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1.
Sci Total Environ ; 773: 145442, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33940727

RESUMO

Cadmium (Cd) has been confirmed as an environmental contaminant, which potential threats health impacts to humans and animals. Selenium (Se) as a beneficial element that alleviates the negative effects of Cd toxicity. Se mainly exists in two forms in food nutrients including organic Se usually as (Se-enriched yeast (SeY)) and inorganic Se (sodium selenite (SSe)). Nanoparticle of Se (Nano-Se), a new form Se, which is synthesized by the bioreduction of Se species, which attracted significant attention recently. However, compared the superiority alleviation effects of Nano-Se, SeY or SSe on Cd-induced toxicity and related mechanisms are still poorly understood. The purpose of this study was to compare the superiority antagonism effects of Nano-Se, SeY and SSe on Cd-induced inflammation response via NF-kB/IκB pathway in the heart. The present study demonstrated that exposed to Cd obviously increased the accumulation of Cd, disruption of ion homeostasis and depressed the ratios of K+/Na+ and Mg2+/Ca2+ via ion chromatography mass spectrometry (ICP-MS) detecting the heart specimens. In the results of histological and ultrastructure observation, typical inflammatory infiltrate characteristics and mitochondria and nuclear structure alterations in the hearts of Cd group were confirmed. Cd treatment enhanced the inducible nitric oxide synthase (iNOS) activities and NOS isoforms expression via NF-kB/IκB pathway to promote inflammation response. However, the combined treatment of Cd-exposed animals with Nano-Se was more effective than SeY and SSe in reversing Cd-induced histopathological changes and iNOS activities increased, reducing Cd accumulation and antagonizing Cd-triggered inflammation response via NF-kB/IκB pathway in chicken hearts. Overall, Se applications, especially Nano-Se, can be most efficiently used for relieving cardiotoxicity by exposed to Cd compared to other Se compound.


Assuntos
Nanopartículas , Selênio , Animais , Cádmio/toxicidade , Humanos , Inflamação/induzido quimicamente , NF-kappa B , Nanopartículas/toxicidade , Saccharomyces cerevisiae , Selenito de Sódio
2.
Artigo em Inglês | MEDLINE | ID: mdl-33955722

RESUMO

OBJECTIVE: The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown. METHODS: We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants. RESULTS: Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids. INTERPRETATION: Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.

3.
Surv Ophthalmol ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33811911

RESUMO

Dry eye disease (DED) is a common ocular surface condition causing symptoms of significant discomfort, visual disturbance, and pain. With recent advancements, DED has become recognized as a chronic self-perpetuating inflammatory condition triggered by various internal and environmental factors. DED has been shown to arise from the activation of both the innate and adaptive immune systems, leading to significant corneal epithelium and lacrimal gland dysfunction. While the cornea is normally avascular and thus imbued with angiogenic and lymphangiogenic privilege, various DED models have revealed activated corneal antigen-presenting cells in regional lymph nodes, suggesting the formation of new corneal lymphatic vessels in DED. The recent availability of reliable lymphatic cell surface markers such as LYVE-1 has made it possible to study lymphangiogenesis. Accordingly, numerous studies have been published within the last decade discussing the role of lymphangiogenesis in DED pathology. We systematically review the literature to identify and evaluate studies presenting data on corneal lymphangiogenesis in DED. There is significant evidence supporting corneal lymphangiogenesis as a central mediator of DED pathogenesis. These findings suggest that anti-lymphangiogenic therapeutic strategies may be a viable option for the treatment of DED, a conclusion supported by the limited number of reported clinical trials examining anti-lymphangiogenic modalities in DED.

4.
Inflamm Res ; 70(5): 591-603, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33891136

RESUMO

BACKGROUND: FOXO3a is a widely studied transcription factor and plays an important role in a variety of biology. The purpose of this study was to explore the role and potential mechanism of FOXO3a on lipid accumulation and adipocyte inflammation in adipocytes through regulation of autophagy. METHODS: The obese mouse model was successfully induced by high-fat diet. SiRNA targeting FOXO3a was transfected into differentiation of 3T3-L1 adipocytes to reduce the expression of FOXO3a. The culture medium of RAW264.7 cells was added to the differentiated 3T3-L1 adipocytes to form a co-culture system. Subsequently, ELISA or AdipoRed assay was performed to measure the expression of triglyceride (TG) and cholesterol (TC) in mouse adipose tissue or differentiation of 3T3-L1 adipocytes. Adipocyte differentiation was detected by Oil Red O-staining. Ad-mCherry-GFP-LC3II was used to detect the level of autophagy in differentiation of 3T3-L1 adipocytes. Western blotting or qRT-PCR was used to detect the expression of FOXO3a, autophagy-related proteins (beclin 1, CEBPß, PPARγ, ACC1 and KLF4), inflammatory cytokines (TNF-α, IL-1ß, IL-6 and MCP1), NF-κB signal pathway-related proteins or adipokines (Adiponectin, AdipoR1 and resistin) in differentiated 3T3-L1 or RAW264.7 cells. RESULTS: The expression of FOXO3a and autophagy levels were significantly increased in visceral adipose tissue of obese mice and differentiation of 3T3-L1 adipocytes. Downregulation of FOXO3a significantly inhibited the autophagy and lipid accumulation in differentiation of 3T3-L1 adipocytes. In addition, FOXO3a knockdown significantly reduced Lipopolysaccharide (LPS)-induced inflammation and adipokines release in RAW264.7 cells treated with the culture medium of 3T3-L1 adipocytes. These above activity changes could be reversed by autophagy inducer rapamycin. CONCLUSION: FOXO3a could promote lipid accumulation and inflammation in differentiated 3T3-L1 adipocytes by targeting autophagy. Our results provide a new theoretical basis for FOXO3a to regulate obesity.

5.
J Physiol Biochem ; 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33893994

RESUMO

The objective of this study is to evaluate the role of miR-137 in low-intensity shear stress-induced endoplasmic reticulum (ER) stress and cell apoptosis in human aortic endothelial cells (HAECs). HAECs were transfected with miR-137 mimic, miR-137 inhibitor, or the corresponding negative control and then exposed to pulsatile shear stress in a parallel-plate flow chamber at 1, 2, 5, 10, and 15 dyn/cm2 for 3 h. Real-time polymerase chain reaction was used to detect mRNA expression of miR-137 and SDS22. A dual-luciferase reporter assay was employed to verify the direct interaction between miR-137 and SDS22. The internal morphology of cells and cell apoptosis was assessed by TUNEL staining observed under a transmission electron microscope. Meanwhile, the protein expression of oxidative stress-related, apoptosis-related, and activated c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling-related genes were analyzed by western blotting. Low strength shear stress (0-5 dyn/cm2) caused a negative change of HAEC surface and internal morphology in an intensity-dependent manner, and these changes were gradually weakened when shear stress was increased more than 5 dyn/cm2. Furthermore, low-intensity shear stress promoted oxidative stress response, accelerated cell apoptosis, and upregulated miR-137 expression and JNK/AP-1 signaling in HAECs. MiR-137 directly targets SDS22. Knockdown of miR-137 noticeably reduced activation of JNK/AP-1 signaling, oxidative stress response, and cell apoptosis induced by shear stress. MiR-137 regulated low-intensity shear stress-induced human aortic endothelial cell ER stress and cell apoptosis via JNK/AP-1 signaling.

6.
Org Biomol Chem ; 19(14): 3207-3212, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33885575

RESUMO

A green and efficient approach for the synthesis of selenium-substituted iminoisobenzofuran using 2-vinylbenzamides and diselenides in a continuous electrochemical microreactor has been developed. This strategy enabled the preparation of a series of iminoisobenzofuran derivatives in moderate to good yields under metal-free and oxidant-free conditions. The application of the electrochemical flow system successfully overcomes the difficulty of process control in traditional electrochemistry and achieves efficient transformation of electricity. Moreover, the continuous-flow system combined with electrosynthesis overcomes the difficulty in realizing a scale-up reaction in conventional batch-type electrolysis.

7.
Huan Jing Ke Xue ; 42(5): 2422-2431, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884813

RESUMO

As carbon sources for the denitrification process, agricultural wastes have some problems, such as excess release of organic carbon; unclear release characteristics of nitrogen, phosphorus, and colorimetric substances; and unclear components, release mechanisms, and potential effects of the released dissolved organic matter (DOM) in the start-up period. To resolve those problems, rice straw, wheat straw, corn stalk, corncob, soybean stalk, and soybean hull were selected as denitrification carbon sources to investigate the release mechanisms and potential influences of the organic matter, secondary pollutants, and DOM. The results showed that the six agricultural wastes could be used as the denitrification carbon source. The carbon content in the wheat straw was the highest and the secondary pollution risk from the corncob was the lowest. For the six carbon sources, the second-order kinetic equation and Ritger-Peppas equation were followed during the 1-120 h carbon release process. The fitting results demonstrated that corncob was more suitable for use as the denitrification carbon source because of its moderate cm value and longer t1/2 value, and the release mechanisms of the six types of carbon sources were mainly controlled by the diffusion process. The NH4+-N, TN, and TP contents in the immersion water of the rice straw were higher than those of the five other agricultural wastes, and there was heavy chromaticity in the immersion water of the wheat straw and corn stalk. The amounts of nitrogen, phosphorus, and chromatic substances released from the corncob were the lowest. The leachates of the corncob and soybean hull had higher biodegradability and lower risks of secondary pollution than those of the other sources. The aromaticity and molecular weight of DOM increased as the reaction time increased, and the humification of DOM was low. Five components were identified by PARAFAC. The main component was protein-like matter, which was mainly composed of tyrosine-like and tryptophan-like substances. There was less humic acid-like matter in the immersion water. The component characteristics of DOM might have had an adverse effect on the subsequent water treatment process. These results could provide theoretical support for the impact on effluent water quality and risk assessment when the agricultural wastes are used as an additional denitrification carbon source at the start-up stage.

8.
Anim Biotechnol ; : 1-12, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847240

RESUMO

The purpose of this study was to investigate the role of urea-N recycling, rumen bacterial community, and rumen epithelial gene expression in nitrogen utilization of calves. Here, 12 Holstein calves were divided into two dietary treatments: a high-protein diet (HP, 173 g/kg), and a low-protein diet (LP, 125 g/kg). Urea-N kinetics was evaluated using urea-15N15N isotope labeling method. Gene expression in rumen epithelium and liver, bacterial diversity, and metabolites in rumen were characterized using transcriptomic, Illumina HiSeq-based 16S rRNA, and LC/QTOF-MS-based metabolomics, respectively. We demonstrated that the bone weight, dressing percentage, and nitrogen utilization efficiency (NUE) increased in calves fed HP compared with LP. The urea synthesized, eliminated in urine, and return to ornithine cycle were higher in calves fed HP than LP, while the urea-N reused for anabolism were the opposite. Differentially expressed genes participated in amino acid metabolism and molecular transport in rumen epithelium. The increased abundance of bacteria and metabolites involved in protein and/or amino acid metabolism reflected the larger protein utilization in rumen of calves fed HP. In conclusion, the urea-N recycling could not fully compensate for the reduced NUE caused by N deficiency. Rumen bacteria and rumen epithelial metabolism contribute to improving NUE of calves.

9.
Biomark Med ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834858

RESUMO

Objective: This study is to explore the predictive value of erythrocyte-derived microparticles (ErMPs) in patients with acute coronary syndrome (ACS). Materials & methods: Total 305 subjects were enrolled and divided into the control group and ACS group. Flow cytometry was used to detect the ErMPs. The Gensini score was calculated based on the results of the coronary angiography. Results: Compared with that in the control group, the ErMPs concentration in the ACS group increased significantly and the concentration of ErMPs was correlated with the ACS risk. The concentration of ErMPs and the percentage of ErMPs were positively correlated with the Gensini score. Conclusion: ErMPs may be a new biomarker for predicting the ACS risk and the coronary artery disease severity.

10.
Phytochemistry ; 187: 112780, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33915419

RESUMO

Whole plants of Gentianella turkestanorum are commonly used as a traditional Uighur medicine. A phytochemical investigation led to the isolation of eight undescribed gentianellane-type sesterterpenoids (18-epi-nitidasin, gentianelloids D-F, and 18-epi-gentianelloids C-F), one undescribed 11,12-seco-gentianellane (18-epi-alborosin), and three known analogs (nitidasin, gentianelloid C and alborosin) among which gentianelloid C was found for the first time from a natural source. The structures of these compounds were elucidated by extensive spectroscopic analyses (including 1D and 2D NMR, HRMS, IR, and specific rotation) and in the case of 18-epi-gentianelloid C by the single-crystal X-ray diffraction analysis. A putative biosynthetic route for these sesterterpenoids was proposed. The immunosuppressive activity of the isolated compounds was also evaluated by their ability to inhibit the proliferation of T cells and T cell cytokine IFN-γ production. Nitidasin suppressed IFN-γ production with an IC50 value of 16.50 µM, while gentianelloid F and alborosin inhibited the proliferation of and IFN-γ production in T cells with IC50 values of 12.40-14.66 µM.

11.
IEEE Trans Cybern ; PP2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33872169

RESUMO

This article proposes an effective optimal bounded ellipsoid (OBE) identification algorithm for neural networks to reconstruct the dynamics of the uncertain Euler-Lagrange systems. To address the problem of unbounded growth or vanishing of the learning gain matrix in classical OBE algorithms, we propose a modified OBE algorithm to ensure that the learning gain matrix has deterministic upper and lower bounds (i.e., the bounds are independent of the unpredictable excitation levels in different regressor channels and, therefore, are capable of being predetermined a priori). Such properties are generally unavailable in the existing OBE algorithms. The upper bound prevents blow-up in cases of insufficient excitations, and the lower bound ensures good identification performance for time-varying parameters. Based on the proposed OBE identification algorithm, we developed a closed-loop controller for the Euler-Lagrange system and proved the practical asymptotic stability of the closed-loop system via the Lyapunov stability theory. Furthermore, we showed that inertial matrix inversion and noisy acceleration signals are not required in the controller. Comparative studies confirmed the validity of the proposed approach.

12.
Nanoscale ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913459

RESUMO

Owing to their scientific and technological importance, the development of highly efficient photocatalytic water oxidation systems with rapid photogenerated charge separation and high surface catalytic activity is highly desirable for the storage and conversion of solar energy. A promising candidate is rutile phase titanium dioxide (TiO2), which has been widely studied over half a century. Specifically, oriented single-crystalline TiO2 surfaces with high oxidative reactivity would be most desirable, but achieving these structures has been limited by the availability of synthetic techniques. In this study, a facile and green synthetic approach was developed for the first time to synthesize rutile TiO2 single crystals with regulable reductive and oxidative facets. Glycolic acid (GA) and sodium fluoride (NaF) are used as the crucial and effective phase and facet controlling agents, respectively. The selective adsorption of F- ions on the facets of rutile TiO2 crystals not only plays a key role in driving the nucleation and preferential growth of the crystals with desired facets but also significantly affects their photocatalytic gas evolution reactivity. With heat treatment, the highly stable F--free rutile TiO2 single crystals with a high percentage of oxidative facets exhibit a superior photocatalytic gas evolution rate (≈116 µmol h-1 per 0.005 g catalyst), 8.5 times higher than that of previous F--containing samples.

13.
Org Lett ; 23(6): 2232-2237, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33667109

RESUMO

Eurysoloids A (1) and B (2), two novel diastereomeric sesterterpenoids possessing a pentacyclic 5/6/5/10/5 framework with an unusual macrocyclic ether system, were isolated from Eurysolen gracilis Prain. Their structures were unambiguously determined by spectroscopic, single-crystal X-ray diffraction and DP4+ analyses. A plausible biosynthetic pathway for compounds 1 and 2 was proposed. Both compounds exhibited immunosuppressive activity via inhibiting the production of cytokine IFN-γ of T cells, and compound 2 inhibited adipogenesis in 3T3-L1 adipocytes.

14.
Abdom Radiol (NY) ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710383

RESUMO

PURPOSE: To evaluate the ability of inferior vena cava-lesion-attenuation-difference (ILAD) and lesion-cortex-attenuation-ratio (LCAR) to differentiate renal oncocytomas (RO) from chromophobe renal cell carcinomas (chRCC). METHODS: Retrospective study with analysis of 84 cases of chRCC and 30 cases of RO confirmed by surgical pathology. ILAD was calculated by measuring the difference in Hounsfield units (HU) between the inferior vena cava and the lesion of interest on the same image slice on preoperative CT scan. Calculating LCAR using the CT attenuation ratio of lesion to renal cortex at the same image slice. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of ILAD and LCAR for disease activity. RESULTS: There were no statistically significant differences in demographic and lesion characteristics between patients with chRCC and RO (p > 0.05). ILAD has significant statistical differences in the identification of RO and chRCC in the arterial (p = 0.031), venous (p = 0.047), and delayed phase (p = 0.002). And LCAR showed a statistically significant difference between two lesions during the arterial (p = 0.043), venous (p = 0.026), and delayed phase (p = 0.008). When all significant variables were used in combination to build a predicting model (Mix), the AUC was 0.871 (95% CI 0.759-0.984) with 67.9% sensitivity and 100% specificity. CONCLUSION: ILAD and LCAR at the arterial phase, venous phase and delayed phase were shown to be useful CT attenuation parameter in discriminating RO from chRCC when histologic evaluation on biopsy is indeterminate.

15.
Environ Sci Technol ; 55(6): 4017-4026, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33656869

RESUMO

Investigating catalytic reaction mechanisms could help guide the design of catalysts. Here, aimed at improving both the catalytic performance and SO2 resistance ability of catalysts in the selective reduction of NO by NH3 (NH3-SCR), an innovative CeO2-SiO2 mixed oxide catalyst (CeSi2) was developed based on our understanding of both the sulfur poisoning and reaction mechanisms, which exhibited excellent SO2/H2O resistance ability even in the harsh working conditions (containing 500 ppm of SO2 and 5% H2O). The strong interaction between Ce and Si (Ce-O-Si) and the abundant surface hydroxyl groups on CeSi2 not only provided fruitful surface acid sites but also significantly inhibited SO2 adsorption. The NH3-SCR performance of CeSi2 was promoted by an enhanced Eley-Rideal (E-R) mechanism in which more active acid sites were preserved under the reaction conditions and gaseous NO could directly react with adsorbed NH3. This mechanism-enhanced process was even further promoted on sulfated CeSi2. This work provides a reaction mechanism-enhanced strategy to develop an environmentally friendly NH3-SCR catalyst with superior SO2 resistance.


Assuntos
Amônia , Óxidos , Catálise , Oxirredução , Dióxido de Silício , Enxofre
16.
Chemistry ; 27(21): 6522-6528, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33751675

RESUMO

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33742485

RESUMO

Achieving a selective 2 e- or 4 e- oxygen reduction reaction (ORR) is critical but challenging. Herein, we report controlling ORR selectivity of Co porphyrins by tuning only steric effects. We designed Co porphyrin 1 with meso-phenyls each bearing a bulky ortho-amido group. Due to the resulted steric hinderance, 1 has four atropisomers with similar electronic structures but dissimilar steric effects. Isomers αßαß and αααα catalyze ORR with n=2.10 and 3.75 (n is the electron number transferred per O2 ), respectively, but ααßß and αααß show poor selectivity with n=2.89-3.10. Isomer αßαß catalyzes 2 e- ORR by preventing a bimolecular O2 activation path, while αααα improves 4 e- ORR selectivity by improving O2 binding at its pocket, a feature confirmed by spectroscopy methods, including O K-edge near-edge X-ray absorption fine structure. This work represents an unparalleled example to improve 2 e- and 4 e- ORR by tuning only steric effects without changing molecular and electronic structures.

18.
Phytochemistry ; 186: 112731, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33721797

RESUMO

The Lamiaceae plant Ajuga forrestii Diels is a traditional Chinese herbal medicine with abundant glandular trichomes (GTs), but their chemistry and biological functions remain uninvestigated. Here, a panel of six highly functionalized neo-clerodane diterpenoids was localized to the peltate GTs of A. forrestii using laser microdissection coupled with HPLC analysis, indicating that the GTs of A. forrestii are an excellent material for the elucidation of the yet unclear biosynthetic pathway of natural neo-clerodane diterpenoids. In addition, four undescribed neo-clerodane diterpenoids with an acyclic C-9 side chain including two pairs of 1:1 mixture of inseparable diastereomers, ajuforrestins D-G, were isolated from the fresh leaves of A. forrestii together with six known compounds. The structures of the undescribed compounds were elucidated by spectroscopic (including 1D and 2D NMR and HR-ESI-MS) analyses. Biological assays indicated that the major GT compound ajugacumbin B and undescribed ajuforrestins D/E showed antifeedant activity against Helicoverpa armigera, suggesting that neo-clerodanes in A. forrestii should be involved in plant defence against insects. Moreover, the abietane diterpenoid ajuforrestin B exhibited significant anti-inflammatory activity on the secretion of interleukin-2 (IL-2) and cytotoxicity against three cancer cell lines, NCI-H1975, HepG2 and MCF-7, suggesting that ajuforrestin B could positively contribute to the therapeutic effects of this traditional Chinese medicine.


Assuntos
Ajuga , Diterpenos Clerodânicos , Anti-Inflamatórios/farmacologia , Diterpenos Clerodânicos/farmacologia , Estrutura Molecular , Folhas de Planta , Tricomas
19.
Chem Commun (Camb) ; 57(27): 3379-3382, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33683244

RESUMO

A copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins was developed, affording valuable 2,3-dihydrooxazole-spirooxindoles in moderate to good yields with excellent diastereoselectivity. The reaction sequence involves Cu(i) initiated N-O bond cleavage, 1,5-HAT and C-N bond formation. The protocol features mild reaction conditions and broad substrate scope. DFT calculations demonstrated that the [3+2] annulation pathway is more energetically favourable in both kinetics and thermodynamics.

20.
Oxid Med Cell Longev ; 2021: 5589612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763168

RESUMO

Endothelial dysfunction, which is characterized by damage to the endoplasmic reticulum (ER) and mitochondria, is involved in a variety of cardiovascular disorders. Here, we explored whether mitochondrial damage and ER stress are associated with endothelial dysfunction. We also examined whether and how melatonin protects against oxidized low-density lipoprotein- (ox-LDL-) induced damage in endothelial cells. We found that CHOP, GRP78, and PERK expressions, which are indicative of ER stress, increased significantly in response to ox-LDL treatment. ox-LDL also induced mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential, increased mitochondrial ROS levels, and downregulation of mitochondrial protective factors. In addition, ox-LDL inhibited antioxidative processes, as evidenced by decreased antioxidative enzyme activity and reduced Nrf2/HO-1 expression. Melatonin clearly reduced ER stress and promoted mitochondrial function and antioxidative processes in the presence of ox-LDL. Molecular investigation revealed that ox-LDL activated the JNK/Mff signaling pathway, and melatonin blocked this effect. These results demonstrate that ox-LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox-LDL-induced damage.

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