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1.
Environ Toxicol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747344

RESUMO

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using "ConsensusClusterPlus" based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

3.
Mar Drugs ; 21(6)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367654

RESUMO

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.


Assuntos
Glioblastoma , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Caspase 3/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Pelados , Proliferação de Células , Transdução de Sinais , Apoptose , Glioblastoma/patologia , Linhagem Celular Tumoral
4.
Microbiome ; 11(1): 144, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37370187

RESUMO

BACKGROUND: Marine prokaryotes are a rich source of novel bioactive secondary metabolites for drug discovery. Recent genome mining studies have revealed their great potential to bio-synthesize novel secondary metabolites. However, the exact biosynthetic chemical space encoded by the marine prokaryotes has yet to be systematically evaluated. RESULTS: We first investigated the secondary metabolic potential of marine prokaryotes by analyzing the diversity and novelty of the biosynthetic gene clusters (BGCs) in 7541 prokaryotic genomes from cultivated and single cells, along with 26,363 newly assembled medium-to-high-quality genomes from marine environmental samples. To quantitatively evaluate the unexplored biosynthetic chemical space of marine prokaryotes, the clustering thresholds for constructing the biosynthetic gene cluster and molecular networks were optimized to reach a similar level of the chemical similarity between the gene cluster family (GCF)-encoded metabolites and molecular family (MF) scaffolds using the MIBiG database. The global genome mining analysis demonstrated that the predicted 70,011 BGCs were organized into 24,536 mostly new (99.5%) GCFs, while the reported marine prokaryotic natural products were only classified into 778 MFs at the optimized clustering thresholds. The number of MF scaffolds is only 3.2% of the number of GCF-encoded scaffolds, suggesting that at least 96.8% of the secondary metabolic potential in marine prokaryotes is untapped. The unexplored biosynthetic chemical space of marine prokaryotes was illustrated by the 88 potential novel antimicrobial peptides encoded by ribosomally synthesized and post-translationally modified peptide BGCs. Furthermore, a sea-water-derived Aquimarina strain was selected to illustrate the diverse biosynthetic chemical space through untargeted metabolomics and genomics approaches, which identified the potential biosynthetic pathways of a group of novel polyketides and two known compounds (didemnilactone B and macrolactin A 15-ketone). CONCLUSIONS: The present bioinformatics and cheminformatics analyses highlight the promising potential to explore the biosynthetic chemical diversity of marine prokaryotes and provide valuable knowledge for the targeted discovery and biosynthesis of novel marine prokaryotic natural products. Video Abstract.


Assuntos
Produtos Biológicos , Genômica , Filogenia , Biologia Computacional , Metabolismo Secundário/genética , Vias Biossintéticas/genética
5.
Mil Med Res ; 10(1): 10, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872349

RESUMO

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.


Assuntos
Inteligência Artificial , Descoberta de Drogas , Humanos , Microscopia Crioeletrônica , Quimera de Direcionamento de Proteólise , Qualidade de Vida
6.
Endocr Connect ; 12(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524799

RESUMO

Background: Papillary thyroid carcinoma is the most common thyroid carcinoma worldwide. Papillary thyroid carcinoma metastasis to the cervical region increases the probability of local or regional recurrence and the requirement for further surgery. Contrast-enhanced ultrasound has been suggested as a possible adjunct diagnostic technique for evaluating papillary thyroid carcinoma metastatic lymph nodes in several studies. This meta-analysis aims to evaluate the diagnostic accuracy of contrast-enhanced ultrasound for cervical lymph nodes metastatic in papillary thyroid carcinoma patients. Methods: A search for studies evaluating the role of contrast-enhanced ultrasound for assessing cervical lymph nodes metastatic in papillary thyroid carcinoma patients from January 2000 to May 2022 was performed in PubMed, Embase, OVID, and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies 2 evaluated the quality of the studies. All analyses were performed using Review Manager 5.3 and Stata 17.0. Results: A total of seven articles were finally included in this study. Perfusion type, enhancement homogeneous, hilum absent, and perfusion defect were involved in the meta-analysis as the standard of contrast-enhanced ultrasound, among which, perfusion type showed the best diagnostic performance. The pooled estimated sensitivity, specificity, positive likelihood, negative likelihood ratio, and diagnostic odds ratio of perfusion type in contrast-enhanced ultrasound for detecting lymph node metastasis were 0.95 (0.91, 0.97), 0.87 (0.69, 0.96), 7.51 (2.80, 20.14), 0.06 (0.03, 0.10), and 124.17 (42.78, 360.46), respectively. Heterogeneity was moderate. Conclusion: The perfusion type in contrast-enhanced ultrasound has good diagnostic performance for cervical lymph nodes metastasis in papillary thyroid carcinoma patients.

7.
Pharmacol Res ; 187: 106565, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36414124

RESUMO

A primary strategy employed in cancer therapy is the inhibition of topoisomerase II (Topo II), implicated in cell survival. However, side effects and adverse reactions restrict the utilization of Topo II inhibitors. Thus, investigations focus on the discovery of novel compounds that are capable of inhibiting the Topo II enzyme and feature safer toxicological profiles. Herein, we upgrade an old antibiotic chrysomycin A from Streptomyces sp. 891 as a compelling Topo II enzyme inhibitor. Our results show that chrysomycin A is a new chemical entity. Notably, chrysomycin A targets the DNA-unwinding enzyme Topo II with an efficient binding potency and a significant inhibition of intracellular enzyme levels. Intriguingly, chrysomycin A kills KRAS-mutant lung adenocarcinoma cells and is negligible cytotoxic to normal cells at the cellular level, thus indicating a capability of potential treatment. Furthermore, mechanism studies demonstrate that chrysomycin A inhibits the Topo II enzyme and stimulates the accumulation of reactive oxygen species, thereby inducing DNA damage-mediated cancer cell apoptosis. Importantly, chrysomycin A exhibits excellent control of cancer progression and excellent safety in tumor-bearing models. Our results provide a chemical scaffold for the synthesis of new types of Topo II inhibitors and reveal a novel target for chrysomycin A to meet its further application.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Inibidores da Topoisomerase II , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , DNA Topoisomerases Tipo II/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
8.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6408-6413, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38211998

RESUMO

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22ß,25-expoxy-26-[(O-ß-D-glucopyranosyl)oxy]-1ß,3ß-dihydroxyfurosta-5-en(1), ß-sitosterol myristate(2), ß-sitosterol lactate(3), ß-sitosterol 3-O-ß-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 µmol·L~(-1).


Assuntos
Helleborus , Helleborus/química , Estrutura Molecular , Raízes de Plantas/química , Rizoma/química , Espectroscopia de Ressonância Magnética
9.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234681

RESUMO

Chrysomycin A (Chr-A), an antibiotic from Streptomyces, is reported to have anti-tumor and anti-tuberculous activities, but its anti-glioblastoma activity and possible mechanism are not clear. Therefore, the current study was to investigate the mechanism of Chr-A against glioblastoma using U251 and U87-MG human cells. CCK8 assays, EdU-DNA synthesis assays and LDH assays were carried out to detect cell viability, proliferation and cytotoxicity of U251 and U87-MG cells, respectively. Transwell assays were performed to detect the invasion and migration abilities of glioblastoma cells. Western blot was used to validate the potential proteins. Chr-A treatment significantly inhibited the growth of glioblastoma cells and weakened the ability of cell migration and invasion by down regulating the expression of slug, MMP2 and MMP9. Furthermore, Chr-A also down regulated Akt, p-Akt, GSK-3ß, p-GSK-3ß and their downstream proteins, such as ß-catenin and c-Myc in human glioblastoma cells. In conclusion, Chr-A may inhibit the proliferation, migration and invasion of glioblastoma cells through the Akt/GSK-3ß/ß-catenin signaling pathway.


Assuntos
Glioblastoma , beta Catenina , Aminoglicosídeos , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA/farmacologia , Glioblastoma/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo
10.
Anal Bioanal Chem ; 414(27): 7911-7922, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36138121

RESUMO

To investigate the diagnostic efficiency of Raman spectroscopy for the diagnosis of breast cancer, we searched PubMed, Web of Science, Cochrane Library, and Embase for articles published from the database establishment to May 20, 2022. Pooled sensitivity, specificity, diagnostic odds ratio, and area under the receiver pooled operating characteristic curve were derived for the included studies as outcome measures. The methodological quality was assessed according to the questionnaires and criteria suggested by the Diagnostic Accuracy Research Quality Assessment-2 tool. Sixteen studies were included in this meta-analysis. The pooled sensitivity and specificity of Raman spectroscopy for breast cancer diagnosis were 0.97 (95% CI, [0.92-0.99]) and 0.96 (95% CI, [0.91-0.98]). The diagnostic odds ratio was 720.89 (95% CI, [135.73-3828.88]) and the area under the curve of summary receiver operating characteristic curves was 0.99 (95% CI, [0.98-1]). Subgroup analysis revealed that all subgroup types in our analysis, including different races, sample types, diagnostic algorithms, number of spectra, instrument types, and laser wavelengths, turned out to have a sensitivity and specificity greater than 0.9. Significant heterogeneity was found between studies. Deeks' funnel plot demonstrated that publication bias was acceptable. This meta-analysis suggests that Raman spectroscopy may be an effective and accurate tool to differentiate breast cancer from normal breast tissue, which will help us diagnose and treat breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Curva ROC , Sensibilidade e Especificidade , Análise Espectral Raman/métodos
11.
Front Endocrinol (Lausanne) ; 13: 952113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966062

RESUMO

Background: Papillary thyroid cancer (PTC) is the most common thyroid tumor, and early diagnosis and treatment can effectively improve prognosis. Many controversies surround the treatment method of T1N0M0 PTC. Recently, thermal ablation (TA) has shown some benefits in the treatment of PTC patients, but the safety and efficacy of its treatment remain controversial. This article performs a meta-analysis of TA in patients with T1aN0M0 and T1bN0M0 PTC. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for retrospective or prospective studies of TA for treating patients with T1N0M0 PTC from the database establishment to May 1, 2022. Data on volume reduction rate (VRR), disease progress, and complication rate were collected. In addition, a meta-analysis was performed using the Stata 12.0 and Review Manager 5.3. Results: A total of 9 eligible studies were included. Our study demonstrated the effectiveness of VRR and disease progress. The VRR was reduced after 3 months (-75.90%; 95% CI [-118.46-33.34%]), 6 months (34.33%; 95% CI [15.01-53.65%]), 12 months (78.69%; 95% CI [71.69-85.68%]), and 24 months (89.97%; 95% CI [84.00-95.94%]). The disease progress was 1.9% (95% CI [1.1-3.0]). Safety is justified by the complication rate, which was 6.5% (95% CI [3.5-10.2]). Pain and hoarseness were the most common complications, and no life-threatening complications were reported. Egger's test demonstrated that publication bias was acceptable. Conclusions: TA is an effective and safe method for managing T1aN0M0 and T1bN0M0 papillary thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia de Intervenção
12.
Carbohydr Polym ; 290: 119411, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550744

RESUMO

Low molecular weight seaweed polysaccharides exhibit promising potential as novel therapeutics for the prevention of obesity and gut microbiota dysbiosis. The interplay between polysaccharides and gut microbiota may play crucial roles in their anti-obesity effects, but is largely unknown, including the impact of polysaccharides on the composition of the gut microbiota with polysaccharide-degrading capacity. The primary structure of a 5.1 kDa fucan (J2H) from Saccharina japonica was characterized and oral administration of J2H effectively suppressed high-fat diet-induced obesity, blood glucose metabolic dysfunction, dyslipidemia, and gut microbiota dysbiosis. Furthermore, the Jensen-Shannon divergence analysis demonstrated that J2H enriched at least four gut bacterial species with fucoidan-degrading potential, including Bacteroides sartorii and Bacteroides acidifaciens. Our findings suggest that the low molecular weight S. japonica fucan, J2H, is a promising potential agent for obesity prevention and its enrichment of gut bacteria with fucoidan-degrading potential may play a vital role in the anti-obesity effects.


Assuntos
Dieta Hiperlipídica , Laminaria , Animais , Bactérias , Dieta Hiperlipídica/efeitos adversos , Disbiose , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Polissacarídeos/química
14.
J Clin Ultrasound ; 50(2): 224-226, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34889462

RESUMO

This case illustrates the untypical presentation of primary bladder malacoplakia. The patient was in her mid-50s have impaired immunity by the long-term hyperglycemic condition. She presented with symptoms of urinary tract infection and dysuria, and had multiple nodulars in bladder and significantly mass in urethra. Although the diagnosis of bladder malacoplakia was established on bladder biopsy, transperineal ultrasound examination can find its distinct clinical presentation.


Assuntos
Malacoplasia , Infecções Urinárias , Feminino , Humanos , Malacoplasia/diagnóstico por imagem , Masculino , Ultrassonografia , Uretra/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem
15.
Front Genet ; 13: 1104338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685904

RESUMO

Background: Circadian dysregulation is linked to the onset and progression of cancer, but current knowledge of the role of circadian rhythm-related genes (CRRGs) in breast cancer (BC) is limited and incomplete. The purpose of this study was to investigate the potential role and immune-related prognostic significance of CRRGs in BC. Methods: The Cancer Genome Atlas breast cancer (TCGA-BRCA) genetic data were combined with 1369 CRRGs to create a model of BC prognosis-related CRRGs. To validate the model's predictive power in TCGA and other external datasets, the Kaplan-Meier survival curve and receptor operation characteristic curve were plotted. The relationship between CRRGs model and gene enrichment pathways, immune cell infiltration, and differences in patient response to immune checkpoint inhibitors (ICIs) therapy was then discussed. Results: A CRRG-based eighteen-gene model was developed that accurately predicted the survival time of BC patients. Based on this model, BC patients can be classified as high or low risk. The high-risk group has negative immune cell infiltration (such as macrophages M0 and M2) and a poor therapeutic response to ICIs due to lower immune checkpoint gene expression. Furthermore, TCF7 and IFNG were found to be strongly associated with immune checkpoints in CRRGs model. Conclusion: The 18 CRRGs may be useful in assessing the prognosis of BC patients, studying immune infiltration, and developing more effective immunotherapy strategies.

16.
Environ Microbiol ; 23(11): 6981-6992, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490968

RESUMO

Bacterial secondary metabolites are rich sources of novel drug leads. The diversity of secondary metabolite biosynthetic gene clusters (BGCs) in genome-sequenced bacteria, which will provide crucial information for the efficient discovery of novel natural products, has not been systematically investigated. Here, the distribution and genetic diversity of BGCs in 10 121 prokaryotic genomes (across 68 phyla) were obtained from their PRISM4 outputs using a custom python script. A total of 18 043 BGCs are detected from 5743 genomes with non-ribosomal peptide synthetases (25.4%) and polyketides (15.9%) as the dominant classes of BGCs. Bacterial strains harbouring the largest number of BGCs are revealed and BGC count in strains of some genera vary greatly, suggesting the necessity of individually evaluating the secondary metabolism potential. Additional analysis against 102 strains of discovered bacterial genera with abundant amounts of BGCs confirms that Kutzneria, Kibdelosporangium, Moorea, Saccharothrix, Cystobacter, Archangium, Actinosynnema, Kitasatospora, and Nocardia, may also be important sources of natural products and worthy of priority investigation. Comparative analysis of BGCs within these genera indicates the great diversity and novelty of the BGCs. This study presents an atlas of bacterial secondary metabolite BGCs that provides a lot of key information for the targeted discovery of novel natural products.


Assuntos
Vias Biossintéticas , Cianobactérias , Família Multigênica , Vias Biossintéticas/genética , Cianobactérias/genética , Metabolismo Secundário/genética
17.
Ying Yong Sheng Tai Xue Bao ; 32(6): 2021-2027, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34212607

RESUMO

A method for geographical discrimination of Portunus trituberculatus was explored to provide technical support for the protection of geographical indication products and for tracing the origin of seafood. P. trituberculatus were collected from three major production areas, including the Yellow Sea, the Bohai Sea, and the East China Sea. The variations of carbon and nitrogen stable isotope values of origins and the correlation of stable isotope ratios in different tissues were analyzed. The results showed that there were significant differences in carbon and nitrogen stable isotope ratio among different origins. Significant isotope fractionation effects were observed among different tissues. The discriminant model was developed and the origin discriminant analysis was performed by the stable isotope ratios of different tissues in P. trituberculatus. The correct rate of origin diffe-rentiationf using carbon and nitrogen stable isotopes in muscle and gills (>95%) was significantly higher than that of hepatopancreas and gonad, indicating that stable isotope ratios of muscle and gills could effectively differentiate P. trituberculatus in different sea areas. This study filled the gap of stable isotope tracing technology for P. trituberculatus.


Assuntos
Braquiúros , Animais , Isótopos de Carbono/análise , China , Hepatopâncreas/química , Nitrogênio , Isótopos de Nitrogênio/análise
18.
Prep Biochem Biotechnol ; 51(10): 998-1003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600297

RESUMO

Chrysomycin A is one of the valuable drug leads used to treat infectious diseases such as tuberculosis and methicillin-resistant Staphylococcus aureus. In order to increase its yield, this work firstly focuses on optimization of fermentation conditions and medium compositions of a wild-type chrysomycin A-producing strain Streptomyces sp. 891 from marine sediment. By single-factor experiment, effects of fermentation conditions (fermentation time, seed age, initial pH, inoculum amount, liquid loading, shaking speed) and medium composition (carbon sources, nitrogen sources, inorganic salts) on the yield of chrysomycin A were carefully evaluated and analyzed followed by optimization at shake-flask level. The results indicated its optimal fermentation conditions for producing chrysomycin A were as follows: fermentation time 168 h, seed age 48 h, initial pH 6.5, inoculum amount 5.0%, liquid loading 30 mL in 250-mL Erlenmeyer flask and shaking speed 220 rpm. By orthogonal test, the optimal fermentation medium constitutes 40 g/L glucose, 20 g/L corn starch, 25 g/L hot-pressed soybean flour, 3 g/L CaCO3. Verification tests suggested the yield of chrysomycin A under optimized conditions reaches up to 3648 ± 119 mg/L, which is increased by almost 5 times. These findings definitely pave the way for scale-up preparation of chrysomycin A and application in the pharmaceutical industry.


Assuntos
Aminoglicosídeos/metabolismo , Antibacterianos/metabolismo , Fermentação , Streptomyces/metabolismo , Microbiologia Industrial/métodos , Streptomyces/crescimento & desenvolvimento
19.
Food Chem ; 341(Pt 1): 128148, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33038776

RESUMO

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.


Assuntos
Hipoglicemiantes/farmacologia , Polissacarídeos/farmacologia , Alga Marinha/química , Undaria/química , Animais , Fracionamento Químico , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Glucose/farmacocinética , Células Hep G2 , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Hipoglicemiantes/química , Insulina/farmacologia , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Micro-Ondas , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Período Pós-Prandial , Sulfatos/química
20.
Mar Drugs ; 18(9)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867177

RESUMO

A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this study, five polysaccharides were prepared from Sargassumfusiforme and their effects on HFD-induced fasting hypoglycemia and gut microbiota dysbiosis were investigated. The results indicated that C57BL/6J male mice fed an HFD for 4 weeks developed severe hypoglycemia and four Sargassumfusiforme polysaccharides (SFPs), consisting of Sf-2, Sf-3, Sf-3-1, and Sf-A, significantly prevented early fasting hypoglycemia without inducing hyperglycemia. Sf-1 and Sf-A could also significantly prevent HFD-induced weight gain. Sf-2, Sf-3, Sf-3-1, and Sf-A mainly attenuated the HFD-induced decrease in Bacteroidetes, and all five SFPs had a considerable influence on the relative abundance of Oscillospira, Mucispirillum, and Clostridiales. Correlation analysis revealed that the fasting blood glucose level was associated with the relative abundance of Mucispinllum and Oscillospira. Receiver operating characteristic analysis indicated that Mucispinllum and Oscillospira exhibited good discriminatory power (AUC = 0.745-0.833) in the prediction of fasting hypoglycemia. Our findings highlight the novel application of SFPs (especially Sf-A) in glucose homeostasis and the potential roles of Mucispinllum and Oscillospira in the biological activity of SFPs.


Assuntos
Glicemia/efeitos dos fármacos , Dieta Hiperlipídica , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemia/prevenção & controle , Intestinos/microbiologia , Polissacarídeos/farmacologia , Sargassum/metabolismo , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Modelos Animais de Doenças , Hipoglicemia/sangue , Hipoglicemia/etiologia , Masculino , Camundongos Endogâmicos C57BL , Polissacarídeos/isolamento & purificação , Aumento de Peso/efeitos dos fármacos
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