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1.
Environ Sci Technol ; 57(11): 4481-4491, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36881938

RESUMO

The effects of sex and pregnancy on the bioaccumulation and tissue distribution of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in Chinese water snakes were investigated. The bioaccumulation factor of PFASs showed a positive correlation with their protein-water partition coefficients (log KPW), and steric hindrance effects were observed when the molecular volume was > 357 Å3. PFAS levels in females were significantly lower than those in males. The chemical composition of pregnant females was significantly different from that of non-pregnant females and males. The maternal transfer efficiencies of perfluorooctane sulfonic acid were higher than those of other PFASs, and a positive correlation between the maternal transfer potential and log KPW was observed for other PFASs. Tissues with high phospholipid content exhibited higher concentrations of ∑PFASs. Numerous physiological changes occurred in maternal organ systems during pregnancy, leading to the re-distribution of chemicals among different tissues. The change in tissue distribution of PFASs that are easily and not-so-easily maternally transferred was in the opposite direction. The extent of compound transfer from the liver to the egg determined tissue re-distribution during pregnancy.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Feminino , Gravidez , Humanos , Bioacumulação , Distribuição Tecidual , Poluentes Químicos da Água/análise , Água , Fluorocarbonos/análise , China
2.
Molecules ; 28(1)2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36615351

RESUMO

Natural products (NPs) have historically played a primary role in the discovery of small-molecule drugs. However, due to the advent of other methodologies and the drawbacks of NPs, the pharmaceutical industry has largely declined in interest regarding the screening of new drugs from NPs since 2000. There are many technical bottlenecks to quickly obtaining new bioactive NPs on a large scale, which has made NP-based drug discovery very time-consuming, and the first thorny problem faced by researchers is how to dereplicate NPs from crude extracts. Remarkably, with the rapid development of omics, analytical instrumentation, and artificial intelligence technology, in 2012, an efficient approach, known as tandem mass spectrometry (MS/MS)-based molecular networking (MN) analysis, was developed to avoid the rediscovery of known compounds from the complex natural mixtures. Then, in the past decade, based on the classical MN (CLMN), feature-based MN (FBMN), ion identity MN (IIMN), building blocks-based molecular network (BBMN), substructure-based MN (MS2LDA), and bioactivity-based MN (BMN) methods have been presented. In this paper, we review the basic principles, general workflow, and application examples of the methods mentioned above, to further the research and applications of these methods.


Assuntos
Produtos Biológicos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Produtos Biológicos/química , Inteligência Artificial , Extratos Vegetais/química , Descoberta de Drogas/métodos
3.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5481-5487, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471963

RESUMO

The present study aimed to explore the regulatory targets and anti-inflammatory mechanism of Jingfang Mixture based on network pharmacology and animal tests. The active ingredients of Jingfang Mixture and the corresponding targets were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Inflammation-related targets were searched from GeneCards and DisGeNET, and the targets of active ingredients of Jingfang Mixture against inflammation were obtained. The protein-protein interaction(PPI) network was analyzed by STRING and plotted. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out based on DAVID. The results of network pharmacology showed 159 active ingredients and 276 targets of Jingfang Mixture and 664 inflammation-related targets were screened out, and 90 targets of active ingredients of Jingfang Mixture against inflammation were obtained. As revealed by the PPI network, protein kinase B1(AKT1), caspase-3(CASP3), interleukin-1ß(IL1 B), prostaglandin-endoperoxide synthase 2(PTGS2), and tumor necrosis factor(TNF) might be the key proteins for the anti-inflammatory effect of Jingfang Mixture. KEGG enrichment analysis demonstrated the pathways involved TNF, nuclear factor-kappa B(NF-κB), and mitogen-activated protein kinase(MAPK). The anti-inflammatory effect of Jingfang Mixture was explored through the mouse model of urticaria. The results indicated that Jingfang Mixture could down-regulate the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases(ERK1/2), and NF-κB. The present study revealed the anti-inflammatory effect of Jingfang Mixture with multi-component and multi-target characteristics, which is expected to provide a scientific basis and important support for further research, development, and application.


Assuntos
Anti-Inflamatórios , Medicamentos de Ervas Chinesas , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , NF-kappa B/genética
4.
Invest New Drugs ; 39(1): 66-76, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32794135

RESUMO

The use of small interfering RNA (siRNA) in melanoma treatment remains limited owing to its biological properties. Herein, we developed a carrier system containing hyaluronic acid and protamine for siRNA delivery. Considering zeta potential and particle size as standards, the ratio of each component in liposome nanoparticles prepared was screened using the control variable method, and siRNA cationic liposome nanoparticles were prepared based on the optimal results obtained. The encapsulation rate of the cationic liposome nanoparticles was measured, and particle morphology was observed. B16F10 cells were treated with the nanoparticles; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell scratch experiments, and cell uptake experiments were performed to determine the effectiveness of the loaded siRNA. A mouse model was then established, and tumour tissues were subjected to haematoxylin-eosin staining. The inhibition of the survivin gene and protein expression were assessed using reverse transcription-polymerase chain reaction and western blotting, respectively. The results showed that the optimal mass ratio of hyaluronic acid (HA)-siRNA-to-protamine was 1.0; in the HA-siRNA-protamine complex containing 25 µg siRNA, the addition of 50 µL liposomes yielded optimal particles. And encapsulation rate was 85.07%. The nanoparticles demonstrated a significant inhibitory effect against melanoma cells; siRNA liposomes may inhibit tumour growth by down-regulating survivin. Survivin-siRNA cationic liposome nanoparticles could effectively inhibit the proliferation and migration of melanoma B16F10 cells in vitro and the proliferation of subcutaneous melanoma B16F10 cells, probably by inhibiting survivin mRNA and protein expression. Graphical abstract.


Assuntos
Ácido Hialurônico/química , Melanoma/patologia , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Estabilidade de Medicamentos , Feminino , Lipossomos/química , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Distribuição Aleatória , Propriedades de Superfície , Survivina/efeitos dos fármacos
5.
Pharmazie ; 76(8): 351-358, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34412733

RESUMO

Background: 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) from Polygonum multijiorum Thunb. (PMT), is a major bioactive component. This review is aimed to summarize the present development of TSG regarding pharmaceutics, pharmacology and toxicology, with a focus on the novel mechanism of drug-induced toxicity and provides insight for its potential developments and applications in the future on traditional Chinese medicine. Methods: Studies about TSG's activities and toxicity were searched and summarized. Targets and mechanisms were predicted and analyzed with network pharmacology methods. Affinities and binding modes of key targets with TSG were verified by AutoDock Vina software. Results: TSG plays an essential role among the chemical components of PMT because of multiple pharmacological activities, which suggests a potential application of TSG for a variety of diseases, like atherosclerosis, Alzheimer's disease, Parkinson's disease, cerebral I/R injury, diabetes, osteoporosis, colitis. However, mild liver toxicity of TSG is also pointed out. Conclusions: As a biologically active natural product in PMT, TSG has shown prospective pharmacological activities, particularly as an agent for cardiovascular protection and neuroprotection.


Assuntos
Biologia Computacional , Estilbenos , Glucosídeos/toxicidade , Estudos Prospectivos , Estilbenos/toxicidade
6.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3087-3090, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467699

RESUMO

Endometriosis(EMs) is a stubborn gynecological disease caused by persistent immune-inflammatory effects, and is known as "benign tumor" because of its similar characteristics to malignant tumors. National physician master Professor BAN Xiu-wen believes that the spread of damp-evil is the pathologic foundation for inflammatory response of ectopic endometrium; accumulation of blood stasis is the pathological product of continuous inflammatory attacks, and the combination of dampness and stasis is the main pathogenesis for refractory EMs. Modern researches have shown that immune-inflammatory effect is the key mechanism for development of EMs, and is closely related to cell autophagy, all of which have made it become the hot spots in research of the pathogenesis, diagnosis and treatment of EMs. Therefore, with immune-inflammatory effect as the breakthrough point in this research, and with reference to the related research of autophagy, the correlation between "combination of dampness and stasis" and abnormal autophagy-induced immune inflammatory response in ectopic endometrium was discussed, to provide guidance for the clinical application of traditional Chinese medicine and modern research.


Assuntos
Endometriose , Autofagia , Endométrio , Feminino , Humanos , Medicina Tradicional Chinesa
7.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1139-43, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26226760

RESUMO

OBJECTIVE: To study the anti-immune inflammation efficacy and toxicity of Tripterygium wilfordii decoction, in order to provide experimental basis for studies on its "efficacy-toxicity" correlation. METHOD: The delayed hypersensitivity model was established by dinitrofluorobenzene in mice. Different doses of T. wilfordii decoction was administered for 5 consecutive days. The ear swelling inhibition ratio and the toxic action were observed. After the final administration, the biochemical indexes of PGE2, TNF-α, IL-2, ALT, AST, PA, TBA, TBIL in serum were detected, and the visceral indexes of heart, liver, spleen and kidney were measured. RESULT: The DNFB-induced ear swelling could be notably inhibited by multiple oral administration of T. wilfordii decoction, with the ED50 and its 95% confidence limit of 0.34 (0.21-0.42) g x kg(-1). The contents of PGE2, TNF-α, IL-2 in serum decreased in a dose-dependent manner. The activities of serum AST, ALT, TBA, TBIL and the PA content reduced. CONCLUSION: T. wilfordii decoction shows a significant anti-immune inflammation efficacy within the dosage range between 0.59 and 2.34 g x kg(-1) in a dose-dependent manner. With a certain hepatotoxicity, high dose (2.34-4.68 g x kg(-1)) of T. wilfordii decoction can cause substantial liver injury, with a dose dependence in liver function index. Therefore, the efficacy and toxicity of T. wilfordii is dose dependent, which provides reference for preventing adverse drug reactions in clinic and developing early-warning schemes and ensure the clinical medication safety of T. wilfordii.


Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Edema/tratamento farmacológico , Tripterygium/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Cálculos da Dosagem de Medicamento , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Edema/genética , Edema/imunologia , Humanos , Interleucina-2/genética , Interleucina-2/imunologia , Masculino , Camundongos , Tripterygium/toxicidade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
8.
Zhongguo Zhong Yao Za Zhi ; 40(5): 927-32, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26087558

RESUMO

OBJECTIVE: To study the effect of single administration of aqueous extracts from aconite on "dose-toxicity" relationship and "time-toxicity" relationship of mice hearts, through changes in electrocardiogram (ECG) and serum biochemical indexes. METHOD: Mice were grouped according to different drug doses and time points, and orally administered with water extracts from aconite for once to observe the changes of mice ECG before and after the administration, calculate visceral indexes heart, liver and kidney, and detect levels of CK, LDH, BNP and CTn-I in serum. RESULT: According to the "time-toxicity" relationship study, at 5 min after oral administration with aqueous extracts from aconite in mice, the heart rate of mice began rising, reached peak at 60 min and then slowly reduced; QRS, R amplitude, T duration and amplitude and QT interval declined at 5 min, reduced to the bottom at 60 min and then gradually elevated. The levels of CK, LDH, BNP and CTn-I in serum elevated at 5 min and reached the peak at 60 min, with no significant change in ratios of organs to body at different time points. On the basis of the "dose-toxicity" relationship, with the increase in single dose of aqueous extracts from aconite, the heart rate of mice. QRS, T duration and amplitude and QT interval declined gradually, and levels of CK, LDH, BNP and CTn-I in serum slowly elevated, with a certain dose dependence and no significant change in ratios of organs to body in mice. CONCLUSION: Single oral administration of different doses of aqueous extracts from aconite could cause different degrees of heart injury at different time points, with a certain dose dependence. Its peak time of toxicity is at 60 min after the administration of aqueous extracts from aconite.


Assuntos
Aconitum/química , Medicamentos de Ervas Chinesas/toxicidade , Coração/efeitos dos fármacos , Aconitum/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Coração/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos
9.
Zhongguo Zhong Yao Za Zhi ; 40(14): 2760-4, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26666023

RESUMO

Models of throat excess-heat mice were established and different dosages of water extract of STRR were ig given to mice to observe anti-inflammatory effect and its mechanism. The activities of ALT, AST and the contents of TNF-α, T3, rT3, T4, SOD, MDA, PEG2, NO, NOS, Cr, BUN, GSH and GSH-Px in serum were tested while liver index, kidney index, spleen index and thymus index were measured. The anti-inflammatory efficacy accompanied by side effects and mechanisms of water extract of Sophorae Tonkinensis Radix et Rhizoma (STRR) in excess-heat mice were investigated to clear safety dose-dependence range and the relationship of efficacy, toxicity and syndrome. In the experiment, water extract of STRR showed a strong inhibitory effect on ear edema by croton oil in throat excess-heat mice. The activities of ALT, AST in serum and liver index were all higher than that of normal group after multiple administration. PEG2, SOD, MDA, NO, NOS, GSH and GSH-Px had obvious changes. According to the results, water extract of STRR has an anti-inflammatory effect on acute inflammation in throat excess-heat mice and it is stronger than that in normal mice. The anti-inflammatory effect of STRR is related to the reduction of inflammatory mediators release. Side effects and hepatotoxicity will be produced on clinical efficacy dosage. The mechanisms of anti-inflammation and hepatotoxicity are all in connection with oxidative damnification.


Assuntos
Anti-Inflamatórios/uso terapêutico , Medicina Tradicional Chinesa , Fitoterapia , Extratos Vegetais/uso terapêutico , Rizoma , Sophora , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Extratos Vegetais/toxicidade
10.
Pak J Med Sci ; 30(3): 519-24, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24948971

RESUMO

OBJECTIVE: To preliminarily explore the association of rs12979860 and rs8099917 SNPs with chronic HCV infection in Chinese Han children. METHODS: Chronic HCV infection patients (n=277; 1-17 years old, 4.5 years old in average) and healthy subjects (n=150, children; 2-17 years old, 5.2 years old in average) were recruited and tested by PCR combining direct sequencing. The differences between the rs12979860 and rs8099917 genotypes in patients and healthy subjects were compared. RESULTS: The genetic variations at rs12979860 and rs8099917 in chronic hepatitis C (CHC) children and healthy subjects did not differ significantly. The frequency of spontaneous clearance in CHC children was higher (47%), which is related to the genetic variations. The histological changes of patients were more significant compared to their clinical and biochemical indices, but they did not correlate with the genetic mutations at rs12979860 and rs8099917 significantly. CONCLUSION: The rs12979860 and rs8099917 SNPs are independent factors predicting the spontaneous clearance of Chinese CHC children patients. The correlation between diseases outcomes are in need of further study.

11.
Pigment Cell Melanoma Res ; 37(2): 247-258, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37777339

RESUMO

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch-like ECH-associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1-Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1-Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.


Assuntos
Melanoma , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Melanoma/terapia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
12.
Immunol Res ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096420

RESUMO

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a significant modulator of inflammation in various clinical contexts, including infection, cellular stress, and tissue injury. The extensive participation of the cGAS-STING pathway can be attributed to its ability to detect and control the cellular reaction to DNAs originating from both microorganisms and hosts. These DNAs are well recognized as molecules linked with potential risks. At physiological levels, the STING signaling system exhibits protective effects. However, prolonged stimulation of this pathway contributes to autoimmune disorder pathogenesis. The present paper provides an overview of the activation mechanism of the cGAS-STING signaling pathways and their associated significant functions, as well as therapeutic interventions in the context of systemic lupus erythematosus (SLE). The primary objective is to enhance our comprehension of SLE and facilitate more effective diagnosis and treatment strategies for this condition.

13.
Acta Histochem ; 126(1): 152118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039796

RESUMO

BACKGROUND: Dysregulated inflammation and osteoblast differentiation are implicated in osteoporosis. Exploring the activity of catalpol in inflammation and osteoblast differentiation deepens the understanding of osteoporosis pathogenesis. METHODS: LPS was used to treated hFOB1.19 cells to induce inflammation and repress osteoblast differentiation. FOB1.19 cells were induced in osteoblast differentiation medium and treated with LPS and catalpol. Cell viability was assessed using CCK-8. ALP and Alizarin red S staining were conducted for analyzing osteoblast differentiation. The levels of IL-1ß, TNF-α and IL-6 were examined by ELISA. The methylation of TRAF6 promoter was examined through MS-PCR. The binding of miR-124-3p to DNMT3b and DNMT3b to TRAF6 promoter was determined with dual luciferase reporter and ChIP assays. RESULTS: LPS enhanced secretion of inflammatory cytokines and suppressed osteoblast differentiation. MiR-124-3p and TRAF6 were upregulated and DNMT3b was downregulated in LPS-induced hFOB1.19 cells. Catalpol protected hFOB1.19 cells against LPS via inhibiting inflammation and promoting osteoblast differentiation. MiR-124-3p targeted DNMT3b, and its overexpression abrogated catalpol-mediated protection in LPS-treated hFOB1.19 cells. In addition, DNMT3b methylated TRAF6 promoter to restrain its expression. Catalpol exerted protective effects through suppression of the miR-124-3p/DNMT3b/TRAF6 axis in hFOB1.19 cells. CONCLUSION: Catalpol antagonizes LPS-mediated inflammation and suppressive osteoblast differentiation via controlling the miR-124-3p/DNMT3b/TRAF6 axis.


Assuntos
Glucosídeos Iridoides , MicroRNAs , Osteoporose , Humanos , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Osteoblastos
14.
Chemosphere ; 359: 142353, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761828

RESUMO

Microorganisms in the waterline zone can secrete pigments to avoid damage caused by ultraviolet radiation, some of which have corrosive effects. In this work, we found that the secretion of pyomelanin by P3 strain of Pseudoalteromonas lipolytica significantly increases under strong lighting conditions, accelerating the corrosion of the material. Molecular mechanisms indicate that strong light, as a stressful environmental factor, enhances the expression of melanin secretion-related genes to prevent bacteria from being damaged by ultraviolet radiation. Therefore, this work proposes a new corrosion mechanism in the waterline zone, pigment-producing microorganisms are also involved in the waterline corrosion process.


Assuntos
Ligas , Melaninas , Aço , Corrosão , Aço/química , Melaninas/metabolismo , Ligas/química , Pseudoalteromonas/metabolismo , Raios Ultravioleta , Luz
15.
Lipids ; 59(4): 101-109, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38741514

RESUMO

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.


Assuntos
HDL-Colesterol , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Insuficiência Renal Crônica/sangue , Estudos Transversais , HDL-Colesterol/sangue , Lipídeos/sangue , Triglicerídeos/sangue , Taxa de Filtração Glomerular , Dislipidemias/sangue , Colesterol/sangue
16.
Explore (NY) ; 20(5): 102992, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503613

RESUMO

OBJECTIVE: The aim of this study is to comprehensively evaluate both the efficacy and safety profile of integrating the Tongxin formula with optimal medical therapy (OMT) for patients experiencing acute coronary syndromes subsequent to coronary stenting, over the course of one year. METHODS: We enrolled 150 patients diagnosed with acute coronary syndromes who had received stent placement within one month and exhibited a TCM syndrome characterized by Qi deficiency and blood stasis. This group comprised patients with unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. The participants were divided equally, allocating 75 to the Tongxin formula group and 75 to a placebo-controlled group. After undergoing percutaneous coronary intervention (PCI) surgery, both groups received conventional Western medical care, including dual antiplatelet therapy and lipid-lowering medications. The placebo-controlled group received a placebo, while the Tongxin formula group were administered Tongxin formula granules orally. Both study cohorts were monitored for a duration of 6 months. The primary endpoints included the occurrence of major adverse cardiovascular events and the rate of lumen diameter reduction post-treatment in both groups, with the Seattle Angina Scale serving as a secondary assessment tool. Safety evaluations encompassed the measurement of liver and kidney function, coagulation parameters, and other relevant indicators. RESULTS: The rate of adverse cardiovascular events in the placebo-controlled group was 42.46 % within a year of surgery, whereas it was 16.90 % in the Tongxin formula group (P < 0.05). Comparing the Tongxin formula group to the placebo-controlled group, there was a decrease in the frequency of unstable angina and readmission due to cardiovascular events (P < 0.05). Coronary angiography performed 6 months after surgery revealed that the Tongxin formula group had considerably less lumen loss than the placebo-controlled group in a number of segments, including the entire segment, within the stent, at the proximal end, and at the distal end (P < 0.05). Six months after surgery, the Seattle angina score was higher in the Tongxin formula group than in the placebo-controlled group (P < 0.05). There were no significant changes in indicators such as liver and renal function as well as coagulation indexes in both groups within the first 12 months after surgery (P > 0.05). CONCLUSION: Tongxin formula has been shown to lower the occurrence of major adverse cardiovascular events, minimize narrowing of blood vessel lumen, enhance clinical symptoms, and enhance the quality of life of patients following PCI surgery, all while maintaining a good safety profile.

17.
J Org Chem ; 78(22): 11444-9, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24131444

RESUMO

Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.


Assuntos
Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Estrutura Molecular , Estereoisomerismo
18.
Chem Biol Drug Des ; 101(4): 873-882, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36527176

RESUMO

Previous study has shown that icaritin (ICT) has meaningful protective effect on cerebral ischemic stroke, and this study aimed to investigate its mechanism from the aspect of protecting astrocytes from oxidative stress. Murine primary astrocytes were pretreated by ICT and exposed to H2 O2 to induce oxidative stress. The results indicated that ICT inhibited H2 O2 -induced astrocytes apoptosis, decreased Bax and cleaved caspase-3, and increased Bcl-2. In addition, ICT inhibited H2 O2 -induced oxidative stress, increased mitochondrial membrane potential (ΔΨm ), and maintained mitochondrial morphology. ICT decreased the synthesis of malondialdehyde and increased the activity of glutathione peroxidase, catalase, and superoxide dismutase. Moreover, ICT suppressed the transient and resting intracellular Ca2+ overload. Further investigation revealed that ICT could target the combination with Orai1 to block store-operated calcium channel induced by H2 O2 . However, ICT did not enhance the protective effect of RO2959, a selective blocker of Orai1. These results indicate that ICT can play a neuroprotective role against oxidative stress injury by binding to Orai1 to block SOCC.


Assuntos
Astrócitos , Canais de Cálcio , Camundongos , Animais , Canais de Cálcio/metabolismo , Astrócitos/metabolismo , Estresse Oxidativo , Flavonoides/farmacologia , Cálcio/metabolismo , Proteína ORAI1/metabolismo , Proteína ORAI1/farmacologia
19.
Ultrasound Med Biol ; 49(2): 569-577, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36369213

RESUMO

The aim of this prospective study was to compare the diagnostic accuracy of oral contrast-enhanced transabdominal ultrasound imaging (OCTU) with that of contrast-enhanced computed tomography (CT) for the pre-operative tumor staging of gastric cancer, with post-operative pathology as the standard. We included 108 cases of gastric cancer with simultaneous OCTU and enhanced CT pre-operative tumor staging diagnoses. Results were compared with post-operative pathology based on the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging guidelines for gastric cancer. The accuracy of each tumor stage was obtained by comparing OCTU and enhanced CT diagnoses with post-operative pathology. The McNemar test was used to compare the overall accuracy of the two methods. There was no statistical difference in accuracy between OCTU (72.2%) and enhanced CT (75.9%, p = 0.644) for overall pre-operative tumor staging diagnosis. For stages T1 to T4, the accuracy rates of OCTU were 84.2%, 81.8%, 69.4% and 65.5%, respectively, and those for enhanced CT were 52.6%, 72.7%, 87.8% and 72.4%, respectively. OCTU is comparable to enhanced CT in the preoperative overall T-stage diagnosis of gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Estadiamento de Neoplasias , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia
20.
Plants (Basel) ; 12(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37765363

RESUMO

Trisomy harbouring an extra copy of the chromosome generally causes a variety of physical and intellectual disabilities in mammals but is an extremely rare and important genetic stock in plants. In this study, a spontaneous trisomy plant in a Chinese kale accession (Brassica oleracea var. alboglabra, CC, 2n = 18) that showed significantly smaller plant architecture when compared to other normal plants was found and subsequently confirmed by cytological analysis in which the chromosome set of 2n = 19 and abnormal chromosome behaviour were observed. Then, based on the gene expression deviation determined by RNA-seq, the extra chromosome copy in this trisomy was identified as chromosome C2 (TC2). Compared to normal plants, TC2 not only showed generally upregulated differentially expressed genes (DEGs) on chromosome C2 (97.21% of 573 DEGs in chromosome C2) but also exhibited a whole-genome expression perturbation, in which 1329 DEGs (69.87% of total DEGs) were observed along two-copy chromosomes (trans-effect). The genes in the high (gene expression value > 100) and medium (100 > gene expression value > 10) groups were more prone to decreased gene expression, but the genes in the low group (10 > gene expression value > 0.1) showed upregulated expression deviation. In addition, GO (Gene ontology) annotation analysis revealed that the upregulated DEGs in the trans-effect group were overrepresented by the genes involved in the response to stress category, while the downregulated DEGs in the trans-effect group were mostly enriched in pathways related to DNA synthesis. In conclusion, we think our results can provide important resources for genetic analysis in B. oleracea and show some novel insights for understanding trisomy plant biology.

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