RESUMO
Pulmonary fibrosis is a lung disorder characterized by the accumulation of abnormal extracellular matrix, scar tissue formation, and tissue stiffness. Type II alveolar epithelial cells (AEII) play a critical role in repairing lung tissue after injury, and repeated injury to these cells is a key factor in the development of pulmonary fibrosis. Chronic exposure to PM2.5, a type of air pollution, has been shown to increase the incidence and severity of pulmonary fibrosis by enhancing the activation of EMT in lung epithelial cells. Melatonin, a hormone with antioxidant properties, has been shown to prevent EMT and reduce fibrosis in previous studies. However, the mechanism through which melatonin targets EMT to prevent pulmonary fibrosis caused by PM2.5 exposure has not been extensively discussed before. In this current study, we found that melatonin effectively prevented pulmonary fibrosis caused by prolonged exposure to PM2.5 by targeting EMT. The study demonstrated changes in cellular morphology and expression of EMT markers. Furthermore, the cell migratory potential induced by prolonged exposure to PM2.5 was greatly reduced by melatonin treatment. Finally, in vivo animal studies showed reduced EMT markers and improved pulmonary function. These findings suggest that melatonin has potential clinical use for the prevention of pulmonary fibrosis.
Assuntos
Transição Epitelial-Mesenquimal , Melatonina , Material Particulado , Fibrose Pulmonar , Melatonina/farmacologia , Melatonina/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Animais , Fibrose Pulmonar/prevenção & controle , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Material Particulado/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Movimento Celular/efeitos dos fármacos , Humanos , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
BACKGROUND: The safety and efficacy of 17-gauge needles used in CT-guided percutaneous cryoablation for lung nodules were explored in this study. The purpose of the study was to compare the findings with earlier research and multi-center clinical trials that used various needle sizes. METHODS: Between 2016 and 2020, a retrospective study was conducted with approval from the institutional review board. A total of 41 patients were enrolled, and 71 lung nodules were treated in 63 cryoablation procedures using local anesthesia. Complication rates were recorded, and overall survival rates as well as tumor progression-free rates were calculated using the Kaplan-Meier method. RESULTS: Self-limited hemoptysis was caused by 12.9% of the procedures, and drainage was required for pneumothoraces resulting from 11.3% of them. The overall survival rates at one, two, three, and four years were 97%, 94%, 82%, and 67%, respectively. The tumor progression-free rates at one, two, three, and four years were 86.2%, 77%, 74%, and 65%, respectively. CONCLUSION: Cryoablation for lung nodules using 17-Gauge needles can achieve similar rates of survival and tumor control rates, similar or even lower complication rates as compared with other studies and multi-center trials using mixed sized needles.
Assuntos
Criocirurgia , Neoplasias , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pulmão/patologiaRESUMO
Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1-9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2-4 showed anti-inflammatory activity (9.52-32.48% inhibition at the concentration 10 µm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.
Assuntos
Anti-Inflamatórios , Callicarpa/química , Diterpenos Clerodânicos , Neutrófilos/metabolismo , Adulto , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Feminino , Humanos , Masculino , Neutrófilos/patologia , Superóxidos/metabolismoRESUMO
We evaluated the analytical and clinical performance of a novel circulating tumor cell (CTC)-based blood test for determination of programmed death ligand 1 (PD-L1) protein expression status in real time in treatment-naïve non-small cell lung cancer (NSCLC) patients. CTCs were detected in 86% of patients with NSCLC (I-IV) at the time of diagnosis, with a 67% PD-L1 positivity rate (≥ 1 PDL + CTC). Among 33 NSCLC patients with PD-L1 results available via both tissue immunohistochemistry (IHC) and CTC assays, 78.9% were positive according to both methods. The CTC test identified an additional ten cases that were positive for PD-L1 expression but that tested negative via IHC analysis. Detection of higher PD-L1 expression on CTCs compared to that in the corresponding tissue was concordant with data obtained using other platforms in previously treated patients. The concordance in PD-L1 expression between tissue and CTCs was approximately 57%, which is higher than that reported by others. In summary, evaluation of PD-L1 protein expression status on CTCs isolated from NSCLC patients is feasible. PD-L1 expression status on CTCs can be determined serially during the disease course, thus overcoming the myriad challenges associated with tissue analysis.
Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Reações Falso-Negativas , Estudos de Viabilidade , Feminino , Humanos , Imuno-Histoquímica , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Silibinin is a flavonolignan that is well established for its robust antiviral activity against HCV infection and has undergone several clinical trials for the management of hepatitis C. Despite its potency, silibinin suffers from poor solubility and bioavailability, restricting its clinical use. To overcome this limitation, we developed highly bioavailable silibinin nanoparticles (SB-NPs) and evaluated their efficiency against HCV infection. DESIGN: SB-NPs were prepared using a nanoemulsification technique and were physicochemically characterised. Infectious HCV culture systems were used to evaluate the influence of SB-NP on the virus life cycle and examine their antioxidant activity against HCV-induced oxidative stress. The safety profiles of SB-NP, in vivo pharmacokinetic studies and antiviral activity against infection of primary human hepatocytes were also assessed. RESULTS: SB-NP consisted of nanoscale spherical particles (<200â nm) encapsulating amorphous silibinin at >97% efficiency and increasing the compound's solubility by >75%. Treatment with SB-NP efficiently restricted HCV cell-to-cell transmission, suggesting that they retained silibinin's robust anti-HCV activity. In addition, SB-NP exerted an antioxidant effect via their free radical scavenging function. Oral administration of SB-NP in rodents produced no apparent in vivo toxicity, and pharmacokinetic studies revealed an enhanced serum level and superior biodistribution to the liver compared with non-modified silibinin. Finally, SB-NP efficiently reduced HCV infection of primary human hepatocytes. CONCLUSIONS: Due to SB-NP's enhanced bioavailability, effective anti-HCV activity and an overall hepatoprotective effect, we suggest that SB-NP may be a cost-effective anti-HCV agent that merits further evaluation for the treatment of hepatitis C.
Assuntos
Antioxidantes/farmacologia , Hepacivirus/efeitos dos fármacos , Silimarina/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Células Cultivadas , Sistemas de Liberação de Medicamentos , Hepacivirus/patogenicidade , Hepatócitos/virologia , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Nanosferas , Ratos , Silibina , Silimarina/administração & dosagem , Silimarina/farmacocinéticaRESUMO
BACKGROUND & AIMS: A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection. METHODS: Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated. RESULTS: BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes. CONCLUSIONS: Due to its potency, SSb2 may be of value for development as an antagonist of HCV entry and could be explored as prophylactic treatment during the course of liver transplantation.
Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Animais , Antivirais/isolamento & purificação , Antivirais/toxicidade , Bupleurum , Linhagem Celular , Hepatite C/prevenção & controle , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Transplante de Fígado , Masculino , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Ácido Oleanólico/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Saponinas/toxicidade , Vírion/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or ß as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.
Assuntos
Estrogênios/farmacologia , Liriope (Planta)/química , Compostos Fitoquímicos/química , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Cromanos/química , Cromanos/isolamento & purificação , Cromanos/farmacologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/química , Estrogênios/isolamento & purificação , Humanos , Isocumarinas/química , Isocumarinas/isolamento & purificação , Isocumarinas/farmacologia , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
In an effort to develop potent cyclooxygenase-1 (COX-1) inhibitors used as anticancer agent, a series of 2',5'-dimethoxychalcones was screened to evaluate their antiplatelet effect on human washed platelets suspension. Compound 2 exhibited potent inhibition of human washed platelet aggregation induced by collagen, significantly inhibited collagen- and arachidonic acid-induced thromboxane B2 release, and revealed inhibitory effect on COX-1 activity. Molecular docking studies showed that 1, 2, and 4 were bound in the active site of COX-1. These indicated that the antiplatelet effect of these compounds were mainly mediated through the suppression of COX-1 activity and reduced the thromboxane formation. To investigate the mechanistic action of COX-1 inhibitor enhanced the cytotoxic effect against human bladder cancer cells, NTUB1, we assessed the cytotoxic effect of 2 against NTUB1. Treatment of NTUB1 cells with various concentrations of 2 led to a concentration-dependent increase of cell death and decrease of reactive oxygen species levels. The flow-cytometric analysis showed that 2 induced a G1 phase cell cycle arrest but did not accompany an appreciable sub-G1 phase in NTUB1 cells. In addition, compound 2 increased p21 and p27 expressions and did not inhibit the expression of COX-1 in NTUB1 cells. Our results suggested that 2 enhanced cell growth inhibition or antiproliferative activity in NTUB1 cells through G1 arrest by COX-1 independent mechanism.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Chalcona/análogos & derivados , Chalcona/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chalcona/química , Ciclo-Oxigenase 1/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Inibidores da Agregação Plaquetária/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
A novel benzoylphloroglucinol derivative, garcimultiflorone G (1), was isolated from the fruits of Garcinia multiflora. The structure of 1 was determined through extensive 1D- and 2D-NMR, and MS analyses. Garcimultiflorone G (1) showed inhibitory effects against superoxide anion (O·2(-) generation and elastase release by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB), with IC50 values of 6.97 ± 1.56 and 11.70 ± 1.58 µM, respectively.
Assuntos
Anti-Inflamatórios/farmacologia , Garcinia/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Neutrófilos/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Humanos , N-Formilmetionina Leucil-Fenilalanina/imunologia , Neutrófilos/imunologia , Elastase Pancreática/imunologiaRESUMO
Ten new lantabetulic acid (1) derivatives 2-11 were synthesized and their cytotoxicities against human prostate cancer cells were evaluated. PC3 cells treated with 10 µM 8 exhibited the most potent G1 phase arrest. In addition, 10 µM 8 markedly decreased the levels of cyclin E and cdk2 and caused an increase in the p21 and p27 levels, while 20 µM 8 mainly led to cell death through the apoptotic pathway, which correlated with an increase in reactive oxygen species levels, decreased expression levels of Bcl-2 and caspase-8, the induction of mitochondrial changes, and decreased levels of cytochrome c in mitochondria. The dual action of 8 could provide a new approach for the development of chemotherapeutic drugs.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Neoplasias da Próstata/patologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estrutura Molecular , Neoplasias da Próstata/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo , Triterpenos/síntese químicaRESUMO
Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract.
Assuntos
Antineoplásicos/farmacologia , Artocarpus/química , Lectinas de Ligação a Manose/farmacologia , Extratos Vegetais/farmacologia , Lectinas de Plantas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Células Hep G2 , Humanos , Lectinas de Ligação a Manose/análise , Extratos Vegetais/química , Lectinas de Plantas/análiseRESUMO
BACKGROUND: This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm. METHODS: Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures. RESULTS: Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09-1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96-1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10-1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size < 1 cm. CONCLUSIONS: In patients with stage I NSCLC and tumor size < 1 cm, thermal ablation has similar OS and CSS with wedge resection.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Programa de SEER , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estados Unidos/epidemiologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Pneumonectomia/métodos , Pneumonectomia/mortalidade , Taxa de SobrevidaRESUMO
Bioassay-guided fractionation of the CHCl3 layer of Solanum violaceum areal parts methanolic extract led to the isolation of four new steroidal sapogenins, indiosides L-O (1-4), along with eight known steroids, one lignin, and a coumarin. Indioside L is a rare spirostanoid possessing a 1,4-dien-3-one moiety in ring A. Moreover, compounds 3 and 4 represent rare examples of spirostene with the 3ß,7α-diol-5,6-ene moiety compared to the normal 3ß,7ß-diol-5,6-ene derivatives. The cytotoxic activity of the isolates (5-14) was evaluated against human hepatoma (HepG2 and Hep3B), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231 and MCF-7).
Assuntos
Antineoplásicos/química , Solanum/química , Espirostanos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Conformação Molecular , Folhas de Planta/química , Caules de Planta/química , Espirostanos/isolamento & purificação , Espirostanos/toxicidadeRESUMO
BACKGROUND: Many natural products used in preventive medicine have also been developed as cosmeceutical ingredients in skin care products, such as Scutellaria baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant and antityrosinase activity compound in Artocarpus communis; however, the cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin have not been investigated yet. METHODS: In the present study, cell viability in vitro and skin irritation in vivo are used to determine the safety of norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we examined the related-melanogenesis protein by western blot analysis for elucidating the antimelanogenesis mechanism of norartocarpin. RESULTS: The result of the present study demonstrated that norartocarpetin not only present non-cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in mice. Moreover, our result also first found that norartocarpetin downregulated phospho-cAMP response element-binding (phospho-CREB) and microphthalmia-associated transcription factor (MITF) expression, which in turn decreased both synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This process is dependent on norartocarpetin phosphorylation by mitogen-activated protein kinases such as phospho-JNK and phospho-p38, and it results in decreased melanogenesis. CONCLUSION: The present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study.
Assuntos
Artocarpus/química , Sobrevivência Celular/efeitos dos fármacos , Flavonas/farmacologia , Monofenol Mono-Oxigenase/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Flavonas/química , Humanos , Masculino , Medicina Tradicional , Melaninas/análise , Melaninas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição Associado à Microftalmia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/química , Testes de Irritação da PeleRESUMO
The methanolic extract of Flemingia macrophylla roots exhibited significant estrogenic activity in the transgenic plant assay system which was comparable to the activity of soybean extract. Utilizing estrogenic activity-guided fractionation, one new compound, fleminigin, together with 23 known compounds were isolated from F. macrophylla roots' methanolic extract. The structure of the new compound was identified based on intensive spectroscopic analysis and the full spectral data for one of the isolated compounds, flemichin E, was introduced for the first time in the current investigation. The estrogenic and anti-estrogenic activities of the isolated compounds were evaluated revealing that the isolated isoflavonoids may act as partial estrogen agonists, as well as antagonists. Additionally, the anti-inflammatory and the cytotoxic activities of the isolated compounds were studied. These results suggested the potential applications of F. macrophylla extract and its isolated compounds as selective estrogen receptor modulators (SERMs).
Assuntos
Anti-Inflamatórios/química , Fabaceae/química , Receptores de Estrogênio/metabolismo , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Receptores de Estrogênio/genética , Superóxidos/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
INTRODUCTION: The effectiveness of using intraoperative robotic C-arm cone-beam computerized tomography (CT) to locate rib fractures during surgery was compared to using pre-operative CT. METHODS: Patients diagnosed with multiple rib fracture and treated surgically in the hospital between January 2019 and September 2020 were included. The study included two groups of patients. One group had their rib fractures identified using pre-operative CT, while the other group had their fractures localized using intraoperative cone-beam CT during surgery. The operative time, blood loss, number of incisions, length of incision, duration of chest drains, visual analogue scale (VAS) score, and duration of post-operation stays were measured. RESULTS: A total of 12 patients received intraoperative cone-beam CT, while the remaining 18 patients only received pre-operative CT. Statistical analysis showed that the group treated with cone-beam CT had lower blood loss (p = 0.012), shorter incisions (p = 0.005), and better post-operation VAS scores (p = 0.027). There were also non-significant trends towards fewer incisions, shorter operation times, and shorter duration of chest drains in the group treated with cone-beam CT. CONCLUSIONS: Intraoperative localization of rib fracture sites with cone-beam CT is an effective method for rib fracture stabilization.
Assuntos
Fraturas das Costelas , Procedimentos Cirúrgicos Robóticos , Humanos , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/cirurgia , Fixação Interna de Fraturas/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ)-induced diabetic mice and high-glucose (HG)-exposed rat mesangial cell (RMC) as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-ß1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H(2)DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-ß1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders.
RESUMO
A novel benzoylphloroglucinol derivative, garcimultiflorone D (1), with an unusual adamantyl-caged skeleton was isolated from the fruits of Garcinia multiflora, together with four known compounds. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Garcimultiflorone D (1) exhibited inhibitory activities with IC(50) values of 7.21±1.07 and 6.01±0.37â µg/ml against fMLP/CB-induced superoxide anion generation and elastase release, respectively.
Assuntos
Adamantano/química , Garcinia/química , Neutrófilos/efeitos dos fármacos , Floroglucinol/análogos & derivados , Floroglucinol/química , Frutas/química , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Elastase Pancreática/metabolismo , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Superóxidos/metabolismoRESUMO
This study aimed to examine the chemical and anti-aging properties of chicken essence (CE) prepared with Sesamum indicum, Angelica acutiloba, and Zingiber officinale (HCE). HCE was analyzed for nutritional and phytochemical composition, and its anti-aging effects were investigated on the D-galactose (Gal)-induced aging mice. Results showed that HCE possessed significantly higher calories and contents of valine and total phenols than CE; it also contained significant amounts of ferulic acid, sesamin, and sesamolin. HCE significantly decreased MDA and NO levels in serum and liver and increased liver GSH levels in the D-Gal-induced mice. HCE greatly enhanced SOD and CAT activities in serum and liver, and liver GPx activity, as well as upregulating SIRT1 expression and downregulating TNF-α, IL-1ß, IL-6, iNOS, Cox-2, and MCP-1 expression in liver tissues. This study demonstrates that HCE was effective in suppressing the aging process through enhancing antioxidant and anti-inflammatory activities and modulating the aging-related gene expression.
RESUMO
Objective: Harmonizing formulas are associated with beneficial renal outcomes in chronic kidney disease (CKD), but the therapeutic mechanisms are unclear. The study aims to explore the associations of intentions and independent factors with harmonizing formulas prescriptions for patients with CKD. Methods: We conducted a population-based cross-sectional study to explore factors associated with harmonizing formulas prescription. Patients who had been prescribed harmonizing formulas after CKD diagnosis was defined as the using harmonizing formulas group. Disease diagnoses when having harmonizing formula prescriptions and patient characteristics related to these prescriptions were collected. Results: In total, 24,971 patients were enrolled in this analysis, and 5,237 (21%) patients were prescribed harmonizing formulas after CKD diagnosis. The three most frequent systematic diseases and related health problems for which harmonizing formula prescriptions were issued in CKD were symptoms, signs, and ill-defined conditions (24.5%), diseases of the digestive system (20.67%), and diseases of the musculoskeletal system (12.9%). Higher likelihoods of harmonizing formula prescriptions were associated with young age (adjusted odds ratio: 0.98, 95% confidence interval: 0.97-0.98), female sex (1.79, 1.68-1.91), no diabetes (1.20, 1.06-1.36), no hypertension (1.38, 1.27-1.50), no cerebrovascular disease (1.34, 1.14-1.56), less disease severity (0.85, 0.83-0.88), using nonsteroidal anti-inflammatory drugs (NSAIDs) (1.65, 1.54-1.78), and using analgesic drugs other than NSAIDs (1.47, 1.35-1.59). Conclusion: Harmonizing formulas are commonly used for treating symptoms of the digestive and musculoskeletal systems in CKD cases. Further research on harmonizing formula effectiveness with regard to particular characteristics of CKD patients is warranted.