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1.
RNA Biol ; : 1-18, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110962

RESUMO

Pancreatic cancer has the worst prognosis of all common cancers. Pancreatic cancer cells have a metabolic advantage due to their swiftly adaptive responses to hypoxic and low-nutrient medium. This advantage contributes to the aggressivity of pancreatic cancer. In this study, lncRNA MIR210HG was abnormally upregulated within pancreatic cancer. It acted as a key oncogenic regulator of pancreatic cancer aggressiveness and glycolysis. Knockdown of MIR210HG significantly inhibited the aggressive phenotype of pancreatic cancer cells and inhibited the growth of xenograft tumours. More importantly, MIR210HG knockdown inhibited pancreatic cancer cell glycolysis via regulating the glycolysis-related hexokinase 2 (HK2) and Pyruvate kinase muscle isozyme M2 (PKM2) expression. Compared with the MIR210HG knockdown group, miR-125b-5p inhibition promoted the aggressive phenotypes and glycolysis of pancreatic cancer cells. Furthermore, the effects of MIR210HG knockdown on HK2 and PKM2 expression, pancreatic cancer cell aggressive phenotypes, and glycolysis were significantly reversed by miR-125b-5p inhibition. In tissue samples, MIR210HG expression was negatively correlated with miR-125b-5p levels and positively correlated with HK2 and PKM2 expression. miR-125b-5p expression was negatively correlated with HK2 and PKM2 expression. In conclusion, MIR210HG affected the phenotypes of pancreatic cancer cells, including proliferation, invasion, migration, and glycolysis, via modulating the miR-125b-5p/HK2/PKM2 axis.

2.
Ecotoxicol Environ Saf ; 220: 112408, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111662

RESUMO

BACKGROUND: Epidemiologic evidence suggests that PM2.5 exposure aggravates asthma, but the molecular mechanisms are not fully discovered. METHODS: Ovalbumin (OVA)-induced mice exposed to PM2.5 were constructed. Pathological staining and immunofluorescence were performed in in vivo study. Gene set enrichment analysis (GSEA) was performed to identify the pathway involved in asthma severity by using U-BIOPRED data (human bronchial biopsies) and RNA-seq data (Beas-2B cells treated with PM2.5). Lentiviruses transfection, Real-time qPCR, immunofluorescence staining and trans-epithelial electrical resistance (TEER) measurement were performed for mechanism exploration in vitro. RESULTS: PM2.5 exposure aggravated airway inflammation and mucus secretion in OVA-induced mice. Based on transcriptome analysis of mild-to-severe asthma from human bronchial biopsies, gene set enrichment analysis (GSEA) showed that up-regulated reactive oxygen species (ROS) pathway gene set and down-regulated apical junction gene set correlated with asthma severity. Consistent with the analysis of mild-to-severe asthma, after PM2.5 exposure, the ROS pathway in Beas-2B cells was up-regulated with the down-regulation of apical junction. The expression levels of genes involved in the specific gene sets were validated by using qPCR. The mRNA levels of junction genes, ZO-1, E-cadherin and Occludin, were significantly decreased in cells exposed to PM2.5. Moreover, it confirmed that inhibition of ROS recovered the expression levels of E-cadherin, Occludin and ZO-1, and ameliorated inflammation and mucus secretion in airway in OVA-induced mice exposed to PM2.5. Meanwhile, ROS level was elevated by PM2.5. By checking trans-epithelial electrical resistance (TEER) value, we also found that epithelial barrier was damaged after PM2.5 exposure. Importantly, Stanniocalcin 2 (STC2) was identified as a key gene in regulation of epithelial barrier. It showed that STC2 expression was up-regulated by PM2.5, which was recovered by NAC as well. Over-expression of STC2 could decrease the expression levels of ZO-1, Occludin and E-cadherin. Contrarily, suppression of STC2 could increase the expression levels of ZO-1, Occludin and E-cadherin reduced by PM2.5. CONCLUSIONS: By using transcriptome analysis, we revealed that STC2 played a key role in PM2.5 aggravated airway dysfunction through regulation of epithelial barrier in OVA-induced mice.

3.
Ecotoxicol Environ Saf ; 218: 112272, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33962274

RESUMO

BACKGROUND: Particulate matter of 2.5 µm or less in diameter (PM2.5) is one of the most complex pollutants in the atmospheric environment and harmful to human health. Epidemiologic evidence suggests that asthma exacerbation is associated with PM2.5 exposure. However, the molecular mechanism of PM2.5 in the development of asthma is not fully addressed. METHODS: PM2.5 was collected from Chengdu, China, and the components were analyzed. The relationship between PM2.5 exposure and asthma severity was investigated in an Ovalbumin (OVA)-induced murine model of asthma. U-BIOPRED data from public database and our own RNA-seq data were analyzed to identify the hub genes. Real-time qPCR, immunofluorescence, immunohistochemistry and pathological staining were applied for mechanism dissection in both in vitro and in vivo studies. RESULTS: In PM2.5 samples, a total of 11 elements including major elements and trace elements were identified, 14 of the 16 Polycyclic aromatic hydrocarbons (PAHs) were detected except Acenaphthene and Fluorene. PM2.5 exposure aggravated pulmonary inflammation, mucus secretion, and neutrophils infiltration in asthma model. Based on transcriptome analysis of mild-to-severe asthma dataset, it showed that mucus secretion and neutrophil degranulation correlated with asthma severity. Moreover, NAD(P)H:quinone oxidoreductase 1 (NQO1) was screened out as a hub gene whose expression positively correlated with MUC5AC expression in patient with asthma by performing joint analysis. Furthermore, in OVA-induced asthma model and in vitro assay, it also revealed that PM2.5-induced MU5AC expression was regulated by NQO1 through neutrophil extracellular traps (NETs) caused by oxidative stress. CONCLUSION: Taken together, we discovered a potential relationship between asthma severity and PM2.5 exposure. In addition, neutrophil depletion, NETs inhibition or anti-NQO1 might be novel potential therapeutic options for treatment of PM2.5-induced mucus hyper-secretion.

4.
RNA Biol ; : 1-11, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998370

RESUMO

tRNA-derived small RNA (tsRNA) is a novel class of non-coding RNA that is usually produced from tRNA following endonuclease cleavage which occurs under stress conditions. There are two types of tsRNAs: tRNA-derived fragments (tRFs) and stress-induced tRNA halves (tiRNAs), which differ in their cleavage position. Many studies have demonstrated that tsRNAs are involved in various physiological and pathological processes apart from cancer and gene expression. In this review, we briefly described the biogenesis, classification, and characteristics of tsRNAs and summarized the current research progress of tsRNAs in metabolic diseases, senescence, reproduction, stress, and organ injury, and finally put forward some problems to be solved.

5.
J Am Chem Soc ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848146

RESUMO

The end-capping group (EG) is the essential electron-withdrawing component of nonfullerene acceptors (NFAs) in bulk heterojunction (BHJ) organic solar cells (OSCs). To systematically probe the impact of two frequent EG functionalization strategies, π-extension and halogenation, in A-DAD-A type NFAs, we synthesized and characterized four such NFAs: BT-BIC, LIC, L4F, and BO-L4F. To assess the relative importance of these strategies, we contrast these NFAs with the baseline acceptors, Y5 and Y6. Up to 16.6% power conversion efficiency (PCE) in binary inverted OSCs with BT-BO-L4F combining π-extension and halogenation was achieved. When these two factors are combined, the effect on optical absorption is cumulative. Single-crystal π-π stacking distances are similar for the EG strategies of π-extension. Increasing the alkyl substituent length from BT-L4F to BT-BO-L4F significantly alters the packing motif and eliminates the EG core interactions of BT-L4F. Electronic structure computations reveal some of the largest NFA π-π electronic couplings observed to date, 103.8 meV in BT-L4F and 47.5 meV in BT-BO-L4F. Computed electronic reorganization energies, 132 and 133 meV for BT-L4F and BT-BO-L4F, respectively, are also lower than Y6 (150 meV). BHJ blends show preferential π-face-on orientation, and both fluorination and π-extension increase NFA crystallinity. Femto/nanosecond transient absorption spectroscopy (fs/nsTA) and integrated photocurrent device analysis (IPDA) indicate that π-extension modifies the phase separation to enhance film ordering and carrier mobility, while fluorination suppresses unimolecular recombination. This systematic study highlights the synergistic effects of NFA π-extension and fluorination in affording efficient OSCs and provides insights into designing next-generation materials.

6.
Toxicology ; 456: 152779, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33862173

RESUMO

Dibutyltin (DBT) is an organotine widely applied in stabilizing plastics and de-worm poultry agents. But the effects of DBT on immature Leydig cells remain elusive. Thus, the present study aims to investigate whether in vitro exposure to DBT affects immature Leydig cell function of androgen production and delineate the underlying mechanisms. 35 days old rat immature Leydig cells were isolated and exposed to DBT at different concentrations (0, 0.1, 0.5, and 1 µM). It was found that 0.5 and 1 µM DBT lowered androgen production from immature Leydig cells under basal conditions. DBT at 1 µM lowered androgen production from immature Leydig cells under the stimulations from luteinizing hormone or 8-Br-cAMP. DBT at 1 µM lowered 22R-hydroxycholesterol and pregnenolone-mediated androgen production from immature Leydig cells. DBT at 0.1, 0.5, and 1 µM down-regulated the mRNA expression levels of Lhcgr, Star, Cyp11a1, Hsd3b1, and Nr5a1. Further investigation found that DBT at 1 µM directly inhibited CYP11A1 and 3ß-HSD1 enzyme activities. In conclusion, this study told us that in vitro exposure to DBT inhibited androgen biosynthesis in immature Leydig cells by selectively interfering with the expressions and enzyme activities of CYP11A1 and 3ß-HSD1.

7.
J Am Chem Soc ; 143(3): 1590-1597, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33393301

RESUMO

A series of novel bismuth-bridged viologen analogues, bismoviologens (BiV2+), synthesized through a combination of a bismuth atom and viologen skeleton is reported. Their optical and electrochemical properties were fine-tuned through the N-arylation or N-alkylation reactions. Bismolviologens not only showed good redox properties but also exhibited phosphorescence under ambient conditions (in air at room temperature). This phenomenon makes BiV2+ the first examples of phosphorescent viologen analogues reported to date. On the basis of the excellent and unique redox and optical properties of BiV2+, their electrophosphorochromic devices were fabricated. Furthermore, BiV2+ was used for the first time as both a photocatalyst and electron mediator in visible light-induced cross-dehydrogenative coupling reactions.

8.
GM Crops Food ; 12(1): 115-124, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33084486

RESUMO

Transgenic crops that produce Bacillus thuringiensis (Bt) toxins are effective tools for controlling lepidopteran pests. However, the degree of susceptibility to Bt toxins differs among various pest species due to relatively narrow spectrum and high selectivity of such toxins. Bt corn hybrids for Chinese market were designed to target Asian corn borer Ostrinia furnacalis (Guenée), while their efficacy against other lepidopteran pests are not well defined, such as Conogethes punctiferalis (Guenée), Helicoverpa armigera (Hübner), Agrotis ypsilon (Rottemberg), and Mythimna separata (Walker), which are also important lepidopteran pests on corn in the Huang-Huai-Hai Summer Corn Region of China. To determine what type of Bt corn is suitable for this region, the efficacy of five Bt toxins, i.e., Cry1Ab, Cry1Ac, Cry1F, Cry2Ab, and Vip3A, to these five lepidopteran species was evaluated in laboratory. Both O. furnacalis and C. punctiferalis showed similar high susceptibility to all five Bt toxins. A. ypsilon and M. separate were less sensitive to Cry1Ab and Cry1Ac than the other species. H. armigera, A. ypsilon and M. separate were less sensitive to Cry1F than O. furnacalis and C. punctiferalis. H. armigera was more sensitive to Cry2Ab than other tested species. All five species were equally sensitive to Vip3A, though their LC50s were all relatively higher. These findings suggest that the first generation Bt corn expressing single Cry1 toxin should not be the first choice because of the potential risk of control failure or less efficacy against H. armigera, A. ypsilon or M. separate. The second-generation Bt corn expressing Cry1 and Cry2 toxins, or the third generation Bt corn expressing Cry1, Cry2 and Vip3A toxins might produce better protection of corn in the Huang-Huai-Hai Summer Corn Region of China.


Assuntos
Bacillus thuringiensis , Animais , Bacillus thuringiensis/genética , China , Produtos Agrícolas , Fatores de Transcrição , Zea mays/genética
9.
Brachytherapy ; 20(2): 446-453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33309002

RESUMO

PURPOSE: The purpose of this study was to assess the efficacy of an iodine-125 (125I) seed strand combined with a metal stent compared with a metal stent for treatment of obstructive jaundice caused by pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: A retrospective analysis was carried out of patients who were referred to Shanghai Zhongshan Hospital of Fudan University with a diagnosis of PDAC between January 1, 2010 and January 31, 2019. A total of 110 consecutive patients with obstructive jaundice caused by PDAC were divided into the iodine-125 seed strand combined with a metal stent group (Group A = 48) and the metal stent group (Group B = 62). The primary outcome was stent obstruction-free survival time, and secondary outcomes were overall survival and complications. RESULTS: The median stent obstruction-free survival time was 133.0 (95% confidence interval (CI): 166.093-149.907) days, and the median overall survival was 212.0 (95% CI: 187.183-236.817) days in all patients. Median stent obstruction-free survival time was 175 days (95% CI 103.165-246.835 days) in Group A versus 120 days (95% CI 87.475-152.525 days) in Group B (p = 0.035). A lower Eastern Cooperative Oncology Group (ECOG) score (p = 0. 000) and iodine-125 seed strand combined with metal stent implantation (p = 0.008) were associated with a longer stent obstruction-free survival time. Obstruction length (p = 0.083), ECOG score (p = 0.000), and iodine-125 seeds (p = 0.037) might have potential impact on stent obstruction-free survival time and were included for multivariable analysis using the Cox proportional hazards model. Stent restenosis was observed in 18.8% (9/48) of patients in Group A and 54.8% (34/62) in Group B, respectively. There was no significant difference in median survival between Group A and Group B (p = 0.409). The median survival in Group A was 209 days (95% CI 150.750-267.250) and 202 days (95% CI 190.624-233.376) in Group B. The median survival of patients with a lower ECOG score was better than that of patients with a higher ECOG score (267 days vs 132 days, p = 0.000). The Grade 3 or 4 complications occurred in 4 (8.3%) of the 48 patients in Group A (one case of hemobilia, one case of liver abscess, two cases of choleperitonitis) and in 5 (8.1%) of the 62 patients in Group B (one case of hemobilia, two cases of liver abscess, two cases of choleperitonitis) (p = 0.972). CONCLUSIONS: Implantation of an iodine-125 seed strand combined with a metal stent provides longer obstruction-free survival time compared with a metal stent in patients with obstructive jaundice caused by PDAC. It seems reasonable to choose an iodine-125 seed strand combined with a metal stent as a treatment for these patients.

10.
Anal Chem ; 93(3): 1771-1778, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33382576

RESUMO

A green analytical strategy has been developed for the analysis of 10 perfluorinated compounds (PFCs) incorporating supramolecular solvent (SUPRAS)-based extraction and ultra-high-performance supercritical fluid chromatography (UHPSFC)-tandem mass spectrometry. The SUPRAS was prepared through self-assembly of reverse micelles by mixing heptanol, tetrahydrofuran, and water at optimized volume ratios. An imidazolium-based germinal dicationic ionic liquid (DIL), 1,1-bis(3-methylimidazolium-1-yl) butylene difluoride ([C4(MIM)2]F2), was dissolved in the make-up solvent of UHPSFC and introduced post-column but before the electrospray ionization source. After chromatographic separation on a Torus DIOL analytical column (100 mm × 2.1 mm, 1.7 µm), the PFC analytes associated with the DIL reagent through charge complexation. The formation of positively charged complexes resulted in improved ionization efficiency and analytical sensitivity. Enhancement in signal intensity by one to two magnitudes was achieved in the positive ionization mode compared to the negative ionization mode without using the dicationic ion-pairing reagent. The developed protocol was applied to 32 samples of real textiles and 6 samples of real food packaging materials, which exhibited great potential for the analysis of anionic compounds.

11.
Acta Neuropathol Commun ; 8(1): 221, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308315

RESUMO

Cancer-associated fibroblasts (CAFs) are activated fibroblasts constituting the major stromal components in many types of cancer. CAFs contribute to hallmarks of cancer such as proliferation, invasion and immunosuppressive tumor microenvironment, and are associated with poor prognosis of patients with cancer. However, in glioblastoma (GBM), the most common and aggressive primary malignant brain tumor, our knowledge about CAFs or CAF-like stromal cells is limited. Here, using commonly accepted CAF markers, we characterized CAF-like cell populations in clinical glioma specimens and datasets along with mouse models of GBM. We found that tumor-associated pericytes marked by co-expression of fibroblast activation protein α (FAP) and PDGFRß represent major stromal cell subsets in both human GBM and mouse GBM models, while a fraction of mesenchymal neoplastic cells also express FAP in patient tumors. Since oncolytic viruses can kill cancer cells and simultaneously modulate the tumor microenvironment by impacting non-neoplastic populations such as immune cells and tumor vasculature, we further investigated the ability of oncolytic viruses to target GBM-associated stromal cells. An oncolytic adenovirus, ICOVIR15, carrying ∆24-E1A and an RGD-fiber, infects and depletes FAP+ pericytes as well as GBM cells in murine GBM. Our study thus identifies FAP+/PDGFRß+ pericytes as a major CAF-like stromal cell population in GBM, and highlights the unique property of this oncolytic adenovirus to target both GBM cells and GBM-associated stromal FAP+ cells.

12.
Epigenomics ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33242255

RESUMO

Aim: To elucidate the transcriptional characteristics of COVID-19. Materials & methods: We utilized an integrative approach to comprehensively analyze the transcriptional features of both COVID-19 patients and SARS-CoV-2 infected cells. Results: Widespread infiltration of immune cells was observed. We identified 233 genes that were codifferentially expressed in both bronchoalveolar lavage fluid and lung samples of COVID-19 patients. Functional analysis suggested upregulated genes were related to immune response such as neutrophil activation and antivirus response, while downregulated genes were associated with cell adhesion. Finally, we identified LCN2, STAT1 and UBE2L6 as core genes during SARS-CoV-2 infection. Conclusion: The identification of core genes involved in COVID-19 can provide us with more insights into the molecular features of COVID-19.

13.
Int J Hyperthermia ; 37(1): 1322-1329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33243047

RESUMO

OBJECTIVE: To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. METHODS: A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman's correlation test. RESULTS: The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = -0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = -0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). CONCLUSION: Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

14.
FASEB J ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184968

RESUMO

Secretory phospholipase A2 group IB (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) are closely associated with proteinuria in idiopathic membranous nephropathy (IMN). Podocytes constitute an important component of glomerular filtration, and high basal autophagy is indispensable for podocyte function. The current study aimed to analyze the relationship between sPLA2-IB and podocyte autophagy in IMN and determine whether sPLA2-IB mediates abnormal autophagy regulation in podocytes. The serum sPLA2-IB level and podocyte autophagy were detected, and clinical data were collected from IMN patients with different proteinuria levels. Then, the effects of sPLA2-IB on autophagy signaling pathways were evaluated in cultured human podocytes treated with sPLA2-IB, rapamycin, p38 inhibition, and PLA2R-siRNA in vitro. We found that IMN patients with nephrotic-range proteinuria have a significantly higher level of sPLA2-IB and fewer autophagosomes than those with non-nephrotic-range proteinuria. In vitro sPLA2-IB-induced insufficient autophagy in podocytes and promoted podocyte injury via activation of the mTOR/ULK1ser757 signaling pathway. Moreover, inhibition of p38 MAPK evidently abrogated sPLA2-IB-induced autophagy and the activation of mTOR/ULK1ser757 . Additionally, PLA2R silencing demonstrated that sPLA2-IB-induced abnormal autophagy was also PLA2R-dependent. In conclusion, the results revealed that sPLA2-IB downregulated autophagy and contributed to podocyte injury via PLA2R though activation of the p38MAPK/mTOR/ULK1ser757 signaling pathway.

15.
Exp Ther Med ; 20(5): 120, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33005246

RESUMO

A growing number of 'Young' patients less than 40 years of age are being hospitalized with a diagnosis of acute myocardial infarction (AMI) due to increased prevalence of risk factors for atherosclerosis. The aim of this study was to compare clinical characteristics and performances of AMI between young and elderly patients. We conducted a retrospective study to compare AMI in young patients and elder patients. Based on the medical record databases in our hospital, we enrolled 114 'young' AMI patients (age ≤42 years) and 179 'elder' AMI patients (≥60 years), and then collected and analyzed their demographic information, clinical performances, and coronary angiography results. In the young AMI group, the proportion of male patients was higher than that in the elder AMI group (94.7 vs. 64.2%, P<0.05). Compared with the elder AMI patients, young patients had higher rates of smoking history and positive family medical history, but lower rates of hypertension and diabetes. Elder patients with AMI were more likely to develop various clinical performances, and multiple-branch lesions; however, young AMI patients had relatively fewer symptoms, and the tissue lesions were more limited. The clinical profiles of AMI in young patients were different from that in elder AMI patients. Specific interventions should be carried out to prevent and control the prevalence of AMI in the young population.

16.
J Craniofac Surg ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038187

RESUMO

BACKGROUND: Advances in the understanding of wrinkling crow's feet while improving the safety and efficacy of botulinum toxin type A injection has pointed to drug dispersion in the lateral orbital wrinkles as a cause of adverse events of botulinum toxin type A injection. The purpose of this study is to identify the distribution of temporal and zygomatic branches of facial nerve in the orbicularis oculi muscles. METHODS: Anatomical dissection of cadavers was performed in 31 cadavers, 13 females and 18 males, with ages ranging from 20 to 60 years, which of all had been embalmed by 10% formalin solution. The facial nerve was identified within subcutaneous tissue close periorbital region and both traced proximal and distal. Its temporal branch, zygomatic branch, facial and muscular entrance were located and accurately measured relative to established surface landmarks. RESULTS: Dissection of the facial nerve revealed 2 to 6 entrances of the temporal branch into the orbicularis oculi and 1 to 5 entrances of the zygomatic branch into the orbicularis oculi. Concerning the measurements of neural entering points, distance and angle from orbicularis oculi muscle to lateral ocular angle, a distribution map of its muscular entrance and their patterns of distribution were constructed. According to the dense area of the coordinate map, there were 3 points determined as the muscular entrance points to established surface landmarks. CONCLUSIONS: An anatomical dissection of cadavers was performed to identify the distribution of temporal and zygomatic branches of the facial nerve in the orbicularis oculi. According to the dense area of the coordinate map, the surface landmarks of 3 points were established as the muscular entrance of the facial nerve (MEF).

18.
EMBO Rep ; 21(11): e50283, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016573

RESUMO

A microdeletion within human chromosome 5q14.3 has been associated with the occurrence of neurodevelopmental disorders, such as autism and intellectual disability, and MEF2C haploinsufficiency was identified as main cause. Here, we report that a brain-enriched long non-coding RNA, NDIME, is located near the MEF2C locus and is required for normal neural differentiation of mouse embryonic stem cells (mESCs). NDIME interacts with EZH2, the major component of polycomb repressive complex 2 (PRC2), and blocks EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) at the Mef2c promoter, promoting MEF2C transcription. Moreover, the expression levels of both NDIME and MEF2C were strongly downregulated in the hippocampus of a mouse model of autism, and the adeno-associated virus (AAV)-mediated expression of NDIME in the hippocampus of these mice significantly increased MEF2C expression and ameliorated autism-like behaviors. The results of this study reveal an epigenetic mechanism by which NDIME regulates MEF2C transcription and neural differentiation and suggest potential effects and therapeutic approaches of the NDIME/MEF2C axis in autism.

19.
Pharmacol Res ; : 105242, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075491

RESUMO

Over a short span of two decades, the central role of angiogenesis in the treatment of wound healing, diverse cancers, nerve defect, vascular injury and several ophthalmic diseases has become evident. Tetrahydropalmatine, as the index component of Corydalis yanhusuo W. T. Wang, is inseparable from protecting cardiovascular system, yet its role in angiogenesis has been poorly characterized. We have demonstrated the binding potential of THP and VEGFR2 using molecular docking based on the clinical experience of traditional Chinese medicine in the pretest study. Here, we identified tetrahydropalmatine (THP) as one proangiogenic trigger via regulation of arginine biosynthesis by pharmacological assays and DESI-MSI/GC-MS based metabolomics. First, the proangiogenic effects of THP were evaluated by quail chorioallantoic membrane test in vivo and multiple models of endothelial cells in vitro. According to virtual screening, the main mechanisms of THP (2/5 of the top terms with smaller p-value) were metabolic pathways. Hence, metabolomics was applied for the main mechanisms of THP and results showed the considerable metabolite difference in arginine biosynthesis (p < 0.05) altered by THP. Finally, correlated indicators were deteced using targeted metabolomics and pharmacological assays for validation, and results suggested the efficacy of THP on citrulline to arginine flux, arginine biosynthesis, and endothelial VEGFR2 expression sequentially, leading to the promotion of angiogenesis. Overall, this manuscript identified THP as the proangiogenic trigger with the potential to develop as pharmacological agents for unmet clinical needs.

20.
Circ Res ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092465

RESUMO

Rationale: Previous translational studies implicate plasma extracellular microRNA-30d (miR-30d) as a biomarker in left ventricular (LV) remodeling and clinical outcome in heart failure (HF) patients, though precise mechanisms remain obscure. Objective: To investigate the mechanism of miR-30d-mediated cardioprotection in HF. Methods and Results: In rat and mouse models of ischemic HF, we show that miR-30d gain of function (genetic, lentivirus or agomiR-mediated) improves cardiac function, decreases myocardial fibrosis, and attenuates cardiomyocyte (CM) apoptosis. Genetic or locked nucleic acid (LNA)-based knock-down of miR-30d expression potentiates pathological LV remodeling, with increased dysfunction, fibrosis, and CM death. RNA-seq of in vitro miR-30d gain and loss of function, together with bioinformatic prediction and experimental validation in cardiac myocytes and fibroblasts, were used to identify and validate direct targets of miR-30d. miR-30d expression is selectively enriched in CMs, induced by hypoxic stress and is acutely protective, targeting mitogen-associate protein kinase (MAP4K4) to ameliorate apoptosis. Moreover, miR-30d is secreted primarily in extracellular vesicles by CMs and inhibits fibroblast proliferation and activation by directly targeting integrin α5 in the acute phase via paracrine signaling to cardiac fibroblasts. In the chronic phase of ischemic remodeling, lower expression of miR-30d in the heart and plasma EVs is associated with adverse remodeling in rodent models and human subjects, and is linked to whole blood expression of genes implicated in fibrosis and inflammation, consistent with observations in model systems. Conclusions: These findings provide the mechanistic underpinning for the cardioprotective association of miR-30d in human HF. More broadly, our findings support an emerging paradigm involving intercellular communication of EV-contained miRNAs to trans regulate distinct signaling pathways across cell types. Functionally validated RNA biomarkers and their signaling networks may warrant further investigation as novel therapeutic targets in HF.

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