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1.
Am J Hypertens ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32161960

RESUMO

BACKGROUND: Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of ENaC-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS: Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS: Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS: This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents is important to prevent the development of hypertensive end-organ disease.

2.
BMC Vet Res ; 16(1): 81, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138735

RESUMO

BACKGROUND: Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. RESULTS: Gamithromycin was well absorbed and fully bioavailable (87.2-101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC24h/MIC ratio correlated well with ex vivo efficacy (R2 = 0.97). The AUC24h/MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (COPD) was determined to be 0.25 mg/L. CONCLUSION: The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.

4.
Biomacromolecules ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32202418

RESUMO

Chitosan (CS), a natural biopolymer, has been extensively explored for multiple applications including tissue engineering, gene therapy, bioimaging, and sewage treatment due to its abundant availability, intrinsic biocompatibility, biodegradability, and tunable biological properties. Nevertheless, the actual use of CS is limited because of its water-insolubility in physiological circumstances, which could be optimized by chemical modifications via active side groups. Etherification is one of the most widely used reactions to obtain water-soluble CS derivatives, such as hydroxybutyl CS (HBC). HBC, synthesized by grafting hydroxybutyl groups to the functional hydroxyl and amino groups of CS skeleton, has been demonstrated to possess superior biological properties over those of CS, especially satisfactory water solubility in neutral condition and reversible stimulus-response against external heat. Meanwhile, the unique characteristics of thermally sensitive "sol-gel" and "sol-micelle" transition have gained tremendous attention, which differ in heterogeneously and homogeneously synthesized HBC. Herein, we discuss the synthesis (heterogeneously and homogeneously) of HBC, favorable physiochemical properties of HBC, and HBC-centered biocomposites in a range of formulations or dosage forms such as sponges, gels, nanoparticles, nanofibers, and films. Meanwhile, we summarize the potential bioapplications and trends of HBC and HBC centered biocomposites and offer our perspectives on the plausible advances in this field in the near future.

5.
Fitoterapia ; 143: 104547, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173419

RESUMO

Five new indole alkaloids, kopsiofficines H-L (1-5), along with fourteen known alkaloids (6-19) were isolated from the stems of Kopsia officinalis. Their structures were elucidated by extensive NMR, mass spectroscopic analyses and comparison to the reported data. All the isolated compounds were evaluated their anti-inflammatory activities by inhibiting IL-1ß, PGE2 and TNF-α secretion in lipopolysaccharide (LPS)-activated RAW264.7 cells. Compounds 2, 3, 6, 7, 11, 12, 15, and 17 show significant anti-inflammatory activities. These results demonstrate pharmacodynamic substance basis of these folkloric claims.

6.
Int J Biol Macromol ; 154: 433-445, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32194103

RESUMO

The oral drug administration was convenient and comfortable route for patients. Nevertheless, the oral uptake efficiency of many therapeutic agents was limited by physiological barriers of the gastrointestinal (GI) tract. This review summarized the challenges toward the oral delivery systems including instability and poor permeability in gastrointestinal environment. The transcellular and paracellular transport were main pathways of nanocarriers across intestinal epithelium. Chitosan is a nature and safe polymer that possesses the capacity of opening intercellular tight junctions of epithelium and excellent mucoadhesive property. Chitosan-based nanocarriers have recently attracted considerable attentions, aiming to overcome GI limitations and enhance drug absorption. Recently developed chitosan-based nanocarriers administered via oral route were highlighted for protecting drugs against degradation, releasing drugs in small intestine, enhancing drug uptake, thus improving oral bioavailability. Finally, various biotherapeutics including hydrophobic and hydrophilic drugs applied in chitosan-based nanovectors were also reviewed.

7.
BMC Genomics ; 21(1): 220, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32151242

RESUMO

BACKGROUND: Circular RNA (circRNA) is produced during the splicing of mRNA (in addition to linear splicing) and is part of the gene regulatory network. The temporal expression patterns the different developmental stages were inseparable from these molecules' function. RESULTS: Skeletal muscles of Anhui white goat (AWG) across seven fetal to postnatal development stages were sequenced and 21 RNA sequencing libraries were constructed. We thereby identified 9090 circRNAs and analyzed their molecular properties, temporal expression patterns, and potential functions at the different stages. CircRNAs showed complexities and diversity of formation as the same host gene produces multiple isoforms of these nucleic acids with different expression profiles. The differential expression of 2881 circRNAs (DECs, P < 0.05) was identified and four were randomly selected and validated by qPCR. Moreover, 1118 DECs under strict selected (SDECs, |log2FC| > 2 and P-adj value < 0.01) showed 4 expression trends (Clusters 0, 19, 16 and 18). Cluster 0 molecules had increasing expression at all stages with effects on muscle through metabolism, regulation of enzyme activity, and biosynthesis. Cluster 16 circRNAs had high expression in the early and late stages and are involved in "Wnt signaling pathway", "AMPK signaling pathway" and others. Cluster 18 molecules were mainly expressed at F120 and participate in "cytoskeletal protein binding", "Notch signaling pathway" and so on. Cluster 19 circRNAs were down-regulated at all stages and related to muscle structure and development. Lastly, the SDECs divided the period of skeletal muscle development into three transitional stages: stage 1 (F45 to F90), which related to muscle satellite cell proliferation and muscle fiber structure; stage 2 (F90 to B1), in which the attachment of the cytoplasmic surface to the actin cytoskeleton initiates; and stage 3, which involved the "cGMP-PKG signaling pathway". Moreover, the paraffin sections messages also validated that there are three transitional stages of skeletal muscle development. CONCLUSION: Our current study provides a catalog of goat muscle-related circRNAs that can stratify skeletal muscle development fetus 45 days to newborn 90 days into three developmental stages. These findings better our understanding of functional transitions during mammalian muscle development.

8.
J Biomol Struct Dyn ; : 1-19, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32189570

RESUMO

PPARα and PPARγ play important roles in regulating glucose and lipid metabolism. In recent years, the development of dual PPAR agonists has become a hot topic in the field of anti-diabetic medicinal chemistry. The dual PPARα/γ agonists can both improve metabolism and reduce side effects caused by single drugs, and has become a promising strategy for designing effective drugs for the treatment of type 2 diabetes. In this study, by means of virtual screening, molecular docking and ADMET prediction technology, a representative compound with higher docking score, lower toxicity than original ligands was gained from the Ligand Expo Components database. It was observed through MD simulation that the representative compound not only has the function of activating the PPARα target and the PPARγ target, but also show a more favorable binding mode when the representative compound binds to the two receptors compared to the original ligands. Our results provided an approach to rapidly find novel PPARα/γ dual agonists for the treatment of type 2 diabetes mellitus (T2DM).HighlightsThe results show that the skeleton of compound M80 is not only similar to Saroglitazar but also higher than that of Saroglitazar in activity.This study explained the binding modes of saroglitazar-PPARα/γ complexes and provided structure reference for the research and development of novel PPARα/γ dual agonists.

9.
Medicine (Baltimore) ; 99(11): e19501, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176092

RESUMO

BACKGROUND: Clinical and basic research supports that blood glucose fluctuation is an important predictor of diabetic vascular disease and an etiology of lower extremity atherosclerosis, which is an important pathological basis for lower extremity vascular diseases. Previous Chinese National Natural Science Foundation trials (No. 81503566) have reported that the traditional Chinese medicine Shenqi compound can reduce blood glucose fluctuation and low-grade inflammation, and protect blood vessels; however, there are no high-quality clinical evidences available to support the same. This multicenter randomized controlled trial aims to obtain more clinical evidence to confirm the efficacy and safety of Shenqi compound in type 2 diabetes with lower extremity atherosclerosis. METHODS: A multicenter RCT will be implemented in this study for a 32-week study period (8 weeks for intervention and 24 weeks for follow-up). Participants will be recruited from the Teaching Hospital of Chengdu University of TCM, Mianyang Hospital of TCM, and Shuangliu Hospital of TCM. Sixty participants will be randomly divided into a treatment group (basic treatment combined with traditional Chinese medicine Shenqi Compound) or a control group (basic treatment combined with Chinese medicine placebo) with 30 participants in each group. Patients will be selected considering the following inclusion criteria: age between 35 and 65 years, and a positive diagnosis for type 2 diabetes with lower extremity atherosclerosis and TCM syndromes. Primary outcome indicator is an arterial color Doppler ultrasound. Secondary outcome indicators include: blood glucose fluctuation indicators (MBG, SDBG, LAGE), islet ß-cell function evaluation indicators (Homa-IR, Homa-islet, SG, SCP), inflammation indicators (NLR, CRP, IL-6), blood lipids, and HbA1c. Safety index includes vital signs (T, P, R, BP), blood, urine, stool routine, liver and renal function, electrocardiogram, and adverse event records. The endpoint event is defined as the presence of gangrene in the lower limbs. DISCUSSION: Explore the clinical effect of traditional Chinese medicine "Shenqi Compound" to reduce blood glucose fluctuation and use HOMA-IR, the area under the glucose curve, and the area under the C-peptide curve to evaluate the effect of protecting islet ß cell function. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR-1900027693). Registered on November 23, 2019. http://www.chictr.org.cn.


Assuntos
Aterosclerose/tratamento farmacológico , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Extremidade Inferior/irrigação sanguínea , Medicina Tradicional Chinesa , Aterosclerose/sangue , Aterosclerose/fisiopatologia , Glicemia , China , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Fitoterapia , Fluxo Pulsátil , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluxo Sanguíneo Regional , Projetos de Pesquisa
10.
Nat Commun ; 11(1): 1427, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188862

RESUMO

Anthropogenic environments have been implicated in enrichment and exchange of antibiotic resistance genes and bacteria. Here we study the impact of confined and controlled swine farm environments on temporal changes in the gut microbiome and resistome of veterinary students with occupational exposure for 3 months. By analyzing 16S rRNA and whole metagenome shotgun sequencing data in tandem with culture-based methods, we show that farm exposure shapes the gut microbiome of students, resulting in enrichment of potentially pathogenic taxa and antimicrobial resistance genes. Comparison of students' gut microbiomes and resistomes to farm workers' and environmental samples revealed extensive sharing of resistance genes and bacteria following exposure and after three months of their visit. Notably, antibiotic resistance genes were found in similar genetic contexts in student samples and farm environmental samples. Dynamic Bayesian network modeling predicted that the observed changes partially reverse over a 4-6 month period. Our results indicate that acute changes in a human's living environment can persistently shape their gut microbiota and antibiotic resistome.

11.
Med Sci Monit ; 26: e920394, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170053

RESUMO

BACKGROUND Oxidative stress and myocardial apoptosis are features of doxorubicin-induced cardiac toxicity that can result in cardiac dysfunction. Previous studies showed that microRNA-143 (miR-143) was expressed in the myocardium and had a role in cardiac function. This study aimed to investigate the effects and possible molecular mechanisms of miR-143 on oxidative stress and myocardial cell apoptosis in a mouse model of doxorubicin-induced cardiac toxicity. MATERIAL AND METHODS Mice underwent intraperitoneal injection of doxorubicin (15 mg/kg) daily for eight days to develop the mouse model of doxorubicin-induced cardiac toxicity. Four days before doxorubicin administration, a group of mice was pretreated daily with a miR-143 antagonist (25 mg/kg/day) for four consecutive days by tail vein injection. The study included the use of a miR-143 antagomir, or anti-microRNA, an oligonucleotide that silenced endogenous microRNA (miR), and an agomir to miR-143, and also the AKT inhibitor, MK2206. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblot analysis were used to measure mRNA and protein expression, respectively. RESULTS Doxorubicin treatment increased the expression of miR-143, which was reduced by the miR-143 antagomir. Overexpression of miR-143 increased doxorubicin-induced myocardial apoptosis and oxidative stress. The use of the miR-143 antagomir significantly activated protein kinase B (PKB) and AKT, which were reduced in the presence of the AKT inhibitor, MK2206. However, the use of the miR-143 antagomir further down-regulated AKT phosphorylation following doxorubicin treatment and increased AKT activation. CONCLUSIONS In a mouse model of doxorubicin-induced cardiac toxicity, miR-143 increased oxidative stress and myocardial cell apoptosis following doxorubicin treatment by inhibiting AKT.

12.
J Med Food ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119798

RESUMO

Much research has indicated that alcoholic liver disease (ALD) is associated with oxidative stress and inflammation induced by ethanol, and that numerous antioxidants could effectively alleviate such injuries. Moreover, recent studies have identified andrographolide (AD) as having strong anti-inflammatory and antioxidant activities, which can block oxidative damage associated with nuclear factor kappa B (NF-κB)-mediated inflammation. However, the biological role and potential mechanism of AD in its protection against ALD have not been fully characterized. To observe the possible effect of AD, male C57BL/6J mice received ethanol through intragastrical gavage for 12 weeks in this study. The ethanol group was separated into five subgroups: (1) model group (n = 10); (2) silymarin group (0.1 mg/g body weight [BW], n = 10); (3) AD (0.05 mg/g BW) group (n = 10); (4) AD (0.1 mg/g BW) group (n = 10); and (5) AD (0.2 mg/g BW) group (n = 10). Mice in AD groups were treated orally by gavage once per day. The experimental results show that serum aminotransferase, liver lipids, lipid peroxidation, and antioxidant capacities were significantly changed in the model group after alcohol treatment, and the liver tissue histological findings showed pathological changes. Compared with the model group, treatment with AD improved serum aminotransferase, liver function, lipid accumulation, and hepatic reactive oxygen species levels. And AD decreased the hepatic NF-κB and tumor necrosis factor alpha (TNF-α) protein expression of ALD mice. This research demonstrated that AD can alleviate liver pathological injury and oxidative stress in mice exposed to ethanol by decreasing the expression of NF-κB and TNF-α.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32122894

RESUMO

Tigecycline serves as one of the last-resort antibiotics to treat multidrug-resistant (including carbapenem-resistant) pathogens. However, the recently emerged plasmid-mediated tigecycline resistance mechanisms, Tet(X), challenge the clinical efficacy of this class of antibiotics. In this study, we detected one hundred and eighty tet(X)-harboring Acinetobacter isolates (8.9%, n=180) from 2018 samples collected from the avian farms and adjacent environment in China. Eighteen tet(X)-harboring isolates (10.0%) were found to co-carry the carbapenemase gene bla NDM-1, mostly from waterfowls samples (94.4%, 17/18). Interestingly, among six Acinetobacter strains, the tet(X) and bla NDM-1 were found to co-localize on the same plasmids. Moreover, WGS revealed a novel orthologue of tet(X) in the six tet(X)- and bla NDM-1-co-harboring isolates. Inverse PCR suggested that the two tet(X) genes form a single transposable unit and may be co-transferred. Sequence comparison between six tet(X) and bla NDM-1-co-harboring plasmids showed they shared a highly homologous plasmid backbone, even though they were isolated from different Acinetobacter species (3 A. indicus, 2 A. schindleri, and 1 A. lwoffii) in various sources and from different geological regions, suggesting the horizontal genetic transfer of a common tet(X) and bla NDM-1-co-harboring plasmid among Acinetobacter species in China. Emergence and spread of such plasmids and strains are of great clinical concern, and measures must be implemented to avoid their dissemination.

14.
Acta Pharmacol Sin ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123300

RESUMO

Herbal and dietary supplements (HDS)-induced liver injury has been a great concern all over the world. Polygonum multiflorum Thunb., a well-known Chinese herbal medicine, is recently drawn increasing attention because of its hepatotoxicity. According to the clinical and experimental studies, P. multiflorum-induced liver injury (PM-DILI) is considered to be immune-mediated idiosyncratic liver injury, but the role of immune response and the underlying mechanisms are not completely elucidated. Previous studies focused on the direct toxicity of PM-DILI by using animal models with intrinsic drug-induced liver injury (DILI). However, most epidemiological and clinical evidence demonstrate that PM-DILI is immune-mediated idiosyncratic liver injury. The aim of this review is to assess current epidemiological, clinical and experimental evidence about the possible role of innate and adaptive immunity in the idiosyncratic hepatotoxicity of P. multiflorum. The potential effects of factors associated with immune tolerance, including immune checkpoint molecules and regulatory immune cells on the individual's susceptibility to PM-DILI are also discussed. We conclude by giving our hypothesis of possible immune mechanisms of PM-DILI and providing suggestions for future studies on valuable biomarkers identification and proper immune models establishment.

15.
Acta Pharmacol Sin ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123301

RESUMO

Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.

16.
Biopharm Drug Dispos ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017134

RESUMO

Methotrexate (MTX) pharmacokinetics has substantial inter-individual variability and toxicity. In children with medulloblastoma treated with high-dose methotrexate (HD-MTX), the pharmacokinetic properties of methotrexate have not been established. A total of 660 serum samples from 105 pediatric patients with medulloblastoma were included in a population pharmacokinetic (PPK) analysis of methotrexate by using the nonlinear mixed-effects modeling method. The basic one-compartment population pharmacokinetic model was established by NONMEM software and the first-order conditional estimation (FOCE) method, and the final covariate model was obtained by the stepwise regression method. Weight (WT), creatinine clearance (CrCL), and whether the treatment was combined with dexamethasone (DEX) were covariates that had significant effects on the clearance rate (CL) of the model. The pharmacokinetic equation of CL in the final covariate model was as follows: CLi = 9.23× (1 + 0.0005× (θCrCL -105.78)) × (1 + 0.0017× (θWT -16)) × eηcl,i (L/h), IF (θDEX ) CLi = 1.19× CLi (L/h). The estimation accuracy of all pharmacokinetic parameters were acceptable (relative standard error < 14.74%). The goodness-of-fit diagram and bootstrap tests indicated that the final PPK model was stable with acceptable predictive ability. The PPK model may be useful for determining personalized medication levels in pediatric medulloblastoma patients undergoing HD-MTX therapy.

17.
Plant Cell ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32102844

RESUMO

Maize is one of the most important crops in the world. However, few agronomically important maize genes have been cloned and used for trait improvement, due to the complex genome and genetic architecture. Here we integrated multiplexed CRISPR/Cas9-based high-throughput targeted mutagenesis with genetic mapping and genomic approaches to successfully knock-out 743 candidate genes corresponding to agronomic and nutritional traits. After low-cost barcode-based deep sequencing, 412 edited sequences covering 118 genes were precisely identified from individuals showing clear phenotypic changes. This mutant profile was similar to the ones identified in human cell lines and predictable. An unexpectedly frequent homology-directed repair through endogenous templates was observed and likely caused by the spatial contact between distinct chromosomes. Through several case studies on validation and interpretation of gene function, this targeted mutagenesis library suggested that the integration of forward- and reverse- genetics promises rapid validation of important agronomic genes for crops with complex genomes. Beyond specific findings, this study also guides further optimization of high-throughput CRISPR experiments in plants.

18.
Lab Chip ; 20(6): 1072-1082, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32100806

RESUMO

Cell isolation from blood is an important process for diagnosing immune diseases. There are still demands for a user-friendly approach to achieve high cell extraction efficiency and purity of a target immune cell subtype for more promising diagnosis and monitoring. For selective immune cell isolation, we developed a microstructured device, which consists of antibody-coated micropillars and micro-sieve arrays, for isolating a target immune cell subtype from bovine blood samples. The focusing micropillars can guide immune cells flowing to the subsequent micro-sieves based on deterministic lateral shifts of the cells. The arrangement of these microstructures is characterized and configured for the maximal cell capture rate. Surface modification with a selected antibody offers selective cell capture in the micro-sieves based on the antigen-antibody reaction. We prepare a cell mixture of human CD14-expressing leukemia cells (THP-1) and epithelial cells (MDA-MB-231) in diluted blood to characterize the cell isolation operation, with a selective cell isolation yield of >80%, cell purity of ∼100% and cell viability of >93%. Together, this microstructured device strategy can achieve high-yield selective isolation of immune cells from blood samples and support downstream genetic and biochemical cell analyses, contributing to the medical diagnosis of a broad range of immune diseases.

19.
J Agric Food Chem ; 68(10): 3079-3087, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059104

RESUMO

The fruits of Lycium barbarum have a long history as an edible and medicinal food in Asian regions and have multiple consumption methods; the polysaccharides (LBPs) are commonly considered as their major immunological constituents. The current study revealed that the total phenolic amide moieties from L. barbarum fruits showed greater potential immunomodulatory activity in vivo than did LBPs. Through subsequent investigation on the immunological bioactive phenolic amides, three new phenolic amides, lyciumamides L-N (1-3), as well as 12 analogues, were obtained from the total phenolic amide fraction. Extensive spectroscopic methods were used to elucidate the new structures. Compounds 4-6 and 15 significantly promoted LPS-stimulated B splenocyte, while compounds 4-6 displayed accelerative effects on the proliferation of Con A-stimulated T lymphocytes at a concentration of 20.0 µg/mL. These data indicated that extracts from L. barbarum fruits enriched with phenolic amides could be developed as a nutritional dietary supplement for immunocompromised individuals.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fatores Imunológicos/farmacologia , Lycium/química , Fenóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Frutas/química , Humanos , Ativação Linfocitária/efeitos dos fármacos , Fenóis/química , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-32091874

RESUMO

Electroreduction of N2 represents a promising technique for ambient NH3 synthesis, but exploring efficient electrocatalysts for nitrogen reduction reaction (NRR) remains a key challenge. Herein, we reported our experimental and theoretical findings that FeMoO4 could be a new candidate for effective and durable NRR in neutral solution. The developed FeMoO4 nanorods exhibited a fascinating NRR activity with an NH3 yield of 45.8 µg h-1 mg-1 (-0.5 V) and a Faradaic efficiency of 13.2% (-0.3 V). Mechanistic studies disclosed that Fe and Mo synergistically promoted the N2 adsorption and accelerated the electron transfer on FeMoO4, whereas the unsaturated 3-fold coordinated Mo (Mo3c) sites served as the main active centers for stabilizing the key *N2H intermediate and reducing the reaction energy barrier.

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