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1.
Oncogenesis ; 9(12): 103, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277463

RESUMO

Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples. Functional assays based on site-directed mutagenesis showed that UCK2 promoted cell proliferation in a metabolic manner, but non-catalytically facilitates HCC metastasis. Mechanistically, in response to EGF, UCK2 interacted with EGFR to block EGF-induced EGFR ubiquitination and degradation, which resulted in elevated EGFR-AKT pathway activation and metastasis enhancement in HCCs. Concurrent pharmacological targeting on UCK2 and EGFR showed synergistic effects on HCC treatment. This study disclosed the non-metabolic role of UCK2 and suggested the therapeutic potential of concurrent blocking the metabolic and non-metabolic roles of UCK2 in HCC treatment.

2.
BMC Gastroenterol ; 20(1): 391, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213378

RESUMO

BACKGROUND: To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. METHODS: In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. RESULTS: The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). CONCLUSIONS: Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. TRIAL REGISTRATION: NCT01349348. Retrospectively registered May 2011.

3.
FEBS Lett ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070312

RESUMO

Global organ shortage has led to the acceptance of steatotic livers for transplantation, taking the risk of graft dysfunction associated with the higher sensitivity of steatotic livers to ischemia and reperfusion injury (IRI). Data about circular RNAs (circRNAs) in steatotic livers following IRI are practically nonexistent. In our study, a high-fat diet-fed mouse model of hepatic steatosis was generated, and RNA sequencing was performed both on IRI and on sham liver tissues of these mice to screen for circRNAs with significant differential expression. To further validate our bioinformatics data, one upregulated circRNA and four downregulated circRNAs were examined. The circularity of these circRNAs was demonstrated using RNaseR digestion and Sanger sequencing. The expression of four stable circRNAs undigested by RNaseR was further validated by quantitative PCR. In summary, this study unearths several circRNAs as novel and potentially effective targets involved in the more severe damage of steatotic livers following IRI.

4.
Antiviral Res ; 184: 104953, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33065138

RESUMO

BACKGROUND & AIMS: Normal/mildly elevated ALT (<2 × ULN) CHB patients are potentially at risk of progression to cirrhosis and/or hepatocellular carcinoma (HCC). We aimed to assess the outcomes of anti-viral therapy for normal/mild elevation of ALT CHB patients. METHODS: CHB patients (n = 432) who have had liver biopsied were determined. It was determined that the outcomes of anti-viral therapy in CHB patients with normal/mild elevation of ALT, in response to nucleoside/nucleotide analogues (NAs) (n = 190) and pegylated interferon (PEG-IFN) (n = 30) treatment for up to 72 weeks. Non-anti-viral treated patients were used as control (n = 40). RESULTS: There was about 50% of the CHB patients showed hepatic inflammatory necrosis ≥ G2 and/or fibrosis ≥ S2 among >30-years-old. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ~50%, ~80% or ~90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P < 0.05). ALT normalization rate was increased by 1.18-fold at week 72. HBsAg decline in HBeAg+ patients treated with NAs or PEG-IFN was 0.418 or 1.217 log IU/mL (P < 0.0001) at week 48; whereas HBsAg decline was 0.176 or 0.816 log IU/mL (P < 0.001) in HBeAg- patients. HBsAg at baseline and week 24 were strong predictors of "low HBsAg at week 48". CONCLUSION: Long term anti-viral therapy inhibits HBV replication effectively in ALT<2 × ULN CHB patients. PEG-IFN therapy is recommended for HBeAg+ patients with baseline HBsAg<4.37 log IU/ml and HBeAg- patients with baseline HBsAg<2.66 log IU/ml to achieve "low HBsAg at week 48".

5.
Artigo em Inglês | MEDLINE | ID: mdl-32831863

RESUMO

Objective: To evaluate the impact of long-term Traditional Chinese Medicine (TCM) syndrome differentiation combined with antiviral therapy with Nucleos (t) ide analogues (NAs) on the incidence of cirrhosis in patients with chronic hepatitis B. Methods: This retrospective cohort study included 521 patients with chronic hepatitis B who underwent a treatment course of ≥3 years from 1998-2019. Of the 521 patients, 261 were defined as TCM users while 260 were TCM nonusers (control group). All the enrolled subjects were followed up until February 2019 to measure the incidence and hazard ratio (HR) of cirrhosis, and the Cox proportional hazards regression model was used to analyze the independent factors affecting the occurrence of cirrhosis. Results: The cumulative incidence of TCM users and nonusers was 6.9% and 13.5%, respectively (P=0.013). Results of the Kaplan-Meier analysis demonstrated that TCM users had a significantly lower cumulative incidence of cirrhosis than TCM nonusers (P=0.011), and TCM users had a significantly lower liver cirrhosis risk than TCM nonusers (adjusted HR = 0.416, 95% CI, 0.231-0.749). The histological evaluation revealed improved fibrosis in 45.0% of TCM users and 11.1% of TCM nonusers (P=0.033). The analysation of the prescriptions including total 119 single Chinese herbs medicinal demonstrated that "replenish qi and fortify the spleen," "clear heat and dispel dampness," and "soothe the liver and regulate qi" are the main treatment methods of TCM for CHB. Conclusions: Our study demonstrated that long-term TCM use may attenuate liver cirrhosis risk in patients with chronic hepatitis B (CHB).

6.
J Immunol Res ; 2020: 1826587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766317

RESUMO

Helping B cells and antibody responses is a major function of CD4+T helper cells. Follicular helper T (Tfh) cells are identified as a subset of CD4+T helper cells, which is specialized in helping B cells in the germinal center reaction. Tfh cells express high levels of CXCR5, PD-1, IL-21, and other characteristic markers. Accumulating evidence has demonstrated that the dysregulation of Tfh cells is involved in infectious, inflammatory, and autoimmune diseases, including lymphocytic choriomeningitis virus (LCMV) infection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), IgG4-related disease (IgG4-RD), Sjögren syndrome (SS), and type 1 diabetes (T1D). Activation of subset-specific transcription factors is the essential step for Tfh cell differentiation. The differentiation of Tfh cells is regulated by a complicated network of transcription factors, including positive factors (Bcl6, ATF-3, Batf, IRF4, c-Maf, and so on) and negative factors (Blimp-1, STAT5, IRF8, Bach2, and so on). The current knowledge underlying the molecular mechanisms of Tfh cell differentiation at the transcriptional level is summarized in this paper, which will provide many perspectives to explore the pathogenesis and treatment of the relevant immune diseases.

7.
Cell Oncol (Dordr) ; 43(6): 1129-1145, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32623699

RESUMO

PURPOSE: Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), which has a male predominance, lacks effective therapeutic options. Previously, the cardiac glycoside analogue bufalin has been found to inhibit HBV infection and HCC development. As yet, however, its molecular role in HBV-associated HCC has remained obscure. METHODS: Colony formation and soft agar assays, xenograft and orthotopic mouse models and HBV X protein (HBx) transgenic mice with exposure to diethylnitrosamine were used to evaluate the effect of bufalin on HBV-associated HCC growth and tumorigenicity. HBx-induced oncogenic signaling regulated by bufalin was assessed using PCR array, chromatin immunoprecipitation, site-directed mutagenesis, luciferase reporter, transcription and protein expression assays. Synergistic HCC therapeutic effects were examined using combinations of bufalin and sorafenib. RESULTS: We found that bufalin exerted a more profound effect on inhibiting the proliferation of HBV-associated HCC cells than of non HBV-associated HCC cells. Bufalin significantly inhibited HBx-induced malignant transfromation in vitro and tumorigenicity in vivo. Androgen receptor (AR) signaling was found to be a target of bufalin resistance to HBV-associated hepatocarcinogenesis. We also found that bufalin induced both AR dephosphorylation and cell cycle-related kinase (CCRK) degradation to inhibit ß-catenin/TCF signaling, which subsequently led to cell cycle arrest via cyclin D1 down-regulation and p21 up-regulation, resulting in HCC regression. Furthermore, we found that bufalin reduced > 60% diethylnitrosamine-induced hepatocarcinogenesis in HBx transgenic mice, and improved the sensitivity of refractory HBV-associated HCC cells to sorafenib treatment. CONCLUSION: Our results indicate that bufalin acts as a potential anti-HCC therapeutic candidate to block HBx-induced AR/CCRK/ß-catenin signaling by targeting AR and CCRK, which may provide a novel strategy for the treatment of HBV-associated HCC.

8.
ACS Nano ; 14(4): 4816-4828, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32188241

RESUMO

Hepatocellular carcinoma (HCC) resistant to both chemotherapy and immunotherapy is among the deadliest malignancies. Doxorubicin widely used in transarterial chemotherapy in HCC can induce immunogenic cell death (ICD), but the resulting immunogenicity is still weak. We aim to seek a strategy for improving the efficacy of ICD in HCC based on an immunoregulatory drug called icaritin. Icaritin induced mitophagy and apoptosis to provoke ICD both in mouse Hepa1-6 and human Huh7 HCC cells. A combination of icaritin and doxorubicin with a molar ratio of 1:2 played a synergistic role in ICD induction. The poly lactic-co-glycolic acid (PLGA)-polyethylene glycol (PEG)-aminoethyl anisamide (AEAA) nanoparticle (NP) targeted codelivery of icaritin and doxorubicin remodeled the immunosuppressive tumor microenvironment and triggered a robust immune memory response, which efficiently improved anti-HCC effect at an early stage in mouse HCC model. In addition, the combo PLGA-PEG-AEAA NP together with lenvatinib significantly prolonged survival time of mice at the advanced stage of HCC. Collectively, our findings reveal an anti-HCC mechanism of icaritin on mitophagy and provide an effective immune-based therapeutic strategy for HCC.

9.
Int J Biol Sci ; 16(5): 869-881, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071556

RESUMO

Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database. The Least absolute shrinkage and selection operator (LASSO) regression model was used to establish a 7-mRNA-based signature that was significantly related to the recurrence-free survival (RFS) in two test series. Based on the 7-mRNA signature, the cohort TCGA patients could be divided into high-risk or low-risk subgroups with significantly different RFS [p < 0.001, hazard ratio (HR): 48.886, 95% confidence interval (CI): 6.226-3.837E+02]. Simultaneously, the prognostic value of the 7-mRNA signature was confirmed in clinical samples of Ren Ji hospital (p < 0.001, HR: 4.558, 95% CI: 1.829-11.357). Further analysis including multivariable and sub-group analyses revealed that the 7-mRNA signature was an independent prognostic value for recurrence of patients with CCA. In conclusion, our results might provide an efficient tool for relapse prediction and were beneficial to individualized management for CCA patients.

10.
Cell Mol Immunol ; 17(7): 753-764, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31481754

RESUMO

Despite the diverse etiologies of drug-induced liver injury (DILI), innate immunity activation is a common feature involved in DILI progression. However, the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains obscure. Herein, we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI. First, we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury (AILI) mouse model. Interestingly, both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver injury. Functional experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration, which are associated with an increased number of hepatic M2 macrophages. Mechanistically, CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1- and CCR5-mediated activation of the MAPK and NF-κB pathways. We then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse model. Our data demonstrate CCL5 induction during DILI, identify CCL5 as a novel innate immunity regulator in macrophage polarization, and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.

11.
J Autoimmun ; 107: 102372, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810856

RESUMO

The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQß1-Pro55, HLA-DPB1*17:01 or HLA-DPß1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRß1-Ala74, HLA-DQß1-Pro55 and HLA-DPß1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQß1 position 55 and HLA-DPß1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

12.
Artif Cells Nanomed Biotechnol ; 48(1): 336-344, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31884829

RESUMO

Cytoplasmic p27 plays an important role in regulating the cell cycle. Recent studies have revealed p27 protein translocation from the nucleus to the cytoplasm in many tumour cells. The aim of this study was to investigate the role and molecular mechanisms of cytoplasmic p27 in the progression of nasopharyngeal carcinoma (NPC) and to explore its prognostic value. We found increased cytoplasmic p27 expression by immunohistochemistry in NPC tissues, and its expression level was significantly correlated with the T classification and TNM clinical stage of NPC. The survival rate was significantly lower for NPC patients with cytoplasmic p27 immunopositivity than for NPC patients with cytoplasmic p27 immunonegativity, and cytoplasmic p27 was an independent risk factor that affected the prognosis of patients with NPC. Cytoplasmic p27 promoted the proliferation, cell cycle progression, migration, and invasion of NPC cells, increased Bim-1 and Twist1 protein levels, and decreased RhoA-GTP level. Collectively, these findings suggest that cytoplasmic relocalization of p27 is involved in the pathogenesis of NPC and is closely related to the unfavourable prognosis of patients with NPC. Therefore, cytoplasmic p27 might be a useful prognostic factor and potential therapeutic target for patients with NPC.


Assuntos
Biomarcadores Tumorais/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Citoplasma/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Citoplasma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Prognóstico
13.
Biochem Biophys Res Commun ; 518(3): 492-499, 2019 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-31443963

RESUMO

Dysregulated microRNAs (miRNAs) play crucial roles in the occurrence and development of multiple tumours, but their roles in the progression of nasal squamous cell carcinoma (NSCC) remain unknown. The aim of our study was to investigate the potential function and molecular mechanism of miR-143-3p in NSCC. Expression of miRNA and mRNA was detected by quantitative real-time reverse transcription-PCR (qRT-PCR). Forced overexpression of miR-143-3p was established by transfecting mimics into NSCC cell line. Then, we investigated the role of miR-143-3p in human NSCC cell proliferation, apoptosis, cycle and migration by using MTT, flow cytometry and transwell assays. Bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter analysis were performed to validate the relationship between miR-143-3p and its potential targets. We found that miR-143-3p was substantially downregulated in human NSCC tissues and cell line. Forced upregulation of miR-143-3p significantly attenuated cell proliferation and migration. Furthermore, this change could induce apoptosis and G1-phase arrest of NSCC cells. Mechanistically, miR-143-3p directly targeted and significantly suppressed Bcl-2 and IGF1R expression. In summary, miR-143-3p regulation of the proliferation, apoptosis, cell cycle and migration of NSCC probably partly depends on inhibition of Bcl-2 and IGF1R, indicating that miR-143-3p may be a novel molecular therapeutic target for NSCC.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias Nasais/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor IGF Tipo 1/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/patologia
15.
J Invest Surg ; : 1-10, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412745

RESUMO

Background: Tumor-associated macrophages (TAMs) are key components of the cancer microenvironment. This meta-analysis aimed to determine the association between TAMs and hepatocellular carcinoma (HCC). Methods: All studies investigating macrophages in HCC from January 2008 to May 2018 were retrieved by searching the Cochrane Library, EMBASE, PubMed, Chinese National Knowledge Infrastructure, and Wanfang databases. The associations of TAMs with overall survival (OS), disease-free survival (DFS) and the corresponding hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for analysis. Heterogeneity was assessed by using the Q test and I2 statistic. Statistical analyses were performed with Stata 13.0. Results: Seventeen articles with a total of 3547 patients were included in this meta-analysis. The pooled analysis showed that a high density of M2 TAMs in intratumor (IT) was significantly correlated with OS (HR = 1.58, 95%CI = 1.15-2.00), and the subgroup analysis suggested the significant difference in CD206+M2 TAMs (HR = 1.74, 95%CI = 1.26-2.21). However, the high expression levels of CD68+M1 TAMs in the IT or peritumor (PT) were not related with OS (CD68 in IT:HR = 1.30, 95%CI = 0.88-1.72;CD68 in PT:HR = 1.39, 95%CI = 0.93-1.85). Furthermore, a high density of CD206+M2 TAMs in IT showed a significant association with vascular invasion (OR = 2.18, 95%CI = 1.38-3.44) and more advanced TNM stage (OR = 2.38, 95%CI = 1.12-5.07). Conclusions: CD68+M1 TAMs have no prognostic effects on OS.A high density of M2 TAMs in IT is associated with poor prognosis in HCC, and CD206+ M2 TAMs can be used as a prognostic biomarker in HCC. However, the limit sample sizes might cause potential publication bias, thus more trails on CD206 are needed.

16.
Medicine (Baltimore) ; 98(35): e16844, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464911

RESUMO

RATIONALE: Facial nerve schwannoma (FNS) is a rare slow-growing nerve sheath tumor derived from Schwann cells. FNS with normal facial nerve function may sometimes be misdiagnosed as otitis media because of similar ontological symptoms such as purulence, tympanic membrane damage, and hearing loss. PATIENT CONCERNS: A 68-year-old woman was referred to our department because of otorrhea and hearing loss in the right ear for 20 years. Otoscopy revealed abundant purulent secretions deep in the right external auditory canal, and granulation proliferation in the posterior part of membranae tensa. Audiogram showed a right mixed hearing loss with an 85-dB pure-tone average and 35-dB air-bone gap. DIAGNOSIS: This patient was misdiagnosed as chronic suppurative otitis media before surgery. During surgery, a mass was found, and intraoperative frozen section histopathology confirmed an FNS. INTERVENTIONS: This patient was subjected to mastoidectomy for curing chronic suppurative otitis media initially. During surgery, a mass was found attached and widely extended into the tympanic and mastoid segments. We removed most part of the mass, however found the mass deriving from the vertical part of the facial nerve. Intraoperative frozen section histopathology confirmed an FNS. So we removed the incurs and malleus, and searched for the edge of the mass. The mass involved multisegments of facial nerve including the tympanic, vertical and pyramidal segments. The tumor was removed completely, and nerves were repaired using greater auricular nerves. OUTCOMES: After surgery, the patient had facial nerve paralysis of House-Brackmann (HB) Grade VI. Facial function recovered to HB Grade III at 30 months after surgery. The patient was followed up for 5 years. She had a facial function of HB grade III at the most recent follow-up. LESSONS: FNS is rare and tend to be misdiagnosed. It is important to combine the imaging modalities of computed tomography and magnetic resonance imaging to evaluate FNS before surgery. The primary goal of managing FNS is to maintain normal facial function as long as possible; therefore, tailored strategy should be taken for managing FNS.


Assuntos
Nervo Facial/cirurgia , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Idoso , Erros de Diagnóstico , Nervo Facial/patologia , Feminino , Humanos , Mastoidectomia , Neurilemoma/patologia , Otite Média Supurativa/cirurgia , Recuperação de Função Fisiológica
17.
Int J Biol Macromol ; 141: 410-421, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465803

RESUMO

The medicinal plant Morinda officinalis How and its root have long been used in traditional medicines in China. The aims of the present study were to investigate the chemical composition and liver-protective effect of crude polysaccharides (MOP-100) from the processed root of Morinda officinalis against Concanavalin A (ConA)-induced liver damage in vivo and vitro. The processed root of the herbal medicine was extracted with water at 100 °C, then precipitated with ethanol, dialyzed and freeze-dried to obtain MOP-100. The molecular weight of MOP-100 was a wide distribution. However, the processed root was extracted consecutively at 60 °C and 100 °C to obtain two crude polysaccharides MOP-60 and MOP-60-100. MOP-60 mainly contained an inulin-type fructooligosaccharide with molecular weight of 2071 Da. MOP-100 significantly inhibited the infiltration of neutrophils and macrophages into liver, improved the hepatic injury induced by ConA in mice. It stimulated the proliferation of human liver LO2 cells and decreased the cell death induced by ConA. MOP-100 also significantly inhibited the HBeAg secretion of Hep2.5.5 hepatocytes in vitro. MOP-60 and MOP-60-100 both exhibited good activity of protecting hepatocytes against ConA-induced damage in vitro. These results suggested Morinda officinalis polysaccharides exert significant hepatoprotective effect, and it might be used for treatment of immune-mediated liver disease in the future.


Assuntos
Inulina , Hepatopatias/tratamento farmacológico , Fígado/metabolismo , Morinda/química , Raízes de Plantas/química , Substâncias Protetoras , Linhagem Celular , Humanos , Inulina/química , Inulina/isolamento & purificação , Inulina/farmacologia , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31320916

RESUMO

Objective. To ascertain the efficacy and safety of Ganji Formulation (GF) for patients with Hepatocellular carcinoma (HCC) who had undergone surgery. Materials and Methods. A total of 262 HCC patients who had undergone liver resection, local ablation, or transcatheter arterial chemoembolization (TACE) were divided randomly into the treatment group and control group. The former was treated with GF and the later with placebo, both for 6 months. The primary endpoint was overall survival (OS). Second endpoints were disease-free survival (DFS) or time to disease progression (TTP). Results. OS of the treatment group was significantly longer than that of the control group (P < 0.05). Subgroup analysis showed that, for patients who received TACE, the TTP was significantly longer in the treatment group than in the control group (P < 0.05). However, for patients who underwent liver resection or local ablation, there was no significant difference in DFS between the two groups (P > 0.05). Conclusion. GF could improve postoperative cumulative survival and prolong the TTP. This clinical trial number is registered with ChiCTR-IOR-15007349.

19.
Hepatology ; 70(1): 294-307, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30854688

RESUMO

Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRß1-Asn77/Arg74, DRß1-Ser37, and DPß1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.


Assuntos
Anticorpos Antinucleares/genética , Antígenos Nucleares/imunologia , Autoantígenos/imunologia , Cirrose Hepática Biliar/genética , Idoso , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-Idade
20.
J Immunol Res ; 2019: 8983903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30766891

RESUMO

Aim: To compare the clinical efficacy of the combination therapy with Bushen formula (BSF) plus entecavir (ETV) in naïve chronic hepatitis B (CHB) patients and that in CHB patients with partial virological response to ETV and explore the relevant immunoregulatory mechanism. Materials and Methods: Two hundred and twenty CHB patients were enrolled in the historical prospective cohort study. Patients were categorized into a treatment group (T-Group: combination therapy with BSF plus ETV) and a control group (C-Group: ETV). Patients in T-Group and C-Group were grouped into T1/C1 (treatment-naïve patients) and T2/C2 (patients with partial virological response to ETV). Biochemical assessment, viral load quantitation, and HBV markers were tested. Chinese medicine symptom complex score was evaluated and recorded as well. In addition, peripheral blood mononuclear cells were separated from blood samples in 56 patients and 11 healthy donors. The frequencies of Th1, Treg, and dendritic cells (DCs) and expression levels of PD-1/PD-L1 were examined by flow cytometry. Results: In treatment-naïve CHB patients, complete viral suppression rates in HBeAg(-) patients were higher than those in HBeAg(+) patients in both T and C groups. In patients with partial virological response to ETV, the rate of HBsAg decline ≥ 20% in HBeAg(+) patients of T2-Group was higher than that in HBeAg(+) patients of C2-Group. A significant reduction of Chinese medicine symptom complex score was only observed in T-Group. The study of mechanism showed that, compared with healthy controls, Th1 and DC frequencies were decreased in all CHB patients, while Treg frequency was increased only in treatment-naïve patients. In addition, compared with healthy controls, PD-1 expression levels on Th1 and Treg were increased in all patients and PD-L1 expression levels on DCs were increased only in treatment-naïve patients. In treatment-naïve patients, the combination therapy with BSF plus ETV increased Th1 and DC frequencies and decreased Treg frequency, which was correlated with HBsAg decline. In addition, in patients with partial virological response to ETV, the combination therapy downregulated PD-L1 levels on DCs and the frequency of Treg, which was related with HBsAg decline. Conclusions: In patients with partial virological response to ETV, HBeAg(+) patients tend to achieve ideal effects after the combination therapy with BSF plus ETV, which may correlate with the decrease of Treg frequency and the downregulation of PD-L1 levels on DCs.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/terapia , Leucócitos Mononucleares/efeitos dos fármacos , Adulto , Antivirais , Terapia Combinada , Quimioterapia Combinada , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/imunologia , Humanos , Imunomodulação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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