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1.
Acta Pharm Sin B ; 12(5): 2239-2251, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35646547

RESUMO

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

2.
Nat Commun ; 13(1): 2964, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618727

RESUMO

Photocatalytic CO2 reduction reaction has been developed as an effective strategy to convert CO2 into reusable chemicals. However, the reduction products of this reaction are often of low utilization value. Herein, we effectively connect photocatalytic CO2 reduction and amino carbonylation reactions in series to reconvert inexpensive photoreduction product CO into value-added and easily isolated fine chemicals. In this tandem transformation system, we synthesize an efficient photocatalyst, NNU-55-Ni, which is transformed into nanosheets (NNU-55-Ni-NS) in situ to improve the photocatalytic CO2-to-CO activity significantly. After that, CO serving as reactant is further reconverted into organic molecules through the coupled carbonylation reactions. Especially in the carbonylation reaction of diethyltoluamide synthesis, CO conversion reaches up to 85%. Meanwhile, this tandem transformation also provides a simple and low-cost method for the 13C isotopically labeled organic molecules. This work represents an important and feasible pathway for the subsequent separation and application of CO2 photoreduction product.

3.
J Alzheimers Dis ; 86(3): 1255-1273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35180113

RESUMO

BACKGROUND: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer's disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown. OBJECTIVE: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation. METHODS: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-ß (Aß) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD. RESULTS: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and Aß deposits, a significant reduction in the expression of FOXG1 was observed in APP/PS1 mice at 6 months of age. Using the APP/PS1;Foxg1fl/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and Aß deposition. CONCLUSION: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Fatores de Transcrição Forkhead , Proteínas do Tecido Nervoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ciclo Celular , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Presenilina-1/metabolismo , Quinases Ativadas por p21/metabolismo
4.
Adv Mater ; 34(17): e2108646, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35181946

RESUMO

Nanomaterials-based artificial enzymes (AEs) have flourished for more than a decade. However, it is still challenging to further enhance their biocatalytic performances due to the limited strategies to tune the electronic structures of active centers. Here, a new path is reported for the de novo design of the d electrons of active centers by modulating the electron transfer in vanadium-based AEs (VOx -AE) via a unique Zn-O-V bridge for efficient reactive oxygen species (ROS)-catalysis. Benefiting from the electron transfer from Zn to V, the V site in VOx -AE exhibits a lower valence state than that in V2 O5 , which results in charge-filled V-dyz orbital near the Fermi level to interfere with the formation of sigma bonds between the V- d z 2 and O-pz orbitals in H2 O2 . The VOx -AE exhibits a twofold Vmax and threefold turnover number than V2 O5 when catalyzing H2 O2 . Meanwhile, the VOx -AE shows enhanced catalytic eradication of drug-resistant bacteria and achieves comparable wound-treatment indexes to vancomycin. This modulating charge-filling of d electrons provides a new direction for the de novo design of nanomaterials-based AEs and deepens the understanding of ROS-catalysis.


Assuntos
Desinfecção , Vanádio , Catálise , Elétrons , Espécies Reativas de Oxigênio , Vanádio/química
5.
Nanomicro Lett ; 14(1): 16, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870788

RESUMO

Some precision electronics such as signal transmitters need to not only emit effective signal but also be protected from the external electromagnetic (EM) waves. Thus, directional electromagnetic interference (EMI) shielding materials (i.e., when the EM wave is incident from different sides of the sample, the EMI shielding effectiveness (SE) is rather different) are strongly required; unfortunately, no comprehensive literature report is available on this research field. Herein, Ni-coated melamine foams (Ni@MF) were obtained by a facile electroless plating process, and multiwalled carbon nanotube (CNT) papers were prepared via a simple vacuum-assisted self-assembly approach. Then, step-wise asymmetric poly(butylene adipate-co-terephthalate) (PBAT) composites consisting of loose Ni@MF layer and compact CNT layer were successfully fabricated via a facile solution encapsulation approach. The step-wise asymmetric structures and electrical conductivity endow the Ni@MF/CNT/PBAT composites with unprecedented directional EMI shielding performances. When the EM wave is incident from Ni@MF layer or CNT layer, Ni@MF-5/CNT-75/PBAT exhibits the total EMI SE (SET) of 38.3 and 29.5 dB, respectively, which illustrates the ΔSET of 8.8 dB. This work opens a new research window for directional EMI shielding composites with step-wise asymmetric structures, which has promising applications in portable electronics and next-generation communication technologies.

6.
Molecules ; 26(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885971

RESUMO

Rhizoma Coptidis (RC) is a widely used traditional Chinese medicine. Although modern research has found that some alkaloids from RC are the pharmacologically active constituents, the differences in their biological effects are not completely clear. This study analyzed the differences in the typical alkaloids in RC at a systematic level and provided comprehensive information on the pharmaceutical mechanisms of the different alkaloids. The ethanol RC extract (RCE) was characterized using HPLC assay. HepG2, 3T3-L1, and RAW264.7 cells were used to detect the cytotoxicity of alkaloids. Transcriptome analyses were performed to elucidate the cellular pathways affected by RCE and alkaloids. HPLC analysis revealed that the typical alkaloids of RCE were berberine, coptisine, and palmatine. Coptisine and berberine displayed a stronger inhibitory effect on cell proliferation than palmatine. The overlapping ratios of differentially expressed genes between RCE and berberine, coptisine, and palmatine were 70.8%, 52.6%, and 42.1%, respectively. Pathway clustering analysis indicated that berberine and coptisine possessed a certain similarity to RCE, and both compounds affected the cell cycle pathway; moreover, some pathways were uniquely enriched by berberine or coptisine. Berberine and coptisine had different regulatory effects on genes involved in lipid metabolism. These results provide comprehensive information on the pharmaceutical mechanisms of the different RC alkaloids and insights into their better combinatory use for the treatment of diseases.


Assuntos
Alcaloides de Berberina/farmacologia , Berberina/análogos & derivados , Coptis/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Rizoma/química , Células 3T3-L1 , Animais , Berberina/análise , Berberina/farmacologia , Alcaloides de Berberina/análise , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Camundongos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
7.
ACS Med Chem Lett ; 12(12): 1948-1954, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34917259

RESUMO

Phenanthrene-based tylophorine-1 (PBT-1) was identified previously as a lead compound in an anticancer drug discovery effort based on natural Tylophora alkaloids. An expanded structural optimization using a new more efficient synthetic route provided 14 PBT-derivatives. Eleven compounds displayed obvious antiproliferative activities in cellular assays (GI50 0.55-9.32 µM). The most potent compounds 9c, 9g, and 9h (GI50 < 1 µM) contained a 7-hydroxy group on the phenanthrene B-ring in addition to a pendant piperidine E-ring with different 4-substituents. Compound 9h with NH2 as the piperidine substituent was at least 4-fold more potent against triple-negative breast cancer MDA-MB-231 than estrogen-responsible breast cancer MCF-7 cell growth. In further biological evaluations, the new active compounds induced cell cycle accumulation in the late S and G2/M phase without interfering with microtubule formation or cell morphology. These results on the optimization of the B- and E-rings of PBT-1 should benefit further development of novel antitumor agents.

8.
Anesth Analg ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34744156

RESUMO

BACKGROUND: CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. METHODS: Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. RESULTS: To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). CONCLUSIONS: Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(5): 716-726, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34728032

RESUMO

Objective To compare the effects of carbohydrate-electrolyte beverage on post-exercise rehydration of healthy young men in different seasons,and to explore the influence of seasonal adaptability on fluid and electrolyte balance.Methods Fifteen healthy men,aged(24.4±0.5)years,completed 2 trails in a random crossover design both in summer and winter.During recovery,they consumed a drink volume equivalent to 100% of their sweat loss with plain boiled water(the water group)or carbohydrate-electrolyte beverage(the beverage group).Recovery was monitored for further 180 minutes by the collection of blood and urine samples.Results The dehydration time in summer was significantly shorter by about 20 minutes than that in winter(t=3.045,P=0.004).In summer,the fluid retention rate of the beverage group was significantly higher than that of the water group at 120 minutes after rehydration [(83.7±2.8)% vs.(73.7±3.7)%,F=5.312,P=0.028],and significantly higher than the water group at 180 minutes [(74.8±3.6)% vs.(66.1±4.3)%,F=4.340,P=0.046].In winter,the fluid retention rate of the beverage group at 180 minutes after rehydration was significantly higher than that of the water group [(74.9±4.7)% vs.(68.0±6.0)%,F=4.128,P=0.048].There was no significantly seasonal difference in the fluid retention effect of carbohydrate-electrolyte beverage at 180 minutes after rehydration.In the beverage group,the changes of blood glucose and serum sodium levels(all P<0.05)in summer were significantly higher than those in winter at 10-180 minutes after rehydration,and the fractional excretion of sodium in summer was significantly higher in summer than in winter at 120 and 180 minutes after rehydration(F120=4.972,P=0.034;F180=8.425,P=0.007);however,there was no significant difference in plasma osmolality(all P> 0.05).For the water group,the plasma osmolality in winter was lower than that in summer,while the degree of dryness and thirst was higher in winter than in summer.Conclusions Seasonal adaptability influenced the hydration status and its regulating factors.People dehydrated faster after exercise in summer than in winter,and the hydration status was relatively stable in winter.However,in summer,the blood glucose and electrolytes responded more rapidly to carbohydrate-electrolyte beverage supply,and the plasma osmolality and subjective perception recovered faster.Therefore,during the 180-minute recovery period,the carbohydrate-electrolyte beverage had a higher rehydration efficiency in a short recovery time in summer although there was no significantly seasonal difference in the fluid retention rate.


Assuntos
Carboidratos da Dieta , Hidratação , Adulto , Bebidas , Estudos Cross-Over , Eletrólitos , Humanos , Masculino , Estações do Ano
10.
Scand J Clin Lab Invest ; 81(7): 564-572, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34570657

RESUMO

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Catecolaminas/sangue , Dopamina/análogos & derivados , Metanefrina/sangue , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/sangue , Anticoagulantes/farmacologia , Dopamina/sangue , Epinefrina/sangue , Hemoglobinas/análise , Humanos , Metaboloma , Norepinefrina/sangue , Normetanefrina/sangue , Paraganglioma/sangue , Feocromocitoma/sangue , Triglicerídeos/sangue
11.
J Clin Hypertens (Greenwich) ; 23(9): 1734-1743, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34390121

RESUMO

The purpose of this study was to explore the effects of brisk walking on blood pressure (BP) in Chinese Han occupational populations to identify the appropriate volume of exercise needed for BP management. Eight-hundred and two office staff with sedentary lifestyles were recruited to receive a prescription pedometer-assisted brisk walking intervention for 3 months. To evaluate exercise intervention efficiency using statistical methods, the effective steps was divided as follows: 4000- < 8000 (Level 1), 8000- < 10 000 (Level 2), 10 000-12 000 (Level 3), and > 12 000 (Level 4) steps/day. The data of 688 participants who completed the study were analyzed. After intervention, Systolic BP (SBP) and Diastolic BP (DBP) at Levels 1-3 were significantly decreased (p < .05). For participants with hypertension at baseline, all four levels demonstrated a significantly reduced SBP and DBP. In addition, there was a significant dose-effect relationship between the effective steps and the SBP. Compared with the maximum effective steps level (Level 4), the average change of SBP between level 1-3 and level 4 were statistically significant, with -3.24 mm Hg (95%CI: -5.74 to -0.74, p = .011), -2.58 mm Hg (95%CI: -4.73 to -0.43, p = .019), and -2.19 mm Hg (95%CI: -4.20 to -0.18, p = .033), respectively. For the hypertensive cohort, only the difference between Level 1 and 4 was statistically significant (Level 1 vs. Level 4: difference in means = -6.22 mm Hg, 95%CI: -12.68 to -0.24, p = .036). No significant dose-effect relationship of DBP was observed. Our findings showed brisk walking can effectively control BP in Chinese populations and a significant dose-effect relationship was found between exercise and SBP.


Assuntos
Hipertensão , Caminhada , Pressão Sanguínea , China/epidemiologia , Humanos , Hipertensão/epidemiologia , Comportamento Sedentário
12.
Nat Prod Res ; : 1-7, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34304659

RESUMO

Eight cadinane-type sesquiterpenes, including a new cadinane-type sesquiterpene, named as mappianiodene (1), and seven known analogues (2-8), were isolated and identified from the stems and leaves of Mappianthus iodoides. The chemical structure and absolute configurations of 1 was elucidated by extensive spectral methods and the known compounds were identified by comparing their experimental spectral data with the reported spectral data in the literature. The anti-inflammatory and anti-HIV activities of those isolated cadinane-type sesquiterpenes were tested. As a result, cadinane-type sesquiterpenes 1-8 displayed notable inhibitory effects on NO (nitric oxide) production with IC50 values equivalent to that of the hydrocortisone. Moreover, compounds 1-8 exhibited pronounced anti-HIV-1 reverse transcriptase (RT) activities with the EC50 values in range of 0.17 to 9.28 µM.

13.
Front Cell Dev Biol ; 9: 672590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095142

RESUMO

Podophyllotoxin (POD) is one of the most characterized lignans that is commonly found in podophyllum, and its preparations and derivatives are widely used in clinical treatment due to strong antitumor and antivirus activities. POD has been reported for its neurotoxicity, liver toxicity, and potential reproductive toxicity. In the present study, we investigated the effects of POD on the organelles of mouse oocytes during meiosis. Our results showed that exposure to POD significantly reduced the developmental competence of mouse oocytes. Further analysis revealed that the endoplasmic reticulum (ER) failed to accumulate to the spindle periphery, suggesting that POD exposure might affect protein synthesis during oocyte meiotic maturation. Similarly, abnormal Golgi apparatus distribution was found after POD exposure, which could be confirmed by the aberrant localization of Rab11a-related vesicles, indicating that POD induced vesicle-based protein transport disorder. We also found the aberrant accumulation of lysosomes in the cytoplasm of POD-exposed oocytes, which implied that POD might lead to aberrant protein degradation. Moreover, the perinuclear distribution of mitochondria was also significantly disturbed, indicating the mitochondrial dysfunction after POD exposure. In all, our study illustrated that exposure to POD might disrupt protein synthesis, transport, degradation, and ATP production by its effects on the distribution and functions of organelles during mouse oocyte meiotic maturation.

14.
Biomed Pharmacother ; 142: 111652, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34112534

RESUMO

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Brusatol (Bru) has been reported to decrease Nrf2 protein expression specifically by ubiquitin degradation of Nrf2. However, it remains elusive whether combination of Brusatol and Cytarabine (Ara-C) elicits a synergistic antitumor effect in AML. Our results demonstrated that combination of Ara-C and Brusatol synergistically exerted remarkable pro-apoptosis effect in HL-60 and THP-1 cells. Mechanistically, synergistic anti-tumor effect of Ara-C/Brusatol in AML cells is mediated by attenuating Nrf2 expression. To our surprise, Nrf2 inhibition by Brusatol causes downregulation of the expression of glycolysis-related proteins and decreased glucose consumption and lactate production, whereas the level of ROS production was unaffected. The activation of Nrf2 by Sulforaphane (SFP) could reverse the chemotherapeutic effect and changes of glycolysis of concomitant of Ara-C with Brusatol in AML cell lines. Additionally, Ara-C/Brusatol co-treatment decreased Glucose-6-phosphate dehydrogenase (G6PD) protein expression and increased the sensitivity of Ara-C. Moreover, the mouse xenograft in vivo experiment confirmed that combining Ara-C with Brusatol exerted stronger antileukemia than Ara-C alone. The efficacy, together with the mechanistic observations, reveals the potential of simultaneously giving these two drugs and provides a rational basis for targeting glucose catabolism in future clinical therapeutic approach.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Citarabina/farmacologia , Glucose/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Quassinas/farmacologia , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Citarabina/uso terapêutico , Sinergismo Farmacológico , Feminino , Glucosefosfato Desidrogenase/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glicólise/efeitos dos fármacos , Células HL-60 , Humanos , Fígado/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quassinas/uso terapêutico , Células THP-1 , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Nat Prod Res ; : 1-8, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960216

RESUMO

A chemical study on the stems and leaves of Melodinus cochinchinensis resulted in the isolation and identification of a new monoterpenoid indole alkaloid, melodicochine A (1), together with seven known monoterpenoid indole alkaloids (2-8). The chemical structure of 1 was elucidated on the basis of extensive spectral data analyses and the known compounds were identified by comparing their experimental spectral data with the reported data in the literature. All isolated indole alkaloids were evaluated for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Monoterpenoid indole alkaloids 1-8 exhibited notable neuroprotective effects with EC50 values in range of 0.72 ± 0.06 to 17.89 ± 0.16 µM.

16.
Org Biomol Chem ; 19(18): 4037-4042, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33876174

RESUMO

Methylthioether is involved in the methylthiotransfer process in organisms, and therefore its functionality is of paramount importance to living organisms. Several methods for the installation of the methylthio group in small molecules have been reported previously; however, procedures starting from unactivated alkenes are rare. Herein, we report a formal hydro/deuteromethylthiolation of alkenes by using dimethyl(methylthio)sulfonium trifluoromethanesulfonate as the stimulator and sodium borohydride/deuteride as the hydrogen/deuterium source. The process represents a mild, transition metal-free and methanethiol-free route towards the synthesis of methylthioethers from unactivated alkenes.

19.
Sci Bull (Beijing) ; 66(9): 884-888, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33457042

RESUMO

Coronavirus disease-2019 (COVID-19) has become a major global epidemic. Facilitated by HTS2 technology, we evaluated the effects of 578 herbs and all 338 reported anti-COVID-19 TCM formulae on cytokine storm-related signaling pathways, and identified the key targets of the relevant pathways and potential active ingredients in these herbs. This large-scale transcriptional study innovatively combines HTS2 technology with bioinformatics methods and computer-aided drug design. For the first time, it systematically explores the molecular mechanism of TCM in regulating the COVID-19-related cytokine storm, providing an important scientific basis for elucidating the mechanism of action of TCM in treating COVID-19.

20.
Eur J Pharmacol ; 895: 173894, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476656

RESUMO

Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3'-UTR correlated positively with TBC1D16 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D16 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D16 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Ativadoras de GTPase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Regiões 3' não Traduzidas , Adolescente , Adulto , Idoso , Proliferação de Células/efeitos dos fármacos , Metilação de DNA , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Células HEK293 , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Células THP-1 , Fatores de Tempo , Células U937 , Adulto Jovem
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