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1.
Chem Biodivers ; : e202400939, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38752887

RESUMEN

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC50 values of 27.6 and 13.3 µM, respectively.

2.
Macromol Rapid Commun ; 44(15): e2300159, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37159536

RESUMEN

In this work, π-conjugated block copolymers consisting of poly(phenyl isocyanide) (PPI) and polyfluorene (PF) segments are facilely prepared by one-pot sequential polymerization of phenyl isocyanide (monomer 1) and 7-bromo-9,9-dioctylfluorene-2-boronic acid pinacol ester (monomer 2). The Pd(II)-terminated PPI is first prepared via polymerizing monomer 1 catalyzed with phenyl alkyne-Pd(II) complex and then utilized to initiate the controlled Suzuki cross-coupling polymerization of monomer 2, yielding various PPI-b-PF copolymers possessing controlled molar mass and narrow dispersity. Owing to the helical conformation of PPI segment and π-conjugated structure of PF segment, PPI-b-PF copolymers present distinctive optical property and fascinating chiral self-assembly behavior. During the self-assembly process, chirality transfer from helical PPI block to the supramolecular aggregates of helical nanofibers occurs to afford optically active helical nanofibers with high optical activity. Furthermore, the self-assembled helical nanofibers exhibit excellent circularly polarized luminescence performance.


Asunto(s)
Cianuros , Luminiscencia , Cianuros/química , Polímeros/química , Conformación Molecular , Polimerizacion
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(1): 101-107, 2023 Feb.
Artículo en Zh | MEDLINE | ID: mdl-36861162

RESUMEN

Craniovertebral junction anomalies are a group of diseases characterized by the pathological changes of occipital bone,atlantoaxial bone,cerebellar tonsil,surrounding soft tissue,and nervous system,which are caused by a variety of factors.Chiari malformation is a common type of craniovertebral junction anomalies,the conventional surgical therapy of which is posterior fossa decompression.Currently,scholars represented by Goel have proposed a new theory on the classification,pathogenesis,and treatment of Chiari malformation based on posterior atlantoaxial fixation (Goel technique).This article introduces the progress in Goel technique,aiming to provide reference for the clinical work.


Asunto(s)
Malformación de Arnold-Chiari , Humanos , Malformación de Arnold-Chiari/cirugía
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 570-578, 2022 Aug.
Artículo en Zh | MEDLINE | ID: mdl-36065688

RESUMEN

Objective To systematically review the overall status of postoperative recurrence in patients with atypical meningiomas. Methods China National Knowledge Infrastructure,Wanfang Database,Chinese Biomedical Literature Database,VIP Database,PubMed,Embase,Web of Science,and Cochrane Library were searched for collection of the relevant literature on the recurrence of atypical meningioma from database establishment to July 2021.Two investigators independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and then performed a meta-analysis by using R 5.0. Results A total of 29 studies involving 3122 patients were included in this study.The meta-analysis showed that the overall postoperative recurrence rate of atypical meningioma was 38%.The subgroup analysis showed that the tumor recurrence rate of patients ≥60 years old and<60 years old was 51% and 40%,respectively,with no significant difference.The tumor recurrence rates in male and female patients were 42% and 44%,respectively,which showed no significant difference.The recurrence rates of the patients with parasagittal meningiomas,brain tissue infiltration,Ki-67>8%,mitotic count ≥6/10 high-power fields,and tissue necrosis were 52%,47%,63%,53%,and 69%,respectively.The recurrence rate after subtotal tumor resection was as high as 58%,and the patients who received radiotherapy had higher tumor recurrence rate than that those who did not receive radiotherapy (38% vs.29%,P=0.007). Conclusions The current evidence demonstrates that atypical meningioma has a high recurrence rate after surgery.It is essential to pay more attention and take corresponding measures to improve the tumor-free survival rate of the patients.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Periodo Posoperatorio , Factores de Riesgo
5.
Beilstein J Org Chem ; 18: 374-380, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35495775

RESUMEN

Four new polyhydroxylated steroids lobophysterols E-H (1-4), together with three known compounds (5-7), were isolated from the soft coral Lobophytum pauciflorum collected at Xisha Island, China. The structures of the new compounds were elucidated by extensive spectroscopic analysis and comparison with NMR data of structurally related compounds reported in the literature. The absolute configuration of 1-3 was determined by X-ray diffraction. All the compounds have assessed the cytotoxicity against HL-60, K562, and Hela cells. Compound 1 showed weak cytotoxicity against K562 cells with an IC50 value of 19.03 µM. In addition, compound 1 also showed a moderate anti-inflammatory effect in zebrafish.

6.
BMC Infect Dis ; 21(1): 1025, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34592958

RESUMEN

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.


Asunto(s)
Brucelosis , Linfocitos T Reguladores , Citocinas , Factores de Transcripción Forkhead , Humanos , Proteínas de Punto de Control Inmunitario , Leucocitos Mononucleares
7.
Clin Exp Pharmacol Physiol ; 48(2): 238-249, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33051888

RESUMEN

Glucose homeostasis is tightly controlled by balance between glucose production and uptake in liver tissue upon energy shortage condition. Altered glucose homeostasis contributes to the pathophysiology of metabolic disorders including diabetes and obesity. Here, we aimed to analyse the change of proteomic profile upon prolonged fasting in mice with isobaric tag for relative and absolute quantification (iTRAQ) labelling followed by liquid chromatography-mass spectrometry (LC/MS) technology. Adult male mice were fed or fasted for 16 hours and liver tissues were collected for iTRAQ labelling followed by LC/MS analysis. A total of 322 differentially expressed proteins were identified, including 189 upregulated and 133 downregulated proteins. Bioinformatics analyses, including Gene Ontology analysis (GO), Kyoto encyclopaedia of genes and genomes analysis (KEGG) and protein-protein interaction analysis (PPI) were conducted to understand biological process, cell component, and molecular function of the 322 differentially expressed proteins. Among 322 hepatic proteins differentially expressed between fasting and fed mice, we validated three upregulated proteins (Pqlc2, Ehhadh and Apoa4) and two downregulated proteins (Uba52 and Rpl37) by western-blotting analysis. In cultured HepG2 hepatocellular cells, we found that depletion of Pqlc2 by siRNA-mediated knockdown impaired the insulin-induced glucose uptake, inhibited GLUT2 mRNA level and suppressed the insulin-induced Akt phosphorylation. By contrast, knockdown of Pqlc2 did not affect the cAMP/dexamethasone-induced gluconeogenesis. In conclusion, our study provides important information on protein profile change during prolonged fasting with iTRAQ- and LC-MS/MS-based quantitative proteomics, and identifies Pqlc2 as a potential regulator of hepatic glucose metabolism and insulin signalling pathway in this process.


Asunto(s)
Proteómica , Animales , Glucosa , Masculino , Ratones , Transducción de Señal
8.
J Nat Prod ; 83(5): 1641-1645, 2020 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-32367724

RESUMEN

Microeunicellols A (1) and B (2), two undescribed eunicellin diterpenoids, were isolated from the culture of a bacterial symbiont, Streptomyces albogriseolus SY67903. Their structures, including absolute configurations revealed by spectroscopic data and single-crystal X-ray diffraction analysis, are closely related with the diterpenoids from its host, a South China Sea gorgonian, Muricella sibogae. This is the first report of eunicellin diterpenoids, commonly coral-derived, from a bacterial symbiont of coral. The chemical metabolic relationship between the bacterium and its host is discussed. Biological evaluation revealed that compound 1 possessed cytotoxicities against several human cancer cell lines.


Asunto(s)
Diterpenos/farmacología , Streptomyces/química , Terpenos/farmacología , Animales , Antozoos/química , Línea Celular Tumoral , China , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Terpenos/aislamiento & purificación
9.
Molecules ; 25(4)2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32075151

RESUMEN

Marine sponges are well known as rich sources of biologically natural products. Growing evidence indicates that sponges harbor a wealth of microorganisms in their bodies, which are likely to be the true producers of bioactive secondary metabolites. In order to promote the study of natural product chemistry and explore the relationship between microorganisms and their sponge hosts, in this review, we give a comprehensive overview of the structures, sources, and activities of the 774 new marine natural products from sponge-derived microorganisms described over the last two decades from 1998 to 2017.


Asunto(s)
Organismos Acuáticos/metabolismo , Bacterias/metabolismo , Productos Biológicos/metabolismo , Poríferos/metabolismo , Animales , Organismos Acuáticos/microbiología , Poríferos/microbiología
10.
Crit Care Med ; 47(2): 219-228, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30371520

RESUMEN

OBJECTIVES: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. DESIGN: Prospective study. SETTING: A university hospital ICU. PATIENTS: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. INTERVENTIONS: A standardized treatment protocol. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021-3.296; p < 0.001) was most strongly associated with mortality, such that neither blood paraquat concentration nor PaO2 provided any additional prognostic information. The ratio of residual volume to total lung capacity as a percentage of the predicted value (adjusted hazard ratio, 1.041; 95% CI, 1.026-1.057; p < 0.001) was the only variable that added prognostic value to Exp(%Wpoor/15). While controlling for Exp(%Wpoor/15) and percentage of predicted residual volume/total lung capacity, increases in dynamic strain (adjusted hazard ratio, 2.041/0.1 U; 95% CI, 1.283-3.248; p = 0.003) and/or decreases in respiratory system reactance at 5 Hz (adjusted hazard ratio, 1.19/0.1 U; 95% CI, 1.03-1.386; p = 0.02) were independently associated with increased 90-day mortality. CONCLUSIONS: In patients with paraquat poisoning, Exp(%Wpoor/15) and percentage of residual volume/total lung capacity are independent prognostic indicators. Higher dynamic strain and increased ventilation heterogeneity during unassisted spontaneous breathing were associated with worsened survival independent of Exp(%Wpoor/15) and percentage of residual volume/total lung capacity.


Asunto(s)
Herbicidas/envenenamiento , Pulmón/fisiopatología , Paraquat/envenenamiento , Edema Pulmonar/mortalidad , Lesión Pulmonar Aguda , Adulto , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Estudios Prospectivos , Edema Pulmonar/diagnóstico por imagen , Pruebas de Función Respiratoria , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
11.
Environ Sci Technol ; 53(6): 3238-3249, 2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30768244

RESUMEN

Flow-through configuration for electrochemical disinfection is considered as a promising approach to minimize the formation of toxic byproducts and energy consumption via the enhanced convective mass transport as compared with conventional flow-by one. Under this hydrodynamic condition, it is essential to ascertain the effect of sequential electro-redox processes with the cathode/anode then anode/cathode arrangements on disinfection performance. Here, carbon fiber felt (CFF) was utilized to construct two flow-through electrode systems (FESs) with sequential reduction-oxidation (cathode-anode) or oxidation-reduction (anode-cathode) processes to systematically compare their disinfection performance toward a model Escherichia coli ( E. coli) pathogen. In-situ sampling and live/dead backlight staining experiments revealed that E. coli inactivation mainly occurred on anode via an adsorption-inactivation-desorption process. In reduction-oxidation system, after the cathode-pretreatment, bulk solution pH increased significantly, leading to the negative charge of E. coli cells. Hence, E. coli cells were adsorbed and inactivated easily on the subsequent anode, finally resulting in its much better disinfection performance and energy efficiency than the oxidation-reduction system. Application of 3.0 V resulted in ∼6.5 log E. coli removal at 1500 L m-2 h-1 (50 mL min-1), suggesting that portable devices can be designed from CFF-based FES with potential application for point-of-use water disinfection.


Asunto(s)
Desinfección , Agua , Fibra de Carbono , Técnicas Electroquímicas , Electrodos , Escherichia coli , Oxidación-Reducción
12.
Acta Pharmacol Sin ; 40(9): 1184-1192, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30833708

RESUMEN

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD) salvage biosynthesis in mammals, and is involved in fundamental physiological processes and pathophysiology of many diseases. Thus far, however, the role of Nampt in atherosclerosis development is still in debate. In this study, we crossed global Nampt transgenic mice (Nampt-Tg) with a well-established atherosclerosis animal model (ApoE knockout mice, ApoE-/-) to generate ApoE-/-;Nampt-Tg mice and investigated the effects of Nampt overexpression on atherosclerosis development in ApoE-/- mice. Both ApoE-/- and ApoE-/-;Nampt-Tg mice were fed with a pro-atherosclerotic high-fat diet (HFD) for 16 weeks. Their serum lipid contents and atherosclerotic lesion were assessed. The results showed that there was no significant difference in body weight or serum levels of glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol between the two strains of mice, but ApoE-/-;Nampt-Tg mice had a significantly higher level of serum non-esterified fatty acid. Compared with ApoE-/- mice, ApoE-/-;Nampt-Tg mice displayed significantly increased atherosclerotic lesion area and thickness, lower collagen content, decreased collagen I/III ratio (collagen immaturation), increased number of apoptotic cells, and enhanced activities of caspase-3, caspase-8, and caspase-9. Moreover, macrophage infiltration (F4/80 staining), tumor necrosis factor signaling, and chemokines expression (ICAM-1 and CXCR-4) were all activated in aortic atherosclerotic plaque of ApoE-/-;Nampt-Tg mice compared with ApoE-/- mice. Our results provide in vivo evidence that Nampt transgene aggravates atherosclerotic inflammation and promotes atherosclerosis development in ApoE-/- mice.


Asunto(s)
Aterosclerosis/fisiopatología , Citocinas/fisiología , Inflamación/fisiopatología , Nicotinamida Fosforribosiltransferasa/fisiología , Animales , Aorta/patología , Apolipoproteínas E/genética , Aterosclerosis/etiología , Aterosclerosis/genética , Caspasas/metabolismo , Colágeno/metabolismo , Citocinas/genética , Dieta Alta en Grasa , Ácidos Grasos no Esterificados/metabolismo , Inflamación/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Nicotinamida Fosforribosiltransferasa/genética , Placa Aterosclerótica/patología , Receptores CXCR4/metabolismo , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/metabolismo
13.
Mar Drugs ; 17(4)2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-30959843

RESUMEN

Three new furanocembranoids-briaviodiol F (1) and briaviotriols A (2) and B (3)-along with a known analogue, briaviodiol A (4), were obtained from a cultured-type octocoral Briareum violaceum. The structures of cembranoids 1⁻3 were elucidated by using spectroscopic methods. In vitro study demonstrated that compounds 2 and 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW 264.7, a macrophage cell line that originated from a mouse monocyte macrophage, stimulated with lipopolysaccharides.


Asunto(s)
Antozoos/química , Antiinflamatorios/farmacología , Diterpenos/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Ratones , Modelos Moleculares , Estructura Molecular , Células RAW 264.7
14.
Molecules ; 24(21)2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31671644

RESUMEN

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.


Asunto(s)
Alcanos/síntesis química , Alcanos/farmacología , Sesquiterpenos/síntesis química , Sesquiterpenos/farmacología , Alcanos/química , Vías Biosintéticas , Modelos Moleculares , Sesquiterpenos/química
15.
Mar Drugs ; 17(1)2018 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-30597876

RESUMEN

Chemical investigation of MeOH extract of a South China Sea sponge Cacospongia sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C17 γ-lactone norditerpenoids (1⁻3), the rare C21 pyridine meroterpenoid (7), and the notable C25 manoalide-type sesterterpenoids (4⁻6, 8⁻10). Compounds 1⁻5 were initially obtained as enantiomers, and were further separated to be optically pure compounds (1a, 1b, 2a, 2b, 3a-r, 3b-r, 4a, 4b, 5a and 5b) by chiral HPLC, with a LiAlH4 reduction aid for 3. Compounds 3a/3b (a pair of inseparable enantiomers), 4a, 5a, 6, and 7 were identified as new compounds, while 1a/1b and 2a/2b were obtained from a natural source and were determined for their absolute configurations for the first time. This is also the first time to encounter enantiomers of the well-known manoalide-type sesterterpenoids from nature. The structures with absolute configurations of the new compounds were unambiguously determined by comprehensive methods including HR-ESI-MS and NMR data analysis, optical rotation comparison, experimental and calculated electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD) methods. The cytotoxicity of the isolates against selected human tumor cell lines was evaluated, however, the tested compounds showed no activity against selected cell lines.


Asunto(s)
Poríferos/química , Terpenos/química , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión/métodos , Dicroismo Circular/métodos , Diterpenos/química , Humanos , Espectroscopía de Resonancia Magnética/métodos , Rotación Óptica , Estereoisomerismo
16.
Mar Drugs ; 16(4)2018 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-29652789

RESUMEN

Three new sesquiterpenoids (sinuketal (1), sinulins A and B (2 and 3)) and two new cembranoids (sinulins C and D (4 and 5)), as well as eight known sesquiterpenoids (6–13) and eight known cembranoids (14–21), were isolated from the Xisha soft coral Sinularia sp. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 possesses an unprecedented isopropyl-branched bicyclo [6.3.0] undecane carbon skeleton with unique endoperoxide moiety, and a plausible biosynthetic pathway of it was postulated. According to the reported biological properties of endoperoxide, the antimalarial, cytotoxic, antiviral, and target inhibitory activities of 1 were tested. Compound 1 showed mild in vitro antimalarial activity against Plasmodium falciparum 3D7, weak cytotoxic activities toward Jurkat, MDA-MB-231, and U2OS cell lines, inhibitory effects against influenza A viruses H1N1 and PR8, as well as mild target inhibitory activity against acetylcholinesterase. The other compounds were evaluated for cytotoxicities against HeLa, HCT-116, and A549 tumor cell lines and target inhibitory activities against protein tyrosine phosphatase 1B (PTP1B). Compound 20 exhibited cytotoxicities against HeLa and HCT-116, and compounds 5, 11, and 15 showed mild target inhibitory activities against PTP1B.


Asunto(s)
Antozoos/química , Terpenos/química , Terpenos/farmacología , Células A549 , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antivirales/química , Antivirales/farmacología , Línea Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacología , Células HCT116 , Células HeLa , Humanos , Células Jurkat , Plasmodium falciparum/efectos de los fármacos , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores
17.
Mar Drugs ; 16(12)2018 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-30572615

RESUMEN

Five new oxygenated sesquiterpenes, molestins A⁻D (1, 3⁻5) and epi-gibberodione (2), three new cyclopentenone derivatives, ent-sinulolides C, D, and F ((+)-9⁻(+)-11), one new butenolide derivative, ent-sinulolide H ((+)-13), and one new cembranolide, molestin E (14), together with 14 known related metabolites (6⁻8, (⁻)-9⁻(⁻)-11, (±)-12, (⁻)-13, 15⁻19) were isolated from the Paracel Islands soft coral Sinularia cf. molesta. The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia. Molestin E (14) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC50 values of 5.26 and 8.37 µM, respectively. Compounds 4, 5, and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 218, 344, and 1.24 µM, respectively.


Asunto(s)
Antozoos/química , Citotoxinas/química , Sesquiterpenos/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/farmacología , Animales , Línea Celular Tumoral , Ciclopentanos/química , Ciclopentanos/aislamiento & purificación , Ciclopentanos/farmacología , Células HCT116 , Células HeLa , Humanos , Conformación Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología
18.
Cell Physiol Biochem ; 44(3): 1242-1250, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29179204

RESUMEN

BACKGROUND/AIMS: To investigate the clinical significance of myeloid zinc finger 1 (MZF1) expression in various gastric mucosal lesions including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC) in comparison with normal tissues and gastric cell lines. METHODS: MZF1 protein expression was detected using immunohistochemical staining in 37 CSG, 88 CAG, 77 IM, 51 DYS, 165 GC and 8 normal tissue samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect the level of MZF1 in gastric cell lines, 15 normal tissues and 34 GC samples, as well as 2 groups of paired primary GC and adjacent normal samples. RESULTS: Reduced MZF1 expression was detected in most GC cells and tissues. Among the gastric tissues consisting of various stages of lesions (normal, CSG, CAG, IM, DYS and GC), MZF1 protein expression was downregulated in precancerous lesions and GC. The data from clinical analyses showed that decreased MZF1 expression was correlated with tumour invasion (p = 0.044), lymph node metastasis (p = 0.048) and poor prognosis of GC patients (p = 0.003). Moreover, MZF1 was identified as an independent prognostic biomarker for GC patients in multivariate Cox regression analysis (p = 0.009). CONCLUSION: Downregulation of MZF1 was associated with gastric tumourigenesis, which may be a novel early predictive and prognostic biomarker in GC patients.


Asunto(s)
Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias Gástricas/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis/metabolismo , Gastritis/patología , Humanos , Inmunohistoquímica , Factores de Transcripción de Tipo Kruppel/genética , Metástasis Linfática , Masculino , Metaplasia/metabolismo , Metaplasia/patología , Microscopía Fluorescente , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Lesiones Precancerosas , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores Sexuales , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia
19.
Chem Biodivers ; 14(7)2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28222487

RESUMEN

Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC50 values of 12.4, 16.0, and 19.8 µm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 µg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 µg/ml).


Asunto(s)
Agelas/química , Alcaloides/aislamiento & purificación , Diterpenos/aislamiento & purificación , Pirroles/aislamiento & purificación , Alcaloides/química , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Diterpenos/química , Células HCT116 , Células HL-60 , Humanos , Células K562 , Estructura Molecular , Pirroles/química
20.
Chem Biodivers ; 14(1)2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27584719

RESUMEN

Six new pentacyclic triterpenoids were isolated from the fruit of Camptotheca acuminata. The chemical structures of the new compounds were elucidated by extensive spectroscopic analysis including HR-ESI-MS, IR, UV, 1D- and 2D-NMR. Moreover, the antibacterial activities of compounds 1, 2, 4, 5, and 6 were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Dickeya zeae. All these tested compounds showed moderate antibacterial activity against Bacillus subtilis and Dickeya zeae.


Asunto(s)
Antibacterianos/aislamiento & purificación , Camptotheca/química , Triterpenos Pentacíclicos/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Frutas/química , Estructura Molecular , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacología
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