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1.
Eur Radiol ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38724768

RESUMEN

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

2.
Fitoterapia ; 175: 105946, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38575087

RESUMEN

Four compounds (1-4) featuring with an L-rhodinose and spiroketal, possess uncommon continuous hydroxy groups in the macrolide skeleton, and a dichloro-diketopiperazine (5) were isolated from a marine derived Micromonospora sp. FIMYZ51. The determination of the relative and absolute configurations of all isolates was achieved by extensive spectroscopic analyses, single-crystal X-ray diffraction analysis, and ECD calculations. According to structural characteristic and genomic sequences, a plausible biosynthetic pathway for compound 1-4 was proposed and a spirocyclase was inferred to be responsible for the formation of the rare spirocyclic moiety. Compounds 1-4 exhibited potent antifungal activities which is equal to itraconazole against Aspergillus niger. Compounds 1-5 exhibited different degree of inhibitory activities against opportunistic pathogenic bacteria of endocarditis (Micrococcus luteus) with MIC values ranging from 0.0625 µg/mL to 32 µg/mL. Compounds 2 and 3 showed moderate cytotoxicity against drug-resistant tumor cell lines (Namalwa and U266). The result not only provides active lead-compounds, but also reveal the potential of the spirocyclase gene resources from Micromonospora sp., which highlights the promising potential of the strain for biomedical applications.

4.
Microb Pathog ; 190: 106614, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38492825

RESUMEN

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.


Asunto(s)
Aeromonas hydrophila , Antioxidantes , Carpas , Eleutherococcus , Fermentación , Enfermedades de los Peces , Lacticaseibacillus rhamnosus , Probióticos , Animales , Lacticaseibacillus rhamnosus/metabolismo , Carpas/microbiología , Probióticos/farmacología , Probióticos/administración & dosificación , Antioxidantes/metabolismo , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/inmunología , Alimentación Animal , Inflamación/prevención & control , Citocinas/metabolismo , Acuicultura
5.
Anal Chem ; 96(14): 5399-5406, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38523322

RESUMEN

Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from Aspergillus sp. GE2-6, revealing 27 undescribed compounds. Compounds 7-22 were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (5). Compounds 23 and 24 were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A (1) and asperphenalenone E (28) exhibited potent anti-influenza (PR8) activities, with IC50 values of 21.9 ± 0.2 and 12.9 ± 0.1 µM, respectively. Meanwhile, asperphenalenone (26) and asperphenalenone P (27) treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC50 values of 6.1 ± 0.9 and 4.6 ± 1.1 µM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.


Asunto(s)
Productos Biológicos , Productos Biológicos/farmacología , Espectroscopía de Resonancia Magnética , Aspergillus/química , Estructura Molecular
6.
Int J Pharm ; 654: 123963, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38430952

RESUMEN

Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.


Asunto(s)
Ginsenósidos , Minoxidil , Ratones , Animales , Humanos , Minoxidil/farmacología , Minoxidil/uso terapéutico , Ginsenósidos/farmacología , Andrógenos/uso terapéutico , Ratones Endogámicos C57BL , Alopecia/tratamiento farmacológico , Folículo Piloso , Dihidrotestosterona , Colesterol
7.
Surg Endosc ; 38(2): 586-596, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38151677

RESUMEN

BACKGROUND: Endoscopic drainage has become the preferred treatment for pancreatic fluid collections (PFCs). There is still a lack of reliable evidence to prove which metal stent is the best choice for endoscopic ultrasound (EUS)-guided drainage of PFCs. In this study, we aimed to evaluate the efficacy and safety of lumen-apposing metal stents (LAMS) compared to traditional self-expanding metal stents (SEMS) in meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to July 15, 2023. Relevant publications that compared LAMS with traditional SEMS for drainage of patients' PFCs under EUS-guidance were included. This meta-analysis assessed endpoints using Review Manager 5.3 and Stata 14.0 statistical software. RESULT: Nine citations comprising 707 patients with PFCs were included. The clinical success rate of LAMS tended to be higher than that of SEMS (RR = 1.07, 95%CI [1.00, 1.15], P = 0.05). LAMS had a lower technical success rate (RR = 0.97, 95%CI [0.94, 0.99], P = 0.02) and faster procedure time (minutes) (MD = - 24.29, 95%CI [- 25.59, - 22.99], P < 0.00001) compared to SEMS. In addition, LAMS had fewer overall adverse events (RR = 0.64, 95%CI [0.48, 0.87], P = 0.004). For specific adverse events, LAMS had fewer migration (RR = 0.37, 95%CI [0.19, 0.72], P = 0.003), occlusion (RR = 0.43, 95%CI [0.22, 0.82], P = 0.01) and infection (RR = 0.38, 95%CI [0.20, 0.70], P = 0.002). There was no significant difference in bleeding and perforation between the two stents. For hospital stay (days), LAMS group was similar to SEMS group (MD = - 3.34, 95%CI [- 7.71, - 1.03], P = 0.13). Regarding recurrence, LAMS group was fewer than SEMS group (RR = 0.41, 95%CI [0.21, 0.78], P = 0.007). CONCLUSION: Compared to traditional SEMS, LAMS has a higher clinical success rate, faster procedure time, fewer adverse events, similar hospital stay and lower recurrence rate in EUS-guided drainage of PFCs. LAMS is a good choice with a high technical success rate over 95%, and using a shorter length or "one-step" operation can further improve it. Richer placement experience is required for LAMS placement under EUS-guidance.


Asunto(s)
Enfermedades Pancreáticas , Humanos , Resultado del Tratamiento , Enfermedades Pancreáticas/cirugía , Enfermedades Pancreáticas/etiología , Endosonografía/métodos , Stents/efectos adversos , Drenaje/métodos , Metales/efectos adversos , Ultrasonografía Intervencional
8.
Toxins (Basel) ; 15(11)2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37999520

RESUMEN

Microbial interactions including competition, mutualism, commensalism, parasitism, and predation, which can be triggered by nutrient acquisition and chemical communication, are universal phenomena in the marine ecosystem. The interactions may influence the microbial population density, metabolism, and even their environmental functions. Herein, we investigated the interaction between a heterotrophic bicosoecid flagellate, Pseudobodo sp. (Bicoecea), and a dinoflagellate, Gambierdiscus balechii (Dinophyceae), which is a well-known ciguatera food poisoning (CFP) culprit. The presence of Pseudobodo sp. inhibited the algal proliferation and decreased the cardiotoxicity of zebrafish in the algal extract exposure experiment. Moreover, a significant difference in microbiome abundance was observed in algal cultures with and without Pseudobodo sp. Chemical analysis targeting toxins was performed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with molecular networking (MN), showing a significant alteration in the cellular production of gambierone analogs and some super-carbon chain compounds. Taken together, our results demonstrated the impact of heterotrophic flagellate on the photosynthetic dinoflagellates, revealing the complex dynamics of algal toxin production and the ecological relationships related to dinoflagellates in the marine environment.


Asunto(s)
Intoxicación por Ciguatera , Ciguatoxinas , Dinoflagelados , Animales , Dinoflagelados/metabolismo , Cromatografía Liquida , Ecosistema , Pez Cebra , Espectrometría de Masas en Tándem , Cromatografía de Gases y Espectrometría de Masas , Ciguatoxinas/toxicidad
9.
Chem Biodivers ; 20(12): e202301345, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37985414

RESUMEN

Marine actinomycetes are known for their production of remarkable organic molecules, particularly those featuring polyoxygenated long-chain backbones. Determining the absolute configurations of these compounds remains a challenging task even today. In this study, we successfully established the planar structures and absolute configurations of two highly flexible amide alkaloids from Streptomyces sp. WU20: kueishanamides A (1) and B (2). These compounds possess a C13 linear backbone and each contains five stereogenic carbon centers. Our approach involved a combination of spectroscopic and computational methods, including J-based configurational analysis and VCD calculations, ensuring the unambiguous determination of their configurations. Kueishanamide A (1) and kueishanamide B (2) showed moderate antifungal activity against pathogenic fungus Crytococcus neoformans, with MIC values of 25 µg/mL each.


Asunto(s)
Respiraderos Hidrotermales , Streptomyces , Antibacterianos/química , Streptomyces/química , Respiraderos Hidrotermales/microbiología , Antifúngicos/farmacología , Antifúngicos/química , Hongos , Estructura Molecular
10.
Exp Ther Med ; 26(5): 518, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37854500

RESUMEN

Esophageal foreign body impaction is a notable clinical emergency. If the high-risk esophageal foreign bodies are not removed in time, life-threatening complications, such as perforation, infection and injury to the vessels, may occur. In the present study, the case of a patient experiencing a foreign body sensation in the throat after ingesting a fish bone by mistake is presented. A high risk of impending arterial puncture was confirmed using thoracic CT and thoracic aorta CT angiography scanning. The ends of the fish bone were first confirmed using a fibro-bronchoscopy light source passing through the bronchial and esophageal walls, before biopsy forceps were used to successively free the thoracic aorta and bronchial ends under gastroscopy. Finally, the fish bone was safely removed using a combination of gastroscopy and the rarely used fibro-bronchoscopy, and the patient recovered well after standard care. In certain cases of foreign bodies, it is necessary to use multiple strategies in a timely manner according to the type and location of the ingested foreign body.

11.
Sensors (Basel) ; 23(12)2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37420713

RESUMEN

The design of a metasurface array consisting of different unit cells with the objective of minimizing its radar cross-section is a popular research topic. Currently, this is achieved by conventional optimisation algorithms such as genetic algorithm (GA) and particle swarm optimisation (PSO). One major concern of such algorithms is the extreme time complexity, which makes them computationally forbidden, particularly at large metasurface array size. Here, we apply a machine learning optimisation technique called active learning to significantly speed up the optimisation process while producing very similar results compared to GA. For a metasurface array of size 10 × 10 at a population size of 106, active learning took 65 min to find the optimal design compared to genetic algorithm, which took 13,260 min to return an almost similar optimal result. The active learning optimisation strategy produced an optimal design for a 60 × 60 metasurface array 24× faster than the approximately similar result generated by GA technique. Thus, this study concludes that active learning drastically reduces computational time for optimisation compared to genetic algorithm, particularly for a larger metasurface array. Active learning using an accurately trained surrogate model also contributes to further lowering of the computational time of the optimisation procedure.


Asunto(s)
Algoritmos , Aprendizaje Automático
12.
J Control Release ; 359: 347-358, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37277054

RESUMEN

Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O6-benzylguanine (O6-BG). TMZ was loaded in poly (D, l-lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O6-BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O6-BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies.


Asunto(s)
Nanopartículas , Neoplasias , Dacarbazina/farmacología , Saccharomyces cerevisiae , O(6)-Metilguanina-ADN Metiltransferasa , Temozolomida , Membrana Celular/metabolismo , Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico
13.
Clin Appl Thromb Hemost ; 29: 10760296231164355, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37131319

RESUMEN

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.


Asunto(s)
COVID-19 , Neoplasias , Tromboembolia Venosa , Humanos , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Anticoagulantes/efectos adversos , Estudios Retrospectivos , Tromboembolia Venosa/etiología , COVID-19/complicaciones , Hemorragia/inducido químicamente , Neoplasias/complicaciones
14.
Ecotoxicol Environ Saf ; 255: 114825, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36989948

RESUMEN

Intestinal inflammation is a protective response that is implicated in bacterial enteritis triggered by gastrointestinal infection. The immune mechanisms elicited in teleost against the infection of Aeromonas veronii are largely unknown. In this study, we performed a de novo northern snakehead (Channa argus) transcriptome assembly using Illumina sequencing platform. On this basis we performed a comparative transcriptomic analysis of northern snakehead intestine from A. veronii-challenge and phosphate buffer solution (PBS)-challenge fish, and 2076 genes were up-regulated and 1598 genes were down-regulated in the intestines infected with A. veronii. The Gene Ontology (GO) enrichment analysis indicated that the differentially expressed genes (DEGs) were enriched to 27, 21 and 20 GO terms in biological process, cellular component, and molecular function, respectively. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 420 DEGs were involved in 194 pathways. Moreover, 33 DEGs were selected for quantitative real-time PCR analysis to validate the RNA-seq data. The results reflected the consistency of the expression levels between qRT-PCR and RNA-seq data. In addition, a time-course analysis of the mRNA expression of 33 immune-related genes further indicated that the intestinal inflammation to A. veronii infection simultaneously regulated gene expression alterations. The present study provides transcriptome data of the teleost intestine, allowing us to understand the mechanisms of intestinal inflammation triggered by bacterial pathogens. DATA AVAILABILITY STATEMENT: All data supporting the findings of this study are available within the article and Supplementary files. The RNA-seq raw sequence data are available in NCBI short read archive (SRA) database under accession number PRJNA615958.


Asunto(s)
Aeromonas veronii , Transcriptoma , Animales , Aeromonas veronii/genética , Perfilación de la Expresión Génica , Intestinos , Inmunidad , Inflamación
15.
Phytochemistry ; 205: 113479, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36270410

RESUMEN

A previously unreported alkaloid, bearing an undescribed 5/7/8 tricyclic heterocyclic skeleton, shornephine D, an undescribed diketomorpholine (DKM) shornephine B, two undescribed diketomorpholine derivatives shornephine C and seco-shornephine B methyl ester, an undescribed indole-isoquinoline alkaloid asterresin C, three undescribed indole alkaloids asterresins A-B and D, together with five known compounds, were isolated from the culture of hydrothermal vent associated fungus Aspergillus terreus CXX-158-20. Their structures were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry, Mosher's method, 13C NMR calculation in combination with DP4+, and ECD calculations. Shornephine D and asterresin C represent two undescribed heterocyclic skeletons. Asterresin D and giluterrin exhibited cytotoxicity activities with IC50 values of 3.96 µM and 7.97 µM against A549 cell line. Asterresin D exhibited cytotoxicity activities with IC50 values of 12.36 µM and 12.48 µM against Namalwa and U266 cell lines. Asterresin A and giluterrin exhibited synergistic effect with adriamycin against MCF-7 cell line.


Asunto(s)
Alcaloides , Antineoplásicos , Respiraderos Hidrotermales , Humanos , Aspergillus/química , Células MCF-7 , Alcaloides/metabolismo , Alcaloides Indólicos/metabolismo , Antineoplásicos/farmacología , Estructura Molecular
16.
J Nat Prod ; 85(11): 2620-2625, 2022 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-36318598

RESUMEN

We report the discovery of talaropeptins A (1) and B (2), tripeptides with an unusual 5/6/5 heterocyclic scaffold and an N-trans-cinnamoyl moiety, which were identified from the marine-derived fungus Talaromyces purpureogenus CX11. A bioinformatic analysis of the genome of T. purpureogenus CX11 and gene inactivation revealed that the biosynthesis of talaropeptins involves a nonribosomal peptide synthase gene cluster. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 1 and 2 were established by electronic circular dichroism calculations and Marfey's method. The plausible biosynthesis of 1 and 2 is also proposed on the basis of gene deletion, substrate feeding, and heterologous expression. Compounds 1 and 2 showed moderate antifungal activity against phytopathogenic fungus Fusarium oxysporum with MIC values of 12.5 and 25 µg/mL, respectively.


Asunto(s)
Antifúngicos , Oligopéptidos , Talaromyces , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Estructura Molecular , Talaromyces/química , Oligopéptidos/química , Oligopéptidos/aislamiento & purificación , Oligopéptidos/farmacología
17.
Fish Shellfish Immunol ; 131: 682-696, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36341871

RESUMEN

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.


Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Probióticos , Sanguisorba , Animales , Aeromonas hydrophila/fisiología , Resistencia a la Enfermedad , Carpa Dorada , Inmunidad , Extractos Vegetales , Probióticos/farmacología
18.
BMC Pediatr ; 22(1): 598, 2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-36253748

RESUMEN

BACKGROUND: In-home unintentional injuries (IUIs) seriously threatened children's safety. Three factors, including risky behaviors, parental supervision, and home environmental risks, have been identified as major causes for IUIs. Studies considering the interrelations between the three were limited and no relative studies has been carried out among Chinese children. The purpose of this study is to fully explore the influences of behavioral, supervisory and environmental risk factors on IUIs and their associations among Chinese children on the bases of our self-developed scales. METHODS: Through stratified cluster sampling, a cross-sectional survey was conducted with 798 parents of children aged 0 ~ 6 years in Changsha, China. Social demographics and IUIs history in the past year were collected by self-administered questionnaires. Three IUI-related scales, which had been developed and validated by our team, aimed to measure risks from children behavior, parental supervision and in-home environment. Structural equation models were constructed to analyze the relationship of these factors and their influences on IUIs using SPSS 26.0 and AMOS 22.0. RESULTS: Seven hundred ninety-eight parents were surveyed in total, and 33.58% of them reported with IUIs history of their children. X2/df, goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI) and the root-mean-square error of approximation (RMSEA) for the model of the whole children were 4.832, 0.879, 0.856 and 0.069 respectively, indicating an acceptable level of model fit. Direct influences were discovered between risky behaviors and children's IUIs. Home environmental risks indirectly exerted impacts on IUIs by the mediating effect of risky behaviors, while the significant effect of parental supervision only existed in children aged 4-6 and girls. CONCLUSIONS: Risky behaviors played a mediating role in IUIs among children. Supervision and environmental risks affected IUIs indirectly by the exposure to risky behaviors. Parental supervision may not be able to offset the risks posed by the environmental and behavioral factors, so effective IUIs prevention strategies should focus on behavioral and environmental interventions, with appropriate supervision strategies based on the age and sex characteristics of the child.


Asunto(s)
Ecosistema , Padres , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Factores de Riesgo , Encuestas y Cuestionarios
19.
Polymers (Basel) ; 14(17)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36080615

RESUMEN

Combining molecular imprinted polymers and water-soluble manganese-doped zinc sulfide quantum dots (Mn2+: ZnS QDs), a new molecule imprinted polymers-based fluorescence sensor was designed. The molecule imprinted quantum dots (MIP@QDs) were constructed by coating molecular imprinted polymers layer on the surface of ZnS: Mn2+ QDs using the surface molecular imprinting technology. The developed MIP@QDs-based sensor was used for rapid and selective fluorescence sensing of sulfanilamide in water samples. The binding experiments showed that the MIP@QDs has rapid fluorescent responses, which are highly selective of and sensitive to the detection of sulfanilamide. The respond time of the MIP@QDs was 5 min, and the imprinting factor was 14.8. Under optimal conditions, the developed MIP@QDs-based sensor shows a good linearity (R2 = 0.9916) over a sulfanilamide concentration range from 2.90 × 10-8 to 2.90 × 10-6 mol L-1, with a detection limit of 3.23 × 10-9 mol L-1. Furthermore, the proposed MIP@QDs-based sensor was applied to the determination of sulfanilamide in real samples, with recoveries of 96.80%-104.33%, exhibiting good recyclability and stability. Experimental results showed that the prepared MIP@QDs has the potential to serve as a selective and sensitive sensor for the fluorescence sensing of sulfonamides in water samples.

20.
Eur J Med Chem ; 242: 114699, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36001934

RESUMEN

ß-Glucuronidase catalyzes the cleavage of glucuronosyl-O-bonds, whose inhibitors reduce the level of toxic substances present in the intestine caused by anti-cancer and anti-inflammatory therapies. Herein, we presented a new tool, Bioactive Fractions Filtering Platform (BFFP), which is able to reliably discern active candidate node from crude extracts. The source code for the BFFP is available on GitHub (https://github.com/BioGavin/msbff). With the assistant of BFFP, 25 gabosine and chlorogentisyl alcohol derivatives including 19 new compounds were isolated from a marine-derived fungus Epicoccum sp. GST-5. Compounds 7, 9-15 possessed an unusual hybrid skeleton of gabosine and chlorogentisyl alcohol units. Compounds 9-12, 16 and 17 possessed a novel three-membered spiral ring skeleton with one/two gabosine and one/two chlorogentisyl alcohol units. Compound 25 represented new gabosine-derived skeleton possessing an unusual 6/6/6/5/6 condensed ring system. All isolates were evaluated for in vitro E. coli ß-glucuronidase (EcGUS) inhibitory activity. 14 Compounds demonstrated superior inhibitory activity (IC50 = 0.24-4.61 µM) to that of standard d-saccharic acid 1,4-lactone (DSL, IC50 = 56.74 ± 4.01 µM). Compounds with chlorogentisyl alcohol moiety, such as 17 (IC50 = 0.24 ± 0.02 µM) and 1 (IC50 = 0.74 ± 0.03 µM), exhibited the most potent inhibitory activity. Furthermore, literature based QSAR profiling by applying PCA and OPLS analysis was carried out to analyze the features of compounds against EcGUS, revealing that the introduction of substituents able to form polar interactions with binding sites of receptor would lead to more active structures.


Asunto(s)
Inhibidores Enzimáticos , Escherichia coli , Alcohol Bencilo , Mezclas Complejas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Hongos/metabolismo , Ácido Glucárico , Glucuronidasa/metabolismo , Informática , Lactonas , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad
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