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2.
Mol Immunol ; 120: 43-51, 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050111

RESUMO

Food protein-induced allergies are primarily aggravated due to imbalance immune responses. Earlier studies by different research groups have reported that the intervention of Lactobacillus pentosus (L. pentosus) S-PT84 can modulate T-helper (Th)1/Th2 balance through regulatory T cells and can effectively promote type 1 immunity by activating dendritic cells and natural killer cells, such biological activity makes L. pentosus S-PT84 a potential mediation in controlling food allergy. Thus, this study aimed to evaluate the effects of L. pentosus S-PT84 against egg ovalbumin (OVA)-induced allergic response in mice. BALB/c mice (n = 12/group) were sensitized with OVA (50 µg/mice) via intraperitoneal injection (IP) for four weeks and subsequently administered with three different doses of L. pentosus S-PT84 via pelleted diet. The allergenic status was assessed by clinical signs, serum histamine, mouse mast cell protease (MMCP) level, and antibody activity, cytokines level in splenocytes, and expression of T regulatory cells (T-regs) in blood. The intervention of L. pentosus S-PT84, precisely at the high dose (0.6 % L. pentosus S-PT84 in pelleted diet) group, significantly reduced the clinical allergenic symptoms and reduced the histamine and MMCP levels in serum. However, the intervention of L. pentosus S-PT84 did not affect the OVA-specific IgE, IgG concentration, but led to lower the total IgE and IgG titers, suggesting that the therapeutic effect of L. pentosus S-PT84 may be due to development of immune tolerance. Moreover, differences in the immune response were observed after L. pentosus S-PT84 intervention, as it significantly reduced the production of IL-4, IL-17, and increased the population of CD25+Foxp3+ cells. Thus, it can be concluded that the intervention of L. pentosus S-PT84 provides a potential therapeutic strategy to reduce the chicken egg OVA-induced allergic symptoms.

3.
Bioresour Technol ; 303: 122949, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32058907

RESUMO

Reduction in water consumption and increase in ethanol concentration are two main challenges for bioethanol production from lignocellulosic materials. To address the two challenges, the aim of this work was to study the production of bioethanol from unwashed-pretreated rapeseed straw (RS) at high solid loading. RS pretreated with 1% (w w-1) H2SO4 at 160 °C for 10 min resulted in excellent digestibility and fermentability of pretreated RS. The unwashed-pretreated RS was subjected to presaccharification and fed-batch simultaneous saccharification and fermentation (P-FB-SSF) at a final solid loading of 22% (w w-1). Ethanol concentration and ethanol yield of 53.1 g L-1 (equivalent to 4.1% (w w-1) based on fermentation slurry) and 72.4% were obtained, respectively. In total, 92.1 g water g-1 ethanol was consumed, a much smaller amount than that observed with washing after pretreatment or fermentation performed at lower solid loading.

4.
Andrology ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020786

RESUMO

BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia. CBAVD is mainly caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene and is also related to the X-linked ADGRG2 (adhesion G protein-coupled receptor G2) gene. Genetic screening and counseling strategies for Chinese CBAVD populations remain controversial because the genetic background of CBAVD in Chinese population is largely unknown. OBJECTIVES: In this study, we aimed to study the mutation spectrum of CFTR and ADGRG2 in a group of CBAVD patients and to evaluate sperm retrieval outcomes in a subset of CBAVD patients. MATERIALS AND METHODS: Next-generation targeted sequencing was used to identify mutations in the CFTR and ADGRG2 genes in 38 CBAVD patients. In addition, we followed and analyzed nine of the 38 patients who were undergoing sperm retrieval surgery. RESULTS: In total, 27 of 38 (71.05%) patients carried at least one likely pathogenic or pathogenic mutation in CFTR or ADGRG2. In addition to the IVS9-5T allele, 15 CFTR and 1 ADGRG2 mutations were identified, including 4 novel mutations. CFTR hot-spot mutations were not identified in our study. Sperm was successfully obtained in all nine patients who underwent MESA or TESE surgery, but most patients had sperm with relatively low motility and high abnormality rates. DISCUSSION AND CONCLUSION: Except for the IVS9-5T allele, hot-spot mutations of CFTR may not exist in Chinese CBAVD patients. Therefore, next-generation targeted sequencing for whole CFTR and ADGRG2 gene may be the appropriate genetic testing method, and genetic counseling may be different from Caucasian populations. We observed a high success rate of sperm retrieval with relatively low motility and high abnormality rates in Chinese CBAVD patients. However, this is only a weak conclusion due to the small sample size.

5.
Clin Rheumatol ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32036586

RESUMO

OBJECTIVE: The diagnosis of relapsing polychondritis (RP) is often mistaken or delayed. In this retrospective cohort, we aimed to unveil the causes responsible for such phenomenon, to determine the associated factors, and to compare diagnosis in clinical settings with the current diagnostic criteria. METHOD: Eighty-seven RP patients followed-up by rheumatologists from January 1, 2008, to October 31, 2018, were retrospectively analyzed. RESULTS: A total of 50 male and 37 female patients were included with a mean age of 45.9 ± 14.5 years. Ninety-three percent were initially admitted by non-rheumatologic specialists .Twenty-eight percent were correctly diagnosed, while 72% were misdiagnosed at the first visits, all by non-rheumatologic specialists. Patients admitted by non-rheumatologic specialists had increased odds of misdiagnosis (odds ratio [OR] = 1.3, 95% confidence interval [95% CI] 1.1-1.7, P = 0.000). Fifty-seven (65.5%) patients did not meet with Michet or Damiani criteria, with 16 (18.4%) patients diagnosed as partial RP and 41( 47.1%) patients diagnosed as limited RP. CONCLUSIONS: Incorrect and delayed diagnosis of RP is common in our cohort, and insufficient awareness of the disease in non-rheumatologic specialists at least partially contributes to this. It is imperative to revise the current criteria for early diagnosis.Key Points• Diagnosing relapsing polychondritis (RP) in early stage remains challenging after all these years, especially among non-rheumatologic specialists, indicating the importance of teaching non-rheumatologic specialists to improve their understanding of this rare disease.• Many RP patients did not fully meet with the current criteria, suggesting that revision of the current criteria is imperative for early diagnosis of this rare disease.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32052078

RESUMO

Dendritic cells are crucial for the initiation and regulation of immune responses against cancer and pathogens. DCs are heterogeneous and highly specialized antigen-presenting cells. Human DCs comprise several subsets with different phenotypes and functional properties. In the steady state, human DC subsets have been well studied. However, the components of DC subsets and their immune functions during the inflamed setting are poorly understood. We identified and characterized DC subsets in the malignant pleural effusions of NSCLC patients. We analyzed the capacity of these DC subsets to induce T-cell differentiation. We observed the presence of inflammatory DCs (infDCs) and macrophages in the malignant pleural effusions of NSCLC patients, as identified by the CD11C+HLA-DR+CD16-BDCA1+ and CD11C+HLA-DR+CD16+BDCA1- phenotypes, respectively. InfDCs represented approximately 1% of the total light-density cells in the pleural effusion and were characterized by the expression of CD206, CD14, CD11b, and CD1α, which were absent on blood DCs. InfDCs also expressed CD80, although at a low level. As infDCs did not express CD40, CD83 and CD275, they remained functionally immature. We found that TLR agonists promoted the maturation of infDCs. Compared with macrophages, infDCs had a weaker capacity to phagocytose necrotic tumor cell lysates. However, only infDCs induced autologous memory CD4+ T-cell differentiation into Th1 cells. For the first time, we found that infDCs were present in the malignant pleural effusions of NSCLC patients. We conclude that infDCs represent a distinct human DC subset and induce Th1 cell differentiation in the presence of TLR agonists.

8.
Epigenomics ; 12(2): 101-125, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31920098

RESUMO

Aim: Circular RNAs (circRNAs) still have many potential functions in the process of tumor development that are not completely understood. The study aims to explore novel circRNAs and their mechanisms of action in breast cancer (BCa). Materials & methods: A combination strategy of RNA-sequencing (RNA-seq) technique, quantitative real-time PCR and bioinformatic analysis was employed to identify the potential mechanisms involving differentially expressed circRNAs in the serum exosomes and tissues of BCa patients. Results: The expression levels of hsa-circRNA-0005795 and hsa-circRNA-0088088 were significantly different both in serum exosomes and tissues and might function as competing endogenous RNAs and play vital roles in BCa development. Conclusion: We constructed two circRNA-miRNA networks and provided new insight into the prognosis and therapy of BCa using circRNAs from serum exosomes.

9.
Nat Immunol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932812

RESUMO

Cancer cells subvert immune surveillance through inhibition of T cell effector function. Elucidation of the mechanism of T cell dysfunction is therefore central to cancer immunotherapy. Here, we report that dual specificity phosphatase 2 (DUSP2; also known as phosphatase of activated cells 1, PAC1) acts as an immune checkpoint in T cell antitumor immunity. PAC1 is selectively upregulated in exhausted tumor-infiltrating lymphocytes and is associated with poor prognosis of patients with cancer. PAC1hi effector T cells lose their proliferative and effector capacities and convert into exhausted T cells. Deletion of PAC1 enhances immune responses and reduces cancer susceptibility in mice. Through activation of EGR1, excessive reactive oxygen species in the tumor microenvironment induce expression of PAC1, which recruits the Mi-2ß nucleosome-remodeling and histone-deacetylase complex, eventually leading to chromatin remodeling of effector T cells. Our study demonstrates that PAC1 is an epigenetic immune regulator and highlights the importance of targeting PAC1 in cancer immunotherapy.

10.
Steroids ; 156: 108583, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982422

RESUMO

Five undescribed ergostane-type C28 sterols, daturmetesides A-E (1-5), were isolated from the leaves of Datura metel L. The chemical structures of these new compounds were characterized through extensive spectroscopic analysis and comparison with literatures. Among them, the absolute structures of daturmetesides A and C were unambiguously determined by X-ray crystallography. The anti-inflammatory effect of daturmetesides A-E was all tested by measuring nitric oxide production in lipopolysaccharide-activated RAW264.7 cells. Daturmetesides A, C and D moderatelylowered the NO production with IC50 values ranging from 17.05 ± 0.35 to 24.88 ± 0.93 µM.

12.
J Cell Biochem ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898357

RESUMO

Cisplatin (CDDP) is commonly used for gastric cancer (GC) chemotherapy. However, after several CDDP-based treatment cycles, patients always acquire chemotherapy resistance, which limits the overall clinical efficacy of the treatment. Clarification of the mechanisms responsible for CDDP resistance is required to improve therapeutic outcomes for patients. Circular RNAs (circRNAs) are noncoding RNAs involved in the pathogenesis of cancer, although their role in the mechanism underlying CDDP resistance in GC remains unknown. In the present study, we explored the underlying roles of circRNAs in the modulation of CDDP resistance in CDDP-sensitive and CDDP-resistant human GC cells. Using RNA sequencing and quantitative reverse transcription polymerase chain reaction, expression of circFN1 (originating from exons 10, 11, and 12 of the FN1 gene hsa_circ_0058147) was higher in CDDP-resistant GC cells and tissues. CircFN1 upregulation in GC patients treated by CDDP was significantly correlated with aggressive biological behavior. CircFN1 promoted viability and inhibited apoptosis of GC cells exposed to CDDP in vivo and in vitro. Furthermore, circFN1 suppressed GC cell apoptosis by "sponging" miR-182-5p. These findings demonstrate the involvement of circFN1 in CDDP resistance of GC and implicate circFN1 as a therapeutic target for GC patients treated with CDDP. It provides novel evidence of the function of circRNAs as microRNA sponges and highlight a potential therapeutic target for extinguishing CDDP resistance in patients with GC.

13.
Autophagy ; : 1-16, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31959090

RESUMO

Mesenchymal stem cell (MSC) transplantation has been widely applied as a potential therapeutic for multiple diseases. However, the underlying therapeutic mechanisms are not fully understood, especially the paradox between the low survival rate of transplanted cells and the beneficial therapeutic effects generated by these cells. Herein, in a myocardial infarction (MI) model, we found that transplanted MSCs released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional recovery via regulating macroautophagy/autophagy in the recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. Then, in the ECs, ABs activated lysosome functions and promoted the expression of TFEB (transcription factor EB), which is a master gene in lysosomal biogenesis and autophagy. Finally, the increase in TFEB enhanced autophagy-related gene expression in ECs and promoted angiogenesis and cardiac functional recovery after MI. Collectively, we found that apoptotic donor MSCs promote angiogenesis via regulating autophagy in the recipient ECs, unveiling the role of donor cell apoptosis in the therapeutic effects generated by cell transplantation.Abbreviations: 3-MA: 3-methyladenine; ABs: apoptotic bodies; BECN1: beclin 1; CASP3: caspase 3; CQ: chloroquine; ECs: endothelial cells; EVs: extracellular vesicles; LAMP1: lysosomal-associated membrane protein 1; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MI: myocardial infarction; MSC: mesenchymal stem cell; NO: nitric oxide; TFEB: transcription factor EB; TUNEL: TdT-mediated dUTP Nick-End Labeling.

14.
J Virol ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996427

RESUMO

Human papillomavirus (HPV) type 58 is the third most commonly detected HPV type in cervical cancer among Eastern Asians. Our previous international epidemiological studies revealed that a HPV58E7 natural variant, T20I/G63S (designated as V1), was associated with a higher risk of cervical cancer. We recently showed that V1 possesses a greater ability to immortalise and transform primary cells, as well as degrading pRB more effectively than the prototype and other common variants. In this study, we performed a series of phenotypic and molecular assays using physiologically relevant in vitro and in vivo models to compare the oncogenicity of V1 with that of the prototype and other common natural variants. Through activation of AKT and K-Ras/ERK signalling pathways, V1 consistently showed greater oncogenicity compared with prototype and other variants, as demonstrated by increased cell proliferation, migration and invasion, as well as induction of larger tumours in athymic nude mice. This study complements our previous epidemiological and molecular observations pinpointing the higher oncogenicity of V1 compared with prototype and all other common variants. Since V1 is more commonly found in Eastern Asia, our report provides insight into the design of HPV-screening assays and selection of components for HPV vaccines in this region.IMPORTANCE Epidemiological studies have revealed that a wild type variant of HPV58 carrying an E7 variation, T20I/G63S (V1), is associated with a higher risk of cervical cancer. We previously reported that this increased oncogenicity could be the result of its greater ability to degrade pRB, thereby leading to an increased ability to grow in an anchorage-independent manner. In addition to this, this report further showed that this HPV variant induced activation of AKT and K-Ras/ERK signalling pathways, thereby, explaining its genuine oncogenicity in promoting cell proliferation, migration, invasion, and formation of tumours, all to a greater extent than prototype HPV58 and other common variants.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31941392

RESUMO

Effects of trehalose lipids produced from Rhodococcus erythropolis ATCC 4277 on phenanthrene (PHE) mineralization by two soil microorganisms were investigated. Biodegradation experiments were conducted, with and without the biosurfactant, in three batch systems: water, soil, and soil-water slurry. PHE sorption to the soil did not limit the mineralization by the test microorganisms, Pseudomonas strain R (PR) and Sphingomonas sp. strain P5-2 (SP5-2). Both microorganisms, however, demonstrated significant difference in the PHE mineralization capability in the systems. While SP5-2 mineralized PHE faster than PR in liquid culture, PR having more hydrophobic surface greatly exceeded SP5-2 in ability to access soil-sorbed PHE. While the addition of the biosurfactant little affected the apparent cell hydrophobicity of SP5-2, it substantially improved PHE mineralization by this strain in all systems tested. Contrary to SP5-2, the apparent cell hydrophobicity was significantly stimulated with increasing concentration of the biosurfactant for PR. However, the biosurfactant had no significant effect on PHE mineralization by this microorganism. The results demonstrated that the addition of the biosurfactant may have great potential for remediation of sites contaminated with polycyclic aromatic hydrocarbons but its effects and benefits may be dependent on characteristics of microorganisms involved and environmental conditions.

16.
Mikrochim Acta ; 187(2): 139, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955247

RESUMO

The authors have incidentally found that the three tandem repeats of a 13-mer G-rich oligomer (with sequence 5'-TGG GAA GGG AGG G-3'; referred to as G3) can directly fold into a stable G3 trimer. The G3 trimer/hemin DNAzyme exhibits an about 3-fold higher peroxidase-mimicking activity compared to the conventional G3/hemin DNAzyme. Combining this finding with rolling circle amplification (RCA), a colorimetric assay was developed for sensitive and specific determination of microRNA. In this method, each cycle of RCA generates three catalytic units. This leads to a significant signal amplification of the RCA. Using let-7a as a model analyte, the colorimetric method (best performed at 420 nm) exhibits high sensitivity toward microRNA-let-7a with a 37 fM detection limit and an analytical range that covers 3 orders of magnitude. The method was applied to the determination of let-7a in some cell lysates. Graphical abstractThis G-triplex trimer-based rolling circle amplification (RCA) method can produce three catalytic units per RCA cycle, which can significantly improve the amplification efficiency of RCA.

17.
CPT Pharmacometrics Syst Pharmacol ; 9(1): 48-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31749251

RESUMO

A two-analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody-conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non-Hodgkin lymphoma. A two-compartment model with a nonspecific, time-dependent linear clearance, a linear time-dependent exponentially declining clearance, and a Michaelis-Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two-compartment model. Population PK parameters, covariate effects, and interindividual variability of model parameters were estimated. The impact of clinically relevant covariates on PK exposures of each analyte were quantified and reported to support key label claims.

18.
Pain ; 161(2): 416-428, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31651582

RESUMO

Chronic pain and anxiety symptoms are frequently encountered clinically, but the neural circuit mechanisms underlying the comorbid anxiety symptoms in pain (CASP) in context of chronic pain remain unclear. Using viral neuronal tracing in mice, we identified a previously unknown pathway whereby glutamatergic neurons from layer 5 of the hindlimb primary somatosensory cortex (S1) (Glu), a well-known brain region involved in pain processing, project to GABAergic neurons in the caudal dorsolateral striatum (GABA). In a persistent inflammatory pain model induced by complete Freund's adjuvant injection, enhanced excitation of the Glu→GABA pathway was found in mice exhibiting CASP. Reversing this pathway using chemogenetic or optogenetic approaches alleviated CASP. In addition, the optical activation of Glu terminals in the cDLS produced anxiety-like behaviors in naive mice. Overall, the current study demonstrates the putative importance of a novel Glu→GABA pathway in controlling at least some aspects of CASP.

20.
Sci Total Environ ; 703: 134805, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31733499

RESUMO

Microplastics (MPs), polymer particles capable of adsorbing heavy metals from ambient environment, have been found in diverse human food resources. Through the consumption of MPs, heavy metals adsorbed on MPs might be transported into human body. This study aims to explore the behavior of heavy metal-contaminated MPs in human digestive system which is not previously researched. Firstly, a chromium (Cr) adsorption/desorption study was conducted with four commonly used nondegradable MPs [polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) and polystyrene (PS)] as well as one degradable MP (polylactic, PLA). Then, the whole digestive system in-vitro method (WDSM), a systematic model including mouth, gastric, small intestine, and large intestine digestive phases, was conducted on the Cr-loaded MPs. Additionally, the bioaccessibilities and hazard quotients (HQs) of Cr(VI) and Cr(III) were evaluated. Among five MPs, although PLA showed the weakest adsorption capacity for Cr, the Cr(VI) bioaccessibilities for PLA reached the highest values of 19.9%, 15.6% and 3.9% in gastric, small intestinal and large intestinal phases, respectively. The bioaccessibilities of Cr(VI) in gastric phase were significantly higher than those in other phases, while no Cr release from MPs was detected in the mouth phase. In gastric phase, the bioaccessibilities of Cr(VI) were significantly higher than those of Cr(III) in the gastric phase, and both of them approached to a similar level in intestinal phases. In the WDSM, the HQs of Cr(VI) and Cr(III) on MPs were lower than the critical level for both adults and children. Based on the measured bioaccessibilities, the maximum daily total Cr intake for different human groups (female children, male children, female adults and male adults) through MP consumption was estimated from 0.50 to 1.18 µg/day. In general, the five tested MPs were potential to serve as Cr vectors in the WDSM.

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