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1.
Food Chem ; 349: 129112, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33581437

RESUMO

Zein/low-acyl gellan gum (GG) composite particles (ZGPs) were fabricated to stabilize Pickering emulsions (termed "ZGPEs"). The wettability of ZGPs was manipulated simply by adjusting the concentration of GG. The effects of GG concentration, oil fraction and pH on ZGPEs were systematically evaluated by confocal laser scanning microscopy (CLSM), cryo-scanning electron microscopy (cryo-SEM), dynamic light scattering technique, stimulated emission depletion (STED) nanoscopy and rheology. The results showed that ZGPEs exhibited robust colloidal properties and distinct advantage over other previously reported zein-polysaccharide-based Pickering emulsions. CLSM, STED and cryo-SEM analyses revealed that the network structures formed by GG and ZGPs at the continuous phase and oil-water interface were the main contributors to the emulsion's characteristics. This study provides insights into the fabrication of food-grade Pickering emulsions with distinct characteristics that impart favorable properties to various foods and bioactive delivery systems.

2.
Crit Rev Food Sci Nutr ; : 1-19, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427492

RESUMO

Cardiovascular diseases (CVDs) rank as the first leading cause of death globally. High dietary polyphenol (especially flavonoids) intake has strongly been associated with low incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. Phytogenic flavonoids affect the physiological and pathological processes of CVDs by modulating various biochemical signaling pathways. Non-coding RNAs (ncRNAs) have attracted increasing attention as fundamental regulator of gene expression involved in CVDs. Among the different ncRNA subgroups, long ncRNAs (lncRNAs) have recently emerged as regulatory eukaryotic transcripts and therapeutic targets with important and diverse functions in health and diseases. lncRNAs may be associated with the initiation, development and progression of CVDs by modulating acute and chronic inflammation, adipogenesis and lipid metabolism, and cellular physiology. This review summarizes this research on the modulatory effects of lncRNAs and their roles in mediating cellular processes. The mechanisms of action of flavonoids underlying their therapeutic effects on CVDs are also discussed. Based on our review, flavonoids might facilitate a significant epigenetic modification as part (if not full) of their tissue-/cell-related biological effects. This finding may be attributed to their interaction with cellular signaling pathways involved in chronic diseases. Certain lncRNAs might be the target of specific flavonoids, and some critical signaling processes involved in the intervention of CVDs might mediate the therapeutic roles of flavonoids.

3.
Nat Struct Mol Biol ; 28(2): 128-131, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33402708

RESUMO

The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its receptor binding domain in two conformations, the receptor-accessible 'up' or receptor-inaccessible 'down' states. Here we report that the commonly used stabilized S ectodomain construct '2P' is sensitive to cold temperatures, and this cold sensitivity is abrogated in a 'down' state-stabilized ectodomain. Our findings will impact structural, functional and vaccine studies that use the SARS-CoV-2 S ectodomain.


Assuntos
Glicoproteína da Espícula de Coronavírus/química , Anticorpos Antivirais/química , Temperatura Baixa , Microscopia Crioeletrônica , Ensaio de Imunoadsorção Enzimática , Humanos , Desnaturação Proteica , Domínios Proteicos , Estabilidade Proteica , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Ressonância de Plasmônio de Superfície
4.
Environ Res ; 195: 110682, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33434607

RESUMO

Bioavailability of phosphorus (P) has close relationship with the microbial community in sediments and plays an important role in the sedimentary P release. However, little is known about the relationship between P bioavailability and microbial community under capping conditions. A 62-day experiment was conducted by capping with modified calcium peroxide ceramsite (MCPC) at different addition dosages (from 1:1 to 1:4, the ratio of mobile P in sediment to MCPC). P disappearance and release were expressed by the dissolved inorganic P (DIP) in overlying water. The results show that the proportion of disappeared P in released P was reduced sharply from 44% (Control) to 2% (1:4) under the capping with MCPC. Under the capping, the concentrations of DIP and Fe(Ⅱ) in pore water decreased markedly compared with the control, the removal up to 71.6% and 59.3% (mean, P < 0.05), respectively. The bioavailable P (BAP) presented the obvious decline under the capping with MCPC, which indicates the inhibition on the algae growth. The algae available P (AAP), water soluble P (WSP) and readily desorbable P (RDP) were reduced obviously at the 1:2 ratio compared with the other ratios. On the contrary, the biggest increase of Olsen-P in sediment was at the 1:2 ratio. This may be the explanation why the disappearance of DIP in the pore water was found. The result of microbial community structures in sediment shows that the relative abundance of Proteobacteria and Nitrospirae increased under the MCPC capping. It is analyzed that the microbial diversity is related negatively with the BAP in the sediments under the capping with MCPC, suggesting that microbial diversity is the key to control the BAP.

5.
Aging (Albany NY) ; 13(3): 4428-4451, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428594

RESUMO

A recent study has reported that tsukushi (TSKU) may be related to the development of lung cancer. However, few studies focused on if TSKU associated with the prognosis and immune infiltration cells in non-small cell lung cancer (NSCLC). The effect of TSKU expression on prognosis with NSCLC was analyzed in the PrognoScan database and validated in The Cancer Genome Atlas. The composition of tumor infiltrating cells was quantified by methylation and expression data. We combined levels of tumor infiltrating cells with TSKU to evaluate the survival of patients. The analysis of a cohort (GSE31210, N=204) of lung cancer patients demonstrated that high TSKU expression was strongly associated with poor overall survival (P =1.90E-05). The combination of high TSKU expression and low infiltration B cells identified a subtype of patients with poor survival in NSCLC. Besides, the proportion of B cells in NSCLC patients with TSKU hypermethylation were higher than those patients with TSKU hypomethylation (P <0.001). Overall, high TSKU expression combined with low infiltration of B cells may associate with a poor prognosis of NSCLC patients. TSKU might be a potential prognostic biomarker involved in tumor immune infiltration in NSCLC.

6.
Science ; 371(6526): 255-260, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446550

RESUMO

Many plant specialized metabolites function in herbivore defense, and abrogating particular steps in their biosynthetic pathways frequently causes autotoxicity. However, the molecular mechanisms underlying their defense and autotoxicity remain unclear. Here, we show that silencing two cytochrome P450s involved in diterpene biosynthesis in the wild tobacco Nicotiana attenuata causes severe autotoxicity symptoms that result from the inhibition of sphingolipid biosynthesis by noncontrolled hydroxylated diterpene derivatives. Moreover, the diterpenes' defensive function is achieved by inhibiting herbivore sphingolipid biosynthesis through postingestive backbone hydroxylation products. Thus, by regulating metabolic modifications, tobacco plants avoid autotoxicity and gain herbivore defense. The postdigestive duet that occurs between plants and their insect herbivores can reflect the plant's solutions to the "toxic waste dump" problem of using potent chemical defenses.


Assuntos
Diterpenos/metabolismo , Glucosídeos/biossíntese , Herbivoria , Manduca/fisiologia , Esfingolipídeos/biossíntese , Tabaco/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Hidroxilação , Manduca/enzimologia , Oxirredutases/antagonistas & inibidores , Oxirredutases/metabolismo , Tabaco/enzimologia
7.
Food Funct ; 12(3): 1305-1317, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33439200

RESUMO

Nobiletin, a polymethoxyflavone widely present in the peel of citrus fruits, has significant anti-inflammatory activity. Autophagy plays a critical role in maintaining cell homeostasis by promoting the degradation of intracellular structures in response to various stress. Recent research suggests the involvement of autophagy in the inflammatory process and therefore some inflammation-related diseases. However, the "cross-talk" between autophagy and nobiletin's anti-inflammation response remains not well elucidated. Therefore, this study was initiated with the aim of investigating the role of autophagy in nobiletin's protective effect against inflammation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results showed that nobiletin significantly (P < 0.05) inhibited the release of nitric oxide (NO) and decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Moreover, nobiletin significantly (P < 0.05) promoted autophagy as evidenced by the appearance of more autophagosomes, up-regulated LC3II protein, low-regulated p62 protein, and increased autophagy-related (Atg) genes' expression compared with the control treated with LPS alone. Addition of chloroquine, an autophagy inhibitor, alleviated nobiletin's anti-inflammatory effect, further supporting the requirement of an active autophagy process for the citrus peel flavonoid's biological activity. Mechanistically, we found that nobiletin treatment leads to activation of the IL-6/STAT3/FOXO3a signal pathway through the down-regulation of IL-6 and STAT3 phosphorylation and the upregulation of FOXO3a phosphorylation in the cell nucleus, which is responsible for induction of macrophage autophagy. Taken together, our study provides evidence that nobiletin suppresses inflammatory response through enhancing autophagy through activating the IL-6/STAT3/FOXO3a pathway in macrophage cells.

8.
Semin Cancer Biol ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33453404

RESUMO

In-depth insights in cancer biology over the past decades have highlighted the important roles of epigenetic mechanisms in the initiation and progression of tumorigenesis. The cancer epigenome usually experiences multiple alternations, including genome-wide DNA hypomethylation and site-specific DNA hypermethylation, various histone posttranslational modifications, and dysregulation of non-coding RNAs (ncRNAs). These epigenetic changes are plastic and reversible, and could potentially occur in the early stage of carcinogenesis preceding genetic mutation, offering unique opportunities for intervention therapies. Therefore, targeting the cancer epigenome or cancer epigenetic dysregulation with some selected agents (called epi-drugs) represents an evolving and promising strategy for cancer chemoprevention and therapy. Phytochemicals, as a class of pleiotropic molecules, have manifested great potential in modulating different cancer processes through epigenetic machinery, of which green tea polyphenol epigallocatechin-3-gallate (EGCG) is one of the most extensively studied. In this review, we first summarize epigenetic events involved in the pathogenesis of cancer, including DNA/RNA methylations, histone modifications and ncRNAs' dysregulations. We then focus on the recently discovered roles of phytochemicals, with a special emphasis on EGCG, in modulating different cancer processes through regulating epigenetic machinery. We finally discuss limitations of EGCG as an epigenetic modulator for cancer chemoprevention and treatment and offer potential strategies to overcome the shortcomings.

9.
Crit Rev Food Sci Nutr ; : 1-11, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33401939

RESUMO

With increasing awareness of environmental protection, petroleum-based raw materials are continuously decreasing, which in turn necessitated the development of eco-friendly sustainable biomaterials, as alternative strategy. Starch could be an ideal substitute. Corn starch has been used as a renewable material for development of biodegradable packaging, owing to great varieties, low cost, large-scale industrial production, and good films forming properties. Unfortunately, its poor mechanical and barrier properties have limited the application of starch-based films. Thence, plasticizers were added to overcome the aforementioned pitfalls and improve the films elongation, distribution, flexibility, elasticity, and rigidity. Addition of plasticizers can change the continuity and therefore would enhance the properties of corn starch-based films. While plasticization can improve the tensile strength and percent elongation, it can reduce the water resistance in prepared films. Herein, we focused on changes of starch granules during gelatinization process, types of biodegradable films, as well as the types of modified starch with plasticizers. Furthermore, the influence of plasticizers on corn starch-based films and the physicochemical properties of various types of corn starch-based films were also addressed.

10.
Fish Physiol Biochem ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405063

RESUMO

This study investigated the effect of stocking density on growth performance, blood biochemical profiles, antioxidative capacity, and muscle quality of gibel carp (Carassius gibelio). Gibel carps (initial body weight 57.04 ± 1.89 g) were reared at high stocking density (HSD, 10.85 kg m-3), medium stocking density (MSD, 5.06 kg m-3), and low stocking density (LSD, 1.47 kg m-3) for 60 days. The LSD group exhibited the highest growth rate, while HSD significantly inhibited fish growth. The muscular compositions of crude fat, crude ash, and moisture were significantly changed by stocking density, but crude protein content did not differ significantly. The stocking density altered the muscular texture profiles of gibel carp. Compared to either the HSD group or the MSD group, the highest levels of resilience and springiness occurred in the LSD group. Significant differences were observed in the levels of plasma glucose, alanine aminotransferase, aspartate aminotransferase, cholesterol, and creatinine among three groups. The fish exhibited the highest level of plasma cortisol as well as the lowest levels of triiodothyronine and thyroxine in the HSD group. The fish stocked in the LSD group showed the highest activities of superoxide dismutase, glutathione peroxidase, and catalase as well as the highest content of glutathione in liver. The significant highest total antioxidant capacity occurred in the fish stocked in the LSD group. The results showed that HSD resulted in chronic crowding stress, and exerted negative impact on growth performance, muscle quality, and antioxidative capacity of gibel carp.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33507375

RESUMO

INTRODUCTION: Osteoarthritis (OA), which has a high incidence in the elderly, brings a huge economic burden to society. MSCs (Mesenchymal Stem Cells) have shown great multidirectional differentiation potential which are expected to treat OA, and numerous clinical trials have been conducted. However, the efficacy and safety of the MSCs still need to be further integrated and analyzed. MATERIALS AND METHODS: We searched several databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, Ovid, and ScienceDirect) for assessing eligible trials that randomized controlled trials, hyaluronic acid as control, and MSCs injection to treat OA. Vitro studies and animal studies were excluded. Search terms were: "cartilage," "clinical trial," "mesenchymal," "stromal" and "stem cell", "osteoarthritis". The preliminary guidelines and study protocol were published online at PROSPERO. RESULTS: Many assessment scales could not be improved significantly after 6 months. However, most of the scales were significantly improved after 12 months, indicating that compared with hyaluronic acid, stem cells could relieve OA symptoms significantly. No serious adverse effect was found. CONCLUSION: There are significant therapeutic effects on joint function, symptoms, and no permanent adverse effect has been found after stem cell treatment. It is promising to apply intro-articular injection of stem cells for OA to clinical application. More researches are needed to supplement present deficiencies.

12.
Ecotoxicol Environ Saf ; 207: 111578, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254423

RESUMO

Cadmium (Cd), an environmental pollutant, is evidenced to cause hepatotoxicity. In this study, the potential protective effect of caffeic acid phenethyl ester (CAPE) on cadmium-induced liver damage was investigated. Forty male mice were treated daily with either CdCl2 (1.5 mg/kg body weight (b.w.), gavage) or CAPE (10 µmol/kg b.w., gavage) or both for 4 weeks. CAPE administration significantly reduced Cd level and liver and body weight, and increased AST, ALT and ALP level. Moreover, CAPE prevented CdCl2-induced oxidative stress via PI3K/Akt/mTOR pathway and inhibited apoptosis by regulating apoptosis markers. CAPE also suppressed the CdCl2-induced inflammation by reducing the inflammatory mediators, including TNF-α, IL-6 and IL-1ß. Furthermore, CAPE alleviated CdCl2-induced reduction of TLR4. It should be noted that this effect was achieved by targeting miR-182-5p, and CAPE improved miR-182-5p level. The improvement of the liver tissue histopathology by CAPE confirmed the biochemical data. These results show for the first time that miR-182-5p/TLR4 axis involved in CAPE's protection against CdCl2-induced hepatotoxicity, and may provide novel insights into the treatment of cadmium-related diseases.


Assuntos
Cádmio/toxicidade , Ácidos Cafeicos/farmacologia , Poluentes Ambientais/toxicidade , Álcool Feniletílico/análogos & derivados , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Inflamação , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , MicroRNAs/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Papel (figurativo) , Receptor 4 Toll-Like/metabolismo
13.
J Hazard Mater ; 407: 124737, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33321372

RESUMO

In recent years, special attention has been devoted to biodemulsifiers as a new type of environment-friendly demulsifiers. A novel biodemulsifying oxalate decarboxylase (OxdC) secreted by Bacillus mojavensis XH1 is reported in the present study. A genome-wide comparison showed that strains with high demulsification efficiencies all possess alkane degradation genes. An analysis of the differentially expressed genes and proteins induced by different substrates showed that OxdC secreted by XH1 was an effective demulsifier. Moreover, the demulsification ability was verified by prokaryotic gene expression, knockout and complementation analyses. OxdC from XH1 exhibited a strong demulsification capacity and significantly outperformed the model protein Bacillus subtilis 168 OxdC (Yvrk), which shared a high amino acid similarity but showed limited demulsification ability. Based on a comparison of the structural characteristics, the hydrophobic amino acids on the surface of OxdC were identified as a key factor driving the favorable demulsification activity of XH1. The metabolic pathways of XH1 used liquid paraffin and glucose as substrates, illustrating that hydrocarbons are necessary for biodemulsifier secretion. The present study provides new insight into the application of OxdC as an additional genetic resource in biodemulsification.

14.
Environ Sci Technol ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256403

RESUMO

To understand the chemical evolution of dust in the current East Asian atmosphere, the chemistry of PM2.5 and size-resolved aerosols in Shanghai, China, during the 2019 dust storm event was investigated. Our results showed that concentrations of SO42- in the city during the event highly correlated with Ca2+ and Na+ due to the direct emissions of CaSO4 and Na2SO4 from the upwind deserts. In contrast, during the event, NO3- linearly correlated with NH4+ at a molar ratio close to 1:1, and both almost entirely stayed in coarse particles, suggesting they accumulated on the dust surface as NH4NO3. Based on the field observations and laboratory smog chamber simulations, we found that NO2 and O3 in Shanghai during the dust period reacted to form N2O5, which subsequently hydrolyzed into HNO3 on the surface of saline mineral dusts (e.g., CaSO4 and Na2SO4) and was further neutralized by NH3 as NH4NO3. The relative abundances of NO3- and NH4+ in Shanghai during the dust event were notably higher than those a decade ago, indicating that this heterogeneous formation of NH4NO3 on dust was enhanced by the abundantly coexisting NOx, O3, and NH3 in the current East Asian atmosphere, which should be considered in future modeling studies.

15.
Sci Total Environ ; : 143741, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33288259

RESUMO

The diacid chemistry of summertime PM2.5 and the size-segregated aerosols (9-stages) in Chongming Island, a coastal site in the Yangtze River Delta (YRD), China, were investigated. Our results showed that oxalic acid (C2) was the dominant dicarboxylic acid, followed by succinic acid (C4), malonic acid (C3), adipic acid (C6) and phthalic acid (Ph). Two types of haze pollution events were identified during the sampling period, i.e., Event I, which was mainly caused by the local biomass burning emission, and Event II, which was caused by a long-distance transport of the YRD urban pollution. C2 linearly correlated with SO42- and NO3- in Event I but only with O3 in Event II, indicating that oxalic acid formation was dominated by the aerosol aqueous phase oxidation in Event I and by the gaseous phase oxidation in Event II, respectively. 65.5% of Cl- in sea salts at the site in the clean period was depleted and robustly correlated with oxalic acid (R2 = 0.74). We proposed a mechanism to explain such a significant Cl- depletion, in which anthropogenic VOC oxidize into oxalic acid and its precursors such as glyoxal and methyglyoxal by a photochemical oxidation, and then oxalic acid and the related compounds subsequently react with sea salts and release HCl into the troposphere. The significant Cl- depletion of sea salts related with the organic acid (C2) in coastal China was found for the first time and should be considered in future studies, because oxalic acid and related SOA in the country are abundant and the released HCl may effectively enhance the oxidation capacity of the atmosphere by photolytically producing Cl radicals.

16.
Animals (Basel) ; 10(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266274

RESUMO

In a cold climate, ensuring indoor air quality and heat preservation simultaneously has always been a difficult problem in the poultry house. The current study was carried out in order to determine the effects of chronic low temperature and ammonia concentration on productive performance and egg quality of commercial laying hens. 576 18-week-old Hy-line Brown hens were used in this study. Birds were housed in cages and received for 20-week exposure to low temperature and ammonia in six artificial environmental chambers. Birds were randomly assigned into six treatments: treatment 1 (T1, 20 °C, ≤5 ppm, control group), treatment 2 (T2, 20 °C, 20 ppm), treatment 3 (T3, 20 °C, 45 ppm), treatment 4 (T4, 8 °C, ≤5 ppm), treatment 5 (T5, 8 °C, 20 ppm) and treatment 6 (T6, 8 °C, 45 ppm). Daily feed intake (DFI), feed efficiency (FE), egg production (EP) and body weight (BW) were recorded and calculated from 19 weeks of age. Egg samples were collected at 22, 26, 30, 34 and 38 weeks of age and egg weight (EW), shell breaking strength (SBS), albumen height (AH), yolk weight (YW), shell weight (SW), shell thickness (ST) and Haugh unit (HU) were measured. The results of the present study indicated that low temperature and excessive ammonia decreased the EP of hens compared with those of the T1 birds. Low temperature increased DFI of hens thereby FE showed significant differences among treatments. During the early period of the experiment, low temperature treatment increased the BW of laying hens, but this trend of increase was suppressed by the treatment of ammonia with the prolongation of the experimental period. Egg quality was also affected by low temperature and excessive ammonia. At different experimental periods, egg quality traits of hens exposed to the cold and ammonia stress presented significant differences compared to those of control birds. The present study indicated that the effect of ammonia was more pronounced on hens than that of low temperature at the early and peak laying period in terms of several main traits of productive performance and egg quality under long term hens breeding.

17.
Nutr Cancer ; : 1-10, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33356605

RESUMO

The Geriatric Nutritional Risk Index (GNRI) is widely applied as a prognostic factor in different cancers. We aimed to analyze the prognostic value of the GNRI in 257 patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Patients with GNRI >98, 92-98, and <92 were grouped into normal, low risk and moderate/high risk groups, respectively. There were 45.1% patients at risk for malnutrition. Kaplan-Meier survival curves indicated that patients with lower GNRI scores had a poorer overall survival (OS). Two-year OS for normal, low risk and moderate/high risk groups were 57.4%, 42.3% and 15.8%, respectively. In multivariate survival analysis, GNRI (<92), body mass index (BMI, ≥24 kg/m2), combined therapy, hemoglobin and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS. Stratifying by age groups, GNRI (<92), hemoglobin and NLR were independent prognostic factors of OS in patients aged <65 years. GNRI (<92), smoking, BMI (≥24 kg/m2) and platelet-to-lymphocyte ratio were independent prognostic factors of OS in patients aged ≥65 years. In conclusion, GNRI was a significant prognostic factor in advanced NSCLC patients regardless of age. A decreased GNRI may be considered as a clinical trigger for nutritional support in advanced NSCLC patients, though additional studies are still required to confirm the best cut-point.

18.
Immunohorizons ; 4(11): 713-728, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172842

RESUMO

Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 transcripts are significantly elevated in PBMCs from HIV-1-infected individuals, making broadly HIV-1-neutralizing Abs compared with those without broadly neutralizing Abs; however, the role of Rab11FiP5 in immune functions remains unclear. In this study, a RAB11FIP5 gene knockout (RAB11FIP5 -/-) mouse model was employed to study the role of Rab11Fip5 in immune responses. RAB11FIP5 -/- mice exhibited no perturbation in lymphoid tissue cell subsets, and Rab11Fip5 was not required for serum Ab induction following HIV-1 envelope immunization, Ab transcytosis to mucosal sites, or survival after influenza challenge. However, differences were observed in multiple transcripts, including cytokine genes, in lymphocyte subsets from envelope-immunized RAB11FIP5 -/- versus control mice. These included alterations in several genes in NK cells that mirrored observations in NKs from HIV-infected humans expressing less RAB11FIP5, although Rab11Fip5 was dispensable for NK cell cytolytic activity. Notably, immunized RAB11FIP5 -/- mice had lower IL4 expression in CD4+ T follicular helper cells and showed lower TNF expression in CD8+ T cells. Likewise, TNF-α production by human CD8+ T cells correlated with PBMC RAB11FIP5 expression. These observations in RAB11FIP5 -/- mice suggest a role for Rab11Fip5 in regulating cytokine responses.

19.
Ann Transl Med ; 8(20): 1305, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209885

RESUMO

Background: Hepatocellular carcinoma (HCC) is the fourth most common malignant tumor in China. Temozolomide (TMZ) is a common chemotherapy drug which can effectively kill HCC cells in vitro. However, it is possible that HCC cells possess intrinsic resistance to TMZ. A key mechanism of TMZ resistance is the overexpression of O6-methylguanine-DNA methyltransferase (MGMT). Studies have shown that MAPK may be related to MGMT expression, U0126 is a highly selective inhibitor of MEK1 and MEK2, which were crucial molecule in cascade of mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway. Sorafenib was another widely applicated target drug in HCC which could inhibit multiple kinases including MAPK/ERK. This research was aimed to investigate the efficacy of MAPK/ERK inhibitor U0126 and sorafenib combine with TMZ in the treatment of HCC. Methods: In HCC cells, MAPK/ERK signaling pathway was blocked by U0126 and sorafenib. The effect of blocking MAPK/ERK signaling pathway on TMZ-induced cytotoxicity was evaluated by MTT assay, flow cytometry and TUNEL assay. DNA damage protein and the expression of MGMT were detected by Western-blot. After the downregulation of MAPK/ERK signaling pathway, MGMT mRNA expression and the protein expression of MGMT were quantified by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence assay, respectively. HepG2 cells were transfected with an MGMT over expression plasmid. After transfection, the effect of U0126 on TMZ-induced cytotoxicity was evaluated by MTT and Western-Blot in MGMT OE cells. The influence of Sorafenib on TMZ-induced cytotoxicity to HCC cells was also detected by MTT assay. Results: U0126 can enhance the chemosensitivity of HCC cells to TMZ. At the same time, we also found that U0126 increases the damage to DNA caused by TMZ in HepG2 cells. Moreover, the results from RT-qPCR and Western blot showed that U0126 downregulated MGMT mRNA and MGMT protein expression via blocking MAPK/ERK pathway. Furthermore, after transfection with an MGMT expression plasmid, overexpression of MGMT restored U0126-induced chemosensitivity to TMZ in HCC cells. Sorafenib can also increase the chemosensitivity of HCC cells to TMZ. Conclusions: Our studies suggest great clinical potential for the utilization of combined U0126 and TMZ in patients with advanced HCC.

20.
Environ Pollut ; : 115774, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33143982

RESUMO

Perfluorooctane sulfonate (PFOS) is one of the most widely used and distributed perfluorinated compounds proven to cause adverse health outcomes. Datasets of ecotoxico-genomics and proteomics have given greater insights for PFOS toxicological effect. However, the molecular mechanisms of hepatotoxicity of PFOS on post-translational modifications (PTMs) regulation, which is most relevant for regulating the activity of proteins, are not well elucidated. Protein glycosylation is one of the most ubiquitous PTMs associated with diverse cellular functions, which are critical towards the understanding of the multiple biological processes and toxic mechanisms exposed to PFOS. Here, we exploit the multilayered glycoproteomics to quantify the global protein expression levels, glycosylation sites, and glycoproteins in PFOS exposure and wild-type mouse livers. The identified 2439 proteins, 1292 glycosites, and 799 glycoproteins were displayed complex heterogeneity in PFOS exposure mouse livers. Quantification results reveal that 241 dysregulated proteins (fold change ≥ 2, p < 0.05) in PFOS exposure mouse livers were involved in the lipid and xenobiotic metabolism. While, 16 overexpressed glycoproteins were exclusively related to neutrophil degranulation, cellular responses to stress, protein processing in endoplasmic reticulum (ER). Moreover, the interactome and functional network analysis identified HP and HSP90AA1 as the potential glycoprotein biomarkers. These results provide unique insights into a deep understanding of the mechanisms of PFOS induced hepatotoxicity and liver disease. Our platform of multilayered glycoproteomics can be adapted to diverse ecotoxicological research.

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