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1.
Opt Express ; 31(24): 40592-40603, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041355

RESUMO

Studying the chaotic dynamics of semiconductor lasers is of great importance for their applications in random bit generation and secure communication. While considerable effort has been expended towards investigating these chaotic behaviors through numerical simulations and experiments, the accurate prediction of chaotic dynamics from limited observational data remains a challenge. Recent advancements in machine learning, particularly in reservoir computing, have shown promise in capturing and predicting the complex dynamics of semiconductor lasers. However, existing works on laser chaos predictions often suffer from the need for manual parameter optimization. Moreover, the generalizability of the approach remains to be investigated, i.e., concerning the influences of practical laser inherent noise and measurement noise. To address these challenges, we employ an automated optimization approach, i.e., a genetic algorithm, to select optimal reservoir parameters. This allows efficient training of the reservoir network, enabling the prediction of continuous intensity time series and reconstruction of laser dynamics. Furthermore, the impact of inherent laser noise and measurement noise on the prediction of chaotic dynamics is systematically examined through numerical analysis. Simulation results demonstrate the effectiveness and generalizability of the proposed approach in achieving accurate predictions of chaotic dynamics in semiconductor lasers.

2.
Opt Express ; 31(21): 35343-35353, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859268

RESUMO

This paper demonstrates that the linewidth enhancement factor of quantum dot lasers is influenced by the external carrier transport issued from different external current sources. A model combining the rate equation and semi-classical carrier noise is used to investigate the different mechanisms leading to the above phenomenon in the context of a quantum dot distributed feedback laser. Meanwhile, the linewidth enhancement factor extracted from the optical phase modulation method shows dramatic differences when the quantum dot laser is driven by different noise-level pumps. Furthermore, the influence of external carrier noise on the frequency noise in the vicinity of the laser's threshold current directly affects the magnitude of the linewidth enhancement factor. Simulations also investigate how the external carrier transport impacts the frequency noise and the spectral linewidth of the QD laser. Overall, we believe that these results are of paramount importance for the development of on-chip integrated ultra-low noise oscillators producing light at or below the shot-noise level.

3.
Sci Rep ; 13(1): 18112, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872240

RESUMO

Efficient grating couplers (GCs) for perfectly vertical coupling are difficult to realize due to the second-order back reflection. In this study, apodized GCs (AGCs) are presented for achieving perfectly-vertical coupling to 220 nm thick silicon-on-insulator (SOI) waveguides in the C-band. We compare the performance of the AGCs to that of uniform GCs (UGCs) and demonstrate the superiority of the former. The AGCs were obtained through inverse design using gradient-based optimization and were found to effectively suppress back reflection and exhibit better matching to the Gaussian beam profile. The design and measurement results show that AGCs have a 3 dB lower coupling loss than UGCs. We fabricated focusing AGCs by electron beam lithography with a single, 70 nm shallow etch and a minimum feature size of 100 nm, which makes them compatible with CMOS technology. The AGCs achieved a coupling efficiency of -5.86 dB for perfectly vertical coupling. Overall, our results demonstrate the potential of AGCs for achieving high-performance coupling in the C-band on the SOI platform.

4.
Front Mol Biosci ; 10: 1228771, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719264

RESUMO

Background: Cold exposure (CE) can effectively modulate adipose tissue metabolism and improve metabolic health. Although previous metabolomics studies have primarily focused on analyzing one or two samples from serum, brown adipose tissue (BAT), white adipose tissue (WAT), and liver samples, there is a significant lack of simultaneous analysis of multiple tissues regarding the metabolic changes induced by CE in mice. Therefore, our study aims to investigate the metabolic profiles of the major tissues involved. Methods: A total of 14 male C57BL/6J mice were randomly assigned to two groups: the control group (n = 7) and the CE group (n = 7). Metabolite determination was carried out using gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to identify metabolites exhibiting differential expression between the two groups. Results: In our study, we identified 32 discriminant metabolites in BAT, 17 in WAT, 21 in serum, 7 in the liver, 16 in the spleen, and 26 in the kidney, respectively. Among these metabolites, amino acids, fatty acids, and nucleotides emerged as the most significantly altered compounds. These metabolites were found to be associated with 12 differential metabolic pathways closely related to amino acids, fatty acids, and energy metabolism. Conclusion: Our study may provide valuable insights into the metabolic effects induced by CE, and they have the potential to inspire novel approaches for treating metabolic diseases.

5.
Front Nutr ; 10: 1171806, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492592

RESUMO

Objective: Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice. Methods: For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics. Results: By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism. Conclusion: We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.

6.
Opt Express ; 31(15): 25177-25190, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37475329

RESUMO

This work theoretically investigates the relative intensity noise (RIN) and spectral linewidth characteristics of epitaxial quantum dot (QD) lasers on silicon subject to optical injection. The results show that the RIN of QD lasers can be reduced by optical injection, hence a reduction of 10 dB is achieved which leads to a RIN as low as -167.5 dB/Hz in the stable injection-locked area. Furthermore, the spectral linewidth of the QD laser can be greatly improved through the optical injection locked scheme. It is reduced from 556.5 kHz to 9 kHz with injection ratio of -60 dB and can be further reduced down to 1.5 Hz with injection ratio of 0 dB. This work provides an effective method for designing low intensity noise and ultra-narrow linewidth QD laser sources for photonics integrated circuits on silicon.

7.
J Chromatogr Sci ; 61(7): 699-704, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35397163

RESUMO

How to improve the enantiomer separation efficiency of drugs is a hot topic. In this paper, polydopamine (PDA) coating doped with graphene oxide (GO) by physical adsorption was used to modify the capillary column to enhance the enantioseparation efficiency of the drugs. In the capillary electrochromatography (CEC) system, the novel capillary column with carboxymethyl-ß-cyclodextrin (CM-ß-CD) as a chiral selector has completed the enantioseparation of four basic drugs (propranolol, metoprolol, amlodipine and chlorpheniramine). The optimum separation conditions were obtained by optimizing the pH of the buffer, the concentration of organic modifier, the concentration of the chiral selector and the voltage, and the resolution and peak shape were significantly improved compared with uncoated bare-fused column. The stability and reproducibility of the new capillary column were satisfactory and the relative standard deviation of intra-day and inter-day was <3.2%, and of column-to-column was <4.8%. The rich functional groups of GO are key factors to improve the enantioseparation efficiency, which also indicates that nanomaterials with easy modification of functional groups and large specific surface area are excellent resources for capillary modification applications.

8.
Neurotox Res ; 40(6): 2016-2026, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36550222

RESUMO

Acrylamide (AM) is a potent neurotoxin and carcinogen that is mainly formed by the Maillard reaction of asparagine with starch at high temperatures. However, the toxicity mechanism underlying AM has not been investigated from a proteomic perspective, and the regulation of protein expression by AM remains poorly understood. This research was the first to utilize proteomics to explore the mechanism of AM exposure-induced neuroinflammation. Target proteins were obtained by differential protein analysis, functional annotation, and enrichment analysis of proteomics. Then, molecular biology methods, including Western blot, qPCR, and immunofluorescence, were used to verify the results and explore possible mechanisms. We identified 100 key differential metabolites by proteomic analysis, which was involved in the occurrence of various biological functions. Among them, the KEGG pathway enrichment analysis showed that the differential proteins were enriched in the P53 pathway, sulfur metabolism pathway, and ferroptosis. Finally, the differential target protein we locked was LARP7. Molecular biological verification found that AM exposure inhibited the expression of LARP7 and induced the burst of inflammation, while SRT1720 agonist treatment showed no effect on LARP7, but significant changes in inflammatory factors and NF-κB. Taken together, these findings suggested that AM may activate NF-κB to induce neuroinflammation by inhibiting the LARP7-SIRT1 pathway. And our study provided a direction for AM-induced neurotoxicity through proteomics and multiple biological analysis methods.


Assuntos
NF-kappa B , Sirtuína 1 , Humanos , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Doenças Neuroinflamatórias , Microglia , Acrilamida/toxicidade , Acrilamida/metabolismo , Proteômica , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/farmacologia
9.
Front Pharmacol ; 13: 958882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188576

RESUMO

Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of chemotherapy, especially in regimens containing irinotecan (CPT-11). Several studies on the pathologic mechanisms of CIM focused on both the genomics and molecular pathways triggered by chemotherapy. However, systematic evaluation of metabolomic analysis in irinotecan-induced intestinal mucositis (IIM) has not been investigated. This study aimed to comprehensively analyze metabolite changes in main tissues of IIM mouse models. Male ICR mice were assigned to two groups: the model group (n = 11) treated with CPT-11 (20 mg/kg daily; i.p.) and the control group (n= 11) with solvent for 9 days. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the metabolic alterations in the serum, intestinal, colonic, hepatic, and splenic samples of mice between two groups by multivariate statistical analyses, including GC-MS data processing, pattern recognition analysis, and pathway analysis. Forty-six metabolites, including hydrocarbons, amino acids, lipids, benzenoids, hydroxy acids, and amines, had significant changes in levels in tissues and sera of IIM mouse models. The most important pathways related to the identified metabolites were the glycerolipid metabolism in the colon and aminoacyl-tRNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism in the liver. Our study firstly provided a comprehensive and systematic view of metabolic alterations of IIM using GC-MS analysis. The characterizations of metabolic changes could offer profound and theoretical insight into exploring new biomarkers for diagnosis and treatment of IIM.

10.
Ecotoxicol Environ Saf ; 242: 113888, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35872488

RESUMO

Fluoride is widely present in the environment. Excessive fluoride exposure leads to fluorosis, which has become a global public health problem and will cause damage to various organs and tissues. Only a few studies focus on serum metabolomics, and there is still a lack of systematic metabolomics associated with fluorosis within the main organs. Therefore, in the current study, a non-targeted metabolomics method using gas chromatography-mass spectrometry (GC-MS) was used to research the effects of fluoride exposure on metabolites in different organs, to uncover potential biomarkers and study whether the affected metabolic pathways are related to the mechanism of fluorosis. Male Sprague-Dawley rats were randomly divided into two groups: a control group and a fluoride exposure group. GC-MS technology was used to identify metabolites. Multivariate statistical analysis identified 16, 24, 20, 20, 24, 13, 7, and 13 differential metabolites in the serum, liver, kidney, heart, hippocampus, cortex, kidney fat, and brown fat, respectively, in the two groups of rats. Fifteen metabolic pathways were affected, involving toxic mechanisms such as oxidative stress, mitochondrial damage, inflammation, and fatty acid, amino acid and energy metabolism disorders. This study provides a new perspective on the understanding of the mechanism of toxicity associated with sodium fluoride, contributing to the prevention and treatment of fluorosis.


Assuntos
Fluoretos , Metabolômica , Animais , Biomarcadores , Fluoretos/toxicidade , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Metabolômica/métodos , Ratos , Ratos Sprague-Dawley
11.
Bioorg Chem ; 126: 105906, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661529

RESUMO

In this study, a series of potential candidate molecules with excellent antitumor activity targeting tubulin and PTEN/PI3K/Akt signaling pathway was synthesized by modifying the molecule structure of podophyllotoxin (PPT) at the C-4 position via a structure-guided drug design approach. MTT assay results indicated that compound 12c had stronger anti-proliferative activities against HGC-27, MCF-7 and H460 cell lines than etoposide (VP-16), especially for HGC-27 (12c: IC50 = 0.89 ± 0.023 µM; PPT: IC50 = 6.54 ± 0.69 µM, VP-16: IC50 = 2.66 ± 0.28 µM) with lower affect in healthy human cells (293 T and GES-1). Further pharmacological analysis exhibited that 12c could bind the tubulin at the colchicine site and disrupt the dynamic equilibrium of microtubules. Moreover, 12c also suppressed the expressions/activities of matrix metalloprotease (MMP)-2, vimentin and up-regulation E-cadherin suggesting that 12c could block the epithelial-mesenchymal transition (EMT). The increased cell survival and invasion/migration were associated with the inactivation of PTEN/PI3K/Akt, 12c could regulate this pathway and cascade influence on the mitochondrial pathway, eventually, leading to the cell apoptosis. Thus, 12c may have the potential to become a candidate molecule in gastric cancer clinical treatment.


Assuntos
Antineoplásicos , Podofilotoxina , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Etoposídeo/farmacologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Podofilotoxina/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tubulina (Proteína)/metabolismo
12.
Nutr Metab (Lond) ; 19(1): 41, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761356

RESUMO

OBJECTS: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice. METHODS: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography-mass spectrometry approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. RESULTS: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 6 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, L-isoleucine, L-proline, L-aspartic acid, L-serine, L-hydroxyproline, L-alanine, L-valine, L-threonine, L-glutamic acid, and L-phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 7 different functional pathways related to the metabolism of AAs, lipids, and energy. CONCLUSION: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.

13.
Light Sci Appl ; 11(1): 7, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974532

RESUMO

Chaos in nonlinear dynamical systems is featured with irregular appearance and with high sensitivity to initial conditions. Near-infrared light chaos based on semiconductor lasers has been extensively studied and has enabled various applications. Here, we report a fully-developed hyperchaos in the mid-infrared regime, which is produced from interband cascade lasers subject to the external optical feedback. Lyapunov spectrum analysis demonstrates that the chaos exhibits three positive Lyapunov exponents. Particularly, the chaotic signal covers a broad frequency range up to the GHz level, which is two to three orders of magnitude broader than existed mid-infrared chaos solutions. The interband cascade lasers produce either periodic oscillations or low-frequency fluctuations before bifurcating to hyperchaos. This hyperchaos source is valuable for developing long-reach secure optical communication links and remote chaotic Lidar systems, taking advantage of the high-transmission windows of the atmosphere in the mid-infrared regime.

14.
Amino Acids ; 54(1): 137-146, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34800175

RESUMO

Amino acids are one of the main metabolites in the body, and provide energy for the body and brain. The purpose of this study is to provide a profile of amino acid changes in the serum of patients with Moyamoya disease (MMD) and identify potential disease biomarkers. In this paper, we quantitatively determined the serum amino acid metabolic profiles of 43 MMD patients and 42 healthy controls (HCs). T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis were used to identify candidate markers. Thirty-nine amino acids were quantified, and 12 amino acid levels differed significantly between the MMD patients and HCs. Moreover, based on ROC curve analysis, four amino acid (L-methionine, L-glutamic acid, ß-alanine and o-phosphoserine) biomarkers showed high sensitivity and specificity (AUC > 0.90), and showed the best sensitivity and specificity in MetaboAnalyst 5.0 using binary logistic regression analysis. We have provided serum amino acid metabolic profiles of MMD patients, and identified four potential biomarkers which may both provide clinicians with an objective diagnostic method for early detection of MMD and further our understanding of MMD pathogenesis.


Assuntos
Doença de Moyamoya , Aminoácidos/metabolismo , Biomarcadores , Humanos , Metaboloma , Metabolômica/métodos , Curva ROC
15.
Rev Cardiovasc Med ; 22(3): 769-777, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565075

RESUMO

The renin-angiotensin system (RAS) helps to regulate cardiovascular function, the maintenance of electrolyte and fluid balance, and blood pressure. The RAS contains two axes; the angiotensin-converting enzyme/angiotensin II/Ang II type 1 receptors (ACE/Ang II/AT1) classic axis, which has a role in regulating blood pressure, vascular oxidative stress, coagulation, and cellular proliferation. The other is the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptors (ACE2/Ang-(1-7)/Mas) axis, which can inhibit the former axis, improve fat metabolism, reduce inflammation and oxidative stress, and enhance glucose tolerance and insulin sensitivity. The ACE2/Ang-(1-7)/Mas axis is found in blood vessels, kidneys, liver, pancreas and the brain. It can protect the body from abnormalities in glucose metabolism. The ACE2/Ang-(1-7)/Mas axis can enhance glucose tolerance and improve insulin sensitivity by protecting pancreatic ß cells, increasing insulin secretion, improving glucose metabolism in adipose tissue, enhancing glucose uptake by skeletal muscle, and inhibiting hepatic gluconeogenesis. This article reviews the main characteristics and functions of the ACE2/Ang-(1-7)/Mas axis and its regulation of glucose metabolism in order to demonstrate its potential as a target for the treatment of metabolic diseases such as diabetes.


Assuntos
Angiotensina I , Enzima de Conversão de Angiotensina 2 , Glucose , Humanos , Fragmentos de Peptídeos
16.
J Inflamm Res ; 14: 2941-2953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239317

RESUMO

PURPOSE: Inflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment. METHODS: Male Sprague-Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups. RESULTS: Our results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis). CONCLUSION: Using GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.

17.
Chem Commun (Camb) ; 57(48): 5985, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34095918

RESUMO

Retraction of 'Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis' by Shi-Yuan Zhao et al., Chem. Commun., 2020, 56, 14067-14070, DOI: 10.1039/D0CC05573E.

18.
Environ Pollut ; 287: 117591, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34153608

RESUMO

Acrylamide (ACR) is a widely used environmentally hazardous compound that is known to be neurotoxic, genotoxic, carcinogenic, and reproductive toxicity. It is widely present in soil, water, agents used in chemical industries, and food. It can be distributed to all organs and tissues, and can cause damage to various human systems and those of other animals. Previous metabolomics studies have mainly focused on metabolites in serum and urine, but have lacked comprehensive analysis of major organs and tissues. In the current study, a gas chromatography-massspectrometry method was used to investigate mechanisms underlying organ toxicity, in an effort to identify potentially sensitive biomarkers in the main target tissues of rats after ACR exposure. Male Sprague-Dawley rats were assigned to two groups; a control group and a group treated with 20 mg kg-1 ACR intragastrically for 6 weeks. Metabolite changes in the two groups were statistically analyzed. The respective numbers of altered metabolites in the hippocampus, cortex, kidney, serum, heart, liver, and kidney fat were 21, 21, 17, 5, 15, 14, and 6. There were 14 metabolic pathways related to amino acid, fatty acid, purine, and energy metabolism, revealing that the toxic mechanism of ACR may involve oxidative stress, inflammation, and amino acid metabolism and energy disorders.


Assuntos
Acrilamida , Metabolômica , Acrilamida/toxicidade , Animais , Biomarcadores , Masculino , Metaboloma , Ratos , Ratos Sprague-Dawley
19.
Chem Commun (Camb) ; 56(90): 14067-14070, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33104149

RESUMO

Phosphatidylinositol mannosides (PIMs) have been investigated as lipidic antigens for a new subunit tuberculosis vaccine. A non-natural diacylated phosphatidylinositol mannoside (Ac2PIM2) was designed and synthesized by mimicking the natural PIM6 processing procedure in dentritic cells. This synthetic Ac2PIM2 was achieved from α-methyl d-glucopyranoside 1 in 17 steps in 2.5% overall yield. A key feature of the strategy was extending the use of the chiral myo-inositol building block A to the O-2 and O-6 positions of the inositol unit to allow for introducing the mannose building blocks B1 and B2, and to the O-1 position for the phosphoglycerol building block C. Building block A, being a flexible core unit, may facilitate future access to other higher-order PIM analogues. A preliminary antigenic study showed that the synthetic PIM epitope (Ac2PIM2) was significantly more active than natural Ac2PIM2, which indicated that the synthetic Ac2PIM2 can be strongly immunoactive and may be developed as a potential vaccine.


Assuntos
Antígenos/imunologia , Epitopos/imunologia , Mycobacterium tuberculosis/imunologia , Fosfatidilinositóis/imunologia , Reações Antígeno-Anticorpo , Antígenos/química , Configuração de Carboidratos , Epitopos/química , Mycobacterium tuberculosis/química , Fosfatidilinositóis/síntese química , Fosfatidilinositóis/química
20.
Bioorg Chem ; 104: 104262, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32919135

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease, while there is still no medicine available. Farnesoid X receptor (FXR) is considered as a potential target for the treatment of NAFLD, and there are several FXR agonists reached in clinical trials. Based on better safety, industry and academia are pursuing development of the partial FXR agonists. To extend the chemical space of existing partial FXR agonists, we performed a structure-activity relationship study based on previously reported partial agonist 1 by using bioisosteric strategy. All of these efforts resulted in the identification of novel partial FXR agonist 13, which revealed the best agonistic activity in this series. Notably, compound 13 significantly alleviated the hepatic steatosis and hepatic function index in methionine-choline deficient (MCD) induced db/db mice, a classical nonalcoholic steatohepatitis (NASH) model widely used in preclinical evaluation. These results suggested that partial FXR agonist 13 might be a promising lead compound worthy further researches.


Assuntos
Ácido Benzoico/farmacologia , Desenho de Fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Ácido Benzoico/síntese química , Ácido Benzoico/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Camundongos , Estrutura Molecular , Hepatopatia Gordurosa não Alcoólica/patologia , Relação Estrutura-Atividade
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