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1.
J Nat Prod ; 87(2): 381-387, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38289330

RESUMO

Tryptoquivalines are highly toxic metabolites initially isolated from the fungus Aspergillus clavatus. The relative and absolute configuration of tryptoquivaline derivates was primarily established by comparison of the chemical shifts, NOE data, and ECD calculations. A de novo determination of the complete relative configuration using NMR spectroscopy was challenging due to multiple spatially separated stereocenters, including one nonprotonated carbon. In this study, we isolated a new tryptoquivaline derivative, 12S-deoxynortryptoquivaline (1), from the marine ascidian-derived fungus Aspergillus clavatus AS-107. The correct assignment of the relative configuration of 1 was accomplished using anisotropic NMR spectroscopy, while the absolute configuration was determined by comparing calculated and experimental ECD spectra. This case study highlights the effectiveness of anisotropic NMR parameters over isotropic NMR parameters in determining the relative configuration of complex natural products without the need for crystallization.


Assuntos
Urocordados , Animais , Espectroscopia de Ressonância Magnética/métodos , Aspergillus/química , Fungos , Estrutura Molecular
2.
Prenat Diagn ; 43(6): 763-772, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36670513

RESUMO

OBJECTIVE: To describe the prenatal ultrasound (US) findings, genetic results, and clinical outcomes of fetuses with suspected agenesis of the septum pellucidum (ASP) in the Chinese population. METHODS: This retrospective, single-center study included a cohort of fetuses with ASP diagnosed by prenatal imaging over a 10-year period. We evaluated US findings, associated anomalies, genetic results, and clinical outcomes. Prenatal and postnatal imaging findings were compared as well as the clinical outcome of delivery. RESULTS: Ninety patients were included, with a median follow-up time of 36 months (1-96 months). Thirty-six fetuses (40%) with isolated ASP were diagnosed by prenatal US or magnetic resonance imaging (MRI); 39 cases (43.3%) had ASP with central nervous system malformations and 15 cases (16.6%) had ASP with non-CNS abnormalities. Additional imaging findings were supplemented with prenatal MRI in 13 cases. Genetic tests were performed on 32 patients, of whom six had abnormalities. Prenatal US results of 40 patients (40/70) diagnosed by referral hospitals did not correspond to our findings. Of the 38 patients with postnatal records, 11 had abnormal neurological development. CONCLUSION(S): The outcome of an isolated ASP is usually favorable; however, neurological developmental delay is commonly observed if it is combined with other malformations.


Assuntos
Malformações do Sistema Nervoso , Ultrassonografia Pré-Natal , Gravidez , Feminino , Humanos , Ultrassonografia Pré-Natal/métodos , Septo Pelúcido/diagnóstico por imagem , Septo Pelúcido/anormalidades , Estudos Retrospectivos , Relevância Clínica , Feto/anormalidades , Malformações do Sistema Nervoso/diagnóstico por imagem , Ultrassonografia , Imageamento por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos
3.
BMC Pregnancy Childbirth ; 23(1): 772, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925422

RESUMO

BACKGROUND: Fetal facial profile could be measured during the early pregnancy. Its abnormalities might be associated with certain congenital malformations. We aimed to study the associations between fetal facial profile measurements with crown-rump length and congenital malformations (cleft lip and palate, micrognathia, and open spina bifida) during early pregnancy. METHODS: We performed a prospective cross-sectional study between June 2019 and April 2022. Pregnant women at a gestational age between 11-13+ 6 weeks were enrolled. Two sonographers performed fetal facial profile measurements independently. The associations between these measurements with crown-rump length and congenital malformations were evaluated. RESULTS: There were 406 and 25 fetuses without or with congenital malformations, respectively. Two sonographers showed satisfactory inter- and intra-observer agreements and reproducibility. The maxillary gap was only observed in 7.6% of normal fetuses, whereas all cleft lip and palate fetuses had a maxillary gap ≥ 0.8 mm. The crown-rump length was negatively correlated with frontomaxillary facial angle, inferior facial angle, and profile line distance but positively correlated with maxilla-nasion-mandible angle, facial maxillary angle, frontal space distance, and palatine maxillary diameter. These measurements showed various significant changes with different congenital malformations. CONCLUSIONS: Measurements of fetal facial profile in early pregnancy were feasible with satisfactory reproducibility. These measurements correlated with crown-rump length and showed significant differences with certain fetal congenital malformations.


Assuntos
Fenda Labial , Fissura Palatina , Gravidez , Feminino , Humanos , Lactente , Fenda Labial/diagnóstico por imagem , Primeiro Trimestre da Gravidez , Fissura Palatina/diagnóstico por imagem , Estudos Transversais , Reprodutibilidade dos Testes , Estudos Prospectivos , Ultrassonografia Pré-Natal , Feto/diagnóstico por imagem , Idade Gestacional
4.
Mol Breed ; 42(4): 16, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37309463

RESUMO

Genomic selection is an efficient tool for breeding selection, especially for quantitative traits controlled by multiples genes with low heritability. To validate the application of genomic selection in hybrid rice breeding, the yield and grain quality traits of 404 hybrid rice breeding lines were investigated, and the same accessions were genotyped by using a 56 K SNP chip. There were wide variances among the tested accessions for all the measured traits, and most of the traits were correlated. A total of 67 significant loci were identified for the yield-related traits, and 123 significant loci were identified for the grain quality traits by GWAS. Two of these loci associated with increasing grain yield but decreasing grain quality. The GEBVs of all the yield and grain quality traits were calculated by using 15 different prediction algorithms. The plant height, panicle length, thousand grain weight, grain length and width ratio, amylose content, and alkali value have higher predictability than other traits. However, the predictive accuracy of different GS models is different for different traits. This study provided useful information for genomic selection of specific trait using proper markers and prediction models. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01289-6.

5.
J Nat Prod ; 85(5): 1398-1406, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35576457

RESUMO

Ten new tanzawaic acids, namely, steckwaic acids A-D (1-4), 11-ketotanzawaic acid D (5), 6,15-dihydroxytanzawaic acid M (6), 15R-methoxytanzawaic acid M (7), 15S-methoxytanzawaic acid M (8), 8-hydroxytanzawaic acid M (9), and 8-hydroxytanzawaic acid B (10), together with four known analogues (11-14), were isolated and identified from the endozoic fungus Penicillium steckii AS-324, which was obtained from a deep-sea Acanthogorgiidae sp. coral that was collected from the Magellan seamount in the Western Pacific Ocean. Structurally, steckwaic acids A-D (1-4) represent the first tanzawaic acid derivatives containing a naphthalene ring. Their structures were elucidated by detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis and ECD calculations confirmed their structures and absolute configurations. New compounds 1, 5, and 9 exhibited activities against aquatic pathogenic bacteria Micrococcus luteus, Vibrio anguillarum, and Pseudomonas aeruginosa with MICs of 2, 4, and 4 µg/mL, respectively.


Assuntos
Antozoários , Penicillium , Policetídeos , Animais , Testes de Sensibilidade Microbiana , Estrutura Molecular , Penicillium/química , Policetídeos/química
6.
Bioorg Chem ; 128: 106021, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35882090

RESUMO

As the development of genetic and bioinformatic, the strategy of "bottom-up", combined with genome and transcriptome techniques, was considered as an efficient and practical method to break through the limitation of traditional discovery of natural products. Generally, comparative transcriptome analysis could be useful to guide the optimization of fungal cultivation conditions in which the transcriptional level of interesting compounds is higher. The transcriptome analysis of the algal endophytic fungus Penicillium chermesinum EN-480 indicated that fermentation of this fungus in modified rice solid medium could produce some metabolites different from those cultivated in other media. Four new meroterpenoids (compounds 1-4, namely, chermesins E-H) were characterized and their structures were determined by HRESIMS and NMR spectra. The absolute configurations were confirmed by NOESY experiments, X-ray diffraction analysis, and comparison of ECD cotton effects. Antimicrobial activities against human- and aqua-bacteria as well as against plant-pathogenic fungi were assayed. The plausible biosynthesis pathway of these compounds was discussed.


Assuntos
Penicillium , Rodófitas , Perfilação da Expressão Gênica , Humanos , Estrutura Molecular , Penicillium/química , Penicillium/genética , Transcriptoma
7.
Mar Drugs ; 20(8)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36005532

RESUMO

Five new aromatic polyketides, including a unique benzofuran derivative, talarominine A (1), and four chromone analogs talamins A-D (2-5), along with one known related metabolite, 5-hydroxy-7-methoxy-2,3-dimethylchromone (6), were isolated and identified from the Talaromyces minioluteus CS-138, an endozoic fungus obtained from the deep-sea cold seep mussel Gigantidas platifrons. Their chemical structures were elucidated by detailed analysis of their NMR spectra, HRESIMS and X-ray crystallographic data, and by comparison with literature data as well. The antibacterial and DPPH scavenging activities of compounds 1-6 were evaluated. Compounds 1-3 showed inhibitory activity against some of the tested bacteria whereas compounds 2 and 5 showed potent DPPH radical scavenging activities, which were better than that of the positive control butylated hydroxytoluene (BHT). This work is likely the first report on marine natural products of mussel-derived fungus living in cold seep environments.


Assuntos
Mytilidae , Policetídeos , Talaromyces , Animais , Bactérias , Estrutura Molecular , Mytilidae/metabolismo , Policetídeos/química , Talaromyces/química
8.
Chem Biodivers ; 19(8): e202200550, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35727302

RESUMO

Two new antimicrobial cytochalasin derivatives, 6ß,7ß-epoxydeoxaphomin C (1) and 12-hydroxydeoxaphomin C (2), a new natural occurring product 24-nor-cytochalasin B (3), together with two related known analogs (4-5) were isolated and identified from an endozoic fungus Curvularia verruculosa CS-129, isolated from the deep-sea squat lobster Shinkaia crosnieri which was collected in cold seep region of south China sea. The structures of new compounds were elucidated on the basis of detailed spectroscopic analysis and ECD calculation. The spectroscopic data of 24-nor-cytochalasin B (3) were reported for the first time. All compounds were tested for their antibacterial activities against human and aquatic pathogenic bacteria.


Assuntos
Curvularia , Citocalasinas , Antibacterianos/química , Citocalasina B , Citocalasinas/química , Citocalasinas/farmacologia , Fungos , Humanos , Estrutura Molecular
9.
Int J Mol Sci ; 23(11)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35683011

RESUMO

Four unusual steckwaic acids E-H (1-4), possessing a rarely described acrylic acid unit at C-4 (1-3) or a double bond between C-12 and C-13 (4) are reported for the first time, along with four new analogues (5-8) and two known congeners (9 and 10). They were purified from the organic extract of Penicillium steckii AS-324, an endozoic fungus obtained from a deep-sea coral Acanthogorgiidae sp., which was collected from the Magellan Seamount at a depth of 1458 m. Their structures were determined by the interpretation of NMR and mass spectroscopic data. The relative and absolute configurations were determined by NOESY correlations, X-ray crystallographic analysis, and ECD calculations. All compounds were tested for their antimicrobial activities against human- and aquatic-pathogenic bacteria and plant-related pathogenic fungi.


Assuntos
Antozoários , Penicillium , Policetídeos , Animais , Fungos/química , Estrutura Molecular , Penicillium/química , Policetídeos/química , Policetídeos/farmacologia
10.
J Sci Food Agric ; 102(10): 4140-4150, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34997612

RESUMO

BACKGROUND: Unsaturated fatty acids used to form unstable micro-vesicles, while conjugate linoleic acid (CLA)-sodium dodecyl sulfate (SDS) can self-assembly to stable nano-conjugate linoleic acid vesicles (nano-CLAVs). Generally, micro-capsule could geometrically provide higher loading capacity but also generate concerns in construction convenience, sustained release, bioaccessibility and stability. Hence there is a contradiction between loading capacity and encapsulation efficiency. Therefore, the study of the factors that decide the capsule size falling in nano or micron size with same capsule material would be a benefit to food or drug delivery science. RESULTS: The micron- and nano-CLAVs were constructed for encapsulation and sustained release of ginsenoside Rg3. The formation mechanism of nano or micron capsule,s the effect of vesicle sizes on encapsulation efficiency, drug loading efficiency and stability of the encapsulated Rg3 were investigated. It was found that with the addition of salt (PBS), the size of CLAVs jumped from nano to micron. Furthermore, the salt concentration is the key factor that decides the vesicle size of nano or micron. The pH at fabrication triggers the vesiculation and dramatically affects the vesicle size over the nano and micron scales. CONCLUSION: Compared to the nano-CLAVs, micron vesicles enhanced the loading capacity to 137.6% and the encapsulation efficiency to 138.4%, respectively. Meanwhile, the micron-CLAVs performed similar sustained release of Rg3 as the nano-CLAVs did, and was stable for 120 days at room temperature or sustained 98.9% of capsules after centrifuge at 6090 × g for 20 min. © 2022 Society of Chemical Industry.


Assuntos
Ginsenosídeos , Ácidos Linoleicos Conjugados , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos
11.
J Nat Prod ; 84(12): 3122-3130, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34846891

RESUMO

A new cytochalasin dimer, verruculoid A (1), three new cytochalasin derivatives, including 12-nor-cytochalasin F (2), 22-methoxycytochalasin B6 (3), and 19-hydroxycytochalasin B (4), and 20-deoxycytochalasin B (5), a synthetic product obtained as a natural product for the first time, together with four known analogues (6-9), were isolated and identified from the culture extract of Curvularia verruculosa CS-129, an endozoic fungus obtained from the inner fresh tissue of the deep-sea squat lobster Shinkaia crosnieri, which was collected from the cold seep area of the South China Sea. Structurally, verruculoid A (1) represents the first cytochalasin homodimer containing a thioether bridge, while 12-nor-cytochalasin F (2) is the first 12-nor-cytochalasin derivative. Their structures were elucidated by detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis and ECD calculations confirmed their structures and absolute configurations. Compound 1 displayed activity against the human pathogenic bacterium Escherichia coli (MIC = 2 µg/mL), while compounds 4, 8, and 9 showed cytotoxicity against three tumor cell lines (HCT-116, HepG-2, and MCF-7) with IC50 values from 5.2 to 12 µM. The structure-activity relationship was briefly discussed.


Assuntos
Temperatura Baixa , Crustáceos/química , Curvularia/isolamento & purificação , Citocalasinas/farmacologia , Ecossistema , Animais , Citocalasinas/química , Citocalasinas/isolamento & purificação
12.
Bioprocess Biosyst Eng ; 44(1): 151-159, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32860147

RESUMO

Isosteviol, a prodrug used to be obtained via Wagner-Meerwein rearrangement from steviol with low yield and long reaction time. Herein, an in-situ separation-coupling-reaction is presented to prepare isosteviol from the natural sweetener stevioside. Simply with in-situ water-washing, the product containing 92.98% purity of isosteviol was obtained with a stevioside conversion of 97.23% from a packet bed reactor without further separation. Within the assayed inorganic acid, organic acids and acidic ionic liquids, the acidic ion-exchange resins provided higher product specificity towards isosteviol. Furthermore, comparing to 5-Fluorouracil, the product presented similar and even stronger inhibition on proliferation of the assayed human cancer cells in a time and dose-dependence by causing cell phase arrest. Isosteviol treatment caused G1 arrest on SGC-7901, HCT-8 and HCT-116 cells, S arrest on HepG2, Huh-7 and HepG3B cells, and G2 arrest on MGC-803 cells, respectively. Reaction coupling separation for isosteviol production catalyzed by acidic ion-exchange resin.


Assuntos
Antineoplásicos , Diterpenos do Tipo Caurano/química , Fase G2/efeitos dos fármacos , Glucosídeos/química , Neoplasias/metabolismo , Pró-Fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Catálise , Diterpenos do Tipo Caurano/síntese química , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/farmacologia , Células HCT116 , Células Hep G2 , Humanos , Resinas de Troca Iônica , Neoplasias/tratamento farmacológico , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/isolamento & purificação , Pró-Fármacos/farmacologia
13.
Langmuir ; 36(27): 7765-7774, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32539409

RESUMO

Nonylphenol ethoxylates (NPEOn) exhibit outstanding application performances, especially in stabilizing silicone oil emulsions, but have been globally banned or use-restricted for serious ecological toxicity. A homologous series of nonionic surfactants, n-dodecylbenzyloxy ethoxylates (DBEOn), are molecularly designed and synthesized as alternatives to NPEOn, where the phenolic group of NPEOn was replaced by a benzyloxy group to counteract the harmful characteristics of NPEOn, while retaining the benefits. Based on computational studies, we propose a hypothesis that has a conjugation reduction effect (CRE) of DBEOn relative to NPEOn on the surfactant structure and properties that solves the biodegradation problem while maintaining the outstanding emulsifying capacity of NPEOn. A 7-day activated sludge assessment shows that DBEO8, a representative member of DBEOn, is almost 100% biodegradable and that the poor biodegradability of NPEOn may be improved by maintaining the vital benzene ring in DBEOn molecules, because the oxygen atom of the benzyloxy group is separated from the smaller conjugation system of DBEOn. Compared to NPEO10, DBEO8 has a similar cloud point but exhibits higher benzene solubilization and considerably higher emulsion stabilities for mineral oil, biomass oil, and especially silicone oil; this outcome is ascribed to a probable random coil configuration of PEO caused by the CRE of DBEOn. Therefore, molecular design produces DBEOn with both excellent biodegradability and outstanding application performances, especially in terms of excellent emulsion stabilities of various oils, as predicted by the CRE hypothesis, thereby serving as an effective alternative to NPEOn.


Assuntos
Óleos , Tensoativos , Biodegradação Ambiental , Emulsões , Fenóis
14.
Mar Drugs ; 18(4)2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272624

RESUMO

Secondary metabolites obtained from marine-derived fungi are rich sources of drug candidates. Three new sesquiterpenoids, chermesiterpenoids A-C (1-3), along with four known alkaloids (4-7), were isolated and identified from the marine red algal-derived fungus Penicillium chermesinum EN-480. The structures of these new sesquiterpenoids were elucidated using detailed analysis of the NMR data and their relative configurations were elucidated using nuclear overhauser effect spectroscopy (NOESY) spectra as well as gauge-independent atomic orbital (GIAO) NMR shift calculations and DP4+ probability analysis. Their absolute configurations were determined using electronic circular dichroism (ECD) calculations and modified Mosher's method. Compounds 2 and 3 exhibited potent activities against human and aquatic pathogenic bacteria and plant pathogenic fungi.


Assuntos
Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Penicillium/química , Sesquiterpenos/química , Alcaloides/química , Dicroísmo Circular , Humanos , Estrutura Molecular
15.
Langmuir ; 35(8): 3116-3125, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30758969

RESUMO

A series of novel anionic e-surfactants n-C cP pS was molecular designed and synthesized from long-chain fatty alcohols by polypropoxylation and sulfation followed by neutralization. Excellent all-round performance of extended surfactants (e-surfactants) interests us how a simple polypropylene oxide (PPO) spacer has great effects on properties. By a comparative study of conventional/ethoxylated/extended n-alkylsulfate surfactants, we were surprised to find that e-surfactants are in an obvious rugby shape at the air/water surface according to molecular surface area ( am), and it comes down to the intramolecular PPO spacer coiling and surface-induced collapse. On the basis of the interfacial properties of the e-surfactants, it is found that the PPO spacer can provide both hydrophilic and lipophilic contributions to an e-surfactant molecule. The synergism between PPO spacers and alkyl chains indicates that a certain PPO spacer can adjust the contributions in view of different alkyl chain lengths. Therefore, it is both the rugby-shaped molecular geometry of e-surfactants and the dynamic amphipathicity of a PPO spacer that makes e-surfactants behave with excellent interfacial and solution properties for household cleaning. Therefore, this work gives us a hint that the molecular geometry of surfactants plays a vital role in interfacial and solution properties similar to molecular amphipathicity.

16.
Mar Drugs ; 15(5)2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28498358

RESUMO

Three new indolediterpenoids, namely, 22-hydroxylshearinine F (1), 6-hydroxylpaspalinine (2), and 7-O-acetylemindole SB (3), along with eight related known analogs (4-11), were isolated from the sea-anemone-derived fungus Penicillium sp. AS-79. The structures and relative configurations of these compounds were determined by a detailed interpretation of the spectroscopic data, and their absolute configurations were determined by ECD calculations (1 and 2) and single-crystal X-ray diffraction (3). Some of these compounds exhibited prominent activity against aquatic and human pathogenic microbes.


Assuntos
Antozoários/microbiologia , Diterpenos/química , Indóis/isolamento & purificação , Penicillium/isolamento & purificação , Penicillium/metabolismo , Animais , Diterpenos/isolamento & purificação , Diterpenos/metabolismo , Indóis/química , Modelos Moleculares , Estrutura Molecular , Difração de Raios X/métodos
17.
Front Neurol ; 15: 1320653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352136

RESUMO

Purpose: This study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the diagnosis of Alzheimer's disease (AD) and the differential diagnosis between AD and mild cognitive impairment (MCI). Methods: From September 2021 to October 2022, we collected venous blood from patients and healthy individuals who visited our hospital's Neurology Department, and we isolated serum to detect NfL and GFAP using direct chemiluminescence. The results were analyzed using one-way analysis of variance (ANOVA) analysis and receiver operating characteristic (ROC) curves. Results: Pairwise comparisons among the three groups showed that compared with the health checkup (HC) group, serum NfL and GFAP were increased in both AD and MCI (PNfL < 0.05, PGFAP < 0.01). There were significant differences in GFAP between MCI and AD groups, and the level in AD group was higher (p < 0.01), while there was no difference in NfL. Both serum NfL and serum GFAP levels can independently diagnose AD (p < 0.01). The ROC curve showed that GFAP had a higher diagnostic efficacy, with an area under the ROC curve (AUC) of 0.928. The cut-off values of the two serum markers for the diagnosis of AD were NfL > 40.09 pg./mL and GFAP >31.40 pg./mL. Sensitivity and specificity for NfL in the diagnosis of AD were 59.6 and 76.2%, respectively, and for GFAP, they were 90.4 and 82.1%, respectively. The combined diagnosis of GFAP and NfL improved the diagnostic efficiency (AUC = 0.931, sensitivity = 78.8%, specificity = 92.3%). The cut-off value of GFAP for the differential diagnosis of MCI and AD was 46.05 pg./mL. Conclusion: Both serum NfL and serum GFAP can be used as biomarkers for the diagnosis of AD. Serum GFAP has better diagnostic efficacy and can distinguish AD from MCI. A combined diagnosis can improve diagnostic specificity.

18.
Acta Biomater ; 173: 457-469, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984631

RESUMO

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.


Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Humanos , Glucose Oxidase , Peróxido de Hidrogênio , Nanopartículas de Magnetita/uso terapêutico , Estresse Oxidativo , Arginina , Glutationa , Nanopartículas/uso terapêutico , Neoplasias/terapia , Oxidantes , Dissulfetos , Fenômenos Magnéticos , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Regen Biomater ; 11: rbad111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173764

RESUMO

Titanium (Ti) implants have been extensively used after surgical operations. Its surface bioactivity is of importance to facilitate integration with surrounding bone tissue, and ultimately ensure stability and long-term functionality of the implant. The plasmid DNA-activated matrix (DAM) coating on the surface could benefit osseointegration but is still trapped by poor transfection for further application, especially on the bone marrow mesenchymal stem cells (BMSCs) in vivo practical conditions. Herein, we constructed a DAM on the surface of fibrous-grained titanium (FG Ti) composed of phase-transition lysozyme (P) as adhesive, cationic arginine-rich lipid (RLS) as the transfection agent and plasmid DNA (pDNA) for bone morphology protein 2 (BMP2) expression. The cationic lipid RLS improved up to 30-fold higher transfection than that of commercial reagents (Lipofectamine 2000 and polyethyleneimine) on MSC. And importantly, Ti surface topology not only promotes the DAM to achieve high transfection efficiency (∼75.7% positive cells) on MSC due to the favorable combination but also reserves its contact induction effect for osteoblasts. Upon further exploration, the fibrous topology on FG Ti could boost pDNA uptake for gene transfection, and cell migration in MSC through cytoskeleton remodeling and induce contact guidance for enhanced osteointegration. At the same time, the cationic RLS together with adhesive P were both antibacterial, showing up to 90% inhibition rate against Escherichia coli and Staphylococcus aureus with reduced adherent microorganisms and disrupted bacteria. Finally, the FG Ti-P/pBMP2 implant achieved accelerated bone healing capacities through highly efficient gene delivery, aligned surface topological structure and increased antimicrobial properties in a rat femoral condylar defect model.

20.
Front Oncol ; 13: 1141417, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959811

RESUMO

Objective: Spondin-2 (SPON2) is highly expressed in a variety of tumors and has been associated with poor prognosis, but the relationship to triple-negative breast cancer (TNBC) is unclear. The aim of this study is to investigate the expression of SPON2 in TNBC and its function. Methods: Immunohistochemistry was used to detect the expression of the SPON2 protein in TNBC and in normal tissue adjacent to cancer and breast fibroadenoma. The GEO database GSE76275 dataset was used to study the expression of SPON2 mRNA in TNBC and non-TNBC. ​The expression of SPON2 mRNA was detected by qPCR in TNBC cells MDA-MB-231, non-TNBC breast cancer cells MCF-7, and normal breast cells MCF-10A. ​Kaplan Meier-Plotter database was used to analyze the relationship between SPON2 expression and TNBC prognosis. ​ShRNA lentivirus was used to knock down high expression of SPON2 in TNBC cells. The effects of knockdown of SPON2 expression on the proliferation, migration, invasion, apoptosis, and subcutaneous tumorigenic ability of TNBC cells in nude mice were analyzed using CCK8, clone formation assay, scratch assay, transwell migration assay, transwell invasion assay, Hoechst apoptosis assay, and tumorigenic ability in nude mice. Transcriptome sequencing of TNBC cells with knockdown SPON2 expression. ​In combination with the GEO database, GO and KEGG analyses were performed, and psychophysiological interaction Protein-Protein Interaction Networks (PPI) analysis was performed for transcriptome sequencing of the differentially expressed genes. ​The changes in the expression of PI3K-ATK pathway proteins after SPON2 knockdown were detected by Western blot. Results: Our study shows that upregulation of SPON2 in TNBC is associated with poorer patient outcomes. Knockdown of SPON2 inhibited TNBC cell proliferation, clone formation, migration, invasion, and tumorigenic ability and promoted apoptosis. Knockdown of SPON2 up-regulated TNBC cell adhesion and down-regulated PI3K-ATK pathway, and PPI results showed that CCL2 was the key protein. Conclusions: SPON2 may be a valuable biomarker for the diagnosis and prognosis of TNBC and is a potential therapeutic target for TNBC.

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