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1.
Acta Pharmacol Sin ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085407

RESUMO

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

2.
Phytochemistry ; 226: 114206, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38972440

RESUMO

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.


Assuntos
Células 3T3-L1 , Croton , Diterpenos , Hipoglicemiantes , Folhas de Planta , Ratos Sprague-Dawley , Folhas de Planta/química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Croton/química , Animais , Camundongos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Ratos , Estrutura Molecular , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Resistência à Insulina , Glicemia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos
3.
J Vis Exp ; (204)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38372363

RESUMO

DNA double-strand breaks (DSBs) represent the most perilous DNA lesions, capable of inducing substantial genetic information loss and cellular demise. In response, cells employ two primary mechanisms for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). Quantifying the efficiency of NHEJ and HR separately is crucial for exploring the relevant mechanisms and factors associated with each. The NHEJ assay and HR assay are established methods used to measure the efficiency of their respective repair pathways. These methods rely on meticulously designed plasmids containing a disrupted green fluorescent protein (GFP) gene with recognition sites for endonuclease I-SceI, which induces DSBs. Here, we describe the extrachromosomal NHEJ assay and HR assay, which involve co-transfecting HEK-293T cells with EJ5-GFP/DR-GFP plasmids, an I-SceI expressing plasmid, and an mCherry expressing plasmid. Quantitative results of NHEJ and HR efficiency are obtained by calculating the ratio of GFP-positive cells to mCherry-positive cells, as counted by flow cytometry. In contrast to chromosomally integrated assays, these extrachromosomal assays are more suitable for conducting comparative investigations involving multiple established stable cell lines.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Humanos , Proteínas de Fluorescência Verde/genética , Células HEK293 , Recombinação Homóloga , Reparo do DNA por Junção de Extremidades
4.
DNA Repair (Amst) ; 133: 103603, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029687

RESUMO

Cytoplasmic FAM21 works as a guiding protein in Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is involved in the nuclear WASH localization and DNA repair remains to be clarified. Here, we show that FAM21 interacts with Ku and the interaction between C-terminal FAM21 and Ku is essential for its recruitment to DSB sites. Moreover, FAM21 depletion led to decreases in WASH recruitment to damaged DNA and repair capacity upon DNA damage. Taken together, these results reveal that FAM21 promotes DNA repair by orchestrating the recruitment of WASH to DSB sites, providing a mechanistic insight into WASH-dependent DNA DSB repair.


Assuntos
Reparo do DNA , Proteínas , Reparo do DNA por Junção de Extremidades , Dano ao DNA , DNA , Autoantígeno Ku
5.
Acta Anatomica Sinica ; (6): 17-24, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015146

RESUMO

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1039059

RESUMO

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

7.
PLoS One ; 18(10): e0293327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883350

RESUMO

BACKGROUND: Psoriasis is a systemic immune-mediated chronic inflammatory skin disease; its systemic manifestations and periodic recurrence negatively affect a patient's quality of life. Inflammatory cytokines are known to have an important role in the onset and progression of psoriasis, however, data on the association between circulating inflammatory cytokines and psoriasis risk is inconclusive. Here, we explore the relevance of circulating proinflammatory factors to the pathogenesis of psoriasis using a meta-analysis. OBJECTIVE: To explore the association between circulating levels of inflammatory factors and psoriasis to elucidate the mechanisms underlying psoriasis and improve clinical diagnosis and treatment. METHODS: We systematically retrieved articles published in PubMed, EMBASE, the Cochrane Library and the Web of Science from the establishment of each database to January 2023. The standard mean difference (SMD) in cytokine levels of individuals with psoriasis and healthy controls was used to check for correlations between circulating inflammatory factor levels and psoriasis. RESULTS: Fifty-seven studies, with data from 2838 patients, were retrieved and included in the meta-analysis. Eleven inflammatory factors were studied (circulating interleukin-2 (IL-2), IL-4, IL-12, IL-17, IL-18, IL-22, IL-23, IL-35, IL-36, transforming growth factor-beta (TGF-ß) and gamma-interferon (IFN-γ)). Of these, IL-2 [SMD = 1.29 (95% CI: 0.61-1.97; P <0.001)], IL-17 [SMD = 0.71 (95% CI: 0.12-1.30; P = 0.018)], IL-18 [SMD = 1.27 (95% CI: 0.64-1.90; P <0.001)], and IFN-γ [SMD = 1.90 (95% CI: 1.27-2.52; P <0.001)] levels had significant correlations with psoriasis. CONCLUSION: Increased serum concentrations of the circulating inflammatory cytokines IL-2, IL-17, IL-18 and IFN-γ were significantly correlated with psoriasis.


Assuntos
Citocinas , Psoríase , Humanos , Interferon gama , Interleucina-17 , Interleucina-18 , Interleucina-2 , Psoríase/tratamento farmacológico , Qualidade de Vida
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 655-665, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37654146

RESUMO

Objective By review of the studies comparing the measurements properties of EuroQol five-dimensional questionnaire (EQ-5D) and short-form 6-dimension health survey (SF-6D) in Chinese populations,this study aims to provide a reference for selecting,applying,and improving the health-related quality of life and health utility measurement tools for Chinese populations.Methods We retrieved the original studies which compared the two tools from both Chinese and English databases and then summarized the findings of the included studies from the measurement properties.Results A total of 12 studies were screened out,including 9 studies about diseased populations and 3 studies about the general populations.The included studies generally demonstrated that both EQ-5D and SF-6D had good feasibility,while the utility scores generated from them cannot be used interchangeably.For the diseased populations,both EQ-5D and SF-6D and their utility scores had good construct validity,including convergent and known-groups validity,while only the utility scores had good construct validity for the general populations.For the diseased populations,SF-6D had smaller ceiling effect and better sensitivity than EQ-5D-3L,while the comparison results between SF-6D and EQ-5D-5L were inconsistent.For the general populations,SF-6D also had better sensitivity than EQ-5D.In addition,there was little comparative evidence for reliability such as test-retest reliability and responsiveness between SF-6D and SF-6D in the two populations.Conclusion This review summarized the characteristics,methods,results,and conclusions of the studies that directly compared the two tools for the populations in China.Although only the studies directly comparing EQ-5D and SF-6D are included in this review,the common findings in these studies provide a basis for better comparison between the two in the future.

9.
J Nat Prod ; 86(1): 199-208, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36635870

RESUMO

Fifteen compounds including nine new diterpenes were isolated from the roots of Croton yunnanensis. By HRESIMS, NMR, ECD data, and X-ray diffraction analysis, the new compounds were characterized as eight neo-clerodane diterpenes (compounds 1-8) and one 15,16-dinor-ent-pimarane diterpene (9). All diterpenes were assayed for their hypoglycemic activities. Compounds 1-4, 6, 7, and 10 promoted glucose uptake activity in insulin-resistant 3T3-L1 adipocytes. Compounds 1 and 6 showed insulin sensitizing activity, potentiating conspicuously their glucose uptake activity at a concentration of 20 µM when treated synergistically with low-concentration insulin at 1 nM.


Assuntos
Croton , Diterpenos Clerodânicos , Diterpenos , Insulinas , Croton/química , Hipoglicemiantes/farmacologia , Diterpenos/farmacologia , Diterpenos/química , Diterpenos Clerodânicos/química , Glucose , Estrutura Molecular
10.
J Asian Nat Prod Res ; 25(9): 842-848, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36562123

RESUMO

Further investigation on the roots of Aconitum weixiense led to the isolation of two new bis-diterpenoid alkaloids, named as weisaconitines E and F (1-2), which were elucidated by IR, HR-ESI-MS, 1D- and 2D-NMR analyses. Their structures are characterized as denudatine-atisine-type bis-diterpenoid alkaloids.


Assuntos
Aconitum , Alcaloides , Diterpenos , Medicamentos de Ervas Chinesas , Aconitum/química , Estrutura Molecular , Alcaloides/química , Medicamentos de Ervas Chinesas/química , Diterpenos/química , Raízes de Plantas/química
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008113

RESUMO

Objective By review of the studies comparing the measurements properties of EuroQol five-dimensional questionnaire (EQ-5D) and short-form 6-dimension health survey (SF-6D) in Chinese populations,this study aims to provide a reference for selecting,applying,and improving the health-related quality of life and health utility measurement tools for Chinese populations.Methods We retrieved the original studies which compared the two tools from both Chinese and English databases and then summarized the findings of the included studies from the measurement properties.Results A total of 12 studies were screened out,including 9 studies about diseased populations and 3 studies about the general populations.The included studies generally demonstrated that both EQ-5D and SF-6D had good feasibility,while the utility scores generated from them cannot be used interchangeably.For the diseased populations,both EQ-5D and SF-6D and their utility scores had good construct validity,including convergent and known-groups validity,while only the utility scores had good construct validity for the general populations.For the diseased populations,SF-6D had smaller ceiling effect and better sensitivity than EQ-5D-3L,while the comparison results between SF-6D and EQ-5D-5L were inconsistent.For the general populations,SF-6D also had better sensitivity than EQ-5D.In addition,there was little comparative evidence for reliability such as test-retest reliability and responsiveness between SF-6D and SF-6D in the two populations.Conclusion This review summarized the characteristics,methods,results,and conclusions of the studies that directly compared the two tools for the populations in China.Although only the studies directly comparing EQ-5D and SF-6D are included in this review,the common findings in these studies provide a basis for better comparison between the two in the future.

12.
Ann Allergy Asthma Immunol ; 129(3): 360-365.e1, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35598882

RESUMO

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.


Assuntos
Etanercepte , Síndrome de Stevens-Johnson , Corticosteroides/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Esteroides/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico
13.
Reprod Biol ; 22(2): 100637, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338913

RESUMO

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.


Assuntos
MicroRNAs , Síndrome do Ovário Policístico , Apoptose , Proliferação de Células , Feminino , Humanos , Insulina/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Síndrome do Ovário Policístico/metabolismo , RNA Circular/genética
14.
J Nat Prod ; 85(2): 405-414, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35080403

RESUMO

Thirty-five tigliane diterpenoids and two ent-kaurane diterpenoids were isolated from the leaves of Croton damayeshu, and, among them, compounds 1-10 were characterized as new tigliane diterpenoids. The structures of compounds 1-10 were determined by analysis of their HRESIMS, NMR, and ECD data and by chemical methods. The isolates were assayed for their larvicidal, antifungal, and α-glucosidase inhibitory activities, and compounds 8-10 were found to possess larvicidal activities against Plutella xylostella with LC50 values of 0.19, 0.16, and 0.26 µM, respectively, comparable to the LC50 of 0.14 µM for the positive control, flubendiamide.


Assuntos
Croton , Diterpenos do Tipo Caurano , Diterpenos , Forbóis , Antifúngicos/farmacologia , Croton/química , Diterpenos/química , Diterpenos do Tipo Caurano/farmacologia , Estrutura Molecular , alfa-Glucosidases
15.
Acta Pharmaceutica Sinica ; (12): 3224-3232, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-906849

RESUMO

In this study, exosomes were extracted from human malignant melanoma cell A375. Folic acid (FA) receptor was used as target and triptolide (TPL) was used as model drug to prepare exosome targeted drug delivery system, FA-Exo/TPL. The physicochemical properties and antitumor effect were evaluated in vivo and in vitro. Gradient centrifugation method was applied to collect exosomes. Then, exosome was modified with FA for loading TPL. The particle sizes of the FA-Exo/TPL were about 100 nm with a double-layer membrane structure like a tray. It is characteristic of high encapsulation efficiency and drug loading. In vitro experiments showed that FA-Exo/TPL could be effectively uptaken by A375 cells, thus significantly inhibiting proliferation and promoting apoptosis the cells. In vivo experiment results showed that FA-Exo/TPL could effectively inhibit the growth of tumor tissue, prolong the model mice life cycle, and significantly reduce the systemic toxicity of the free drug, playing a synergistic and toxic role. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Fudan University Shanghai Cancer Center. This study provides a new strategies and methods for the preparation of TPL against malignant melanoma.

16.
Chinese Journal of Biotechnology ; (12): 2845-2855, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-887847

RESUMO

Production of biofuels such as ethanol from non-grain crops may contribute to alleviating the global energy crisis and reducing the potential threat to food security. Tobacco (Nicotiana tabacum) is a commercial crop with high biomass yield. Breeding of starch-rich tobacco plants may provide alternative raw materials for the production of fuel ethanol. We cloned the small subunit gene NtSSU of ADP-glucose pyrophosphorylase (NtAGPase), which controls starch biosynthesis in tobacco, and constructed a plant expression vector pCAMBIA1303-NtSSU. The NtSSU gene was overexpressed in tobacco upon Agrobacterium-mediated leaf disc transformation. Phenotypic analysis showed that overexpression of NtSSU gene promoted the accumulation of starch in tobacco leaves, and the content of starch in tobacco leaves increased from 17.5% to 41.7%. The growth rate and biomass yield of the transgenic tobacco with NtSSU gene were also significantly increased. The results revealed that overexpression of NtSSU gene could effectively redirect more photosynthesis carbon flux into starch biosynthesis pathway, which led to an increased biomass yield but did not generate negative effects on other agronomic traits. Therefore, NtSSU gene can be used as an excellent target gene in plant breeding to enrich starch accumulation in vegetative organs to develop new germplasm dedicated to fuel ethanol production.


Assuntos
Biomassa , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Folhas de Planta/genética , Plantas Geneticamente Modificadas/metabolismo , Amido , Nicotiana/metabolismo
17.
J Asian Nat Prod Res ; 22(8): 738-745, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131622

RESUMO

Two new isopimarane diterpenoids, named 1α-hydroxy-7-oxoisopimara-8, 15-diene (1), 11ß-hydroxy-7-oxoisopimara-8(14), 15-diene (2), together with six known compounds (3-8), were isolated from the medicinal plant Salacia cochinchinensis. All isolates were assayed for their cytotoxicity and α-glucosidase inhibitory activity. Results suggested compounds 1, 3 possessed significant cytotoxic activity against HepG2, HL60, and Hela cell lines with IC50 values ranging from 0.23 to 0.35 µM, and compounds 7, 8 exhibited noticeable α-glucosidase inhibitory ability with IC50 values of 0.25 and 0.31 µM, respectively.


Assuntos
Diterpenos , Salacia , Células HeLa , Humanos , Estrutura Molecular , alfa-Glucosidases
18.
Chinese Journal of Biotechnology ; (12): 716-731, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-826904

RESUMO

Stearoyl-ACP Δ⁹ desaturase (SAD) catalyzes the synthesis of monounsaturated oleic acid or palmitoleic acid in plastids. SAD is the key enzyme to control the ratio of saturated fatty acids to unsaturated fatty acids in plant cells. In order to analyze the regulation mechanism of soybean oleic acid synthesis, soybean (Glycine max) GmSAD family members were genome-wide identified, and their conserved functional domains and physicochemical properties were also analyzed by bioinformatics tools. The spatiotemporal expression profile of each member of GmSADs was detected by qRT-PCR. The expression vectors of GmSAD5 were constructed. The enzyme activity and biological function of GmSAD5 were examined by Agrobacterium-mediated transient expression in Nicotiana tabacum leaves and genetic transformation of oleic acid-deficient yeast (Saccharomyces cerevisiae) mutant BY4389. Results show that the soybean genome contains five GmSAD family members, all encoding an enzyme protein with diiron center and two conservative histidine enrichment motifs (EENRHG and DEKRHE) specific to SAD enzymes. The active enzyme protein was predicted as a homodimer. Phylogenetic analysis indicated that five GmSADs were divided into two subgroups, which were closely related to AtSSI2 and AtSAD6, respectively. The expression profiles of GmSAD members were significantly different in soybean roots, stems, leaves, flowers, and seeds at different developmental stages. Among them, GmSAD5 expressed highly in the middle and late stages of developmental seeds, which coincided with the oil accumulation period. Transient expression of GmSAD5 in tobacco leaves increased the oleic acid and total oil content in leaf tissue by 5.56% and 2.73%, respectively, while stearic acid content was reduced by 2.46%. Functional complementation assay in defective yeast strain BY4389 demonstrated that overexpression of GmSAD5 was able to restore the synthesis of monounsaturated oleic acid, resulting in high oil accumulation. Taken together, soybean GmSAD5 has strong selectivity to stearic acid substrates and can efficiently catalyze the biosynthesis of monounsaturated oleic acid. It lays the foundation for the study of soybean seed oleic acid and total oil accumulation mechanism, providing an excellent target for genetic improvement of oil quality in soybean.


Assuntos
Ácidos Graxos Dessaturases , Genética , Metabolismo , Perfilação da Expressão Gênica , Ácido Oleico , Filogenia , Proteínas de Plantas , Genética , Sementes , Química , Glycine max , Classificação , Genética
19.
Carbohydr Res ; 484: 107777, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446303

RESUMO

Four new triterpene glycosides, named salaciacochinosides A-D (1-4) were isolated from the 90% ethanol extract of Salacia cochinchinensis, together with five known compounds 2α,3ß,23-trihydroxyurs-12,18-dien-28-oic acid 28-O-ß-d-glucopyranoside (5), racemiside (6), alangiplatanoside (7), acantrifoside E (8), and syringin (9). The structures of the four new triterpenoids were characterized by chemical methods and MS, IR, 1D and 2D NMR spectral analyses. The α-glucosidase inhibitory activities of the nine compounds were assessed, compounds 6 and 7 showed remarkable α-glucosidase inhibitory activities, with IC50 values of 0.44 and 0.75 µM, respectively. Compounds 1-5 exhibited moderate α-glucosidase inhibitory activities, and compounds 8 and 9 showed none α-glucosidase inhibitory activity in our current experiments.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Glicosídeos/química , Salacia/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologia
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-816323

RESUMO

OBJECTIVE: To analyze the distribution and pathogenicity of 27 HPV(Human papillomavirus)subtypes in cervical lesions.METHODS: A retrospective analysis was carried out in 5735 patients with cervical lesions admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2017,including 997 cases of cervicitis,1568 cases of LSIL(low-grade squamous intraepithelial lesion),2576 cases of HSIL(high-grade squamous intraepithelial lesion)and 594 cases of cervical cancer. The HPV subtypes,histopathological results and ages were obtained for analysis.RESULTS: The positive rates of HPV in cervicitis group,LSIL,HSIL group and cervical cancer group were 57.0%,78.3%,90.5%,and 93.9%(P<0.05)respectively. The five most prevalent HPV types in cervicitis and LSIL group were 52,53,16,58 and 18;in HSIL and cervical cancer they were 16,52,58,33 and 18. The cumulative attribution rates of HPV16,18,58,52,33,31 and 45 in cervicitis,LSIL,HSIL and cervical cancer were 22.2%,38.4%,68.4% and 80.1%,respectively. The incidence of cervical cancer after HPV16,31 and 45 infection was 27.7,14.3 and8.2 times higher than that of cervicitis. Among the 36 cervical cancer tissue samples with negative HPV,8 cases were detected positive by HPV E6/E7 DNA detection.CONCLUSION: HPV16,18,58,52,33,31 and 45 have a high prevalence,cumulative attribution rates and risk values in patients with squamous intraepithelial lesions and cervical cancer. The above-mentioned subtypes of HPV should be included in the prevention and screening of cervical cancer.HPV E6/E7 DNA detection may be a reliable assay for HPV-based screening for prevention of cervical cancer.

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