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1.
Mar Drugs ; 22(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38667762

RESUMEN

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.


Asunto(s)
Antozoos , Caenorhabditis elegans , Sesquiterpenos , Animales , Antozoos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Caenorhabditis elegans/efectos de los fármacos , Cristalografía por Rayos X , Enfermedad de Alzheimer/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Estructura Molecular
2.
J Appl Clin Med Phys ; 25(2): e14154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37683120

RESUMEN

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.


Asunto(s)
Radiocirugia , Radioterapia de Intensidad Modulada , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , Algoritmos , Pelvis , Radiometría/métodos , Radioterapia de Intensidad Modulada/métodos , Garantía de la Calidad de Atención de Salud
3.
J Appl Clin Med Phys ; 25(7): e14348, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38561975

RESUMEN

INTRODUCTION: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. METHODS: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. RESULTS: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. CONCLUSION: With the proposed approach, we can perform four QA items in the TG224 within 10 min.


Asunto(s)
Terapia de Protones , Garantía de la Calidad de Atención de Salud , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Terapia de Protones/métodos , Terapia de Protones/normas , Humanos , Garantía de la Calidad de Atención de Salud/normas , Planificación de la Radioterapia Asistida por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/normas , Neoplasias/radioterapia , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/normas , Fantasmas de Imagen , Algoritmos , Radiometría/métodos
4.
Angew Chem Int Ed Engl ; 62(14): e202216977, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-36753392

RESUMEN

Post-synthetic modification (PSM) is an effective approach for the tailored functionalization of metal-organic architectures, but its generalizability remains challenging. Herein we report a general covalent PSM strategy to functionalize Pdn L2n metal-organic cages (MOCs, n=2, 12) through an efficient Diels-Alder cycloaddition between peripheral anthracene substituents and various functional motifs bearing a maleimide group. As expected, the solubility of functionalized Pd12 L24 in common solvents can be greatly improved. Interestingly, concentration-dependent circular dichroism and aggregation-induced emission are achieved with chiral binaphthol (BINOL)- and tetraphenylethylene-modified Pd12 L24 , respectively. Furthermore, Pd12 L24 can be introduced with two different functional groups (e.g., chiral BINOL and achiral pyrene) through a step-by-step PSM route to obtain chirality-induced circularly polarized luminescence. Moreover, similar results are readily observed with a smaller Pd2 L4 system.

5.
Diabetes Obes Metab ; 24(11): 2182-2191, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35762489

RESUMEN

AIMS: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. MATERIALS AND METHODS: LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. RESULTS: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2 , corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: -0.7 (95% confidence interval: -0.9, -0.6)%; p < .0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p < .0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: -0.9 (95% confidence interval: -1.4, -0.5) kg; p = .0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. CONCLUSIONS: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Adulto , Glucemia , China/epidemiología , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Combinación de Medicamentos , Hemoglobina Glucada/análisis , Control Glucémico , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Persona de Mediana Edad , Obesidad/tratamiento farmacológico , Péptidos/uso terapéutico
6.
Diabetes Obes Metab ; 24(8): 1522-1533, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35441412

RESUMEN

AIMS: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). MATERIALS AND METHODS: LixiLan-O-AP (NCT03798054) was a 24-week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2 ) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open-label once-daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium-glucose cotransporter-2 inhibitors. The primary efficacy endpoint was change in HbA1c. RESULTS: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P < 0.0001) and Lixi (-10 mmol/mol; -0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). CONCLUSIONS: iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Administración Oral , Adulto , Glucemia , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Combinación de Medicamentos , Hemoglobina Glucada , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Metformina/efectos adversos , Persona de Mediana Edad , Péptidos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Aumento de Peso
7.
Inorg Chem ; 61(12): 5092-5098, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35289170

RESUMEN

When compared to industrially stable zeolites, the instability of metal-organic frameworks (MOFs) has been denounced by researchers. Boosting the stability of existing MOFs is highly important for practical applications. In this report, we develop a new strategy to prepare MOFs/poly(tetrafluoroethylene) (PTFE) composites, which can highly improve the chemical, pressure, and photostabilities of zeolitic imidazolate framework (ZIF)-8. Composite materials were prepared by a physical blending of ZIF-8 and PTFE emulsion with different ratios and annealing at 370 °C. Transmission electron microscopy (TEM) studies reveal that the nanoparticles of ZIF-8 are coated by PTFE to form the composite materials. Upon mixing with 20 or 50 wt % PTFE, the ZIF-8/PTFE materials show a superhydrophobic property with water contact angles of around 156°. Pristine ZIF-8 is not stable in water with stirring under acidic, basic, and irradiation conditions, while the ZIF-8/PTFE materials are stable under the same conditions. The ZIF-8/PTFE materials can also maintain their crystalline structure after being compressed with a 10 MPa pressure, while pristine ZIF-8 changes to an amorphous solid after the same pressure treatment. Using water as a solvent, ZIF-8/PTFE can be used as a highly efficient and recyclable catalyst for Knoevenagel reaction at room temperature. The successful preparation of stable ZIF-8/PTFE composite materials provides a useful method to enhance the chemical, pressure, and photostabilities of MOFs.

8.
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.

9.
Sensors (Basel) ; 21(7)2021 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-33916549

RESUMEN

Due to the aging population, home care for the elderly has become very important. Currently, there are many studies focusing on the deployment of various sensors in the house to recognize the home activities of the elderly, especially for the elderly living alone. Through these, we can detect the home situation of the single person and ensure his/her living safety. However, the living environment of the elderly includes, not only the person living alone, but also multiple people living together. By applying the traditional methods for a multi-resident environment, the "individual" activities of each person could not be accurately identified. This resulted in an inability to distinguish which person was involved in what activities, and thus, failed to provide personal care. Therefore, this research tries to investigate how to recognize home activities in multi-resident living environments, in order to accurately distinguish the association between residents and home activities. Specifically, we propose to use the special characteristics of historical activity of residents in a multi-person environment, including activity interaction, activity frequency, activity period length, and residential behaviors, and then apply a suite of machine learning methods to train and test. Five traditional models of supervised learning and two deep learning methods are explored to tackle this problem. Through the experiments with real datasets, the proposed methods were found to achieve higher precision, recall and accuracy with less training time. The best accuracy can reach up to 91% and 95%, by J48DT, and LSTM, respectively, in different living environments.


Asunto(s)
Actividades Cotidianas , Servicios de Atención de Salud a Domicilio , Anciano , Envejecimiento , Femenino , Humanos , Aprendizaje Automático , Masculino , Tecnología
10.
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
11.
Ann Emerg Med ; 83(4): 407-408, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38519205
12.
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
13.
N Engl J Med ; 373(23): 2247-57, 2015 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-26630143

RESUMEN

BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Péptidos/uso terapéutico , Síndrome Coronario Agudo/complicaciones , Anciano , Angina Inestable/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Péptidos/efectos adversos , Modelos de Riesgos Proporcionales , Insuficiencia del Tratamiento
14.
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
15.
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
16.
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
17.
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
18.
Molecules ; 22(8)2017 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-28792469

RESUMEN

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A-E (1-4, and 11) together with twelve known analogues (5-10, 12-17). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC50 value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC50 value of 28.4 µg/mL. A preliminary structure activity relationship was discussed.


Asunto(s)
Antivirales/farmacología , Embryophyta/química , Extractos Vegetales/química , Triterpenos/química , Triterpenos/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular , Descubrimiento de Drogas , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Ratones , Estructura Molecular , Relación Estructura-Actividad , Triterpenos/toxicidad
19.
BMC Public Health ; 16: 56, 2016 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-26796115

RESUMEN

BACKGROUND: The prevalence of hypertension in Chinese Mainland has increased rapidly in the recent decades. This study aimed to determine the prevalence of hypertension and sodium intake in an economically booming area in China. METHODS: 9600 adults aged from 18 to 69 years old in Jiangsu Province of China were recruited using a complex, multistage sampling method. Blood pressure was measured and a face-to-face interview was conducted among all participants. 24 hours (24-h) urine sample was collected from each participant and then measured for sodium and potassium. Hypertension was determined by blood pressure and use of anti-hypertension medications. All of the analyses were weighted according to the population distribution in the province. RESULTS: Overall, the weighted means of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 128.8 mm Hg (95 % confidence interval, CI, 128.3-129.3) and 82.2 mm Hg (95 % CI, 81.4-83.1). The weighted hypertension prevalence of Jiangsu residents was 33.0 % (95 % CI, 29.4-36.7 %). Among those with hypertension, 31.4 % (95 % CI, 24.6-38.1) were aware of their blood pressure condition. In total, 88.4 % (95 % CI, 83.5-93.3) of those with known hypertension took anti-hypertension medications. Only 23.7 % (95 % CI, 13.3-34.2) of those under anti-hypertension medications had their blood pressure controlled. The mean of 24-h urinary sodium excretion was 188.2 mmol (standard deviation, SD, 69.5), representing that the mean intake of salt was 11.0 g (SD, 4.1) through conversion. CONCLUSION: Hypertension and excessive sodium intake in adults are prevalent in Jiangsu Province, China. These observations suggest that a public health approach is necessary to prevent hypertension and manage hypertensive patients.


Asunto(s)
Antihipertensivos/uso terapéutico , Concienciación , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Cloruro de Sodio Dietético/administración & dosificación , Adolescente , Adulto , Anciano , Antihipertensivos/administración & dosificación , Presión Sanguínea , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Salud Pública , Cloruro de Sodio Dietético/orina , Adulto Joven
20.
Chem Biodivers ; 13(2): 233-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26880436

RESUMEN

Twenty-four steroid-based natural products, 9,10-secosteroids (1-10), 1,4-dien-3-one steroids (11-19), and 4-en-3-one steroids (20-24), containing varying side-chains, were isolated from the South China Sea gorgonian Muricella sibogae. The structures of one new 9,10-secosteroid, sibogol D (1), and two new 1,4-dien-3-one steroids, sibogols E and F (11 and 12), were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Cytotoxicities for all the isolates were evaluated against four selected tumor cell lines, HL-60, HCT116, K562, and P388. Compounds 3, 9, and 13 exhibited potent cytotoxic activities against the HL-60 cell line, with IC50 values ranging from 1.27 to 10.05 µM, and compound 3 was also cytotoxic against HCT116 with an IC50 value of 5.8 µM. The bioassay results also indicated a potential relationship between structural patterns and activity. The newly presented series of 1,4-dien-3-one and 4-en-3-one types of steroids relating to the unique 9,10-secosteroids in biogenesis were found in this species for the first time, which is of considerable chemotaxonomic significance.


Asunto(s)
Antozoos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Secoesteroides/química , Secoesteroides/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células HL-60 , Humanos , Neoplasias/tratamiento farmacológico , Secoesteroides/aislamiento & purificación
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