth deviated to the right side, drinking cough, nystagmus, and developmental regression. Cranial MRI showed softening lesions formed after infarction of the right dorsolateral medulla oblongata, while head CT angiography showed no imaging of the proximal part of the V4 segment of the right vertebral artery. The child was diagnosed with dorsolateral medulla oblongata syndrome and was treated with gamma globulin to regulate immune function, with mannitol to reduce neuronal edema, with low-molecular-weight heparin sodium to improve local hypercoagulation of occluded blood vessels, with hyperbaric oxygen to improve local ischemia and hypoxia and promote the recovery of brain function, and with neuromuscular electrical stimulation to promote the recovery of neuromuscular function. Before discharge, only mild right ataxia and Horner syndrome remained. This article reports the first case of infantile dorsolateral medulla oblongata syndrome and provides experience for the diagnosis and treatment of the disease.


Assuntos
Blefaroptose/etiologia , Disartria/etiologia , Síndrome Medular Lateral/diagnóstico , Bulbo/diagnóstico por imagem , Pré-Escolar , Humanos , Síndrome Medular Lateral/complicações , Imagem por Ressonância Magnética , Masculino
8.
Int Immunopharmacol ; 89(Pt A): 107139, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33191179

RESUMO

Accumulating evidence has indicated that inflammation is required for the initiation and progression of hepatocellular carcinoma (HCC). The annexin family protein, which has a highly similar structure, has been demonstrated to participate in pro- or anti-inflammatory regulation in the developing of tumours. However, the potential effects of ANXA3 in the immune microenvironment of HCC remain unknown. In present study, we found that increased ANXA3 expression is associated with a higher infiltrated neutrophil-lymphocyte ratio (iNLR) in HCC. Moreover, HCC patients with a high iNLR and high ANXA3 expression confer the highest risk of death. ANXA3 can be detected in both cell lysates and culture supernatants. However, the secretory ANXA3 did not directly regulate the iNLR. Further study demonstrated that ANXA3 upregulated the iNLR by inducing chemokine CXCL8 and CCL25 release from HCC cells. We further confirmed that ANXA3 promotes tumourigenesis and detected the same associations between ANXA3 and the iNLR or chemokines in vivo. Our findings indicate that ANXA3 regulates the chemokine to remodel the iNLR and promotes tumourigenicity in HCC. These results further expanded our understanding of ANXA3 in the microenvironment of HCC and might provide novel targets for the investigation of molecular treatments for HCC patients.

9.
Mol Genet Genomic Med ; 8(9): e1314, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32643267

RESUMO

BACKGROUND: Homozygous spinocerebellar ataxia type 3 (SCA3) patients, which have an expanded cytosine-adenine-guanine (CAG) repeat mutation in both alleles of ATXN3, are extremely rare. Clinical features and genetic characteristics of them were seldom studied. METHODS: We analyzed seven newly homozygous SCA3 patients from five families and 14 homozygotes reported previously. An additional cohort of 30 heterozygous SCA3 patients were analyzed to compare age at onset (AAO). RESULTS: Two out of seven SCA3 homozygotes had the minimum CAG repeats reported so far (55/56 and 56/58). Five patients appeared peripheral neuropathy and two had mild cognitive impairment. The AAO was significantly inversely correlated with both the large and small expanded CAG repeats (r = -.7682, p < .0001). The AAO was significantly earlier in homozygous SCA3 than heterozygous ones (32.81 ± 11.86 versus. 49.90 ± 9.73, p < .0001). In addition, the AAO of our seven homozygotes is elder compared to those reported previously (41.29 years vs. 28.57 years), which may be related to the fewer CAG repeats in our seven patients. CONCLUSION: Gene dosage effect may play an important role in the AAO and severity of disease, and homozygosity for ATXN3 enhances phenotypic severity. Our findings expand clinical features and genetic characteristics of homozygous SCA3 patients.

10.
Exp Neurol ; 331: 113380, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32540359

RESUMO

The trichothiodystrophy group A protein (TTDA) functions in nucleotide excision repair and basal transcription. TTDA plays a role in cancers and serves as a prognostic and predictive factor in high-grade serous ovarian cancer; however, its role in human glioma remains unknown. Here, we found that TTDA was overexpressed in glioma tissues. In vitro experiments revealed that TTDA overexpression inhibited apoptosis of glioma cells and promoted cell growth, whereas knockdown of TTDA had the opposite effect. Increased TTDA expression significantly decreased the Bax/Bcl2 ratio and the level of cleaved-caspase3. TTDA interacted with the p53 gene at the -1959 bp and -1530 bp region and regulated its transcription, leading to inhibition of the p53-Bax/Bcl2 mitochondrial apoptosis pathway in glioma cells. These results indicate that TTDA is an upstream regulator of p53-mediated apoptosis and acts as an oncogene, suggesting its value as a potential molecular target for the diagnosis and treatment of glioma.

11.
Aging (Albany NY) ; 12(11): 10663-10675, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32516130

RESUMO

Programmed cell death 1 (PD-1) checkpoint inhibitor therapy leads to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with the treatment response in Chinese patients with advanced melanoma. In this study, we conducted a retrospective study of advanced melanoma patients who received PD-1 inhibitor therapy in China between August 2014 and March 2018. A total of 93 patients treated with PD-1 inhibitors including pembrolizumab and nivolumab were enrolled. The most frequent irAEs were pruritus, rash, vitiligo, and fatigue. The median time to onset of irAEs was 6.1 weeks. The overall response rate (ORR) and disease control rate (DCR) were higher in patients with irAEs than those without irAEs (P = 0.004 and P = 0.003, respectively), and better in patients who experienced three or more irAEs than those with none (P <0.001 and P <0.001, respectively). The ORR and DCR were significantly better in patients with grade 1 to 2 irAEs when compared with those with none (P = 0.002 and P = 0.003, respectively). In addition, the median progression-free survival and overall survival were longer in patients with irAEs than in those without irAEs (P = 0.007 and P = 0.002, respectively). In conclusion, our data demonstrated that irAEs were associated with a better clinical outcome after treatment with PD-1 inhibitor therapy in Chinese patients with advanced melanoma.

12.
Oncoimmunology ; 9(1): 1752563, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32363125

RESUMO

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC. The present study aimed to determine the effect of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with CRC. 122 patients with CRC treated with postoperative adjuvant chemotherapy were retrospectively included in this study. Among them, 62 patients received adjuvant chemotherapy only (control group), while the other 60 patients, with similar demographic and clinical characteristics, received adjuvant chemotherapy and sequential CIK cell immunotherapy (CIK group). Survival analysis showed significantly improved disease free survival (DFS) and OS rates in the CIK group compared with the control group (log-rank test, P = .0024; P = .008, respectively). Univariate and multivariate analyses indicated that sequential CIK cell treatment was an independent prognostic factor for patients' DFS and OS. Subgroup analyses showed that sequential CIK cell treatment significantly improved the DFS and OS of patients with high-risk T4 stage and insufficient chemotherapy duration. In conclusion, these data indicate that sequential adjuvant CIK cell treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with CRC, particularly for patients with high-risk T4 stage and insufficient chemotherapy duration.

13.
Seizure ; 79: 97-102, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32460217

RESUMO

PURPOSE: To compare the antiepileptic drug (AED) treatment patterns, seizure control, and folic acid supplementation between planned and unplanned pregnancy in women with epilepsy (WWE) and to investigate the effects of planned pregnancy on fetal outcomes. METHODS: A prospectively collected database including WWE with pregnancy from Feb 2010 to Dec 2018 was retrospectively analyzed. Planned pregnancy was defined as WWE being regularly supervised by epileptologists from the time of intended pregnancy until delivery. Clinical characteristics and fetal outcomes were compared between the planned and unplanned pregnancy groups. Logistic regression was used to identify modifiable factors associated with adverse fetal outcomes. RESULTS: A total of 188 planned pregnancies and 289 unplanned pregnancies were enrolled in our study. Among planned pregnancies, 66.0 % took AED monotherapy, and 32.4 % received polytherapy. Among unplanned pregnancies, 58.1 % didn't take AEDs, 28.0 % took monotherapy, and 12.8 % received polytherapy. The planned pregnancies had less generalized tonic-clonic seizures (P = 0.002) and higher proportion of being seizure-free (41.0 % vs. 22.8 %; P <0.001). All planned pregnancies took folic acid while 39.8 % of unplanned pregnancies never took it (P <0.001). The planned pregnancies had less rates of induced abortions (2.7 % vs. 13.5 %; P <0.001), preterm births (3.3 % vs. 20.4 %; P <0.001), and major congenital malformations (1.6 % vs. 7.5 %; P = 0.016). Pregnancy planning was independently associated with adverse fetal outcomes (adjusted OR, 0.14; 95 % CI, 0.08-0.27; P <0.001). CONCLUSION: Planned pregnancy in WWE contributes to more optimized AED pattern, better seizure control, more appropriate folic acid supplementation, and less adverse fetal outcomes.

14.
Sleep Med ; 69: 204-212, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32143064

RESUMO

OBJECTIVE: To investigate the potential prognostic value of sleep electroencephalography (EEG) pattern and serum circadian rhythm biomarkers in the recovery of consciousness in patients at the acute stage of coma. METHODS: A prospective observational study which included 75 patients with coma was conducted. Twenty-four-hour continuous polysomnography (PSG) was performed to determine the sleep EEG pattern according to the modified Valente's Grade (mVG) that we proposed. Serum levels of melatonin and orexin-A at four consecutive time points during the PSG were examined. Patients were then followed for one month to determine their level of consciousness. Multivariate logistic regression analysis was performed to examine associations between demographics, aetiology, baseline clinical features (pupillary and corneal reflex, and neuron-specific enolase [NSE]), clinical scores (Glasgow Coma Scale-Motor Response [GCS-M], Full Outline of Unresponsiveness [FOUR] scale, Acute Physiology and Chronic Health Evaluation II [APACHE II] scale), mVG, serum circadian biomarkers, and recovery of consciousness within one month. RESULTS: Within one month of enrolment, 34 patients regained consciousness and 36 patients remained non-conscious. Spearman rank correlation revealed a significant association between mVG and state of consciousness after one month. Significant variation in serum melatonin or orexin-A was not detected in either the conscious or non-conscious groups. Hypoxic aetiology, APACHE II, and mVG were independently associated with recovery of consciousness within one month. CONCLUSION: Sleep EEG structure, hypoxic aetiology, and APACHE II can independently predict recovery of consciousness in patients with acute coma. Taken together, we encourage neurologists to use sleep elements to assess patients with acute coma.

15.
Clin Transl Immunology ; 9(2): e1113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076550

RESUMO

Objectives: Fluoropyrimidine-based chemotherapy regimens are the current first-line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine-induced killer (CIK) cell immunotherapy and first-line chemotherapy in patients with mCRC. Methods: This retrospective study included 252 patients with mCRC treated with first-line chemotherapy. Among them, 126 patients received first-line chemotherapy only (control group), while the other 126 patients, with similar demographic and clinical characteristics, received CIK cell immunotherapy combined with first-line chemotherapy (CIK group). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method. Results: The median OS for the CIK group was 54.7 versus 24.1 months for the controls, and the median PFS for the CIK group was 25.7 versus 14.6 months for the controls. Univariate and multivariate analyses indicated that CIK cell treatment was an independent prognostic factor for patients' OS and PFS. Subgroup analyses showed that CIK cell treatment significantly improved the OS and PFS of patients with metastatic colon cancer, but not those with metastatic rectal cancer. Additionally, the change in CD3+CD56+ subsets after the fourth treatment cycle might be an indicator of successful CIK cell treatment: Patients with increased CD3+CD56+ subsets had better survival than those with decreased CD3+CD56+ subsets. Conclusion: Cytokine-induced killer cell immunotherapy combined with first-line chemotherapy could significantly improve the OS and PFS of patients with mCRC, particularly for patients with metastatic colon cancer.

16.
Cancer Immunol Immunother ; 69(5): 825-834, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32060687

RESUMO

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Induzidas por Citocinas/transplante , Citotoxicidade Imunológica , Imunoterapia/métodos , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Técnicas de Cultura de Células , Células Cultivadas/imunologia , Células Cultivadas/transplante , Terapia Combinada/métodos , Células Matadoras Induzidas por Citocinas/imunologia , Testes Imunológicos de Citotoxicidade , Feminino , Citometria de Fluxo , Hepatectomia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Análise de Sobrevida , Transplante Autólogo/métodos
17.
Thyroid ; 30(7): 1025-1036, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031055

RESUMO

Background: Sporadic medullary thyroid carcinoma (MTC) is a relatively uncommon neuroendocrine malignancy and the molecular tumorigenesis of its sporadic type (sMTC) is only partially understood. In this study, we performed a study focusing on the genomic and transcriptomic characterization of sMTC. Methods: Twenty-nine sMTC patients were included. Whole-exome sequencing (WES) was carried out in 18 patients, including both tumor samples and matched noncancerous tissues. Whole transcriptome sequencing (RNA-Seq) was performed in all 29 tumors. WES, RNA-Seq, and copy number alteration (CNA) data were analyzed. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell proliferation. Results: Among the somatic mutations, RET was the only recurrently cancer-related mutated gene (5/18, 27.8%). In the germline, FAT1 and FAT4, two members of the FAT gene family, were identified as the two most common mutated genes. CNA analysis found that FAT1 and FAT4, both located on chromosome 4q, were also two of the genes most commonly affected by somatic chromosomal deletions (4/18, 22.2%). Using TT and MZ-CRC-1 cell lines, the CCK-8 assay showed that FAT1 and FAT4 knockdown could promote MTC cell proliferation. Based on the gene expression profile, patients were clustered into two molecular subtypes: the mesenchymal-like subtype is characterized by epithelial-mesenchymal transition, while the proliferative-like subtype is associated with enrichment of cell cycle pathways. Most events of structural recurrence (80%) occurred in the proliferative-like subtype. Conclusion: In addition to RET, these findings demonstrate that FAT1/FAT4 genomic alterations appear to be frequent in sMTC. Two molecular subtypes of sMTC with distinct biological behavior could be identified. However, these results need to be validated by larger samples and more comprehensive experiments in the future, especially for the frequency and function of FAT1/FAT4 germline variants.

18.
J Hematol Oncol ; 13(1): 2, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900208

RESUMO

BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3ß signalling pathway in RCC, AGK can increase nuclear accumulation of ß-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3ß signalling pathway and might be a potential target for the further research of RCC.

19.
Biochem Biophys Res Commun ; 522(3): 749-756, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31787230

RESUMO

Sleep deprivation (SD) has detrimental effects on the physiological function of the brain. However, the underlying mechanism remains elusive. In the present study, we investigated the expression of candidate plasticity-related gene 15 (cpg15), a neurotrophic gene, and its potential role in SD using a REM-SD mouse model. Immunofluorescent and Western blot analysis revealed that the expression of cpg15 protein decreased in the hippocampus, ventral group of the dorsal thalamus (VENT), and somatosensory area of cerebral cortex (SSP) after 24-72 h of REM-SD, and the oxidative stress in these brain regions was increased in parallel, as indicated by the ratio of glutathione (GSH) to its oxidative product (GSSG). Over-expression of cpg15 in thalamus, hippocampus, and cerebral cortex mediated by AAV reduced the oxidative stress in these regions, indicating that the decrease of cpg15 might be a cause that augments oxidative stress in the sleep deprived mouse brain. Collectively, the results imply that cpg15 may play a protective function in the SD-subjected mouse brain via an anti-oxidative function. To our knowledge, this is the first time to provide evidences in the role of cpg15 against SD-induced oxidative stress in the brain.


Assuntos
Encéfalo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo , Privação do Sono/metabolismo , Animais , Encéfalo/patologia , Células COS , Chlorocebus aethiops , Proteínas Ligadas por GPI/metabolismo , Glutationa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Privação do Sono/patologia
20.
Huan Jing Ke Xue ; 40(6): 2773-2782, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854670

RESUMO

To improve the adsorption capacity of wheat biochar (BC) for arsenic (As), wheat stalks were selected as biomass to generate nano-sized goethite modified biochar (Goethite@BC) by co-precipitation. The adsorption capacities of BC, Goethite, and Goethite@BC for As(Ⅲ) were compared. The samples were analyzed by scanning electron microscopy (SEM) along with energy dispersive spectrometry (EDS), Brunauer-Emmett-Teller (BET), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. The results showed that the nano-goethite coating was uniformly attached to the surface of the BC and improved the surface area and total pore volume of the biochar. The adsorption of As(Ⅲ) by the three adsorbents was proved to fit well with the pseudo-second-order kinetic model and the Langmuir model. Compared to BC, the Goethite@BC increased the adsorption rate of As(Ⅲ) by 62.10 times, and the maximum adsorption capacity of Goethite@BC was 65.20 mg·g-1. The adsorption mechanism of Goethite@BC included non-specific adsorption (electrostatic attraction) and specific adsorption (coordination, complexation, ion exchange, etc.), and nano-goethite particles on the Goethite@BC surface played an important role in the adsorption of As. Goethite@BC has a good application prospects in the field of environmental remediation.

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