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1.
Food Funct ; 11(5): 3964-3974, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32400787

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose prevalence is increasing globally. A synbiotic has probiotic and prebiotic components and is regarded as a promising candidate for alleviating UC-associated inflammation. The purpose of this study is to determine whether there is an additive efficacy between the probiotic Bifidobacterium infantis (B. infantis) and the prebiotic xylooligosaccharide (XOS) against UC. C57BL/6 mice were treated with B. infantis, XOS, or synbiotic (combination of B. infantis and XOS) for 21 d. During the final 7 d of treatment, the mice were administered dextran sulfate sodium (DSS) dissolved in drinking water to induce colitis. All treatments decreased the disease activity index (DAI) and pathological scores, and synbiotic treatment was more efficacious than either the probiotic or prebiotic alone. Compared with the DSS-induced colitis group, all treatment groups significantly downregulated the proinflammatory cytokines TNF-α and IL-1ß, and synbiotic treatment significantly upregulated the anti-inflammatory cytokine IL-10 in the colon tissues. Furthermore, all treatments significantly reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome mRNA level in the colon tissues. All treatments significantly inhibited oxidative stress and increased zonula occludens-1 (ZO-1), occludin, and claudin-1 tight junction (TJ) molecule mRNA levels in the colon tissues. Therefore, the observed efficacy of synbiotics against colitis may be explained by the additive combination of the direct anti-inflammatory effects of the probiotic and prebiotic components and their ability to fortify colonic epithelial barrier integrity. Our findings suggest that a synbiotic is a promising dietary supplement or functional food for the effective management of UC.

2.
Behav Brain Res ; 390: 112671, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437889

RESUMO

Although recent studies have shown that angiotensin (1-7) (Ang [1-7]) exerts anti-stress and anxiolytic-like effects, the underlying mechanisms remain elusive. The ventral hippocampus (VH) is proposed to be a critical brain region for mood and stress management through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway. However, the role of VH NMDAR signaling in the effects of Ang (1-7) remains unclear. In the present study, Ang (1-7) was injected into the bilateral VH of stressed rats, or in combination with a Fyn kinase inhibitor, NMDAR antagonist, neuronal nitric oxide synthase (nNOS) inhibitor, or nitric oxide (NO) scavenger. Anxiety-like behaviors were assessed using the open field test and elevated plus maze test, while alterations in NMDAR-nNOS-NO signaling and serotonergic metabolism were examined in the VH. After 21 days of chronic restraint stress, anxiety-like behaviors were evident. Levels of phosphorylated NR2B (a key NMDAR subunit), its upstream kinase Fyn, as well as activity of nNOS and monoamine oxidase (MAO) were markedly reduced. In contrast, levels of serotonin were increased. Bilateral VH infusion of Ang (1-7) recovered NMDAR-nNOS-NO signaling and MAO-mediated serotonin metabolism, as well as reducing anxiety-like behaviors in stressed rats. These effects were diminished by blockade of MasR (Ang [1-7]-specific receptor), Fyn kinase, NMDAR, nNOS, or NO production. Altogether, these findings indicate that Ang (1-7) exerts anxiolytic effects through modulation of the NMDAR-nNOS-NO pathway and serotonergic metabolism. Future translational research should focus on the relationship between Ang (1-7), glutamatergic neurotransmission, and serotonergic neurotransmission in the VH.

3.
Sci Total Environ ; 733: 139218, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32422463

RESUMO

The quantification of microplastics (MPs), especially small MPs (20-100 µm), in freshwater environment and wastewaters is a great challenge due to the complexity of environmental compartment. In the present study, a novel method based on the optimization of sampling, pretreatment, and detection was developed for small MPs (20-100 µm) in freshwater and wastewaters. A customized plankton sampler was installed to efficiently collect MPs and avoid sampler clogging; a novel dual filter system simplified the pretreatment, achieving full examination for small MPs in the samples. The recoveries of small MPs at environmental abundance, which were specified for the first time, verified the feasibility of the developed method. The method was successfully applied for small MPs detection in river, municipal wastewaters and landfill leachates, demonstrating a large bias in the determination of MPs if small MPs were not involved in quantification. To the authors' knowledge, it is the first study that realized the determination of such small MPs in the high-strength wastewater, i.e. landfill leachates.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32455789

RESUMO

Housing adaptation is recognized as an effective intervention for successful independent living and has been given a greater political priority. However, the current adaptation implementation is fragmented and sometimes confusing. This study is aimed at examining blockages in the adaptation system in the United Kingdom (UK) and identifying practical ways to tackle them. It adopted a mixed-method sequential explanatory research strategy. A questionnaire survey was first conducted in all local authorities in England, Scotland and Wales. This was followed by individual interviews and a focus group with professionals and older clients. The study found that multiple organizations are involved during the delivery of housing adaptations; poor cooperation between them is a major barrier to a seamless service. The adaptation process involves five key stages; there are many inconsistencies and inequities in the process across local authorities. Significant delays are found at all stages, the average length of time taken to complete an adaptation is unacceptably long. There are also many inconsistencies and inequities across different local authorities. This study identified some common deficiencies, which cause inefficiencies and ineffectiveness in housing adaptation practices and makes some recommendations on specific actions that need to be taken at both national and local levels to address them.

5.
Eur J Ophthalmol ; : 1120672120926855, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460537

RESUMO

INTRODUCTION: The Epstein-Barr virus is a rare causative pathogen identified in the posterior segment. The majority of cases were presented with a serious condition of acute retinal necrosis, and most of these eyes had poor outcomes. The clinical features and effective treatment options for this condition are still unclear. Case description: A 10-year-old boy with leukaemia and receiving immunosuppressive regimen presented with decreasing visual acuity to counting fingers in his left eye for 2 weeks. Fundus examination revealed disc swelling, retinitis, retinal exudates and haemorrhages. Aqueous polymerase chain reaction was positive for Epstein-Barr virus DNA but negative for cytomegalovirus, herpes simplex virus and varicella zoster virus DNA. Systemic acyclovir and intravitreal ganciclovir injection were administered. Seven months later, retinitis resolved with remnant retinal fibrosis, and visual acuity improved to 20/500. CONCLUSION: Epstein-Barr virus is rarely identified as a sole pathogen in retinitis. Peripapillary predilection might be another type of presenting feature apart from the more-commonly reported peripheral acute retinal necrosis.

6.
Arch Virol ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32462286

RESUMO

Enterovirus D68 (EV-D68) infection may cause severe respiratory system manifestations in pediatric populations. Because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of EV-D68-specific vaccines and antibodies has become increasingly important. In this study, we prepared an experimental EV-D68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated EV-D68 vaccine exhibited potent neutralizing activity against EV-D68 virus in vitro. Subsequently, the antibody-mediated immune response of B cells elicited by the inactivated vaccine was evaluated in a rhesus monkey model. The binding activity, in vitro neutralization activity, and sequence properties of 28 paired antibodies from the rhesus macaques' EV-D68-specific single memory B cells were analyzed, and the EV-D68 VP1-specific antibody group was found to be the main constituent in vivo. Intriguingly, we also found a synergistic effect among the E15, E18 and E20 monoclonal antibodies from the rhesus macaques. Furthermore, we demonstrated the protective efficacy of maternal antibodies in suckling C57BL/6 mice. This study provides valuable information for the future development of EV-D68 vaccines.

8.
PLoS Pathog ; 16(5): e1008501, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369532

RESUMO

Plant-parasitic nematodes cause huge agricultural economic losses. Two major families of Bacillus thuringiensis crystal proteins, Cry5 and Cry6, show nematicidal activity. Previous work showed that binding to midgut receptors is a limiting step in Cry toxin mode of action. In the case of Cry5Ba, certain Caenorhabditis elegans glycolipids were identified as receptors of this toxin. However, the receptors for Cry6 toxin remain unknown. In this study, the C. elegans CUB-like-domain containing protein RBT-1, released by phosphatidylinositol-specific phospholipase C (PI-PLC), was identified as a Cry6Aa binding protein by affinity chromatography. RBT-1 contained a predicted glycosylphosphatidylinositol (GPI) anchor site and was shown to locate in lipid rafts in the surface of the midgut cells. Western ligand blot assays and ELISA binding analysis confirmed the binding interaction between Cry6Aa and RBT-1 showing high affinity and specificity. In addition, the mutation of rbt-1 gene decreased the susceptibility of C. elegans to Cry6Aa but not that of Cry5Ba. Furthermore, RBT-1 mediated the uptake of Cry6Aa into C. elegans gut cells, and was shown to be involved in triggering pore-formation activity, indicating that RBT-1 is required for the interaction of Cry6Aa with the nematode midgut cells. These results support that RBT-1 is a functional receptor for Cry6Aa.

9.
Eur J Med Chem ; 197: 112309, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375077

RESUMO

Using a rational design strategy for isoform-selective inhibition of PI3Kα, two series of novel 2,3,4,5-tetra-substituted thiophene derivatives containing either diaryl urea or N-Acylarylhydrazone scaffold were designed and synthesized. The most promising compound 12k was demonstrated to bear nanomolar PI3Kα inhibitory potency with 12, 28, 30, 196-fold selectivity against isoforms ß, γ, δ and mTOR. Besides, it also showed good developability profiles in cell-based proliferation against a panel of human tumor cells as well as ADME assays. We herein report on their design, synthesis, SAR and potential developability properties.

10.
Chin J Integr Med ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418175

RESUMO

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

11.
Horm Metab Res ; 52(5): 316-321, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32403146

RESUMO

The aim of the study was to evaluate the remission rate with short-term premixed insulin therapy in newly diagnosed type 2 diabetes outpatients and investigate predictors contributing to the remission rate. A 5-year prospective study was conducted with a total of 170 patients enrolled. Patients were treated with premixed insulin monotherapy or insulin in combination with one or two oral drugs. After glucose levels were well controlled, insulin and oral drugs were discontinued in a stepwise manner. The prolonged and partial remission rates were calculated and the possible factors contributing to remission were also analyzed. A total of 164 subjects completed the research study. The prolonged remission, partial remission and non-remission rates at the 5-year follow-up were 9.8, 59.8, and 30.5%, respectively. The remission rate was negatively correlated with disease duration (r=0.39). The combined rate of remission (prolonged and partial remission) significantly decreased when the duration was longer than 16 days, and reduced to approximately 50% after 1 month. Moreover, 75% of prolonged remission patients had duration of < 16 days. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. Furthermore, the duration after diagnosis is an independent predictor of remission rate, and initiation of short-term premixed insulin therapy within the first 16 days of diabetes diagnosis is very important for remission. This is the first study to evaluate the remission rate associated with short-term premixed insulin therapy in recently diagnosed type 2 diabetes outpatients. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. The duration of diabetes was identified as an independent predictor of drug-free remission. The initiation of short-term premixed insulin therapy within 15 days of diabetes onset is particular importance for remission.

12.
Int J Nanomedicine ; 15: 3251-3266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440122

RESUMO

Background: Peripheral neuropathy is a common and painful side effect that occurs in patients with cancer induced by Oxaliplatin (OXL). The neurotoxicity correlates with the damage of dorsal root ganglion (DRG) neurons and Schwann cells (SCs). Hydroxysafflor yellow A (HSYA), icariin, epimedin B and 3, 4-dihydroxybenzoic acid (DA) are the main neuroprotective ingredients identified in Wen-Luo-Tong (WLT), a traditional Chinese medicinal topical compound. The purpose of this study was to prepare and evaluate the efficacy of an ethosomes gel formulation loaded with a combination of HSYA, icariin, epimedin B and DA. However, the low LogP value, poor solubility and macromolecule are several challenges for topical delivery of these drugs. Methods: Ethosomes were prepared by the single-step injection technique. Particle size, entrapment efficiency and in vitro drug deposition studies were determined to select the optimum ethosomes. The optimized ethosomes were further incorporated into carbopol to obtain a gel. The rheological properties, morphology, in vitro drug release, in vitro gel application and skin distribution of the ethosomes gels were studied. A rat model of oxaliplatin-induced neuropathy was established to assess the therapeutic efficacy of the ethosomes gel. Results: Seventy percent (v/v) ethanol, cinnamaldehyde and Phospholipon 90G were employed to develop ethosomes a carrier system. This system had a high entrapment efficiency, carried large amounts of HSYA, epimedin B, DA and icarrin, and penetrated deep into the epidermis and dermis. The optimized ethosomes had the maximum deposition of icariin, HSYA, epimedin B and relative higher amount of DA in epidermis (2.00±0.13 µg/cm2, 5.72±0.75 µg/cm2, 1.97±0.27 µg/cm2 and 9.25±1.21 µg/cm2, respectively). 0.5% carbopol 980 was selected to develop the ethosomes gel with desirable viscoelasticity and spreadability, which was suitable for topical application. The mechanical allodynia and hyperalgesia induced by OXL in rats were significantly reduced after the new ethosomes gel was applied to rats compared to model group. Conclusion: Based on our findings, the ethosomes gel delivery system provided a new formulation for the topical delivery of HSYA, icariin, epimedin B and DA to counteract OXL-induced peripheral neuropathy.

13.
Int J Nanomedicine ; 15: 3267-3279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440123

RESUMO

Vitiligo is a depigmentation disease that seriously affects the physical health, mental health and quality of life of a patient. Therapeutic aim at control immunoreaction by relieving oxidative stress. Unfortunately, the cuticle barrier function and lack of specific accumulation lead to unsatisfactory therapeutic outcomes and side effects. The introduction and innovation of nanotechnology offers inspiration and clues for the development of new strategies to treat vitiligo. However, not many studies have been done to interrogate how nanotechnology can be used for vitiligo treatment. In this review, we summarize and analyze recent studies involving nano-drug delivery systems for the treatment of vitiligo, with a special emphasis on liposomes, niosomes, nanohydrogel and nanoparticles. These studies made significant progress by either increasing drug loading efficiency or enhancing penetration. Based on these studies, there are three proposed principles for topical nano-drug delivery systems treatment of vitiligo including the promotion of transdermal penetration, enhancement of drug retention and facilitation of melanin regeneration. The presentation of these ideas may provide inspirations for the future development of topical drug delivery systems that will conquer vitiligo.

14.
Technol Health Care ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32444582

RESUMO

BACKGROUND: Gout is the most common inflammatory arthritis affecting 1.1% of the population in mainland China with a higher prevalence in coastal areas. OBJECTIVE: The purpose of the study was to investigate the clinical outcomes following urate-lowering therapy (ULT) in a real-world group study of primary gout patients in China. METHODS: Electronic medical records of all the gout patients (n= 1588) that visited the Clinical Medical Center of Gout of the Affiliated Hospital of Qingdao University from September 2016 to February 2018 were analyzed in this study. The patients were treated with a standard treat-to-target (T2T) ULT strategy according to the 2016 EULAR Guidelines. Clinical data were collected in the first visit and one-month (defined as the baseline of ULT), 7-month, and 13-month follow-ups were completed. RESULTS: Amongst the patients in the study, 92.70% accepted ULT and 82.93% completed ULT for 3 months, 63.54% for 6 months, and 40.49% (n= 643) for 12 months. Further analysis of the 643 patients included the following data: the sUA level reduced at month 7 and reduced further at month 13. The gout flares, patient global pain visual analogue score, and health assessment questionnaire score improved at month 7 but did not improve further at month 13, and the index tophus size did not change at month 7 but reduced at month 13. The eGFR deteriorated to below the baseline in month 13 for group A (established) but not for group B (newly-onset). Both the SBP and DBP improved above the baseline at month 13 in group B but not in group A. CONCLUSIONS: The long-term standard treat-to-target ULT strategy benefits patients for both gout-related issues and their extra-articular organs. The current study suggests that there is a better chance to achieve the rates of adherence to ULT and the target of sUA levels in the setting of a dedicated gout clinic.

15.
Biomed Pharmacother ; 127: 110215, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32413671

RESUMO

The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-ß stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.

16.
Sci Total Environ ; 729: 138936, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32361451

RESUMO

Marine protected areas (MPAs) have been increasingly used as a primary tool for fisheries management and conservation. Over the past few decades, the implementation of MPAs has achieved mixed results with regard to conservation goals, which has driven the scientific community to contemplate what factors may determine the effectiveness of an MPA. Most previous analyses have tended to focus on the design criteria of MPAs as well as post-closure management capabilities, but pre-closure conditions are seldom considered. Here, we investigate the effects of varying pre-closure fishing effort scenarios on MPA performance by applying a developed evaluation framework and age-structured dynamic model for the small yellow croaker (Larimichthys polyactis) in Haizhou Bay, China. We specifically focus on the overall fishing pressure imposed on the fish population and the spatial heterogeneity of fishing effort. We used ecological and social indicators to evaluate the effects of MPAs. Our results demonstrate that MPAs with lower pre-closure fishing pressure are more effective than those with higher pre-closure fishing pressure in recovering the fish population. Highly aggregated fishing efforts inside the MPAs prior to their implementations could also make MPAs less effective. By comparing our findings to other studies, we noticed that evaluation metrics and time frames could make a difference in determining the effects of a given MPA, which indicates the importance of monitoring programs. From a social perspective, placing MPAs in heavily exploited areas without additional harvest regulations may result in a tragedy of the commons situation that leads to a significant loss in catches. This study highlights the ecological and social risks of establishing MPAs under different pre-closure fishing scenarios and provides insights for the development of marine conservation plans.

17.
J Int Med Res ; 48(5): 300060520925680, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32436459

RESUMO

Bilateral Tessier no. 7 clefts are rarely reported in the literature. Here, we describe the presence of accessory maxilla with supernumerary teeth in a patient who exhibited bilateral Tessier no. 7 clefts; the diagnosis was established based on the patient's history, clinical presentation, and computed tomography images. A review of the available literature revealed 24 patients with Tessier no. 7 clefts from 2000 to 2020, including our patient. The most common clinical manifestation in patients with Tessier no. 7 clefts comprises bilateral facial clefts. Additionally, Tessier no. 7 clefts are more frequently found in boys or men, rather than in girls or women. The presence of an accessory maxilla with supernumerary teeth in a patient with bilateral Tessier no. 7 clefts is extremely rare. Early detection of craniofacial abnormalities is important, because it may influence patient prognosis and management.

18.
J Exp Clin Cancer Res ; 39(1): 70, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326970

RESUMO

BACKGROUND: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were used to detect the expression levels of ETV6, CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) and miR-429 in HCC tissues and cells; Transwell chamber and F-actin cytoskeleton staining assay to examine the effects of ETV6 and CRKL deregulation on the migration, invasion and cytoskeleton of HCC cells; Co-immunoprecipitation assay to determine the interaction between CRKL and ETV6; Chromatin immunoprecipitation assay to investigate the interaction between ETV6 and miR-429. RESULTS: We established a novel ETV6-miR-429-CRKL regulatory circuitry contributes to HCC metastasis. ETV6 and CRKL were frequently increased, while miR-429 was downregulated in both hepatocarcinoma tissues and hepatocarcinoma cells. Moreover, ETV6 upregulation was positively correlated with CRKL upregulation, and two negative correlations were also established for ETV6 and CRKL upregulation with miR-429 downregulation in both hepatocarcinoma patients' tumorous tissues and hepatocarcinoma cells. Functional investigations revealed that overexpression and knockdown of ETV6 was remarkably effective in promoting and suppressing HCC cell migration, invasion, cytoskeleton F-actin expression and arrangement, whereas, CRKL overexpression exhibited similar effects to the overexpression of ETV6. Mechanistically, ETV6 negatively regulates miR-429 expression by directly binding to the promoter region of miR-429; miR-429 negatively regulates CRKL expression by selectively targeting CRKL-3'-UTR; ETV6 directly binds to CRKL and positively regulates its expression, which in turn CRKL positively regulates ETV6 expression. CONCLUSIONS: Our data demonstrated that ETV6 promotes migration and invasion of HCC cells by directly binding to promoter region of miR-429 via modulating CRKL expression. The newly identified ETV6-miR-429-CRKL regulatory circuitry contributes to the aggressiveness of HCC, which provides new clues for fundamental research on diagnosis and treatment parameters for HCC.

19.
Plant Physiol Biochem ; 151: 391-399, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278293

RESUMO

Lily, a famous cut flower with highly fragrance, has high ornamental and economic values. Monoterpenes are the main components contributing to its fragrance, and terpene synthase (TPS) genes play critical roles in the biosynthesis of monoterpenoids. To understand the function of TPS and to explore the molecular mechanism of floral scent in cultivar Lilium 'Siberia', transcriptomes of petal at different flowering stages and leaf were obtained by RNA sequencing and three unigenes related to TPS genes were selected for further validation. Quantitative real-time PCR showed that the expression level of LiTPS2 was greater than that of the other two TPS genes. Phylogenetic analysis indicated that LiTPS2 belonged to the TPSb subfamily, which was responsible for monoterpenes synthesis. Subcellular localization demonstrated that LiTPS2 was located in the chloroplasts. Furthermore, functional characterization showed that LiTPS2 utilized both geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) to produce monoterpenoids such as linalool and sesquiterpenes like trans-nerolidol, respectively. Ectopic expression in transgenic tobacco plants suggested that the amount of linalool from the flowers of transgenic plants was 2-3 fold higher than that of wild-type plants. And the emissions of myrcene and (E)-ß-ocimene were also accumulated from the flowers of LiTPS2 transgenic lines. Surprisingly, these three compounds were the main fragrance components of oriental lily hybrids. Our results indicated that LiTPS2 contributed to the production of monoterpenes and could effectively regulate the aroma of Lilium cultivars, laying the foundation for biotechnological modification of floral scent profiles.

20.
Mol Ther ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32246902

RESUMO

The discovery of long noncoding RNAs (lncRNAs) has increased our understanding of the development and progression of many cancers, but their contributions to non-small cell lung cancer (NSCLC) remain poorly understood. Here, we profiled lncRNA expression in NSCLC and investigated in detail the molecular function of one upregulated lncRNA, LINC01234. LINC01234 was overexpressed in NSCLC compared with normal lung tissue and correlated positively with poor prognosis. Downregulation of LINC01234 impaired cell proliferation in vitro and tumor growth in vivo. RNA pull-down/mass spectrometry experiments showed that LINC01234 interacted with the RNA-binding protein heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), which, in turn, led to the recruitment of DiGeorge syndrome critical region gene 8 (DGCR8), a subunit of the microRNA (miRNA) microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including primary microRNA (pri-miR)-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating cryptochrome 2 (CRY2), thereby increasing c-Myc expression. Finally, we found that activated c-Myc binds to the LINC01234 promoter to increase its transcription, creating a c-Myc-LINC01234-HNRNPA2B1-miR-106b-5p-CRY2-c-Myc positive-feedback loop. We identified numerous lncRNAs with dysregulated expression in NSCLC and demonstrated a novel oncogenic axis involving LINC01234, HNRNPA2B1, miR-106b-5p, CRY2, and c-Myc. Components of this axis may be potential novel targets for NSCLC.

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