RESUMO
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Células T de Memória , Reinfecção , SARS-CoV-2 , Humanos , Adolescente , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Masculino , Reinfecção/imunologia , Reinfecção/virologia , Feminino , Células T de Memória/imunologia , Estudos Prospectivos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Formação de Anticorpos , Glicoproteína da Espícula de Coronavírus/imunologia , Memória Imunológica , Criança , Linfócitos T/imunologiaRESUMO
Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed.Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs).Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy.Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1ß in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05).Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Fibroblastos/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cloroquina/administração & dosagem , Cloroquina/farmacologia , Diterpenos do Tipo Caurano/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fibroblastos/citologia , Humanos , Concentração Inibidora 50 , Sinoviócitos/citologia , Fatores de TempoRESUMO
OBJECTIVES: To observe the age-related changes of sulfated glycosaminoglycan (sGAG) content of hip joint cartilage of elderly people based on Equilibrium Partitioning of an Ionic Contrast Agent (EPIC) micro-CT. METHODS: Seventy human hip cartilage-bone samples were collected from hip-fracture patients (ages 51-96) and divided into five groups (10 years in an age group). They were first immersed in 20% concentration of the contrast agent Meglumine Diatrizoate (MD) for 6 h at 37 °C, and then scanned by micro-CT. Following scanning, samples were stained for sGAG with toluidine blue. The X-ray attenuation and sGAG optical density were calculated by image processing. The correlation between X-ray attenuation and sGAG optical density was then analyzed. RESULTS: The X-ray mean attenuation of the cartilage increased by 18.81% from the 50-80 age groups (p < 0.01), but decreased by 7.15% in the 90 age group compared to the 80 age group. The X-ray mean attenuation of the superficial layer and middle layer increased by 31.60 % and 44.68% from the 50-80 age groups, respectively (p < 0.01), but reduced by 4.67% and 6.05% separately in the 90 age group. However, the deep layer showed no significant change with aging. The sGAG optical density showed a linear correlation (r = -0.91, p < 0.01) with the X-ray attenuation. CONCLUSION: The sGAG content of hip joint cartilage varied with aging in elderly people. The changes in superficial layer and middle layer were more evident than deep layer.
Assuntos
Cartilagem Articular/patologia , Glicosaminoglicanos/metabolismo , Articulação do Quadril/patologia , Osteoartrite do Quadril/patologia , Microtomografia por Raio-X , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Humanos , Pessoa de Meia-Idade , Microtomografia por Raio-X/métodosRESUMO
BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).
Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Antifibróticos , Estudos Prospectivos , Progressão da Doença , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/complicações , FibroseRESUMO
The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.
RESUMO
INTRODUCTION: Emerging evidence suggests that metformin has a potential antitumor effect both in vitro and in vivo. Increasing epidemiological studies indicate that diabetic patients receiving metformin therapy have lower incidences of cancer and have better survival rates. However, there are limited and inconsistent studies available about the effect of metformin therapy on ovarian cancer (OC). Thus, we conducted this meta-analysis to study the effect of metformin therapy on OC. Meanwhile, we systematically reviewed relevant studies to provide a framework for future research. EVIDENCE ACQUISITION: We conducted a systematic literature search on PubMed, Web of Science, Springerlink, CNKI, VIP, SinoMed, and Wanfang up to the period of October 2018. A random-effects meta-analysis model was used to derive pooled effect estimates. EVIDENCE SYNTHESIS: A total of 13 studies were retrieved of which 5 studies explained the prevention and 8 studies explained the treatment for OC. Our pooled results showed that metformin has a potential preventive effect on OC in diabetic women (pooled odds ratio [OR] 0.62, 95% confidence interval [95% CI] 0.34, 1.11; P<0.001). In addition, metformin can also significantly prolong progression-free survival (PFS) (pooled hazard ratio [HR] 0.49, 95% CI 0.34, 0.70; P=0.002), and overall survival (OS) (HR 0.71, 95%CI 0.61, 0.82; P<0.001) in patients with OC, regardless of whether they had diabetes. CONCLUSIONS: The use of metformin can potentially reduce the risk of OC among diabetics, and it also can significantly improve PFS and OS in patients with OC. A further large clinical investigation would be needed to adopt our finding in practice, however, our systematic review provides an insight for future study designs.
Assuntos
Diabetes Mellitus , Metformina , Neoplasias Ovarianas , Humanos , Feminino , Metformina/uso terapêutico , Prognóstico , Neoplasias Ovarianas/tratamento farmacológico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Modelos de Riscos ProporcionaisRESUMO
AIM: Schizophrenia is associated with abnormal hippocampal structure and function. Available evidence suggests that the anterior and posterior hippocampus are differentially affected by schizophrenia pathology. This study was designed to provide new insight into the anterior and posterior hippocampus in schizophrenia from the perspective of functional connectivity. METHODS: Based on resting-state functional magnetic resonance imaging data of 71 schizophrenia patients and 74 normal controls, we utilized a data-driven approach to functionally segment the hippocampus into anterior and posterior segments and then investigated the functional connectivity patterns within and between the two hippocampal networks at the network, edge, and nodal levels. RESULTS: We found that schizophrenia patients showed hyperconnectivity of both the anterior and posterior hippocampal networks. We also observed that the network alterations appear somewhat greater in the anterior hippocampal network than the posterior network, the left side than the right, and the intranetwork connectivity than the internetwork connectivity. CONCLUSION: The results reveal convergent and divergent intranetwork and internetwork connectivity patterns of the anterior and posterior hippocampus in schizophrenia, providing novel and important insights into the mechanisms of hippocampal pathology in schizophrenia.
Assuntos
Encéfalo , Esquizofrenia , Humanos , Encéfalo/patologia , Esquizofrenia/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Vias Neurais/diagnóstico por imagemRESUMO
There are more than 200 subtypes of human papillomavirus (HPV), and high-risk HPVs are a leading cause of cervical cancer. Identifying the genotypes of HPV is significant for clinical diagnosis and cancer control. Herein, we used programmable and modified DNA as the backbone to construct fluorescent genotyping nanodevice for HPV subtype distinction. In our strategy, the dye-labeled single-stranded recognize-DNA (R-DNA) was hybridized with Black Hole Quencher (BHQ) labeled single-stranded link-DNA (L-DNA) to form three functionalized DNA (RL-DNA). Through the extension of polycytosine (poly-C) in L-DNA, three RL-DNAs can be more firmly adsorbed on graphene oxide to construct reliable genotyping nanodevice. The genotyping nanodevice had low background noise since the dual energy transfer, including Förster resonance energy transfer (FRET) from dye to BHQ and the resonance energy transfer (RET) from dye to graphene oxide. Meanwhile, the programmability of DNA allows the proposed strategy to simultaneously and selectively distinguish several HPV subtypes in solution using DNA labeled with different dyes. To demonstrate clinical potential, we show multiplexed assay of HPV subtypes in cervical scrapes, and it has been successfully applied in HPV-DNA analysis in cervical scrapes samples. The genotyping nanodevice could be developed for simultaneous and multiplex analysis of several oligonucleotides in a homogeneous solution by adjusting the recognition sequence, demonstrating its potential application in the rapid screening of multiple biomarkers.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Genótipo , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Papillomaviridae/genética , Neoplasias do Colo do Útero/diagnóstico , DNA Viral/genética , DNA Viral/análiseRESUMO
Zika virus (ZIKV) infection during pregnancy threatens pregnancy and fetal health. However, the infectivity and pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using human trophoblast stem cells (hTSCs), we demonstrated that hTSCs were permissive to ZIKV infection, and resistance to ZIKV increased with hTSC differentiation. Combining gene knockout and transcriptome analysis, we demonstrated that the intrinsic expression of AXL and TIM-1, and the absence of potent interferon (IFN)-stimulated genes (ISGs) and IFNs contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived trophoblast organoid (hTSC-organoid), we demonstrated that ZIKV infection disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further demonstrated that ZIKV infection of hTSC-organoids disrupted the stemness of hTSCs and the proliferation of cytotrophoblast cells (CTBs) and probably led to a preeclampsia (PE) phenotype. Overall, our results clearly demonstrate that hTSCs represent the major target cells of ZIKV, and a reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepen our understanding of the characteristics and consequences of ZIKV infection of hTSCs in early human embryos.
Assuntos
Infecção por Zika virus , Zika virus , Gravidez , Humanos , Feminino , Trofoblastos , Placenta , OrganoidesRESUMO
BACKGROUND: Physical loading leads to a deformation of bone microstructure and may influence quantitative ultrasound (QUS) parameters. This study aims at evaluating the effect of physical loading on bone QUS measurement, and further, on the potential of diagnosing osteoporosis using QUS method under physical loading condition. METHODS: 16 healthy young females (control group) and 45 postmenopausal women (divided into 3 groups according to the years since menopause (YSM)) were studied. QUS parameters were measured at calcaneus under self-weight loading (standing) and no loading (sitting) conditions. Weight-normalized QUS parameter (QUS parameter measured under loading condition divided by the weight of the subject) was proposed to evaluate the influence of loading. T-test, One-Way analysis of variance (one way ANOVA) and receiver operating characteristic (ROC) analysis were applied for analysis. RESULTS: In QUS parameters, mainly normalized broadband ultrasound attenuation (nBUA), measured with loading significantly differed from those measured without loading (p < 0.05). The relative changes of weight-normalized QUS parameters on postmenopausal women with respect to premenopausal women under loading condition were larger than those on traditional QUS parameters measured without loading. In ROC analysis, weight-normalized QUS parameters showed their stronger discriminatory ability for menopause. CONCLUSIONS: Physical loading substantially influenced bone QUS measurement (mainly nBUA). Weight-normalized QUS parameters can discriminate menopause more effectively. By considering the high relationship between menopause and osteoporosis, an inference was drawn that adding physical loading during measurement may be a probable way to improve the QUS based osteoporosis diagnosis.
Assuntos
Calcâneo/diagnóstico por imagem , Osteoporose Pós-Menopausa/diagnóstico por imagem , Ultrassonografia/métodos , Suporte de Carga/fisiologia , Adulto , Fatores Etários , Idoso , Calcâneo/patologia , Calcâneo/fisiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/patologia , Pós-Menopausa , Valor Preditivo dos Testes , Curva ROC , Estresse Mecânico , Adulto JovemRESUMO
BACKGROUND: Early diagnosis of osteoarthritis (OA) is essential for preventing further cartilage destruction and decreasing severe complications. The aims of this study are to explore the relationship between OA pathological grades and quantitative acoustic parameters and to provide more objective criteria for ultrasonic microscopic evaluation of the OA cartilage. METHODS: Articular cartilage samples were prepared from rabbit knees and scanned using ultrasound biomicroscopy (UBM). Three quantitative parameters, including the roughness index of the cartilage surface (URI), the reflection coefficients from the cartilage surface (R) and from the cartilage-bone interface (Rbone) were extracted. The osteoarthritis grades of these cartilage samples were qualitatively assessed by histology according to the grading standards of International Osteoarthritis Institute (OARSI). The relationship between these quantitative parameters and the osteoarthritis grades was explored. RESULTS: The results showed that URI increased with the OA grade. URI of the normal cartilage samples was significantly lower than the one of the OA cartilage samples. There was no significant difference in URI between the grade 1 cartilage samples and the grade 2 cartilage samples. The reflection coefficient of the cartilage surface reduced significantly with the development of OA (p < 0.05), while the reflection coefficient of the cartilage-bone interface increased with the increase of grade. CONCLUSION: High frequency ultrasound measurements can reflect the changes in the surface roughness index and the ultrasound reflection coefficients of the cartilage samples with different OA grades. This study may provide useful information for the quantitative ultrasonic diagnosis of early OA.
Assuntos
Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Microscopia Acústica , Osteoartrite do Joelho/diagnóstico por imagem , Animais , Cartilagem Articular/patologia , Modelos Animais de Doenças , Diagnóstico Precoce , Feminino , Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Valor Preditivo dos Testes , Coelhos , Índice de Gravidade de Doença , Propriedades de SuperfícieRESUMO
Depending on the experimental design, micro-CT can be used to examine bones either in vivo or ex vivo (excised fresh or formalin-fixed). In this study we investigated if differences exist in the variables measured by micro-CT between in vivo and ex vivo scans and which kind of scan is more sensitive to the changes of bone microstructure induced by simulated weightlessness. Rat tail suspension was used to simulate the weightless condition. The same bone from either normal or tail-suspended rats was scanned by micro-CT both in vivo and ex vivo (fresh and fixed by formalin). Then, bone mineral density (BMD) and microstructural characteristics were analyzed. The results showed that no significant differences existed in the microstructural parameters of trabecular bone among in vivo, fresh, and formalin-fixed bone scans from both femurs and tibias, although BMD exhibited differences. On the other hand, most parameters of the tail-suspended rats measured by micro-CT deteriorated compared with controls. Ex vivo scanning appeared to be more sensitive to bone microstructural changes induced by tail suspension than in vivo scanning. In general, the results indicate that values obtained in vivo and ex vivo (fresh and fixed) are comparable, thus allowing for meaningful comparison of experimental results from different studies irrespective of the type of scans. In addition, this study suggests that it is better to use ex vivo scanning when evaluating bone microstructure under weightlessness. However, researchers can select any type of scan depending upon the objective and the demands of the experiment.
Assuntos
Biomarcadores/análise , Doenças Ósseas/etiologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/ultraestrutura , Simulação de Ausência de Peso/efeitos adversos , Animais , Biomarcadores/metabolismo , Densidade Óssea , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/metabolismo , Doenças Ósseas/patologia , Osso e Ossos/patologia , Suscetibilidade a Doenças , Feminino , Elevação dos Membros Posteriores/efeitos adversos , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
Matrine is the major active component of the traditional Chinese medicine Sophora flavescens, but the molecular mechanisms of matrine on tumor invasion inhibition remain unclear. The aim of this study is to elucidate the effects of matrine on invasion ability of human hepatocellular carcinoma (HCC) cells, matrix metalloproteinase-9 (MMP-9), and nuclear factor (NF)-kappa B expression. The expression activity of MMP-9 was measured by reverse transcription polymerase chain reaction, Western blot, and gelatin zymography analysis. The expression of NF-kappa B was measured by the Western blot analysis. Matrine significantly inhibited MMP-9 expression of SMMC-7721 cells. NF-kappa B inhibitor PTDC induced a marked reduction in MMP-9 expression, and it suggested that NF-kappa B could play an important role in MMP-9 expression. Furthermore, matrine significantly suppressed NF-kappa B expression and the invasion of SMMC-7721 cells. Our results showed that matrine inhibited MMP-9 expression and the invasion of human HCC cells. The inhibitory effects are partly associated with the downregulation of the NF-kappa B signaling pathway.
Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz , Quinolizinas/farmacologia , Alcaloides/química , Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Medicamentos de Ervas Chinesas/química , Humanos , Metaloproteinase 9 da Matriz/genética , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Quinolizinas/química , Quinolizinas/uso terapêutico , Sophora/química , MatrinasRESUMO
BACKGROUND: Baicalin has anti-inflammatory, antibacterial, blood platelet aggregation-inhibiting, free oxygen radical-clearing, and endotoxin-decreasing properties. However, its molecular mechanism involved in the treatment of Adriamycin-induced nephrotic syndrome (NS) is still unclear. OBJECTIVE: This study aimed to explore the effects of baicalin on Adriamycin-induced nephrotic syndrome (NS) and to characterize the genes involved in this progression. METHODS: We established Adriamycin-induced NS model in 32 rats and used six rats in Sham group. Urinary total protein content and creatinine serum were assessed as physiological indicators. H&E staining was used to observe the pathological changes. We determined gene expression profiles using transcriptome sequencing in the rat kidney tissues from Sham, Adriamycin, and Adriamycin + baicalin groups. KEGG was carried out to analyze the enriched pathways of differentially expressed genes among these groups. RESULTS: Baicalin treatment relieved renal injury in NS rats. Expression of 363 genes was significantly different between the Adriamycin and Adriamycin + baicalin M groups. Most of the differentially expressed genes were enriched in pathways involved in epithelial-mesenchymal transition (EMT), fibrosis, apoptosis, and inflammation. CONCLUSIONS: Overall, these data suggest that Adriamycin-induced NS can be attenuated by baicalin through the suppression of fibrosis-related genes and inflammatory reactions. Baicalin is a potential drug candidate for the treatment of NS, and the identified genes represent potential therapeutic targets.
Assuntos
Fibrose/tratamento farmacológico , Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose/induzido quimicamente , Fibrose/genética , Fibrose/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , RatosRESUMO
BACKGROUND/AIMS: Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. The aim of the present study was to determine the inhibitory effect of resveratrol on vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) and to explore its mechanism. METHODOLOGY: VEGF protein was detected by western blot, whereas VEGF mRNA expression was investigated by RT-PCR. Nuclear factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA). Xenograft sections were stained for CD34 to study microvessels in vivo. RESULTS: We found that VEGF protein and mRNA expressions in the cells treated with resveratrol were significantly decreased. The activation of NF-kappa B was also intensely inhibited by resveratrol. Growth of tumours in nude mice was inhibited by resveratrol. Microvessel density was decreased with resveratrol treatment. CONCLUSIONS: The inhibitory effect of resveratrol on VEGF activity may occur partly through suppression of the activation of NF-kappa B in HepG2 cells. Resveratrol also significantly inhibited tumour growth and angiogenesis.
Assuntos
Inibidores da Angiogênese/farmacologia , Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Estilbenos/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/fisiologia , RNA Mensageiro/análise , Resveratrol , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Taking the advantages of excellent optical properties, biocompatibility, and photostability of carbon dots, herein, we developed polarity-sensitive polymer carbon dots (PCDs) for visualizing of cellular polarity to real-time monitoring autophagy changes without perturbing the cellular status. The PCDs can be prepared by simply mixing dopamine (DA), H2O2, and o-phenylenediamine (o-PDA) in a common beaker without the need for any special equipment or external energy supply, and the preparation could be completed within 3 min at room temperature. Interestingly, the polarity-sensitive PCDs could emit various types of fluorescence and are insensitive to the excitation light when dispersed in different water/dioxane systems with different polarities. Based on the polarity-sensitive emission of the PCDs, the change of polarity during autophagy has been successfully monitored in living cells. Moreover, the change of polarity detected by PCDs is autophagy-specific (does not occur during apoptosis), occurs under different autophagy-inducing situations (starvation, rapamycin, and trehalose), and requires a normal autophagic flux, showing that PCDs rapidly prepared by polymerization cross-linking at room temperature can be functionally applied in the case of autophagy-related physiological or pathological processes.
Assuntos
Autofagia , Carbono/química , Polaridade Celular , Pontos Quânticos/química , Células HeLa , HumanosRESUMO
BACKGROUND: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. OBJECTIVE: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. METHODS: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1ß levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. RESULTS: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1ß secretion in RA-FLS. CONCLUSION: Melittin may be useful in preventing damage to the joints during accidental local stimulation.
Assuntos
Apoptose/efeitos dos fármacos , Artrite Reumatoide/patologia , Autofagia/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Meliteno/farmacologia , Sinoviócitos/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Artrite Reumatoide/imunologia , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/imunologia , Fibroblastos/patologia , Humanos , Interleucina-1beta/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sinoviócitos/imunologia , Sinoviócitos/patologiaRESUMO
PURPOSE: This study aims to evaluate the value of quantitative analysis of ultrasound real-time tissue diffusion elastography in the diagnosis of benign and malignant prostate lesions. MATERIALS AND METHODS: From March 2010 to June 2013, 52 patients suspected with prostate cancer based on laboratory or clinical test results and underwent prostate biopsy in our hospital were enrolled into this study. The age of these patients ranged between 45-82 years, with an average age of 67.2 ± 6.8 years. All patients underwent transrectal real-time ultrasound elastography (TRTE) before biopsy. A total of 63 prostate nodules were detected, and the 11 elastic characteristic quantities of these nodules were quantitatively analyzed via tissue diffusion quantitative analysis. The results of ultrasonography were compared with the results of operation and pathology. RESULT: Among these 11 characteristic quantities, which include the mean (MEAN) and standard deviation (SD), blue area ratio (AREA%), complexity (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT), equality (ENT), entropy (IDM), consistency (ASM) and correlation (CORR), except for COMP and CORR, the differences in other nine characteristic quantities between benign and malignant prostatic nodules were statistically significant (P<0.05). Among these, the AREA% and MEAN had the highest correlation, which were 0.791 and -0.791, respectively. The Youden's index (sensitivity and specificity) of AREA% in the ROC curves was the highest, the cutoff value was 80.65% for the diagnosis of prostate cancer, sensitivity was 87.9%, and specificity was 96.6%. CONCLUSION: Quantitative analysis of ultrasound real-time tissue diffusion elastography is helpful in the diagnosis of benign and malignant prostate lesions, provides a relatively accurate evaluation method in clinical practice, and has broad application prospects.
Assuntos
Técnicas de Imagem por Elasticidade , Doenças Prostáticas/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Avaliação como Assunto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the role of miR-26a-5p in cell proliferation and doxorubicin sensitivity in hepatocellular carcinoma. METHODS: We evaluated miR-26a-5p expression in hepatocellular carcinoma tissues and cell lines by reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to examine cell proliferation. Relationship between miR-26a-5p and aurora kinase A was evaluated by luciferase report system. Western blot was used to detect expression of aurora kinase A. RESULTS: In this study, we observed miR-26a-5p was downregulated in hepatocellular carcinoma tissues and cell lines. Gain-of-function experiments showed that proliferation rate of hepatocellular carcinoma cells decreased under condition of miR-26a-5p mimics. We found miR-26a-5p mimics could enhance doxorubicin sensitivity of hepatocellular carcinoma cells. Further study showed that aurora kinase A was target gene of miR-26a-5p. Suppression of aurora kinase A could lead to lower cell proliferation and higher doxorubicin sensitivity of hepatocellular carcinoma cells. CONCLUSION: Our study found that miR-26a-5p could inhibit cell proliferation and enhance doxorubicin sensitivity in hepatocellular carcinoma cells by targeting aurora kinase A.
Assuntos
Aurora Quinase A/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The present study investigated the expression and potential influence of SHC SH2 domainbinding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC803 and SGC7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4cyclin D1 cascade and suppressed caspase3, caspase PARPdependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumorpromoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC.