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1.
Biomed Pharmacother ; 171: 116150, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38242040

RESUMEN

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. OBJECTIVE: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. RESULTS: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. CONCLUSIONS: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Hipoglucemiantes/uso terapéutico , Metaanálisis en Red , Obesidad/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Peso
2.
ACS Appl Mater Interfaces ; 15(31): 37442-37453, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37494549

RESUMEN

V-based sulfides are considered as potential cathode materials for Mg2+/Li+ hybrid ion batteries (MLIBs) due to their high theoretical specific capacities, unique crystal structure, and flexible valence adjustability. However, the formation of irreversible polysulfides, poor cycling performance, and severe structural collapse at high current densities impede their further development. Herein, VS4 microspheres with various controllable nanoarchitectures were successfully constructed via a facile solvothermal method by adjusting the amount of hydrochloric acid and were used as cathode materials for MLIBs. The VS4 microsphere self-assembled by bundles of paralleled-nanorods and some intersected-nanorods (VS4@NC-5) exhibits an outstanding initial discharge capacity of 805.4 mAh g-1 at 50 mA g-1 that is maintained at 259.1 mAh g-1 after 70 cycles. Moreover, the VS4@NC-5 cathode can deliver a superior rate capability (146.1 mAh g-1 at 2000 mA g-1) and ultralong cycling life (134.5 mAh g-1 at 2000 mA g-1 after 2000 cycles). The extraordinary electrochemical performance of VS4@NC-5 could be attributed to its special multi-hierarchical microsphere structure and the formation of N-doped carbon layers and V-C bonds, resulting in unobstructed ion diffusion channels, multidimensional electron transfer pathways, and enhancements of electrical conductivity and structure stability. Furthermore, the electrochemical reaction mechanism and phase conversion behavior of the VS4@NC-5 cathode at various states are investigated by a series of ex situ characterization methods. The VS4 well-designed through morphological engineering in this work can pave a way to explore more sulfides with high-rate performance and long cycling stability for energy storage devices.

3.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2490-2499, 2023 May.
Artículo en Chino | MEDLINE | ID: mdl-37282878

RESUMEN

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.


Asunto(s)
Colitis Ulcerosa , Ratones , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Interleucina-10 , Metabolómica/métodos , Cromatografía Líquida de Alta Presión
4.
Pharmacol Res ; 191: 106754, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37019194

RESUMEN

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. G protein-coupled receptors (GPRs) participate in a variety of physiologic functions, and several GPRs have critical fibrosis-promoting or -inhibiting roles in pulmonary fibrosis. Here, we explored the role of GPR41 in the pathobiology of pulmonary fibrosis. We found that GPR41 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Knockout of GPR41 attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung weight and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, GPR41 knockout inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that GPR41 regulated TGF-ß1-induced fibroblast-to-myofibroblast differentiation and Smad2/3 and ERK1/2 phosphorylation via its Gαi/o subunit but not Gßγ subunit. Together, our data indicate that GPR41 is involved in pulmonary fibroblast activation and fibrosis, and GPR41 represents a potential therapeutic target for pulmonary fibrosis.


Asunto(s)
Fibrosis Pulmonar , Animales , Ratones , Bleomicina , Diferenciación Celular , Fibroblastos/metabolismo , Proteínas de Unión al GTP/metabolismo , Pulmón , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , Ratones Noqueados , Miofibroblastos/metabolismo , Fosforilación , Fibrosis Pulmonar/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
5.
Front Nutr ; 9: 970019, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36046137

RESUMEN

Miracle berry is well-known for its ability to convert sour foods to sweet. In this study, the secondary metabolites of miracle berry leaves (MBL) were identified by UPLC-DAD-MS, and its antiangiogenesis and anticancer activities were evaluated by using a zebrafish model and the MCF-7 xenograft mouse model, respectively. The result showed that 18 phenolic compounds were identified in MBL extract, and dominated by the derivatives of quercetin and myricetin. The MBL extract showed low toxicity and high antiangiogenesis activity, it significantly inhibited the subintestinal vein vessels development in zebrafish at very low concentration. Furthermore, the MBL extract could promote the apoptosis of tumor cells and significantly inhibit the growth of MCF-7 xenograft tumor. In addition, the analysis of metabolites revealed that the MBL extract inhibited tumor growth by activating the metabolic pathways of unsaturated fatty acids and purines. Overall, this study suggests that MBL extract can be used as a natural anticancer adjuvant in the fields of functional foods.

6.
Medicine (Baltimore) ; 101(51): e30703, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36595758

RESUMEN

BACKGROUND: Insomnia is a sleep disorder with insufficient sleep time or/and poor sleep quality. Relevant epidemiological studies have shown that insomnia symptoms occur in about 35% to 50% of the adult population, and it is one of the most common diseases in the elderly. Patients who often suffer from insomnia are prone to symptoms such as fatigue, weakened cognitive function, depression, and even mental illness, which bring serious physical and mental damage to individuals and a heavy economic burden to social medical care and families. Traditional Chinese medicine and modern medicine have their own advantages in the treatment of insomnia, and there is currently a lack of reports on the comparison of acupuncture combined with massage and conventional medicine. OBJECTIVE: To evaluate the clinical efficacy of acupuncture combined with Tuina in the treatment of insomnia. METHODS: Search for clinical randomized controlled trials (RCTs) of acupuncture combined with Tuina in the treatment of insomnia from PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, and China Science and Technology Journal Database. The RevMan5.4 software was used for Meta- analysis after literature screening, data extraction and quality evaluation. RESULTS: A total of 29 studies were included with a total of 2688 cases. Compared with drugs or acupuncture alone, acupuncture combined with Tuina has advantages in the total clinical effectiveness, as well as the Pittsburgh Sleep Quality Index (PSQI) and Statistical Self-Rating Anxiety Scale score (SAS) (OR = 3.59, 95% confidence interval [CI] [2.77, 4.66], Z = 9.62 [P < .00001]) (MD = -2.44, 95% CI [-2.93, -1.95], Z = 9.72 [P < .00001]) (MD = -8.42, 95% CI [-10.23, -6.61], Z = 9.09 [P < .00001]). There was no statistically significant difference in Statistical Self-rating Depression Scale score (SDS) (MD = -5.26, 95% CI [-11.29, 0.78], Z = 1.71 [P > .05]). CONCLUSION: Acupuncture combined with Tuina has obvious clinical advantages in the treatment of insomnia. This result is expected to provide a reference for the clinical treatment of insomnia, but the long-term effect of clinical efficacy still needs further study.


Asunto(s)
Terapia por Acupuntura , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Anciano , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Medicina Tradicional China , Resultado del Tratamiento , Ansiedad
7.
EMBO Mol Med ; 13(8): e14059, 2021 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-34125490

RESUMEN

In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate the unexplored role of CRAMP in celiac disease. By applying a mouse model of gluten-induced enteropathy (GIE) recapitulating small intestinal enteropathy of celiac disease, we observed defective CRAMP production in duodenal epithelium during GIE. CRAMP-deficient mice were susceptible to the development of GIE. Exogenous CRAMP corrected gliadin-triggered epithelial dysfunction and promoted regulatory immune responses at the intestinal mucosa. Additionally, GIE-associated gut dysbiosis with enriched Pseudomonas aeruginosa and production of the protease LasB contributed to defective intestinal CRAMP production. These results highlight microbiota-CRAMP axis in the modulation of barrier function and immune responses in GIE. Hence, modulating CRAMP may represent a therapeutic strategy for celiac disease.


Asunto(s)
Enfermedad Celíaca , Microbioma Gastrointestinal , Animales , Péptidos Catiónicos Antimicrobianos , Glútenes , Inmunidad , Mucosa Intestinal , Ratones , Catelicidinas
8.
Medicine (Baltimore) ; 100(18): e25639, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33950941

RESUMEN

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.


Asunto(s)
Uso Fuera de lo Indicado , Extractos Vegetales/efectos adversos , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia Venosa/epidemiología , China/epidemiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Periodo Perioperatorio/estadística & datos numéricos , Extractos Vegetales/administración & dosificación , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Tiempo de Protrombina , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
10.
Food Sci Nutr ; 9(3): 1688-1697, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33747479

RESUMEN

Macadamia nuts have high nutritional value and positive health attributes. Changes to the composition and availability of these compounds during roasting contribute to product quality. In this study, changes to the chemical composition of lipids (fatty acids, triglycerides, and free fatty acids) and other phytochemicals were analyzed, and a sensory evaluation was carried out of two major varieties of macadamia nuts planted in China, after roasting. Only small changes in fatty acid (FA) content and a slight decrease in total triglycerides (TAGs) were observed after roasting. The free fatty acid (FFA) content and the peroxide value were increased by roasting. The total available polyphenol content increased by 25.6% and the oxidative stability index of kernels increased by 21.6%. The sensory scores for taste and aroma were doubled by roasting. Overall, the sensory, nutritional quality, and oxidative stability of roasted macadamia nuts were greatly improved, compared with raw nuts.

11.
J Chem Neuroanat ; 109: 101852, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32781134

RESUMEN

The senile plaque formed by ß-amyloid (Aß) deposition in the brain is one of the main pathological features of Alzheimer's disease (AD), and the c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the pathogenesis of AD. This study aimed to investigate that D-serine may ameliorate motor and cognitive impairment in Aß injected mice by inhibiting JNK signaling pathway. Firstly, Kunming mice were injected intrahippocampally with Aß1-42 to build AD model. The mice were injected intraperitoneally with saline, D-serine, D-amino acid oxidase (DAAO), and Sodium benzoate (BE) for 10 consecutive days, respectively. Subsequently, the motor and cognitive functions of mice were detected by behavioral tests. The silver staining and immunohistochemical methods were used to detect the distributions of Aß in the hippocampus of mice. 18F-2-Fluro-D-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans were performed to detected glucose metabolism of Aß1-42 induced lesions. The expressions of relative JNK factors were detected by immunohistochemistry and Western blot methods. These results showed that Aß severely impaired the motor and memory abilities of mice. The expressions of glial fibrillary acidic protein (GFAP), tumor necrosis factor (TNF-α), N-methyl-D-aspartate receptor 1 (NMDAR1), phospho-JNK (p-JNK), p-c-Jun and activating transcription factor 2 (ATF2) increased significantly. After D-serine treatment, the abilities of movement and memory of mice were improved, and the clearance rate of Aß was accelerated. The expressions of GFAP, TNF-α, NMDAR1, p-JNK, p-c-Jun and ATF2 decreased significantly. DAAO and BE were administered to further validate these results. Therefore, this study showed that D-serine could alleviate the cognitive impairment of Aß1-42 injected mice by inhibiting JNK signaling pathway. These results provide more evidences for the effect of D-serine on AD and relevant mechanism to treat AD.


Asunto(s)
Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Serina/uso terapéutico , Péptidos beta-Amiloides/farmacología , Animales , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Masculino , Ratones , Serina/farmacología
12.
J Org Chem ; 85(11): 7036-7044, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32383594

RESUMEN

A new single Pd-catalyzed decarboxylative allylation-nucleophilic cyclization relay is reported by using α-alkynyl arylols and vinylethylene carbonates (or vinyl carbamates), and a wide range of 3-allyl benzofurans with generally good yields were stereoselectively synthesized under mild conditions, among which the complete stereoselectivity of some cases was also observed. Notably, the present catalysts can tolerate air conditions without any ligand, additive, or base, opening new avenues to build up oxa-heterocycle frameworks through catalytic difunctionalization of internal alkynes.

13.
Pharmacol Res ; 152: 104592, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31830521

RESUMEN

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. The aberrantly activated lung myofibroblasts with resultant excessive accumulation of extracellular matrix is a central event in the progression of pulmonary fibrosis. Lysine-specific demethylase 1 (LSD1) has been suggested to epigenetically regulate cell differentiation, migration and invasion in tumor microenvironment. However, its function in pulmonary fibrosis remains unclear. The present study aimed to investigate the potential effect and underlying mechanisms of LSD1 in pulmonary fibrosis. Here, we found that LSD1 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). In vivo knockdown of LSD1 by lentiviral shRNA transfection attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung coefficient and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, in vitro knockdown of LSD1 inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that knockdown of LSD1 prevented fibroblast--to-myofibroblast differentiation and subsequent pulmonary fibrosis by suppressing TGF-ß1/Smad3 signaling pathway through modulation of a balance between histone H3 lysine 9 methylation and histone H3 lysine 4 methylation. Together, our data indicate that LSD1 activation contributes to pulmonary myofibroblast differentiation and fibrosis by targeting TGF-ß1/Smad3 signaling, and suggest LSD1 as a therapeutic target for the treatment of pulmonary fibrosis.


Asunto(s)
Fibroblastos/metabolismo , Histona Demetilasas/metabolismo , Fibrosis Pulmonar/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Bleomicina , Diferenciación Celular , Fibroblastos/citología , Células HEK293 , Histona Demetilasas/genética , Humanos , Masculino , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , ARN Interferente Pequeño/genética
14.
J Org Chem ; 84(24): 16027-16035, 2019 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-31769289

RESUMEN

A double-base copromoted 1,4-oxo-migration/cyclization cascade of ß-alkynyl ketones was reported, enabling to form a range of functionalized 1-indanones with moderate to good yields and high diastereoselectivity in the presence of t-BuOK as a Brønsted base and N,N'-dimethylethanediamine (DMEDA) as a Lewis base. Some of these 1-indanones were successfully transformed into 2-haloethyl benzoates with one all-carbon quaternary stereocenter by 1,2-dichloroethane (DCE) or 1,2-dibromoethane (DBE) as both a reactant and a reaction media. This method also features high atomic utilization (100%), high diastereoselectivity, and mild reaction conditions.

15.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3303-3315, 2019 Oct.
Artículo en Chino | MEDLINE | ID: mdl-31621216

RESUMEN

Urban greenspace, which serves as a place for residents to connect with nature and relax, provides important ecosystem services. Access to greenspace is often related to the socio-economic characteristics of residents, which received a lot attention from researchers and practitioners. Previous studies have mostly focused on single city to analyze the spatial relationship between greenspace distribution and residents' characteristics. We conducted a meta-analysis with global studies. The objectives were to classify findings from different cases and investigate the impacts from the location of research area, indicator and analytical method, and summarized major factors influen-cing the relationship between greenspace distribution and residents' characteristics. The results showed that more than half of the cases (58.2%) found that the socially advantaged population benefited more from greenspace. About a quarter cases (25.4%) revealed the opposite, that was, the disadvantaged population benefited more from greenspace. The remaining case studies (16.4%) did not find significant correlation between them. The studies reviewed here were diverse in terms of scale, indicator selection, and analytical method. Overall, we found no connection between finding and the choice of scale/indicator/analytical method. The reviewed case studies were mostly conducted in cities of western countries, which differed in their development trajectories and urban characteristics from cities in China. To understand association between urban greenspace and residents' characteristics in China, we urged to carry out more local studies, which would potentially provide scientific evidence for building sustainable cities during rapid urbanization.


Asunto(s)
Ecosistema , Urbanización , China , Ciudades , Factores Socioeconómicos , Población Urbana
16.
J Org Chem ; 84(21): 13686-13695, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31545056

RESUMEN

Two types of new oxidant-free radical multicomponent reactions of ß-alkynyl ketones, aryldiazonium salts, and DABCO·(SO2)2 (DABSO) were established, leading to the tunable generation of two class of sulfonated 1,3-dihydroisobenzofurans with moderate to good yields and complete stereoselectivity under the mild conditions. The radical-induced scission/recombination of the C(sp3)-C(sp3) bond enabled direct 1,8-halosulfonylation of ß-alkynyl ketones, giving 1,3-dimethylene-substituted (1Z,3Z)-1,3-dihydroisobenzofurans with substituent diversity by p-nitrobenzyl bromide (PNBB) or p-nitrobenzyl chloride (PNBC) as the halo source. Fine-tuning substituents to strong electron-withdrawing ones, such as nitro, cyano, and trifluoromethyl, linked to aryldiazonium tetrafluoroborates allowed a different annulation/1,5-azosulfonylation process to access sulfonated (Z)-1,3-dihydroisobenzofurans with one quaternary carbon-amino functionality.

17.
Anat Rec (Hoboken) ; 302(12): 2261-2270, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31443117

RESUMEN

In recent years, the extraction fraction of volatile oil from Acorus gramineus has significant effects on anti-dementia and improving the learning and memory of animals. To date, limited studies have determined whether volatile oil from A. gramineus has the protective effect on neuronal damage. The aim of this study was to investigate the protective effects of volatile oil from A. gramineus on Alzheimer's disease (AD) mice, by means of behavior test, immunohistochemistry and western blot methods. In this study, mice were injected with Aß1-42 in the bilateral hippocampus to establish the AD model. On the seventh day after modeling, the mice with cognitive dysfunction were selected by the novel object recognition task. Subsequently, the volatile oil treatment groups underwent intragastric administration for per 10 g body weight 2.5 or 5 µL volatile oil from A. gramineus for 3 weeks. The control group and the AD group were given the same amount of saline. Our results showed that after treatment of volatile oil from A. gramineus, the number of Doublecortin and Nestin positive cells increased significantly, suggesting that the volatile oil from A. gramineus may induce the regeneration of hippocampal neurons in mice, and promote the growth of hippocampal neurons by upregulation of brain-derived neurotrophic factor, tyrosine protein kinase B, and neurotrophin-3 expression. These results might provide more experimental evidences for underlying mechanism about the neuroprotective effects of volatile oil from A. gramineus against AD relevant symptoms. Anat Rec, 302:2261-2270, 2019. © 2019 American Association for Anatomy.


Asunto(s)
Acorus/química , Péptidos beta-Amiloides/toxicidad , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Aceites Volátiles/farmacología , Animales , Modelos Animales de Enfermedad , Hipocampo/patología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/patología , Ratones , Neuronas/patología
18.
Br J Pharmacol ; 176(23): 4446-4461, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31347703

RESUMEN

BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a common acute abdominal condition, frequently associated with intestinal barrier dysfunction, which aggravates AP retroactively. Butyrate exhibits anti-inflammatory effects in a variety of inflammatory diseases. However, its potential beneficial effect on AP and the underlying mechanisms have not been investigated. EXPERIMENTAL APPROACH: Experimental AP was induced by caerulein hyperstimulation in wild-type and GPR109A-/- mice. Sodium butyrate was administered intragastrically for 7 days prior to caerulein hyperstimulation. Anti-inflammatory mechanisms of butyrate were further investigated in peritoneal macrophages. KEY RESULTS: Butyrate prophylaxis attenuated AP as shown by reduced serum amylase and lipase levels, pancreatic oedema, myeloperoxidase activity, and improved pancreatic morphology. Amelioration of pancreatic damage by butyrate was associated with reduced levels of TNF-α, IL-6, and CCL2 and suppressed activation of the NLRP3 inflammasome in both pancreas and colon. Further, butyrate ameliorated pancreatic inflammation by suppressing interactions between histone deacetylase 1 (HDAC1) and AP1 and STAT1 with increased histone acetylation at H3K9, H3K14, H3K18, and H3K27 loci, resulting in suppression of NLRP3 inflammasome activation and modulation of immune cell infiltration in pancreas. Additionally, butyrate mediated STAT1/AP1-NLRP3 inflammasome suppression via HDAC1 inhibition was demonstrated in peritoneal macrophage. In colon, butyrate inhibited NLRP3 inflammasome activation via GPR109A. Accordingly, the modulatory effects of butyrate on AP, AP-associated gut dysfunction, and NLRP3 inflammasome activation were diminished in GPR109A-/- mice. CONCLUSION AND IMPLICATIONS: Our study dissected tissue-specific anti-inflammatory mechanisms of butyrate during AP, suggesting that increased colonic levels of butyrate may be a strategy to protect against AP.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Butiratos/farmacología , Enfermedades Intestinales/tratamiento farmacológico , Intestino Delgado/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/análisis , Butiratos/administración & dosificación , Butiratos/análisis , Ceruletida , Femenino , Enfermedades Intestinales/inducido químicamente , Enfermedades Intestinales/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo
19.
Artículo en Chino | MEDLINE | ID: mdl-31245947

RESUMEN

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1ß and TNF-α in serum were decreased significantly. CONCLUSION: Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1ß and TNF-α in serum.


Asunto(s)
Medicamentos Herbarios Chinos , Faringitis , Animales , Medicamentos Herbarios Chinos/farmacología , Interleucina-1beta/metabolismo , Faringitis/tratamiento farmacológico , Faringitis/inmunología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
20.
Cell Mol Neurobiol ; 39(7): 953-961, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31147852

RESUMEN

Grape seed proanthocyanidin extract (GSPE), an active component extracted from the grape, has been reported to demonstrate antioxidant, anti-inflammatory, anticancer, and antiapoptosis effects. However, little is known about the role of GSPE on neonatal hypoxic-ischemic (HI) brain injury. The aim of this study was to evaluate the neuroprotective effect of GSPE pretreatment on neonatal HI brain injury in mice. A modified Rice-Vannucci method was performed to induce neonatal HI brain injury in the 7-day-old mouse pups pretreated with GSPE or vehicle. The infarct volumes were determined by TTC staining. TUNEL staining was used to detect cells apoptosis, and the expressions of apoptosis-related proteins: bax, bcl2, and cleaved caspase-3 were assayed by Western blot. Behavioral tests were also conducted to assess the functional recovery after injury. We showed that the brain damage and neurobehavioral outcomes improvement was observed in GSPE pretreated group. GSPE was proved to suppress apoptosis through inhibition of bax and cleaved caspase-3 expression. It demonstrates that GSPE could alleviate brain damage maybe through its antiapoptotic activity in a neonatal HI brain injury model, and GSPE has the potential to be a new drug for effective prevention of this disorder.


Asunto(s)
Apoptosis , Lesiones Encefálicas/tratamiento farmacológico , Extracto de Semillas de Uva/uso terapéutico , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Proantocianidinas/uso terapéutico , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Conducta Animal , Lesiones Encefálicas/complicaciones , Modelos Animales de Enfermedad , Extracto de Semillas de Uva/farmacología , Hipoxia-Isquemia Encefálica/complicaciones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Proantocianidinas/farmacología
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