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1.
Front Genet ; 12: 732376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646306

RESUMO

Background: Gliomas are the most common intracranial malignant neoplasms and have high recurrence and mortality rates. Recent literatures have reported that centromere protein N (CENPN) participates in tumor development. However, the clinicopathologic significance and biological functions of CENPN in glioma are still unclear. Methods: Clinicopathologic data and gene expression profiles of glioma cases downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were utilized to determine the associations between the expression of CENPN and clinical features of glioma. Kaplan-Meier and ROC curves were plotted for prognostic analysis. Gene set enrichment analysis (GSEA) and single sample gene set enrichment analysis (ssGSEA) were applied to identify immune-related functions and pathways associated with CENPN' differential expression. In vitro experiments were conducted to investigate the impacts of CENPN on human glioma cells. Results: Elevated CENPN expression was associated with unfavorable clinical variables of glioma patients, which was validated in clinical specimens obtained from our institution by immunohistochemical staining (IHC). The GSEA and ssGSEA results revealed that CENPN expression was strongly correlated with inflammatory activities, immune-related signaling pathways and the infiltration of immune cells. Cell experiments showed that CENPN deficiency impaired cell proliferation, migration and invasion ability and increased glioma apoptosis. Conclusion: CENPN could be a promising therapeutic target for glioma.

2.
Clin Neurol Neurosurg ; 208: 106838, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34339901

RESUMO

BACKGROUND: We conducted a meta-analysis to comprehensively assess the predictive role of MYC, BCL2, and BCL6 genetic alterations and protein expression in PCNSL for clinical application. METHODS: A systematic retrieval was performed on PubMed, Embase, the Cochrane library, Web of Science, Scopus, and 2 Chinese databases. Cohort studies discussing the prognostic impact of MYC, BCl2, or BCL6 genetic alterations or gene expression in PCNSL were selected. The pooled hazard ratio (HR) and median survival ratio (MSR) were calculated. RESULTS: 31 studies involving 1739 patients fulfilled our inclusion criteria. MYC expression was significantly associated with short median OS (MSR = 0.62; 95%CI, 0.44-0.88) and PFS (HR = 1.53; 95%CI, 1.06-2.20). No significant association was found between BCL2 expression and OS or PFS (P > 0.05). BCL6 protein positivity was significantly associated with extended median OS (MSR = 1.62; 95%CI, 1.10-2.40). MYC and BCL2 coexpression was significantly associated with short median OS (MSR = 0.61; 95%CI, 0.45-0.84). Subgroup analysis demonstrated that MYC protein positivity remained as a significant indicator for short median OS in studies whose sample size ≥ 45, treatment without WBRT, quality scale score ≥ 7, and positivity threshold set at 40% stratum (MSR < 1 and P < 0.05), but failed to reach a statistically significant difference in the other stratum. CONCLUSIONS: MYC expression predicts inferior median OS and PFS in PCNSL. BCL6 protein positivity is associated with a favorable prognosis. The sample size, average age of subjects, WBRT treatment, study quality, and cut-off values for discriminating positive and negative protein expression in IHC may be origins of heterogeneity.

3.
Front Neurosci ; 15: 706105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335175

RESUMO

Background: Among the effective approaches developed for blood-brain barrier (BBB) opening, ultrasound is recognized as a non-invasive technique that can induce localized BBB opening transiently and repeatedly. This technique has aroused broad attention from researchers worldwide, and numerous articles have been published recently. However, no existing study has systematically examined this field from a scientometric perspective. The aim of this study was to summarize the knowledge structure and identify emerging trends and potential hotspots in this field. Methods: Publications related to ultrasound-induced BBB opening published from 1998 to 2020 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: ("blood brain barrier" OR "BBB") AND topic: (ultrasound OR ultrason* OR acoustic* OR sonopora*). The document type was set to articles or reviews with language restriction to English. Three different analysis tools including one online platform, VOS viewer1.6.16, and CiteSpace V5.7.R2 software were used to conduct this scientometric study. Results: A total of 1,201 valid records were included in the final analysis. The majority of scientific publication was produced by authors from North America, Eastern Asia, and Western Europe. Ultrasound in Medicine and Biology was the most prominent journal. The USA, China, and Canada were the most productive countries. Hynynen K, and Mcdannold N were key researchers with considerable academic influence. According to analysis of keywords, four main research directions were identified: cluster 1 (microbubbles study), cluster 2 (management of intracranial tumors), cluster 3 (ultrasound parameters and mechanisms study), and cluster 4 (treatment of neurodegenerative diseases). The current research hotspot has shifted from the basic research of ultrasound and microbubbles to management of intracranial tumors and neurodegenerative diseases. Burst detection analysis showed that Parkinson's disease, doxorubicin, gold nanoparticle, glioblastoma, gene therapy, and Alzheimer's disease may continue to be the research frontiers. Conclusion: Ultrasound-induced BBB opening research is in a period of robust development. This study is a starting point, providing a comprehensive overview, development landscape, and future opportunities of this technology, which standout as a useful reference for researchers and decision makers interested in this area.

4.
Mol Cell ; 81(16): 3339-3355.e8, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352206

RESUMO

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.


Assuntos
Colangiocarcinoma/genética , Proteínas de Ligação ao GTP/genética , Metiltransferases/genética , Biossíntese de Proteínas , Animais , Carcinogênese/genética , Colangiocarcinoma/patologia , Progressão da Doença , Receptores ErbB/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Camundongos , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
5.
Front Pharmacol ; 12: 717192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322030

RESUMO

Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective. Methods: All relevant publications during 1998-2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords. Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R 2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention. Conclusion: To the authors' knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.

6.
Front Mol Neurosci ; 14: 634631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122006

RESUMO

Excessive inflammation leads to secondary immune damage after traumatic brain injury (TBI). The intestinal mucosa is a key component of immune tolerance due to gut-brain axis regulation, but the curative effect is not optimal. Intestinal dysfunction impairs the establishment of immune tolerance in patients with TBI. Therefore, we orally administered brain protein (BP) combined with probiotics to induce immune tolerance and explored the mechanism by which the homeostasis of the microbiota contributes to the enhancement of curative effects by BPs. Herein, we demonstrated that patients with TBI and surgical brain injury (SBI) models of rats had obvious dysbiosis. Notably, the intestinal barrier, proinflammatory cytokines, and activation of microglia demonstrated that excessive inflammatory damage was better controlled in the combined group (oral administration of BP combined with probiotics) than in the BP group (oral administration of BP). Fundamentally, tandem mass tag (TMT)-based quantitative proteomics analysis revealed that BP and probiotics preferentially affect Try-related pathways. A series of experiments further confirmed that Indoleamine 2,3 dioxygenase (IDO)/Kynurenine (Kyn)/Aryl hydrocarbon receptor (AhR) expression was high in the BP group, while Tryptophan hydroxylase 1(TpH1)/5-hydroxytryptamine (5-HT) only changed in the combined group. This study suggests that probiotics can enhance the efficacy of oral BP-induced immune tolerance through the Try pathway.

7.
J Gastroenterol Hepatol ; 36(9): 2531-2539, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33948991

RESUMO

BACKGROUND AND AIM: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients who underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in a hepatitis B virus (HBV)-related HCC population. METHODS: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection and remote site infection were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rates with different durations of POA was investigated. RESULTS: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of surgical site infection and 2.0% (19/934) of remote site infection. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (odds ratio = 0.50, 95% confidence interval = 0.30 to 0.83; P = 0.008). Albumin-bilirubin score, Barcelona Clinic Liver Cancer (BCLC) stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection. CONCLUSIONS: Postoperative antibiotic is necessary for HBV-related HCC patients to prevent postoperative infection, especially for those with higher albumin-bilirubin score, at BCLC stage B-C, or who underwent major hepatectomy. For HBV-related HCC patients, postoperative second-generation cephalosporins, or ceftriaxone for 3 days after surgery might be proper.

8.
Kidney Int ; 100(2): 377-390, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34051263

RESUMO

Receptor activator of NF-κB (RANK) expression is increased in podocytes of patients with diabetic nephropathy. However, the relevance of RANK to diabetic nephropathy pathobiology remains unclear. Here, to evaluate the role of podocyte RANK in the development of diabetic nephropathy, we generated a mouse model of podocyte-specific RANK depletion (RANK-/-Cre T), and a model of podocyte-specific RANK overexpression (RANK TG), and induced diabetes in these mice with streptozotocin. We found that podocyte RANK depletion alleviated albuminuria, mesangial matrix expansion, and basement membrane thickening, while RANK overexpression aggravated these indices in streptozotocin-treated mice. Moreover, streptozotocin-triggered oxidative stress was increased in RANK overexpression but decreased in the RANK depleted mice. Particularly, the expression of NADPH oxidase 4, and its obligate partner, P22phox, were enhanced in RANK overexpression, but reduced in RANK depleted mice. In parallel, the transcription factor p65 was increased in the podocyte nuclei of RANK overexpressing mice but decreased in the RANK depleted mice. The relevant findings were largely replicated with high glucose-treated podocytes in vitro. Mechanistically, p65 could bind to the promoter regions of NADPH oxidase 4 and P22phox, and increased their respective gene promoter activity in podocytes, dependent on the levels of RANK. Taken together, these findings suggested that high glucose induced RANK in podocytes and caused the increase of NADPH oxidase 4 and P22phox via p65, possibly together with the cytokines TNF- α, MAC-2 and IL-1 ß, resulting in podocyte injury. Thus, we found that podocyte RANK was induced in the diabetic milieu and RANK mediated the development of diabetic nephropathy, likely by promoting glomerular oxidative stress and proinflammatory cytokine production.


Assuntos
Nefropatias Diabéticas , Podócitos , Receptor Ativador de Fator Nuclear kappa-B , Albuminúria/genética , Animais , Diabetes Mellitus , Nefropatias Diabéticas/genética , Camundongos , Estreptozocina
9.
J Nanobiotechnology ; 19(1): 142, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001148

RESUMO

BACKGROUND: Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. RESULTS: HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. CONCLUSION: Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

10.
Front Genet ; 12: 649270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859674

RESUMO

Background: Growth arrest-specific 2 like 3 (GAS2L3) is a cytoskeleton-associated protein that interacts with actin filaments and tubulin. Abnormal GAS2L3 expression has been reported to be associated with carcinogenesis. However, the biological role of GAS2L3 in glioma remains to be determined. Methods: The transcriptome level of GAS2L3 and its relationship with clinicopathological characteristics were analyzed among multiple public databases and clinical specimens. Bioinformatics analyses were conducted to explore biological functions and prognostic value of GAS2L3 in glioma. Results: GAS2L3 was substantially expressed in glioma, and high GAS2L3 expression correlated with shorter overall survival time and poor clinical variables. Gene set enrichment analysis (GSEA), single-sample gene-set enrichment analysis, and CIBERSORT algorithm analyses showed that GAS2L3 expression was closely linked to immune-related pathways, inflammatory activities, and immune cell infiltration. Moreover, GAS2L3 was synergistic with T cell-inflamed gene signature, immune checkpoints, T-cell receptor diversities, and neoantigen numbers. Conclusion: This study suggests that GAS2L3 is a prognostic biomarker for glioma, providing a reference for further study of the potential role of GAS2L3 in the immunomodulation of glioma.

11.
Hepatology ; 74(3): 1339-1356, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33638162

RESUMO

BACKGROUND AND AIMS: The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote HCC progression; however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains open for study. APPROACH AND RESULTS: Using an IRFA HCC orthotopic mouse model, we detected a higher level of m6 A reader YTH N6-methyladenosine RNA binding protein 1-3 (YTHDF1) in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model, and patients' HCC tissues. Functionally, gain-of-function/loss-of-function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases epidermal factor growth receptor (EGFR) m6 A modification in the vicinity of the 5' untranslated region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal-heat-induced up-regulation of EGFR level was further confirmed in the IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically. CONCLUSIONS: The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery combined with EGFR inhibitors to suppress HCC metastasis after RFA.

12.
Acta Biochim Biophys Sin (Shanghai) ; 53(4): 446-453, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637977

RESUMO

Long non-coding RNAs (lncRNAs) have been proposed to play pivotal roles in the tumorigenesis of various malignant tumors. Previous studies have found that lncRNA LBX2-AS1 is involved in the progression of various tumors. However, currently, the expression and exact mechanism of LBX2-AS1 in glioma remain unclear. In this study, using online-available datasets combined with clinical glioma tissues collected, we found that LBX2-AS1 was significantly increased and negatively correlated with prognosis in glioma. In vitro functional assays such as CCK-8, Annexin V, transwell assay, and western blot analysis showed that silencing of LBX2-AS1 suppressed the proliferation, migration, and invasion of glioma cells and increased apoptosis. RNA sequencing and western blot analysis confirmed that LBX2-AS1 regulates the Akt/GSK3ß pathway. In conclusion, this study showed that lncRNA LBX2-AS1 depletion inhibits the proliferation, migration, and invasion of glioma cells and increases apoptosis through the Akt/GSK3ß pathway. lncRNA LBX2-AS1 is expected to become a new target for glioma therapy.


Assuntos
Inativação Gênica , Glioma/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Glioma/genética , Glioma/patologia , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética
13.
Rev. esp. enferm. dig ; 112(11): 843-849, nov. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-198768

RESUMO

OBJECTIVE: hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common pathological type of hepatitis B virus-associated glomerulonephritis. This study evaluated the efficacy of entecavir antiviral therapy for HBV-MN patients due to the intolerable side effects of interferon-alpha and high incidence rate of drug-resistance in lamivudine therapy. METHOD: thirty-two patients with HBV-MN were identified by biopsy and treated with entecavir for 52 weeks. These patients were followed up to evaluate outcomes of entecavir-treatment. Descriptive statistics were used to summarize patient demographics and treatment outcomes. RESULTS: entecavir treatment reduced 24-h urinary protein excretion. The total probability of partial proteinuria and complete remission at 24 and 52 weeks was 53.1 and 78.1 %, respectively. A decrease of circulating HBV-DNA was observed in all patients with active HBV replication. The significant decrease of 24-h urinary protein began at 12 weeks, as early as the decrease of serum HBV-DNA level. The serum HBV DNA titers at baseline and after 52 weeks of treatment were 4.3 ± 2.8 log10 and 2.3 ± 1.7 log10, respectively. Meanwhile, eGFR increased from 100.3 ± 20.5 ml/min/1.73 m2 at baseline to 107.7 ± 15.9 ml/min/1.73 m2 after 52 weeks of treatment. The serum alanine aminotransferase level (ALT) gradually decreased to normal during entecavir antiviral treatment. CONCLUSIONS: entecavir treatment in HBV-MN patients was carefully described. Complete remission and HBV replication suppression were induced by entecavir treatment in HBV-MN patients. Patients with high serum creatinine (Scr), ALT and low eGFR levels benefit more from entecavir treatment. Entecavir therapy is well tolerated by patients and no adverse reactions were observed


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/virologia , Guanina/análogos & derivados , Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Proteinúria/urina , Taxa de Filtração Glomerular , Glomerulonefrite Membranosa/fisiopatologia , Vírus da Hepatite B/isolamento & purificação , Alanina Transaminase/sangue , Creatinina/sangue , DNA Viral
14.
Rev Esp Enferm Dig ; 112(11): 843-849, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33054304

RESUMO

OBJECTIVE: hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common pathological type of hepatitis B virus-associated glomerulonephritis. This study evaluated the efficacy of entecavir antiviral therapy for HBV-MN patients due to the intolerable side effects of interferon-alpha and high incidence rate of drug-resistance in lamivudine therapy. METHOD: thirty-two patients with HBV-MN were identified by biopsy and treated with entecavir for 52 weeks. These patients were followed up to evaluate outcomes of entecavir-treatment. Descriptive statistics were used to summarize patient demographics and treatment outcomes. RESULTS: entecavir treatment reduced 24-h urinary protein excretion. The total probability of partial proteinuria and complete remission at 24 and 52 weeks was 53.1 and 78.1 %, respectively. A decrease of circulating HBV-DNA was observed in all patients with active HBV replication. The significant decrease of 24-h urinary protein began at 12 weeks, as early as the decrease of serum HBV-DNA level. The serum HBV DNA titers at baseline and after 52 weeks of treatment were 4.3 ± 2.8 log10 and 2.3 ± 1.7 log10, respectively. Meanwhile, eGFR increased from 100.3 ± 20.5 ml/min/1.73 m2 at baseline to 107.7 ± 15.9 ml/min/1.73 m2 after 52 weeks of treatment. The serum alanine aminotransferase level (ALT) gradually decreased to normal during entecavir antiviral treatment. CONCLUSIONS: entecavir treatment in HBV-MN patients was carefully described. Complete remission and HBV replication suppression were induced by entecavir treatment in HBV-MN patients. Patients with high serum creatinine (Scr), ALT and low eGFR levels benefit more from entecavir treatment. Entecavir therapy is well tolerated by patients and no adverse reactions were observed.


Assuntos
Glomerulonefrite Membranosa , Guanina/análogos & derivados , Hepatite B Crônica , Antivirais/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Guanina/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Resultado do Tratamento
15.
Nat Commun ; 11(1): 5211, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060583

RESUMO

Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.


Assuntos
Cromatina/fisiologia , Células Endoteliais/metabolismo , RNA/metabolismo , Estresse Fisiológico/fisiologia , DNA/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Epigenômica , Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Glucose/metabolismo , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
Exp Ther Med ; 20(3): 2903-2908, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32765788

RESUMO

Efficacy and safety of vascular intervention combined with intravenous thrombolysis (IVT) was investigated in the treatment of acute intracranial arterial occlusion (AIAO). Ninety-two patients with AIAO treated in People's Hospital of Tongchuan from January 2014 to February 2016 were enrolled in this retrospective study. Forty-two patients were treated with vascular intervention (control group), while another 50 patients were treated with vascular intervention combined with IVT (study group). They were observed in terms of the improvement of clinical efficacy after treatment, the comparison of complications after treatment, the National Institute of Health Stroke Scale (NIHSS) score after treatment, the modified Rankin Scale (mRS) score at 3 months after treatment, and the Mini-Mental State Examination (MMSE) score at 3 months after treatment. Compared with those in the control group, patients in the study group had statistically significantly higher marked effectiveness and statistically significantly lower ineffectiveness (P=0.018), and a statistically significantly higher overall effective rate (P=0.042). The NIHSS score in the study group was statistically significantly lower than that in the control group after treatment (P=0.001). There was a statistically significant difference between the two groups in the mRS score at 3 months after treatment (Z=8.764, P>0.05). Compared with those in the control group, patients in the study group had a statistically significantly higher MMSE score after treatment, and a statistically significantly lower total incidence of postoperative complications (P=0.001). Vascular intervention combined with IVT has good efficacy and high safety in the treatment of AIAO, and the combination can statistically significantly improve patients' quality of life, so it has a good clinical application value.

17.
Clin Cancer Res ; 26(18): 4947-4957, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32527942

RESUMO

PURPOSE: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms. EXPERIMENTAL DESIGN: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti-programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated. RESULTS: The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti-PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti-PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma. CONCLUSIONS: The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti-PD-1 therapy.

18.
FEBS Open Bio ; 10(5): 904-911, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32237064

RESUMO

Glioblastoma multiforme (GBM) and primary central nervous system lymphoma (PCNSL) are both malignant cerebral tumors; however, their treatments are vastly different. Early and precise diagnosis is vital for subsequent adequate treatment to improve prognosis. Reliable biomarkers that can easily distinguish GBM and PCNSL are urgently needed. We evaluated the diagnostic potential of lymphocyte-specific protein tyrosine kinase (LCK) as a biomarker in differentiating PCNSL from GBM using established computational approaches (Gene Expression Profiling Interactive Analysis, The Cancer Proteome Atlas, Tumor Immune Estimation Resource, GEO, Oncomine) and immunohistochemistry. The results showed that LCK was expressed at a high level in PCNSL patients but at a low level in GBM patients. Moreover, LCK expression positively correlated with the levels of infiltrating B cells in diffuse large B-cell lymphoma (DLBCL) and GBM. Overall, bioinformatics analysis and immunohistochemistry revealed that LCK expression is a potential biomarker for distinguishing PCNSL from GBM.

19.
J Cancer ; 11(10): 2874-2886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226505

RESUMO

Aims: Aberrant hypermethylation of CpG islands is an important hallmark of colorectal cancer (CRC). We previously utilized methyl-DNA immunoprecipitation assays to identify a novel methylated gene, chondrolectin (CHODL), preferentially methylated in human CRC. In this study, we examined the epigenetic inactivation, biological effects and prognostic significance of CHODL in CRC. Main methods: The methylation status of CHODL in CRC was evaluated by bisulfite genomic sequencing (BGS). The functions of CHODL in CRC were determined by proliferation, apoptosis, cell migration and invasion assays. The impact and underlying mechanisms of CHODL in CRC were characterized by western blot and RNA-Seq analyses. The association between CHODL and CRC clinical features was examined using The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. Key findings: CHODL was downregulated in 10 CRC cell lines and CRC tissues, and promoter hypermethylation contributed to its inactivation. Ectopic expression of CHODL inhibited colony formation, suppressed cell viability, induced apoptosis, and restrained cell migration and invasion in vitro and in vivo. Furthermore, high CHODL expression in CRC was a predictor of improved survival, though CHODL hypermethylation was a poor prognostic factor for CRC patients, especially those with early-stage CRC. Significance: CHODL promoter hypermethylation silences CHODL expression in CRC, and CHODL suppresses CRC tumorigenesis. CHODL methylation and expression levels can be used as potential markers to evaluate the prognosis of CRC patients.

20.
Kidney Med ; 2(3): 354-358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292904

RESUMO

Coronavirus disease 2019 (COVID-19) is a highly infective disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2). Previous studies of the COVID-19 pneumonia outbreak were based on information from the general population. Limited data are available for hemodialysis patients with COVID-19 pneumonia. This report describes the clinical characteristics of COVID-19 in an in-center hemodialysis patient, as well as our experience in implementing steps to prevent the spread of COVID-19 pneumonia among in-center hemodialysis patients. The diagnosis, infection control, and treatment of COVID-19 in hemodialysis patients are discussed in this report, and we conclude with recommendations for how a dialysis facility can respond to COVID-19 based on our experiences.

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