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1.
Cereb Cortex ; 34(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38451300

RESUMO

Although previous studies have reported the sex differences in behavior/cognition and the brain, the sex difference in the relationship between memory abilities and the underlying neural basis in the aging process remains unclear. In this study, we used a machine learning model to estimate the association between cortical thickness and verbal/visuospatial memory in females and males and then explored the sex difference of these associations based on a community-elderly cohort (n = 1153, age ranged from 50.42 to 86.67 years). We validated that females outperformed males in verbal memory, while males outperformed females in visuospatial memory. The key regions related to verbal memory in females include the medial temporal cortex, orbitofrontal cortex, and some regions around the insula. Further, those regions are more located in limbic, dorsal attention, and default-model networks, and are associated with face recognition and perception. The key regions related to visuospatial memory include the lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and were associated with object recognition. These findings imply the memory performance advantage of females and males might be related to the different memory processing tendencies and their associated network.


Assuntos
Reconhecimento Facial , Caracteres Sexuais , Idoso , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Encéfalo , Cognição , Citoplasma
2.
Curr HIV Res ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38310467

RESUMO

BACKGROUND: Second-line antiretroviral therapy (ART) was introduced in Henan Province in 2009. The number of people living with human immunodeficiency virus (HIV) starting this therapy is increasing. OBJECTIVE: This study aimed to investigate the survival and factors affecting mortality among this group. METHODS: We conducted a retrospective cohort study of people living with HIV (PLHIV) who switched to second-line ART between May 1, 2010, and May 1, 2016., using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: We followed 3,331 PLHIV for 26,988 person-years, of whom 508 (15.3%) died. The mortality rate was 1.88/100 person-years. After adjusting for confounding factors, we found being a woman (hazard ratio [HR], 0.66; 95% confidence interval [CI] 0.55-0.79), > 50 years old (HR, 2.69; 95%CI, 2.03-3.56), single/windowed (HR, 1.26; 95%CI, 1.04-1.52), having > 6 years of education (HR, 0.78; 95%CI, 0.65-0.94), Chinese medicine (HR, 0.75; 95%CI, 0.52-0.96), liver injury (HR, 1.58; 95%CI, 1.19-2.10), and CD4+ T cell count <200 cells/µl (HR, 1.94; 95%CI, 1.47-2.55), or 200-350 cells/µl (HR, 1.37; 95%CI, 1.03-1.82) were associated with mortality risk. CONCLUSIONS: We found lower mortality among PLHIV who switched to second-line ART than most previous studies. The limitations of a retrospective cohort may, therefore, have biased the data, and prospective studies are needed to confirm the results. Moreover, Chinese medicine combined with second-line ART shows potential as a treatment for HIV.

3.
J Cereb Blood Flow Metab ; : 271678X231214073, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950676

RESUMO

The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment and a subgroup of 233 people with imaging data were recruited and divided into 3 groups (short duration: <5 years, medium duration: 5-20 years, long duration: >20 years). We found that greater HTN duration was preferentially related to worse executive function (EF), processing speed (PS), and more severe WMH, which became more significant during long duration stage. The reductions in WM integrity were evident at the early stage especially in long-range association fibers and then scattered through the whole brain. Increasing WMH and decreasing integrity of specific tracts consistently undermined EF. Furthermore, free water imaging method greatly enhanced the sensitivity in detecting HTN-related WM alterations. These findings supported that the neurological damaging effects of HTN is cumulative and neuroimaging markers of WM at macro- and microstructural level underlie the progressive effect of HTN on cognition.

4.
J Mater Chem B ; 11(42): 10234-10251, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869993

RESUMO

Uncontrollable hemorrhage and subsequent wound infection pose severe threats to life, especially in the case of deep, non-compressible, massive bleeding. Here, a wool keratin/zeolitic imidazolate framework-8 (WK/ZIF-8) composite shape memory sponge is prepared by incorporating ZIF-8 nanoparticles into wool keratin. The combination of keratin and ZIF-8 particles not only reduces the effect of ZIF-8 particles on cell viability but also bolsters the mechanical properties of the keratin sponge and endows it with antibacterial efficacy. Due to the synergistic effect of the excellent hemostatic performance of keratin and Zn2+ release from ZIF-8 nanoparticles, the porous structure suitable for blood cell adhesion and the shape recovery ability of sponges, the WK/ZIF-8 composite sponge exhibits superior hemostatic performance to commercial medical sponges in SD rat and rabbit hemorrhage models. In addition, in vitro and in vivo antibacterial experiments demonstrate the anti-infection activity of the composite sponge. Overall, the WK/ZIF-8 composite sponge provides a promising approach to rapidly control bleeding and promote wound healing.


Assuntos
Hemostáticos , Zeolitas , Animais , Coelhos , Ratos , Ratos Sprague-Dawley , Hemostáticos/farmacologia , , Queratinas , Hemorragia/tratamento farmacológico , Antibacterianos/farmacologia
5.
Cereb Cortex ; 33(23): 11329-11338, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37859548

RESUMO

It is helpful to understand the pathology of Alzheimer's disease by exploring the relationship between amyloid-ß accumulation and cognition. The study explored the relationship between regional amyloid-ß accumulation and multiple cognitions and study their application value in the Alzheimer's disease diagnosis. 135 participants completed 18F-florbetapir Positron Emission Tomography (PET), structural MRI, and a cognitive battery. Partial correlation was used to examine the relationship between global and regional amyloid-ß accumulation and cognitions. Then, a support vector machine was applied to determine whether cognition-related accumulation regions can adequately distinguish the cognitively normal controls (76 participants) and mild cognitive impairment (30 participants) groups or mild cognitive impairment and Alzheimer's disease (29 participants) groups. The result showed that amyloid-ß accumulation regions were mainly located in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Episodic memory-related regions included the frontoparietal cortices; executive function-related regions included the frontoparietal, temporal, and occipital cortices; and processing speed-related regions included the frontal and occipital cortices. Support vector machine analysis showed that only episodic memory-related amyloid-ß accumulation regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in frontoparietal regions, can aid in the early detection of amyloid-related decline in cognitive function.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Peptídeos beta-Amiloides , Cognição , Tomografia por Emissão de Pósitrons/métodos , Amiloide
6.
Colloids Surf B Biointerfaces ; 232: 113590, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37862950

RESUMO

Uncontrolled expansion of shape memory sponges face a significant challenge in the treatment of lethal incompressible hemorrhage, which can lead to blood overflow or damage to the surrounding tissue. Herein, we developed a polydopamine functionalized polyurethane shape memory sponge (PDA-TPI-PU) with a controllable degree of expansion by near-infrared (NIR) light-triggered stimulation for the treatment of incompressible hemorrhage. The sponge has excellent liquid absorption performance and robust mechanical strength as well as good photothermal conversion ability. Under NIR light of 0.32 W/cm2, the maximum recovery rate of the fixed-shape compression sponge was 91% within 25 s in air and 80% within 25 s in blood. In the SD rat liver penetrating injury model, compared with commercial medical gelatin sponge and PVA sponge, the PDA-TPI-PU sponge could effectively control the bleeding under the NIR light irradiation and did not cause excessive compression of the wound. The sponge with these characteristics shows potential application prospects as a hemostatic material.


Assuntos
Hemostáticos , Poliuretanos , Ratos , Animais , Poliuretanos/farmacologia , Ratos Sprague-Dawley , Hemorragia/terapia
7.
Bioorg Med Chem ; 93: 117454, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37659218

RESUMO

Bacterial infection, which is still one of the leading causes of death in humans, poses an enormous threat to the worldwide public health system. Antibiotics are the primary medications used to treat bacterial diseases. Currently, the discovery of antibiotics has reached an impasse, and due to the abuse of antibiotics resulting in bacterial antibiotic resistance, researchers have a critical desire to develop new antibacterial agents in order to combat the deteriorating antibacterial situation. Natural chalcones, the flavonoids consisting of two phenolic rings and a three-carbon α, ß-unsaturated carbonyl system, possess a variety of biological and pharmacological properties, including anti-cancer, anti-inflammatory, antibacterial, and so on. Due to their potent antibacterial properties, natural chalcones possess the potential to become a new treatment for infectious diseases that circumvents existing antibiotic resistance. Currently, the majority of research on natural chalcones focuses on their synthesis, biological and pharmacological activities, etc. A few studies have been conducted on their antibacterial activity and mechanism. Therefore, this review focuses on the antibacterial activity and mechanisms of seventeen natural chalcones. Firstly, seventeen natural chalcones have been classified based on differences in antibacterial mechanisms. Secondly, a summary of the isolation and biological activity of seventeen natural chalcones was provided, with a focus on their antibacterial activity. Thirdly, the antibacterial mechanisms of natural chalcones were summarized, including those that act on bacterial cell membranes, biological macromolecules, biofilms, and quorum sensing systems. This review aims to lay the groundwork for the discovery of novel antibacterial agents based on chalcones.


Assuntos
Chalconas , Humanos , Chalconas/farmacologia , Flavonoides , Antibacterianos/farmacologia , Biofilmes , Carbono
8.
Adv Exp Med Biol ; 1419: 99-108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37418209

RESUMO

Despite recent substantial progress in neuroscience, the mechanisms and principles of the complex structure, functions, and the relationship between the brain and cognitive functions have not been fully understood. The modeling method of brain network can provide a new perspective for neuroscience research, and it is possible to provide new solutions to the related research problems. On this basis, the researchers define the concept of human brain connectome to highlight and emphasize the importance of network modeling methods in neuroscience. For example, using diffusion-weighted magnetic resonance imaging (dMRI) technology and fiber tractography methods, a white matter connection network of the whole brain can be constructed. From the perspective of brain function, functional magnetic resonance imaging (fMRI) data can build the brain functional connection network. A structural covariation modeling method is used to obtain a brain structure covariation network, and it appears to reflect developmental coordination or synchronized maturation between areas of the brain. In addition, network modeling and analysis methods can also be applied to other types of image data, such as positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). This chapter mainly reviews the research progress of researchers on brain structure, function, and other aspects at the network level in recent years.


Assuntos
Encéfalo , Substância Branca , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Envelhecimento , Imagem de Difusão por Ressonância Magnética
9.
Adv Exp Med Biol ; 1419: 85-97, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37418208

RESUMO

The normal aging process brings changes in brain structure, function, and energy metabolism, which are presumed to contribute to the age-related decline in brain function and cognitive ability. This chapter aims to summarize the aging patterns of brain structure, function, and energy metabolism to distinguish them from the pathological changes associated with neurodegenerative diseases and explore protective factors in aging. We first described the normal atrophy pattern of cortical gray matter with age, which is negatively affected by some neurodegenerative diseases and is protected by a healthy lifestyle, such as physical exercise. Next, we summarized the main types of age-related white matter lesions, including white matter atrophy and hyperintensity. Age-related white matter changes mainly occurred in the frontal lobe, and white matter lesions in posterior regions may be an early sign of Alzheimer's disease. In addition, the relationship between brain activity and various cognitive functions during aging was discussed based on electroencephalography, magnetoencephalogram, and functional magnetic resonance imaging. An age-related reduction in occipital activity is coupled with increased frontal activity, which supports the posterior-anterior shift in aging (PASA) theory. Finally, we discussed the relationship between amyloid-ß deposition and tau accumulation in the brain, as pathological manifestations of neurodegenerative disease and aging.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Envelhecimento/patologia , Doença de Alzheimer/metabolismo , Imageamento por Ressonância Magnética , Metabolismo Energético , Atrofia/patologia
10.
Neuroimage Clin ; 38: 103389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37004321

RESUMO

Hypertension has been well recognized as a risk factor for cognitive impairment and dementia. Although the underlying mechanisms of hypertension-affected cognitive deterioration are not fully understood, white matter changes (WMCs) seem to play an important role. WMCs include low microstructural integrity and subsequent white matter macrostructural lesions, which are common on brain imaging in hypertensive patients and are critical for multiple cognitive domains. This article provides an overview of the impact of hypertension on white matter microstructural and macrostructural changes and its link to cognitive dysfunction. Hypertension may induce microstructural changes in white matter, especially for the long-range fibers such as anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFOF), and then macrostructural abnormalities affecting different lobes, especially the periventricular area. Different regions' WMCs would further exert different effects to specific cognitive domains and accelerate brain aging. As a modifiable risk factor, hypertension might provide a new perspective for alleviating and delaying cognitive impairment.


Assuntos
Disfunção Cognitiva , Hipertensão , Substância Branca , Humanos , Idoso , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Fibras Nervosas/patologia , Hipertensão/complicações , Hipertensão/diagnóstico por imagem
11.
Luminescence ; 38(4): 497-504, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36894301

RESUMO

An organic chemical with fluorescence quenching properties [aggregation-caused quenching (ACQ)] may often be transformed by adding functional groups that cause aggregation-induced emission (AIE) to its molecular scaffold. Such structural change techniques, however, sometimes require challenging chemical reactions. SF136 is a type of chalcone, and it is an typical ACQ organic compound. In this study, cationic surfactants like hexadecyltrimethylammonium bromide (CTAB) and polyethyleneimine (PEI) were used to convert the ACQ compound SF136 into an AIE compound without adding any AIE structure units. In comparison to SF136, the SF136-CTAB NPS system not only demonstrated improved bacterial fluorescence imaging capabilities, but also increased photodynamic antibacterial activity, which is connected to its improved targeting and reactive oxygen species (ROS) production abilities. It is a promising theranostic substance against bacteria owing to these enhanced qualities. Other ACQ fluorescent compounds may also benefit from using this approach, broadening the scope of their potential applications.


Assuntos
Imagem Óptica , Medicina de Precisão , Cetrimônio , Corantes Fluorescentes/química
12.
Talanta ; 257: 124343, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36791596

RESUMO

Prostate cancer is one of the most common cancers in the world, and its early diagnosis can effectively reduce mortality. A new label-free photoelectrochemical (PEC) immunosensor on the basis of Bi2WO6/BiOBr nanocomposite materials has been successfully prepared for the test of prostate-specific antigen (PSA) in human serum in this work. The Ag2S-sensitized Bi2WO6/BiOBr heterojunction was used as a photosensitive material, which effectively improved the photocurrent response. On Bi2WO6/BiOBr surface, dopamine immobilized PSA antibody by self-polymerizing to form polydopamine membrane. Antigen and antibody are specifically combined to achieve quantitative detection of PSA according to the current changes at different concentrations of antigen. Under the optimal experimental conditions, the PEC immunosensor has an ideal linear relationship between 1 pg/mL - 50 ng/mL, and the detection limit is 0.084 pg/mL. In addition, the prepared immunosensor has good stability, reproducibility and selectivity, providing a new method for the detection of PSA in actual sample analysis.


Assuntos
Técnicas Biossensoriais , Antígeno Prostático Específico , Humanos , Masculino , Técnicas Biossensoriais/métodos , Reprodutibilidade dos Testes , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Anticorpos , Limite de Detecção
13.
Artigo em Inglês | MEDLINE | ID: mdl-36748466

RESUMO

A yellow, Gram-stain-positive, strictly aerobic, thermotolerant, non-motile and rod-shaped bacterial strain, designated RY-1T, was isolated from a silt sample of Fuyang River, Wuqiang County, Hengshui City, Hebei Province, PR China. Cells showed oxidase- and catalase-positive activities. Growth occurred at 20-45 °C (optimum, 37 °C) and pH 6.0-8.0 (optimum, pH 7.0), and in the presence of 0-1.5 % (w/v) NaCl (optimum, 0%). A phylogenetic tree based on 16S rRNA gene sequences revealed that strain RY-1T formed a phylogenetic lineage with Flavihumibacter members within the family Chitinophagaceae. A comparison of 16S rRNA gene sequences showed that strain RY-1T was most closely related to Flavihumibacter cheonanensis WS16T (98.6 %), Flavihumibacter sediminis CJ663T (97.7 %) and Flavihumibacter solisilvae 3-3T (97.6 %). The genome size of strain RY-1T was 4.71 Mb, and the DNA G+C content was 44.3  %. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between strain RY-1T and reference strains were all lower than the threshold values for species delineation. Strain RY-1T contained menaquinone-7 and iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1G as the sole respiratory isoprenoid quinone and major cellular fatty acids (≥5 %), respectively. The major polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. According to the results of phenotypic, phylogenetic and chemotaxonomic characteristics, strain RY-1T represents a novel species of the genus Flavihumibacter, for which the name Flavihumibacter fluminis sp. nov. is proposed. The type strain is RY-1T (=GDMCC 1.2775T=JCM 34870T).


Assuntos
Bacteroidetes , Filogenia , Rios , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Rios/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química , Bacteroidetes/classificação , Bacteroidetes/isolamento & purificação , China
15.
Bioorg Med Chem Lett ; 78: 129041, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36332882

RESUMO

Proteolysis Targeting Chimeras (PROTACs) based on multi-target inhibitors have been reported several times recently. The advantages of PROTACs technology and the synergistic mechanism of multi-target drugs endow this class of protein degraders with special research significance. Herein, twelve new PROTACs based on Sunitinib and VHL-ligand were synthesized and evaluated for their in vitro anticancer activities. Among them, PROTACs 5 (IC50 = 2.9 ± 1.5 µM) exhibited the most significant antiproliferative activity against HL-60 cells. Western blot results showed that PROTAC 5 reduced the protein levels of FLT-3 and c-KIT in HL-60 cells, and induced the degradation of FLT-3 via the ubiquitin-proteasome system. Moreover, PROTACs 5 and 6 reduced the protein levels of FLT-3 in K562 cells. These results suggest that PROTAC 5 has the potential for further research, especially in combination with small molecule kinase inhibitors to study multidrug resistance of tyrosine kinase inhibitors in cancer treatment.


Assuntos
Leucemia , Humanos , Sunitinibe/farmacologia , Proteólise , Leucemia/tratamento farmacológico , Células HL-60 , Complexo de Endopeptidases do Proteassoma
16.
Front Pharmacol ; 13: 1035882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339566

RESUMO

Glycolysis is a complex metabolic process that occurs to convert glucose into pyruvate to produce energy for living cells. Normal cells oxidized pyruvate into adenosine triphosphate and carbon dioxide in the presence of oxygen in mitochondria while cancer cells preferentially metabolize pyruvate to lactate even in the presence of oxygen in order to maintain a slightly acidic micro-environment of PH 6.5 and 6.9, which is beneficial for cancer cell growth and metastasis. Therefore targeting glycolytic signaling pathways provided new strategy for anti-cancer therapy. Natural products are important sources for the treatment of diseases with a variety of pharmacologic activities. Accumulated studies suggested that natural products exhibited remarkable anti-cancer properties both in vitro and in vivo. Plenty of studies suggested natural products like flavonoids, terpenoids and quinones played anti-cancer properties via inhibiting glucose metabolism targets in glycolytic pathways. This study provided an updated overview of natural products controlling glycolytic pathways, which also provide insight into druggable mediators discovery targeting cancer glucose metabolism.

17.
Front Chem ; 10: 964089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046729

RESUMO

Chalcones have a three-carbon α,ß-unsaturated carbonyl system composed of two phenolic rings. Many chalcones have shown broad spectrum of biological activities with clinical potentials against various diseases. They are usually abundant in seeds, fruit skin, bark and flowers of most edible plants. Among them, chalcones bearing 2-hydroxy-3-methyl-3-butenyl (HMB) group have been reported several times in the past few decades due to their novel scaffolds and numerous interesting biological activities. In this paper, we reviewed the isolation of twelve natural chalcones and a natural chalcone-type compound bearing 2-hydroxy-3-methyl-3-butenyl group discovered so far, and reviewed their synthesis methods and biological activities reported in the literature. We anticipate that this review will inspire further research of natural chalcones.

18.
Curr HIV Res ; 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35929632

RESUMO

OBJECTIVE: In this study, we aimed to determine the prevalence and effectors of hyperlipidemia among people living with HIV/AIDS (PLWHA) and taking second-line antiretroviral therapy (ART) using registry data in central China. METHODS: We conducted a cross-sectional study and collected information of PLWHA on second-line ART during 2018 from two medical registries. Hyperlipidemia was defined according to the 2016 Chinese guidelines for the management of dyslipidemia in adults. Univariate and multivariate logistic regression analyses were performed to explore the influencing factors of hyperlipidemia. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2886 PLWHA taking second-line ART were included in this study, and 978 (33.9%) had hyperlipidemia. Female patients, those with hyperglycemia, and patients with CD4+ cell counts >500 cells/µL had a higher prevalence of hyperlipidemia with 37.0%, 49.0%, and 41.3%, respectively. Multivariate analysis showed that CD4+ cell count 350-500 cells/µL (OR=1.72, 95% CI: 1.26-2.38), CD4+ cell count >500 cells/µL (OR=2.49, 95% CI: 1.85-3.38), and FPG >6.2 mmol/L (OR=2.08, 95% CI:1.64-2.65) were risk factors for hyperlipidemia. Male sex (OR=0.72, 95% CI: 0.61-0.85) and Hb <110 g/L (OR=0.59, 95% CI: 0.45-0.76) were protective factors against hyperlipidemia. CONCLUSIONS: PLWHA on second-line ART had a higher prevalence of hyperlipidemia. Gender, CD4+ cell count, FPG, and hemoglobin were influencing factors of hyperlipidemia.

19.
Drug Des Devel Ther ; 16: 2731-2753, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003311

RESUMO

Purpose: This study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS). Methods: The main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of "Chinese herbs-active compounds-targets" for JAKCP was constructed by Cytoscape, and protein-protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of "main active compounds-core targets-pathways" was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot. Results: A total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1ß, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of "T cell activation" demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1ß, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro. Conclusion: JAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.


Assuntos
Síndrome de Imunodeficiência Adquirida , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Imunidade , Interleucina-10 , Interleucina-6 , Simulação de Acoplamento Molecular , Farmacologia em Rede/métodos , RNA Mensageiro
20.
Artigo em Inglês | MEDLINE | ID: mdl-35990823

RESUMO

Background: Biejiajian pill (BJJP), a classical traditional Chinese formula, has been reported that it has an effective treatment for diabetic atherosclerosis in recent years, but its underlying mechanisms remain elusive. The study aimed to explore the potential mechanisms of BJJP on diabetic atherosclerosis by integrating network pharmacology, molecular docking, and molecular dynamics simulation. Methods: The active components of BJJP were collected by TCMSP and TCMID, and then the potential targets were obtained from the SwissTargetPrediction database. The targets related to diabetic atherosclerosis were identified from the GeneCards and OMIM databases. The intersection of the potential targets regulated by active components of BJJP and the targets of diabetic atherosclerosis were common targets, which were visualized by the Venn diagram. The common targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. The network of "Medicine-Compound-Target" was constructed with Cytoscape 3.7.1 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using the DAVID database and visualized through bioinformatics. The intersecting targets were input into Cytoscape 3.7.1 software, and the Network Analyzer tool was employed to screen out the key targets. Then molecular docking was used to verify the binding affinity between the active compounds and the key targets, and molecular dynamics simulation was used to investigate the stability of the binding models. Results: A total of 81 active components, 186 targets of BJJP, and 4041 targets of diabetic atherosclerosis were obtained. Furthermore, 121 overlapping targets were identified. GO functional enrichment analysis revealed that these targets were correlated with the oxidation-reduction process, negative regulation of apoptotic process, inflammatory response, and other biological processes. The results of the KEGG pathway enrichment analysis showed that the common targets mainly participated in proteoglycans in cancer, PPAR signaling pathway, adherens junction, insulin resistance, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking confirmed that the core active components in BJJP could bind well to the key targets. Results from molecular dynamics simulation showed that the binding energies of AKT1-Luteolin, MMP9-quercetin, and MMP9-luteolin complexes were -28.93 kJ·mol-1, -37.12 kJ·mol-1, and -62.91 kJ·mol-1, respectively. Conclusion: The study revealed that BJJP is characterized as multicomponent, multitarget, and multipathway to treat diabetic atherosclerosis, which is helpful to provide ideas and a basis for pharmacological research and clinical application in the future.

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