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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35552648

RESUMO

Thousands of genome-wide epigenetic (epigenomic) datasets determined in the past decade have generated maps of chromatin accessibility, histone modifications, and binding by transcription factors and structural proteins in a large number of cell types in humans and model species. Such maps have revealed many informative associations between groups of epigenetic features and different classes of cis-regulatory elements (CREs), and they enable a prediction of the locations of candidate CREs (cCREs) in many genomes. The actuation (opening of chromatin) and epigenetic state (combination of features such as histone modifications) acquired at specific cCREs has been associated with specific gene activation. However, despite the large number and rich variety of available epigenomic datasets, it is difficult for researchers to effectively utilize all the data relevant to their projects. Furthermore, comprehensive rules and catalogs have not been established for which CREs regulate specific target genes and how. Integrative analysis can help meet these needs, and our VISION project provides a ValIdated Systematic IntegratiONof epigenomic data in hematopoiesis in human and mouse blood cells. After careful curation and normalization of epigenomic data from many sources, we systematically integrated these data to generate a comprehensive view of the regulatory landscape (epigenetic states) and predicted cCREs in differentiating hematopoietic cell types jointly in both mouse and human. Multiple machine learning approaches reveal target genes predicted to be regulated by each element in different cell types. These approaches include predicting the regulatory impact of each element on targets by regression models, finding linkages between distinctive clusters of elements and potential target genes from self-organizing maps, and visual overlays of chromatin interaction maps. Directed mutation and expression analysis around selected genes supports the utility of the assignments. These catalogs of highly annotated regulatory elements are useful for many applications, including interpretation of the phenotypic impact of genetic variants in noncoding genomic regions. Resources from the VISION project are available at our website usevision.org.

2.
Sex Transm Infect ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534231

RESUMO

OBJECTIVES: Despite a high risk of human papillomavirus (HPV) infection among men who have sex with men (MSM), few have ever tested. This study aimed to evaluate the feasibility and accuracy of HPV self-sampling among Chinese MSM, with the purpose of measuring the feasibility of self-sampling as an alternative in HPV testing scenarios. METHODS: Eligible participants were those who were assigned male at birth, aged 18 or above, had sex with men in the past year and had never gotten HPV vaccine. Participants followed the instructions to self-sample and were also clinician-sampled from the same anatomical sites (oral fluid, penis and rectum) in both approaches. All specimens were processed using multiplex PCR assay. The reference standard of an individual with a true positive for HPV is determined via PCR test, regardless of sampling methods. Sensitivity and specificity were calculated for each approach independently and kappa test was used to assess the consistency between the two approaches. RESULTS: Overall, 211 MSM were recruited at the local clinic from April to October 2020 in Zhuhai, China. The mean age was 31 years old. Only 3% of the participants sought help from healthcare providers during self-sampling. The prevalence of HPV was 49% (103 of 211). Clinician sampling detected 91 of 103 MSM infected with HPV, with a sensitivity of 88.3% (95% CI 80.2 to 93.6) and a specificity of 100.0% (95% CI 95.7 to 100.0). Self-sampling detected 81 of 103 MSM infected with HPV, with a sensitivity of 78.6% (95% CI 69.2 to 85.9) and a specificity of 100.0% (95% CI 95.7 to 100.0). The level of agreement was moderate between clinician sampling and self-sampling (k=0.67). CONCLUSIONS: Self-sampled HPV testing demonstrated comparable accuracy and consistency to clinician sampling among MSM in China. It holds the potential to complement sexual health services especially among key populations.

3.
Mediators Inflamm ; 2022: 7338692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431654

RESUMO

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper airway inflammatory disease with a high postoperative recurrence rate. This study is aimed at exploring the expression of B cell-activating factor (BAFF) in CRSwNP and its association with postoperative recurrence. Methods: A total of 80 CRSwNP patients, including 40 primary CRSwNP patients and 40 recurrent CRSwNP patients, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 40 healthy controls (HC) were enrolled in this study, and the serum and tissue samples were collected. The circulating and tissue BAFF expressions were detected by enzyme-linked immunosorbent assay reverse transcription-polymerase chain reaction and immunohistochemistry. Their clinical values for predicting postoperative recurrence of CRSwNP were evaluated. Results: We determined serum levels of BAFF were remarkably increased in the CRSwNP group than the CRSsNP and HC groups (P < 0.05), and higher concentrations of BAFF were associated with peripheral eosinophil percentage (r = 0.614, P < 0.001). The serum BAFF concentrations were significantly higher in the recurrent CRSwNP group in comparison with the primary group (P < 0.05). Multivariate analysis and receiver operating characteristic (ROC) curve presented that serum BAFF levels were associated with the postoperative recurrence in CRSwNP patients (P < 0.05). Moreover, tissue BAFF levels were significantly increased in the CRSwNP group than the HC group, especially in the recurrent CRSwNP group (P < 0.05), and enhanced BAFF RNA expressions were correlated with serum BAFF levels (r = 0.703, P < 0.001). Conclusion: Our results elucidated that the BAFF expression was enhanced in CRSwNP patients and associated with postoperative recurrence. BAFF could be a serologic biomarker for predicting postoperative recurrence in CRSwNP patients.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Eosinófilos/metabolismo , Humanos , Interleucina-4 , Pólipos Nasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 276: 121196, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35390755

RESUMO

The proposition of ratiometric detection mode has demonstrated great superiority in improving analysis accuracy by forming self-calibration. Herein, the novel dual-reverse-signal ratiometric fluorescence detection for malachite green (MG) was first achieved based on synergistic effect of fluorescence resonance energy transfer (FRET) and inner filter effect (IFE). The ratiometric fluorescence probe (B-RCDs) was self-assembled via electrostatic attraction between blue-emission carbon dots (BCDs) and red-emission carbon dots (RCDs), followed with FRET effect from BCDs to RCDs and exhibited dual-emission at 450 nm and 627 nm. In the presence of MG, the IFE effect between MG and RCDs quenched the fluorescence at 627 nm and restored the fluorescence at 450 nm, sending out two reverse signals along with an obvious color change from pink to purple (302 nm UV lamp). This ratiometric method not only simplified the preparation process, but also improved the detection sensitivity, showing a low limit of detection (LOD) of 41.8 nM, which exhibited superiority than that of single-signal RCDs (157.3 nM). This method held a rapid response of 10 min and represented satisfactory recoveries (99.14%-109.08%) in real water samples, revealing it was a promising candidate in the fast, sensitive and practical detection of MG. Moreover, the design of synergistic effect supplied a new perspective for the development of ratiometric sensing in the future.


Assuntos
Pontos Quânticos , Carbono , Corantes Fluorescentes , Corantes de Rosanilina
6.
Acta Biomater ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489607

RESUMO

The reduction of ROS and inflammatory factor levels plays important role in the treatment of colitis. A series of ROS-responsive lipids (ZnDPA-R) based on the thioketal structure were designed and synthesized. It was hoped that the lipidic materials could combine ROS consumption and siRNA delivery capacity to achieve synergistic treatment of colitis. The target liposomes could combine with the phosphate backbone of siRNA to form lipoplexes with the size of ∼100 nm, and could deliver siRNA cargo into the cell. The results of in vitro anti-inflammatory experiments showed that the lipids may effectively consume ROS in cells. Meanwhile, the lipoplexes significantly reduced the expression levels of TNF-α mRNA and related inflammatory factors in macrophages. After PEGylation, the lipoplex was used for the treatment of mouse colitis, and biodistribution results proved that the lipoplexes effectively aggregated in the intestine. The delivery system could not only response to the high ROS level at colitis via thioketal breaking, but also could assist in the treatment of inflammation by ROS consumption. The treatment results revealed that the levels of TNF-α mRNA and related inflammatory factors at the colon lesion were largely reduced, and the inflammatory symptoms were significantly relieved. Hematology test results indicated that the treatment was safe and induced no obvious side effects on mice. This study may shed light on the synergistic treatment for colitis via anti-inflammatory siRNA delivery and ROS depletion strategies. STATEMENT OF SIGNIFICANCE: Downregulation of inflammatory factors and reactive oxygen species (ROS) levels is critical in treating colitis. In the present study, a series of ROS-responsive lipid molecules based on the Zn-DPA headgroup and thioketal linkage were synthesized for delivering TNF-α siRNA and for treating colitis. In addition to silencing the expression of TNF-α mRNA and the related inflammatory factors, the material also achieved synergistic treatment by simultaneous consumption of ROS in the colon lesion. In vitro cell experiments and in vivo colitis treatment in mice showed that the lipoplex exerted a satisfactory therapeutic effect on colitis, and the symptoms of colitis in mice were significantly alleviated. The present study may shed light on the synergistic treatment for colitis through anti-inflammatory siRNA delivery and ROS depletion strategies.

7.
Front Vet Sci ; 9: 852545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433897

RESUMO

Objective: This study was conducted to investigate the effects of different oligosaccharides on the growth performance and intestinal function in broilers. Methods: A total of 360 1-day-old yellow-feather chickens were randomly divided into 5 groups and fed with a basal diet supplemented with 50 mg/kg chlortetracycline (ANT), 3 g/kg isomalto-oligosaccharide (IMO), 3 g/kg raffinose oligosaccharide (RFO), and 30 mg/kg chitooligosaccharide (COS). The experiment lasted for 56 days, with 1-28 days as the starter phase and 29-56 days as the grower phase. Results: The results showed that dietary supplementation with RFO and COS significantly improved average daily gain (ADG) and average daily feed intake (ADFI) (p < 0.05). Relative to the control group, diets supplemented with oligosaccharides dramatically increased the level of serum IgM (RFO, COS), T-SOD (COS), and GSH-Px (IMO and RFO) and the expression of ZO-1(IMO) and claudin-1 (RFO) (p < 0.05). Adding antibiotics or oligosaccharides to the diet could remarkedly increase the villus height and villus height (VH)/crypt depth (CD) ratio of each group (p < 0.05). Through the ileum α-diversity analysis and comparison of OTU number in each group showed that the microbial richness of the IMO group increased in the starter phase, and that of the RFO and CSO group increased in the grower phase. Additionally, compared with the control group, IMO supplementation increased the level of ileum sIgA (p < 0.05) and the content of valeric acid (p < 0.05) in the cecum. Conclusions: In summary, the addition of oligosaccharides in diet can improve the immune function and antioxidant capacity and improve intestinal health of broilers.

8.
J Hepatol ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35452693

RESUMO

BACKGROUND & AIMS: Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests that VMP1 plays a critical role in lipoprotein secretion in zebra fish and cultured cells. However, the pathophysiological roles and mechanisms by which VMP1 regulates lipoprotein secretion and lipid accumulation in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are unknown. METHODS: Liver-specific and hepatocyte-specific Vmp1 knockout mice as well as Vmp1 knockin mice were generated by crossing Vmp1flox or Vmp1KI mice with albumin Cre mice or by injecting AAV8-TBG-cre, respectively. These mice were characterized for lipid and energy metabolism, metabolomics and transcriptome analyses. Hepatic VMP1 overexpressed mice fed on a NASH diet were also characterized. RESULTS: Hepatocyte-specific deletion of Vmp1 severely impaired VLDL secretion resulting in massive hepatic steatosis, hepatocyte death, inflammation and fibrosis, which are hallmarks of NASH. Mechanistically, loss of Vmp1 led to decreased hepatic levels of phosphatidylcholine and phosphatidylethanolamine as well as the changes of phospholipid composition. Deletion of Vmp1 in mouse liver also led to neutral lipids accumulated in endoplasmic reticulum (ER) bilayer and impaired mitochondrial beta-oxidation. Overexpression of VMP1 ameliorated steatosis in diet-induced NASH by improving VLDL secretion. Importantly, we also show decreased liver VMP1 is associated with NAFLD/NASH in humans. CONCLUSIONS: Our results provide novel insights on the role of VMP1 in regulating hepatic phospholipid synthesis and lipoprotein secretion in the pathogenesis of NAFLD/NASH. LAY SUMMARY: Lack of hepatic VMP1 in mice decreases levels of phospholipids and causes impaired lipoprotein secretion and fatty acid ß oxidation resulting in the development of NASH. Decreased VMP1 is associated with human NAFLD/NASH. Overexpression of VMP1 ameliorates diet-induced impaired VLDL secretion and NAFLD in mice.

9.
J Anim Sci ; 100(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35417554

RESUMO

This study was aimed to investigate the effects of dietary arctiin (ARC) supplementation (100, 200, and 400 mg/kg) on the growth performance and immune response of broilers after a Salmonella pullorum (S. pullorum) challenge, and we conducted in vitro antibacterial test to explore the bacteriostatic mechanism of ARC. The in vivo trial was randomly assigned to six groups: noninfected control (NC) group and positive control (PC) group received a basal diet; TET group, received a basal diet supplemented with 100 mg/kg chlortetracycline; ARC100, ARC200, and ARC400 groups received a basal diet containing 100, 200, and 400 mg/kg ARC, respectively. From days 14 to 16, all birds (except the NC group) were infected with 1 mL (1 × 108 CFU per mL) fresh S. pullorum culture by oral gavage per day. In vivo results showed that dietary supplementation of 200 mg/kg ARC significantly increased average daily gain (P < 0.05) and decreased feed-to-gain ratio of broilers vs. the PC group during days 15 to 28 after being challenged with S. pullorum (P < 0.05). The jejunal crypt depth (CD) was decreased by supplementing 100 or 200 mg/kg ARC in diets compared with PC birds at day 19 (P < 0.05). The jejunal villi height (VH) was increased by supplementing 100, 200, or 400 mg/kg ARC in diets compared with PC birds at day 28 (P < 0.05). Besides, dietary supplementation of 200 mg/kg ARC increased the jejunal VH to CD ratio than the PC group both at days 19 and 28 (P < 0.05). Notably, the broilers had lower serum lipopolysaccharide and diamine oxidase levels in the ARC100 and ARC200 groups at day 28 than those in the PC group (P < 0.05). Furthermore, in comparison to PC birds, the birds in ARC groups (100, 200, and 400 mg/kg) had higher serum contents of IgM and IL-10, and the birds in the ARC200 group had higher serum contents of IgA at day 19 (P < 0.05). At day 28, the birds in ARC groups (100, 200, and 400 mg/kg) had lower serum contents of IL-8, and the birds in the ARC200 group had lower serum contents of IFN-γ compared with PC birds (P < 0.05). The in vitro experiment showed that ARC significantly inhibited the biofilm formation and adhesion of S. pullorum (P < 0.05). Metabonomics analysis revealed that ARC can restrain the formation of the biofilm by affecting a variety of metabolic pathways of S. pullorum. Therefore, dietary supplementation of 200 mg/kg ARC might be a potential way to substitute antibiotics to control S. pullorum infection in broilers.


Pullorosis caused by Salmonella pullorum (S. pullorum) is a severe contagious disease and could cause great economic loss to the poultry industry. Antibiotics are usually used to control pullorosis, while prolonged use of antibiotics has led to the emergence of multidrug-resistant bacterial strains. Therefore, it is necessary to find safer and more effective alternatives to substitute antibiotics. In this study, we established a model of S. pullorum infection in broilers and conducted in vitro antibacterial test to explore the preventive effect and mechanisms of dietary arctiin (ARC) supplementation on S. pullorum infection in broilers. The results showed that ARC could not only improve the immune function of infected broilers by regulating the immune system but also directly inhibit the invasion of S. pullorum to broilers by inhibiting the formation and adhesion rate of S. pullorum biofilm. Dietary supplementation of 200 mg/kg ARC might be a potential way to substitute antibiotics to control S. pullorum infection in broilers.

10.
J Microbiol Biotechnol ; 32(6): 1-10, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35484971

RESUMO

EHT1 and EEB1 are the key Saccharomyces cerevisiae genes involved in the synthesis of ethyl esters during wine fermentation. We constructed single (Δeht1, Δeeb1) and double (Δeht1Δeeb1) heterogenous mutant strains of the industrial diploid wine yeast EC1118 by disrupting one allele of EHT1 and/or EEB1. In addition, the aromatic profile of wine produced during fermentation of simulated grape juice by these mutant strains was also analyzed. The expression levels of EHT1 and/or EEB1 in the relevant mutants were less than 50% of the wild-type strain when grown in YPD medium and simulated grape juice medium. Compared to the wild-type strain, all mutants produced lower amounts of ethyl esters in the fermented grape juice and also resulted in distinct ethyl ester profiles. ATF2, a gene involved in acetate ester synthesis, was expressed at higher levels in the EEB1 downregulation mutants compared to the wild-type and Δeht1 strains during fermentation, which was consistent with the content of acetate esters. In addition, the production of higher alcohols was also markedly affected by the decrease in EEB1 levels. Compared to EHT1, EEB1 downregulation had a greater impact on the production of acetate esters and higher alcohols, suggesting that controlling EEB1 expression could be an effective means to regulate the content of these aromatic metabolites in wine. Taken together, the synthesis of ethyl esters can be decreased by deleting one allele of EHT1 and EEB1 in the diploid EC1118 strain, which may modify the ester profile of wine more subtly compared to the complete deletion of target genes.

11.
Microbiol Spectr ; 10(2): e0221121, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35262393

RESUMO

Pseudomonas aeruginosa is an opportunistic and nosocomial pathogen of humans with hundreds of its virulence factors regulated by quorum sensing (QS) system. Small noncoding RNAs (sRNAs) are also key regulators of bacterial virulence. However, the QS regulatory sRNAs (Qrrs) that have been characterized in P. aeruginosa are still largely unknown. Here, sRNA AmiL (PA3366.1) in the amiEBCRS operon of PAO1 was identified as a novel Qrr by transcriptome sequencing (RNA-Seq). The expression of AmiL was negatively regulated by the las or rhl system, of which RhlR probably inhibited its transcription. AmiL deletion mutant and overexpressing strains were constructed in PAO1. Broad phenotypic changes were found, including reduced pyocyanin synthesis, elastase activity, biofilm formation, hemolytic activity, and cytotoxicity, as well as increased rhamnolipid production and swarming motility. AmiL appears to be a new regulator that influences diverse QS-mediated virulence. Furthermore, AmiL directly targeted PhzC, a key member of pyocyanin synthesis. AmiL also negatively regulated lasI expression in the early growth of PAO1, but predominantly increased rhlI expression and C4-HSL production in the middle and late stages. Therefore, a novel QS-sRNA signaling cascade of las/rhl (RhlR)-AmiL-PhzC/las/rhl was demonstrated, and it will help to shed new light on the virulence regulatory network of P. aeruginosa PAO1. IMPORTANCE P. aeruginosa is a common nosocomial pathogen that causes diverse opportunistic infections in humans. The virulence crucial for infection is mainly regulated by QS. Small noncoding RNAs (sRNAs) involved in virulence regulation have also been identified in many bacteria. Recently, there is a growing interest in the new sRNA species, QS regulatory sRNAs (Qrrs). Understanding Qrrs-mediated regulation in P. aeruginosa virulence is therefore important to combat infection. In this study, a previously uncharacterized sRNA AmiL in PAO1 has been identified as a novel Qrr. It has been found to influence diverse QS-mediated virulence factors including pyocyanin, elastase, rhamnolipid, and hemolysin, as well as biofilm formation, swarming motility, and cytotoxicity. Furthermore, PhzC essential for pyocyanin synthesis was a direct target of AmiL. QS gene expression and C4-HSL production were also regulated by AmiL. This study provides insights into the roles of Qrr AmiL in modulating P. aeruginosa virulence.


Assuntos
Infecção Hospitalar , Pequeno RNA não Traduzido , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica , Humanos , Elastase Pancreática/genética , Elastase Pancreática/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Percepção de Quorum , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Virulência/genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
Food Funct ; 13(7): 3946-3956, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35293398

RESUMO

The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.


Assuntos
Colite Ulcerativa , Colite , Platycodon , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Sulfato de Dextrana , Fermentação , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Platycodon/metabolismo
13.
Biol Trace Elem Res ; 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35332437

RESUMO

Dental calculus is a potential material that can be used for assessing chronic exposure to trace heavy metals in oral cavity as it is a long-term reservoir. The aim of this study was to investigate the correlation between dental calculus copper levels and risk of oral submucous fibrosis (OSF) due to chewing dried areca-nut quids in Mainland China. This study included 34 OSF (grade 1) sufferers with dried areca-nut quids chewing as the patient group and 23 healthy individuals without areca-nut chewing as the control group. The dental calculus sample was obtained from all 57 participants and evaluated by inductively coupled plasma mass spectrometry (ICP-MS) for dental calculus level of copper. This work revealed that the mean copper level of dental calculus was significantly higher in OSF (grade 1) sufferers with areca-nut chewing than those in healthy individuals without areca-nut chewing (p < 0.001). This work provided an evidence to support that there may be a positive correlation between elevated levels of copper in dental calculus caused by chewing dried areca-nut quids and an increased risk of developing OSF in Mainland China.

14.
Comput Math Methods Med ; 2022: 2474951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265167

RESUMO

Particle crowd algorithmic rule is a mayor examination hotspot in the authentic optimization algorithmic rule respond. Based on the PSO algorithmic rule to make optimal the RBFNN example, an amended order of nonlinear adaptable laziness power supported on the contest of population variegation is intended to extend the fixedness of population unlikeness performance and hunt capabilities to preclude the algorithmic rule from dripping into a topical extreme point prematurely, thereby further improving the prophecy correctness. Simulation experience shows that the amended PSO-RBFNN standard has open advantageous in the fixedness and sharp convergency of the prognosis proceed. In fashion to reprove the justness of reverse kinematics of robots with composite make and supercilious degrees of liberty, an amended adaptative suffix abound optimization (IAPSO) is spoken. First, the motoric equality of the 6-DOF strength-example avaricious robot design is established by the amended DH (Denavit-Hartenberg) argument course; second, on the base of the existent morsel abound algorithmic rule, the population Manhattan ceremoniousness is interested to lead the maneuver condition of the population in aqiqiy measure. And bound the adaptative lore substitute accordingly to the dissimilar maneuver possession and then adopt distinct site and hurry update modes; lastly, the fitness province with handicap substitute is present to trial the honest-prick and extended course transposition of the robot mold, and the delusion is not joint product major than 0.005 rad. The feint inference shows that the established kinematics shape is chasten, and the amended algorithmic program captures into recital the nicety, uniqueness, and velocity of the inverted resolution of the existent PSO algorithmic program, as well as higher deliverance truths. We conduct an experiment on the Brazilian jiu-jitsu. The results have clearly shown the advantage of our method.


Assuntos
Algoritmos , Exercício Físico/fisiologia , Indicadores Básicos de Saúde , Brasil , Biologia Computacional , Simulação por Computador , Teste de Esforço/estatística & dados numéricos , Nível de Saúde , Humanos , Artes Marciais/fisiologia , Redes Neurais de Computação , Dinâmica não Linear , Aptidão Física/fisiologia
15.
Purinergic Signal ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35235139

RESUMO

Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35235199

RESUMO

Overcoming the bacterial infection and promoting angiogenesis are challenge and imperious demands in wound healing and skin regeneration. Hereby, we developed a multifunctional AMP/S1P@PLA/gelatin wound dressing fabricated by electrospinning poly (L-lactic acid) (PLA)/gelatin with antimicrobial polypeptides (AMPs) and sphingosine-1-phosphate (S1P) in order to inhibit the bacteria growth and induce angiogenesis. In our work, AMP/S1P@PLA/gelatin wound dressing was obtained by two-step method of electrospinning and dopamine adsorption. Our results showed that incorporating AMP into PLA/gelatin nanofibrous membranes significantly improved antibacterial properties against both Escherichia coli and Staphylococcus aureus. S1P releasing from AMP/S1P@PLA/gelatin nanofibrous membranes could significantly enhance tube formation. Simultaneously, we found that the AMP/S1P@PLA/gelatin nanofibrous membranes facilitated the adhesion, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) and murine fibroblast (L929). AMP/S1P@PLA/gelatin membranes could also accelerate infected wound healing and skin regeneration by antibacterial and pro-angiogenesis effects. In summary, our developed AMP/S1P@PLA/gelatin nanofibrous membranes could be multifunctional dressing for infected wound healing and skin regeneration. Schematic figure to describe the characterizations and preparation of AMP/S1P@PLA/gelatin nanofibrous membranes.

17.
Environ Toxicol ; 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35297523

RESUMO

Benzo(a)pyrene(B(a)P), as the main representative of polycyclic aromatic hydrocarbons, can promote inflammation and many chronic pulmonary diseases. However, the underlying mechanism of Benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced human bronchial epithelial cell pyroptosis related to endoplasmic reticulum stress (ERS) has not been elucidated. This study focused on the effects of BPDE on ERS and pyroptosis in human bronchial epithelial cells (BEAS-2B), and explored the relationship between ERS and pyroptosis. BEAS-2B cells were stimulated with 0.50, 0.75, and 1.00 µmol/L BPDE for 24 h to detect ERS and pyroptosis. After inhibition of ERS with 4-phenylbutyrate (4-PBA), pyroptosis of BEAS-2B cells was tested. The results showed that BPDE decreased the cell viability, changed the morphological structure of endoplasmic reticulum and increased the expression levels of GRP78 and p-PERK. After BPDE treatment, the cell membrane was damaged and incomplete under transmission electron microscope; Hoechst 33342/PI fluorescence staining showed that the number of PI-positive cells was enhanced. The expression levels of GSDMD-N, cleaved-caspase 1, and cleaved-IL-1ß were elevated, and the expression levels of IL-1ß, IL-18, and NLRP3 protein were improved. In BPDE combined with 4-PBA intervention group, the rate of PI-positive cells was reduced, the expression levels of GRP78, GSDMD-N, and cleaved-caspase 1 were decreased, and the expression levels of IL-1ß, IL-18, and NLRP3 were decreased. In conclusion, BPDE could induce ERS and pyroptosis in BEAS-2B cells, and ERS may promote the occurrence of BPDE-induced pyroptosis.

18.
Int J Biol Sci ; 18(4): 1363-1380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280694

RESUMO

Cancer-associated adipocytes (CAAs), which are adipocytes transformed by cancer cells, are of great importance in promoting the progression of breast cancer. However, the underlying mechanisms involved in the crosstalk between cancer cells and adipocytes are still unknown. Here we report that CAAs and breast cancer cells communicate with each other by secreting the cytokines leukemia inhibitory factor (LIF) and C-X-C subfamily chemokines (CXCLs), respectively. LIF is a pro-inflammatory cytokine secreted by CAAs, which promotes migration and invasion of breast cancer cells via the Stat3 signaling pathway. The activation of Stat3 induced the secretion of glutamic acid-leucine-arginine (ELR) motif CXCLs (CXCL1, CXCL2, CXCL3 and CXCL8) in tumor cells. Interestingly, CXCLs in turn activated the ERK1/2/NF-κB/Stat3 signaling cascade to promote the expression of LIF in CAAs. In clinical breast cancer pathology samples, the up-regulation of LIF in paracancerous adipose tissue was positively correlated with the activation of Stat3 in breast cancer. Furthermore, we verified that adipocytes enhanced lung metastasis of breast cancer cells, and the combination of EC330 (targeting LIF) and SB225002 (targeting C-X-C motility chemokine receptor 2 (CXCR2)) significantly reduced lung metastasis of breast cancer cells in vivo. Our findings reveal that the interaction of adipocytes with breast cancer cells depends on a positive feedback loop between the cytokines LIF and CXCLs, which promotes breast cancer invasion and metastasis.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Adipócitos/metabolismo , Neoplasias da Mama/metabolismo , Retroalimentação , Feminino , Humanos , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Neoplasias Pulmonares/metabolismo
19.
AIDS Care ; : 1-6, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287504

RESUMO

ABSTRACTSecondary distribution of HIV self-test is promising to increase testing uptake while the facilitators and barriers of secondary distribution remain unclear. In-depth interviews were conducted with 22 MSM who had participated in secondary distribution of HIVST in southern China. Data were thematically analyzed to capture participants' motivations, procedures, and challenges when accessing and distributing self-tests. MSM in China are willing to distribute HIVST to members in their social network, but their decision-making is impacted by their ability to broach sexual health conversations, evaluations of the recipients, and perceived trustworthiness of the self-test. Our study suggested that several strategies, including creating a friendly environment for sexual health conversations and establishing nationwide policies related to quality assured self-tests and standardized self-testing protocols, may be helpful to advance this approach in China.

20.
FEBS Lett ; 596(8): 1037-1046, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35182431

RESUMO

Wnt signalling pathways play pivotal roles in development, homeostasis and human diseases, and are tightly regulated. We previously identified Tiki as a novel family of Wnt inhibitory proteases. Tiki proteins were predicted as type I transmembrane proteins and can act in both Wnt-producing and Wnt-responsive cells. Here, we characterize Tiki proteins as glycosylphosphatidylinositol (GPI)-anchored proteases. TIKI1/2 proteins are enriched on the detergent-resistant membrane microdomains and can be released from the plasma membrane by GPI-specific glycerophosphodiesterases GDE3 and GDE6, but not by GDE2. The GPI anchor determines the cellular localization of Tiki proteins and their regulation by GDEs, but not their inhibitory activity on Wnt signalling. Our study uncovered novel characteristics and potential regulations of the Tiki family proteases.


Assuntos
Glicosilfosfatidilinositóis , Peptídeo Hidrolases , Endopeptidases/metabolismo , Glicosilfosfatidilinositóis/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Peptídeo Hidrolases/metabolismo , Transdução de Sinais/fisiologia
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