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1.
Antioxidants (Basel) ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34829536

RESUMO

The objective of this study is to evaluate the effects of organic acids on piglet growth performance and health status. A total of 360 weanling pigs (5.3 ± 0.6 kg) were randomly allotted to 3 treatment groups with 12 replicates of 10 pigs/pen. Piglets were fed the same basal diet and given either water (control) or water plus 2.0 L/Ton organic acid (OA) blends, such as OA1 or OA2, respectively, for 7 weeks. Compared to the control, OA1 and OA2 improved growth performance and/or reduced the piglets' diarrhea rate during the various periods and improved small intestinal morphology at days 14 and/or 49. OA1 and OA2 also increased serum CAT and SOD activities and/or T-AOC and, as expected, decreased MDA concentration. Moreover, at day 14 and/or day 49, OA1 and OA2 increased the jejunal mRNA levels of host defense peptides (PBD1, PBD2, NPG1, and NPG3) and tight junction genes (claudin-1) and decreased that of cytokines (IL-1ß and IL-2). Additionally, the two acidifiers regulated the abundance of several cecum bacterial genera, including Blautia, Bulleidia, Coprococcus, Dorea, Eubacterium, Subdoligranulum, and YRC2. In conclusion, both of the organic acid blends improved piglet growth performance and health status, potentially by regulating intestinal redox homeostasis, immunity, and microflora.

2.
Toxicol Lett ; 355: 88-99, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838997

RESUMO

Liver fibrosis is a reversible wound healing reaction characterized by abnormal accumulation of extracellular matrix (ECM) in response to liver injury. Recent studies have shown that it can be epigenetically regulated, especially by microRNAs (miRNAs). It has been acknowledged that activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Notably, our results showed that miR-195-3p was increased in HSCs isolated from CCl4-treated mice and that the increase was more pronounced as the degree of liver fibrosis increased. Moreover, treatment of LX-2 cells, a human immortalized hepatic stellate cell line, with TGF-ß1 resulted remarkable upregulation of miR-195-3p. Gain-of-function and loss-of-function experiments have suggested that the increased levels of miR-195-3p inhibit the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR signaling pathway in liver fibrosis, thereby contributing to HSC activation and proliferation and promoting the expression of profibrotic genes, such as α-SMA and collagen I, in LX-2 cells, which accelerates the accumulation of fibrous extracellular matrix deposition in the liver, while knockdown of miR-195-3p induced the opposite effect. Taken together, these results provide evidence for the harmful role of miR-195-3p in CCl4-treated mouse liver fibrosis.

3.
Zhongguo Zhen Jiu ; 41(11): 1273-5, 2021 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-34762383

RESUMO

The elements of ethical review related to clinical research of acupuncture and moxibustion is discussed to provide ideas for various institutions to carry out relevant ethical review. It is believed that the ethical review of clinical research of acupuncture and moxibustion needs to focus on the specificity of acupuncture and moxibustion. Starting from the basic theory of traditional Chinese medicine, the theory of meridians and acupoints and the theory of syndrome differentiation along meridians, the key contents of ethical review such as intervention methods, grouping design and placebo control should be considered, so as to standardize the clinical research of acupuncture and moxibustion and protect the health and rights and interests of participants.


Assuntos
Terapia por Acupuntura , Pesquisa Biomédica , Revisão Ética , Moxibustão , Pontos de Acupuntura , Humanos , Meridianos
4.
Dalton Trans ; 50(45): 16685-16693, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34758054

RESUMO

In this study, we reported the covalent post-synthetic modification (PSM) of a luminescent complex to achieve aggregation-induced emission (AIE), prepared using the Schiff base reaction of TPE-CHO and HLC-NH2, denoted by HLC-NH2-TPE. HLC-NH2 formed a 2D luminescent complex which was constructed using 4,4'-diamino-[1,1'-biphenyl]-2,2'-dicarboxylic acid and zinc ions via a solvothermal reaction. HLC-NH2-TPE inherited the luminescence properties of HLC-NH2 and exhibited noticeable AIE properties in response to environmental viscosities and temperature changes. Interestingly, HLC-NH2-TPE displayed a time-dependent luminescence conversion phenomenon in a mixed solution of DMF/H2O (v : v/1 : 9).

5.
Sci Rep ; 11(1): 21830, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750414

RESUMO

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10-10, OR 0.17, 95% CI 0.09-0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10-5, OR 0.33, 95% CI 0.19-0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

6.
Front Immunol ; 12: 731842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630412

RESUMO

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N 6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

7.
Enzyme Microb Technol ; 151: 109919, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649690

RESUMO

Improving enzyme stability is very important for enzyme applications. Structural modification is a reliable and effective method to improve the characteristics of protein. By artificially extending the C-terminus, 6 domain modification variants of different sizes were constructed, and a new enzyme species with high stability was obtained. Experimental results affirmed that high stability can be achieved by decreasing the degree of domain freedom. The optimum temperatures of domain modification variants were improved by 10 °C compared with the original enzyme. Specifically, compared with the original enzyme, the half-life of the variant dexYG-fdx (D-F) was increased to 280% under 35 °C and 200% under 45 °C, and the pH tolerance range was wider. Further structural simulations and molecular docking studies provided a reasonable explanation (The increased domain reduced the degree of freedom of the enzyme terminal to some extent) for this variant to increase stability and produce dextran. This study can provide valuable information for increasing the characteristics of recombinant dextransucrase.


Assuntos
Glucosiltransferases , Estabilidade Enzimática , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Simulação de Acoplamento Molecular , Temperatura
8.
Eur J Pharmacol ; 911: 174462, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536366

RESUMO

Liver fibrosis is a persistent pathological repair of chronic liver injury, which is characterized by excessive deposition of collagen-dominated extracellular matrix (ECM). It is well known that hepatic fibrosis can be reversed in the absence of etiology. Studies have shown that long non-coding RNA (Lnc RNA) maternally expressed gene3 (MEG3) has strong effects on the activation of hepatic stellata cells (HSCs). However, the function of MEG3 in the reversal of liver fibrosis has not been studied. In this experiment, we studied the content expression, function, and part of the potential mechanism of MEG3 in reversing liver fibrosis. In in vivo and in vitro models, we found that MEG3 was down-regulated during the formation of liver fibrosis, while it was up-regulated during the reversal of liver fibrosis. Then, it was found that the silencing of MEG3 could gradually restore the activity of the inactivated LX-2 cells, Overexpression of MEG3 can inhibit the activation of LX-2 cells, accelerate the reversal of liver fibrosis. Through catRAPID analysis, it was found that NLR family CARD domain containing 5 (NLRC5) may be a target of MEG3. We found that, after MEG3 silencing, NLRC5 expression was upregulated in LX-2 cells in the reverse phase, while, after MEG3 overexpression, NLRC5 expression was decreased. Further, we verified that MEG3 can target NLRC5 through RNA pull down experiment. Therefore, MEG3 may inhibit the activation of hepatic stellate cells by targeting NLRC5, thus accelerating the reversal of hepatic fibrosis.

9.
Front Mol Biosci ; 8: 681955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395522

RESUMO

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486-0.801; adjusted HR = 0.011, 95% CI = 0.002-0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731-0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

10.
Front Pharmacol ; 12: 700373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305608

RESUMO

Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.

11.
Redox Biol ; 45: 102048, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34167027

RESUMO

Selenoprotein V (SELENOV) is a new and the least conserved member of the selenoprotein family. Herein we generated Selenov knockout (KO) mice to determine its in vivo function. The KO led to 16-19% increases (P < 0.05) in body weight that were largely due to 54% higher (P < 0.05) fat mass accumulation, compared with the wild-type (WT) controls. The extra fat accumulation in the KO mice was mediated by up-regulations of genes and proteins involved in lipogenesis (Acc, Fas, Dgat, and Lpl; up by 40%-1.1-fold) and down-regulations of lipolysis (Atgl, Hsl, Ces1d, and Cpt1a; down by 36-89%) in the adipose tissues. The KO also decreased (P < 0.05) VO2 consumption (14-21%), VCO2 production (14-16%), and energy expenditure (14-23%), compared with the WT controls. SELENOV and O-GlcNAc transferase (OGT) exhibited a novel protein-protein interaction that explained the KO-induced decreases (P < 0.05) of OGT protein (15-29%), activity (33%), and function (O-GlcNAcylation, 10-21%) in the adipose tissues. A potential cascade of SELENOV-OGT-AMP-activated protein kinase might serve as a central mechanism to link the biochemical and molecular responses to the KO. Overall, our data revealed a novel in vivo function and mechanism of SELENOV as a new inhibitor of body fat accumulation, activator of energy expenditure, regulator of O-GlcNAcylation, and therapeutic target of such related disorders.


Assuntos
Metabolismo Energético , Lipólise , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Metabolismo Energético/genética , Camundongos , Camundongos Knockout
13.
FASEB J ; 35(6): e21622, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33982351

RESUMO

Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-ß1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-ß1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-ß2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-ß2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.


Assuntos
Regulação da Expressão Gênica , Cirrose Hepática/patologia , MicroRNAs/genética , RNA Circular/genética , Fator de Crescimento Transformador beta2/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Animais , Tetracloreto de Carbono , Proliferação de Células , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator de Crescimento Transformador beta2/genética
14.
Front Pharmacol ; 12: 609702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025396

RESUMO

Dried ginger-aconite decoction (DAD) is a traditional Chinese medicine (TCM) formula that has been extensively used in the treatment of myocardial ischemia reperfusion injury (MI/RI). However, its specific mechanism against MI/RI has not been reported yet. Therefore, this paper studies the potential active components and mechanism of DAD against MI/RI based on network pharmacology and experimental verification. Sixteen active components of DAD were screened according to oral bioavailability and drug similarity indices. Through Cytoscape 3.7.0, a component-target network diagram was drawn, and potential active components of DAD against MI/RI were determined. Protein-protein interaction (PPI) and compound-target-pathway (C-T-P) networks were established through the software to discover the biological processes, core targets and core pathways of DAD against MI/RI. High Performance Liquid Chromatography (HPLC) analysis identified the presence of potentially active core components for network pharmacological prediction in DAD. It was found that DAD might have played a therapeutic role in anti-MI/RI by activating the PI3K/Akt/GSK-3ß signaling pathway in order to reduce mitochondrial hypoxia injury and myocardial cell apoptosis. The network pharmacological prediction was validated by Hypoxia/reoxygenation(H/R) model in vitro and ligation model of the ligation of the left anterior descending branch in vivo. It was verified that DAD had activated PI3K/AKT/GSK-3ß to reduce myocardial apoptosis and play a therapeutic function in MI/RI.

15.
Huan Jing Ke Xue ; 42(6): 2583-2594, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032058

RESUMO

High value-added extracellular polymer substance (EPS) extracted from excess sludge can effectively promote resource recovery from wastewater. EPS can replace traditional alginate in the food, medicine, textile, printing and dyeing, papermaking, and household chemicals industries. Moreover, its unique performance as a flame retardant has shown attractive potential for aircraft including space shuttles. This is due to the complicated chemical structure and composition of EPS, the excellent compatibility, adhesion, and other advantages of which could yield environmental-friendly flame-retardants. Therefore, a systematic analysis and summary on the mechanisms of EPS as flame retardants is of significance for future application. On the basis of the advantages and disadvantages of other fire-resistant materials on the market, the characteristics and application potential of EPS are analyzed and summarized. Second, the possible fire-resistant mechanisms of phosphorus and alginate-like substance (ALE) in EPS are revealed, and the synergistic flame-retardant effects of extracellular-proteins are also elucidated. Based on this, the flame-retardant characteristics of EPS are comprehensively evaluated and compared with other fire-resistant materials. To further improving the performance of EPS as a flame-retardant material, some modification strategies are proposed, such as increasing their phosphorus content, purifying and enhancing the content of ALE in EPS, and optimizing the modification methods of EPS on their substrates.

16.
Curr Med Sci ; 41(2): 336-341, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877551

RESUMO

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Cesárea , Artéria Ilíaca/cirurgia , Placenta Acreta/cirurgia , Placenta Prévia/cirurgia , Adulto , Cateterismo , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Período Pós-Parto , Gravidez , Ultrassonografia Doppler em Cores
17.
Toxins (Basel) ; 13(2)2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671260

RESUMO

The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying hens were randomly allocated into four experimental groups with 10 replicates of nine birds each. The four groups received either a basal diet (BD; Control), a BD supplemented with 0.15 mg/kg AFB1 + 1.5 mg/kg DON + 0.12 mg/kg OTA (Toxins), a BD + Toxins with Toxo-HP binder (Toxins + HP), or a BD + Toxins with TOXO XL binder (Toxins + XL) for 12 weeks. Compared to the control, dietary supplementation of mycotoxins decreased (P < 0.10) total feed intake, total egg weight, and egg-laying rate, but increased feed/egg ratio by 2.5-6.1% and mortality during various experimental periods. These alterations induced by mycotoxins were alleviated by supplementation with both TOXO HP and XL binders (P < 0.10). Furthermore, dietary mycotoxins reduced (P < 0.05) eggshell strength by 12.3% and caused an accumulation of 249 µg/kg of DON in eggs at week 12, while dietary supplementation with TOXO HP or XL mitigated DON-induced changes on eggshell strength and prevented accumulation of DON in eggs (P < 0.05). Moreover, dietary mycotoxins increased relative liver weight, but decreased spleen and proventriculus relative weights by 11.6-22.4% (P < 0.05). Mycotoxin exposure also increased alanine aminotransferase activity and reduced immunoglobulin (Ig) A, IgM, and IgG concentrations in serum by 9.2-26.1% (P < 0.05). Additionally, mycotoxin exposure induced histopathological damage and reduced villus height, villus height/crypt depth, and crypt depth in duodenum, jejunum and (or) ileum (P < 0.05). Notably, most of these histological changes were mitigated by supplementation with both TOXO HP and XL (P < 0.05). In conclusion, the present study demonstrated that the mycotoxin binders TOXO HP and XL can help to mitigate the combined effects of AFB1, DON, and OTA on laying hen performance, egg quality, and health.


Assuntos
Aflatoxina B1/análise , Ração Animal/análise , Bentonita/administração & dosagem , Parede Celular , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais , Ovos , Ocratoxinas/análise , Tricotecenos/análise , Leveduras , Aflatoxina B1/toxicidade , Ração Animal/microbiologia , Ração Animal/toxicidade , Criação de Animais Domésticos , Animais , Galinhas/microbiologia , Feminino , Microbiologia de Alimentos , Ocratoxinas/toxicidade , Tricotecenos/toxicidade
18.
Front Genet ; 12: 603195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767727

RESUMO

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3'-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.

19.
Phytomedicine ; 82: 153458, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33486267

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with high morbidity, which leads to poor quality of life. The Xianglian pill (XLP) is a classical Chinese patent medicine and has been clinically proven to be an effective treatment for UC. PURPOSE: The pharmacological mechanism of the key bioactive ingredients of XLP for the treatment of UC was investigated by a network pharmacology and pharmacokinetics integrated strategy. STUDY DESIGN AND METHODS: Network pharmacology was used to analyze the treatment effect of nine quantified XLP ingredients on UC. Key pathways were enriched and analyzed by protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses. The effect of XLP on Th17 cell differentiation was validated using a mouse model of UC. The binding of nine compounds with JAk2, STAT3, HIF-1α, and HSP90AB1 was assessed using molecular docking. A simple and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of nine ingredients from XLP in plasma and applied to a pharmacokinetic study following oral administration. RESULTS: Nine compounds of XLP, including coptisine, berberine, magnoflorine,berberrubine, jatrorrhizine, palmatine, evodiamine, rutaecarpine, and dehydrocostus lactone, were detected. Network pharmacology revealed 50 crossover genes between the nine compoundsand UC. XLP treats UC mainly by regulating key pathways of the immune system, including Th17 cell differentiation, Jak-Stat, and PI3K-Akt signaling pathways. An in vivo validation in mice found that XLP inhibits Th17 cell differentiation by suppressing the Jak2-Stat3 pathway, which alleviates mucosal inflammation in UC. Molecular docking confirmed that eight compounds are capable of binding with JAk2, HIF-1α, and HSP90AB1, further confirming the inhibitory effect of XLP on the Jak2-Stat3 pathway. Moreover, apharmacokinetic study revealed that the nine ingredients of XLP are exposed in the plasma and colon tissue, which demonstrates its pharmacological effect on UC. CONCLUSION: This study evaluates the clinical treatment efficacy of XLP for UC. The network pharmacology and pharmacokinetics integrated strategy evaluation paradigm is efficient in discovering the key pharmacological mechanism of herbal formulae.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Camundongos , Simulação de Acoplamento Molecular , Proteínas Quinases/metabolismo , Qualidade de Vida , Fator de Transcrição STAT3/metabolismo , Células Th17/efeitos dos fármacos
20.
Sci Rep ; 10(1): 19001, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149251

RESUMO

Two epiphytic lichens (Xanthoria alfredii, XAa; X. ulophyllodes, XAu) and soil were sampled at three sites with varied distances to a road in a semiarid sandland in Inner Mongolia, China and analyzed for concentrations of 42 elements to assess the contribution of soil input and road traffic to lichen element burdens, and to compare element concentration differences between the two lichens. The study showed that multielement patterns, Fe:Ti and rare earth element ratios were similar between the lichen and soil samples. Enrichment factors (EFs) showed that ten elements (Ca, Cd, Co, Cu, K, P, Pb, S, Sb, and Zn) were enriched in the lichens relative to the local soil. Concentrations of most elements were higher in XAu than in XAa regardless of sites, and increased with proximity to the road regardless of lichen species. These results suggested that lichen element compositions were highly affected by soil input and road traffic. The narrow-lobed sorediate species were more efficient in particulate entrapment than the broad-lobed nonsorediate species. XAa and XAu are good bioaccumulators for road pollution in desert and have similar spatial patterns of element concentrations for most elements as response to road traffic emissions and soil input.

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