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1.
Diagn Pathol ; 18(1): 97, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644531

RESUMO

BACKGROUND: Malakoplakia is a rare inflammatory disease of the urogenital tract. There have been no reports of malakoplakia expressing anaplastic lymphoma kinase (ALK) to date. Here, we present one case of malakoplakia with aberrant ALK expression by immunohistochemistry and discuss the clinical significance. CASE PRESENTATION: A 65-year-old Chinese woman with a history of diabetes presented with solid masses in the liver and kidney and elevated lesions on the mucosal surface of the colon. Right nephrectomy and partial liver resection were performed. Microscopically, sheets of histiocytes with poor intercellular adhesion were seen, with Michaelis-Gutmann bodies present in both the intracellular and extracellular interstitium. CD10-, CD68-, and CD163-positive cells were present, with Michaelis-Gutmann bodies confirmed by staining with Alcian blue, periodic acid-Schiff (PAS), periodic acid-Schiff with diastase, Von Kossa, and Prussian blue. Aberrant ALK1 and ALK (D5F3) expression was observed in the cytoplasm and nucleus of cells. However, ALK gene mutation was not detected by fluorescence in situ hybridization or whole exome next-generation sequencing. NGS revealed nine individual somatic gene mutations: GOT1L1, GLIS2, SPOUT1, TMEM97, MUC3A, NSD2, SFXN5, ADAD1 and RAD50. The significance of the somatic gene mutations detected in this study is not clear, and the relationship between them and malakoplakia cannot be clarified by existing scientific studies. The pathological diagnosis was malakoplakia with aberrant ALK expression by immunohistochemistry. The antibiotics imipenem and vancomycin were started based on the results of drug sensitivity analysis and the patient was subsequently discharged. She experienced no discomfort during 30 months of follow-up. CONCLUSION: This is the first reported case of malakoplakia with aberrant ALK expression, it should be differentiated from ALK-positive histiocytosis to avoid misdiagnosis.


Assuntos
Malacoplasia , Feminino , Humanos , Idoso , Quinase do Linfoma Anaplásico , Imuno-Histoquímica , Malacoplasia/diagnóstico , Hibridização in Situ Fluorescente , Ácido Periódico
2.
Int J Rheum Dis ; 26(7): 1268-1275, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37170730

RESUMO

OBJECTIVE: To investigate the clinical characteristics of systemic lupus erythematosus accompanied by autoimmune liver cirrhosis (SLE-ALC) patients and differences from the non-cirrhosis group. METHODS: Forty-three patients with SLE-ALC were enrolled in this study from 2653 patients with SLE in Peking University People's Hospital. A descriptive case-control study was performed between SLE-ALC patients and the entry time-matched non-cirrhosis group. RESULTS: Among the 43 SLE-ALC patients, 41 (95.3%) were female. Eight patients (18.6%) were first found to have cirrhosis and then diagnosed with SLE. Eighteen patients (41.9%) had jaundice and 27 (62.8%) had esophageal and gastric varices. The age of SLE-ALC patients was 51.1 ± 17.2 years, which was significantly older than the non-cirrhosis group (P < 0.001). Lung involvement was more common as initial manifestations in SLE-ALC patients during the SLE course (P=0.027). Compared with the non-cirrhosis group, SLE-ALC patients had worse liver function. A significantly higher rate of hematological system involvement (anemia, leucopenia, and thrombocytopenia) and a higher level of immunoglobulins were observed in SLE-ALC patients (P<0.05). Moreover, SLE-ALC patients displayed a lower positive rate of anti-double-stranded DNA and anti-ribosomal P protein (P<0.05). The most common radiologic manifestations are ascitic fluid (72.1%) and splenomegaly (71.4%) in SLE-ALC patients. Six SLE-ALC patients underwent liver biopsy, and interface hepatitis was present in all patients. CONCLUSIONS: Cirrhosis is rare in SLE patients but is manifested as a unique pattern of clinical features characterized by late-onset age, lung involvement, high immunoglobulins, and impaired liver function.


Assuntos
Hepatopatias , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Estudos de Casos e Controles , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Cirrose Hepática/diagnóstico
3.
Chin J Integr Med ; 29(5): 434-440, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36474083

RESUMO

OBJECTIVE: To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy. METHODS: H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells. RESULTS: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05). CONCLUSION: Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Autofagia
4.
BMC Complement Med Ther ; 22(1): 310, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434600

RESUMO

BACKGROUND: Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear. METHODS: Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim's ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim's ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim's ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds' anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock. RESULTS: Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski's rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets. CONCLUSIONS: The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.


Assuntos
Gentiana , Masculino , Animais , Ratos , Gentiana/metabolismo , Espectrometria de Massas em Tandem , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Oxigênio , Peso Corporal
5.
World J Clin Cases ; 10(15): 4886-4894, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35801029

RESUMO

BACKGROUND: Nonfunctional pancreatic neuroendocrine tumours are difficult to diagnose in the early stage of disease due to a lack of clinical symptoms, but they can rarely manifest as autoimmune pancreatitis. Autoimmune pancreatitis is an uncommon disease that may cause recurrent acute pancreatitis and is therefore often regarded as a special type of chronic pancreatitis. CASE SUMMARY: We report a case of a 42-year-old female who had nonspecific upper abdominal pain for 4 years and radiological abnormalities of the pancreas that mimicked autoimmune pancreatitis. The symptoms and pancreatic imaging did not improve following 1 year of steroid therapy. Finally, pancreatic biopsy was performed through endoscopic ultrasonography-guided fine-needle aspiration biopsy, and nonfunctional pancreatic neuroendocrine tumours were ultimately diagnosed. Pancreatectomy has resolved her symptoms. CONCLUSION: Therefore, the differentiation of nonfunctional pancreatic neuroendocrine tumours from autoimmune pancreatitis is very important, although it is rare. We propose that endoscopic ultrasonography-guided fine-needle aspiration biopsy should be performed if imaging characteristics are equivocal or the diagnosis is in question.

6.
J Mater Chem B ; 10(19): 3624-3636, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35420616

RESUMO

Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the commercial antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clinical wound management and skin regeneration.


Assuntos
Fator de Crescimento Epidérmico , Fibroínas , Antibacterianos/farmacologia , Bandagens , Fator de Crescimento Epidérmico/farmacologia , Gelatinases , Peptídeos , Cicatrização
7.
Artigo em Inglês | MEDLINE | ID: mdl-34655890

RESUMO

Bufei-Huoxue Capsule (BFHX) was applied to treat chronic obstructive pulmonary disease (COPD) in China. It is composed of Astragali Radix, Paeoniae Radix Rubra, and Psoralea Fructus. A sensitive and reliable ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated to quantify the eight main bioactive compounds (psoralen, isopsoralen, neobabaisoflavone, corylin, bavachin, astragaloside IV, ononin and formononetin) in rat plasma after oral administration of BFHX. Osthol was used as an internal standard (IS). Plasma samples were pretreated with methanol to precipitate protein. Chromatographic separation was accomplished using Hypersil GOLDTM C18 column (2.1 mm × 100 mm, 1.9 µm) with a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile and the flow rate was set at 0.2 mL/min. Multiple reaction monitoring (MRM) mode was applied to perform mass spectrometric analyses. All calibration curves were linear (r > 0.9908) in tested ranges. The intra- and inter-day accuracy and precisions of eight compounds at three different concentration levels were within the acceptable limits. The extraction recovery was within the range of 76.4 âˆ¼ 105.2% and the matrix effects were within the range of 88.3 âˆ¼ 115.0% (RSD ≤ 15.6%). The dilution effects were within the range of 90.2 âˆ¼ 114.9%. These 8 compounds were stable under the tested conditions. So the developed method was valid to evaluate the pharmacokinetic study of eight bioactive compounds after oral administration of BFHX.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Flavonoides , Furocumarinas , Espectrometria de Massas em Tandem/métodos , Animais , Medicamentos de Ervas Chinesas/química , Flavonoides/sangue , Flavonoides/química , Flavonoides/farmacocinética , Furocumarinas/sangue , Furocumarinas/química , Furocumarinas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
8.
Technol Cancer Res Treat ; 20: 15330338211033064, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34496678

RESUMO

BACKGROUND: With the knowledge of oligometastases, primary surgery plays an increasingly vital role in metastatic non-small cell lung cancer. We aimed to evaluate the survival benefit of primary surgery based on metastatic patterns. MATERIALS AND METHODS: The selected patients with stage IV extrathoracic metastatic (m1b) non-small cell lung cancer between 2010 and 2015 were included in a retrospective cohort study from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple imputation was used for the missing data. Patients were divided into 2 groups depending on whether surgery was performed. After covariate balancing propensity score (CBPS) weighting, multivariate Cox regression models and Kaplan-Meier survival curve were built to identify the survival benefit of different metastatic patterns. RESULTS: Surgery can potentially increase the overall survival (OS) (adjusted HR: 0.68, P < 0.001) of non-small cell lung cancer. The weighted 3-year OS in the surgical group was 16.9%, compared with 7.8% in the nonsurgical group. For single organ metastasis, surgery could improve the survival of metastatic non-small cell lung cancer. Meanwhile, no significant survival improvements in surgical group were observed in patients with multiple organ metastases. CONCLUSION: The surgical survival benefits for extrathoracic metastatic non-small cell lung cancer could be divided by metastatic pattern.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
9.
Medicine (Baltimore) ; 100(35): e26777, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477117

RESUMO

ABSTRACT: Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ±â€Š11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.


Assuntos
Doenças Pulmonares Intersticiais/classificação , Síndrome de Sjogren/mortalidade , Idoso , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/classificação , Síndrome de Sjogren/epidemiologia , Estatísticas não Paramétricas
10.
Quant Imaging Med Surg ; 11(5): 1751-1762, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33936962

RESUMO

BACKGROUND: We aimed to investigate the efficacy and safety of echo contrast-enhanced ultrasound (CEUS) during high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). METHODS: A total of 67 patients with AWE were treated with HIFU ablation, and their demographic characteristics were retrospectively analysed. Blood perfusion of the focal lesion was assessed before the operation, during ablation and after the operation with the use of an ultrasound contrast agent, and the effect of the ultrasound contrast agent on treatment was assessed over a 1-year follow-up period. The degree of symptom relief and adverse effects were evaluated after HIFU ablation. RESULTS: Eighty-two lesions were ablated in 67 patients. CEUS showed that all lesions were successfully ablated with HIFU. The shrinkage ratio of the lesions significantly increased over the follow-up period. Intermittent pain disappeared at 1 month after the operation, and the patients' pain scores significantly decreased at the 1-year follow-up. The mean [± standard deviation (SD)] lesion volume was 7.64±8.95 cm3 on B-mode ultrasound. The post-HIFU non-perfused volume was 18.34±24.08 cm3, and the rate of massive changes on greyscale imaging was 96.16%±5.44% at 12 months. During the procedure, the main complications were a prickling sensation and tenderness in the treatment area and/or a transient "hot" sensation on the skin. After the procedure, there was no obvious discomfort except for pain. Two patients developed an approximately 1-cm area of skin that exhibited a waxy appearance. Seven patients had haematuria. No severe complications were observed. CONCLUSIONS: Ultrasound contrast agents are effective and safe for evaluating the effect of HIFU ablation on AWE, and this approach provides significant guidance and evaluation benefits for the use of HIFU treatment for AWE without obvious side effects.

11.
Appl Microbiol Biotechnol ; 105(11): 4731-4741, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34021812

RESUMO

Genome sequencing has revealed that each Streptomyces contains a wide range of biosynthetic gene clusters (BGCs) and has the capability to produce more novel natural products than what is expected. However, most gene clusters for secondary metabolite biosynthesis are cryptic under normal growth conditions. In Streptomyces tsukubaensis, combining overexpression of the putative SARPs (Streptomyces antibiotic regulatory proteins) and bioactivity-guided screening, the silent gene cluster (tsu) was successfully activated and a novel bioactive anthracycline tsukubarubicin was further isolated and identified. Biological activity assays demonstrated that tsukubarubicin possessed much better antitumor bioactivities against various human cancer cell lines (especially the breast cancer cell lines) than clinically used doxorubicin. Moreover, the previously unreported gene cluster (tsu) for biosynthesis of tsukubarubicin was first characterized and detailed annotations of this gene cluster were also conducted. Our strategy presented in this work is broadly applicable in other Streptomyces and will assist in enriching the natural products for potential drug leads. KEY POINTS: • Generally scalable strategy to activate silent gene clusters by manipulating SARPs. • The novel anthracycline tsukubarubicin with potent antitumor bioactivities. • Identification and annotation of the previously uncharacterized tsu gene cluster.


Assuntos
Streptomyces , Antibacterianos/farmacologia , Humanos , Família Multigênica , Metabolismo Secundário , Streptomyces/genética
12.
World J Clin Cases ; 9(6): 1318-1328, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33644198

RESUMO

BACKGROUND: During surgery for gastric cancer, peritoneal lavage using warm distilled water can cause temporary hemodynamic changes. AIM: To examine the associations between changes in heart rate and single nucleotide polymorphisms (SNPs). METHODS: This was a prospective observational study of patients with gastric cancer who underwent gastrectomy and peritoneal hypotonic lavage at the Third Affiliated Hospital of Soochow University from March 2018 to March 2019. Related SNPs were selected, and the verified exons were analyzed. Heart rate and blood pressure (BP) were measured before and after lavage. The patients were grouped as heart rate change ≥ 30% vs < 30%. Comparison and regression analyses of the selected SNPs were performed between the two groups. RESULTS: According to the inclusion/exclusion criteria, 194 patients were included in the analysis. Of these patients, 138 were male, with a mean age of 65.9 ± 0.8 years, and 56 were female, with a mean age of 65.0 ± 1.3 years. Heart rate dropped by 0%-10% in 65 participants, by 10%-15% in 29, by 15%-20% in 23, by 20%-50% in 39, by 50%-100% in four, six had a cardiac arrest, and 28 had an increase in heart rate. Considering the possible impact of exonic SNPs on the phenotypes, TEP1 (rs938886), TEP1 (rs1713449), and RECQL5 (rs820196) were analyzed. The haplotype analysis suggested that the haplotypes CTT [odds ratio (OR) = 2.018, 95% confidence interval (CI): 1.012-4.025, P = 0.0430] and GCC (OR = 2.293, 95%CI: 1.174-4.477, P = 0.0131) of TEP1 (rs938886), TEP1 (rs1713449), and RECQL5 (rs820196) increased the risk of a drop in heart rate > 30%. CONCLUSION: The TEP1 (rs938886), TEP1 (rs1713449), and RECQL5 (rs820196) SNPs were associated with changes in heart rate ≥ 30% during intraperitoneal lavage using distilled water after gastrectomy for gastric cancer.

13.
Acta Pharmacol Sin ; 42(7): 1139-1149, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33318625

RESUMO

This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Lactonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
14.
J Mol Cell Biol ; 13(5): 347-360, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-33196842

RESUMO

Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer development and progression. The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer. Howeve-r, little is known about the functional targets and regulatory mechanism of QKI-5. Here, we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3 (ADD3) significantly correlates with a poor prognosis in lung cancer. QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14. Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis, we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner. By binding to multiple sites in an upstream intron region, QKI-5 represses the splicing of ADD3 exon 14. We also identified several QKI mutations in tumors, which cause dysregulation of the splicing of QKI targets ADD3 and NUMB. Taken together, our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event, which underlies in part the tumor suppressor function of QKI.


Assuntos
Processamento Alternativo/genética , Proteínas de Ligação a Calmodulina/genética , Citoesqueleto/genética , Neoplasias Pulmonares/genética , Proteínas de Ligação a RNA/genética , Células A549 , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Éxons/genética , Genes Supressores de Tumor/fisiologia , Células HEK293 , Humanos , Íntrons/genética , Neoplasias Pulmonares/patologia , RNA Mensageiro/genética , Regulação para Cima/genética
15.
Cancer Nurs ; 44(3): E131-E141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31789937

RESUMO

BACKGROUND: The treatment-related decision-making process is a highly emotional time for parents of children with incurable cancer, and they tend to continue the cancer-directed treatment even when they realize that there is no cure for their child. OBJECTIVE: To evaluate whether parents involved in different treatment decisions regretted their treatment decision after their child's death. METHODS: We collected prospective data from 418 parents of children who died of incurable cancer after receiving cancer care at 1 of 4 hospitals. We assessed parent decisional regret and its association with the type of treatment decision made (non-cancer-directed vs cancer-directed). Propensity score-matched analysis (at a ratio of 1:1) was performed. RESULTS: One hundred forty-eight parents (35.4%) reported heightened regret. Two isonumerical arms with 103 (non-cancer-directed) and 103 (cancer-directed) resulted after propensity score matching. Parents with a cancer-directed treatment decision (relative risk, 1.53; 95% confidence interval, 1.24-1.90; P = .002) were more likely to report decisional regret compared with those with a non-cancer-directed decision. CONCLUSION: Bereaved parents with a cancer-directed treatment decision are more likely to experience increased regret for their decision than bereaved parents involved in a non-cancer-directed treatment decision. IMPLICATIONS: Shared-decision aids should be prepared for young parents with low education to improve disease-related knowledge, accurate risk perceptions, and options congruent with parents' values.


Assuntos
Luto , Neoplasias/psicologia , Pais/psicologia , Adulto , Criança , Pré-Escolar , Conflito Psicológico , Tomada de Decisões , Família/psicologia , Pesar , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários
16.
Health Qual Life Outcomes ; 18(1): 381, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298059

RESUMO

BACKGROUND: The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25). METHODS: From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs. RESULTS: 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38-0.44, all p < 0.001). Linear regression estimated + 8.9 and - 6.7 as the MCIDs of RS-SC-25, and + 3.4 and - 2.5 for RS-SC-10. Distribution-based methods estimated + 9.9 and - 9.9 as the MCIDs of RS-SC-25, and + 4.0 and - 4.0 for RS-SC-10. ROC estimated + 5.5 and - 4.5 as the MCIDs of RS-SC-25, and + 2.0 and - 1.5 for RS-SC-10. CONCLUSIONS: The most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.


Assuntos
Diferença Mínima Clinicamente Importante , Neoplasias/psicologia , Qualidade de Vida , Resiliência Psicológica , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Inquéritos e Questionários
17.
Oncol Lett ; 20(5): 184, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32934751

RESUMO

[This retracts the article DOI: 10.3892/ol.2016.5093.].

18.
Oncol Lett ; 20(5): 185, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32934752

RESUMO

[This retracts the article DOI: 10.3892/ol.2016.5107.].

19.
Oncol Lett ; 20(5): 195, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32952664

RESUMO

[This retracts the article DOI: 10.3892/ol.2016.5200.].

20.
Oncol Lett ; 20(5): 196, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32952665

RESUMO

[This retracts the article DOI: 10.3892/ol.2016.5134.].

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