RESUMO
INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.
Assuntos
Bupleurum , Espectrometria de Massas em Tandem , Camundongos , Animais , Peixe-Zebra , Cromatografia Líquida de Alta Pressão , Bupleurum/química , Células RAW 264.7 , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise , Inflamação/tratamento farmacológico , Componentes Aéreos da Planta/químicaRESUMO
Low sensitivity to chemotherapy has been a major challenge in the treatment of non-small-cell lung cancer (NSCLC). It is of great clinical significance to discover its mechanisms to improve cell sensitivity to chemotherapeutic drugs. The forkhead box subfamily O (FOXO) transcriptional factors are downstream factors of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and are reported to play pro-apoptotic roles in a variety of cells including NSCLC cells. But their roles and mechanisms in mediating cell response to chemotherapy remain to be discovered. We proposed that FOXO1 and FOXO3a may increase the sensitivity of NSCLC cells to cisplatin. Moreover, we presumed that LY294002, an inhibitor of the PI3K/AKT pathway, may enhance the cytotoxic effects of cisplatin through upregulating FOXO1 and FOXO3a. In the present study, we found that cisplatin initially increased the expressions and nuclear accumulation of FOXO1 and FOXO3a in NSCLC. Knockdown of FOXO1 and FOXO3a significantly decreased the cell sensitivity to cisplatin in vitro and in vivo. Moreover, inhibition of FOXO1 and FOXO3a attenuated cisplatin-induced cell apoptosis independent of Bim, a pro-apoptotic protein downstream of the FOXOs. Moreover, LY294002 synergistically increased the cytotoxic effects of cisplatin. Mechanistically, LY294002 increased the expressions and nuclear accumulation of FOXO1 and FOXO3a. Knockdown of FOXO1 and FOXO3a abrogated the enhancing effect of LY294002 on cisplatin. Taken together, our results suggested that FOXO1 and FOXO3a sensitize NSCLC cells to cisplatin and mediate the enhancing effects of LY294002 on cisplatin.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Neoplasias Pulmonares/genética , Animais , Antineoplásicos/farmacologia , Proteína 11 Semelhante a Bcl-2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Cisplatino/farmacologia , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Células HEK293 , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos Nus , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)-guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. MATERIAL AND METHODS Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. RESULTS No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ²=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ²=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ²=0.25, P=0.88). CONCLUSIONS The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach.
Assuntos
Procedimentos Endovasculares/métodos , Artéria Oftálmica/cirurgia , Oclusão da Artéria Retiniana/terapia , Angiografia Digital/métodos , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Papaverina/uso terapêutico , Terapia Trombolítica/métodos , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Acuidade VisualRESUMO
The projection algorithm used in mixture analysis to determine whether there is unknown disturbance existing in grey system can not accurately identify different samples and similar samples at the same time when it is used in the identification of drugs, because of the insufficient criteria. In the present study, one of its criteria for whether the size of measurement error of testing sample is at a limited level is improved for whether the size and distribution of measurement error is equal and similar between testing sample and standard sample. By testing 6 kinds of normal drugs (including BAYER Aspirin Enteric-coated Tablets, TYLENOL Acetaminophen Sustained Release Tablets, BAYER Compound Paracetamol Tablets(II), HUAZHONG Compound Vitamin C, HUAZHONG Vitamin B and MADINGLIN Demperidone Tablets) and 3 kinds of similar drugs of aspirin (including BAYER Aspirin Enteric-coated Tablets, Shanghai SINE Aspirin Enteric-coated Tablets and Bamyl Aspirin Effervescent Tablets), it was found that the un-improved projection algorithm directly used in discrimination of drugs shows poor performance with many problems existing, however, the improved projection algorithm can discriminate different drugs and similar drugs with accuracy up to 100%. The improved projection algorithm can be a universal, accurate and reliable automated pharmaceutical identification algorithm and can provide a reference for the study on identification of substance.
Assuntos
Algoritmos , Química Farmacêutica/métodos , Análise Espectral Raman , Acetaminofen/análise , Aspirina/análise , ComprimidosRESUMO
Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain-containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination-mediated glycogen synthase kinase-3 beta (GSK-3ß) degradation by interaction with myosin-9 (MYH9) and TNF receptor-associated factor 6 (TRAF6), which in turn activated Wnt/ß-catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or ß-catenin, or overexpressing GSK-3ß inhibited SAMD9-stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9/MYH9/GSK3ß/ß-catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Via de Sinalização Wnt , Humanos , beta Catenina/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Via de Sinalização Wnt/genéticaRESUMO
Myopia has become an important public health problem to be solved urgently. Posterior chamber phakic implantable Collamer lens (ICL) implantation is one of the latest and safest products for myopia correction worldwide. This prospective cross-sectional case series aimed to observe changes in the macular retinal thickness, retinal nerve fiber layer (RNFL) thickness of para-optic disk region, and blood flow density after posterior ICL implantation in patients with high myopia using optical coherence tomography angiography (OCTA). A total of 67 eyes of 67 patients with high myopia, who underwent ICL implantation at The Affiliated Eye Hospital of Nanjing Medical University from January 2020 and December 2020, were included. The spherical equivalent (SE) of the operative eyes was >-6.00 D. The changes in vision, intraocular pressure (IOP), SE, and vault were observed pre-operatively, and follow-up were performed 1 week, 1 month, and 3 months. OCTA was used to observe the changes in the CRT, retinal thickness of paracentral fovea, FAZ, superficial and deep retinal blood flow density in the macular area, RNFL thickness of para-optic disk region, and blood flow density before and after ICL implantation. The uncorrected distance visual acuity (UDVA) and best corrected distance visual acuity (CDVA) of the patients post-operation were significantly improved (P < 0.001). The IOP increased in comparison with other time points at 1 week post-operation (P < 0.05). There were no significant changes in CRT post-operation. The retinal thickness in the upper, lower, nasal, and temporal quadrants of the paracentral fovea increased significantly at 1 month and 3 months post-operation (P < 0.05). The FAZ area at all postoperative time points were decreased (P < 0.001). At 3 months post-operation, the blood flow density of the superficial and deep retinal layers in the upper, lower, and nasal macular area were significantly reduced (P < 0.05). At 1 month post-operation, the RNFL thickness in the temporal para-optic disk region and blood flow density were significantly reduced (P = 0.001 and P < 0.05, respectively). ICL implantation for highly myopic eyes led to an increase of the retinal thickness in the upper, lower, nasal, and temporal regions of the paracentral fovea; reduction of RNFL thickness in the temporal area of para-optic disk; decrease in FAZ area; and decrease in the blood flow density of some deep and superficial retinal layers as well as that of the temporal para-optic disk region.
RESUMO
PURPOSE: To investigate the changes of corneal higher order aberrations (HOAs) before and after phacoemulsification in patients with different central corneal thickness (CCT). METHODS: In this retrospective non-randomized, non- comparative cases series, 51 eyes of 51 patients who underwent phacoemulsification were enrolled. The corneal total HOAs and Zernike coefficients (3rd and 4th order) over the 3- and 4-mm zones were measured by the iTrace aberrometer (Tracey Technologies). Participants were divided into three groups (528 µm or less, 529 to 550 µm, and greater than 550 µm) depending on the CCT tested by the LenStar LS900 (Haag Streit AG). The corneal aberrations between groups were compared with analysis of variance, the variation of corneal aberrations before and after phacoemulsification was analyzed by the paired-samples t test, and generalized linear models were used to compare postoperative aberrations between groups. RESULTS: Significant differences were found in oblique trefoil at 3 mm and vertical trefoil, oblique trefoil, and HOAs at 4 mm in the 528 µm or less group; vertical trefoil, oblique trefoil, oblique quadrafoil, and oblique secondary astigmatism at 3 mm and oblique trefoil and oblique secondary astigmatism at 4 mm in the 529 to 550 µm group; and vertical quadrafoil at 3 mm in the greater than 550 µm group. After corrected deviation of preoperative aberrations, there were significant differences in postoperative vertical coma and oblique secondary astigmatism at 4 mm when compared to the 528 µm or less and greater than 550 µm groups. CONCLUSIONS: The lower the CCT, the greater the change in corneal aberrations in patients with cataract after phacoemulsification. Surgeons should be aware of the potential for worse visual quality related to surgically induced aberrations in patients with thin corneas. [J Refract Surg. 2021;37(12):842-847.].
Assuntos
Catarata , Córnea , Humanos , Estudos RetrospectivosRESUMO
Reduced sensitivity to chemotherapeutic drugs is almost inevitable in lung adenocarcinoma patients. Thus, understanding the relevant mechanisms is urgent. Positive cofactor 4 (PC4) was at first revealed to be a coactivator of basal transcription. Previous research has shown that PC4 participates in various cellular processes in normal and malignant cells. However, it is still unknown whether PC4 participates in altering the lung adenocarcinoma cell sensitivity to chemotherapy, and the relevant mechanisms remain to be explained. In this study, we discovered that PC4 was overexpressed in cisplatin-resistant lung adenocarcinoma cells. PC4 decreased cisplatin's cytotoxic effects on lung adenocarcinoma in vivo and in vitro. Furthermore, PC4 positively correlated with SOX9 in multiple cancers. PC4 was an upstream regulator of SOX9 in lung adenocarcinoma. Furthermore, PC4 mediated lung adenocarcinoma cell sensitivity to the HIF-PH inhibitor DMOG and the mTOR inhibitor rapamycin, and PC4 mediated the synergistic effect of DMOG and cisplatin. Finally, PC4 destabilized HIF-1α upon cisplatin treatment. Our research showed that PC4 participates in mediating lung adenocarcinoma cell sensitivity to multiple drugs. Mechanistically, PC4 governs multiple downstream pathways associated with chemotherapy resistance, including the SOX9 and HIF-1α pathways. Thus, PC4 is a promising chemotherapeutic target in lung adenocarcinoma.
RESUMO
Background: We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.
Assuntos
Adenocarcinoma de Pulmão/genética , Proteína Substrato Associada a Crk/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/patologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Antígeno B7-H1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Substrato Associada a Crk/metabolismo , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To observe the distributions and changes in angle kappa and angle alpha preoperatively and postoperatively in patients with cataract who were implanted with a multifocal intraocular lens (mIOL). SETTING: The First Affiliated Hospital of Northwest University, Shaanxi, China. DESIGN: Prospective nonrandomized noncomparative case series. METHODS: Eyes that underwent phacoemulsification were included. The magnitudes and orientations of angle kappa and angle alpha preoperatively and postoperatively were compared, respectively. RESULTS: The study comprised 81 eyes of 70 patients. The magnitude of angle kappa significantly decreased after phacoemulsification. No significant differences were observed between preoperative and postoperative angle kappa in orientation, as well as between preoperative and postoperative angle alpha. The correlations between preoperative and postoperative angle kappa and angle alpha were significant. There were displacement vectors for angle kappa (0.15 ± 0.10) and angle alpha (0.12 ± 0.12) after phacoemulsification. Locations of angle kappa of right and left eyes were scattered mostly in the temporal side of corneal light reflection, whereas locations of angle alpha were well organized in the horizontal position on temporal sides of corneal light reflection. CONCLUSIONS: The distribution of angle alpha was more organized compared with angle kappa. Angle kappa may change after phacoemulsification. During preoperative evaluation for patients with cataract planning for mIOLs implanted angle alpha may be a more reliable and stable factor compared with angle kappa.
Assuntos
Segmento Anterior do Olho/fisiopatologia , Implante de Lente Intraocular , Lentes Intraoculares Multifocais , Facoemulsificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pupila/fisiologia , Acuidade Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: This study was designed to investigate the effects of a novel carcinogenetic molecule, p130cas (breast cancer antiestrogen resistance protein 1 or BCAR1) on proliferation and cell growth in lung adenocarcinoma. The study also aimed to identify the possible underlying signal networks of BCAR1. METHODS: First, we evaluated proliferation, cell colony formation, apoptosis, and cell cycle after BCAR1 was knocked out (KO) using CRISPR-Cas9 technology in H1975 and H1299 human lung adenocarcinoma cells. Subsequently, BCAR1 was upregulated in 293T cells and immunoprecipitation-mass spectrometry (IP-MS) was used with bioinformatics analysis to screen for potential networks of BCAR1 interacting proteins. Ultimately, we validated the correlated expressions of BCAR1 and a selected hub gene, RNA polymerase II subunit A (POLR2A), in 54 lung adenocarcinoma tissues, as well as in H1975 and H1299 cells. RESULTS: Cell proliferation of H1975 and H1299 was significantly inhibited following BCAR1-KO. Colony formation of H1975 cells was also significantly decreased following BCAR1-KO. IP-MS demonstrated 419 potential proteins that may interact with BCAR1. Among them, 68 genes were significantly positively correlated to BCAR1 expression, as verified by TCGA. Six hub genes were revealed by PPI String. High expression of POLR2A, MAPK3, MOV10, and XAB2 predicted poor prognosis in lung adenocarcinoma, as verified by the K-M plotter database. POLR2A and MAPK3 are involved in both catalytic activity and transferase activity. POLR2A and BCAR1 were significantly increased in lung cancer tissues as compared with matched normal tissues. High expression of POLR2A was significantly positively correlated to BCAR1 overexpression and predicted poor prognosis in 54 lung cancer cases. POLR2A expression was significantly decreased following BCAR1-KO in H1975 and H1299 cells. CONCLUSIONS: BCAR1 promotes proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic and transferase activities. However, additional robust studies are required to elucidate the mechanisms involved.
Assuntos
Adenocarcinoma de Pulmão/genética , Proteína Substrato Associada a Crk/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transfecção , Regulação para CimaAssuntos
Migração do Implante de Lente Intraocular/etiologia , Extração de Catarata , Pressão Intraocular/fisiologia , Implante de Lente Intraocular , Câmara Anterior , Migração do Implante de Lente Intraocular/diagnóstico por imagem , Migração do Implante de Lente Intraocular/fisiopatologia , Comprimento Axial do Olho , Catarata/congênito , Criança , Pré-Escolar , Endoftalmite/etiologia , Feminino , Glaucoma/etiologia , Humanos , Lentes Intraoculares , Masculino , Microscopia Acústica , Período Pós-Operatório , Erros de Refração/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the protein expression of HIF-2α in condylar chondrocytes under the different stress loading, to investigate the possible effects of HIF-2α involved in the mortality of condylar chondrocytes under overloaded- stress. MATERIALS AND METHODS: Chondrocytes were isolated from TMJ condylar cartilage and cultured in hypoxia-incubator. Chondrocytes were divided into 4 groups: 0, 1000, 2000, 3000 ustrain group, which was subjected to cyclic tensile strain (CTS) of 0.5Hz for 2h. The rate of cell mortality was calculated. Western blot was used to measure the expression of HIF-2α and it's downstream catabolic factors (MMP3, MMP13, ADAMTS4) in protein levels respectively. RESULTS: With the increase of CTS, both of the rate of cell mortality and protein expression of HIF-2α increased significantly (p<0.05). The same tendency was also found in it's downstream catabolic factors (MMP3, MMP13, ADAMTS4) in protein levels (p<0.05). CONCLUSIONS: The results indicated that elevated expression of HIF-2α may be a possible mechanism related to overloaded- stress induced mortality of condylar chondrocytes.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Condrócitos/metabolismo , Côndilo Mandibular/metabolismo , Proteína ADAMTS4/metabolismo , Apoptose , Western Blotting , Células Cultivadas , Humanos , Côndilo Mandibular/citologia , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Estresse MecânicoRESUMO
The antiherpetic drugs acyclovir (ACV, valaciclovir) and penciclovir (famciclovir) are phosphorylated by viral thymidine kinase and terminate DNA synthesis. ASP2151 (amenamevir) and foscavir (PFA) directly inhibit viral helicase-primase and DNA polymerase, respectively, and inhibit replication of herpes simplex virus (HSV) and varicella-zoster virus. ACV, ASP2151, and PFA all inhibit HSV with a different mechanism of action and as a consequence, the kinetics of viral DNA accumulation and progeny virus production differ. This study focused on how viral DNA synthesis and its related events in the replication cycle would influence anti-HSV action of ACV, ASP2151, and PFA. ASP2151 suppressed HSV replication more efficiently than ACV at 10 × 50% effective concentration of plaque formation (EC50), when treatments were started 0-24 h after infection. ASP2151 and PFA were more potent than ACV in suppressing viral DNA synthesis and infectious virus production when they were added up to 3 h following infection. The virus replicated in the presence of ACV was compared for the ratios of HSV DNA copy number to infectivity with that without ACV and infectivity of ACV-treated virus was less efficient than that without ACV-treatment. The EC50 of infected cells in the time course after infection was preserved in PFA, limited in ASP2151, and much increased for ACV, indicating that viral DNA synthesis had little effect on antiviral action of PFA and ASP2151 but reduced the susceptibility of ACV. ASP2151 showed a preferable profile as an anti-herpetic agent with a better pharmacokinetic profile than ACV.
Assuntos
DNA Helicases/antagonistas & inibidores , DNA Primase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herpesviridae/efeitos dos fármacos , Oxidiazóis/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular , Chlorocebus aethiops , DNA Viral/efeitos dos fármacos , Herpes Simples/tratamento farmacológico , Herpesviridae/enzimologia , Herpesviridae/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/enzimologia , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/enzimologia , Herpesvirus Humano 2/metabolismo , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/enzimologia , Herpesvirus Humano 3/metabolismo , Humanos , Oxidiazóis/química , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to chronic medicated patients with schizophrenia and examined the association of IL-3 with their psychopathological symptoms. Serum IL-3 levels were assessed in 55 FEDN patients, 52 chronic medicated patients and 43 healthy controls. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). We found significantly lower IL-3 levels in FEDN patients than both chronic patients and healthy controls (both p<0.001), while IL-3 levels in chronic patients were markedly higher than in healthy controls. No significant association was observed between IL-3 and any clinical psychopathology in FEDN patients; however, we found a significant correlation between serum IL-3 levels and the PANSS general psychopathology subscore in chronic medicated patients (p<0.05). Decreased IL-3 levels in FEDN patients suggest that suppressed immune function may be associated with developing schizophrenia, but as the disease progresses IL-3 levels increase perhaps related to medication treatment or other factors that occur during chronic illness.
Assuntos
Antipsicóticos/uso terapêutico , Interleucina-3/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Doença Aguda , Adulto , Biomarcadores/sangue , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/imunologiaRESUMO
AIM: To evaluate the recurrence and complications after bare sclera resection (BSR) combined with mitomycin C (MMC) treatment and/or autograft limbus conjunctiva (ALC) in the surgery for pterygium. METHODS: Meta-analysis was used to evaluate the differences in patient outcomes between BSR of pterygium with or without MMC and/or ALC. All included studies were randomized trials of patients with pterygium who received BSR followed by MMC and/or ALC in the surgery. The recurrence of pterygium and other complications resulting from different treatments were extracted for analysis. RESULTS: Thirteen studies met the inclusion criteria. The recurrence of pterygium with intraoperative (IO) MMC was higher than that with ALC (OR=2.38, 95% confidence interval 1.45-3.91, I (2)=29%). Postoperative MMC resulted in an incidence of recurrence similar to that of ALC (OR=0.66, 95% confidence interval 0.30-1.42, I (2)=0%), and IO MMC treatment in combination with ALC produced similar patient outcomes to ALC alone (OR=0.41, 95% confidence interval 0.16-1.01, I (2)=16%). Other complications such as punctate epitheliopathy, scleral thinning and ischemia, irritation and persistent epithelium defect, were more common in patients in the MMC group as compared to those treated with ALC. CONCLUSION: The recurrence of pterygium with BSR followed by ALC is lower than that of BSR followed by MMC, and the incidence of other complications is lower. While ALC is a more effective strategy for treating pterygium, the quality of the ALC transplant should be considered when the patient has a history of glaucoma.
RESUMO
PURPOSE: To describe the electrophysiological, histologic, and hereditary features of a naturally occurring rat model of cone function loss. METHODS: Dark- and light-adapted electroretinograms (ERGs) were used to evaluate retinal function. The thickness and architecture of the retina were observed by light microscopy. The cone density was investigated by wholemount immunocytochemistry. The inheritance pattern was defined by mating with control female rats. RESULTS: In affected rats, light-adapted ERGs were nearly absent, whereas dark-adapted responses were of normal amplitude with delays in b-wave implicit time. Overall retinal structure was normal at the light microscopic level. There was no difference in cone density between control and affected rats. The cone function abnormality is inherited as an X-linked trait. CONCLUSIONS: A spontaneous rat mutant was identified that has markedly affected cone function, whereas rod-mediated function is largely spared. The presence of the normal number of cone outer segments indicates that the defect does not involve cone photoreceptor degeneration. This rat model provides a model of X-linked cone dysfunction, and may also be used to examine aspects of rod-mediated visual function in the rat. Further studies are needed to identify the gene that is involved.
Assuntos
Modelos Animais de Doenças , Doenças Genéticas Ligadas ao Cromossomo X/genética , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Degeneração Retiniana/genética , Animais , Adaptação à Escuridão , Eletrorretinografia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Masculino , Microscopia de Fluorescência , Linhagem , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologiaRESUMO
AIM: To analyze the factors that influence the prediction error (PE) after intraocular lens (IOL) implantation in pediatric cataract. METHODS: The medical records of cataract patients of no more than 14 years old who had primary IOL implantation were reviewed from 2006 to 2010. The PE, absolute value of PE (APE), and predictability between in different axial length, mean corneal curvature, corneal astigmatism, and age at the surgery were analyzed. RESULTS: Seventy-five children (119 eyes) were included, with a mean age of (5.09±2.54) years. At the follow-up of (1.19±0.69) months, the mean postoperative PE was (-0.22±1.12) D, and APE was (0.87±0.73)D. The PE in eyes with an axial length >20mm but ≤22mm were significantly under-corrected than that in eyes with longer axis, and the APE in eyes with an axial length ≤20mm was more obvious compared with the others. The correlations between PE and axial length, as well as corneal astigmatism, and between APE and axial length were significant. The predictability was significantly poorer in the eyes with an axial length ≤20mm than the others. CONCLUSION: The axial length is closely related with the PE after IOL implantation in pediatric cataract patients, especially when it is ≤20mm, PE is more significant. The formula that is more suitable to very short axial length should be explored.
RESUMO
PURPOSE: To describe a possible spontaneous rat model of X-linked congenital stationary night blindness (CSNB). METHODS: Experimental animals were generated by mating the affected animal to normal rats, and from interbreeding littermates. To define the inheritance pattern, full-field electroretinograms (ERGs) were recorded from all progeny. RESULTS: During the course of other experiments, an affected male rat was identified by a reduced amplitude ERG b-wave. When this rat was mated to normal Sprague-Dawley rats, all of the F1 progeny had normal ERG waveforms. When F1 offspring were interbred, 51% of the male offspring had b-wave reductions while all female offspring had normal ERG waveforms. When F1 females were backcrossed to the original affected male, b-wave reductions were noted in both male and female offspring; overall, 46.8% of the backcross progeny exhibited a b-wave reduction. In affected animals, the b-wave was selectively affected as the a-wave appeared to retain normal amplitude and kinetics at 1-4 months old. Cone ERGs were significantly reduced in amplitude and somewhat delayed. Similar ERG results were also obtained under the same stimulus conditions from human patients with complete CSNB (CSNB1). CONCLUSIONS: The inheritance pattern is consistent with an X-linked recessive trait. The electrophysiological results suggest that this mutant rat line may provide another model for CSNB1.