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1.
Anal Bioanal Chem ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602542

RESUMO

Natural attapulgite (ATP) is a promising substitute for existing artificial nanozymes due to its intrinsic enzymatic activity. However, the active center of ATP's inherent enzymatic activity has not yet been revealed, which limits its further design and activity optimization. Studying the active center of mineral materials can be extremely challenging due to their complexity. Here, we demonstrated that Fe is the primary element in ATP responsible for peroxidase (POD)-like activity through theoretical speculation and experimental verification. More importantly, we found that the ratio of Fe2+/Fe3+ is responsible for the district POD-like activity of ATP from different regions with the same Fe content. Additionally, three facile strategies, including grinding, heat treatment, and acid treatment, were demonstrated to increase the relative Fe content and thus optimize the POD-like activity of ATP. Finally, ATP was used to detect the concentration of H2O2, enabling the detection of low concentrations (0.11-1.76 mM) of H2O2. This study serves as a novel reference for the future design and performance optimization of nanozymes that are based on ATP and clay minerals.

2.
ACS Omega ; 9(16): 17760-17783, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38680370

RESUMO

Natural nano-minerals (NNMs) are minerals that are derived from nature with a size of less than 100 nm in at least one dimension in size. NNMs have a number of excellent properties due to their unique nanostructure and have been applied in various fields in recent years. They are rising stars in various disciplines, such as materials, biomedicine, and chemistry, taking advantage of their huge surface area, multiple active sites, excellent adsorption capacity, large quantity, low cost, and nontoxicity, etc. To provide a more comprehensive overview of NNMs and the biomedical applications of NNMs-based nanocomposites, this review classifies NNMs into three types by dimension, lists the structure and properties of typical NNMs, and illustrates their biomedical applications. Furthermore, a novel concept of natural nanomineral medical materials (NNMMs) is proposed, focusing on the medical value of NNMs. In addition, this review attempts to address the current challenges and delineate future directions for the advancement of NNMs. With the deepening of biomedical applications, it is believed that NNMMMs will inevitably play an important role in the field of human health and contribute to its promotion.

3.
Heliyon ; 9(12): e22970, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144278

RESUMO

Background: Cardiac aging progressively decreases physiological function and drives chronic/degenerative aging-related heart diseases. Therefore, it is crucial to postpone the aging process of heart and create products that combat aging. Aims & methods: The objective of this study is to examine the effects of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata, on anti-aging and its underlying mechanism. To assess the senescent biomarkers, cardiac function, cardiac weight/body weight ratio, cardiac transcriptomic changes, and cardiac histopathological features, heart tissue samples were obtained from young mice (12 weeks), aged mice (19 months) treated with parishin, and aged mice that were not treated. Results: Parishin treatment improved cardiac function, ameliorated aging-induced cardiac injury, hypertrophy, and fibrosis, decreased cardiac senescence biomarkers p16Ink4a, p21Cip1, and IL-6, and increased the "longevity factor" SIRT1 expression in heart tissue. Furthermore, the transcriptomic analysis demonstrated that parishin treatment alleviated the cardiac aging-related Gja1 downregulation and Cyp2e1, Ccna2, Cdca3, and Fgf12 upregulation in the heart tissues. The correlation analysis suggested a strong connection between the anti-aging effect of parishin and its regulation of gut microbiota and metabolism in the aged intestine. Conclusion: The present study demonstrates the protective role and underlying mechanism of parishin against cardiac aging in naturally aged mice.

4.
J Cell Mol Med ; 27(10): 1398-1409, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37032511

RESUMO

Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.


Assuntos
Envelhecimento , Glucosídeos , Proteínas Klotho , Animais , Camundongos , Envelhecimento/sangue , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Células Endoteliais , Proteínas Klotho/sangue , Proteínas Klotho/metabolismo , Ativação Transcricional/efeitos dos fármacos , Regulação para Cima , Humanos , Glucosídeos/farmacologia
5.
Rejuvenation Res ; 26(3): 116-124, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36943260

RESUMO

Intestinal epithelial cellular senescence contributes to the physiological decline of intestine and induces age-associated intestinal diseases. Therefore, the intestine is a vital target to delay intestinal epithelial cellular senescence and extend healthy lifespan. Alginate oligosaccharides (AOSs) have a wide range of biological and pharmacological activities. However, there are no related reports of AOSs on intestinal epithelial cellular senescence. Our study aimed to investigate the effect of AOSs on hydrogen peroxide (H2O2)-induced senescent intestinal epithelial cells (IEC-6) and its antiaging mechanism. A senescent model was successfully constructed by H2O2 (200 µmol/L) treatment on IEC-6 for 4 hours. Different concentrations of AOSs (10, 50, 100 µg/mL) were used to intervene in H2O2-induced senescent IEC-6. The number of ß-galactosidase staining-positive cells was significantly reduced by AOS intervention. The expression levels of p21 and p16, known as the senescent biomarkers, were also decreased. In addition, AOSs alleviated oxidative stress by reducing reactive oxygen species and improving antioxidative ability. To understand how AOSs rejuvenate H2O2-induced senescent IEC-6, we detected the expression level of genes in autophagy process. The results indicated that AOSs restored the expression level of Beclin 1, Atg7, and LC3 to enhance autophagy process by activating activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin in H2O2-induced senescent IEC-6. Compound C, an AMPK inhibitor, abolished the effect of AOSs on activating autophagy and rejuvenating senescent IEC-6. Altogether, our study suggests that AOS is a promising drug for delaying intestinal epithelial cellular senescence.


Assuntos
Proteínas Quinases Ativadas por AMP , Peróxido de Hidrogênio , Peróxido de Hidrogênio/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Senescência Celular , Autofagia , Intestinos , Células Epiteliais/metabolismo
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(5): 600-608, 2022 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-35570635

RESUMO

Objective: To investigate the effect of the sequence of intermediate instrumentation with long screws and distraction-reduction on mild to moderate thoracolumbar fractures treated by posterior open and short-segmental fixation. Methods: The clinical data of 68 patients with mild to moderate thoracolumbar burst fractures who met the selection criteria between January 2016 and June 2019 were retrospectively analyzed. The patients were divided into group ISDRF (intermediate screws then distraction-reduction fixation, 32 cases) and group DRISF (distraction-reduction then intermediate screws fixation, 36 cases) according to the different operation methods. There was no significant difference between the two groups in age, gender, body mass index, fracture segment, cause of injury, and preoperative load-sharing classification score, thoracolumbar injury classification and severity score, vertebral canal occupational rate, back pain visual analogue scale (VAS) score, anterior height of fractured vertebra, and Cobb angle ( P>0.05). The operation time, intraoperative blood loss, complications, and fracture healing time were recorded and compared between the two groups. The vertebral canal occupational rate, anterior height of fractured vertebra, kyphosis Cobb angle, and back pain VAS score before and after operation were used to evaluate the effectiveness. Results: There was no significant difference in intraoperative blood loss and operation time between the two groups ( P>0.05). No vascular or spinal nerve injury and deep infections or skin infections occurred in both groups. At 1 week after operation, the vertebral canal occupational rate in the two groups was significantly improved when compared with that before operation ( P<0.05), no significant difference was found in the difference of vertebral canal occupational rate before and after operation and improvement between the two groups ( P>0.05). The patients in both groups were followed up 18-24 months, with an average of 22.3 months. All vertebral fractures reached bone union at 6 months postoperatively. At last follow-up, there was no internal fixation failures such as broken screws, broken rods or loose screws, but there were 2 cases of mild back pain in the ISDRF group. The intra-group comparison showed that the back pain VAS score, the anterior height of fractured vertebra, and the Cobb angle of the two groups were significantly improved at each time point postoperatively ( P<0.05); the VAS scores at 12 months postoperatively and last follow-up were also improved when compared with that at 1 week postoperatively ( P<0.05). At last follow-up, the anterior height of fractured vertebra in the ISDRF group was significantly lost when compared with that at 1 week and 12 months postoperatively ( P<0.05), the Cobb angle had a significant loss when compared with that at 1 week postoperatively ( P<0.05); the anterior height of fractured vertebra and Cobb angle in DRISF group were not significantly lost when compared with that at 1 week and 12 months postoperatively ( P>0.05). The comparison between groups showed that there was no significant difference in the remission rate of VAS score between the two groups at 1 week postoperatively ( P>0.05), the recovery value of the anterior height of fractured vertebra in ISDRF group was significantly higher than that in DRISF group ( P<0.05), the loss rate at last follow-up was also significantly higher ( P<0.05); the correction rate of Cobb angle in ISDRF group was significantly higher than that in DRISF group at 1 week postoperatively ( P<0.05), but there was no significant difference in the loss rate of Cobb angle between the two groups at last follow-up ( P>0.05). Conclusion: In the treatment of mild to moderate thoracolumbar burst fractures with posterior short-segment fixation, the instrumentation of long screws in the injured vertebrae does not affect the reduction of the fracture fragments in the spinal canal. DRISF can better maintain the restored anterior height of the fractured vertebra and reduce the loss of kyphosis Cobb angle during the follow-up, indicating a better long-term effectiveness.


Assuntos
Fraturas Ósseas , Fraturas Cominutivas , Cifose , Parafusos Pediculares , Fraturas da Coluna Vertebral , Dor nas Costas , Perda Sanguínea Cirúrgica , Fixação Interna de Fraturas/métodos , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do Tratamento
7.
Front Microbiol ; 13: 877099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547139

RESUMO

The physiological and pathological processes that accompany aging can seriously affect the quality of life of the elderly population. Therefore, delaying aging and developing antiaging products have become popular areas of inquiry. Gut microbiota plays an important role in age-related phenotypes. The present study aimed to investigate the antiaging effects and underlying mechanism of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata. Samples from adult (12 weeks), low-dose (10 mg/kg/d) or high-dose (20 mg/kg/d) parishin-treated and untreated aged (19 months) mice were collected to determine blood indicators, gut microbiota and metabolome, and cardiopulmonary histopathological features. The results showed that parishin treatment ameliorates aging-induced cardiopulmonary fibrosis and increase in serum p16 Ink4a , GDF15, and IL-6 levels. Furthermore, parishin treatment alleviated dysbiosis in gut microbiota, including altered microbial diversity and the aberrant abundance of opportunistic pathogenic bacteria such as Turicibacter and Erysipelatoclostridium. Gene function prediction and gut metabolome analysis results indicated that the parishin treatment-altered gut microbiota played important roles in sugar, lipid, amino acid and nucleic acid metabolism, and improved gut metabolic disorders in aged mice. In conclusion, the present study provides an experimental basis of potential applications of parishin against aging.

8.
J Am Chem Soc ; 143(44): 18643-18651, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34726407

RESUMO

Although great progress has been made in artificial enzyme engineering, their catalytic performance is far from satisfactory as alternatives of natural enzymes. Here, we report a novel and efficient strategy to access high-performance nanozymes via direct atomization of platinum nanoparticles (Pt NPs) into single atoms by reversing the thermal sintering process. Atomization of Pt NPs into single atoms makes metal catalytic sites fully exposed and results in engineerable structural and electronic properties, thereby leading to dramatically enhanced enzymatic performance. As expected, the as-prepared thermally stable Pt single-atom nanozyme (PtTS-SAzyme) exhibited remarkable peroxidase-like catalytic activity and kinetics, far exceeding the Pt nanoparticle nanozyme. The following density functional theory calculations revealed that the engineered P and S atoms not only promote the atomization process from Pt NPs into PtTS-SAzyme but also endow single-atom Pt catalytic sites with a unique electronic structure owing to the electron donation of P atoms, as well as the electron acceptance of N and S atoms, which simultaneously contribute to the substantial enhancement of the enzyme-like catalytic performance of PtTS-SAzyme. This work demonstrates that thermal atomization of the metal nanoparticle-based nanozymes into single-atom nanozymes is an effective strategy for engineering high-performance nanozymes, which opens up a new way to rationally design and optimize artificial enzymes to mimic natural enzymes.


Assuntos
Engenharia Química/métodos , Enzimas/síntese química , Enzimas/metabolismo , Nanopartículas Metálicas/química , Platina/química , Catálise
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(8): 1014-1020, 2021 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-34387431

RESUMO

OBJECTIVE: To explore the clinical characteristics and surgical treatment strategies of delayed spinal cord injury (SCI) caused by atypical compression of old thoracolumbar fracture. METHODS: Between January 2011 and June 2018, 32 patients with delayed SCI caused by atypical compression of old thoracolumbar fracture who met the inclusion criteria were admitted and divided into group A (20 cases, underwent anterior subtotal vertebral body resection+titanium mesh reconstruction+screw rod internal fixation) and group B (12 cases, underwent posterior 270° ring decompression of vertebral canal+titanium mesh reconstruction+screw rod internal fixation) according to the different operation approaches. There was no significant difference between the two groups in age, gender, cause of injury, fracture segment, disease duration, preoperative American Spinal Injury Association (ASIA) classification, and preoperative back pain visual analogue scale (VAS) score, lumbar Japanese Orthopaedic Association (JOA) score, kyphosis angle, and vertebral canal occupational ratio ( P>0.05). The incision length, operation time, intraoperative blood loss, complications, and bone fusion time of reconstructed vertebrae were recorded and compared between the two groups; the kyphosis angle, back pain VAS score, and lumbar JOA score were used to evaluate the effectiveness. RESULTS: Except that the incision length in group A was significantly shorter than that in group B ( t=-4.865, P=0.000), there was no significant difference in intraoperative blood loss and operation time between the two groups ( P>0.05). There was no deaths or postoperative paraplegia cases in the two groups, and no deep infection or skin infection occurred. There was 1 case of cerebrospinal fluid leakage, 1 case of inferior vena cava injury, and 1 case of chyle leakage in group A. No serious complications occurred in group B. There was no significant difference in the incidence of complications between the two groups ( P=0.274). All 32 patients were followed up 12-61 months, with an average of 20.8 months. The follow-up time for groups A and B were (19.35±5.30) months and (23.25±12.20) months respectively, and the difference was not significant ( t=-1.255, P=0.219). The reconstructed vertebrae in all cases obtained bony fusion postoperatively. The fusion time of groups A and B were (8.85±2.27) months and (8.50±2.50) months respectively, and the difference was not significant ( t=0.406, P=0.688). The kyphosis angle, back pain VAS score, and lumbar JOA score of the two groups at each time point after operation and last follow-up were significantly improved when compared with preoperatively ( P<0.05); the lumbar JOA score was further improved with time postoperatively ( P<0.05), while the kyphosis angle and the VAS score of back pain remained similarly ( P>0.05). Comparison of kyphosis angle, back pain VAS score, and lumbar JOA score between the two groups at various time points postoperatively showed no significant difference ( P>0.05). At last follow-up, the JOA score improvement rate in groups A and B were 83.87%±0.20% and 84.50%±0.14%, respectively, and the difference was not significant ( t=-0.109, P=0.914); the surgical treatment effects of the two groups were judged to be significant. CONCLUSION: In the later stage of treatment of old thoracolumbar fractures, even mild kyphosis and spinal canal occupying may induce delayed SCI. Surgical correction and decompression can significantly promote the recovery of damaged spinal cord function. Compared with anterior approach surgery, posterior approach surgery has the advantages of less trauma, convenient operation, and fewer complications, so it can be preferred.


Assuntos
Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Fixação Interna de Fraturas , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do Tratamento
10.
Front Oncol ; 11: 629597, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026609

RESUMO

BACKGROUND: Angiosarcoma is a rare, highly malignant tumor prone to recurrence and metastasis. Angiosarcoma is insidious in the initial stage, and its clinical manifestation lacks specificity. The diagnosis is based on histopathology and immunohistochemistry findings. CASE PRESENTATION: A 73-year-old man was hospitalized following complaints of persistent cough 6 months and hemoptysis for 2 months. Anti-infective treatment was ineffective. A CT-guided percutaneous core needle biopsy of pulmonary lesions revealed organized pneumonia, and the removed skin of purpuric rash area on the left calf revealed vasculitis. Chest CT was used during the patient follow-up. Hormonal therapy combined with immunoglobulins did not lead to improvement, and there was rapid progression of the lung lesions. Subsequently, the patient underwent a surgery, the diseased tissue was separated and removed completely beside the left submandibular gland under local anaesthesia. The immunohistochemical staining indicated CD31 (+) and CD34 (+) confirming a diagnosis of metastatic angiosarcoma. The expression of PD-L1 was 70%, therefore, anlotinib and pembrolizumab treatments were initiated. The patient eventually died. CONCLUSION: Angiosarcoma is a malignant tumor in the clinic that lacks typical and specific signs and symptoms. The diagnosis depends on immunohistochemistry, which requires repeated biopsies of multiple sites in highly suspected cases.

11.
ACS Synth Biol ; 9(5): 1181-1189, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32268063

RESUMO

Genome-scale gene knockout is an important approach to the study of global genetic interactions. SCRaMbLEing of synthetic yeast chromosomes provides an efficient way to generate random deletion mutants. Here, we demonstrate the use of SCRaMbLE to explore synthetic lethal interactions. First, all essential genes of yeast chromosome III (chrIII) were clustered in a centromeric plasmid. We found that three types of reorganized clustered chrIII essential genes had similar transcriptional levels. Further, SCRaMbLEing of synthetic chromosome III (synIII) with supplementary clustered essential genes enables deletion of large chromosomal regions. Investigation of 141 SCRaMbLEd strains revealed varied deletion frequencies of synIII chromosomal regions. Among the no deletion detected regions, a hidden synthetic lethal interaction was revealed in the region of synIII 82-88 kb. This study shows that SCRaMbLE with clustered essential genes enhances streamlining of synthetic yeast chromosome and provides a novel strategy to uncover complex genetic interactions.


Assuntos
Cromossomos Fúngicos , Engenharia Genética/métodos , Saccharomyces cerevisiae/genética , Genes Essenciais , Plasmídeos/genética , Plasmídeos/metabolismo , Deleção de Sequência
12.
Artigo em Inglês | MEDLINE | ID: mdl-32117909

RESUMO

Nanozymes are nanomaterials with intrinsic enzyme-like properties. They can specifically catalyze substrates of natural enzymes under physiological condition with similar catalytic mechanism and kinetics. Compared to natural enzymes, nanozymes exhibit the unique advantages including high catalytic activity, low cost, high stability, easy mass production, and tunable activity. In addition, as a new type of artificial enzymes, nanozymes not only have the enzyme-like catalytic activity, but also exhibit the unique physicochemical properties of nanomaterials, such as photothermal properties, superparamagnetism, and fluorescence, etc. By combining the unique physicochemical properties and enzyme-like catalytic activities, nanozymes have been widely developed for in vitro detection and in vivo disease monitoring and treatment. Here we mainly summarized the applications of nanozymes for disease imaging and detection to explore their potential application in disease diagnosis and precision medicine.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31824932

RESUMO

MicroRNAs (miRNA) have been identified as oncogenic drivers and tumor suppressors in every major cancer type. In this work, we design an artificial intelligent signal amplification (AISA) system including double-stranded SQ (S, signal strand; Q, quencher strand) and FP (F, fuel strand; P, protect strand) according to thermodynamics principle for sensitive detection of miRNA in vitro and in vivo. In this AISA system for miRNA detection, strand S carries a quenched imaging marker inside the SQ. Target miRNA is constantly replaced by a reaction intermediate and circulatively participates in the reaction, similar to enzyme. Therefore, abundant fluorescent substances from S and SP are dissociated from excessive SQ for in vitro and in vivo visualization. The versatility and feasibility for disease diagnosis using this system were demonstrated by constructing two types of AISA system to detect Hsa-miR-484 and Hsa-miR-100, respectively. The minimum target concentration detected by the system in vitro (10 min after mixing) was 1/10th that of the control group. The precancerous lesions of liver cancer were diagnosed, and the detection accuracy were larger than 94% both in terms of location and concentration. The ability to establish this design framework for AISA system with high specificity provides a new way to monitor tumor progression and to assess therapeutic responses.

14.
Sheng Wu Gong Cheng Xue Bao ; 35(12): 2215-2226, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31880131

RESUMO

DNA assembly is the core technology of synthetic biology. With the development of synthetic biology, researchers have developed different DNA assembly technologies that rely on DNA polymerase or DNA ligase, and also have developed some non-enzyme-dependent DNA assembly techniques to facilitate the automation of DNA assembly. The assembly of large fragments of DNA from a few hundred kb to Mb is mostly dependent on microbial recombination. In this paper, the three types of DNA assembly technologies, including enzyme-dependent, non-enzymatic and in vivo homologous recombination, are reviewed.


Assuntos
Biologia Sintética , DNA
15.
World J Clin Cases ; 7(21): 3595-3602, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31750343

RESUMO

BACKGROUND: Necrotizing fasciitis is a severe bacterial skin infection that spreads quickly and is characterized by extensive necrosis of the deep and superficial fascia resulting in the devascularization and necrosis of associated tissues. Because of high morbidity and mortality, accurate diagnosis and early treatment with adequate antibiotics and surgical intervention are vital. And timely identification and treatment of complications are necessary to improve survival of patient. CASE SUMMARY: We report a case of necrotizing fasciitis caused by Staphylococcus aureus in a patient using high doses of glucocorticoid and suffering from secondary diabetes mellitus. He was admitted to our hospital due to redness and oedema of the lower limbs. After admission, necrotizing fasciitis caused by Staphylococcus aureus was considered, and he was discharged after B-ultrasound drainage and multiple surgical operations. In the process of treatment, multiple organ functions were damaged, but with the help of multi-disciplinary treatment, the patient got better finally. CONCLUSION: The key to successful management of necrotizing fasciitis is an early and accurate diagnosis. The method of using vacuum sealing drainage in postoperative patients can keep the wound dry and clean, reduce infection rate, and promote wound healing. Interdisciplinary collaboration is a vital prerequisite for successful treatment.

16.
J Nat Prod ; 82(2): 183-193, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30730729

RESUMO

Two ingenane- (1 and 2), two ent-atisane- (3 and 4), two ent-kaurane- (5 and 6), two ent-abietane- (7 and 8), and one ent-isopimarane-type (9) diterpenoid and 12 known analogues have been isolated from the methanolic extract of the stems of Euphorbia royleana. Their structures, including absolute configurations, were determined by extensive spectroscopic methods and ECD data analysis. The nitric oxide inhibitory activities of those diterpenoids were examined biologically in lipopolysaccharide-stimulated BV-2 cells, with compounds 1, 2, 5-7, 10, and 12 having IC50 values lower than 40 µM. Molecular docking was used to investigated the possible mechanism of compounds 1, 2, 5-7, 10, and 12.


Assuntos
Diterpenos/isolamento & purificação , Euphorbia/química , Diterpenos/química , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/análise , Caules de Planta/química
17.
Nanomedicine ; 14(7): 2259-2270, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30056091

RESUMO

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P < 0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P < 0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.


Assuntos
Antígenos CD/metabolismo , Apoferritinas/metabolismo , Endoscopia/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Nanopartículas/administração & dosagem , Receptores da Transferrina/metabolismo , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Animais , Apoferritinas/administração & dosagem , Apoferritinas/química , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Pessoa de Meia-Idade , Nanopartículas/química , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Nat Commun ; 9(1): 1440, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29650959

RESUMO

Nanomaterials with intrinsic enzyme-like activities (nanozymes), have been widely used as artificial enzymes in biomedicine. However, how to control their in vivo performance in a target cell is still challenging. Here we report a strategy to coordinate nanozymes to target tumor cells and selectively perform their activity to destruct tumors. We develop a nanozyme using nitrogen-doped porous carbon nanospheres which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase) responsible for reactive oxygen species regulation. We then introduce ferritin to guide nitrogen-doped porous carbon nanospheres into lysosomes and boost reactive oxygen species generation in a tumor-specific manner, resulting in significant tumor regression in human tumor xenograft mice models. Together, our study provides evidence that nitrogen-doped porous carbon nanospheres are powerful nanozymes capable of regulating intracellular reactive oxygen species, and ferritinylation is a promising strategy to render nanozymes to target tumor cells for in vivo tumor catalytic therapy.


Assuntos
Terapia Enzimática , Enzimas/metabolismo , Nanosferas/metabolismo , Nanosferas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Animais , Biocatálise , Carbono/química , Enzimas/química , Feminino , Ferritinas/metabolismo , Células HT29 , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanosferas/química , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Nitrogênio/química , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Bioorg Chem ; 76: 53-60, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29128707

RESUMO

A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of five new spiro diterpenoids (1 -5) from the aerial parts of Scutellaria formosana. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The nitric oxide (NO) inhibitory effects were evaluated and all of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.


Assuntos
Diterpenos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Scutellaria/química , Animais , Domínio Catalítico , Linhagem Celular , Diterpenos/química , Diterpenos/isolamento & purificação , Camundongos , Microglia/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/química , Componentes Aéreos da Planta/química
20.
Phytochemistry ; 144: 141-150, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28934646

RESUMO

A phytochemical study on Scutellaria formosana afforded five previously undescribed spiro-diterpenoids, scutellapenes A-E. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Scutellapenes B-E possess a spiro-diterpenoid skeleton. All of the compounds showed inhibitory effects on LPS-induced nitric oxide (NO) production in murine microglial BV-2 cells. The further molecular docking studies revealed that these bioactive compounds had strong interactions with the iNOS protein.


Assuntos
Diterpenos Clerodânicos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/antagonistas & inibidores , Scutellaria/química , Animais , Células Cultivadas , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Relação Dose-Resposta a Droga , Camundongos , Conformação Molecular , Simulação de Acoplamento Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/química , Relação Estrutura-Atividade
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