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1.
J Am Chem Soc ; 146(20): 13894-13902, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38728606

RESUMO

Despite the fascinating developments in design and synthesis of artificial molecular machines operating at the nanoscales, translating molecular motion along multiple length scales and inducing mechanical motion of a three-dimensional macroscopic entity remains an important challenge. The key to addressing this amplification of motion relies on the effective organization of molecular machines in a well-defined environment. By taking advantage of long-range orientational order and hierarchical structures of liquid crystals and unidirectional rotation of light-driven molecular motors, we report here photoresponsive biomimetic functions of liquid crystal elastomers (LCEs) by the repetitive unidirectional rotation of molecular motors using 3D printing. Molecular motors were built in the main chain of liquid crystals oligomers to serve as photoactuators. The oligomers were then used as the ink, and liquid crystal elastomers with different morphologies were printed. The obtained LCEs are able to conduct multiple types of motions including bending, helical coiling, closing of petals, and flipping of wings of a butterfly upon UV illumination, which paves the way for future design of responsive materials with enhanced complex actuating functions.

2.
Metabolomics ; 19(2): 6, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645548

RESUMO

INTRODUCTION: Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated. OBJECTIVES: Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3). METHODS: Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting. RESULTS: Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect. CONCLUSIONS: All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.


Assuntos
Bufanolídeos , Neoplasias da Próstata , Masculino , Humanos , Células PC-3 , Hidrólise , Multiômica , Metabolômica , Fosfolipídeos/metabolismo , Neoplasias da Próstata/metabolismo
3.
Anal Bioanal Chem ; 414(17): 4999-5007, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35639139

RESUMO

Uncaria species (Rubiaceae) are used as traditional Chinese medicines (TCMs) to treat central nervous system (CNS) diseases, and monoterpene indole alkaloids are the main bioactive constituents. Localization and quantification of CNS drugs in fine brain regions are important to provide insights into their pharmacodynamics, for which quantitative mass spectrometry imaging (MSI) has emerged as a powerful technique. A systematic study of the quantitative imaging of seven Uncaria alkaloids in rat brains using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was presented. The distribution of the alkaloids in thirteen brain regions was quantified successfully using the calibration curves generated by a modified on-tissue approach. The distribution trend of different Uncaria alkaloids in the rat brain was listed as monoterpene indole alkaloids > monoterpene oxindole alkaloids, R-configuration epimers > S-configuration epimers. Particularly, Uncaria alkaloids were detected directly in the pineal gland for the first time and their enrichment phenomenon in this region had an instructive significance in future pharmacodynamic studies.


Assuntos
Alcaloides , Produtos Biológicos , Uncaria , Alcaloides/química , Animais , Encéfalo , Alcaloides Indólicos , Monoterpenos , Ratos , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
Int J Mol Sci ; 21(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143538

RESUMO

Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein-protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids' anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer's disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.


Assuntos
Alcaloides/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Hipertensão/tratamento farmacológico , Uncaria/química , Algoritmos , Butirilcolinesterase/metabolismo , Química Farmacêutica/métodos , Biologia Computacional , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Software
5.
Biomed Chromatogr ; 33(2): e4385, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30242797

RESUMO

Salvia miltiorrhiza, one of the most well-known herbal medicines, is commonly used for the treatment of coronary heart diseases in China. Besides traditional decoction slices (TDS), another relatively new product of S. miltiorrhiza, ultrafine granular powder (UGP; D90 < 45 µm), is also increasingly being used. In this paper, a UHPLC-LTQ-Orbitrap MS technique was developed for a metabolite profile study after oral administration of UGP and TDS of S. miltiorrhiza. The results showed that the number of in vivo absorbed compounds from UGP was much greater than that from TDS, and different types of products from S. miltiorrhiza will have different metabolic processes in vivo. Furthermore, a UHPLC-Q-Trap MS/MS method for simultaneously determining four tanshinones (tanshinone IIA, dihydrotanshinone I, tanshinone I and cryptotanshinone) was established and applied to assess the pharmacokinetics of the two types of products. All of the analytes displayed significant higher area under the concentration-time curve and peak concentration after oral administration of UGP than after TDS, indicating that ultrafine powder product could improve the bioavailability and absorption of cryptotanshinon,tanshinone II A,dihydrotanshinonE I and tanshinone I in vivo. The present study provides scientific information for further exploration of the pharmacology of these two types of S. miltiorrhiza and offers a reference for clinical administration of S. miltiorrhiza.


Assuntos
Abietanos/sangue , Abietanos/farmacocinética , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Salvia miltiorrhiza , Abietanos/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Modelos Lineares , Masculino , Espectrometria de Massas , Pós , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Molecules ; 23(12)2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30544925

RESUMO

By investigating of the roots of Salvia miltiorrhiza, which is one of the most widely used Chinese herbs, we used phytochemical methods successfully to obtain twelve depsides: four depsides (1⁻4) that were previously undescribed, along with eight known ones (5⁻12). Their structure characteristics were assessed by HR-ESIMS, CD, NMR (¹H, 13C, HSQC, HMBC) data analyses. These four newly isolated compounds (1⁻4), as well as the other eight compounds (5⁻12), show extraordinary protective effects on hydrogen peroxide-induced apoptosis in HS-SY5Y cells. Among them, depside 4 and depside 6 displayed more obviously protective effects than others.


Assuntos
Depsídeos/química , Depsídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Salvia miltiorrhiza/química , Linhagem Celular , Dicroísmo Circular , Depsídeos/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fármacos Neuroprotetores/química , Plantas Medicinais/química
7.
Molecules ; 23(11)2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30463184

RESUMO

The mass spectrometry (MS) has been widely used for profiling chemical components of traditional Chinese medicine (TCM). However, there are few studies reporting quality control of TCM based on mass spectrometry fingerprint (MSF) due to its complicated operation and high cost. The aim of this study was to extend the application of MSF for quality evaluation of TCM. In this study, an MSF based on single quadrupole mass spectrometry method was established, and was successfully used for the quality control of Venenum bufonis (VB), a famous TCM which was used clinically for cancer treatment in China. The results showed that the superiority of MSF for more chemical information exposure and the finding of more potential chemical markers (eight versus four) compared with the traditional photo-diode array (a kind of ultra violet detector, PDA). Besides, the performance of MSF was also validated by similarity and principle component analysis (PCA) of MS data acquired on two other mass spectrometry (low-resolution, triple quadrupole, QQQ, and high-resolution, quadruple time-of-flight, Q-TOF), showing high consistency with QQQ and Q-TOF, but robustness with few parameters' settings. Based on our study, MSF could be widely applied for the quality control of TCM.


Assuntos
Bufanolídeos/análise , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas/métodos , Análise de Componente Principal/métodos , Bufanolídeos/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Extratos Vegetais/análise , Extratos Vegetais/química , Controle de Qualidade
8.
Acta Pharmacol Sin ; 36(5): 597-605, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25891086

RESUMO

AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. METHODS: Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. RESULTS: The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. CONCLUSION: EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.


Assuntos
Camellia sinensis , Catequina/análogos & derivados , Hipoglicemiantes/farmacologia , Resistência à Insulina , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Catequina/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Insulina/sangue , Insulisina/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fitoterapia , Plantas Medicinais , Fatores de Tempo
9.
Int J Mol Sci ; 16(12): 29345-56, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26690140

RESUMO

Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.


Assuntos
Benzofuranos/toxicidade , Fármacos Cardiovasculares/toxicidade , Ginsenosídeos/toxicidade , Animais , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Feminino , Dose Letal Mediana , Masculino , Camundongos
10.
Light Sci Appl ; 13(1): 63, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429259

RESUMO

In the past two decades, the research and development of light-triggered molecular machines have mainly focused on developing molecular devices at the nanoscale. A key scientific issue in the field is how to amplify the controlled motion of molecules at the nanoscale along multiple length scales, such as the mesoscopic or the macroscopic scale, or in a more practical perspective, how to convert molecular motion into changes of properties of a macroscopic material. Light-driven molecular motors are able to perform repetitive unidirectional rotation upon irradiation, which offers unique opportunities for responsive macroscopic systems. With several reviews that focus on the design, synthesis and operation of the motors at the nanoscale, photo-responsive macroscopic materials based on light-driven molecular motors have not been comprehensively summarized. In the present review, we first discuss the strategy of confining absolute molecular rotation into relative rotation by grafting motors on surfaces. Secondly, examples of self-assemble motors in supramolecular polymers with high internal order are illustrated. Moreover, we will focus on building of motors in a covalently linked system such as polymeric gels and polymeric liquid crystals to generate complex responsive functions. Finally, a perspective toward future developments and opportunities is given. This review helps us getting a more and more clear picture and understanding on how complex movement can be programmed in light-responsive systems and how man-made adaptive materials can be invented, which can serve as an important guideline for further design of complex and advanced responsive materials.

11.
Sci Total Environ ; 946: 174275, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38936727

RESUMO

Schwertmannite (Sch) is found in environments abundant in iron and sulfate. Microorganisms that utilize iron or sulfate can induce the phase transition of Schwertmannite, consequently leading to the redistribution of coexisting pollutants. However, the impact of the molar ratio of sulfate to iron (S/Fe) on the microbial-mediated transformation of Schwertmannite and its implications for the fate of cadmium (Cd) have not been elucidated. In this study, we examined how S/Fe influenced mineral transformation and the fate of Cd during microbial reduction of Cd-loaded Schwertmannite by Desulfovibrio vulgaris. Our findings revealed that an increase in the S/Fe ratio facilitated sulfate-reducing bacteria (SRB) in mitigating the toxicity of Cd, thereby expediting the generation of sulfide (S(-II)) and subsequently triggering mineral phase transformation. As the S/Fe ratio increased, the predominant minerals in the system transitioned from prismatic-cluster vivianite to rose-shaped mackinawite. The Cd phase and distribution underwent corresponding alterations. Cd primarily existed in its oxidizable state, with its distribution being directly linked not only to FeS content but also showing a robust correlation with phosphorus. The coexistence of vivianite and FeS minerals proved to be more favorable for Cd immobilization. These findings have significant implications for understanding the biogeochemistry of iron (oxyhydr)oxides and Cd fate in anaerobic environments.


Assuntos
Cádmio , Sulfatos , Cádmio/metabolismo , Sulfatos/metabolismo , Compostos de Ferro/metabolismo , Desulfovibrio vulgaris/metabolismo , Oxirredução , Ferro/metabolismo , Biodegradação Ambiental , Sulfetos/metabolismo
12.
Int J Antimicrob Agents ; 63(2): 107073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141837

RESUMO

This quasi-experimental study aimed to investigate the changes in antibiotic use tailored by adjusting provincial antibiotic restriction lists in China using interrupted time-series analysis from 2013 to 2019. Antibiotic use was assessed as defined daily dose (DDD) per 1000 patients per day. Trends and level changes were analysed with segmented regression. The study identified 19 antibiotic formulations in four provinces with adjusted restriction levels (intervention group) and 110 formulations in the rest provinces without adjustments (comparison group). Antibiotics restriction level changed between two categories: (1) between 'highly-restricted' and 'restricted' and (2) between 'restricted' and 'non-restricted'. Analysis revealed distinct trend changes for antibiotics moving between 'highly-restricted' and 'restricted' (ß = 0.0211, P = 0.003) and 'restricted' to 'highly-restricted' (ß = -0.0039, P = 0.128) compared to the comparison group. After a 2-y adjustment period, when moving from 'restricted' to 'highly-restricted', absolute antibiotic utilisation significantly decreased (P < 0.001), with a relative decrease of 100.8% (P < 0.001) compared to the comparison group. Besides, individual antibiotics with higher consumption displayed greater responsiveness to adjustment. These findings underscore the changes in restriction level adjustments on antibiotics, highlighting antibiotic restriction list policies as crucial tools for antimicrobial stewardship.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Humanos , Antibacterianos/uso terapêutico , China , Análise de Séries Temporais Interrompida
13.
Int J Biol Macromol ; 262(Pt 2): 130084, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350584

RESUMO

Accidental bleeding is an unavoidable problem in daily life. To avoid the risk of excessive blood loss, it is urgent to design a functional material that can quickly stop bleeding. In this study, an efficient wound dressing for hemostasis was investigated. Based on the characteristics that Ca2+ and fish skin collagen (FSC) could activate the coagulation mechanism, hemostatic cotton was prepared by solvent replacement method using CaCl2, FSC, soluble starch (SS), and polyvinyl alcohol (PVA) as raw materials. The cytotoxicity test showed the Ca2+PVA/FSC-SS hemostatic cottons had good biocompatibility. The activated partial thromboplastin time (APTT) of Ca2+PVA/FSC-SS(4) was 35.34 s, which was 22.07 s faster than that of PVA/FSC-SS, indicating Ca2+PVA/FSC-SS mediated the endogenous coagulation system. In vitro coagulation test, Ca2+PVA/FSC-SS(4) could stop bleeding rapidly within 39.60 ± 5.16 s, and the ability of wound healing was higher than commercial product (Celox). This study developed a rapid procoagulant and hemostatic material, which had a promising application in a variety of environments.


Assuntos
Hemostáticos , Animais , Hemostáticos/farmacologia , Amido/farmacologia , Hemostasia , Coagulação Sanguínea , Colágeno , Álcool de Polivinil , Hemorragia , Etanol , Antibacterianos
14.
Pharmaceutics ; 15(5)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37242789

RESUMO

The poor bioavailability of curcumin and its derivatives limits their antitumor efficacy and clinical translation. Although curcumin derivative C210 has more potent antitumor activity than curcumin, it has a similar deficiency to curcumin. In order to improve its bioavailability and accordingly enhance its antitumor activity in vivo, we developed a redox-responsive lipidic prodrug nano-delivery system of C210. Briefly, we synthesized three conjugates of C210 and oleyl alcohol (OA) via different linkages containing single sulfur/disulfide/carbon bonds and prepared their nanoparticles using a nanoprecipitation method. The prodrugs required only a very small amount of DSPE-PEG2000 as a stabilizer to self-assemble in aqueous solution to form nanoparticles (NPs) with a high drug loading capacity (~50%). Among them, the prodrug (single sulfur bond) nanoparticles (C210-S-OA NPs) were the most sensitive to the intracellular redox level of cancer cells; therefore, they could rapidly release C210 in cancer cells and thus had the strongest cytotoxicity to cancer cells. Furthermore, C210-S-OA NPs exerted a dramatic improvement in its pharmacokinetic behavior; that is, the area under the curve (AUC), mean retention time and accumulation in tumor tissue were 10, 7 and 3 folds that of free C210, respectively. Thus, C210-S-OA NPs exhibited the strongest antitumor activity in vivo than C210 or other prodrug NPs in mouse models of breast cancer and liver cancer. The results demonstrated that the novel prodrug self-assembled redox-responsive nano-delivery platform was able to improve the bioavailability and antitumor activity of curcumin derivative C210, which provides a basis for further clinical applications of curcumin and its derivatives.

15.
Environ Pollut ; 328: 121592, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37044254

RESUMO

The widespread distribution of nanoplastics and dissolved organic matter (DOM) in sewage raises concerns about the potential impact of DOM on the bioavailability of nanoplastics. In this study, the effects of different sizes (100 nm and 350 nm) of polystyrene nanoplastics (PS-NPs, 50 mg/L) and combined with 10 mg/L or 50 mg/L DOMs (fulvic acid, humic acid and sodium alginate) on the growth and denitrification ability of Thiobacillus denitrificans were investigated. Results showed that 100 nm PS-NPs (50 mg/L) cause a longer delay in the nitrate reduction (3 days) of T. denitrificans than 350 nm PS-NPs (2 days). Furthermore, the presence of DOM exacerbated the adverse effect of 100 nm PS-NPs on denitrification, resulting in a delay of 1-4 days to complete denitrification. Fulvic acid (50 mg/L) and humic acid (50 mg/L) had the most significant adverse effect on increasing 100 nm PS-NPs (50 mg/L), causing a reduction of 20 mmol/L nitrate by T. denitrificans in nearly 7 days. It is noteworthy that the presence of DOM did not modify the adverse effect of 350 nm PS-NPs on denitrification. Further analysis of toxicity mechanism of PS-NPs revealed that they could induce reactive oxygen species (ROS) and suppressed denitrification gene expression. The results suggested that DOM may assist in the cellular internalization of PS-NPs by inhibiting PS-NPs aggregation, leading to the increased ROS levels and accelerated T. denitrificans death. This study highlights the potential risk of nanoplastics to autotrophic denitrifying bacteria in the presence of DOM and provides new insights for the treatment of nitrogen-containing wastewater by T. denitrificans.


Assuntos
Thiobacillus , Thiobacillus/metabolismo , Matéria Orgânica Dissolvida , Microplásticos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Nitratos/toxicidade , Nitratos/metabolismo , Poliestirenos/metabolismo
16.
Ibrain ; 9(4): 463-472, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38680511

RESUMO

Nowadays, with the development of the social health care system, there is an increasing trend towards an aging society. The incidence of Alzheimer's disease (AD) is also on the rise. AD is a kind of neurodegenerative disease that can be found in any age group. For years, scientists have been committing to discovering the cause of AD. DNA methylation is one of the most common epigenetic mechanisms in mammals and plays a vital role in the pathogenesis of several diseases, including tumors. Studying chemical changes in the epigenome, or DNA methylation can help us understand the effects of our environment and life on diseases, such as smoking, depression, and menopause, which may affect people's chances of developing Alzheimer's or other diseases. Recent studies have identified some crucial genes like ANK1, RHBDF2, ABCA7, and BIN1, linking DNA methylation to AD. This review focuses on elucidating the relationship between DNA methylation and the pathogenesis of AD and provides an outlook on possible targeted therapeutic modalities.

17.
Sci Total Environ ; 861: 160551, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36460112

RESUMO

Schwertmannite (Sch) is an iron-hydroxysulfate mineral commonly found in acid mine drainage contaminated environment. The transformation mechanism of Sch mediated by pure cultured iron-reducing bacteria (FeRB) or sulfate-reducing bacteria (SRB) has been studied. However, FeRB and SRB widely coexist in the environment, the mechanism of Sch transformation by the consortia of FeRB and SRB is still unclear. This study investigated the Sch reduction by co-cultured Shewanella oneidensis (FeRB) and Desulfosporosinus meridiei (SRB). The results showed that co-culture of FeRB and SRB could accelerate the reductive dissolution of Sch, but not synergistically, and there were two distinct phases in the reduction of Sch mediated by FeRB and SRB: an initial phase in which FeRB predominated and Fe3+ in Sch was reduced, accompanied with the release of SO42-, and the detected secondary minerals were mainly vivianite; the second phase in which SRB predominated and mediated the reduction of SO42-, producing minerals including mackinawite and siderite in addition to vivianite. Compared to pure culture, the abundance of FeRB and SRB in the consortia decreased, and more minerals aggregated inside and outside the cell; correspondingly, the transcription levels of genes (cymA, omcA, and mtrCBA) related to Fe3+ reduction in co-culture was down-regulated, while the transcription levels of SO42--reducing genes (sat, aprAB, dsr(C)) was generally up-regulated. These phenomena suggested that secondary minerals produced in co-culture limited but did not inhibit bacterial growth, and the presence of SRB was detrimental to dissimilatory Fe3+ reduction, while existed FeRB was in favor of dissimilatory SO42- reduction. SRB mediated SO42- reduction by up-regulating the expression of SO42- reduction-related genes when its abundance was limited, which may be a strategy to cope with external coercion. These findings allow for a better understanding of the process and mechanism of microbial mediated reduction of Sch in the environment.


Assuntos
Desulfovibrio , Ferro , Ferro/metabolismo , Técnicas de Cocultura , Compostos Férricos/metabolismo , Minerais/metabolismo , Desulfovibrio/metabolismo , Bactérias/metabolismo , Sulfatos/metabolismo , Oxirredução
18.
J Drug Target ; 31(4): 411-420, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36866593

RESUMO

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.


Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Feminino , Humanos , Camundongos , Albuminas , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Portadores de Fármacos/química , Nanopartículas/química , Proteólise , Albumina Sérica Humana/química , Proteínas de Choque Térmico HSP90/metabolismo
19.
Ibrain ; 8(4): 442-452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37786587

RESUMO

The sympathetic nervous system is involved in the physiological pathogenesis of many different types of chronic pain. Sympathetic blocks can interrupt the reflex control system by intercepting the noxious afferent fibers accompanying autonomic nerves, resulting in changes in peripheral or central sensory processing. A lumbar sympathetic ganglion block (LSGB), as a treatment method, refers to the injection of nerve blockers into the corresponding lumbar sympathetic nerve segments, usually requiring imaging assistance (CT, X-ray, ultrasound) to guide. At present, LSGB has been widely used in the clinical treatment of lower limb pain, such as neuropathic pain, lower limb ischemic pain, and so on. Its mechanism of action may be through inhibiting sympathetic nerve activity and dilating blood vessels, thereby alleviating pain and inhibiting stress response. However, there are few reports of LSGB during the perioperative period, especially in postoperative pain and gastrointestinal function. Therefore, by studying the literature about LSGB-related studies, this article reviews the anatomy of the lumbar sympathetic nerve (LSN), with its clinical application and possible mechanism. We reviewed the analgesic effect of LSGB in patients with lower limb pain and postoperative pain and the potential application prospects in the recovery of gastrointestinal function, finally providing a reference for its clinical application.

20.
Front Cardiovasc Med ; 9: 888724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757330

RESUMO

Introduction: The Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism. Methods/Design: The study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial. Discussion: The purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism. Trial Registration: China Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020.

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