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1.
J Nat Prod ; 87(6): 1563-1573, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38856635

RESUMO

Ten new ergone derivatives (1-10) and five known analogues (11-15) were isolated from the deep-sea-derived fungus Aspergillus terreus YPGA10. The structures including the absolute configurations were established by detailed analysis of the NMR spectroscopic data, HRESIMS, ECD calculation, and coupling constant calculation. All the structures are characterized by a highly conjugated 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one nucleus. Structurally, compound 2 bearing a 15-carbonyl group and compounds 5-7 possessing a 15ß-OH/OCH3 group are rarely encountered in ergone derivatives. Bioassay results showed that compounds 1 and 11 demonstrated cytotoxic effects on human colon cancer SW620 cells with IC50 values of 8.4 and 3.1 µM, respectively. Notably, both compounds exhibited negligible cytotoxicity on the human normal lung epithelial cell BEAS-2B. Compound 11 was selected for preliminary mechanistic study and was found to inhibit cell proliferation and induce apoptosis in human colon cancer SW620 cells. In addition, compound 1 displayed cytotoxic activity against five human leukemia cell lines with IC50 values ranging from 5.7 to 8.9 µM. Our study demonstrated that compound 11 may serve as a potential candidate for the development of anticolorectal cancer agents.


Assuntos
Apoptose , Aspergillus , Neoplasias do Colo , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Aspergillus/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34548396

RESUMO

Elevated levels of MUC5AC, one of the major gel-forming mucins in the lungs, are closely associated with chronic obstructive lung diseases such as chronic bronchitis and asthma. It is not known, however, how the structure and/or gel-making properties of MUC5AC contribute to innate lung defense in health and drive the formation of stagnant mucus in disease. To understand this, here we studied the biophysical properties and macromolecular assembly of MUC5AC compared to MUC5B. To study each native mucin, we used Calu3 monomucin cultures that produced MUC5AC or MUC5B. To understand the macromolecular assembly of MUC5AC through N-terminal oligomerization, we expressed a recombinant whole N-terminal domain (5ACNT). Scanning electron microscopy and atomic force microscopy imaging indicated that the two mucins formed distinct networks on epithelial and experimental surfaces; MUC5B formed linear, infrequently branched multimers, whereas MUC5AC formed tightly organized networks with a high degree of branching. Quartz crystal microbalance-dissipation monitoring experiments indicated that MUC5AC bound significantly more to hydrophobic surfaces and was stiffer and more viscoelastic as compared to MUC5B. Light scattering analysis determined that 5ACNT primarily forms disulfide-linked covalent dimers and higher-order oligomers (i.e., trimers and tetramers). Selective proteolytic digestion of the central glycosylated region of the full-length molecule confirmed that MUC5AC forms dimers and higher-order oligomers through its N terminus. Collectively, the distinct N-terminal organization of MUC5AC may explain the more adhesive and unique viscoelastic properties of branched, highly networked MUC5AC gels. These properties may generate insight into why/how MUC5AC forms a static, "tethered" mucus layer in chronic muco-obstructive lung diseases.


Assuntos
Células Epiteliais/metabolismo , Mucina-5AC/química , Mucina-5AC/metabolismo , Mucina-5B/química , Mucina-5B/metabolismo , Mucosa Respiratória/metabolismo , Células Cultivadas , Células Epiteliais/citologia , Humanos , Mucosa Respiratória/citologia
3.
Int Wound J ; 21(3): e14657, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38472128

RESUMO

To explore the effect of clinical nursing pathway on wound infection in patients undergoing knee or hip replacement surgery. Computerised searches of PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database, China National Knowledge Infrastructure databases were conducted, from database inception to September 2023, on the randomised controlled trials (RCTs) of application of clinical nursing pathway to patients undergoing knee and hip arthroplasty. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. RevMan 5.4 software was employed for data analysis. Overall, 48 RCTs involving 4139 surgical patients were included, including 2072 and 2067 in the clinical nursing pathway and routine nursing groups, respectively. The results revealed, compared with routine nursing, the use of clinical nursing pathways was effective in reducing the rate of complications (OR = 0.17, 95%CI: 0.14-0.21, p < 0.001) and wound infections (OR = 0.29, 95%CI: 0.16-0.51, p < 0.001), shortens the hospital length of stay (MD = -4.11, 95%CI: -5.40 to -2.83, p < 0.001) and improves wound pain (MD = -1.34, 95%CI: -1.98 to -0.70, p < 0.001); it also improve patient satisfaction (OR = 7.13, 95%CI: 4.69-10.85, p < 0.001). The implementation of clinical nursing pathways in clinical care after knee or hip arthroplasty can effectively reduce the incidence of complications and wound infections, and also improve the wound pain, while also improving treatment satisfaction so that patients can be discharged from the hospital as soon as possible.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Infecção da Ferida Cirúrgica , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/enfermagem , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/enfermagem , Dor/complicações , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/enfermagem , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Int Wound J ; 21(3): e14776, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494661

RESUMO

A meta-analysis was conducted to comprehensively evaluate the impact of cluster nursing interventions on the prevention of pressure ulcers (PUs) in intensive care unit (ICU) patients. Computer searches were performed in databases including Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure for randomized controlled trials (RCTs) implementing cluster nursing interventions for PUs prevention in ICU patients, with the search period covering the database inception to November 2023. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 17 RCTs involving 1463 ICU patients were included. The analysis showed that compared with conventional nursing, cluster nursing interventions significantly reduced the incidence of PUs (odds ratio: 0.24, 95% confidence intervals [CI]: 0.17-0.34, p < 0.001) and also significantly improved the levels of anxiety (standardized mean difference [SMD]: -1.39, 95% CI: -1.57 to 1.22, p < 0.001) and depression (SMD: -1.64, 95% CI: -2.02 to 1.26, p < 0.001) in ICU patients. This study indicates that the application of cluster nursing interventions in ICU patients can effectively reduce the incidence of PUs, as well as improve patients' anxiety and depression levels, thereby enhancing their quality of life, which is worth clinical promotion and application.


Assuntos
Úlcera por Pressão , Humanos , Úlcera por Pressão/prevenção & controle , Úlcera por Pressão/epidemiologia , Cuidados Críticos , Ansiedade , Unidades de Terapia Intensiva , Supuração
5.
Planta ; 259(1): 6, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001306

RESUMO

MAIN CONCLUSION: Rpf107 is involved in the infection process of rhizobia and the maintenance of symbiotic nitrogen fixation in black locust root nodules. The LURP-one related (LOR) protein family plays a pivotal role in mediating plant defense responses against both biotic and abiotic stresses. However, our understanding of its function in the symbiotic interaction between legumes and rhizobia remains limited. Here, Rpf107, a homolog of LOR, was identified in Robinia pseudoacacia (black locust). The subcellular localization of Rpf107 was analyzed, and its function was investigated using RNA interference (RNAi) and overexpression techniques. The subcellular localization assay revealed that Rpf107 was mainly distributed in the plasma membrane and nucleus. Rpf107 silencing prevented rhizobial infection and hampered plant growth. The number of infected cells in the nitrogen fixation zone of the Rpf107-RNAi nodules was also noticeably lower than that in the control nodules. Notably, Rpf107 silencing resulted in bacteroid degradation and the premature aging of nodules. In contrast, the overexpression of Rpf107 delayed the senescence of nodules and prolonged the nitrogen-fixing ability of nodules. These results demonstrate that Rpf107 was involved in the infection of rhizobia and the maintenance of symbiotic nitrogen fixation in black locust root nodules. The findings reveal that a member of the LOR protein family plays a role in leguminous root nodule symbiosis, which is helpful to clarify the functions of plant LOR protein family and fully understand the molecular mechanisms underlying legume-rhizobium symbiosis.


Assuntos
Fabaceae , Rhizobium , Robinia , Robinia/genética , Nódulos Radiculares de Plantas/metabolismo , Simbiose/genética , Genes vif , Fixação de Nitrogênio/genética , Rhizobium/fisiologia , Fabaceae/genética , Proteínas de Plantas/metabolismo
6.
BMC Microbiol ; 23(1): 132, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37189022

RESUMO

BACKGROUND: Rhizosphere soil physicochemical, endophytic fungi have an important role in plant growth. A large number of endophytic fungi play an indispensable role in promoting plant growth and development, and they can provide protection for host plants by producing a variety of secondary metabolites to resist and inhibit plant pathogens. Due to the terrain of Gansu province is north-south and longitudinal, different climatic conditions, altitude, terrain and growth environment will affect the growth of Codonopsis pilosula, and the changes in these environmental factors directly affect the quality and yield of C. pilosula in different production areas. However, In C. pilosula, the connection between soil nutrients, spatiotemporal variation and the community structure of endophytic fungi isolated from C. pilosula roots has not been well studied. RESULTS: Seven hundred six strains of endophytic fungi were obtained using tissue isolation and the hyphaend-purification method from C. pilosula roots that picked at all seasons and six districts (Huichuan, HC; Longxi, LX; Zhangxian, ZX; Minxian, MX; Weiyuan, WY; and Lintao, LT) in Gansu Province, China. Fusarium sp. (205 strains, 29.04%), Aspergillus sp. (196 strains, 27.76%), Alternaria sp. (73 strains, 10.34%), Penicillium sp. (58 strains, 8.22%) and Plectosphaerella sp. (56 strains, 7.93%) were the dominant genus. The species composition differed from temporal and spatial distribution (Autumn and Winter were higher than Spring and Summer, MX and LT had the highest similarity, HC and LT had the lowest). physical and chemical of soil like Electroconductibility (EC), Total nitrogen (TN), Catalase (CAT), Urease (URE) and Sucrase (SUC) had significant effects on agronomic traits of C. pilosula (P < 0.05). AK (Spring and Summer), TN (Autumn) and altitude (Winter) are the main driving factors for the change of endophytic fungal community. Moreover, geographic location (such as altitude, latitude and longitude) also has effects on the diversity of endophytic fungi. CONCLUSIONS: These results suggested that soil nutrients and enzyme, seasonal variation and geographical locations have an impact on shaping the community structure of culturable endophytic fungi in the roots of C. pilosula and its root traits. This suggests that climatic conditions may play a driving role in the growth and development of C. pilosula.


Assuntos
Ascomicetos , Codonopsis , Micobioma , Estações do Ano , Codonopsis/química , Fungos , Solo , Raízes de Plantas/microbiologia , Endófitos
7.
Cerebellum ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962773

RESUMO

The cerebellum plays an important role in maintaining balance, posture control, muscle tone, and lower limb coordination in healthy individuals and stroke patients. At the same time, the relationship between cerebellum and motor learning has been widely concerned in recent years. Due to the relatively intact structure preservation and high plasticity after supratentorial stroke, non-invasive neuromodulation targeting the cerebellum is increasingly used to treat abnormal gait in stroke patients. The gamma frequency of transcranial alternating current stimulation (tACS) is commonly used to improve motor learning. It is an essential endogenous EEG oscillation in the gamma range during the swing phase, and rhythmic movement changes in the gait cycle. However, the effect of cerebellar tACS in the gamma frequency band on balance and walking after stroke remains unknown and requires further investigation.

8.
J Nat Prod ; 86(4): 830-841, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36897077

RESUMO

Seven new phenolic bisabolane sesquiterpenoids (1-7), along with 10 biogenetically related analogues (8-17), were obtained from the deep-sea-derived fungus Aspergillus versicolor YPH93. The structures were elucidated based on extensive analyses of the spectroscopic data. Compounds 1-3 are the first examples of phenolic bisabolanes that contain two hydroxy groups attached to the pyran ring. The structures of sydowic acid derivatives (1-6 and 8-10) were carefully studied, leading to the structure revisions of six known analogues, including a revision of the absolute configuration for sydowic acid (10). All metabolites were evaluated for their effects on ferroptosis. Compound 7 exerted inhibition on erastin/RSL3-induced ferroptosis with EC50 values ranging from 2 to 4 µM, while it exhibited no effects on TNFα-induced necroptosis or H2O2-induced cell necrosis.


Assuntos
Ferroptose , Sesquiterpenos , Aspergillus/química , Peróxido de Hidrogênio , Estrutura Molecular , Sesquiterpenos Monocíclicos , Fenóis/farmacologia , Sesquiterpenos/química
9.
Neural Plast ; 2023: 9532713, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37789954

RESUMO

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.


Assuntos
Acidente Vascular Cerebral , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Nervo Vago , Extremidade Superior
10.
Int Wound J ; 21(3): e14489, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973556

RESUMO

To systematically analyse the effects of evidence-based nursing (EBN) in preventing the development of pressure ulcers (PUs) in intensive care unit (ICU) patients. We conducted a computerised search of the Embase, PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials on the prevention of PUs in ICU patients by EBN, published before the respective databases were established until September 2023. Two investigators independently performed literature screening, data extraction and quality assessment. A meta-analysis was performed using Stata 17.0. Eighteen papers were included, comprising 2593 patients, of whom 1297 and 1296 received EBN and conventional nursing, respectively. The incidence of PUs was 2.70% and 12.04% in the EBN and conventional nursing groups, respectively. Meta-analysis showed a statistically significantly lower incidence of PUs in the EBN group than that in the conventional nursing group (risk ratio = 0.22, 95% confidence interval: 0.16-0.32, p < 0.001). EBN interventions are more effective than conventional nursing in preventing PUs in ICU patients. However, since the literature included in this study was from China, the conclusions require further confirmation via higher-quality studies.

11.
Small ; 18(27): e2202248, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35678593

RESUMO

Herein, a strategy of synergetic dual-metal-ion centers to boost transition-metal-based metal organic framework (MOF) alloy nanomaterials as active oxygen reduction reaction (ORR) electrocatalysts for efficient hydrogen peroxide (H2 O2 ) generation is proposed. Through a facile one-pot wet chemical method, a series of MOF alloys with unique Ni-M (M-Co, Cu, Zn) synergetic centers are synthesized, where the strong metallic ions 3d-3d synergy can effectively inhibit O2 cleavage on Ni sites toward a favorable two-electron ORR pathway. Impressively, the well-designed NiZn MOF alloy catalysts show an excellent H2 O2 selectivity up to 90% during ORR, evidently outperforming that of NiCo MOF (45%), and NiCu MOF (55%). Moreover, it sustains efficient activity and robust stability under a continuous longterm ORR operation. The correlative in situ synchrotron radiation X-ray adsorption fine structure and Fourier transform infrared spectroscopy analyses reveal at the atomic level that, the higher Ni oxidation states species, regulated via adjacent Zn2+ ions, are favorable for optimizing the adsorption energetics of key *OOH intermediates toward fast two electron ORR kinetics.

12.
Small ; 17(49): e2105231, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34713574

RESUMO

Accurately manipulating the electronic structure of metal active sites under working conditions is central to developing efficient and stable electrocatalysts in industrial water-alkali electrolyzers. However, the lack of an intuitive means to capture the evolution of metal sites during the reaction state inhibits the manipulation of its electronic structure. Here, atomically dispersed Ru single-sites on cobalt nanoparticles confined onto macro-microporous frameworks (M-Co NPs@Ru SAs/NC) with tunable electron coupling effect for efficient catalysis of alkaline hydrogen evolution reaction (HER) are constructed. Using operando X-ray absorption and infrared spectroscopies, a dynamic CoRu bond shrinkage with strong electron coupling effect under working conditions is identified, which significantly promotes the adsorption of water molecules and then accelerates its dissociation to form the key H* over Ru sites for high HER activity. The well-designed M-Co NPs@Ru SAs/NC delivers efficient HER performance with a small overpotential of 34 mV at 10 mA cm-2 and a high turnover frequency of ≈4284 H2  h-1 at -0.05 V, 40 times higher than that of the benchmark Pt/C. This work provides a new point of view to manipulate the electronic structure of the metal active sites for highly effective electrocatalysis processes.

13.
Biomacromolecules ; 22(4): 1346-1356, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33657790

RESUMO

Developing a versatile bioadhesive which is biocompatible, adhesive, hemostatic, and therapeutic is of great significance to promote wound sealing and healing. Herein, an adhesive (GTT-3 hydrogel) is fabricated by catalysis of tannic acid modified gelatin (Gel-TA) with transglutaminase (TG). The hydrogen bonding, imine linking, and acyl-transfer reaction between GTT-3 hydrogel and tissue enable efficient hydrogel integration and adhesion to tissue instantly, so as to seal the wound and stop bleeding. Moreover, the intrinsic wound healing ability of gelatin and the antibacterial properties of TA provide favorable conditions for wound healing after adhesion. In vitro mechanical property testing and cell experimental results determine the elasticity, adhesion, and biocompatibility of the GTT-3 hydrogel. The wound operation in mouse models and pathological sectioning results indicate that GTT-3 adhesive obviously accelerates hemostasis, wound bonding, and healing. With the special property of instant adhesion and excellent hemostatic and therapeutic repair effects, GTT-3 hydrogel may provide a new option for surgical operation.


Assuntos
Hidrogéis , Cicatrização , Animais , Antibacterianos/uso terapêutico , Catálise , Gelatina , Hemostasia , Camundongos
14.
J Am Chem Soc ; 142(28): 12306-12313, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32579351

RESUMO

The structural dynamics of the solid-liquid interfaces (SLEIs) determines the chemistry in all electrochemical processes. Here, by combining multiple operando synchrotron spectroscopies, we identify at the atomic level a general evolution of single-atom Ni at SLEIs into a near-free atom state in the electrochemical oxygen reduction reaction (ORR). We uncover that the single-atom Ni at SLEIs tends to be dynamically released from the nitrogen-carbon substrate and then forms a near-free, isolated-zigzag active site (Ni1(2-δ)+N2) during the reaction. This isolated-zigzag Ni1(2-δ)+N2 active site facilitates the adsorption and dissociation of O2 into a crucial *O intermediate within the electrical double layers, realizing a highly efficient single-atom catalyst with the best ORR performance in alkaline solutions reported thus far. These findings may pave a general way for dissecting other important structural dynamic processes at SLEIs, such as hydrogen evolution, oxygen evolution, and CO2 reduction reactions.

15.
J Gene Med ; 22(5): e3169, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32028542

RESUMO

BACKGROUND: microRNA (miR)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin (IL)-1ß-induced chondrocyte dysfunction via the miR-148-3p/fibroblast growth factor-2 (FGF-2) signaling pathway. METHODS: Candidate miRs were filtrated using miR microarray assays in chondrocytes with or without IL-1ß stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. Cell growth was evaluated using cell counting kit-8 assays. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate double staining. RESULTS: Treatment with OLA counteracted IL-1ß-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, and release of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine. Additionally, FGF2 protein expression levels elevated by IL-1ß were down-regulated by OLA and transfection with miR-148-3p mimics. IL-1ß-induced down-regulation of miR-148-3p in chondrocytes was evaluated by OLA administration. Bioinformatics algorithms and experimental measurements indicated that FGF2 might be a direct target of miR-148-3p. miR-148-3p mimics exhibited equal authenticity of OLA to protect against IL-1ß-induced chondrocyte dysfunction. CONCLUSIONS: Our present findings highlight a protective effect of OLA on IL-1ß-induced chondrocyte dysfunction, and a novel signal cascade comprising the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA with respect to preventing the progression of osteoarthritis.


Assuntos
Condrócitos/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/metabolismo , Interleucina-1beta/farmacologia , MicroRNAs/metabolismo , Ácido Oleanólico/farmacologia , Regiões 3' não Traduzidas , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Algoritmos , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/patologia , Biologia Computacional , Fator 2 de Crescimento de Fibroblastos/genética , Humanos , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , MicroRNAs/genética , Análise em Microsséries , Ácido Oleanólico/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
16.
J Nat Prod ; 83(9): 2679-2685, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32902982

RESUMO

Twelve new polyketides, including a naphthoquinone derivative, penithoketone (1), and 11 chromone derivatives, penithochromones A-L (2-12), together with three known compounds (13-15) were isolated from the deep-sea-derived fungus Penicillium thomii YPGA3. The structures of the metabolites were elucidated based on extensive analyses of the spectroscopic data, and the configuration of 1 was resolved by quantum chemical calculations of NMR shifts and ECD spectra and comparisons to experimental data. Compound 1, containing a naphthoquinone-derived moiety substituted with a butenolide unit, represents a new modified naphthoquinone skeleton. Interestingly, the 5,7-dioxygenated chromone derivatives 2-13 possessed different alkyl acid or alkyl ester side chain lengths, and those with side chain lengths of seven carbon atoms were discovered from nature for the first time. The metabolites were evaluated for their cytotoxicity against four cancer cell lines; compounds 1 and 15 were found to be active, with IC50 values ranging from 4.9 to 9.1 µM.


Assuntos
Penicillium/química , Policetídeos/química , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oceanos e Mares , Microbiologia da Água
17.
Clin Lab ; 66(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32658428

RESUMO

BACKGROUND: There is currently no clinical biomarker for the early diagnosis of giant cell tumor of bone. Long-chain non-coding RNAs (lncRNAs) have a wide range of important gene regulatory functions and play an important role in the occurrence and development of various malignant tumors. This study mainly screened the differential expression of lncRNAs in patients with giant cell tumor of bone by gene chip technology, verified the biological function. We tried to establish a reference basis for early diagnosis of tumor and prediction of tumor recurrence. METHODS: From September 2018 to September 2019, we randomly selected 20 cases of primary giant cell tumor of bone and 20 cases of recurrent giant cell tumor of bone, and 20 cases of bone trauma tissue. First, the differential expression of incRNAs in the bone tissue of the patients was evaluated via utilizing gene chip technology. The gene chip was Human LncRNA Array v 3.0 (8 x 60 K) was completed by Shanghai Kangcheng Biotechnology Co., Ltd. The DAVID online analysis platform was used to analyze the differentially expressed genes by GO and KEGG pathways. The target lncRNAs were screened; real-time quantitative PCR (qRT-PCR) was used to verify the relative expression levels of target lncRNAs in bone tissue and serum of three groups of patients. RESULTS: Using gene chip technology screening, fold-change (FC) value > 2.0 was used as standard. A total of 1,254 differentially expressed lncRNAs were detected of which 896 were up-regulated and 358 were down-regulated. Additionally, a total of 106 differentially expressed lncRNAs were detected with FC values > 10.0. Among these, 72 lncRNAs were upregulated and 34 lncRNAs were downregulated. We then selected two lncRNAs with up-regulation and down-regulation with the largest fold difference. qRT-PCR analytical results showcased that the expression of AK124776 in bone tissue and serum of patients in the recurrent group was significantly higher than that of the initial group and the normal group. Conversely, for RP11-160A10.2, the expression level in the recurrent group was significantly lower than that in the initial group, and the normal group was the highest; the difference was statistically significant (p < 0.05). Finally, we used the expression levels of AK124776 and RP11-160A10.2 in each group as the diagnostic indicators. According to the receiver operating curve (ROC), the accuracy of AK¬124776 and RP11-160A10.2 in the diagnosis of giant cell tumor of bone (area under the curve), the AUC was 0.865 and 0.877, respectively; the accuracy of predicting recurrence of giant cell tumor of bone was 0.832 and 0.841, respectively. CONCLUSIONS: The early detection of differential expression of lncRNAs in the serum of patients with giant cell tumor of bone is important for the diagnosis of disease and prediction of recurrence. The establishment of stable expression of lncRNAs and simple and easy detection methods are of great value for guiding clinical application.


Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , RNA Longo não Codificante , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Osso e Ossos , China , Perfilação da Expressão Gênica , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/genética , Humanos , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/genética
18.
Mar Drugs ; 18(3)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188160

RESUMO

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (28), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 M. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 M, respectively, being more active than the positive control acarbose (1.33 mM).


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Penicillium , Terpenos/farmacologia , Animais , Antineoplásicos/química , Antioxidantes/química , Linhagem Celular Tumoral/efeitos dos fármacos , Dicroísmo Circular , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Oceanos e Mares , Terpenos/química , alfa-Glucosidases/química
19.
Bioorg Chem ; 91: 103129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31374522

RESUMO

Cyclopianes, featuring a highly rigid 6/5/5/5-fused tetracyclic framework, are structurally unique and biologically significant and belong to a rarely reported diterpenoid family. Chemical investigation of an EtOAc extract of a deep-sea-derived Penicillium sp. led to the isolation of three new cyclopiane diterpenes, namely, conidiogenols C-D (1-2) and conidiogenone L (3). The structures were determined by extensive analyses of the spectroscopic data in association with ECD calculations and chemical conversion for configurational assignments. Compound 1 represents the second example of cyclopianes bearing a hydroxyl group at C-13. Compound 2, the third example of conidiogenols, possesses a distinct α-oriented 1-hydroxy group relative to other analogues. The bioassay study demonstrated that compounds 2 and 4-6 exhibited moderate inhibitory effects against five esophageal cancer cell lines with IC50 values ranging from 25 to 55 µM. The cytotoxicities of all compounds toward esophageal cancer cell lines were evaluated for the first time.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Diterpenos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Penicillium/química , Relação Estrutura-Atividade
20.
Mar Drugs ; 17(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163670

RESUMO

Three new butenolide derivatives, namely aspernolides N-P (1-3), together with six known analogues (4-9), were isolated from the ethyl acetate (EtOAc) extract of the deep sea-derived fungus Aspergillus terreus YPGA10. The structures of compounds 1-3 were determined on the basis of comprehensive analyses of the nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data, and the absolute configurations of 1 and 2 were determined by comparisons of experimental electronic circular dichroism (ECD) with calculated ECD spectra. Compound 1 represents the rare example of Aspergillus-derived butenolide derivatives featured by a monosubstituted benzene ring. Compounds 6-9 exhibited remarkable inhibitory effects against α-glucosidase with IC50 values of 3.87, 1.37, 6.98, and 8.06 µM, respectively, being much more active than the positive control acarbose (190.2 µM).


Assuntos
4-Butirolactona/análogos & derivados , Organismos Aquáticos/química , Aspergillus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Acetatos/química , Dicroísmo Circular , Ativação Enzimática/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
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