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1.
Tissue Cell ; 89: 102440, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39002288

RESUMEN

Abnormal proliferation, migration, and foam cell formation of Vascular smooth muscle cells (VSMCs) each play a role in the development of atherosclerosis (AS). Schisandrin (Sch) is the active lignan ingredient with broad-spectrum pharmacological effects. However, the role of Sch in the AS process is not clear. Therefore, this study was proposed to explore the therapeutic effect and potential mechanism of Sch on VSMCs. Ox-LDL was selected to create an atherosclerosis injury environment for VSMCs and macrophages. The MTT assay, Oil red O staining, wound healing, transwell experiments and ELISA were used to investigate the phenotype effects of Sch. Network pharmacology, molecular docking, flow cytometry, and western blot were used to investigate the underlying mechanisms of Sch on AS progression. Our findings implied that Sch treatment inhibited the proliferation and migration of VSMCs, and suppressed the ROS production and inflammatory cytokines up-regulation of VSMCs and macrophages. Moreover, Sch reduced lipid uptake and foam cell formation through downregulating LOX-1. Mechanistically, we found that Sch can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2, and arrest cell cycle in GO/G1 phase. In summary, Sch can inhibit VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway. Sch may serve as a potential drug for patients with AS.

2.
Food Chem ; 454: 139831, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38838408

RESUMEN

Diquat (DQ) and paraquat (PQ) residues in food are potential hazards to consumers' health. Point-of-care testing (POCT) of them remains challenging. Based on surface-enhanced Raman spectroscopy (SERS) technology, we developed a POCT strategy for DQ and PQ on apple surface and in apple juice. A point-of-use composite was fabricated using a piece of porous melamine sponge (MS) modified with silver nanoflowers (AgNFs), combining the specificity of the SERS fingerprint and the excellent adsorption capacity of MS. Using this dual-functional AgNFs@MS, the on-site determination of the DQ and PQ residues was completed within 3 min without pretreatment. Clear trends were observed between SERS intensity and logarithmic concentrations, with r values from 0.962 to 0.984. The limit of detection of DQ and PQ were 0.14-0.70 ppb in apple juice and on apple surface. This study provides a new point-of-use alternative for rapidly detecting DQ and PQ residues in nonlaboratory settings.


Asunto(s)
Diquat , Contaminación de Alimentos , Malus , Paraquat , Pruebas en el Punto de Atención , Plata , Espectrometría Raman , Triazinas , Plata/química , Paraquat/análisis , Triazinas/análisis , Diquat/análisis , Diquat/química , Malus/química , Contaminación de Alimentos/análisis , Espectrometría Raman/métodos , Residuos de Plaguicidas/análisis , Residuos de Plaguicidas/química , Herbicidas/análisis , Herbicidas/química , Nanopartículas del Metal/química , Límite de Detección , Jugos de Frutas y Vegetales/análisis
3.
ACS Appl Mater Interfaces ; 16(27): 35421-35437, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38940349

RESUMEN

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.


Asunto(s)
Aterosclerosis , Ácido Hialurónico , Nanopartículas , beta-Ciclodextrinas , Ácido Hialurónico/química , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Ratones , beta-Ciclodextrinas/química , Nanopartículas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Portadores de Fármacos/química , Movimiento Celular/efectos de los fármacos , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/prevención & control , Proliferación Celular/efectos de los fármacos
4.
Cell Signal ; 121: 111276, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936786

RESUMEN

(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.

5.
Molecules ; 29(11)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38893337

RESUMEN

mRNA vaccines are entering a period of rapid development. However, their synthesis is still plagued by challenges related to mRNA impurities and fragments (incomplete mRNA). Most impurities of mRNA products transcribed in vitro are mRNA fragments. Only full-length mRNA transcripts containing both a 5'-cap and a 3'-poly(A) structure are viable for in vivo expression. Therefore, RNA fragments are the primary product-related impurities that significantly hinder mRNA efficacy and must be effectively controlled; these species are believed to originate from either mRNA hydrolysis or premature transcriptional termination. In the manufacturing of commercial mRNA vaccines, T7 RNA polymerase-catalyzed in vitro transcription (IVT) synthesis is a well-established method for synthesizing long RNA transcripts. This study identified a pivotal domain on the T7 RNA polymerase that is associated with erroneous mRNA release. By leveraging the advantageous properties of a T7 RNA polymerase mutant and precisely optimized IVT process parameters, we successfully achieved an mRNA integrity exceeding 91%, thereby further unlocking the immense potential of mRNA therapeutics.


Asunto(s)
ARN Polimerasas Dirigidas por ADN , ARN Mensajero , Transcripción Genética , Proteínas Virales , ARN Mensajero/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Vacunas de ARNm
6.
Phytomedicine ; 129: 155678, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754214

RESUMEN

BACKGROUND: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula. PURPOSE: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD). METHODS: Initially, the chemical profile of ZXG was systemically characterized. Subsequently, the representative constituents were quantitatively analyzed. In the third step, the multi-component xenobiotics profile of ZXG was systemically delineated, and the prototypes absorbed into the blood were identified and designated as the primary bioavailable components. Next, an integrated network of "bioavailable components-CHD targets-pathways-therapeutic effects" was constructed, and the crucial bioavailable components of ZXG against CHD were screened out. Lastly, the bioactivities of crucial bioavailable components were further evaluated to pinpoint effective components. RESULTS: First of all, the chemical profile of ZXG was systemically characterized with the detection of 201 components. Secondly, 37 representative components were quantified to comprehensively describe its content distribution characteristics. Thirdly, among the quantified components, 24 bioavailable components of ZXG were identified based on the multi-component xenobiotic profile. Fourthly, an integrated network led to the identification of 11 crucial bioavailable components against CHD. Ultimately, 9 components (honokiol, magnolol, naringenin, magnoflorine, hesperidin, hesperetin, naringin, neohesperidin and narirutin) exhibiting myocardial protection in vitro were identified as effective components of ZXG for the first time. CONCLUSION: Overall, this innovative strategy successfully identified the effective components of ZXG for the first time. It could not only significantly contribute to elucidating the therapeutic mechanism of ZXG in the treatment of CHD, but also serve as a helpful reference for the systematic discovery of effective components as well as ideal quality markers in the quality assessment of TCM formulas.


Asunto(s)
Enfermedad Coronaria , Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicina Tradicional China/métodos , Enfermedad Coronaria/tratamiento farmacológico , Animales , Farmacología en Red , Masculino , Xenobióticos , Humanos
7.
ACS Omega ; 9(16): 18576-18583, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38680347

RESUMEN

Paraquat (PQ) poisoning poses a significant public health concern. Unfortunately, point-of-care testing (POCT) of PQ in biofluids remains challenging. This study developed a portable kit that enables swift and reliable identification and quantification of PQ in human urine and gastric juice. The approach employed the surface-enhanced Raman scattering (SERS) technique, leveraging gold-silver core-shell nanoparticles (Au@Ag NPs) as the substrate. The kit comprised a portable Raman spectrometer and three sealed tubes containing Au@Ag NPs colloid, KI solution, and MgSO4 solution. A discernible correlation was observed between signal intensity and the logarithmic concentration, spanning from 5 to 500 µg/L in urine and 10 µg/L to 1 mg/L in gastric juice. The detection limits, calculated from the characteristic peak at 1648 cm -1, were 1.36 and 4.05 µg/L in human urine and gastric juice, respectively. Notably, this POCT kit obviated the need for pretreatment procedures, and the detection process was accomplished within 1 min, yielding satisfactory recoveries. This expeditious time frame is crucial for clinical diagnosis and rescue operations. Compared to conventional methods, this kit demonstrated real-time determinations in nonlaboratory settings. The simplicity and practicality of this POCT assay suggest its significant potential as an innovative alternative for poisoning detection applications.

8.
Front Bioeng Biotechnol ; 12: 1356354, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655387

RESUMEN

Introduction: Circular RNAs (circRNAs) are endogenous noncoding RNAs (ncRNAs) with transcriptional lengths ranging from hundreds to thousands. circRNAs have attracted attention owing to their stable structure and ability to treat complicated diseases. Our objective was to create a one-step reaction for circRNA synthesis using wild-type T7 RNA polymerase as the catalyst. However, T7 RNA polymerase is thermally unstable, and we streamlined circRNA synthesis via consensus and folding free energy calculations for hotspot selection. Because of the thermal instability, the permuted intron and exon (PIE) method for circRNA synthesis is conducted via tandem catalysis with a transcription reaction at a low temperature and linear RNA precursor cyclization at a high temperature. Methods: To streamline the process, a multisite mutant T7 RNA polymerase (S430P, N433T, S633P, F849I, F880Y, and G788A) with significantly improved thermostability was constructed, and G788A was used. Results: The resulting mutant exhibited stable activity at 45°C for over an hour, enabling the implementation of a one-pot transcription and cyclization reaction. The simplified circRNA production process demonstrated an efficiency comparable to that of the conventional two-step reaction, with a cyclization rate exceeding 95% and reduced production of immunostimulatory dsRNA byproducts.

9.
Vet Sci ; 11(3)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38535872

RESUMEN

Caprine arthritis encephalitis is an infectious disease caused by the caprine arthritis encephalitis virus that infects goats, sheep, and other small ruminants. An outbreak of CAEV could be extremely harmful to the goat farming industry and could cause severe economic losses. We designed specific primers and probes for the gag gene and established a TaqMan real-time quantitative polymerase chain reaction assay. This method's correlation coefficient (R2) was >0.999, and the sensitivity of the assay to the plasmid-carried partial gag gene was approximately 10 copies/µL, 1000 times higher than that of conventional PCR. No specific fluorescence was detected for other sheep viruses. Using this method, we tested 776 asymptomatic sheep blood samples and 4 neurodegenerative sheep brain samples from six farms in eastern China, and the positivity rate was 0.77% (6/780). The gag gene was partially sequenced in the three positive samples and compared with the sequences from other representative strains in GenBank. The results revealed that all three strains belonged to the B1 subtype and were most closely related to the strains from Shanxi and Gansu, previously isolated in China, with their homology ranging from 97.7% to 98.9%. These results suggest that the designed RT-qPCR assay can be used to detect subclinical CAEV in sheep and that the virus is still present in eastern China.

10.
Adv Sci (Weinh) ; 11(18): e2303752, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38311573

RESUMEN

Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP-derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC-markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP-outer subset. Cell lineage tracing further evidence that a small number of Ctsk-expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2-cre-mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.


Asunto(s)
Núcleo Pulposo , Células Madre , Transcriptoma , Animales , Ratones , Núcleo Pulposo/metabolismo , Núcleo Pulposo/citología , Células Madre/metabolismo , Transcriptoma/genética , Diferenciación Celular/genética , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Perfilación de la Expresión Génica/métodos , Modelos Animales de Enfermedad
11.
ACS Nano ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294834

RESUMEN

Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.

12.
Arch Biochem Biophys ; 752: 109873, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38141907

RESUMEN

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.


Asunto(s)
Isoflavonas , Pancreatitis , Ratones , Animales , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Ceruletida/efectos adversos , Enfermedad Aguda , Simulación del Acoplamiento Molecular , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Macrófagos/metabolismo , Amilasas , Lipasa
13.
Science ; 381(6662): 1092-1098, 2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37676935

RESUMEN

Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.


Asunto(s)
Adaptación Fisiológica , Quitina , Quitinasas , Fibras de la Dieta , Obesidad , Estómago , Animales , Ratones , Quitina/metabolismo , Inmunidad Innata , Linfocitos/enzimología , Linfocitos/inmunología , Obesidad/inmunología , Estómago/inmunología , Adaptación Fisiológica/inmunología , Quitinasas/metabolismo , Digestión/inmunología
14.
Macromol Rapid Commun ; 44(21): e2300391, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37690003

RESUMEN

The vibrationally resolved pyrene fluorescence probe method is once popular but now languished, because the vibrationally resolved patterns of pyrene with limited sensitivity and concentration independence have not been updated for over 50 years. During investigation on the polymer interdiffusion of a latex film, it is found that a pyrene acylhydrazone whose vibrationally resolved fluorescence pattern contradictory to those reported in pyrene and most pyrene derivatives. The pyrene acylhydrazone has sensitive concentration- and polarity-dependent fluorescence spectra (the sensitivity on polarity is at most 26 times higher than the old vibrationally resolved patterns), and the sensitivity well remains when it is copolymerized in a polymer. The vibrationally resolved spectrum of this pyrene acylhydrazone is a powerful fluorescence probe, which would be as useful as the pyrene excimer probe nowadays popular.


Asunto(s)
Colorantes Fluorescentes , Polímeros , Fluorescencia , Espectrometría de Fluorescencia/métodos , Pirenos
15.
Viruses ; 15(9)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37766229

RESUMEN

Japanese encephalitis (JE), found in pigs, is a serious mosquito-borne zoonotic infectious disease caused by the Japanese encephalitis virus (JEV). JEV is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. It is transmitted to humans through the bite of an infected mosquito, allowing the pathogen to spread and cause disease epidemics. However, there is little research on JEV genotype variation in mosquitoes and pigs in Fujian province. Previous studies have shown that the main epidemic strain of JEV in Fujian Province is genotype III. In this study, a survey of mosquito species diversity in pig farms and molecular evolutionary analyses of JEV were conducted in Fujian, China, in the summer of 2019. A total of 19,177 mosquitoes were collected at four sites by UV trap. Four genera were identified, of which the Culex tritaeniorhynchus was the most common mosquito species, accounting for 76.4% of the total (14,651/19,177). Anopheles sinensi (19.25%, 3691/19,177) was the second largest species. High mosquito infection rateswere an important factor in the outbreak. The captured mosquito samples were milled and screened with JEV-specific primers. Five viruses were isolated, FJ1901, FJ1902, FJ1903, FJ1904, and FJ1905. Genetic affinity was determined by analyzing the envelope (E) gene variants. The results showed that they are JEV gene type I and most closely related to the strains SH-53 and SD0810. In this study, it was found through genetic evolution analysis that the main epidemic strain of JE in pig farms changed from gene type III to gene type I. Compared with the SH-53 and SD0810 strains, we found no change in key sites related to antigenic activity and neurovirulence of JEV in Fujian JEV and pig mosquito strains, respectively. The results of the study provide basic data for analyzing the genotypic shift of JEV in Fujian Province and support the prevention and control of JEV.

16.
Biomed Chromatogr ; 37(9): e5683, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37161606

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease with a 0.5% prevalence worldwide. Inflammation, periosteal proliferation and joint destruction are the main clinical symptoms of RA. Typhonii Rhizoma (TR) is the dry tuber of the Araceae plant Typhonium giganteum Engl, and possesses many uses such as dispelling obstructive wind-phlegm and relieving pain. It is used for the clinical treatment of arthromyodynia and RA. However, the mechanism of action remains unclear. In this study, we first evaluated the effects of TR in type II collagen-induced RA model rats. Secondly, in serum metabolomics, TR could ameliorate 11 potential metabolites in RA model rats and reversed RA through pentose and glucuronate interconversions, sphingolipid metabolism, glycerophospholipid metabolism and tryptophan metabolism. To further explore the mechanisms of TR, 40 chemical constituents were used to establish a component-target interaction network. Some key genes were verified by in vitro pharmacological tests by integrating the results from the network pharmacology and metabolomics. The verification results showed that the mechanisms of TR against RA may be related to the inhibition of the production of inflammatory cytokines and the expression and function of HIF1-α. This study serves as a theoretical basis for the treatment of RA with TR.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Medicamentos Herbarios Chinos , Ratas , Animales , Farmacología en Red , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Metabolómica/métodos , Inflamación/metabolismo , Medicamentos Herbarios Chinos/farmacología
17.
Nanoscale ; 15(13): 6333-6342, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36916219

RESUMEN

CuBi2O4 is a promising photoactive material for photoelectrochemical (PEC) broadband photodetectors due to its suitable band structure, but its photo-responsivity is severely limited by the short carrier diffusion length and long light penetration depth. To address the trade-off between light absorption and charge separation, a nano-structured bipolar Bi2O3 host scaffold was coupled with an ultrathin CuBi2O4 light absorbing layer to construct a host-guest Bi2O3/CuBi2O4 photocathode. The work function of the bipolar Bi2O3 scaffold lies in between FTO and CuBi2O4, making Bi2O3 a suitable back contact layer for hole transport. Compared with the flat CuBi2O4 and Bi2O3 scaffold counterpart, the nanostructured Bi2O3/CuBi2O4 exhibits significantly improved light absorption and enhanced charge separation efficiency. The Bi2O3/CuBi2O4 PEC photodetector can be self-powered and demonstrates a broad photo-response ranging from ultraviolet (UV) to near infrared (NIR). It shows a high responsivity of 75 mA W-1 and a remarkable short response time of 0.18 ms/0.19 ms. Bi2O3/CuBi2O4 prepared by magnetron sputtering demonstrates great potential for rapid PEC photodetection in a wide optical domain.

18.
Animals (Basel) ; 13(4)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36830506

RESUMEN

S. suis is an important zoonotic pathogen from sick and recessive carrier pigs that poses a serious threat to animal husbandry production and public health. It usually causes horizontal transmission among pigs. The morbidity and mortality of this disease are very high. Human infection is caused through direct or indirect contact with sick pigs. The two large-scale outbreaks in China were due to the outbreak of S. suis on pig farms, which spread to human infection; thus, detecting S. suis in pig herds is crucial. At present, the commercial S. suis ELISA type 2 kits on the market can only detect single serotypes, high probabilities of interaction reactions, and biosafety risks when using inactivated S. suis as an antigen. Phosphate-3-glyceraldehyde dehydrogenase (GAPDH), muramidase-released protein (MRP), and dihydrolipoamide dehydrogenase (DLDH) are important S. suis type 2, S. suis type 7, and S. suis type 9 protective antigens. This study purified the GMD protein (B-cell-dominant epitopes of GAPDH, MRP, and DLDH antigens) and used a diverse combination of dominant epitopes of the multiple different antigens as coated antigens, improving the sensitivity and safety of the indirect ELISA experiments. An indirect ELISA method (GMD-ELISA) was developed for detecting S. suis antibodies. The antigen-antibody response was optimized using checkerboard titration. The results of testing using ELISA for Salmonella enterica (S. enterica), Escherichia coli (E. coli), Staphylococcus aureus (SA), and Streptococcus pyogenes (S. pyogenes) were all negative, indicating that this method had strong specificity. The results were still positive when the dilution ratio of S. suis-positive serum reached 1:6, 400, thus indicating that the method had high sensitivity. The results of the reproducibility assay for indirect ELISA showed that the intra-assay coefficient of variation and the inter-assay coefficient of variation were less than 10%, indicating that the method had good repeatability. We investigated the seroprevalence of S. suis in 167 serum samples collected in East China, and 33.5% of the samples were positive for antibodies against S. suis, indicating that the prevalence of S. suis is high in pig farms in Eastern China. The novel GMD-ELISA is a convenient, sensitive, and specific diagnostic method that provides technical support for rapid diagnosis and epidemiological investigation.

19.
J Am Chem Soc ; 145(9): 4969-4974, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36847744

RESUMEN

XOR gate, an important building block in computational circuits, is often constructed by combining other basic logic gates, and the hybridity inevitably leads to its complexity. A photoelectrochemical device could realize XOR function based on the current change of the photoelectrode; however, such signal is highly sensitive to photoelectrode size and therefore requires precise manufacturing at a high cost. Herein we developed a novel XOR gate based on the light-induced open-circuit potential (OCP) of the Bi2O3 photoelectrode. Surprisingly, the OCP of Bi2O3 does not increase with light intensity according to the traditional logarithmic relationship. Instead, an unusual decrease in OCP is observed at high light intensity, which is attributed to the dramatic light-induced increase in surface states that can be easily regulated by varying the oxygen partial pressure during reactive magnetron sputtering. Based on such a nonmonotonic variation of OCP, a facile Bi2O3-based gate is designed to realize the XOR function. Unlike the commonly used current signal, OCP is size independent, and therefore, the Bi2O3-based gate does not require high manufacturing accuracy. Moreover, in addition to XOR, the Bi2O3-based PEC gate also demonstrates great versatility in realizing other logic functions including AND, OR, NOT, NIH, NAND, and NOR. The strategy of modulating and applying nonmonotonic OCP signal opens a new avenue for designing size-independent reconfigurable logic gates at low manufacturing cost.

20.
Food Funct ; 14(5): 2444-2458, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36786689

RESUMEN

Green tea is popular worldwide, so its main active ingredients have attracted people's attention. (-)-Epicatechin gallate (ECG) is the main active component of green tea polyphenols, which has good antioxidant activity, but its cardiovascular intervention is unknown. This study established in vitro and in vivo models of ox-LDL-induced macrophages and HFD-induced ApoE-/- mice to study the effects of ECG on atherosclerotic lesions. Firstly, the study confirmed that ECG has a therapeutic effect in different stages of atherosclerotic plaques. Subsequently, the results showed that the ox-LDL-induced release of pro-inflammatory mediators and the expression of the related protein CD86 in macrophages were inhibited by ECG. ECG blocked the formation of cellular foam by downregulating the expression of CD36 and LOX-1 proteins, thereby increasing SOD activity and reducing MDA production in cells. ECG also prevented ox-LDL-induced apoptosis, promoted macrophage migration, and increased plaque stability. The results confirmed that ECG attenuated ox-LDL-induced green fluorescence of ROS in macrophages by inhibiting the expression of related proteins in the NF-κB signaling pathway and activating the HO-1/Nrf2 signaling pathway. These results indicated that ECG has anti-oxidative stress and anti-inflammatory potential, and its molecular mechanism may be related to the inhibition of intracellular NF-κB signaling pathway proteins and activation of the HO-1/Nrf2 signaling pathway.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , FN-kappa B/genética , Factor 2 Relacionado con NF-E2 , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Aterosclerosis/metabolismo , Placa Aterosclerótica/metabolismo , Lipoproteínas LDL/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico
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