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1.
J Gynecol Obstet Hum Reprod ; 51(6): 102395, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35489712

RESUMO

OBJECTIVES: Previous studies examining the incidence of omental metastasis in uterine serous carcinoma generally suffered from small sample size, retrospective observational design, and single-center setting. So far, there was no systematic review and meta-analysis available on this topic, we conducted this study to quantitatively synthesize the data relating to this topic. DESIGN: systematic review and meta-analysis. MATERIAL AND METHODS: PubMed, Embase, and Web of Science were searched up until August 15, 2020. Two reviewers independently performed study selection, data extraction, and quality assessment. I2 was employed to assess the heterogeneity among the included studies. Effect sizes along with 95% confidence intervals were calculated to analyze outcomes of interest. Funnel plots and the Egger test were used to detect the risk of publication bias. OUTCOME MEASURES: incidence of omental metastasis in uterine serous carcinoma. RESULTS: A total of 16 studies involving 1012 women with uterine serous carcinoma were included in this study. All the included studies were at low risk of bias, and the heterogeneity among them was low. The pooled incidence of overall omental metastasis, occult omental metastasis, and gross omental metastasis in uterine serous carcinoma were 18% (95% CI, 0.15-0.20), 6% (95% CI, 0.04-0.08), and 10% (95% CI, 0.08-0.13), respectively. CONCLUSIONS: Uterine serous carcinoma has a high tendency of omental metastasis. The main form of omentum involvement is gross metastasis. However, occult metastasis in the normal-looking omentum is also worthy of note.

2.
Rapid Commun Mass Spectrom ; 36(1): e9205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34636119

RESUMO

RATIONALE: Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treated as a food intake. Until now, the metabolism feature, tissue distribution and anti-diabetes mechanism of Sal B have not been fully elucidated. METHODS: The metabolites of Sal B in rats were profiled using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-diabetes mechanism of Sal B was predicted by network pharmacology. RESULTS: A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation and isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in Sal B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, etc. CONCLUSIONS: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.


Assuntos
Benzofuranos/farmacocinética , Diabetes Mellitus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacocinética , Hipoglicemiantes/farmacocinética , Animais , Benzofuranos/administração & dosagem , Benzofuranos/química , Caspases/genética , Caspases/metabolismo , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Fezes/química , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Isomerismo , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Pulmão/química , Pulmão/metabolismo , Masculino , Espectrometria de Massas , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Salvia miltiorrhiza/química
3.
Org Lett ; 23(15): 6057-6061, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34279963

RESUMO

The C(sp3)-H functionalization of O-pentafluorobenzoyl ketone oximes was implemented under visible light irradiation with copper complexes as catalysts. The reactions involve iminyl-radical-mediated intramolecular hydrogen atom transfer as the key step, with the iminyl radicals being generated via copper-effected N-O cleavage. The reaction afforded 3,4-dihydro-2H-pyrroles under the conditions of [Cu(DPEphos)(bcp)]PF6 and DABCO, while γ-pentafluorobenzoyloxy ketones were produced predominantly when [Cu(dpp)2]PF6 and InCl3·4H2O were used as catalysts.

4.
Rapid Commun Mass Spectrom ; 35(18): e9157, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34182613

RESUMO

RATIONALE: Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. METHODS: An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. RESULTS: A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4, M5, M9, and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites (M4, M5, and M12) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. CONCLUSION: The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diabetes Mellitus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas/métodos , Quinolizinas/farmacocinética , Animais , Diabetes Mellitus/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Humanos , Masculino , Quinolizinas/administração & dosagem , Quinolizinas/metabolismo , Ratos , Ratos Sprague-Dawley
5.
Food Funct ; 12(10): 4325-4336, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876806

RESUMO

Food additives are widely used in our daily life, and the side-effects caused by them have gained extensive attention around the world. Notably, constituent-oriented metabolites, in some sense, always contribute to pharmacological changes, inducing toxicity, therapeutic effects, etc. Characterization of the metabolites and their potential functions is of great importance to the practical applications. In this work, an integrated strategy by combining metabolite profiling and network pharmacology was applied to characterize the metabolic features and reveal pharmacological changes of neohesperidin dihydrochalcone (NHDC) in vivo to demonstrate its pharmacological mechanism and potential functions. As a result, a total of 19 metabolites (3 in plasma, 19 in urine, 8 in feces, 3 in heart, 5 in liver, 0 in spleen, 1 in lung, 2 in kidneys and 2 in brain) were screened and 18 of them were characterized for the first time. Phase I metabolic reactions of hydrolysis and phase II reactions of glucuronidation, sulfation, glutamylation, N-butyryl glycylation and lactylation were the main metabolic reactions of NHDC in vivo. Moreover, the results analyzed by network pharmacology revealed that, in addition to common pathways (steroid hormone biosynthesis) of NHDC, metabolites' targets were involved in pathways in cancer, ovarian steroidogenesis, proteoglycans in cancer, PI3K-Akt signaling pathway and progesterone-mediated oocyte maturation, indicating that these functional changes might result in potential novel functions or other side-effects, such as a disorder of steroid hormones. Our work provided the metabolic features and functional modifications of NHDC in vivo for the first time, and meaningful information for further pharmacological validations or potential functions is supplied.


Assuntos
Chalconas/farmacologia , Dissecação/métodos , Aditivos Alimentares/farmacologia , Hesperidina/análogos & derivados , Animais , Chalconas/sangue , Chalconas/urina , Modelos Animais de Doenças , Hesperidina/sangue , Hesperidina/farmacologia , Hesperidina/urina , Fígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
6.
J Pharm Biomed Anal ; 193: 113721, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33147537

RESUMO

Lonicerae japonicae flos.(LJF) was widely used as a drug to treat upper respiratory tract infection or a tea to clear heat in Asian countries for thousands of years. Despite of its curative effects confirmed by modern pharmacological methods, its functional materials and mechanism against influenza were still unclear and needed further investigation. In this study, an integrated strategy based on in vivo substances profiling and network pharmacology was proposed and applied to screen out the potential anti-influenza substances and mechanism of LJF. An UHPLC/Q-TOF MS method was utilized to profile the chemical components in LJF and their metabolites in rats. The targets of absorbed prototypes were predicted by Swiss Target Prediction, and they were further analyzed by String and Kyoto Encyclopedia of Genes and Genomes (KEGG). As a result, a total of 126 chemical components mainly featuring three chemical structure types were characterized, including 70 iridoid glycosides, 17 caffeoylquinic acids, 24 flavonoids, and 15 other types compounds. Among them, ten N-contained iridoid glycosides were characterized as potential novel compounds. Moreover, 141 xenobiotics (74 prototypes and 67 metabolites) were clearly screened out in rat plasma and urine after ingestion of LJF. Phase II reactions (sulfation, glucuronidation, methylation) and phase I reactions (dehydroxylation, hydrogenation, hydrolysis, N-heterocyclization) were the main metabolic reactions of LJF in rats. Further, a total of 338 targets were predicted and TNF, PTGS2 and EGFR were the three main targets involved in the pathology of influenza. In addition to normal NF-κB pathway, T cell signal pathway and mTOR signal pathway were the other patterns for LJF to achieve its anti-flu effects. Our work provided the meaningful data for further pharmacological validation of LJF against influenza, and a new strategy was also proposed for minimizing the process to reveal the mechanism and functional basis of TCMs.


Assuntos
Medicamentos de Ervas Chinesas , Influenza Humana , Lonicera , Animais , Cromatografia Líquida de Alta Pressão , Dissecação , Medicamentos de Ervas Chinesas/farmacologia , Ratos
7.
Artigo em Inglês | MEDLINE | ID: mdl-32871375

RESUMO

Traditional Chinese medicine was widely used in China since its definite effects and therapy. The components of TCM were absorbed into the circle system as the format of prototypes or metabolites, which contributed to the therapy or side effects. Declaring the functional changes in this process was of great importance to the clinical applications. In this work, an integrated strategy based on metabolites' profiling and network pharmacology was proposed for exploring the pharmacological changes of compounds in vivo. Arctiin, the main component in Fructus Arctii with various kinds of bioactivities, was used as an example. An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry and metabolynx™software was applied to characterize the metabolites of arctiin in rats at a dosage of 100 mg/kg; network pharmacology was applied to characterize the functional changes. As a result, fifty-three metabolites (32 in plasma, 40 in urine, 19 in bile, 20 in feces, 1 in brain, 12 in liver and 4 in lungs) were screened out and characterized, and 3 of them were unambitiously identified by comparison with standard substances. Among them, 38 metabolites were reported for the first time. It was found the major metabolic pathways of arctiin in rats were demethylation, lactone-opening and phase II conjugations with sulfate and glucuronide.It also confirmed that M14, M15, M18, M23, M22, M43 and M45 were the major circulating forms of arctiin in rats following oral administration. In addition to the above metabolic reactions, phase I reactions of hydrolysis, demethylation, dehydroxylation were also observed, and dehydrogenation were first revealed metabolic patterns of arctiin in rats. Meanwhile, in addition to the main targets of arctiin (MTOR, EGFR and MAPK14), its metabolites targeted additional 392 targets with additional functions of anti-hepatitis B or viral carcinogenesis (SRC, CAPS3, PIK3CA, CDK4, ESR1, MMP9 and ERBB2). The above results provided very important information for understanding the metabolism and functional changes of arctiinin vivo, and supporting data for further pharmacological evaluation. Our work also provided a newsight for elucidation of functional changes of TCMs in vivo.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas , Furanos , Glucosídeos , Espectrometria de Massas/métodos , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Furanos/administração & dosagem , Furanos/metabolismo , Furanos/farmacocinética , Glucosídeos/administração & dosagem , Glucosídeos/metabolismo , Glucosídeos/farmacocinética , Masculino , Redes e Vias Metabólicas , Mapas de Interação de Proteínas , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
8.
J Org Chem ; 84(17): 10978-10989, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31393715

RESUMO

Visible light-driven azidation of vinyl arenes with azidobenziodoxole as the azidating agent was investigated in acetonitrile by using Cu(I)(phenanthroline)2 complex [Cu(dap)2]PF6 as photocatalyst. The reactions generated three types of difunctionalization products, which correspond to reaction patterns of amido-azidation, benzoyloxy-azidation, and diazidation. The electronic nature of the aryl group attached to the olefin moiety was found to play a crucial role in determining the reaction consequence: when the aryl group was electron-rich, the reactions afforded benzoyloxy-azidation products exclusively; for highly electron-deficient vinyl arenes, by contrast, diazidation products were generated in moderate yields. When the aryl group was moderately electron-rich or electron-deficient, on the other hand, a three-component reaction involving acetonitrile as well as azidobenziodoxole took place to give predominantly amido-azidation products. A plausible mechanism is proposed based on the mechanistic studies to rationalize these results. The reactions of electronically less biased vinyl arenes probably proceed via a redox catalysis pathway, while the electron-rich alkenes are believed to be converted through a radical chain process. The present reactions may be of synthetic usefulness as they provide a new means for the amido-azidation of vinyl arenes.

9.
Orthop Surg ; 11(2): 318-324, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31025811

RESUMO

OBJECTIVE: To investigate the biomechanical effects of reduction quality on patients after femoral neck fracture internal fixation. METHODS: The data of individual patients with femoral neck fractures were reviewed. Data for patients with simple unilateral femoral neck fractures whose reduction quality was evaluated as good by hip X-ray films after internal fixation were collected from January 2013 to January 2017. The CT data of the patients was used to reconstruct 3D models of the femur and the screw. The spatial displacement after the operation of femoral neck fracture was measured, which included the displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head, and the rotational angle. The cases were followed up by telephone consultation and clinical review to determine whether the osteonecrosis of the femoral head occurred. Follow-up time should be more than 18 months after surgery. The cases were grouped according to the results into an osteonecrosis of the femoral head group and a non-osteonecrosis of the femoral head group. Finally, the differences in postoperative spatial displacement between the two groups were compared and analyzed. In addition, a mechanical analysis of femoral force during gait was performed via finite element analysis. RESULTS: Data for 241 patients with femoral neck fractures who were treated with closed reduction and internal fixation were collected. 3D measurement showed the average displacement value, including the center of the femoral head (5.90 ± 3.4 mm), the deepest portion of the femoral head fovea (9.32 ± 4.8 mm), and the rotational angle (16.1° ± 9.4°). After telephone consultation and clinical review, osteonecrosis of the femoral head was diagnosed in 28 (11.62%) of the patients. In the osteonecrosis of the femoral head (ONFH) group, the displacement of the deepest portion of the femoral head fovea was 10.92 ± 9.18 mm; the displacement was 8.86 ± 6.29 mm in the non-ONFH group. The displacement of the center of the femoral head in the ONFH group was 7.575 ± 5.69 mm and 5.31 ± 4.05 mm in non-ONFH group. The rotational angle was 20.11° ± 10.27° in the ONFH group and 14.19° ± 11.09° in the non-ONFH group. The statistical analysis showed that the postoperative spatial displacements, including the displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head, and the rotational angle between the two groups, had statistical differences. Finite element analysis showed that as the spatial displacement increased, the stress, the displacement, and the equivalent strain of the proximal femur also increased. CONCLUSION: Poor reduction quality after femoral neck fracture is a risk factor for re-fracture and femoral head necrosis, and the measurement method of this study can be used to predict the occurrence of femoral head necrosis early after femoral neck fracture.


Assuntos
Fraturas do Colo Femoral/cirurgia , Necrose da Cabeça do Fêmur/cirurgia , Fixação Interna de Fraturas , Fenômenos Biomecânicos , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/patologia , Fraturas do Colo Femoral/fisiopatologia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/fisiopatologia , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Radiografia , Estresse Mecânico
10.
Insect Sci ; 20(2): 235-44, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23955863

RESUMO

To understand the adaptive strategies of the overwintering adults of Stenocatantops splendens, the mechanism of maintenance and termination of the reproductive diapause, the variation in mortality between overwintering females and males, and the mating strategy of the males were investigated. The results indicated that the adult reproductive diapause in natural conditions was mainly regulated by photoperiod in the fall - long photoperiods promoted reproductive development and short photoperiods maintained reproductive diapause, and the sensitivity of the overwintering adults to photoperiod was over before the end of the winter. When transferred from natural conditions to controlled laboratory conditions on dates from September through February, pre-oviposition became increasingly shorter with increasingly deferred transfer dates regardless of photoperiod conditions. The adults treated with low temperature for 30 days in September through November had significantly shorter pre-oviposition, suggesting that low temperatures in winter had an important role in the termination of reproductive diapause. The female had a significantly lower supercooling point than the male, which was related to their lower mortality after winter. In addition, observations of wild populations of the species indicated that mating behavior prior to winter and the duration of pre-mating period were not affected by photoperiod; mating and sperm transfer were mostly completed by November. Compared with females only mating before winter, females mating in the spring had shorter life span, longer pre-oviposition, lower hatching rate and laid fewer egg pods while showing no significant difference with regard to ovipositional interval, per pod number of eggs and nymph dry weight.


Assuntos
Adaptação Fisiológica , Diapausa de Inseto/fisiologia , Ortópteros/fisiologia , Estações do Ano , Comportamento Sexual Animal/fisiologia , Animais , Temperatura Baixa , Feminino , Fertilidade/fisiologia , Masculino , Ortópteros/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Fotoperíodo , Reprodução/fisiologia , Caracteres Sexuais
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