RESUMO
Normally, there are multiple microRNAs involved in the pathogenesis of liver fibrosis. In our work, we aimed at identifying the role of miR-34c in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. Our results have shown that during natural activation of HSC, the level of miR-34c was increased significantly whereas acyl-CoA synthetase long-chain family member-1(ACSL1), which is a key enzyme can affect fatty acid(FA) synthesis, was decreased. A double fluorescence reporter assay further confirmed that ACSL1 is a direct target gene of miR-34c. Moreover, the inhibition of miR-34C can attenuate the synthesis of collagen in HSC-T6. In our rescue assay, ACSL1 expression was 1.49-fold higher compared to normal control cells which were transfected with the miR-34c inhibitor in a stable low expression ACSL1 cell line. While at the same time, α-SMA and Col1α expression decreased by 18.22% and 2.58%, respectively. Moreover, we performed an in vivo model using dimethylnitrosamine (DMN) in conjunction with the miR-34c agomir, combined with the treatment of DMN and the miR-34c agomir can increase liver fibrosis. Meanwhile, the degree of hepatic fibrosis was increased and lipid droplets reduced dramatically in rats and HSC-T6 cell treated with miR-34c mimics alone compared to untreated groups. Our results indicate that miR-34c plays an essential role in liver fibrosis by targeting ACSL1 closely associated with lipid droplets, and it might be used as a potential therapeutic target.
Assuntos
Coenzima A Ligases/genética , Células Estreladas do Fígado/patologia , Cirrose Hepática Experimental/genética , Fígado/patologia , MicroRNAs/metabolismo , Animais , Coenzima A Ligases/metabolismo , Colágeno/biossíntese , Dimetilnitrosamina/administração & dosagem , Dimetilnitrosamina/toxicidade , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/citologia , Fígado/efeitos dos fármacos , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , RatosRESUMO
BACKGROUND & AIMS: The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS: We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS: We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION: Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.
Assuntos
Encefalopatia Hepática , Adulto , China , Encefalopatia Hepática/diagnóstico , Humanos , Cirrose Hepática , Masculino , Psicometria , Teste de StroopRESUMO
Lonicerae Japonicae Flos and Artemisiae Annuae Herba(LA or Jinqing) alcohol precipitation has various process parameters and complex process mechanism, and is one of the key units for manufacturing Reduning Injection. In order to identify the critical process parameters(CPPs) affecting the weight of the extract produced from the alcohol precipitation process, 259 batches of historical production data from 2017 to 2018 were collected, with a total of 829 318 data points. These data showed characteristics of large data, such as a large data volume, a low value density, and diverse sources. The data cleaning and feature extraction were first performed, and 48 feature variables were selected. The original data points were reduced to 9 936. Then, a combination of Pearson correlation analysis and grey correlation analysis were used to screen out 15 potential critical process parameters(pCPPs). After that, the partial least squares(PLS) was used in prediction of the weight of the extract, proving that the performance of predictive model based on 15 pCMAs is equivalent to that of predictive model based on 48 feature variables. The variable importance in projection(VIP) index was used to identify 9 CPPs, including 2 alcohol precipitation supernatant volume parameters, 4 initial extract weight parameters and 3 added alcohol volume parameters. As a result, the number of data points was 1 863, accounting for 0.28% of the original data. The big data analysis approach from a holistic point of view can effectively increase the value density of the original data. The critical process parameters obtained can help to accurately describe the quality transfer mechanism of the Jinqing alcohol precipitation process.
Assuntos
Big Data , Medicamentos de Ervas Chinesas/química , Álcoois , Solventes , Tecnologia FarmacêuticaRESUMO
To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D_c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.
Assuntos
Medicamentos de Ervas Chinesas/química , Molhabilidade , Cápsulas , Composição de Medicamentos , PósRESUMO
In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D_c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D_c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D_c+3.59×%H-5.29×%H×D_c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3)<D_c<0.63 g·cm~(-3) and 4.77<%H<7.59 according to the design space. The RTRT model of the disintegration time reflects the understanding of the process system, and lays a foundation for the implementation of intelligent control strategy of the key process of Tianshu Tablets.
Assuntos
Liberação Controlada de Fármacos , Medicamentos de Ervas Chinesas/química , Composição de Medicamentos , Análise dos Mínimos Quadrados , Solubilidade , ComprimidosRESUMO
BACKGROUND: This study aimed to confirm that blocking RasGRP4 can effectively slow down the growth of DLBCL both in vitro and in vivo and ascertain the role of RasGRP4 in the prognosis of DLBCL clinically. METHODS: RasGRP4 expression levels were examined in benign tissues and lymphomas. In order to verify somatic mutation in RasGRP4 gene, cDNA sequencing was performed in DLBCL patients. RasGRP4-dependent cell proliferation, mitochondrial membrane potential, oxidative stress levels and signaling pathway changes were measured by knockdown of RasGRP4. Tumor growth was monitored in xenografted lymphoma model. Clinical data were collected to confirm the role of RasGRP4 in DLBCL. RESULTS: RasGRP4 expression was significantly elevated in DLBCL while no somatic mutations were detected of this gene in DLBCL patients. Decreased RasGRP4 significantly inhibited cell proliferation by simultaneously reducing mitosis and promoting apoptosis and increased the oxidative stress levels. Mechanistically, reduced expression of RasGRP4 decreased ERK while increased JNK expression in SUDHL-4 cells. Knockdown of RasGRP4 also significantly inhibited tumor formation in vivo. Furthermore, RasGRP4 expression levels were significantly higher in patients with larger DLBCL lesions (P = 0.0004), high-risk international prognostic index score groups (P = 0.0042), and its expression was positively correlated with maximum standardized uptake value in DLBCL (P = 0.0004). CONCLUSIONS: These findings indicate the oncogenic role of RasGRP4 in DLBCL, suggesting it as a prognostic biomarker and potential therapeutic target in DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B/metabolismo , Fatores ras de Troca de Nucleotídeo Guanina/metabolismo , Animais , Apoptose , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , Modelos Animais de Doenças , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Transdução de Sinais , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate clinical characteristics and pathological changes of tissue surrounding prosthesis after hip and knee arthroplasty. METHODS: A total of 67 patients receiving hip and knee arthroplasty were included in the study and pathological changes of the revision specimens were evaluated by microscopic examination. RESULTS: Of 67 patients, there were 25 males and 42 females (ratio of 0.6) with a mean age of 64 years. There were 42 cases of revision hip prosthesis and 25 cases of knee prosthesis. The primary causes for the revision varied, including 20 cases of infection (29.9%, within 3 months in 9 cases,3 to 24 months in 3 cases and over 24 months in 8 cases), 14 cases of pain (20.9%), 13 cases of loosening of the prosthesis (19:4%), 9 cases of joint stiffness (13.4%), 8 cases of prosthetic dislocation (11.9%), and 3 cases of prosthesis fracture (4.5%). Pathological findings in the tissue surrounding the prostheses included debris reaction, histiocytes, acute inflammatory, chronic non-specific inflammation, pigmented villonodular synovitis (PVNS), "pseudomembranous", calcification, necrosis, sequestrum, etc. These histological changes were frequently admixed. CONCLUSIONS: Various reasons may lead to hip and knee revision arthroplasty. The main pathological findings include infection, debris granulomas, chronic non-specific inflammatory changes, PVNS. The surgical pathology of the prosthesis provids guidances for clinical treatment and basic research.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Articulação do Quadril/patologia , Articulação do Joelho/patologia , Prótese do Joelho , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Sinovite Pigmentada Vilonodular/patologiaRESUMO
Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n=60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Proteínas de Ligação a RNA/genética , Teniposídeo/uso terapêutico , Inibidores da Topoisomerase II/uso terapêutico , Regulação para Cima , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Glioblastoma/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Prognóstico , TransfecçãoRESUMO
UNLABELLED: MicroRNA 370 (miR-370) is located within the DLK1/DIO3 imprinting region on human chromosome 14, which has been identified as a cancer-associated genomic region. However, the role of miR-370 in malignances remains controversial. Here, we report that miR-370 was repressed in human hepatocellular carcinoma (HCC) tissues and hepatoma cell lines. Using gain-of-function and loss-of-function experiments, we demonstrated that miR-370 inhibited the malignant phenotype of HCC cells in vitro. Overexpression of miR-370 inhibited growth and metastasis of HCC cells in vivo. Moreover, the RNA-binding protein, LIN28A, was identified as a direct functional target of miR-370, which, in turn, blocked the biogenesis of miR-370 by binding to its precursor. LIN28A also mediated the suppressive effects of miR-370 on migration and invasion of HCC cells by post-transcriptionally regulating RelA/p65, which is an important effector of the canonical nuclear factor kappa B (NF-κB) pathway. Interleukin-6 (IL-6), a well-known NF-κB downstream inflammatory molecule, reduced miR-370 but increased LIN28A levels in HCC. Furthermore, miR-370 levels were inversely correlated with LIN28A and IL-6 messenger RNA (mRNA) levels, whereas LIN28A mRNA expression was positively correlated with IL-6 expression in human HCC samples. Interestingly, reduction of miR-370 expression was associated with the development of HCC in rats, as well as with aggressive tumor behavior and short survival in HCC patients. CONCLUSIONS: These data demonstrate the involvement of a novel regulatory circuit consisting of miR-370, LIN28A, RelA/p65 and IL-6 in HCC progression. Manipulating this feedback loop may have beneficial effect in HCC treatment.
Assuntos
Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/fisiologia , NF-kappa B/metabolismo , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Interleucina-6/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , Proteínas de Ligação a RNA , Fator de Transcrição RelA/fisiologiaRESUMO
Background: Immune checkpoint inhibitors (ICIs) represent a groundbreaking approach to cancer therapy. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have emerged as potential indicators strongly associated with tumor prognosis, albeit their prognostic significance remains contentious. The predictive value of NLR, PLR, LMR in patients with gastric cancer (GC) treated with ICIs has not been fully explored; therefore, we conducted a meta-analysis to examine the potential of inflammatory markers NLR, PLR, and LMR as survival predictors in this population. Methods: A comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, with the search cut-off date set as March 2024. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were calculated to assess the prognostic significance of NLR, PLR, and LMR for both progression-free survival (PFS) and overall survival (OS). Results: Fifteen cohort studies involving 1336 gastric cancer patients were finally included in this meta-analysis. The results of the meta-analysis showed that high levels of NLR were associated with poorer OS and PFS in GC patients receiving ICIs, with combined HRs of OS [HR=2.01, 95%CI (1.72,2.34), P<0.01], and PFS PFS[HR=1.59, 95%CI (1.37,1.86), P<0.01], respectively; high levels of PLR were associated with poorer OS and PFS, and the combined HR was OS [HR=1.57, 95%CI (1.25,1.96), P<0.01], PFS [HR=1.52,95%CI (1.20, 1.94), P<0.01], respectively; and there was an association between elevated LMR and prolonged OS and PFS, and the combined HR was OS [HR=0.62, 95%CI (0.47,0.81), P<0.01], and PFS [HR=0.69, 95%CI (0.50,0.95), P<0.01]. Conclusion: In gastric cancer (GC) patients treated with immune checkpoint inhibitors (ICIs), elevated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with poorer overall survival (OS) and progression-free survival (PFS), while high lymphocyte-to-monocyte ratio (LMR) was linked to improved OS and PFS. Subgroup analyses suggested that NLR might be particularly pertinent to the prognosis of GC patients. In conclusion, the inflammatory markers NLR, PLR, and LMR serve as effective biomarkers for prognostic assessment in GC patients, offering valuable insights for therapeutic decision-making in the realm of GC immunotherapy. Prospective studies of high quality are eagerly awaited to validate these findings in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024524321.
Assuntos
Biomarcadores Tumorais , Inibidores de Checkpoint Imunológico , Linfócitos , Neutrófilos , Neoplasias Gástricas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/sangue , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neutrófilos/imunologia , Prognóstico , Linfócitos/imunologia , Biomarcadores Tumorais/sangue , Plaquetas/imunologia , Contagem de Linfócitos , Monócitos/imunologia , Contagem de PlaquetasRESUMO
PURPOSE: Pigmented villonodular synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints, but there is not much information available about the disease's aetiology, clinical history, differential diagnosis, treatment, and long-term effects. We conducted a study to analyse these aspects of PVNS. METHODS: We reviewed all clinical data for 75 patients with PVNS (81 joints) who were treated either by synovectomy alone or synovectomy plus arthroplasty. RESULTS: In all cases, the diagnosis of PVNS was confirmed by pathological examination. The ratio of males to females was 27:48, and the average age of patients was 46 years (range, 15-80 years). Lesions were located in the knee, hip, or ankle, and pain and swelling were the main symptoms. Of 75 patients, 42 had a history of trauma to the involved joint. Forty-one patients (43 joints) underwent synovectomy alone, and 34 patients (38 joints) underwent synovectomy and arthroplasty together. Of the 75 patients, 61 had full follow-up data. Twelve patients had recurrent legions detected by pathological examinations; four patients had more than two recurrences. Moreover, five patients developed PVNS after arthroplasty. CONCLUSIONS: PVNS occurs most often in middle-aged women and most frequently involves the knee, followed by the hip and ankle. The disease's etiology is varied and unclear. Surgical excision alone or with arthroplasty is an effective treatment, but there is a high rate of recurrence.
Assuntos
Articulação do Tornozelo , Articulação do Quadril , Articulação do Joelho , Sinovite Pigmentada Vilonodular , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Artroplastia , Criança , Feminino , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Radiografia , Estudos Retrospectivos , Sinovectomia , Membrana Sinovial/diagnóstico por imagem , Sinovite Pigmentada Vilonodular/diagnóstico , Sinovite Pigmentada Vilonodular/etiologia , Sinovite Pigmentada Vilonodular/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Ochratoxin A (OTA) contamination seriously threatens food safety and human health and requires sensitive and rapid tools for monitoring. In this study, a convenient enzyme-linked immunosorbent assay based on Avi-labeled nanobody Nb-2G/streptavidin-alkaline phosphatase and magnetic beads (MBS-ELISA) was established for the sensitive detection of OTA, which could be used for one-pot detection without immobilization. After optimization, the 50% inhibitory concentration (IC50) and the lowest limit of detection value of the MBS-ELISA was 1.17 ng/mL and 0.07 ng/mL and the linear range was 248.8 pg/mL-5.28 ng/mL, respectively, which accords with state criteria for food safety. The developed one-step MBS-ELISA was almost 20-times more sensitive than the classic BA-ELISA and could generate results within 15 min, which was significantly less than the classic BA-ELISA at approximately 3 h. The MBS-ELISA indicated good recovery (86.4-114.3%) in spiked sorghum, buckwheat, and mung bean. Thus, MBS-ELISA represents a very promising strategy for the simple, rapid, and accurate detection of OTA and other toxic and hazardous contaminants.
Assuntos
Luminescência , Ocratoxinas , Humanos , Limite de Detecção , Estreptavidina , Ensaio de Imunoadsorção Enzimática/métodos , Ocratoxinas/análise , ImunoensaioRESUMO
Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12 months [95 % confidence interval (CI): 10.31-13.69 months], and the median progression-free survival (PFS) was 10 months (95 % CI: 7.33-12.67 months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.
Assuntos
Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Proteínas de Membrana/metabolismo , Western Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Proliferação de Células , Feminino , Seguimentos , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Técnicas Imunoenzimáticas , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Análise Serial de Tecidos , Células Tumorais CultivadasRESUMO
The overuse of antibiotics has aroused widespread concern in recent decades. Their residues in food and environment may pose potential risks to human health. Therefore, highly sensitive and rapid detection methods of antibiotics are urgently needed. Inspired by allosteric transcription factors (aTFs), we proposed a novel strategy for small molecules detection based on antibody controlled isothermal chain displacement amplification (ACISDA). A combination of nicking endonuclease, Klenow Fragment polymerase, specific antibody and a pair of antigen-labeled DNA regulate the synthesis of a G-quadruplex by isothermal chain displacement amplification. The presence of a target induces the antibody dissociation from the antigen-labeled DNA, which induces the synthesis of a G-quadruplex, and a fluorescent signal is produced by thioflavine T (ThT) binding to G-quadruplex. To test this notion, norfloxacin-conjugated DNA (named Primer-NOR) was prepared and ACISDA system was established combining with anti-norfloxacin antibody. This system could detect norfloxacin in a linear range of 0.1 â¼ 500 ng/mL with detection limit of 0.04 ng/mL, and this system could be applied to the detection of norfloxacin in real samples with good performance. Meanwhile, this system could also realize washing-free, immobilization-free and "ready-to-use", and could be used for other small molecules quickly by replacing the antigen-labeled DNA and specific antibody.
Assuntos
Técnicas Biossensoriais , Quadruplex G , Antibacterianos , Técnicas Biossensoriais/métodos , DNA/genética , Humanos , Limite de Detecção , Norfloxacino , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Pigmented villonodular synovitis (PVNS) is a rare benign proliferation lesion of the synovium of the joint, bursa, and the tendon sheath. We report here a case of PVNS in a 78-year-old woman 14 years after she underwent total arthroplasty of her right hip. Diffuse PVNS was detected in her right hip during surgery to replace her prosthesis, which had loosened. Macroscopically, the surface of the resected tissue was black and composed of papillae and nodules. Histologically, the tissue consisted of proliferative synoviocytes with black pigment in the cytoplasm. Beneath the synoviocytes were foamy cells. Pathologic analysis confirmed the diagnosis of PVNS with black pigment and the presence of hemosiderin. This indicates that implantation of the prosthesis might have caused the lesion or might have caused its proliferation.
Assuntos
Artroplastia de Quadril/efeitos adversos , Articulação do Quadril , Sinovite Pigmentada Vilonodular/etiologia , Idoso , Feminino , Humanos , Fatores de TempoRESUMO
In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.
Assuntos
Antioxidantes/uso terapêutico , Hidrogênio/uso terapêutico , Cloreto de Sódio/uso terapêutico , Traumatismos da Medula Espinal/prevenção & controle , Animais , Apoptose , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspases/metabolismo , Morte Celular , Membro Posterior/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Carbonilação Proteica , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Humanos , Microvasos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
BACKGROUND: The T-helper (Th)1/Th2 imbalance has been demonstrated to be involved in chronic heart failure (CHF). We sought to determine whether atorvastatin exhibited any effect on CHF through modulating the Th1/Th2 response. METHODS AND RESULTS: We measured serum concentrations of interleukin (IL)-12, -18, interferon (IFN)-gamma, IL-4, and IL-10 from 20 controls and 72 patients with nonischemic CHF by enzyme-linked immunosorbent assay. To investigate the effect of atorvastatin in vivo, CHF patients were either classified into a usual therapy group (n = 35) or usual therapy plus atorvastatin (10 mg/day) group (n = 37). Patient serum levels of IFN-gamma and IL-4 were measured at time of admission and 2 weeks after treatment. Peripheral blood mononuclear cells from patients of CHF group were cultured in the presence or absence of atorvastatin (0, 0.4, 1, and 4 micromol/L) in vitro, and IFN-gamma and IL-4 levels were detected. Serum levels of IL-12, IL-18, and IFN-gamma were significantly higher in the CHF group than in the control group. The levels of IFN-gamma and the ratios of IFN-gamma:IL-4 were significantly decreased with atorvastatin treatment both in vivo and in vitro, whereas levels of IL-4 did not differ significantly. CONCLUSIONS: Th1 polarization exists in patients with CHF, and atorvastatin can modulate the Th1/Th2 response through inhibiting Th1 cytokine production.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Atorvastatina , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/sangue , Humanos , Hipertensão/tratamento farmacológico , Técnicas Imunoenzimáticas , Inflamação/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-18/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Primary pulmonary lymphoma (PPL) mainly comprises mucosa-associated lymphoid tissue (MALT) lymphoma as well as other subtypes of lymphoma. Different phenotypes of PPL demonstrate various high-resolution computed tomography (HRCT) features. We aimed to evaluate the value of HRCT in the diagnosis and differential diagnosis of PPL, especially between MALT lymphoma and non-MALT lymphoma and the correlation between CT and pathological features. METHODS: We performed a retrospective analysis on 72 patients with PPL confirmed by pathology between 2007 and 2016. We compared the CT characteristics and correlation with pathological findings between MALT lymphoma and non-MALT lymphoma groups. RESULTS: All 72 patients with PPL were classified into two groups: low-grade MALT lymphoma (MALToma) (56/72) and high-grade non-MALT lymphoma (non-MALToma) (16/72). The latter group consisted of diffuse large B cell lymphoma (8/72), Hodgkin's lymphoma (3/72), T-cell lymphoma (4/72), and intravascular large B-cell lymphoma (1/72). A total of 168 lesions were analyzed, including 57 cases with multiple lesions and 15 cases with single lesion. The manifestation of four distribution patterns: nodular or mass-like involvement pattern, diffuse interstitial lung disease (DILD) pattern, pneumonia-like consolidative pattern and mixed pattern was not significantly different between MALToma and non-MALToma (all P>0.05). Signs of air bronchogram and CT angiogram occurred significantly more often in individuals with MALToma group than those with non-MALToma (75% vs. 25%, P=0.001; 64.3% vs. 12.5%, P<0.001; respectively). Conversely, the halo sign presented more often in non-MALToma than in MALToma patients (19% vs. 63.6%, P=0.02). In addition, the butterfly sign was only observed in four patients with MALToma. CONCLUSIONS: HRCT imaging phenotypes were beneficial in the diagnosis of PPL. Solitary or multifocal nodules/masses and consolidation were the most common imaging patterns. The air bronchogram sign, CT angiogram sign, halo sign, and butterfly sign could be potential to help to differentiate MALToma from non-MALToma.
RESUMO
OBJECTIVE: This study was intended to demonstrate the feasibility and efficacy of purge parathyroidectomy (PPTX) for patients with secondary hyperparathyroidism (SHPT). METHODS: The "seed, environment, and soil" medical hypothesis was first raised, following review of the literatures, to demonstrate the possible causes of persistence or recurrence of SHPT after parathyroidectomy. Subsequently, the novel surgical strategy of PPTX was proposed, which involves comprehensive resection of the fibro-fatty tissues, including visible or invisible parathyroid, within the region surrounded by the thyroid cartilage, bilateral carotid artery sheath, and the brachiocephalic artery. The perioperative information and clinical outcomes of patients who underwent PPTX from June 2016 to December 2016 were analyzed. RESULTS: In total, PPTX was performed safely in nine patients with SHPT from June 2016 to December 2016. The operative time for PPTX ranged from 95 to 135 min, and blood loss ranged from 20 to 40 mL. No patients with perioperative death, bleeding, convulsions, or recurrent laryngeal nerve injury were reported. The preoperative concentration of PTH ranged from 1062 to 2879 pg/mL, and from 12.35 to 72.69 pg/mL on the first day after surgery. In total, 37 parathyroid glands were resected. The postoperative pathologic examination showed that supernumerary or ectopic parathyroid tissues were found within the "non-parathyroid" tissues in three patients. No cases encountered persistence or recurrence of SHPT, or severe hypocalcemia during the follow-up period. CONCLUSION: PPTX involves comprehensive resection of supernumerary and ectopic parathyroid tissues, which may provide a more permanent means of reducing PTH levels.