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1.
J Otolaryngol Head Neck Surg ; 52(1): 86, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135871

RESUMO

OBJECTIVE: To quantify the results of superficial parotidectomy (SP) and partial SP (PSP) for benign parotid tumours using a systematic evaluation method. METHODS: A systematic search of English and Chinese databases (PubMed, Web of Science, Cochrane Library, China Knowledge Network, Wanfang and Vipshop) was conducted to include studies comparing the treatment outcomes of SP with PSP. RESULTS: Twenty-three qualified, high-quality studies involving 2844 patients were included in this study. The results of this study showed that compared to the SP surgical approach, the PSP surgical approach reduced the occurrence of temporary facial palsy (OR = 0.33; 95% confidence interval [CI] 0.26-0.41), permanent facial palsy (OR = 0.28; 95% CI 0.16-0.52) and Frey syndrome (OR = 0.36; 95% CI 0.23-0.56) in patients after surgery, and the surgery operative time was reduced by approximately 27.35 min (95% CI - 39.66, - 15.04). However, the effects of PSP versus SP on salivary fistula (OR = 0.70; 95% CI 0.40-1.24), sialocele (OR = 1.48; 95% CI 0.78-2.83), haematoma (OR = 0.34; 95% CI 0.11-1.01) and tumour recurrence rate (OR = 1.41; 95% CI 0.48-4.20) were not statistically significant. CONCLUSION: Compared with SP, PSP has a lower postoperative complication rate and significantly shorter operative time, suggesting that it could be used as an alternative to SP in the treatment of benign parotid tumours with the right indications.


Assuntos
Paralisia Facial , Neoplasias Parotídeas , Humanos , Paralisia Facial/etiologia , Paralisia Facial/prevenção & controle , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Resultado do Tratamento
2.
Nutr Res Pract ; 17(4): 682-697, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37529260

RESUMO

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

3.
Cell Rep Med ; 3(11): 100814, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36384091

RESUMO

ARX788 is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate with AS269 as cytotoxic payload. In this phase 1 multicenter dose-expansion clinical trial, patients with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment were enrolled. Between July 15th, 2019, and March 14th, 2022, 30 participants were enrolled. Twenty-eight (93.3%) patients experienced at least one drug-related adverse event (AE) and 13.3% experienced grade 3 ARX788-related AEs. The confirmed objective response rate is 37.9% (95% confidence interval [CI]: 20.7%-57.7%) and the disease control rate is 55.2% (95% CI: 35.7%-73.6%). With a median follow up of 10 months, the median progression-free survival and overall survival are 4.1 (95% CI: 1.4-6.4) and 10.7 months (95% CI: 4.8-not reached), respectively. The median duration of response is 8.4 (95% CI: 2.1-18.9) months. ARX788 is well tolerated and has promising anti-tumor activity in patients with HER2-positive advanced gastric adenocarcinoma (ChinaDrugTrials.org.cn: CTR20190639).


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Junção Esofagogástrica/patologia
4.
Mol Cancer Ther ; 19(9): 1822-1832, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32499302

RESUMO

Conventional antibody-drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The nonspecific conjugation results in a mixture with variable drug-to-antibody ratios (DAR), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent antitubulin cytotoxic drug-linker, AS269. The site-specific conjugation is achieved by first incorporating the nonnatural amino acid, para-acetyl phenylalanine (pAF), into the antibody, followed by covalent conjugation of AS269 to the pAF to form a highly stable oxime bond resulting in a DAR 2 ADC. ARX788 exhibits significant, dose-dependent antitumor activity against HER2- expressing breast and gastric xenograft tumors. Pharmacokinetic (PK) studies in multiple species showed the highly stable nature of ARX788 with overlapping PK profiles for the intact ADC and total antibody. Metabolism studies demonstrated that pAF-AS269 was the sole major metabolite of ARX788, with no evidence for the release of free drug often observed in conventional ADCs and responsible for adverse side effects. Furthermore, ARX788 demonstrated a favorable safety profile in monkeys with a highest nonseverely toxic dose of 10 mg/kg, which was well above the efficacious dose level observed in preclinical tumor models, thus supporting clinical development of ARX788.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Receptor ErbB-2/metabolismo , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacocinética , Azidas/química , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Feminino , Ferricromo/química , Haplorrinos , Humanos , Masculino , Camundongos , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Ratos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
5.
World J Clin Cases ; 8(9): 1721-1728, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32432146

RESUMO

BACKGROUND: Ventral hernia, also known as incisional hernia, is a common complication of previous surgery. The contents of ventral hernia may include omentum, preperitoneal fat, small intestine or colon. However, ventral hernia with protrusion of more than two parenchymal organs simultaneously is extremely rare, and its repair is very complex and difficult. Surgeons should make a comprehensive assessment based on their own experience and the individual characteristics of the hernia. In addition, psychological therapy should be emphasized in the whole treatment process. CASE SUMMARY: We report a rare case of asymptomatic giant ventral hernia for 15 years in a 21-year-old female. The patient underwent umbilical hernia repair at the age of 1 year. Approximately 5 years later, ventral hernia recurred and repair with Mesh was performed, but the operation failed due to postoperative infection, and a huge mass appeared in the left abdominal wall. The mass increased gradually with the development and maturity of the body. Computerized tomography scan demonstrated that the patient's total spleen, part of the pancreas and left lobe of the liver were simultaneously herniated through the abdominal incisional hernia. As the patient was unable to endure the inconvenience of life and the potential risk of spleen or liver rupture, she underwent a ventral hernia repair with Mesh at our hospital. The operation was successful and the patient had a good recovery. During a 3-mo follow-up, the patient remained asymptomatic and the appearance of the surgical incision was greatly improved. CONCLUSION: Ventral hernia is a common complication of abdominal surgery. Ventral hernia with protrusion of more than two parenchymal organs simultaneously is extremely rare. Surgeons should pay attention to the psychological treatment while restoring the abdominal physiological function in ventral hernia patients.

6.
BMC Cancer ; 20(1): 361, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349713

RESUMO

BACKGROUND: The prognostic nutritional index (PNI), an immunity and nutrition based prognostic score, was correlated with clinical outcomes in different tumors. However, the prognostic significance of PNI has not been investigated in hormone sensitive prostate cancer (PCa). The objective of this study was to determine the prognostic significance of PNI in hormone sensitive PCa. METHODS: Two hundred eighty PCa patients undergoing androgen deprivation therapy (ADT) as first line therapy at three centers were enrolled. The serum albumin levels and peripheral lymphocyte count were measured at the time of diagnosis. PNI was calculated as 10 * serum albumin (g/dL) + 0.005 * total lymphocyte count (per mm3). Patients were categorized in two groups using a cut-off point of 50.2 as calculated by the receiver-operating curve analysis. Univariate and multivariate cox regression analyses were performed to evaluate PNI as a favorable prognostic factor for progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. RESULTS: Multivariate analyses identified PNI as an independent prognostic indicator with respect to PFS (hazard ratio (HR) = 0.521, p = 0.001), CSS (HR = 0.421, p = 0.002) and OS (HR = 0.429, p = 0.001). Patients with elevated PNI had better clinical outcomes. The addition of PNI to the final models improved predictive accuracy (c-index: 0.758, 0.830 and 0.782) for PFS, CSS and OS compared with the clinicopathological base models (c-index: 0.736, 0.801 and 0.752), which included Gleason score and incidence of metastasis. CONCLUSIONS: Elevated pretreatment PNI was a favorable prognostic indicator for PCa patients treated with ADT.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias Hormônio-Dependentes/metabolismo , Avaliação Nutricional , Estado Nutricional , Neoplasias da Próstata/metabolismo , Adulto , Idoso , Seguimentos , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/patologia , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Taxa de Sobrevida
7.
Oncol Rep ; 43(5): 1429-1436, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32323794

RESUMO

Osteosarcoma (OS) is a common malignant bone tumor, presenting particularly in children and young adults, and accounts for approximately 19% of all malignant bone cancers. Despite advances in OS treatment, long­term prognosis remains poor. miRNAs are non­coding single­stranded RNAs ~22 nucleotides in length. Increasing evidence suggests that numerous miRNAs may play critical roles in tumorigenesis and tumor progression; however, the role of miR­95 in OS has not been examined. In the present study, we investigated the role of miR­95 in OS using in vitro and in vivo models and publicly available expression data. Our findings indicate that abnormal miR­95 expression occurs in OS, according to the Gene Expression Omnibus (GEO) database. The miR­95 inhibitor reduced cell proliferation and promoted apoptosis in OS cell lines as detected by EdU staining, TUNEL staining and flow cytometry. Furthermore, a dual luciferase reporter assay revealed that miR­95 regulates the cell cycle of OS cells and apoptosis by targeting sodium channel epithelial 1α subunit (SCNN1A). Additionally, miR­95 antagomir suppressed the growth of U2OS xenograft tumors in a mouse model. In summary, our results suggest that miR­95 induces OS growth in vitro and in vivo by targeting SCNN1A. Our results help clarify the mechanism underlying the miR­95­mediated effects on OS tumor growth, thus potentially establishing it as a diagnostic target.


Assuntos
Neoplasias Ósseas/patologia , Canais Epiteliais de Sódio/genética , MicroRNAs/genética , Osteossarcoma/patologia , Regulação para Cima , Animais , Apoptose , Neoplasias Ósseas/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Canais Epiteliais de Sódio/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Osteossarcoma/genética , Prognóstico
8.
World J Clin Cases ; 6(15): 1042-1046, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30568961

RESUMO

We report a case of intermittent lower abdominal pain and distension accompanied by defecation difficulties for 3 years due to Chilaiditi syndrome in a 59-year-old male. Before admission to our hospital, the patient had undergone gastroscopy, which showed gastritis and duodenitis, and colonoscopy, which showed cecum deformation and cicatricial changes of the mucous membrane in the colon hepatic flexure. A computed tomography (CT) scan of the abdomen at our hospital confirmed right hepatic atrophy and interposition of the colon. Moreover, CT simulation endoscopy identified cystic dilatation in the colon hepatic flexure with the widest diameter of 8.2 cm. The patient was diagnosed with Chilaiditi syndrome. As the patient was unable to endure his defecation difficulties, he underwent a laparoscope-assisted right hemicolectomy. The patient had a good recovery. During the follow-up period of 9 mo, the patient remained symptom-free.

9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 30(8): 980-984, 2016 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-29786229

RESUMO

OBJECTIVE: To evaluate the effectiveness of posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy for treating cervical radiculo-myelopathy. METHODS: Between January 2010 and January 2012, 58 patients with cervical radiculo-myelopathy were treated by posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy. There were 31 males and 27 females, with an average age of 52.7 years (range, 41-72 years). The mean disease course was 5.4 years (range, 3-15 years). The preoperative Japanese Orthopaedic Association (JOA) score was 7.8±1.3, and visual analogue scale (VAS) score was 6.8±1.7. There were 37 cases of inter-vertebral disc herniation and ligamentum flavum hypertrophy, 11 cases of vertebral osteophyte formation with the osteophyte spinal canal occupational ratio of 51.7%±18.1%, and 10 cases of inter-vertebral disc herination with cervical instability. Preoperative cervical curvature was (-5.5±12.5)°. The fixed segments included C3-7 in 29 cases, C4-7 in 19 cases, and C3-6 in 10 cases. Foraminotomy was performed in 135 nerve foramina (mean, 2.33 foramina). RESULTS: The mean operation time was 204 minutes (range, 167-260 minutes), and the mean blood loss was 273 mL (range, 210-378 mL). No injury of vertebral artery or nerve root occurred during operation. Postoperative subcutaneous hematoma and cervical axial pain occurred in 1 case and 8 cases, respectively; and no nerve root palsy was observed. The patients were followed up 2.1-4.3 years (mean, 3.4 years). The postoperative JOA score was significantly increased to 14.1±1.7 (t=-27.672, P=0.000), with an improvement rate of 68.5%±21.9%. Postoperative VAS score was significantly decreased to 2.1±1.1 (t=15.168, P=0.000). The imaging examination showed adjacent segmental degeneration in 1 patient, who had no clinical symptom. There was no screw loosening or pseudoarthrosis formation during follow-up. The cervical curvature was (13.6±5.1)° at 5 days and was (13.2±4.8)° at 2 years, showing significant difference when compared with preoperative one (P<0.05). The osteophyte spinal canal occupational ratio was 36.5%±10.4% at 2 years, showing significant difference when compared with preoperative one (t=6.921, P=0.000). CONCLUSIONS: The procedure of posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy is effect in treating cervical radiculo-myelopathy. The spinal cord and nerve root can be adequately decompressed by laminectomy and foraminotomy. The lateral mass screw fixation can correct the cervical curvature and further reduce the tension to spinal cord.


Assuntos
Parafusos Ósseos , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Foraminotomia , Laminectomia , Radiculopatia/cirurgia , Osteofitose Vertebral/cirurgia , Feminino , Humanos , Ligamento Amarelo , Masculino , Cervicalgia/etiologia , Cervicalgia/fisiopatologia , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Osteofitose Vertebral/complicações , Resultado do Tratamento
10.
J Med Chem ; 58(19): 7763-74, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26331194

RESUMO

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid (UAB30) is currently undergoing clinical evaluation as a novel cancer prevention agent. In efforts to develop even more highly potent rexinoids that prevent breast cancer without toxicity, we further explore here the structure-activity relationship of two separate classes of rexinoids. UAB30 belongs to the class II rexinoids and possesses a 9Z-tetraenoic acid chain bonded to a tetralone ring, whereas the class I rexinoids contain the same 9Z-tetraenoic acid chain bonded to a disubstituted cyclohexenyl ring. Among the 12 class I and class II rexinoids evaluated, the class I rexinoid 11 is most effective in preventing breast cancers in an in vivo rat model alone or in combination with tamoxifen. Rexinoid 11 also reduces the size of established tumors and exhibits a therapeutic effect. However, 11 induces hypertriglyceridemia at its effective dose. On the other hand rexinoid 10 does not increase triglyceride levels while being effective in the in vivo chemoprevention assay. X-ray studies of four rexinoids bound to the ligand binding domain of the retinoid X receptor reveal key structural aspects that enhance potency as well as those that enhance the synthesis of lipids.


Assuntos
Anticarcinógenos/química , Anticarcinógenos/farmacologia , Ácidos Graxos Insaturados/química , Neoplasias Mamárias Experimentais/prevenção & controle , Naftalenos/química , Relação Estrutura-Atividade , Animais , Anticarcinógenos/efeitos adversos , Anticarcinógenos/metabolismo , Sítios de Ligação , Técnicas de Química Sintética , Cristalografia por Raios X , Dislipidemias/induzido quimicamente , Dislipidemias/metabolismo , Feminino , Humanos , Neoplasias Mamárias Experimentais/induzido quimicamente , Conformação Molecular , Ratos Sprague-Dawley , Receptor X Retinoide alfa/química , Receptor X Retinoide alfa/metabolismo , Tamoxifeno/farmacologia , Triglicerídeos/sangue
11.
J Med Chem ; 57(12): 5370-80, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24801499

RESUMO

(2E,4E,6Z,8E)-8-(3',4'-Dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid, 9cUAB30, is a selective rexinoid that displays substantial chemopreventive capacity with little toxicity. 4-Methyl-UAB30, an analogue of 9cUAB30, is a potent RXR agonist but caused increased lipid biosynthesis unlike 9cUAB30. To evaluate how methyl substitution influenced potency and lipid biosynthesis, we synthesized four 9cUAB30 homologues with methyl substitutions at the 5-, 6-, 7-, or 8-position of the tetralone ring. The syntheses and biological evaluations of these new analogues are reported here along with the X-ray crystal structures of each homologue bound to the ligand binding domain of hRXRα. We demonstrate that each homologue of 9cUAB30 is a more potent agonist, but only the 7-methyl-9cUAB30 caused severe hyperlipidemia in rats. On the basis of the X-ray crystal structures of these new rexinoids and bexarotene (Targretin) bound to hRXRα-LBD, we reveal that each rexinoid, which induced hyperlipidemia, had methyl groups that interacted with helix 7 residues of the LBD.


Assuntos
Anticarcinógenos/química , Ácidos Graxos Insaturados/química , Hiperlipidemias/induzido quimicamente , Naftalenos/química , Receptor X Retinoide alfa/agonistas , Animais , Anticarcinógenos/farmacologia , Anticarcinógenos/toxicidade , Apoptose/efeitos dos fármacos , Bexaroteno , Sítios de Ligação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Cristalografia por Raios X , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/toxicidade , Feminino , Humanos , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/prevenção & controle , Modelos Moleculares , Estrutura Molecular , Naftalenos/farmacologia , Naftalenos/toxicidade , Ratos , Receptor X Retinoide alfa/genética , Estereoisomerismo , Relação Estrutura-Atividade , Tetra-Hidronaftalenos/farmacologia , Tetra-Hidronaftalenos/toxicidade , Ativação Transcricional
12.
J Nat Prod ; 77(1): 178-82, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24328283

RESUMO

Six new (leonurusoleanolides E-J, 1-6) and five known (7-11) nortriterpenoids were isolated and characterized from the dried fruits of Leonurus japonicus. They all contain a distinctive 19(18→17)-abeo-28-noroleanane-type spirocylclic skeleton with a trans or a cis acyl substituent at C-3 or C-23. Similar to the previously known leonurusoleanolides A/B (7/8) and C/D (9/10), compounds 1/2 and 3/4 were also found to exist as equilibrium mixtures of trans and cis isomers. The isolated pure compounds and mixtures were evaluated for their cytotoxicity against a small panel of human cancer cell lines (BGC-823 and KE-97 gastric carcinoma, Huh-7 hepatocarcinoma, Jurkat T cell lymphoblasts, and MCF-7 breast adenocarcinoma) using the CellTiter-Glo luminescent cell viability assay method. Among them, (2α,3ß,17R*,18ß)-3-O-(trans-caffeoyl)-19(18→17)-abeo-28-norolean-12-ene-2,18,23-triol (leonurusoleanolide J, 6) showed the most potent cytotoxic activity, with IC50 values less than 10 µM.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Leonurus/química , Compostos de Espiro/isolamento & purificação , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Frutas/química , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Triterpenos/química , Triterpenos/farmacologia
13.
Bioorg Med Chem ; 22(1): 178-85, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24359708

RESUMO

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid, 9cUAB30, is a selective rexinoid for the retinoid X nuclear receptors (RXR). 9cUAB30 displays substantial chemopreventive capacity with little toxicity and is being translated to the clinic as a novel cancer prevention agent. To improve on the potency of 9cUAB30, we synthesized 4-methyl analogs of 9cUAB30, which introduced chirality at the 4-position of the tetralone ring. The syntheses and biological evaluations of the racemic homolog and enantiomers are reported. We demonstrate that the S-enantiomer is the most potent and least toxic even though these enantiomers bind in a similar conformation in the ligand binding domain of RXR.


Assuntos
Neoplasias/prevenção & controle , Neoplasias/terapia , Receptores X de Retinoides/metabolismo , Retinoides/química , Humanos , Fator 4 Semelhante a Kruppel , Ligantes , Conformação Molecular , Retinoides/metabolismo
14.
J Pept Sci ; 19(9): 598-605, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23893560

RESUMO

Glucagon-like peptide 1 receptor (GLP1R) is a promising target for the treatment of type 2 diabetes. Because of the short half-life of endogenous GLP1 peptide, other GLP1R agonists are considered to be appealing therapeutic candidates. A high-throughput assay has been established to screen for GLP1R agonists in a 60 000-well natural product compound library fractionated from 670 different herbs/materials widely used in traditional Chinese medicines (TCMs). The screening is based on primary screen of GLP1R⁺ reporter gene assay with the counter screen in GLP1R⁻ cell line. An active fraction, A089-147, was identified from the screening. Fraction A089-147 was isolated from dried Ophisaurus harti, and the fact that its GLP1R agonist activity was sensitive to trypsin treatment indicates its peptidic nature. The active ingredient of A089-147 was later identified as O. harti GLP1 through transcriptome analysis. Chemically synthesized O. harti GLP1 showed GLP1R agonist activity and sensitivity to dipeptidase IV digestion. This study illustrated a comprehensive screening strategy to identify novel GLP1R agonists from TCMs libraries and at the same time underlined the difficulty of identifying a non-peptidic GLP1R agonist. The novel O. harti GLP1 peptide yielded from this study confirmed broader application of TCMs libraries in active peptide identification.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/farmacologia , Hipoglicemiantes/farmacologia , Lagartos/metabolismo , Receptores de Glucagon/agonistas , Proteínas de Répteis/farmacologia , Sequência de Aminoácidos , Animais , Sequência Conservada , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/química , Avaliação Pré-Clínica de Medicamentos , Trato Gastrointestinal/metabolismo , Peptídeo 1 Semelhante ao Glucagon/química , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1 , Células HEK293 , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Medicina Tradicional Chinesa , Dados de Sequência Molecular , Proteólise , Proteínas de Répteis/química , Proteínas de Répteis/metabolismo , Análise de Sequência de Proteína , Bibliotecas de Moléculas Pequenas , Transcriptoma
15.
Phytochemistry ; 92: 137-45, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23747096

RESUMO

Four (1-4) hitherto unknown and seven (5-11) known ergostane-type sterols were isolated from the EtOH extract of the dried fruiting bodies of the polypore macrofungus Fomes fomentarius. On the basis of spectroscopic analysis, the structures of polyhydroxylated sterols 1-4 were elucidated to be (22E,24R)-3ß,5α,6ß,14α-tetrahydroxyergosta-7,9(11),22-triene (fomentarol A, 1), (22E,24R)-3ß,5ß,6α,7α-tetrahydroxy-8α,9α-dihydroergosta-14,22-diene (fomentarol B, 2), (22E,24R)-3ß,5α-dihydroxy-6ß-ethoxyergosta-7,22-diene (fomentarol C, 3), and (22E,24S)-3ß,25-dihydroxy-15α-O-ß-D-glucopyranosylergosta-7,22-dien-6-one (fomentarol D, 4), respectively. Rings A/B and B/C are in turn cis-fused in compound 2, which is uncommon in natural ergostane-type sterols. The potential biogenetic relationship of 2 and other ergostane-type sterols isolated from F. fomentarius was briefly discussed. Moderate cytotoxic effects of the isolated sterols against a small panel of human cancer cell lines were also established.


Assuntos
Coriolaceae/química , Esteróis/isolamento & purificação , Conformação Molecular , Estereoisomerismo , Esteróis/química
16.
Int J Oral Sci ; 5(1): 44-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23579466

RESUMO

This paper aims to investigate if the dental restoration of nickel-chromium based alloy (Ni-Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni-Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of <1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of <1, 1 to <3 and 3 to <6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni-Cr alloy restoration need to be investigated.


Assuntos
Ligas de Cromo/química , Cromo/urina , Coroas , Níquel/urina , Adulto , Creatinina/urina , Porcelana Dentária/química , Feminino , Humanos , Masculino , Ligas Metalo-Cerâmicas/química , Pessoa de Meia-Idade , Espectrofotometria Atômica , Propriedades de Superfície , Fatores de Tempo
17.
Phytochemistry ; 89: 89-95, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23462587

RESUMO

The roots of the medicinal ornamental plant Clerodendrum trichotomum yielded a series of rearranged abietane diterpenoids, including three 17(15→16)-abeo-abietane (1-3) and three 17(15→16),18(4→3)-diabeo-abietane (4-6) derivatives. Their structures were elucidated by means of spectroscopic methods. The absolute configuration of (10R,16R)-12,16-epoxy-11,14,17-trihydroxy-6-methoxy-17(15→16)-abieta-5,8,11,13-tetraene-7-one (1) was deduced by a combination of single crystal X-ray diffraction analysis and the observed Cotton effects in its circular dichroism (CD) spectrum. All isolates were tested for their cytotoxicities against five human cancer cell lines (BGC-823, Huh-7, KB, KE-97, and Jurkat). Among them, compounds 4, 6, 9, 10, 12, and 14, each possessing a common 17(15→16),18(4→3)-diabeo-abietane framework, were found to have remarkable cytotoxic effects with IC50 values ranging from 0.83 to 50.99 µM.


Assuntos
Abietanos/química , Abietanos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Clerodendrum/química , Raízes de Plantas/química , Abietanos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos
18.
Nat Prod Res ; 27(12): 1136-40, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22889249

RESUMO

The methanol extract of the whole plant of Hedyotis chrysotricha demonstrated cytotoxicity against SK-HEP-1 human hepatocarcinoma cells in a primary screening for novel antitumour agents. Bioassay-guided fractionation and purification led to an active principle (24S)-ergostane-3ß,5α,6ß-triol (1) along with four inactive compounds (2-5). The in vitro transwell migration assay showed that compound 1 remarkably reduced the migration of SK-HEP-1 cells by 78.9% at a dose of 30 µM, without any apoptotic effect on this cell line. Moreover, all the isolated compounds were further evaluated for their cytotoxicities against another four human cancer cell lines (MCF-7, NUGC3, SH-SY5Y and PC-3).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Ergosterol/análogos & derivados , Hedyotis/química , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas/patologia , Medicina Tradicional Chinesa , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Plantas Medicinais/química
19.
Phytochemistry ; 86: 159-67, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23153518

RESUMO

Tetracyclic triterpenoids (named as altissimanins A-E, 1-5) and a terpenylated coumarin (denominated as altissimacoumarin G, 6), along with fifteen known compounds (7-21) were isolated from the bark of Ailanthus altissima. Structures of compounds 1-6 were established by spectroscopic methods and chemical transformations. Altissimanin A (1) is a tirucallane-type triterpenoid bearing an uncommon oxetane ring in the side-chain, while altissimanins D (4) and E (5) are two unprecedented dimers each consisting of one tirucallane-type and one dammarane-type triterpenoid moiety. All the isolates were evaluated for their cytotoxic effects against a small panel of human cancer cell lines.


Assuntos
Ailanthus/química , Cumarínicos/química , Casca de Planta/química , Triterpenos/química , Estrutura Molecular
20.
Shanghai Kou Qiang Yi Xue ; 21(3): 312-6, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22885494

RESUMO

PURPOSE: To explore whether the renal function parameters were associated with urinary nickel(Ni) and chromium(Cr) in patients undergoing dental restoration of nickel-chromium(Ni-Cr). METHODS: Seven hundred and ninety-five Ni-Cr alloy consumers were investigated by the questionnaire and the biological examination of renal function. The correlations between renal function parameters and urinary Ni(or Cr) were determined by Student's t test, one-way ANOVA, and Logistic regression analysis using SPSS12.0 software package. RESULTS: After dividing all subjects into three groups with equal sample size by urinary Ni (<38,38-90, ≥ 90µg/mol crea.), the middle group (38-90µg/mol crea.) had a significantly higher serum creatinine and estimated glomerular filtration rate (eGFR) compared to the other two groups, and there was no significant difference in other serum or urinary parameters of renal function. After dividing all subjects into three groups by urinary Cr(<38,38-88, and ≥ 90µg/mol crea.), no change was found in serum parameters, but urinary N-acetyl-ß-D-glucosaminidase (UNAG) and retinol-binding protein (URBP) showed negative association with urinary Cr. The prevalence of either abnormal eGFR and abnormal urine parameters of renal function did not show significant change between different dose of urinary Ni or Cr. CONCLUSIONS: No association of renal changes with urinary excretion of Ni and Cr was found in patients undergoing dental restoration of Ni-Cr alloy.


Assuntos
Cromo , Restauração Dentária Permanente , Níquel , Ligas de Cromo , Humanos
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