Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.038
Filtrar
1.
Nat Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820995

RESUMO

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.

3.
Oral Dis ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818901

RESUMO

OBJECTIVES: To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine. MATERIALS AND METHODS: In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 d post-irradiation for a total of 7 d. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 wk after irradiation. RESULTS: Salivary secretion of the irradiated glands was reduced at 1 and 12 wk. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment. CONCLUSIONS: Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.

4.
J Appl Clin Med Phys ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829650

RESUMO

BACKGROUND: Hippocampal-avoidance prophylactic cranial irradiation (HA-PCI) offers potential neurocognitive benefits but raises technical challenges to treatment planning. This study aims to improve the conventional planning method using volumetric modulated arc therapy (VMAT) technique and investigate a better patient's head positioning to achieve a high quality of HA-PCI treatment plans. METHODS: The improved planning method set a wide expansion of hippocampus as a special region for dose decline. The whole brain target was divided into two parts according to whether the slice included hippocampus and their optimization objectives were set separately. Four coplanar full arcs with partial field sizes were employed to deliver radiation dose to different parts of the target. The collimator angle for all arcs was 90°. Tilting patient's head was achieved by rotating CT images. The improved planning method and tilted head positioning were verified using datasets from 16 patients previously treated with HA-PCI using helical tomotherapy (HT). RESULTS: For the improved VMAT plans, the max and mean doses to hippocampus were 7.88 Gy and 6.32 Gy, respectively, significantly lower than those for the conventional VMAT plans (P < 0.001). Meanwhile, the improved planning method significantly improved the plan quality. Compared to the HT plans, the improved VMAT plans result in similar mean dose to hippocampus (P > 0.1) but lower max dose (P < 0.02). Besides, the target coverage was the highest for the improved VMAT plans. The tilted head positioning further reduced the max and mean doses to hippocampus (P < 0.05), significantly decreased the max dose to lens (P < 0.001) and resulted in higher plan quality as compared to nontilted head positioning. CONCLUSIONS: The improved planning method enables the VMAT plans to meet the clinical requirements of HA-PCI treatment with high plan quality and convenience. The tilted head positioning provides superior dosimetric advantages over the nontilted head positioning, which is recommended for clinical application.

5.
BMJ Open ; 11(4): e045192, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795307

RESUMO

INTRODUCTION: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk. METHODS AND ANALYSIS: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study. ETHICS AND DISSEMINATION: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation. TRIAL REGISTRATION NUMBER: ChiCTR1800017773. PROTOCOL VERSION: November 11, 2020 (Version #5).

6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(3): 233-239, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33766231

RESUMO

Objective To investigate the effects of knockdown of Aurora-A gene on the proliferation and apoptosis of HepG2 human hepatocellular carcinoma cells. Methods Aurora-A short hairpin RNA (Aurora-A shRNA) was designed and Aurora-A shRNA lentiviral vector was constructed and packed, and then transfected into HepG2 cells. Aurora-A mRNA expression was detected by real-time quantitative PCR. Aurora-A protein expression and phosphorylation level were detected by Western blotting. Cell proliferation was tested by MTT assay. Cell apoptosis was analyzed by flow cytometry. Results The Aurora-A shRNA lentiviral vector was successfully constructed and Aurora-A protein phosphorylation level was significantly reduced in HepG2 cells transfected with the lentiviral vector. When Aurora-a was knocked down, the proliferation of HepG2 cells decreased and the apoptosis rate increased significantly. Conclusion Knockdown of Aurora-A can inhibit the proliferation and promote the apoptosis of HepG2 cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose/genética , Aurora Quinase A , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , RNA Interferente Pequeno/genética
7.
Eur J Oral Sci ; : e12785, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33786924

RESUMO

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

8.
J Colloid Interface Sci ; 594: 173-185, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33756363

RESUMO

In order to improve the electrochemical performance and relieve volume expansion of pure SnFe2O4 anode for lithium-ion batteries (LIBs), we synthesized a novel ZnO/SnFe2O4/nitrogen-doped carbon composites (ZSFO/NC) with flake-like polyhedron morphology by using ZIF-8 as a sacrificial template. Remarkably, it exhibited an initial charge/discharge capacities of 1078.3/1507.5 mAh g-1 with a high initial coulombic efficiency (ICE) of 71.2%, and maintained a steady charge/discharge capacities of 1495.7/1511.8 mAh g-1 at 0.2 A g-1 after 300 cycles. The excellent rate performance of 435.6 mAh g-1 at a higher current density of 10.0 A g-1 and superior reversible capacity of 532.3/536.2 mAh g-1 after 500 cycles at 2.0 A g-1 were obtained. It revealed that the nitrogen-doped carbon matrix and peculiar structure of ZSFO/NC not only effectively buffered large volume expansion upon (de)lithiation through the synergistic interface action between ZnO, SnFe2O4 and NC, but also improved capacity of the composite by large contribution of surface pseudo-capacitance. The excellent charge-discharge performance showed that ZSFO/NC composite has a great potential for LIBs due to the synergistic effect of the multi-components.

9.
Zool Res ; 42(3): 262-266, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33764016

RESUMO

The Dianchi golden-line barbel, Sinocyclocheilus grahami (Regan, 1904), is one of the "Four Famous Fishes" of Yunnan Province, China. Given its economic value, this species has been artificially bred successfully since 2007, with a nationally selected breed (" S. grahami, Bayou No. 1") certified in 2018. For the future utilization of this species, its growth rate, disease resistance, and wild adaptability need to be improved, which could be achieved with the help of molecular marker-assisted selection (MAS). In the current study, we constructed the first chromosome-level genome of S. grahami, assembled 48 pseudo-chromosomes, and obtained a genome assembly of 1.49 Gb. We also performed QTL-seq analysis of S. grahami using the highest and lowest bulks (i.e., largest and smallest size) in both a sibling and random population. We screened two quantitative trait loci (QTLs) (Chr3, 14.9-39.1 Mb and Chr17, 4.1-27.4 Mb) as the major growth-related locations. Several candidate genes (e.g., map2k5, stat1, phf21a, sox6, and smad6) were also identified, with functions related to growth, such as cell differentiation, neuronal development, skeletal muscle development, chondrogenesis, and immunity. These results built a solid foundation for in-depth MAS studies on the growth traits of S. grahami.

10.
J Am Soc Mass Spectrom ; 32(4): 969-976, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33779186

RESUMO

Developing a rapid, simple, and sensitive method to analyze drugs is critical to forensic research study because of the widespread occurrence of the matrix effect. Herein, we develop a method using thermal-assisted carbon fiber ionization mass spectrometry that can be used to directly analyze drugs in biological fluid. The key feature of this technique is that the biological samples such as urine and blood can be achieved online as precipitated protein on the carbon fiber tip and thermally desorbed by the metal ceramics heater, which can reduce the matrix effects and improve the sensitivity. Analytes including raw urine, blood, oral fluid, drink, tobacco tar, drug tablets, and paper cards can be rapidly identified and analyzed within a few minutes regardless of their physical variations. Due to its simplicity and noninvasive analysis, this method can be used for drugged driving analysis and to achieve point-of-care drug testing in clinical and forensic chemistry.

11.
Huan Jing Ke Xue ; 42(4): 1847-1860, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742820

RESUMO

In this work, the influence of an integrated method based on calcium nitrate, denitrifying bacteria, and zirconium-modified zeolite (CN+DB+ZZ) on the transport and transformation of nitrogen (N) and phosphorus (P) in sediments was investigated, and the risk of nitrate release from the calcium nitrate-injected sediment was evaluated. The effects of the single calcium nitrate injection (CN), calcium nitrate, and denitrifying bacteria combined treatment (CN+DB) and the combined treatment using calcium nitrate injection and zirconium-modified zeolite capping (CN+ZZ) on the mobilization of N and P in sediment were compared, and the nitrate releasing risk of these methods was also evaluated. The results indicated that although CN treatment could effectively control the P release from the sediment, this method could not effectively control the release of ammonium-nitrogen from sediment and has a high risk of releasing nitrate-nitrogen. The CN+DB combined method not only could effectively control the liberation of sedimentary P but also reduce the risk of nitrate-nitrogen release from the calcium nitrate-injected sediment compared with the single CN method. However, the CN+DB combined method could not effectively control the release of ammonium-nitrogen from the sediment. The CN+ZZ combined treatment not only could effectively prevent the release of sedimentary P but could also greatly reduce the release of ammonium-nitrogen from the sediment. However, the CN+ZZ combined method could result in a substantial release of nitrate-nitrogen from the calcium nitrate-injected sediment. The CN+DB+ZZ combined technology could effectively control the release of P from sediment as well as greatly reduce the risk of ammonium-nitrogen release from the sediment. Furthermore, the CN+DB+ZZ combined method resulted in a significant reduction of nitrate-nitrogen released from the calcium nitrate-injected sediment compared with the CN and CN+ZZ treatment methods. The prevention of the dissolution of the P-bound iron oxide/hydroxide in the sediment, the reduction of redox-sensitive P in sediment, and the improvement of the phosphate and ammonium adsorption abilities of sediment by the CN+DB+ZZ combined method is critical to control the release of phosphorus and ammonium-nitrogen from sediment using this method. Results of this study reveal that the CN+DB+ZZ combined technology could be a promising method for the control of phosphorus and ammonium-nitrogen release from sediments.


Assuntos
Poluentes Químicos da Água , Zeolitas , Bactérias , Compostos de Cálcio , Sedimentos Geológicos , Nitratos , Nitrogênio/análise , Fósforo , Poluentes Químicos da Água/análise , Zircônio
12.
Food Funct ; 12(7): 2962-2971, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33690750

RESUMO

This study was conducted to compare the effect of raw (WB) or mixed fungi-fermented wheat bran (FWB) on the growth, nutrient digestibility and intestinal health in weaned piglets. After the preparation of FWB, twenty-one cross-bred weaned piglets (7.20 ± 0.5 kg) were separated into three groups for a 40-day trial. The pigs in the control group were fed a basal corn-soybean meal diet. For the other two groups, 8% of expanded corn in the basal diet was replaced by equivalent WB or FWB. Results showed that the content of main nutrients and the composition of dietary fiber in FWB improved compared to that for WB. The digestibility of fiber in pigs fed FWB improved (P < 0.05) compared to the control and/or WB without affecting their growth performance. Both WB and FWB decreased the conditional pathogen (Streptococcus) or/and E. coli virulence factor (STb) in the colon compared to control (P < 0.05), and the ratio of villus height to crypt depth (VCR) in jejunum increased (P < 0.05). The number of goblet cells, the expression of MUC-1 and pBD1 in jejunal mucosa, and the proportion of blood CD4+ T lymphocyte subset improved (P < 0.05) by FWB rather than WB. Furthermore, although only WB elevated (P < 0.05) the concentration of butyrate in the colon, both WB and FWB increased the number of butyrate-producing bacteria (P < 0.05) compared to the control. Thus, the main advantage of FWB over WB in weaned pigs is its improvement in fiber digestibility.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33744599

RESUMO

The determination of cause of death is one of the most important tasks in forensic practice. However, asphyxia is a difficult cause of death to determine, especially when the deceased has an underlying disease that can lead to a sudden unexpected death, such as coronary atherosclerotic heart disease (CAHD, which is the leading cause of sudden cardiac death, SCD), because its determination is currently still based on an exclusion strategy. In this study, gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS)-based untargeted metabolomics was employed to obtain the pulmonary metabolic profiles of rats who died from asphyxia and SCD. First, fourteen metabolites were identified to investigate the mechanism of death from asphyxia, and we proposed some explanations that may account for these metabolic alterations, including the perturbation of amino acid metabolism, lipid metabolism, and energy metabolism (TCA cycle). Second, we discovered eight potential biomarkers to differentiate between asphyxia and SCD as the cause of death. The excellent classification performances of the eight individual biomarkers and their combination in fresh lung tissue were observed. Third, we also explored the relative change in the concentration of the eight metabolites and their classification performance in decomposed tissue (at 24 h postmortem). Lactic acid, pantothenic acid, and the combination of the eight biomarkers can be recognized as perfect classifiers to discriminate asphyxia from SCD even when decomposition has occurred. Our results showed that GC-HRMS-based untargeted metabolomics can be used as a promising tool to explore the metabolic alterations of the death process and to determine the cause of death.

15.
Bioorg Chem ; 110: 104775, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33725509

RESUMO

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33712429

RESUMO

Carbohydrate is the most important energy source in the diet of human and animals. A large number of studies have shown that dietary carbohydrates (DCHO) are related to the bacterial community in the gut, but its relationship with the composition of intestinal fungi is still unknown. Here, we report the response of colonic fungal community to different composition of DCHO in a pig model. Three factors, ratio of (2:1, 1:1 and 1:2) amylose to amylopectin (AM/AP), level of non-starch polysaccharides (NSP, 1%, 2% and 3%) and mannan-oligosaccharide (MOS, 400, 800 and 1,200 mg/kg), were considered according to a L9 (34) orthogonal design to form nine diets with different carbohydrate composition. Sequencing based on an Illumina HiSeq 2500 platform targeting the internal transcribed spacer 1 region showed that the fungal community in the colon of the pigs responded to DCHO in the order of MOS, AM/AP and NSP. A large part of some low-abundance fungal genera correlated with the composition of DCHO, represented by Saccharomycopsis, Mrakia, Wallemia, Cantharellus, Eruotium, Solicoccozyma and Penicillium, were also associated with the concentration of glucose and fructose, as well as the activity of ß-D-Glucosidase in the colonic digesta, suggesting a role of these fungi in the degradation of DCHO in the colon of pigs. Our study provides direct evidences for the relationship between the composition of DCHO and fungal community in the colon of pigs, which is helpful to understand the function of gut microorganisms in pigs.ImportanceAlthough fungi are a large group of microorganisms besides bacteria and archaea in the gut of monogastric animals, the nutritional significance of fungi has been ignored for a long time. Our previous studies have revealed a distinct fungal community in the gut of grazing Tibetan pigs, and a close correlation between fungal species and short-chain fatty acids, the main microbial metabolites of carbohydrates in the hindgut of pigs. These groundbreaking findings indicate a potential relationship between intestinal fungi and the utilization of DCHO. However, no evidence directly proves the response of intestinal fungi to changes in DCHO. Here, we show a clear alteration of colonic fungal community in pigs triggered by different composition of DCHO simulated by varied concentrations of starch, NSP and oligosaccharides. Our results highlight the potential involvement of intestinal fungi in the utilization of nutrients in monogastric animals.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33715204

RESUMO

The present study investigated the effects of Bacillus coagulans and yeast hydrolysate supplementation on growth performance, immune response and intestinal barrier function of weaned piglets. Twenty-four weaned piglets with an average body weight (BW) of 6.89 ± 0.15 kg were divided into four diets for 28 days. The treatments were basal diet (control), basal diet supplemented with antibiotic (20 mg/kg colistin sulphate and 40 mg/kg bacitracin zinc, AT), probiotics (400 mg/kg Bacillus coagulans ≥5 × 109 CFU/g, BC) or yeast hydrolysate (5000 mg/kg yeast hydrolysate, YH). Average daily gain (ADG) and average daily feed intake (ADFI) were improved by AT and YH diets (p < 0.05), while BC diet only increased ADG (p < 0.05). The complement 3 (C3), lysozyme (LZM) and tumour necrosis factor-α (TNF-α) concentrations in serum were increased in BC diet (p < 0.05). Feeding AT and YH caused the increase of jejunal villus height (p < 0.05), and a higher ratio of villus height/crypt depth was observed in AT, BC and YH groups (p < 0.05). The mRNA expression of zonula occludens-1 (ZO-1) in jejunal mucosa was up-regulated by AT, BC and YH diets (p < 0.05). Dietary AT, BC or YH inclusion decreased the interleukin-1ß (IL-1ß) concentration and TNF-α mRNA expression (p < 0.05), and YH supplementation even down-regulated toll-like receptor 4 (TLR4) and CD14 expressions (p < 0.05). In summary, the dietary administration of BC or YH both improves growth performance through promoting the intestinal barrier function, indicating both of them can serve as potential alternatives to antibiotics growth promoters for the piglet production.

18.
Neurosci Lett ; 751: 135830, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33722543

RESUMO

ErbB4 loss-of-function in catecholaminergic neurons induces catecholamine dyshomeostasis. Despite ErbB4's significant role in neuropathology, the signaling pathways that regulate these changes are still widely unknown. In this study, we attempt to identify the downstream pathway of ErbB4 that regulates catecholamine homeostasis. The SH-SY5Y human neuroblastoma cell line was used as the in vitro model for catecholaminergic neurons. Western blotting, enzyme-linked immunosorbent assay, and pharmacological and genetic manipulations by agonist/antagonist or small interference RNA were used to investigate the relationship between ErbB4 and extracellular catecholamines. We confirmed that ErbB4 is abundantly expressed in undifferentiated and retinoic acid-differentiated catecholaminergic cells from the SH-SY5Y cell line. ErbB4 inhibition increase the ratio of phosphorylated p38 to total p38 in SH-SY5Y human neuroblastoma cells. Consistent with previous in vivo observations in mice, ErbB4 deficiency led to increases in extracellular dopamine and norepinephrine levels. However, the resulting increase in extracellular dopamine, but not norepinephrine, could be suppressed by p38 inhibitor SB202190. Our results suggest that both extracellular dopamine and norepinephrine homeostasis could be regulated by ErbB4 in human catecholaminergic cells, and ErbB4 may regulate extracellular dopamine, but not norepinephrine, through the p38 MAPK signaling pathway, thus indicating different regulatory pathways of dopamine and norepinephrine by ErbB4 in catecholaminergic neurons.

19.
BMC Genomics ; 22(1): 164, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750298

RESUMO

BACKGROUND: Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. RESULTS: Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. CONCLUSIONS: By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.

20.
Biomed Pharmacother ; 138: 111511, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33744757

RESUMO

Flavonoids are natural plant-derived dietary bioactive compounds having a substantial impact on human health. Morin hydrate is a bioflavonoid mainly obtained from fruits, stem, and leaves of Moraceae family members' plants. Plenty of evidences supported that morin hydrate exerts its beneficial effects against various chronic and life-threatening degenerative diseases. Our current article discloses the recent advances that have been studied to explore the biological/pharmacological properties and molecular mechanisms to better understand the beneficial and multiple health benefits of morin hydrate. Indeed, Morin hydrate exerts free radical scavenging, antioxidant, anti-inflammatory, anti-cancerous, anti-microbial, antidiabetic, anti-arthritis, cardioprotective, neuroprotective, nephroprotective, and hepatoprotective effects. Moreover, morin hydrate exhibits its pharmacological activities by modulating various cellular signaling pathways such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-қB), Mitogen-activated protein kinase (MAPK), Janus kinases/ Signal transducer and activator of transcription proteins (JAKs/STATs), Kelch-like ECH-associated protein1/Nuclear erythroid-2-related factor (Keap1/Nrf2), Endoplasmic reticulum (ER), Mitochondrial-mediated apoptosis, Wnt/ß-catenin, and Mechanistic target of rapamycin (mTOR). Most importantly, morin hydrate has the potential to modulate a variety of biological networks. Therefore, it can be predicted that this therapeutically potent compound could serve as a dietary agent for the expansion of human health and might be helpful for the development of the novel drug in the future. However, due to the lack of clinical trials, special human clinical trials are needed to address the effects of morin hydrate on various life-threatening disparities to recommend morin and/or morin-rich foods with other foods or bioactive dietary components, as well as dose-response interaction and safety profile.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...