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1.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2710-2721, 2024 May.
Artigo em Zh | MEDLINE | ID: mdl-38812171

RESUMO

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.


Assuntos
Carvão Vegetal , Medicamentos de Ervas Chinesas , Hemostáticos , Ratos Sprague-Dawley , Sanguisorba , Animais , Ratos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hemostáticos/farmacologia , Hemostáticos/química , Sanguisorba/química , Carvão Vegetal/química , Masculino , Culinária , Coagulação Sanguínea/efeitos dos fármacos , Humanos
2.
J Lipid Res ; 64(10): 100436, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37648212

RESUMO

Lipoproteins are complex particles comprised of a neutral lipid core wrapped with a phospholipid monolayer membrane and apolipoproteins on the membrane, which is closely associated with metabolic diseases. To facilitate the elucidation of its formation and dynamics, as well as its applications, we developed an in vitro system in which adiposomes, consisting of a hydrophobic core encircled by a monolayer-phospholipid membrane, were engineered into artificial lipoproteins (ALPs) by recruiting one or more kinds of apolipoproteins, for example, apolipoprotein (Apo) A-I, ApoE, ApoA-IV, and ApoB. In vitro and in vivo studies demonstrated the stability and biological activity of ALPs derived from adiposomes, which resembles native lipoproteins. Of note, adiposomes bearing ApoE were internalized via clathrin-mediated endocytosis following LDLR binding and were delivered to lysosomes. On the other hand, adiposomes bearing ApoA-IV mimicked the existing form of endogenous ApoA-IV and exhibited significant improvement in glucose tolerance in mice. In addition, the construction process was simple, precise, reproducible, as well as easy to adjust for mass production. With this experimental system, different apolipoproteins can be recruited to build ALPs for some biological goals and potential applications in biomedicine.

3.
BMC Genomics ; 24(1): 607, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821824

RESUMO

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes.


Assuntos
Lignanas , Plantas Medicinais , Schisandra , Plantas Medicinais/genética , Schisandra/genética , Transcriptoma , Metabolismo Secundário , Metaboloma
4.
PLoS Comput Biol ; 18(3): e1010009, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35320273

RESUMO

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the ALPL mutations showed a significant difference between the control, mild and severe HPP phenotypes. Molecular dynamics simulations coupled with protein structure network analysis were employed to analyze the effect of single-residue variation on conformational dynamics of TNSALP dimers, and the developed machine learning model suggested that the topological network parameters could serve as a robust indicator of severe mutations. The results indicated that the severity of disease-associated mutations is often linked with mutation-induced modulation of allosteric communications in the protein. This study suggested that ALPL mutations associated with mild and more severe HPPs can exert markedly distinct effects on the protein stability and long-range network communications. By linking the disease phenotypes with dynamic and allosteric molecular signatures, the proposed integrative computational approach enabled to characterize and quantify the allosteric effects of ALPL mutations and role of allostery in the pathogenesis of HPPs.


Assuntos
Fosfatase Alcalina , Hipofosfatasia , Fosfatase Alcalina/genética , Calcificação Fisiológica , Humanos , Hipofosfatasia/genética , Hipofosfatasia/patologia , Mutação , Fenótipo
5.
Phys Chem Chem Phys ; 25(20): 14311-14323, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37183444

RESUMO

Insights into the structures, functions and dynamics of Cordyceps militaris (C. militaris) sugar transporters are necessary for understanding their versatile metabolic capability for fungal growth. The sequence-function relationship study of 85 C. militaris sugar transporters showed that there is a gap between phylogenetic-based subfamily classification and their functions. Beyond protein sequences, structural modeling and principal component analysis of the structural ensemble revealed the different folds of the Car and Org subfamilies. Performing channel detection and network analysis found that the Alp and Hex subfamilies can be specifically distinguished from others by the betweenness of channel residues. Signature dynamics analysis further suggested that the Hex subfamily demonstrates different dynamics, with high flexibility at the H1 region in TM11. Furthermore, the H1 region as an allosteric site was examined by network parameter calculations that guided allosteric pathways between this region and the channel cavity. Together with gene expression data of C. militaris, e.g., Hex06741 in the Hex subfamily, it was promisingly expressed when sugar utilization was altered. This work demonstrates an in silico framework for investigating C. militaris sugar transporters as an example case study of the allosteric activity of the Hex subfamily and can facilitate sugar transporter engineering design that can further optimize the preferable sugar utilization and fermentation process of C. militaris.


Assuntos
Cordyceps , Cordyceps/química , Cordyceps/metabolismo , Regulação Alostérica , Filogenia , Sequência de Aminoácidos , Açúcares
6.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500587

RESUMO

DNA methyltransferases (DNMTs) including DNMT1 are a conserved family of cytosine methylases that play crucial roles in epigenetic regulation. The versatile functions of DNMT1 rely on allosteric networks between its different interacting partners, emerging as novel therapeutic targets. In this work, based on the modeling structures of DNMT1-ubiquitylated H3 (H3Ub)/ubiquitin specific peptidase 7 (USP7) complexes, we have used a combination of elastic network models, molecular dynamics simulations, structural residue perturbation, network modeling, and pocket pathway analysis to examine their molecular mechanisms of allosteric regulation. The comparative intrinsic and conformational dynamics analysis of three DNMT1 systems has highlighted the pivotal role of the RFTS domain as the dynamics hub in both intra- and inter-molecular interactions. The site perturbation and network modeling approaches have revealed the different and more complex allosteric interaction landscape in both DNMT1 complexes, involving the events caused by mutational hotspots and post-translation modification sites through protein-protein interactions (PPIs). Furthermore, communication pathway analysis and pocket detection have provided new mechanistic insights into molecular mechanisms underlying quaternary structures of DNMT1 complexes, suggesting potential targeting pockets for PPI-based allosteric drug design.


Assuntos
Regulação Alostérica/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Histonas/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA/genética , Epigênese Genética/genética , Histonas/genética , Humanos , Simulação de Dinâmica Molecular , Ligação Proteica/genética , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas/genética , Peptidase 7 Específica de Ubiquitina/genética
7.
Molecules ; 26(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919259

RESUMO

Proanthocyanidins are natural glycosidase inhibitors with excellent antioxidant activity. This study aims to search for a new source of proanthocyanidins for the prevention and treatment of type 2 diabetes with higher content and better activity and get their structure elucidated. First, the total proanthocyanidins contents (TOPCs), antioxidant activity, antidiabetic activity of seven common Polygonaceae plants were analyzed and compared. Then proanthocyanidins from the rhizome of Fagopyrum dibotrys were purified, and the detailed structure was comprehensively analyzed by ultraviolet visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), 13C nuclear magnetic resonance spectroscopy (13C NMR), reversed-phase high-performance liquid chromatography-electrospray mass spectrometry (RP-HPLC-ESI-MS), and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The rhizome of F. dibotrys showed the highest TOPCs, the strongest antioxidant, and antidiabetic activities; the TOPCs, antioxidant and antidiabetic activities were all very significantly positively correlated. Proanthocyanidins purified from the rhizome of F. dibotrys showed better antidiabetic activity than grape seed proanthocyanidins (GsPs). Seventy-two proanthocyanidins from trimer to undecamer with a mean degree of polymerization (mDP) of about 5.02 ± 0.21 were identified with catechin and epicatechin as the dominant monomers. Conclusion: Proanthocyanidins are the main antioxidant and antidiabetic active substances of F. dibotrys and are expected to be developed into potential antioxidant and hypoglycemic products.


Assuntos
Antioxidantes/farmacologia , Fagopyrum/química , Hipoglicemiantes/farmacologia , Proantocianidinas/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Rizoma/química , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Int J Med Sci ; 17(7): 931-938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308546

RESUMO

Objective: High-risk human papillomavirus (HPV) E6 and E7 proteins are the major oncoproteins involved in the tumorigenesis of cervical cancer. The long control region (LCR) in HPV plays an important role in regulating the expression of the E6 and E7 oncogenes. In the current study, we investigated the association of HPV16 LCR variations with cervical cancer. Methods: A total of 139 HPV16-positive cervical cancer patients (case group) and 116 HPV16-positive asymptomatic individuals (control group) were enrolled in the current study. Then, the HPV16 LCR was sequenced to determine the association between LCR variations and cervical cancer. Results: In the current study, HPV16 A1-A3 (19.4%), A4 (78.4%) and D3 (2.2%) variants were found in the case group. However, only A1-A3 (34.5%) and A4 variants (65.5%) were found in the control group. The distribution of the HPV16 variants between the case and control groups was significantly different (P=0.009). Moreover, a total of eleven variations (A7167G, A7173C, C7176T, C7200T, T7269C, C7286A, C7729A, C7763T, A7841G, G7867A and T24C) were significantly different between the case and control groups (P<0.05). For the sub-lineage analysis, only C7873G variations were significantly different between the case and control groups in the A4 (As) variant (P=0.039). Conclusion: Our results showed that specific variations in the HPV16 LCR were associated with cervical cancer. Our study will provide a good reference for further understanding of the relationship between HPV16 LCR variation and cervical cancer.


Assuntos
Povo Asiático/genética , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/microbiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Variação Genética , Papillomavirus Humano 16/patogenicidade , Humanos , Filogenia
9.
BMC Genomics ; 20(1): 780, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655539

RESUMO

BACKGROUND: Our previous study finds that male sterility in Salvia miltiorrhiza could result in stunted growth and reduced biomass, but their molecular mechanisms have not yet been revealed. In this article, we investigate the underlying mechanism of male sterility and its impact on plant growth and metabolic yield by using physiological analysis and mRNA sequencing (RNA-Seq). RESULTS: In this study, transcriptomic and physiological analysis were performed to identify the mechanism of male sterility in mutants and its impact on plant growth and metabolic yield. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it is found that the pathways are mainly enriched in processes including organ development, primary metabolic process and secondary metabolic process. Physiological analysis show that the chloroplast structure of male sterile mutants of S. miltiorrhiza is abnormally developed, which could result in decrease in leaf gas exchange (A, E and gs), chlorophyll fluorescence (Fv, Fm and Fv/Fm), and the chlorophyll content. Expression level of 7 differentially expressed genes involved in photosynthesis-related pathways is downregulated in male sterile lines of S. miltiorrhiza, which could explain the corresponding phenotypic changes in chlorophyll fluorescence, chlorophyll content and leaf gas exchange. Transcriptomic analysis establishes the role of disproportionating enzyme 1 (DPE1) as catalyzing the degradation of starch, and the role of sucrose synthase 3 (SUS3) and cytosolic invertase 2 (CINV2) as catalyzing the degradation of sucrose in the S. miltiorrhiza mutants. The results also confirm that phenylalanine ammonialyase (PAL) is involved in the biosynthesis of rosmarinic acid and salvianolic acid B, and flavone synthase (FLS) is an important enzyme catalyzing steps of flavonoid biosynthesis. CONCLUSIONS: Our results from the physiological and transcriptome analysis reveal underlying mechanism of plant growth and metabolic yield in male sterile mutants, and provide insight into the crop yield of S. miltiorrhiza.


Assuntos
Perfilação da Expressão Gênica , Folhas de Planta/genética , Folhas de Planta/fisiologia , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/fisiologia , Clorofila/metabolismo , Cloroplastos/metabolismo , Ontologia Genética , Fotossíntese/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Piridinas/metabolismo , Salvia miltiorrhiza/crescimento & desenvolvimento , Salvia miltiorrhiza/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 41(4): 643-647, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-28871686

RESUMO

To research the expression of key enzymes in saikosaponin biosynthesis and the content of saikosaponin under the drought stress, the study focused on the gene-level and the end product responses to environmental change. Taking the five months of Bupleurum chinense as research materials, the contents of saikosaponin A and saikosaponin D under different stress levels were measured by HPLC. The drought was simulated by poly ethylene glycol. The real-time fluorescence quantitative PCR was used to analyze the expression of four key enzymes genes HMGR, IPPI, FPS, ß-AS and the expression of ß-tubulin was set as a reference gene. The results showed that drought stress significantly improved the content of saikosaponin. The contents of SSa and SSd were highest researching 0.648% and 0.781%, respectively when the concentration of PEG was 10%. Meanwhile, the results reflected that the expression of four key enzymes had risen differently and FPS, ß-AS raised significantly(P<0.01). In addition, the results of correlation analysis showed that there was a significant positive correlation between the expression of the four key enzymes genes and the content of saikosaponin. In a word, the contents of secondary metabolites were regulated by the expression of key enzymes genes under the drought stress in B. chinense.


Assuntos
Bupleurum/enzimologia , Ácido Oleanólico/análogos & derivados , Proteínas de Plantas/genética , Saponinas/biossíntese , Bupleurum/química , Bupleurum/genética , Bupleurum/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Ácido Oleanólico/biossíntese , Ácido Oleanólico/química , Proteínas de Plantas/metabolismo , Saponinas/química , Água/análise , Água/metabolismo
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(3): 435-9, 2014 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-24943024

RESUMO

OBJECTIVE: To investigate the use of antibacterial agents for emergency patients with acute upper respiratory infections in tertiary hospitals in Beijing. METHODS: We used the medical claim data for urban workers in 10 tertiary hospitals in Beijing from Oct. 2010 to Sep. 2012. Medical records of emergency patients with acute upper respiratory tract infections had been selected as the study sample. The proportions of antibacterial prescriptions and categories of antibacterial drugs were described and analyzed. RESULTS: This study included 135 979 visitors (male: 42.7%; mean age: 43.6 ± 16.2 years). The average antibacterial prescription rate was 71.2% (95%CI 71.0%-71.5%), of which the single kind use was 80.0% (95% CI 79.7%-80.2%). Among acute upper respiratory tract infections, the antibacterial prescription rate for acute tonsillitis visits was highest (85.1%, 95%CI 84.5%-85.6%), followed by acute laryngitis and bronchitis (81.69%, 95% CI 80.4%-82.8%), acute pharyngitis (81.4%, 95% CI 77.7%-85.0%), acute sinusitis (77.0%, 95% CI 74.6%-79.4%), acute nasopharyngitis (74.3%, 95% CI 73.7%-75.0%), and common cold (67.6%, 95% CI 67.3%-67.9%). Compared with the female group, the antibacterial prescription rate for the male was higher (73.2%, 95%CI 72.8%-73.6% vs. 69.7%, 95%CI 69.4%-70.0%). Compared with the <60 years age cases, the antibacterial prescription rate for the ≥ 60 years cases was higher (72.1%, 95% CI 71.8%-72.3% vs. 66.8%, 95% CI 66.2%-67.5%). In the visitors who used antibacterial drugs, the average percentage of injection use was 50.6% (95% CI 50.3%-50.9%). The top antibacterial drugs in the list of varieties were the second generation cephalosporins (28.4%), followed by the third generation cephalosporins (21.7%), fluoroquinolones (21.0%) and macrolides (17.6%). CONCLUSION: The antibacterial prescription rate for acute upper respiratory tract infections in the general hospitals in Beijing is high, and the second generation cephalosporins, third generation cephalosporins, fluoroquinolones and macrolides take the lead in the total antibacterial drugs.


Assuntos
Antibacterianos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Infecções Respiratórias/tratamento farmacológico , Centros de Atenção Terciária , Doença Aguda , Adulto , Uso de Medicamentos , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Ophthalmol Ther ; 13(5): 1159-1170, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441857

RESUMO

INTRODUCTION: To analyze the correlation between orbital compliance and retinal vessel density (VD) based on dynamic Scheimpflug analyzer (Corvis ST) and optical coherence tomographic angiography (OCT-A). METHODS: In this prospective observational study, 65 eyes of 44 patients with thyroid-associated ophthalmopathy (TAO) in quiescent stage were included (15 males and 29 females). The whole eye movement (WEM) was detected by Corvis ST. The superficial capillary plexus VD (SCP-VD) and deep capillary plexus VD (DCP-VD) were obtained by scanning the 3 × 3 mm area around the fovea using OCT-A, while the peripapillary vessel density (ppVD) was obtained by scanning the 4.5 × 4.5 mm area around the optic disk. Covariances including biomechanically corrected intraocular pressure (bIOP), axial length, age and gender were adjusted during data analysis. RESULTS: The mean WEM of the participants was 0.235 ± 0.066 mm. The mean SCP-VD and DCP-VD in whole image were 46.20% ± 3.77% and 50.51% ± 3.96%; the mean whole pp-VD was 49.75% ± 2.01%. WEM was positively correlated with SCP-VD (r = 0.327, p = 0.01) and the whole pp-VD (r = 0.394, p < 0.01) after adjusting by gender, axial length (AL), age and bIOP, but it was not significantly correlated with DCP-VD (r = 0.072 p = 0.581). CONCLUSION: Increase in orbital pressure might reduce retinal microvascular perfusion. Our data suggest orbital mechanical compression may be an important cause of retinal VD changes in quiescent patients with TAO.

13.
Drug Deliv ; 31(1): 2361169, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38828914

RESUMO

Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products.


Assuntos
Produtos Biológicos , Membrana Celular , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Humanos , Membrana Celular/metabolismo , Biomimética/métodos , Animais , Materiais Biomiméticos/química , Sistemas de Liberação de Medicamentos/métodos , Disponibilidade Biológica , Solubilidade , Nanopartículas/química
14.
Food Chem ; 442: 138485, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38278106

RESUMO

INTRODUCTION: Ellagic acid (EA), commonly found in foods, offers significant health benefits in combating chronic diseases. However, its therapeutic potential is hindered by its extremely poor solubility and bioavailability. METHOD: In this study, EA nanoparticles (EA NPs) were produced using a sono-assembly method, without additional agents. RESULTS: EA NPs exhibited stick-like nanoparticle structures with an average size of 147.3 ± 0.73 nm. EA NPs likely adopt a tunnel-type solvate structure, with 4 water participating in disruption of intramolecular hydrogen bonds in EA and establishment of intermolecular hydrogen bonds between EAs. Importantly, EA NPs exhibited remarkable enhancements in water solubility, with 120.7-fold increase in water, and 97.8-fold increase in pH 6.8 buffer. Moreover, ex vivo intestinal permeability studies demonstrated significant improvements (P < 0.5). These findings were further supported by in vivo pharmacokinetic studies, where EA NPs significantly enhanced the relative bioavailability of EA by 4.69 times.


Assuntos
Nanopartículas , Nanoestruturas , Solubilidade , Ácido Elágico/química , Disponibilidade Biológica , Nanopartículas/química , Água
15.
Comput Biol Med ; 155: 106665, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36791552

RESUMO

Thymic epithelial tumors (TETs) are rare malignant tumors, and the molecular mechanisms of both primary and recurrent TETs are poorly understood. Here we established comprehensive proteomic signatures of 15 tumors (5 recurrent and 10 non-recurrent) and 15 pair wised tumor adjacent normal tissues. We then proposed an integrative network approach for studying the proteomics data by constructing protein-protein interaction networks based on differentially expressed proteins and a machine learning-based score, followed by network modular analysis, functional enrichment annotation and shortest path inference analysis. Network modular analysis revealed that primary and recurrent TETs shared certain common molecular mechanisms, including a spliceosome module consisting of RNA splicing and RNA processing, but the recurrent TET was specifically related to the ribosome pathway. Applying the shortest path inference to the collected seed gene module identified that the ribonucleoprotein hnRNPA2B1 probably serves as a potential target for recurrent TET therapy. The drug repositioning combined molecular dynamics simulations suggested that the compound ergotamine could potentially act as a repurposing drug to treat recurrent TETs by targeting hnRNPA2B1. Our study demonstrates the value of integrative network analysis to understand proteotype robustness and its relationships with genotype, and provides hits for further research on cancer therapeutics.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Humanos , Proteômica , Neoplasias do Timo/genética , Neoplasias do Timo/metabolismo , Neoplasias do Timo/patologia , Redes Reguladoras de Genes
16.
Cell Mol Immunol ; 20(7): 739-776, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37198402

RESUMO

Over the past thirty years, the importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been increasingly recognized. Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes, including host homeostasis and responses to disease. Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity. Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases, including cancer, immune and inflammatory diseases, and metabolic and neurological disorders, which render the system a focus of studies aiming to discover therapies and important biomarkers. The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states, including, among others, coronavirus disease 2019 (COVID-19). In this review, by reporting the latest advances in chemokine biology and results from analyses of a plethora of sequencing-based datasets, we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network, focusing on chemokine-mediated inflammation and cancer. Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.


Assuntos
COVID-19 , Medicina de Precisão , Humanos , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , COVID-19/genética , Quimiocinas/genética , Quimiocinas/metabolismo , Epigênese Genética
17.
J Autism Dev Disord ; 52(11): 4897-4907, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34800227

RESUMO

Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder with no clinical biomarker. This study used untargeted metabolomic analysis to identify metabolic characteristics in plasma that can distinguish ASD children. 29 boys with ASD (3.02 ± 0.67 years) and 30 typically developing (TD) boys (3.13 ± 0.46 years) were recruited. Developmental and behavioral assessments were conducted in ASD group. Samples of plasma were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between metabolite concentration and scale score was assessed by Spearman rank correlation. Altered metabolic characteristics were found in boys with ASD. In Receiver Operating Characteristic (ROC) analysis, ornithine had the highest AUC (Area under ROC) value. Furthermore, the concentration of choline and ornithine was negatively correlated with ABC-language score in ASD group.


Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/diagnóstico , Biomarcadores , Criança , Colina , Cromatografia Líquida , Humanos , Masculino , Ornitina , Espectrometria de Massas em Tandem
18.
Int J Dev Disabil ; 68(4): 495-499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937175

RESUMO

Objective: This study intends to explore the effect of parent-training program on the rehabilitation intervention in children with autism spectrum disorder (ASD) in Chinese-speaking areas of China by offering parent skill training and psychology counseling. Methods: From January 2018 to June 2019, a total of 80 children diagnosed with ASD from the Department of Children Healthcare of Wuxi Children's Hospital were randomly grouped into the parent training groups and control groups. Parents in the training group received 12 weeks of skill training, including 8 group and 2 individual training sessions, as well as psychology counseling. This enabled them to give their children >2 h of intervention training daily in a natural environment. Children in the control group were placed on a rehabilitation waiting list or received general community training. Before grouping and after the intervention, all children underwent neuropsychological evaluations with Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Gesell Developmental Schedule (GDS). GDS covers five sectors, namely adaptive behavior, gross motor, fine motor, language, and personal-social behavior. Results: Statistically significant differences were not detected between the two groups in ABC, CARS, and GDS scoring at baseline evaluation. And significant differences were detected between the two groups in ABC, CARS, adaptive behavior, and personal-social behavior scoring at endpoint evaluation. Furthermore, the re-evaluation results of ABC scoring and CARS scoring of the children in the parent training group decreased significantly from the preliminary evaluation results when compared before and after the intervention. Moreover, the intragroup comparison of adaptive behavior scoring, language scoring, and personal-social behavior scoring of the experiment group increased significantly from the preliminary evaluation results, while the difference of the same of the children in the control group between re-evaluation and preliminary evaluation did not differ significantly. Conclusions: In China, the parent-training program enables parents to train ASD children in a natural environment, which would markedly improve behavioral problems, core symptoms, adaptability, language competence, and social development capability.

20.
Hum Immunol ; 80(5): 325-334, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30797823

RESUMO

The endoplasmic reticulum aminopeptidases (ERAPs), ERAP1 and ERAP2, makes a role in shaping the HLA class I peptidome by trimming peptides to the optimal size in MHC-class I-mediated antigen presentation and educating the immune system to differentiate between self-derived and foreign antigens. Association studies have shown that genetic variations in ERAP1 and ERAP2 genes increase susceptibility to autoimmune diseases, infectious diseases, and cancers. Both ERAP1 and ERAP2 genes exhibit diverse polymorphisms in different populations, which may influence their susceptibly to the aforementioned diseases. In this article, we review the distribution of ERAP1 and ERAP2 gene polymorphisms in various populations; discuss the risk or protective influence of these gene polymorphisms in autoimmune diseases, infectious diseases, and cancers; and highlight how ERAP genetic variations can influence disease associations.


Assuntos
Aminopeptidases/genética , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Aminopeptidases/química , Aminopeptidases/metabolismo , Apresentação de Antígeno/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Evolução Molecular , Genética Populacional , Genótipo , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Antígenos de Histocompatibilidade Menor/química , Antígenos de Histocompatibilidade Menor/metabolismo , Grupos Raciais/genética , Relação Estrutura-Atividade
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