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1.
Molecules ; 24(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623198

RESUMO

Monosialotetrahexosylganglioside (GM1) has good activity on brain diseases and was developed to be a drug applied in clinics for neurological disorders and nerve injury. It is difficult to isolate GM1 in industry scale from the brains directly. In this work, a simple and highly efficient method with high yield was developed for the isolation, conversion, and purification of GM1 from a pig brain. Gangliosides (GLS) were first extracted by supercritical CO2 (SCE). The optimum extraction time of GLS by SCE was 4 h, and the ratio of entrainer to acetone powder from the pig brain was 3:1 (v/w). GM1 was then prepared from GLS by immobilized sialidase and purified by reverse-phase silica gel. Sodium alginate embedding was used for the immobilization of sialidase. Under the optimized method, the yield of high-purity GM1 was around 0.056%. This method has the potential to be applied in the production of GM1 in the industry.

2.
Nat Commun ; 10(1): 4458, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575867

RESUMO

The use of anion redox reactions is gaining interest for increasing rechargeable capacities in alkaline ion batteries. Although anion redox coupling of S2- and (S2)2- through dimerization of S-S in sulfides have been studied and reported, an anion redox process through electron hole formation has not been investigated to the best of our knowledge. Here, we report an O3-NaCr2/3Ti1/3S2 cathode that delivers a high reversible capacity of ~186 mAh g-1 (0.95 Na) based on the cation and anion redox process. Various charge compensation mechanisms of the sulfur anionic redox process in layered NaCr2/3Ti1/3S2, which occur through the formation of disulfide-like species, the precipitation of elemental sulfur, S-S dimerization, and especially through the formation of electron holes, are investigated. Direct structural evidence for formation of electron holes and (S2)n- species with shortened S-S distances is obtained. These results provide valuable information for the development of materials based on the anionic redox reaction.

3.
Gen Comp Endocrinol ; 285: 113291, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568758

RESUMO

Melanocortin-1 receptor (MC1R) has important roles in regulating pigmentation and inflammation. Melanocortin receptor accessory protein 2 (MRAP2) modulates trafficking, ligand binding, and signaling of mammalian melanocortin receptors. However, the effect of MRAP2 on fish MC1R has not been extensively studied. Herein, we cloned the orange-spotted grouper (Epinephelus coioides) mc1r, which had a 972 bp open reading frame encoding a putative protein of 323 amino acids. Grouper mc1r was mainly expressed in the brain, skin, testis, spleen, head kidney, and kidney. EcoMC1R showed high constitutive activities in both Gs-cAMP and ERK1/2 pathways, which could be differentially modulated by grouper MRAP2 (EcoMRAP2). Three agonists, including α-melanocyte-stimulating hormone (MSH), ß-MSH, and ACTH, could bind to EcoMC1R and dose-dependently increase intracellular cAMP production. EcoMRAP2 had no effect on the IC50 in binding assay or EC50 in cAMP assay; however, it dose-dependently decreased the cell surface expression and maximal response to the three agonists. EcoMRAP2 increased basal ERK1/2 activation but did not alter α-MSH-stimulated ERK1/2 activation. This study extends the knowledge base of fish MC1R pharmacology and its regulation by MRAP2.

4.
J Clin Hypertens (Greenwich) ; 21(11): 1654-1663, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603618

RESUMO

A subgroup analysis of the nationwide, cross-sectional 3B STUDY was performed to understand the current blood pressure (BP) control status and treatment patterns in Chinese diabetes patients as well as to identify factors associated with BP control. The demographic data, anthropometric parameters, and laboratory results were collected from 24 512 type 2 diabetes patients. The BP goal was a systolic BP <130 mm Hg and a diastolic BP <80 mm Hg regardless of a history of hypertension or current antihypertensive treatment. The overall prevalence of hypertension was 59.9% with geographical differences. Among the diabetes patients with hypertension, 76.9% received antihypertensive medicines. Calcium channel blockers (39.3%), angiotensin II receptor antagonists (26.6%), and then ß-blockers (14.0%) or angiotensin-converting enzyme inhibitors (13.6%) were frequently used for BP control. Only 17.5% (n = 2658) of diabetes patients with hypertension reached the recommended target BP. Body mass index <24 kg/m2 , urban resident, frequent physical activity, good adherence to medication, comorbidity with cardiovascular disease, achieving glycemic goal (HbA1c <7.0%), achieving lipid goal (low-density lipoprotein cholesterol <2.59 mmol/L) were independent factors that predicted achievement of target BP goal. On the contrary, comorbidity with chronic kidney disease predicted failure to achieve target BP goal. Patients who were treated in a cardiology department or lived in the North were more likely to achieve BP goals. A considerable proportion of diabetic patients failed to achieve guideline-recommended BP targets. More aggressive efforts should be made to overcome the diverse barriers and facilitate the optimization of diabetes management.

5.
Chem Commun (Camb) ; 55(82): 12384-12387, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31559990

RESUMO

Herein, we report the first example of synthesis of N-substituted lactams via an acceptorless dehydrogenative coupling of diols with primary amines in one step, which was enabled by combining Ru3(CO)12 with a hybrid N-heterocyclic carbene-phosphine-phosphine ligand as the catalyst.

6.
Medicine (Baltimore) ; 98(36): e15719, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490359

RESUMO

BACKGROUND: We evaluated the relationship between the age at first use of oral contraceptives (OC) and breast cancer (BC) risk. METHODS: We searched PubMed, Embase, and related reviews published through June 28, 2018, and used summary relative risk (RR) and 95% confidence intervals (CIs) to evaluate the cancer risks, and fixed-effects dose-response meta-analysis to assess potential linear and non-linear dose-response relationships. RESULTS: We included 10 studies, with 8585 BC cases among 686,305 participants. The pooled RR for BC was 1.24 (95% CI: 1.10-1.41), with moderate heterogeneities (I = 66.5%, P < .001). No significant publication bias was found (P = .584 for Begg test, P = .597 for Egger test). A linear dose-response relationship between the age at first OC use and BC risk was detected (P = .518 for non-linearity). Subgroup analyses were restricted to studies done by BC subtypes, region, sample size, follow-up time and study quality. Inconsistent consequences with no statistical significance were explored when limited to studies from Western countries, study quality <7, sample size <10,000, follow-up time <5 years, and BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression status in tumor tissue. Sensitivity analyses indicated that our results were stable and reliable after removing each study in turn and omitting studies of adjusted unreported variables. CONCLUSION: A significant linear relationship between the age at first OC use and BC risk was confirmed. No further consistent differences are noted in multiple aspects of BC subtypes defined by progesterone or ER status.


Assuntos
Neoplasias da Mama/epidemiologia , Anticoncepcionais Orais/administração & dosagem , Fatores Etários , Relação Dose-Resposta a Droga , Feminino , Humanos , Receptor ErbB-2/biossíntese , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese , Fatores de Risco
7.
Angew Chem Int Ed Engl ; 58(45): 16223-16228, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483553

RESUMO

The current Si production process is based on the high-temperature (1700 °C) reduction of SiO2 with carbon that produces large amounts of CO2 . We report an alternative low-temperature (850 °C) process based on the reduction of SiO2 in molten CaCl2 that does not produce CO2 . It utilizes an anode material (Ti4 O7 ) capable of sustained oxygen evolution. Two types of this anode material, dense Ti4 O7 and porous Ti4 O7 , were tested. The dense anode showed a better performance. The anode stability is attributed to the formation of a protective TiO2 layer on its surface. In situ periodic current reversal and ex situ H2 reduction could be used for extending the lifetime of the anodes. The findings show that this material can be applied as a recyclable anode in molten CaCl2 . Si wires, films, and particles were deposited with this anode under different cathodic current densities. The prepared Si film exhibited ≈30-40 % of the photocurrent response of a commercial p-type Si wafer, indicating potential use in photovoltaic cells.

8.
Brain Res Bull ; 153: 214-222, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499089

RESUMO

Many neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease, are associated with microvascular dysfunction, but the cellular and molecular mechanisms are poorly understood. Recently, microRNAs (miRNAs) have been suggested to be involved in the microvascular dysfunction and subsequent memory impairment. MicroRNA-124 (miR-124) is one of the most abundant miRNAs in the brain that is dysregulated in the hippocampus of AD animals. To explore the role of miR-124 in AD pathology, we employed the APP/PS1 transgenic mice and found downregulation of miR-124 and upregulation of complement C1q-like protein 3 (C1ql3) in the hippocampus and cerebral cortex. Downregulation of miR-124 expression resulted in Aß deposition and a variety of cerebromicrovascular impairments, including the decline in microvascular density, reduced angiogenesis, accompanied by C1ql3 alteration. Treatment with lentivirus-mediated overexpression of miR-124 or the C1q inhibitor C1INH rescued breakdown of blood-brain barrier, promoted angiogenesis and reduced Aß deposition, and finally alleviated learning and memory deficit in APP/PS1 mice. Moreover, we found that C1ql3, a component of the classical complement, might be a potential target of miR-124. These results suggested that miR-124 was involved in the angiogenesis and vascular integrity in the hippocampus and the cerebral cortex of the AD mice by regulating the classical complement C1ql3.

9.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31559011

RESUMO

It is well established that mitochondria play a critical role in the metabolic and physiological adaptation of skeletal muscle to enhanced contractile activity. Several redox-sensitive signaling pathways such as PGC-1α, AMPK, IGF/Akt/mTOR, SIRT, NFκB, and FoxO are involved with extensive crosstalk to regulate vital cellular functions such as mitochondrial biogenesis, mitochondrial fusion and fission dynamics, autophagy/mitophagy, and apoptosis under altered demand and stress. However, when muscles cease contraction, such as during immobilization and denervation, mitochondria undergo a series of detrimental changes characterized by downregulation of PGC-1α and antioxidant defense, increased ROS generation, activated FoxO, NFκB, and inflammation, enhanced ubiquitination, and finally mitophagy and apoptotic cascades. The phenotypic outcome of the discord of mitochondrial homeostasis is elevated proteolysis and muscle atrophy. The demonstration that PGC-1α overexpression via transgene or in vivo DNA transfection can restore mitochondrial homeostasis and reverse myocyte atrophy supports the "mitostasis theory of muscle atrophy".


Assuntos
Degradação Mitocondrial , Atrofia Muscular , Transtornos Musculares Atróficos , Fatores de Transcrição , Humanos , Mitocôndrias , Atrofia Muscular/fisiopatologia
10.
Nat Commun ; 10(1): 3404, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363125

RESUMO

We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets, 15N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.

11.
Phytomedicine ; 64: 153063, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419728

RESUMO

BACKGROUND: Traditional herbal formula Gushukang (GSK) has been clinically applied to treat primary osteoporosis, which can stimulate osteoblastogenesis and improve calcium homeostasis. However, it remains unknown the mechanism that GSK against ovariectomized (OVX) induced damage. PURPOSE: The aim of this study was to investigate the effect of GSK on BMP-2/Smsds signaling pathway and osteocyte apoptosis which has been reported to play a central role in bone remodeling. STUDY DESIGN: OVX in rat was established and GSK was administered. RESULTS: BMP-2/Smsds signaling pathway was inhibited and the number of apoptotic osteocytes was increased in OVX rats. Treatment with GSK significantly enhanced BMP-2/Smsds signaling pathway by up-regulating the expression of BMP-2, p-Smad1 and p-Smad5, Osterix and Runx2, and inhibited osteocyte apoptosis by up-regulating Bcl-xl and down-regulating Bak, which were consistent with histological changes revealed by ALP, Trap and TUNEL staining. GSK treatment improved bone mass and micro-structure of trabecular bone at distal femur in OVX rats shown by BMD, micro-CT measurement and HE staining. CONCLUSION: These data suggest that GSK exhibited protective effects on promoting bone formation and precluding osteocyte apoptosis. The underlying mechanism may be attributed to its regulation on BMP-2/Smads signaling pathway and Bcl2 family.

12.
Med Sci Monit ; 25: 5137-5142, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31292430

RESUMO

BACKGROUND This study aimed to investigate the association between the rs2975760 and rs3792267 single nucleotide polymorphisms (SNPs) of the calpain 10 (CAPN10) gene and gestational diabetes mellitus. MATERIAL AND METHODS The study included 138 patients with gestational diabetes mellitus and 152 healthy pregnant women. Venous blood was separated, and the DNA was extracted. The rs2975760 and rs3792267SNP polymorphisms of CAPN10 were detected using polymerase chain reaction (PCR). The frequencies of different genotypes in patients with gestational diabetes mellitus and healthy pregnant women were determined, and the relationship between different SNP genotypes and the risk of gestational diabetes mellitus was analyzed. RESULTS There were no significant differences in the frequencies of the TT, CT and CC genotypes of rs2975760 and the frequencies of the GG, AG and AA genotypes of rs3792267 between the women with gestational diabetes and the controls. Expression of rs2975760 and rs3792267 were not associated with the risk of gestational diabetes in the dominant model, recessive model, and additive model. However, grade B and grade D diabetes in the CC and TC genotypes of rs2975760 were significantly different from those in the TT genotype (P<0.05). Grade B and grade D diabetes in the AA and AG genotypes of rs3792267 were significantly different compared with those in the GG genotype (P<0.05), and allele A was significantly increased compared with allele G (P<0.05). CONCLUSIONS The rs2975760 and rs3792267 SNP polymorphisms of CAPN10 showed no significant association with the incidence of gestational diabetes mellitus and only a mild association with the severity.

14.
J Biomed Mater Res A ; 107(11): 2567-2575, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356723

RESUMO

Numerous studies have shown that lung injury can be caused by respiratory exposure to nanoparticulate titanium dioxide (nano-TiO2 ), but whether pulmonary inflammation and fibrosis are related to the activation of the TGF-ß/Smad/p38MAPK/Wnt pathways remains unclear. In this study, mice were administrated nano-TiO2 by nasal instillation for nine consecutive months, and the molecular mechanisms of nano-TiO2 on the pulmonary toxicity of mice were examined. The findings suggested that nano-TiO2 caused pneumonia and pulmonary fibrosis. Furthermore, the results also showed that an overproduction of reactive free radicals occurred in mouse lungs, and that the expression of TGF-ß/p38MAPK/Wnt pathway-related factors, including hypoxia-inducible factor 1α (HIF-1α), transforming growth factor-ß1 (TGF-ß1), phosphorylated p38 mitogen activated protein kinases (p-p38MAPK), small mothers against decapentaplegic homolog 2 (Smad2), extracellular matrix (ECM), Wingless/Integrated 3 (Wnt3), Wingless/Integrated 4 (Wnt4), integrin-linked kinase (ILK), ß-catenin, nuclear factor-κB (NF-κB), α-smooth muscle actin (α-SMA), c-Myc, Type I collage (collagen I), and Type collage III (collagen III) were remarkably elevated, while phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß) expression was decreased. Those data implied that the pulmonary inflammation and fibrosis caused by nano-TiO2 exposure may be involved in reactive free radical-mediated activation of the TGF-ß/Smad/p38MAPK/Wnt pathways.

15.
Chin Med J (Engl) ; 132(14): 1666-1672, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31268911

RESUMO

BACKGROUND: The detection of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome at early stage is challenging for neurologists. Since polyneuropathy could be the first manifestation, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). The present study aimed to determine the clinical and electrophysiological features of POEMS syndrome to distinguish from CIDP. METHODS: The data of a group of patients with POEMS (n = 17) and patients with CIDP (n = 17) in Zhongshan Hospital Fudan University from January 2015 to September 2017 were analyzed in this retrospective study. The clinical features, neurological symptoms, and electrophysiological findings were compared between the two groups. RESULTS: Clinically, patients with POEMS demonstrated significantly more neuropathic pain in the lower extremities than patients with CIDP (58.8% vs. 11.8%, P = 0.01). Multisystem features like edema, skin change, organomegaly, and thrombocytosis were also pointed towards the diagnosis of POEMS syndrome. Electrophysiologically, terminal latency index (TLI) was significantly higher in patients with POEMS than that in patients with CIDP (median nerve: 0.39 [0.17-0.52] vs. 0.30 (0.07-0.69), Z = -2.413, P = 0.016; ulnar nerve: 0.55 [0.23-0.78] vs. 0.42 [0.12-0.70], Z = -2.034, P = 0.042). Patients with POEMS demonstrated a higher frequency of absent compound muscle action potential of the tibial nerve (52.9% vs. 17.6%, P = 0.031), less conduction block (ulnar nerve: 0 vs. 35.3%, P = 0.018), and less temporal dispersion (median nerve: 17.6% vs. 58.8%, P = 0.032) than CIDP group. The combination of positive serum monoclonal protein and high TLI (if either one or both were present) discriminated POEMS from CIDP with a sensitivity of 94.1% and 47.1% and specificity of 76.5% and 100.0%, respectively. CONCLUSIONS: POEMS syndrome could be distinguished from CIDP through typical clinical and electrophysiological characteristics in practice. The combination of serum monoclonal protein and high TLI might raise the sensitivity of detecting POEMS syndrome.

16.
Biochem Biophys Res Commun ; 516(3): 991-998, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31277941

RESUMO

Spinal cord injury (SCI) is terrible damage leading to the deficiencies and results in infinite inconvenience to sufferers. The effective treatment for SCI still meets a larger number of problems. Herein, the underlying molecular mechanism and novel therapy of SCI are urgently to investigate. Arachidonate 12-lipoxygenase (ALOX12) is widely expressed in various cell types and plays important role in modulating different cellular processes, such as platelet aggregation, cell migration and cancer cell proliferation. Nevertheless, the effects of ALOX12 on SCI are unclear. In the study, SCI model was established in wild type (WT) mice and ALOX12 knockout mice. First, ALOX12 expression was up-regulated in spinal cord tissues of WT mice after SCI. ALOX12-knockout mice exhibited improved behavior after SCI operation. Glial activation triggered by SCI was also alleviated in mice with the loss of ALOX12, as evidenced by the down-regulated expression of glial fibrillary acidic protein (GFAP) and Iba-1 in spinal cord samples. Further, SCI-induced inflammation was markedly prevented in ALOX12-knockout mice through blocking inhibitor of NF-κB α (IκBα)/nuclear factor-κB (NF-κB) pathway signaling. Additionally, reducing ALOX12 expression attenuated apoptosis in spinal cord tissues of SCI mice by decreasing Cyto-c, cleaved Caspase-3 and poly (ADP-ribose) polymerases (PARP) expression. The protective role of ALOX12-decrease against SCI was verified in LPS-incubated glial cells through repressing inflammatory response and apoptotic formation. Moreover, transgenic mice with ALOX12 over-expression showed accelerated SCI, associated with intensified inflammation and apoptosis. Based on these results, strategies for inhibiting ALOX12 could be used to prevent SCI development by repressing inflammation and apoptosis.

17.
Diabetes Care ; 42(8): 1414-1421, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152121

RESUMO

OBJECTIVE: Type 1 diabetes (T1D) is a highly heritable disease with much lower incidence but more adult-onset cases in the Chinese population. Although genome-wide association studies (GWAS) have identified >60 T1D loci in Caucasians, less is known in Asians. RESEARCH DESIGN AND METHODS: We performed the first two-stage GWAS of T1D using 2,596 autoantibody-positive T1D case subjects and 5,082 control subjects in a Chinese Han population and evaluated the associations between the identified T1D risk loci and age and fasting C-peptide levels at T1D diagnosis. RESULTS: We observed a high genetic correlation between children/adolescents and adult T1D case subjects (r g = 0.87), as well as subgroups of autoantibody status (r g ≥ 0.90). We identified four T1D risk loci reaching genome-wide significance in the Chinese Han population, including two novel loci, rs4320356 near BTN3A1 (odds ratio [OR] 1.26, P = 2.70 × 10-8) and rs3802604 in GATA3 (OR 1.24, P = 2.06 × 10-8), and two previously reported loci, rs1770 in MHC (OR 4.28, P = 2.25 × 10-232) and rs705699 in SUOX (OR 1.46, P = 7.48 × 10-20). Further fine mapping in the MHC region revealed five independent variants, including another novel locus, HLA-C position 275 (omnibus P = 9.78 × 10-12), specific to the Chinese population. Based on the identified eight variants, we achieved an area under the curve value of 0.86 (95% CI 0.85-0.88). By building a genetic risk score (GRS) with these variants, we observed that the higher GRS were associated with an earlier age of T1D diagnosis (P = 9.08 × 10-11) and lower fasting C-peptide levels (P = 7.19 × 10-3) in individuals newly diagnosed with T1D. CONCLUSIONS: Our results extend current knowledge on genetic contributions to T1D risk. Further investigations in different populations are needed for genetic heterogeneity and subsequent precision medicine.

18.
J Cell Biochem ; 120(9): 15268-15279, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172560

RESUMO

Irritable bowel syndrome (IBS) is a common disorder of unknown etiology. Studies have found a close relation between IBS and microRNAs (miRNAs), but the study concerning the relationship between IBS and miR-181c-5p in IBS is still blank. Thus, this study aims to explore the role of miR-181c-5p in IBS via interleukin 1α (IL1A). Initially, microarray analysis was used to retrieve the genes related to IBS and to predict miRNAs regulating IL1A gene. IBS model was then established with abdominal withdraw reflection (AWR) and Bristol stool grading in mice measured. Afterwards, the functional role of miR-181c-5p in IBS was determined using the ectopic expression, depletion and reporter assay experiments, as well as miR-181c-5p and IL1A expression detected. Subsequently, expression of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and IL-6 were detected to further determine the effects of miR-181c-5p and IL1A on inflammation in IBS. miR-181c-5p and IL1A might be involved in IBS. miR-181c-5p was found to be decreased while IL1A was increased in IBS rats. In addition, miR-181c-5p could target and inhibit expression of IL1A, and IBS mice exhibited elevated AWR and Bristol stool grading, namely 6 to 7 points (70.4 [38 of 54]). Moreover, with the overexpression of miR-181c-5p or silencing of IL1A, the expression of TNF-α, IL-2, and IL-6 was decreased. Collectively, this study suggested that overexpressed miR-181c-5p could silence IL1A, thus inhibiting low-grade inflammation in IBS rats. miR-181c-5p/IL1A is expected to serve as a novel target for the treatment of IBS.

19.
Nanoscale ; 11(25): 12388-12396, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31215952

RESUMO

The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.

20.
Blood Cells Mol Dis ; 77: 129-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31059942

RESUMO

Autophagy is primarily considered as an important survival mechanism for both normal cells and cancer cells in response to metabolic stress or chemotherapy; but the role of autophagy in leukemogenesis is not fully understood. The aim of this study is to explore the role of intrinsic autophagy in the leukemogenesis of B-cell acute lymphoblastic leukemia (B-ALL). In this study, conditional knockout mice Atg7f/f;Ubc-Cre, in which an autophagy-essential gene Atg7 is universally deleted, were used as recipients, B-ALL cell line 697 was used as donor cells to generate leukemia mouse model. Compared to wild-type mice, Atg7 knockout mice were more susceptible to engrafted leukemogenesis, shown by increase in white blood cells, lymphocytes, and platelets, decrease in HSPC number and its colony-forming unit (CFU). The liver and spleen displayed hepatosplenomegaly and inflammatory cell infiltration. Furthermore, second competitive transplantation revealed dysfunction of the HSPC in Atg7-knockout leukemia mice represented by destructive self-renew ability (CFU) and reconstitution ability including decreased B220, Ter 119 cells, and increased Gr-1 cell percentage. In summary, Mice with universal deletion of Atg7 are more inclined to the occurrence of engrafted human leukemia, which is largely attributed to the deterioration of the function of HSPC in autophagy deficient mice.

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