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1.
Nat Commun ; 13(1): 79, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013205

RESUMO

Object recognition is among the basic survival skills of human beings and other animals. To date, artificial intelligence (AI) assisted high-performance object recognition is primarily visual-based, empowered by the rapid development of sensing and computational capabilities. Here, we report a tactile-olfactory sensing array, which was inspired by the natural sense-fusion system of star-nose mole, and can permit real-time acquisition of the local topography, stiffness, and odor of a variety of objects without visual input. The tactile-olfactory information is processed by a bioinspired olfactory-tactile associated machine-learning algorithm, essentially mimicking the biological fusion procedures in the neural system of the star-nose mole. Aiming to achieve human identification during rescue missions in challenging environments such as dark or buried scenarios, our tactile-olfactory intelligent sensing system could classify 11 typical objects with an accuracy of 96.9% in a simulated rescue scenario at a fire department test site. The tactile-olfactory bionic sensing system required no visual input and showed superior tolerance to environmental interference, highlighting its great potential for robust object recognition in difficult environments where other methods fall short.

2.
Mitochondrial DNA B Resour ; 7(1): 54-55, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34926822

RESUMO

Citrus australasica (F. Muell.) Swingle belongs to the family Rutaceae. Citrus australasica is native to eastern Australia and southeastern New Guinea, and is mainly concentrated in a small region of northern New South Wales and tropical rainforest areas in southern Queensland. The complete plastome length of C. australasica is 160,335 bp, with the typical structure and gene content of angiosperm plastids, including a 26,592 bp repeat B (IRB) region, 26,952 bp IRA, 87,678 bp large single copy (LSC) region and 18,756 bp small single copy (SSC) region. The plastid contains 135 genes, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The total G/C content of the C. australasica plastome is 38.4%. The complete plastome sequence of C. australasica will provide useful resources for conservation genetics research of this species and phylogenetic research of Rutaceae.

3.
Redox Biol ; 49: 102221, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34952462

RESUMO

Redox regulation of specific cysteines via oxidoreductases of the thioredoxin family is increasingly being recognized as an important signaling pathway. Here, we demonstrate that the cytosolic isoform of the vertebrate-specific oxidoreductase Glutaredoxin 2 (Grx2c) regulates the redox state of the transcription factor SP-1 and thereby its binding affinity to both the promoter and an enhancer region of the CSPG4 gene encoding chondroitin sulfate proteoglycan nerve/glial antigen 2 (NG2). This leads to an increased number of NG2 glia during in vitro oligodendroglial differentiation and promotes migration of these wound healing cells. On the other hand, we found that the same mechanism also leads to increased invasion of glioma tumor cells. Using in vitro (human cell lines), ex vivo (mouse primary cells), and in vivo models (zebrafish), as well as glioblastoma patient tissue samples we provide experimental data highlighting the Yin and Yang of redox signaling in the central nervous system and the enzymatic Taoism of Grx2c.

5.
EBioMedicine ; 74: 103649, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34814051

RESUMO

BACKGROUND: Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. METHODS: A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. FINDINGS: Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. INTERPRETATION: Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. FUNDING: This work was supported by National Science and Technology Major Project of China (2018ZX10102001).

6.
Adv Sci (Weinh) ; : e2102596, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738735

RESUMO

Progress toward intelligent human-robotic interactions requires monitoring sensors that are mechanically flexible, facile to implement, and able to harness recognition capability under harsh environments. Conventional sensing methods have been divided for human-side collection or robot-side feedback and are not designed with these criteria in mind. However, the iontronic polymer is an example of a general method that operates properly on both human skin (commonly known as skin electronics or iontronics) and the machine/robotic surface. Here, a unique iontronic composite (silk protein/glycerol/Ca(II) ion) and supportive molecular mechanism are developed to simultaneously achieve high conductivity (around 6 kΩ at 50 kHz), self-healing (within minutes), strong stretchability (around 1000%), high strain sensitivity and transparency, and universal adhesiveness across a broad working temperature range (-40-120 °C). Those merits facilitate the development of iontronic sensing and the implementation of damage-resilient robotic manipulation. Combined with a machine learning algorithm and specified data collection methods, the system is able to classify 1024 types of human and robot hand gestures under challenging scenarios and to offer excellent object recognition with an accuracy of 99.7%.

7.
Adv Mater ; : e2106606, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618380

RESUMO

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Surgery followed by chemotherapy and radiotherapy remains the standard treatment strategy for GBM patients. However, challenges still exist when surgery is difficult or impossible to remove the tumor completely. Herein, the design, fabrication and application of a heterogenous silk fibroin microneedle (SMN) patch is reported for circumventing the blood-brain barrier and releasing multiple drugs directly to the tumor site for drug combination treatment. The biocompatible and biodegradable SMN patch can dissolve slowly over time, allowing the sustained release of multiple drugs at different doses. Furthermore, it can be triggered remotely to induce rapid drug delivery at a designated stage after implantation. In the GBM mouse models, two clinically relevant chemotherapeutic agents (thrombin and temozolomide) and targeted drug (bevacizumab) are loaded into the SMN patch with individually controlled release profiles. The drugs are spatiotemporally and sequentially delivered for hemostasis, anti-angiogenesis, and apoptosis of tumor cells. Device application is non-toxic and results in decreased tumor volume and increased survival rate in mice. The SMN patch with on-demand multidrug delivery has potential applications for the combined administration of therapeutic drugs for the clinical treatment of brain tumors when other methods are insufficient.

8.
Exp Cell Res ; 408(2): 112863, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626587

RESUMO

Forkhead box M1 (FOXM1) has been reported to play a protective role against acute kidney injury by driving tubular regeneration. This study aims to probe the function of FOXM1 in diabetic nephropathy (DN) and the molecules involved. FOXM1 was poorly expressed in DN-diseased kidney tissues. A murine model of DN was established, and podocytes cells (MPC5) were treated with high-glucose (HG) for in vitro studies. FOXM1 overexpression improved kidney function and reduced pathological changes in mice, and it increased the expression of the podocyte marker Nephrin in kidney tissues. In vitro, FOXM1 increased viability and reduced pyroptosis of the HG-treated MPC5 cells, and it elevated the expression of the podocyte marker Nephrin whereas reduced the expression of pyroptosis-related NLRP3 inflammasome and cleaved caspase 1. FOXM1 bound to the promoter of sirtuin 4 (SIRT4) to induce transcriptional activation. Downregulation of SIRT4 blocked the protective roles of FOXM1 both in vivo and in vitro. Phosphorylation of nuclear factor-kappa B (NF-κB) in HG-treated cells was suppressed by FOXM1 but restored after SIRT4 inhibition. In conclusion, this study suggested that FOXM1 transcriptionally activates SIRT4 and inhibits NF-κB signaling and the NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in DN.

9.
Clin Transl Immunology ; 10(10): e1342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646556

RESUMO

Objectives: Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery. Methods: Stool samples were collected from 10 children with IgAV (6-14 years old) before and after a multi-drug therapy, along with 9 age-matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome. Results: The analyses revealed that compared with healthy controls, treatment-naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV-depleted species and 7 IgAV-elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment-responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram-positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV-depleted bacterial genes, 82 were mainly contributed by gram-positive bacteria and 12 by gram-negative bacteria. Conclusions: Gram-positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease.

10.
Small ; : e2103262, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34672425

RESUMO

The manufacturing of 3D and conformal metamaterials remains a major challenge. The projection micro-stereolithography 3D printing technology combined with the liquid metal filling method is employed here to fabricate the metamaterials, which are characterized with embedded features that can effectively protect the metal resonance layer from external influence, and integrated molding of macro-micro structures and function-structure. To demonstrate the robustness and flexibility of the proposed method, three types of metamaterials are fabricated: 3D orthogonal split-ring resonator metamaterial, bionic compound eye conformal metamaterial, and a five-layer broadband conformal metamaterial in the form of hemispherical moth-eye, which are costly, tedious, and time consuming in conventional fabrication methods. And the layout of the filling channel is optimized and the polydimethylsiloxane coating post-treatment process is applied to smooth the surface roughness caused by the staircase effect of 3D printing to improve the transmission performance of metamaterial devices. The transmission properties are measured using terahertz time-domain spectroscopy system and the experimental results show that the method proposed in this paper makes metamaterial manufacture no longer limited to complex structures, which effectively expands the application range of metamaterials.

11.
Cell Death Dis ; 12(10): 885, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584066

RESUMO

Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and MGMT promoter methylation status. Finally, the role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.

12.
Cancer Nurs ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34560707

RESUMO

BACKGROUND: Fear of cancer recurrence (FCR) is one of the most common and aversive psychological phenomena among cancer survivors. Understanding the independent and potentially modifiable risk factors that contribute toward FCR seen in cancer survivors would inform future interventional trials aimed at reducing this risk. OBJECTIVE: The aim of this study was to provide an evidence synthesis of factors correlated with FCR to inform the development of preventive interventions. METHODS: A literature search was performed of the PsycINFO, EMBASE, and MEDLINE (PubMed) databases. Reports published from inception to 2020 focusing on the correlates of FCR with physical, psychological, and social factors were identified. Authors assessed the studies' risk of bias in accordance with the Standard Quality Assessment Criteria for Quantitative Studies (QualSyst criteria) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. After extracting data and assessing the quality of the included studies, meta-analysis was conducted using RevMan 5.3 software. RESULTS: Thirty-four articles were included in this study with a total sample of more than 13 000 cancer patients. Fear of cancer recurrence was positively correlated with anxiety, depression, avoidance, chemotherapy, distress, intrusive thoughts, fatigue, rumination, and neuroticism. It was negatively correlated with optimism, age, social support, quality of life, time since diagnosis, well-being, and self-efficacy. CONCLUSIONS: We identified 16 factors that are correlated with FCR, 9 positively correlated with FCR and 7 negatively correlated with FCR. IMPLICATIONS FOR PRACTICE: The findings of this study provide direction for the development of precise interventions for FCR in cancer survivors and lay the foundation for the further construction of an FCR-related nursing theoretical framework.

13.
Biomed Chromatogr ; : e5233, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34519055

RESUMO

Aesculetin, a coumarin compound present in the sancho tree and chicory, exhibits excellent antioxidant and anti-inflammatory activities in the vascular and immune system. In this study, a rapid and sensitive ultra-high performance liquid chromatography electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method was established and validated for the determination of aesculetin in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Chromatographic separation was performed on an Acquity UPLC HSS T3 C18 column (2.1 × 100 mm, 1.8 µm) with gradient elution at a flow rate of 0.3 ml/min, using mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Aesculetin and puerarin (internal standard) were detected by multiple reaction monitoring in negative ion mode. The method was fully validated according to the US Food and Drug Administration guidelines. The calibration curve was linear over the range of 2-1,000 ng/ml with correlation coefficient >0.9980. The carry-over, matrix effect, extraction recovery, dilution effect, intra- and inter-day precision and the accuracy were within acceptable limits. The method was then applied to a pharmacokinetic study of aesculetin in rats. After oral administration at doses of 5, 10 and 20 mg/kg, the plasma concentration reached peaks of 95.7, 219.9, 388.6 ng/ml at times of 1.22-1.78 h. The oral bioavailability was calculated as 15.6-20.3% in rat plasma. The result provided pre-clinical information for further application of aesculetin.

14.
Psychophysiology ; 58(12): e13920, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383329

RESUMO

Selective attention is essential when we face sensory inputs with distractions. In the past decades, Lavie's load theory of selective attention delineates a complete picture of distractor suppression under different attentional control load. The present study was originally designed to explore how reward modulates the load effect of attentional selection. Unexpectedly, it revealed new findings under extended attentional load that was not involved in previous work. Participants were asked to complete a rewarded attentive visual tracking task while presented with irrelevant auditory oddball stimuli, with their behavioral performance, event-related potentials and pupillary responses recorded. We found that although the behavioral performance and pupil sizes varied unidirectionally with the attentional load, the processing of distractors as reflected by the mismatch negativity (MMN) increased first and then decreased. In contrast to the prediction of Lavie's theory that attentional control fails to effectively suppress distractor processing under high attentional control load, our finding suggests that extremely high attentional control load may instead require suppression of distractor processing at a stage as early as possible. Besides, P3a, a positive-polarity response sometimes following the MMN, was not affected by the attentional load, but both N1 (a negative-polarity component peaking ~100 ms from sound onset) and P3a were weakened at higher reward, indicating that reward leads to attenuated early processing of distractor and thus suppresses the attentional orienting towards distractors. These findings altogether complement Lavie's load theory of selective attention, presenting a more complex picture of how attentional load and reward affects selective attention.

15.
Nat Commun ; 12(1): 5133, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446721

RESUMO

Electron beam lithography (EBL) is renowned to provide fabrication resolution in the deep nanometer scale. One major limitation of current EBL techniques is their incapability of arbitrary 3d nanofabrication. Resolution, structure integrity and functionalization are among the most important factors. Here we report all-aqueous-based, high-fidelity manufacturing of functional, arbitrary 3d nanostructures at a resolution of sub-15 nm using our developed voltage-regulated 3d EBL. Creating arbitrary 3d structures of high resolution and high strength at nanoscale is enabled by genetically engineering recombinant spider silk proteins as the resist. The ability to quantitatively define structural transitions with energetic electrons at different depths within the 3d protein matrix enables polymorphic spider silk proteins to be shaped approaching the molecular level. Furthermore, genetic or mesoscopic modification of spider silk proteins provides the opportunity to embed and stabilize physiochemical and/or biological functions within as-fabricated 3d nanostructures. Our approach empowers the rapid and flexible fabrication of heterogeneously functionalized and hierarchically structured 3d nanocomponents and nanodevices, offering opportunities in biomimetics, therapeutic devices and nanoscale robotics.


Assuntos
Seda/química , Aranhas/metabolismo , Animais , Fenômenos Biomecânicos , Fibroínas/química , Fibroínas/genética , Fibroínas/metabolismo , Nanoestruturas/química , Seda/genética , Seda/metabolismo , Aranhas/química , Aranhas/genética
16.
Front Cell Infect Microbiol ; 11: 657867, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307189

RESUMO

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum, Fusobacterium hwasookii, Porphyromonas gingivalis, and Bacteroides fragilis, increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage, decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.


Assuntos
Neoplasias Colorretais , Vírus , Bactérias/genética , Neoplasias Colorretais/diagnóstico , Fezes , Fusobacterium , Humanos , Vírus/genética
17.
Bioorg Chem ; 115: 105201, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34329994

RESUMO

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.

18.
Front Nutr ; 8: 685967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249995

RESUMO

Background: Ovarian cancer is the third most common gynecological malignancy in the world and it is under a higher incidence of malnutrition. Chemotherapy is currently a common treatment for ovarian cancer, but the resulting side effects can exacerbate malnutrition. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on ovarian cancer patients undergoing chemotherapy. Methods: Single-blinded randomized controlled trial. Patients with ovarian cancer receiving chemotherapy were randomly assigned either to the ONS or non-ONS groups via a simple randomization. The ONS group was given 250 mL ONS each time (1.06 kcal, 0.0356 g of protein per mL), three times a day, and nutrition education. Control group received nutrition education alone. The primary outcome was the nutritional risk of the patients as assessed by the Patient-Generated Subjective Global Assessment (PG-SGA). The secondary outcome was the results of the participants' biochemical tests at each measurement time point. Data were collected (T0) at baseline, (T1) post intervention at 3 weeks, (T2) 9-week follow-up, (T3) 15-week follow-up. Generalized estimating equation models were used to compare the changes in outcomes over time between groups. Results: 60 participants (30 ONS, 30 controls) completed the trial, and data was analyzed. For baseline comparisons, no significant differences were found between the two groups. A progressive trend toward amelioration in PG-SGA scores over time was found within the ONS group, with scores decreasing from 9.27 ± 1.68 at baseline (T0) to 5.87 ± 2.06 after the intervention (T3). Furthermore, ONS group achieved a significantly greater reduction in PG-SGA score at the T1 (p = 0.03, confidence interval -2.23 to -0.11), T2 (p = 0.001, confidence interval -2.86 to -0.74) and T3 (p < 0.001, confidence interval -3.81 to -1.53), than the control group. In terms of biochemical test results, patients in the ONS group had better leukocytes, lymphocytes, Hemoglobin, Albumin and Total Protein than the control group at different time points, with statistical differences between the two groups (p < 0.05). Conclusions: The present study demonstrated that ONS can significantly reduce the nutritional risk of patients undergoing chemotherapy for ovarian cancer. In addition, we also found that nutritional education seems to have a positive effect on reducing the nutritional risk of patients especially at the beginning of chemotherapy.

19.
Molecules ; 26(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072901

RESUMO

The areca (Areca catechu L.) nut kernel (ANK) is a good potential protein source for its high protein content of 9.89-14.62 g/100 g and a high yield of around 300,000 tons per year in China. However, utilization of the areca nut kernel is limited. To expand the usage of ANK in pharmaceutical or foods industries, areca nut kernel globulin was extracted and angiotensin-I converting enzyme (ACE) inhibition peptides were prepared and identified using gel chromatography, reversed phase HPLC separation, UPLC-ESI-MS/MS analysis and in silico screening. Finally, a novel ACE-inhibitory heptapeptide (Ala-Pro-Lys-Ile-Glu-Glu-Val) was identified and chemically synthesized. The combination pattern between APKIEEV and ACE, and the inhibition kinetics, antihypertensive effect and endothlein-1 inhibition activity of APKIEEV were studied. The results of the molecular docking demonstrated that APKIEEV could bind to four active sites (not the key active sites) of ACE via short hydrogen bonds and demonstrated high ACE-inhibitory activity (IC50: 550.41 µmol/L). Moreover, APKIEEV exhibited a significantly lowering effect on both the systolic blood pressure and diastolic blood pressure of spontaneously hypertensive rats, and had considerable suppression ability on intracellular endothelin-1. These results highlight the potential usage of APKIEEV as ingredients of antihypertensive drugs or functional foods.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Areca/metabolismo , Globulinas/farmacologia , Sequência de Aminoácidos/genética , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Globulinas/metabolismo , Hipertensão/metabolismo , Masculino , Simulação de Acoplamento Molecular/métodos , Nozes/metabolismo , Fragmentos de Peptídeos/farmacologia , Peptídeos/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR , Espectrometria de Massas em Tandem/métodos
20.
Future Med Chem ; 13(13): 1105-1125, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960203

RESUMO

Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Miconazol/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Electrophorus , Cavalos , Humanos , Masculino , Camundongos , Miconazol/síntese química , Miconazol/química , Modelos Moleculares , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Células PC12 , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Ratos
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