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1.
Mycopathologia ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473910

RESUMO

Knowledge about the clinical and laboratory characteristics and prognosis of Talaromyces marneffei infection in children is limited. A retrospective study was conducted on pediatric patients with disseminated T. marneffei infection in a clinical setting. Extracted data included demographic information (age and sex), clinical features, laboratory findings, treatment, and prognosis. Eleven HIV-negative children were enrolled. The male/female ratio was 8:3. The median age of onset was 17.5 months (3.5-84 months). The mortality rate in these children was 36.36% (4/11). Seven children had underlying diseases. All of the children had multiple immunoglobulin abnormalities and immune cell decline. Ten children received voriconazole treatment, and most of the children (7/10) had a complete response to therapy at primary and long-term follow-up assessment; only three children died of talaromycosis. One patient recovered from talaromycosis but died of leukemia. The child who received itraconazole treatment also showed clinical improvement. No adverse events associated with antifungal therapies were recorded during and after the treatment. Talaromycosis is an indicator disease for undiagnosed severe immunodeficiencies in children. Awareness of mycoses in children by pediatricians may prompt diagnosis and timely treatment. Voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection in non-HIV-infected children.

2.
J Med Genet ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501240

RESUMO

BACKGROUND: Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. METHODS AND RESULT: We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF. CONCLUSIONS: Our experimental observations performed on both human subjects and on Cfap65-mutated mice demonstrate that the presence of biallelic mutations in CFAP65 causes the MMAF phenotype and impairs sperm motility.

3.
Mikrochim Acta ; 186(9): 611, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396712

RESUMO

A colorimetric test is described for the rapid detection of Staphylococcus aureus (SA). Gold nanorods (AuNRs) are first labeled with urease and yolk immunoglobulin (IgY). This probe can specifically bind SA. In the next step, nonspecific magnetic beads and sample are added. This leads to the formation of the AuNR-IgY-SA-nMB immunocomplex which is then magnetically separated. Finally, a solution of urea is added to the supernatant. Ureases catalyzes the decomposition of urea which results in an increase in the pH value. The increase in the pH value is detected by using a phenolphthalein test paper which undergoes a color change from white to pink. The analytical process can be completed within 20 min. The method is highly specific and can detect as little as 476 cfu·mL-1. It was verified by analyzing contaminated Chinese cabbage and beef samples, and 1000 cfu·mL-1 of SA were accurately detected. Graphical abstract Schematic representation of a colorimetric method for the detection of Staphylococcus aureus based on the immunocomplex formed from dual-labeled gold nanorod (AuNR) probe, bacteria and non-specific magnetic bead (nMB). This method can be completed within 20 min.

4.
Int J Biol Macromol ; 139: 277-289, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377289

RESUMO

It remains a crucial challenge to achieve efficient cellular uptake in tumor cells for nanoscale drug delivery systems. This work described that two multi-functional pullulan nanogels were prepared by co-polymerization between methacrylated pullulan (Pullulan-M) and different crosslink agents, an acid-labile ortho ester-modified pluronic (L61-MOE) or non-acid-sensitive methacrylated pluronic (L61-M). The prepared nanogels showed a regular spherical structure with the size about 200 nm measured by dynamic light scattering and transmission electron microscopy (TEM). Doxorubicin as a model drug was successfully encapsulated into nanogels. As expected, Pul-L61-MOE showed pH-dependent DOX release, and 25% of DOX was released at pH 7.4 while 84.48% of DOX was released at pH 5.0. In vitro cellular uptake and MTT results indicated that pH-sensitive nanogels (Pul-L61-MOE) displayed higher cellular internalization and cytotoxicity than acid-insensitive nanogels (Pul-L61-M) and free DOX. Flow cytometry assay suggested these nanogels remarkably increased intracellular reactive oxygen species (ROS) level and induced more cell apoptosis by the function of pluronic. Finally, in vivo antitumor results indicated that the multi-functional nanogels exhibit supreme antitumor efficiency, and the tumor growth inhibition (TGI) was 83.37%. Therefore, the pH-sensitive pullulan nanogels can be potential nano-carriers for drug delivery in tumor treatment.

5.
Environ Sci Technol ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31412697

RESUMO

Effluents from wastewater treatment facilities are reclaimed for environmental and landscaping use, resulting in infiltration to groundwater. Trace organic contaminants in these effluents have raised concerns, including the antibiotic resistance contributor sulfamethoxazole (SMX) detected frequently at concentrations exceeding 0.01 µg/L. A push-pull study to evaluate in situ degradation of SMX was undertaken in a shallow alluvial aquifer at the Tongzhou groundwater experimental site in southeast suburban Beijing. Ambient groundwater (1000 L) extracted from an experimental well at a depth of 10 m was spiked with SMX and NaBr, and then injected back into the same well. SMX and Br were "stored" over 15 days and monitored in the experimental well and 4 multilevel (depth: 10, 15, 17.5, 20, 25, and 30 m) observation wells located within 2-3 m distance. The concentration of SMX decreased faster than that of Br in the experimental and one observation well at 10 m depth; samples from all other depths contained little Br and SMX. The half-life of SMX degradation is estimated to be 3.1 ± 0.2 and 6.5 ± 0.6 days in the experimental well and observation well, respectively, under suboxic/anoxic conditions.

6.
World J Pediatr ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31456156

RESUMO

BACKGROUND: Mumps is a common type of respiratory infectious disease caused by mumps virus (MuV), and can be effectively prevented by vaccination. In this study, a reverse genetic system of MuV that can facilitate the rational design of safer, more efficient mumps vaccine candidates is established. METHODS: MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArt™ High-Order Genetic Assembly System, and was rescued via reverse genetic technology. RT-PCR, sequencing, and immunofluorescence assays were used for rMuV-S79 authentication. Viral replication kinetics and in vivo experimental models were used to evaluate the replication, safety, and immunogenicity of rMuV-S79. RESULTS: A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy, and a robust reverse genetic system of MuV-S79 was successfully established. The established rMuV-S79 strain could reach a high virus titer in vitro. The average viral titer of rMuV-S79 in the lung tissues was 2.68 ± 0.14 log10PFU/g lung tissue, and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats. Neutralizing antibody titers induced by rMuV-S79 were high, long-lasting and could provide complete protection against MuV wild strain challenge. CONCLUSION: We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines. rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo. It could also provide complete protection against MuV wild strain challenge.

7.
Mol Ther Nucleic Acids ; 17: 726-740, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31437653

RESUMO

The α-synuclein aggregates are the main component of Lewy bodies in Parkinson's disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology.

8.
Lipids Health Dis ; 18(1): 160, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391046

RESUMO

BACKGROUND: Epidemiological studies have confirmed atmospheric PM2.5 could affect asthma, and dyslipidemia may be related to pathogenesis of asthma. Recent studies show Notch ligands had lipid combination domains which are responsible for regulating lipid levels. However, the effect of PM2.5 on asthmatic rats' lipid levels and the role of Notch signaling pathway is unclear. METHODS: Rats were treat with ovalbumin (OVA) to establish asthma models. Notch signaling pathway inhibitor (DAPT) was injected intraperitoneally. Asthmatic and healthy rats were exposed to different concentrations of PM2.5. Lung tissues were collected and the expression of Hes1 protein was detected by Western Blot. Blood samples were collected to detect the serum lipid levels. RESULTS: Hes1 expression levels in healthy and asthma pathway inhibition groups were lower than those in control groups. Compared with control group, rats exposed to PM2.5 in middle and high dose, the levels of TG and TC were decreased. Similar results were observed after exposure to the same concentration of PM2.5 in asthmatic rats. Rats, which were exposed to PM2.5 after being established the asthma model successfully, could exhibit more significant dyslipidemia than those with direct exposure. After Notch signaling pathway inhibited, TC and LDL in asthma pathway inhibition group were lower than those in healthy group. CONCLUSIONS: PM2.5 can affect the lipid levels of asthmatic rats through the Notch signaling pathway.

9.
FEBS Open Bio ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433577

RESUMO

Polycystic ovary syndrome (PCOS) is a major cause of anovulatory sterility in women, and most PCOS patients exhibit hyperandrogenism (HA). Liver kinase b1 (LKB1) is a tumor suppressor that has recently been reported to be involved in PCOS. However, the mechanism by which LKB1 affects HA has not previously been elucidated. We report here that ovarian LKB1 levels are significantly decreased in a female mouse model of HA. Moreover, we report that LKB1 expression is inhibited by elevated androgens via activation of androgen receptors. In addition, LKB1 treatment was observed to suppress androgen synthesis in theca cells and promote estrogen production in granulosa cells by regulating steroidogenic enzyme expression. As expected, LKB1 knockdown inhibited estrogen levels and enhanced androgen levels, and LKB1-transgenic mice were protected against HA. The effect of LKB1 appears to be mediated via IGF-1 signaling. In summary, we describe here a key role for LKB1 in controlling sex hormone levels.

10.
Exp Dermatol ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31461795

RESUMO

Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphomas (CTCL). Shank-associated RH domain-interacting protein (SHARPIN) participates in the initiation and development of multiple tumors. However, the clinical significance of SHARPIN in MF hasn't been investigated. The c-Jun N-terminal kinases (JNKs) pathway is a member of mitogen-activated protein kinases (MAPKs). Its dysregulation is observed in various tumors including CTCL, whereas the roles of JNKs pathway in MF remain largely unknown, the relationship between SHARPIN and JNKs pathway remains elusive. Herein, we showed that upregulated expression of SHARPIN was related to poor prognosis of MF patients. In vitro experiments found increased SHARPIN expression and activation of JNKs pathway in MF cell line MyLa2059. SHARPIN induced transforming growth factor ß activated kinase-1 (TAK1) transcription, which is an upstream kinase of JNKs, NF-κB and p38 pathway, leading to activation of JNKs and NF-κB pathway. SHARPIN also promoted p38 signalling independent of TAK1 expression, by which overexpression of SHARPIN induced cell proliferation, inhibited apoptosis, enhanced migration and invasion of MyLa2059. Our work provided direct evidences for effects of SHARPIN on JNKs and NF-κB pathway, and the contributing roles of JNKs, NF-κB and p38 pathway regulated by SHARPIN in the development of MF.

11.
Nutr Metab Cardiovasc Dis ; 29(10): 1040-1049, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377179

RESUMO

BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

12.
Hematol Oncol ; 2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31378958

RESUMO

To determine the incidence, risk factors, and relative survival of acute myeloid leukemia (AML) secondary to myelodysplastic syndrome (MDS) in the Surveillance, Epidemiology, and End Results (SEER) database. Retrospective analysis of all patients with new MDS onset in the SEER-18 database from 2001 to 2013. We identified 36 558 patients with primary MDS. The rate of secondary AML (sAML) was 3.7% among patients 40 years or younger and 2.5% among those older than 40 (P = .039). The median transformation interval was significantly shorter for the younger group (4.04 vs 13.1 mo; P < .001). For both age groups, median overall and cancer-specific survival were significantly longer for patients who did not develop sAML. Although the younger patients survived longer than the older patients, sAML development had a more negative effect on the survival of younger patients. Female sex, age, and World Health Organization (WHO) type MDS with single lineage dysplasia (MDS-SLD) were associated with a decreased risk of sAML for older but not younger patients. Among older patients with MDS, a married status, Black race, female sex, shorter time to sAML, and WHO type MDS-SLD or MDS with ringed sideroblasts were favorable prognostic factors for survival. In the SEER database, the rate of sAML among patients with MDS is lower than that in previous reports, but these patients still have worse survival. Risk assessment should include clinical and demographic factors.

13.
World J Pediatr ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31377975

RESUMO

BACKGROUND: To describe mumps virus (MuV) used as a vector to express enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) genes. METHODS: Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses (rMuVs). rMuVs were recovered based on our reverse genetic system of MuV-S79. The properties of rMuVs were determined by growth curve, plaque assay, fluorescent microscopy and determination of fluorescent intensity. RESULTS: Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79, expressed heterologous genes in high levels, and were genetically stable in at least 15 passages. CONCLUSION: rMuV-S79 is a promising platform to accommodate foreign genes like marker genes, other antigens and immunomodulators for addressing various diseases.

15.
Phytochemistry ; 166: 112075, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351332

RESUMO

Isoflavonoids are one of the most important groups of naturally occurring antioxidants. Their structural features are important for evaluating their antioxidative activity. In this work, density functional theory (DFT) methods were applied to investigate the influence of the C2=C3 double bond on the antioxidative activity of isoflavonoids based on three currently accepted radical scavenging mechanisms from the viewpoint of thermodynamics. The C2=C3 double bond can make the compounds more flat, which would extend the conjugated system in the molecule and make the isoflavonoids higher antioxidant activity. The C2=C3 double bond would not alter the strongest antioxidative hydroxyl group of the isoflavonoids. In the gas, benzene and CHCl3 phases, the C2=C3 double bond will enhance the antioxidative activity of isoflavonoids by lowering the bond dissociation enthalpies of the hydroxyl groups in the B ring that are the strongest antioxidative sites for the hydrogen atom transfer (HAT) mechanism. In polar phases, a similar result is obtained by weakening the proton affinity of 7-OH that is the strongest antioxidative hydroxyl group in the sequential proton loss electron transfer (SPLET), mechanism. Thus, the C2=C3 double bond will enhance the antioxidative activity of isoflavonoids irrespective of the studied phases.

16.
Endocrine ; 65(3): 531-541, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313224

RESUMO

OBJECTIVE: Reporting Items for Clinical Practice Guidelines (CPGs) in HealThcare (RIGHT) checklist was used as a tool to assess the reporting quality of 2014-2018 CPGs on diabetes treatment, aiming to promote the application of RIGHT and improve the reporting quality of future guidelines. METHODS: We searched Chinese Biomedical Literature Service System (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP database, Medline, Embase, Allied, and Complementary MEdicine Database (AMED), and Medlive and Google Scholar (Google academics), and collected published CPGs on diabetes with published date during 1st January, 2014 and 7th November, 2018. CPGs on diabetes issued since 2014 were included and filtered by two reviewers independently. Then the basic information extraction and RIGHT evaluation of the included CPG are carried out. RESULTS: A total of 34 guidelines were included, out of which 7 are for Chinese and 27 for other countries. Overall, basic information (domain 1) got the highest (64.66%) reporting rate, while financing and conflict-of-interest statements and management (domain 6) got the lowest (8.1%). For all guidelines, classification of guidelines (item 1c) was sufficiently reported, and description of the specific sources of funding for all stages of guideline development (item 18a) was not reported. For Chinese CPGs, financing and conflict-of-interest statements and management (domain 6) was most insufficiently reported, and only identification of guideline in the title (item 1a), corresponding information of the developer or author (item 4), description of basic epidemiology (item 5), and subgroup description (item 7b) out of 22 items were better reported than foreign guidelines. CONCLUSIONS: Overall, the CPGs on diabetes during 2014-2018 adhered to ~41% RIGHT checklist, of which Chinese CPGs adhered less than that of foreign guidelines. It is suggested that the RIGHT reporting checklist should be endorsed and used by CPG developers to ensure higher quality and adequate use of guidelines.

17.
Virology ; 535: 171-178, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31306912

RESUMO

Human respiratory syncytial virus (RSV) is one of the predominant pathogens causing lower respiratory tract infection in infants and young children worldwide, whereas there is so far no vaccine or drug against RSV infection for clinical use. In this work, we developed and validated a fluorescence-based high-throughput screening (HTS) assay to identify compounds active against RSV, using RSV-mGFP, a recombinant RSV encoding enhanced green fluorescent protein (EGFP). Thereafter, among 54,800 compounds used for our screen, we obtained 62 compounds active against RSV. Among these hits, azathioprine (AZA) and 6-mercaptopurine (6-MP) were identified as RSV inhibitors with half maximal inhibitory concentration (IC50) values of 6.69 ±â€¯1.41 and 3.13 ±â€¯0.98 µM, respectively. Further experiments revealed that they functioned by targeting virus transcription or/and genome replication. In conclusion, the established HTS assay is suitable to screen anti-RSV compounds, and the screened two hits of AZA and 6-MP, as potential anti-RSV agents targeting RSV genome replication/transcription, are worthy of further investigation on their anti-RSV activity in vivo.

18.
Mol Nutr Food Res ; : e1900249, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31271251

RESUMO

BACKGROUND: Calorie restriction (CR) is a therapeutically effective method for nonalcoholic fatty liver disease. However, the compliance of the CR method is relatively poor. New CR methods are needed. METHODS AND RESULTS: Each week, mice are given a 5-day high-fat diet (HFD) ad libitum plus 2 days of an intermittent calorie restriction (ICR) diet (50% calorie restriction) consisting of yogurt, fruit, and vegetables, for 16 weeks. The effect of the ICR diet model on the fatty liver of mice is examined. Compared with continuous HFD-fed mice, the mice feeding HFD+ICR have lower body weight and hepatic steatosis, reduced serum lipid and transaminase levels, increased fatty acid oxidation gene of Cpt1a, and decreased hepatic lipid synthesis gene of Pparγ and Srebf-1c, as well as improved insulin resistance and lower level of inflammation. Moreover, ICR reverses the dysbacteriosis in HFD group, including the lower Shannon diversity indexes and lower abundance of Lactobacillus. CONCLUSION: An ICR diet consisting of yogurt, fruit, and vegetables attenuates the development of HFD-induced hepatic steatosis in mice. Furthermore, HFD+ICR diet is associated with a different fecal microbiota that tends to be more similar to normal diet controls.

19.
ACS Appl Mater Interfaces ; 11(32): 28597-28609, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31314480

RESUMO

An ortho-ester-linked indomethacin (IND) dimer-based nanodrug delivery system was prepared to improve the therapeutic effect of doxorubicin (DOX) by reversing the multidrug resistance. The synthesized dimer (IND-OE) could form stable nanoparticles (IND-OE/DOX) loaded with DOX via the single-emulsion method. Compare to insensitive nanoparticles (IND-C12/DOX), IND-OE/DOX showed a rapid degradation behavior and accelerated drug release at mildly acidic environments. In vitro cell experiments verified that IND-OE nanoparticles could increase DOX concentration due to the efficient intracellular drug release by the degradation of the ortho ester as well as reduced DOX efflux by IND-mediated P-gp downregulation. In vivo studies further demonstrated that IND-OE/DOX displayed the maximized synergetic antitumor efficacy than free DOX or IND-C12/DOX, and the tumor inhibition rates versus saline were 46.78% (free DOX), 60.23% (IND-C12/DOX), and 80.62% (IND-OE/DOX). Overall, this strategy of combination with chemosensitizers and ortho ester linkage has great potential to serve as an amplifying chemotherapy platform against various drug-resistant tumors.

20.
Food Funct ; 10(8): 5046-5058, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31359016

RESUMO

Human and bovine milk fat globule membrane (MFGM) proteins have been identified and characterized; however, their glycosylation during lactation remains unclear. We adopted a glycoproteomics approach to profile and compare MFGM N-glycoproteomes in human and bovine milk during lactation. A total of 843, 718, 614, and 273 N-glycosite peptides corresponding to 465, 423, 334, and 176 glycoproteins were identified in human colostrum, human mature milk, bovine colostrum, and bovine mature milk, respectively. The biological functions of these MFGM N-glycoproteins were revealed through bioinformatics. Substantial differences were observed between human and bovine milk, and immune-related MFGM N-glycoproteins varied between colostrum and mature milk from both species. Our results expand current knowledge of MFGM N-glycoproteomes, and further demonstrate the complexity and biological functions of MFGM N-glycosylation. These data can provide references for the application of bovine MFGM N-glycoproteins in infant formula to resemble human milk and in functional foods.

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