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1.
Acta Pharmaceutica Sinica ; (12): 448-454, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1016649

RESUMO

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

2.
Acta Anatomica Sinica ; (6): 41-419, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1015194

RESUMO

Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.

3.
Chinese Journal of Hematology ; (12): 642-648, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1012206

RESUMO

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.


Assuntos
Masculino , Humanos , Pessoa de Meia-Idade , Asparaginase/uso terapêutico , Prognóstico , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo , Ciclofosfamida , Metotrexato/uso terapêutico , DNA/uso terapêutico , Resultado do Tratamento
4.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 188-197, 2023.
Artigo em Chinês | WPRIM | ID: wpr-965833

RESUMO

ObjectivePeriprosthetic joint infections (PJI) are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI, the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty (TJA). MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 (2 394 with primary TJA, 87 with aseptic revision and 36 with PJI). We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen (FBG), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), PLT / MPV, PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%, a specificity of 93.07% (Primary TJA group vs. PJI group). Similarly, the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%, a specificity of 95.40% between the other two groups (Aseptic revision group vs. PJI group). ROC curve analysis demonstrated moderate diagnostic performance of FBG (AUC value), indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.

5.
Journal of China Pharmaceutical University ; (6): 56-61, 2023.
Artigo em Chinês | WPRIM | ID: wpr-965253

RESUMO

@#Chemical constituents of n-butanol part of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied.Eight glycosides were separated and purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography.Based on the physicochemical properties and spectral data, these compounds were 3-ethyl-4-methyl-pentyl ester-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1), juglanoside E (2), (4S)-α-terpineol-8-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (3), (4S)-α-terpineol-8-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (4), eugenyl-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucuronopyranosyl methylester (6), kaempferol-3-O-β-D-glucuronopyranoside (7), and quercetin-3-O-β-D-glucuronopyranoside (8).Among them, compound 1 was a new compound, and compounds 2-6 were isolated from the genus Cyclocarya for the first time.

6.
China Journal of Chinese Materia Medica ; (24): 2116-2125, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981343

RESUMO

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.


Assuntos
Camundongos , Animais , Imiquimode , Medicamentos de Ervas Chinesas/farmacologia , Ácido Glicirrízico , Cromatografia Líquida de Alta Pressão/métodos
7.
Chinese Journal of Medical Genetics ; (6): 301-307, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970923

RESUMO

OBJECTIVE@#To explore the genetic basis for 4 patients with globozoospermia.@*METHODS@#Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region.@*CONCLUSION@#DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.


Assuntos
Masculino , Humanos , Teratozoospermia/genética , Homozigoto , Sêmen , Deleção de Sequência , Regiões 3' não Traduzidas , Proteínas de Membrana
8.
China Journal of Chinese Materia Medica ; (24): 1553-1557, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970627

RESUMO

Two prenylated 2-arylbenzofurans were isolated from roots of Artocarpus heterophyllus, with a combination of various chromatographic approaches, including ODS, MCI, Sephadex LH-20, and semipreparative high performance liquid chromatography(HPLC). They were identified as 5-[6-hydroxy-4-methoxy-5,7-bis(3-methylbut-2-enyl)benzofuran-2-yl]-1,3-benzenediol(1) and 5-[2H,9H-2,2,9,9-tetramethyl-furo[2,3-f]pyrano[2,3-h][1]benzopyran-6-yl]-1,3-benzenediol(2) with spectroscopic methods, such as HR-ESI-MS, IR, 1D NMR, and 2D NMR, and named artoheterins B(1) and C(2), respectively. The anti-respiratory burst activities of the two compounds were evaluated with rat polymorphonuclear neutrophils(PMNs) stimulated by phorbol 12-myristate 13-acetate(PMA). The results showed that 1 and 2 exhibited significant inhibitory effect on respiratory burst of PMNs with IC_(50) values of 0.27 and 1.53 μmol·L~(-1), respectively.


Assuntos
Ratos , Animais , Estrutura Molecular , Artocarpus/química , Extratos Vegetais/farmacologia , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química
9.
China Journal of Chinese Materia Medica ; (24): 183-192, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970513

RESUMO

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.


Assuntos
Animais , Camundongos , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida de Alta Pressão , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sirtuína 1 , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
10.
Chinese Journal of Hematology ; (12): 479-483, 2023.
Artigo em Chinês | WPRIM | ID: wpr-984647

RESUMO

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.


Assuntos
Humanos , Bacteriemia/epidemiologia , Cefoperazona , Sulbactam , Estudos Retrospectivos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Neoplasias Hematológicas , Sepse , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Combinação Piperacilina e Tazobactam , Escherichia coli
11.
China Journal of Chinese Materia Medica ; (24): 6030-6038, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1008801

RESUMO

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and β,β'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and β,β'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of β,β'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.


Assuntos
Rizosfera , Microbiologia do Solo , Bactérias/genética , Fósforo , Solo , Boraginaceae
12.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 15-27, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1015733

RESUMO

Mitochondria, originated from the last eukaryotic common ancestor by endosymbiosis, are semi-autonomous double-membrane organelles. The oxidative phosphorylation system consists of five complexes that are coordinately encoded by the nuclear and mitochondrial genomes, and establishes the electron transport chain in the mitochondrial inner membrane, concurrently generating ATP using the proton gradient. The proton-pumping Complex I (NADH:ubiquinone oxidoreductase) is the first, large stand most complicated enzyme required in this process. Complex I is an L-shaped multimeric enzyme harbouring over 40 subunits, one FMN molecule and eight Fe-S clusters. In recent years, biochemical, genetic, proteomic and crysta-structure analyses of Complex I in several model systems have provided valuable insights into its function and biogenesis. This review summarizes our current understanding of Complex I structural modules, assembly pathway and factors, discusses their similarities and distinctions between animals and plants, as well as the evolution of Complex I. And we proposes some potentially important but yet unsolved questions of Complex I. Therefore, this review provides a relevant reference for further comprehensively deepening the function and evolution of mitochondrial Complex I.

13.
Journal of Experimental Hematology ; (6): 455-460, 2022.
Artigo em Chinês | WPRIM | ID: wpr-928736

RESUMO

OBJECTIVE@#To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma.@*METHODS@#Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified.@*RESULTS@#44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013).@*CONCLUSION@#CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.


Assuntos
Humanos , Histonas , Mieloma Múltiplo/genética , Recidiva Local de Neoplasia , Oligopeptídeos/uso terapêutico , Prognóstico , Receptores CXCR4
14.
Journal of Experimental Hematology ; (6): 386-392, 2022.
Artigo em Chinês | WPRIM | ID: wpr-928725

RESUMO

OBJECTIVE@#To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia (B-ALL) cells to Vincristine (VCR) and the mechanisms.@*METHODS@#B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels.@*RESULTS@#CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups.@*CONCLUSION@#Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.


Assuntos
Humanos , Actinas/farmacologia , Apoptose , Hipóxia Celular , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Mensageiro , Vincristina/farmacologia , Proteína X Associada a bcl-2/farmacologia
15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 149-156, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906062

RESUMO

Objective:To compare the chemical constituents of Puerariae Flos from three different varieties of <italic>Pueraria montana</italic> var. <italic>lobata</italic>, <italic>P. montana</italic> var. <italic>thomsonii</italic> and <italic>P</italic>. <italic>montana</italic> var<italic>. montana</italic>. Method:Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used with the mobile phase of 0.1% formic acid aqueous solution (A)-acetonitrile (B) for gradient elution (0-20 min, 10%-30%B; 20-30 min, 30%-55%B; 30-35 min, 55%-95%B; 35-37 min, 95%B; 37-40 min, 95%-10%B), the flow rate was 0.25 mL·min<sup>-1</sup>. Electrospray ionization (ESI) was used to scan and collect MS data in positive and negative ion modes with scanning range of <italic>m</italic>/<italic>z</italic> 50-1 500. The chemical components from different sources of Puerariae Flos were identified in combination with the chemical composition database and literature information. After the obtained data were normalized by MarkerView<sup>TM</sup> 1.2.1, they were imported into SICMA-P 14.1 software for principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to select the main differentiated components among the three different varieties. Result:A total of 35 compounds were identified from three different varieties of Puerariae Flos, including 22 isoflavones, 6 flavonoids and 7 saponins. The flowers of <italic>P</italic>. <italic>lobata</italic>, <italic>P. montana</italic> var. <italic>thomsonii</italic> and <italic>P</italic>. <italic>montana</italic> var<italic>. montana</italic> contained 32, 35, 33 compounds, respectively. And 18 differential compounds were screened under the positive and negative ion modes, including kakkalide, tectoridin, 6″-<italic>O</italic>-xylosyl-tectoridin, 4'-methyltectorigenin-7-glucoside, glycitin, 6″-<italic>O</italic>-xylosyl-glycitin, irisolidone, kaikasaponin Ⅲ, 6″-<italic>O</italic>-malonylglycitin, kakkalidone, tectorigenin, rutin, soyasaponin BB, vitexin, biochanin A, genistin, kakkatin, azukisaponin Ⅱ. Conclusion:This research is the first to systematically study the chemical constituents of the flower of <italic>P</italic>. <italic>montana</italic> var<italic>. montana</italic>, although the flower of <italic>P</italic>. <italic>montana</italic> var<italic>. montana</italic> is used as adulterants, it has high contents of tectoridin and 6″-<italic>O</italic>-xylosyl-tectoridin, which has great potential for development. The efficacy components such as kakkalide and tectoridin in Puerariae Flos from the three sources of varieties are obviously different, and it is necessary to carefully consider the application of these three varieties as Puerariae Flos.

16.
Acta Anatomica Sinica ; (6): 913-916, 2021.
Artigo em Chinês | WPRIM | ID: wpr-1015386

RESUMO

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G

17.
China Journal of Chinese Materia Medica ; (24): 2149-2157, 2021.
Artigo em Chinês | WPRIM | ID: wpr-879172

RESUMO

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.


Assuntos
Farmacognosia , Raízes de Plantas/genética , Pueraria
18.
Chinese Medical Journal ; (24): 326-333, 2021.
Artigo em Inglês | WPRIM | ID: wpr-878020

RESUMO

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.


Assuntos
Humanos , Monofosfato de Adenosina , Núcleos Anteriores do Tálamo , Proteínas Quinases Dependentes de AMP Cíclico , Estimulação Encefálica Profunda , Epilepsia/terapia , Epilepsia do Lobo Temporal/terapia , Hipocampo , Fibras Musgosas Hipocampais , Transdução de Sinais
19.
Electron. j. biotechnol ; 47: 59-71, sept. 2020. tab, ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1253080

RESUMO

BACKGROUND: Procambarus clarkii produces high-quality, delicious meat that is high in protein, low in fat, and rich in calcium and phosphorus. It has become an important aquatic resource in China. Our objectives are (i) to analyze the level of genetic diversity of P. clarkii populations; (ii) to explore the genetic differentiation (Gst); and (iii) to propose appropriate strategies for the conservation. RESULTS: In this study, Shannon's index (I) and Nei's gene diversity index (H) for P. clarkii were high (I = 0.3462 and H = 0.2325 on average and I = 0.6264, H = 0.4377 at the species level) based on the SSR markers. The expected heterozygosity value of 17 microsatellite loci in 25 crayfish populations was 0.9317, the observed heterozygosity value was 0.9121, and the observed number of alleles per locus was 2.000; and the effective number of alleles per locus was 1.8075. Among the P. clarkii populations, the inbreeding coefficient within populations (Fis) was 0.2315, overall inbreeding coefficient (Fit) was 0.4438, genetic differentiation coefficient among populations (Fst) was 0.3145 and gene differentiation (Gst) was 0.4785 based on SSR analyses. The cluster analysis results obtained by unweighted pair-group method with arithmetic mean (UPGMA) analysis, principal coordinate analysis (PCoA) and STRUCTURE analysis were similar. A mantel test showed that the isolation-by-distance pattern was not significant. CONCLUSIONS: The high Gst among P. clarkii populations is attributed to genetic drift and geographic isolation. The results indicated that more P. clarkii populations should be collected when formulating conservation and aquaculture strategies.


Assuntos
Animais , Variação Genética , Repetições de Microssatélites , Astacoidea/genética , Filogenia , China , Reação em Cadeia da Polimerase , Aquicultura , Ambiente Aquático , Áreas Alagadas , Triagem de Portadores Genéticos
20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 119-125, 2020.
Artigo em Chinês | WPRIM | ID: wpr-872929

RESUMO

Objective:To study the components with urate anion transporter 1(URAT1) regulation effect and their combination mechanisms of Lagotis brevituba by integrating techniques of HK-2 cell capture,UPLC-Q-TOF-MS and molecular docking,so as to provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba. Method:The HK-2 cells were applied to capture the components of L. brevituba. UPLC-Q-TOF-MS was used to identify those components. The molecular docking technique was adopted to study the interaction mechanism between the compounds and URAT1. Result:Eight components were successfully screened and identified as hyperoside,plantamajoside,kaempferol-3-O-glucoside,lugrandoside,nepitrin,isolugrandoside,homoplantaginin,luteolin,respectively. Those components could combine with URAT1 mainly through hydrogen bond,van der Waals force and hydrophobic action,which were closely related to structure and compound types. Furthermore,the LibDock score of phenylethanoids was higher than that of flavonoids. Conclusion:The integration of target cell capture,UPLC-Q-TOF-MS and molecular docking techniques could be successfully used to identify captured compounds of L. brevituba with URAT1 regulation effects and illustrate their potential combination mechanisms as well as the structure-activity relationships. The findings may provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba.

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