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1.
Chemosphere ; 262: 127968, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182104

RESUMO

Electrocoagulation (EC) coupled with E-peroxone process (ECP) was a promising and cost-effective integrated technology for shale gas fracturing flowback water (SGFFW) treatment. In this study, the ECP process was comprehensively compared with two sequential processes (EC followed by E-peroxone (EC-E-peroxone) and E-peroxone followed by EC (E-peroxone-EC)) to elucidate the synergistic effect of this coupled process. In EC-E-peroxone process, COD decreased by 89.2%, while COD decreased by 82.5% for 180 min in E-peroxone-EC process. However, COD removal efficiency was 82.4% in ECP for only 90 min. Average current efficiency of the ECP process was 29.9%, which was twice than that of the sequential processes. The enhancement factor was calculated to be 1.63, demonstrating the substantial significant synergistic effects for ECP. Only low MW components could be observed for the EC-E-peroxone (average MW = 533 Da with PD ≈ 1) and ECP process (MW = 538 Da with PD ≈ 1). These results suggested that EC-E-peroxone and ECP process had much stronger oxidation ability, demonstrating the enhancement of OH production induced by the Al-based coagulants might be responsible for the significant enhancement of COD removal. These results indicated there could be a synergistic effect between EC and ozone in addition to EC and E-peroxone reactions. Compared to the two sequential processes, ECP was a high efficiency and space-saving electrochemical system with simultaneous coagulation and enhanced OH generation by the products of anode and the cathode.

2.
Mol Med Rep ; 23(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179107

RESUMO

Endometriosis is closely associated with inflammatory reactions and angiogenesis. Whether PPARγ is a target for the treatment of endometriosis remains unknown. The present study was designed to investigate the impact of a PPARγ agonist (rosiglitazone, RSG) on endometriosis in a rat model and to identify the underlying mechanism. The endometriosis model was established in rats. The pathological state of the endometrium was examined using hematoxylin­eosin staining. The microstructures of interest were visualized using electron microscopy. Western blot analysis and reverse transcription­quantitative polymerase chain reaction were used to detect PPARγ and MAT2A expression. VEGF and caspase­3 expression were investigated using immunohistochemistry. Pathological analysis revealed transparent and red nodules in the model group, and that vasoganglions were present all over the nodules. Endometrial epithelial hyperplasia was observed in the model group, and the shape was columnar. Increased interstitial cell numbers, with compact structure and abundant blood supply, were detected in the model group. Compared with the model group, incomplete epithelial structures with sparse interstitial cells and loose structure were observed in the pathological images from RSG treatment groups. Numerous inflammatory cells and poor blood supply were observed in the endometrial tissues, and the gland was filled mostly with vacuolar cells. Electron microscopy revealed that the tissue structure was integrated. Many vacuoles were formed within the endometrial tissue and the classical morphological changes of apoptotic cells were observed in RSG­treated groups. Caspase­3 and PPARγ expression increased and expression of VEGF and MAT2A decreased in RSG­treated groups. Taken together, these results revealed that RSG impacts the development and progression of endometriosis likely by inhibiting angiogenesis and inducing apoptosis.

3.
Sci Total Environ ; 750: 141592, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882494

RESUMO

Various recent studies have shown that societal efforts to mitigate (e.g. "lockdown") the outbreak of the 2019 coronavirus disease (COVID-19) caused non-negligible impacts on the environment, especially air quality. To examine if interventional policies due to COVID-19 have had a similar impact in the US state of California, this paper investigates the spatiotemporal patterns and changes in air pollution before, during and after the lockdown of the state, comparing the air quality measurements in 2020 with historical averages from 2015 to 2019. Through time series analysis, a sudden drop and uptick of air pollution are found around the dates when shutdown and reopening were ordered, respectively. The spatial patterns of nitrogen dioxide (NO2) tropospheric vertical column density (TVCD) show a decreasing trend over the locations of major powerplants and an increasing trend over residential areas near interactions of national highways. Ground-based observations around California show a 38%, 49%, and 31% drop in the concentration of NO2, carbon monoxide (CO) and particulate matter 2.5 (PM2.5) during the lockdown (March 19-May 7) compared to before (January 26-March 18) in 2020. These are 16%, 25% and 19% sharper than the means of the previous five years in the same periods, respectively. Our study offers evidence of the environmental impact introduced by COVID-19, and insight into related economic influences.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Betacoronavirus , California , Monitoramento Ambiental , Humanos , Material Particulado/análise
4.
Food Chem ; 334: 127560, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711271

RESUMO

Post-fermented Pu-erh tea (PFPT) is a microbially-fermented tea with distinct sensory qualities and multiple health benefits. Aspergillus are the dominant fungi in the fermentation and the main contributors to the characteristics of PFPT, so their underlying functions warrant detailed study. Here, tea leaves were fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus, and resulting samples (designated as Asn, Ast and Asf, respectively) were analyzed by proteomic and metabolomic methods. Changes to the composition of flavonoids, glycerophospholipids, organo-oxygen compounds and fatty acids resulting from Aspergillus fermentation were observed. Carbohydrate-active enzymes, e.g., endoglucanases and cellulases, for degradation of cellulose, starch, lignin, pectin, xylan and xyloglucan were identified. Glycoside hydrolase, glycosyltransferases, tannase, laccases, vanillyl-alcohol oxidases and benzoquinone reductase were identified and hypothesized to catalyze hydrolysis, oxidation, polymerization and degradation of phenolic compounds. Together, functions of Aspergillius were demonstrated as production of enzymes to change concentrations and compositions of metabolites in tea leaves.


Assuntos
Aspergillus/fisiologia , Camellia sinensis/microbiologia , Enzimas/metabolismo , Folhas de Planta/microbiologia , Chá , Aspergillus/enzimologia , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/fisiologia , Aspergillus niger/enzimologia , Aspergillus niger/fisiologia , Metabolismo dos Carboidratos , Fermentação , Flavonoides/análise , Flavonoides/metabolismo , Microbiologia de Alimentos/métodos , Proteínas Fúngicas/metabolismo , Glicerofosfolipídeos/metabolismo , Metabolômica/métodos , Fenóis/análise , Fenóis/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Proteínas de Plantas/análise , Proteínas de Plantas/metabolismo , Proteômica/métodos , Chá/química , Chá/metabolismo , Chá/microbiologia
5.
J Ethnopharmacol ; 265: 113228, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777517

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The uses of medicinal plants have a long history and become one of the important sources of the health cares in Gaomi City, Shandong Province, China. However, limited studies have been done to identify these medicinal plant species and to scientifically document their associated traditional knowledge. Many species used by indigenous people could potentially represent a novel resource of medicine. The study can aid in further investigations of modern pharmacology and planning of the wild species conservation. AIM OF THE STUDY: The study aimed to investigate and record the medicinal plant taxa and their associated traditional knowledge in Gaomi City, China. MATERIALS AND METHODS: Field study was conducted from March 2018 to May 2019 with 184 residents of Gaomi City. Traditional medicinal plant specimens were collected from the field with the help of these residents and were identified and authenticated in the Herbarium of the School of Pharmacy, Binzhou Medical University. Ethnobotanical knowledge was collected by semi-structured face-to-face interviews. The quantitative data were analyzed by using the informant consensus factor (ICF) method and the number of citations. RESULTS: A total of 181 species belonging to 137 genera and 65 families were collected in Gaomi City. Asteraceae was the predominant family and Fabaceae took the second place. River basins and the southern hills in Gaomi were rich in vegetation. However, the cultivated area of medicinal plants only accounted for 10% of agricultural acreage. The main preparation method was decocting (170, 94.48%) and the most frequent mode of administration was oral (177, 97.97%). The highest numerical ICF value was recorded for treating endocrine, metabolic, and nutritional (ICF: 0.85) conditions. Seven of the medicinal plant species used by the people in Gaomi have not been reported previously in China. Verbena officinalis L. was found in Gaomi City, which is a new distribution record for this species. CONCLUSIONS: People in Gaomi hold valuable knowledge about the use of medicinal plants; however, their knowledge has not been comprehensively documented. The therapeutic uses of the documented medicinal plants will provide a basis for further pharmacological and phytochemical investigations. Additionally, the result of this study indicated that the elder people in Gaomi have more traditional knowledge of plant medicines than the younger ones.

6.
J Cell Physiol ; 236(2): 1432-1444, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32853427

RESUMO

Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme-linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor-α, interleukin-1α (IL-1α), and IL-1ß to suppress inflammatory responses. The secretion levels of receptor-activated nuclear factor-κB ligand, CTX-1, and osteoclast-associated receptor as well as Ti-induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC-related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogen-activated protein kinase (P38, extracellular signal-regulated kinase, and c-JUN N-terminal kinase) and nuclear factor-κB (inhibitor κB-α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c-Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs.

7.
Int J Cardiol ; 322: 70-76, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860843

RESUMO

BACKGROUND: The novel method of left bundle branch pacing (LBBP) has been reported to produce a narrower QRS duration and lower pacing threshold than right ventricular outflow tract septal pacing (RVOP). However, whether LBBP is superior to traditional RVOP in improving cardiac function still lacks sufficient evidence. OBJECTIVE: The purpose of this study was to compare the changes in cardiac function (especially in brain natriuretic peptide (BNP)levels, left atrial function, and left ventricular diastolic function) within 7 days between LBBP and RVOP. METHODS AND RESULTS: A single-centre prospective controlled registered clinical study was conducted with 84 patients with bradycardia indications. Forty-two patients underwent RVOP, and 42 patients underwent LBBP. The pacemaker parameters were adjusted so that the ventricular ratio was over 90% and rate was 60-70 bpm. The changes in BNP levels and echocardiogram and speckle-tracking echocardiagraphy findings were compared between the two groups before and within 7 days after implantation: (1) BNP: there was no significant difference in BNP level between the two groups before and 1 day after implantation, while the LBBP group had significantly lower levels than the RVOP group on day 7 [(65.15 ± 56.96)pg/ml vs.(129.82 ± 101.92)pg/ml, P < 0.001]. (2) Cardiac echocardiography: the e' value of the LBBP group was higher than that of the RVOP group 7 days after implantation[(6.39 ± 2.65) cm/s vs. (5.45 ± 1.35)cm/s, P = 0.049]. The E/e' and peak E-wave velocity in the LBBP group decreased significantly after 7 days [16.57 ± 6.55 vs. 12.75 ± 5.16 P = 0.043, (88.6 ± 24.37)cm/s vs. (75.68 ± 28.10)cm/s P = 0.030]; in contrast, there were no significant changes in the RVOP group [14.13 ± 3.85 vs.14.10 ± 4.85 P = 0.50, (77.33 ± 21.14)cm/s vs. (74.45 ± 23.03)cm/s P = 0.56). (3)Speckle-tracking echocardiagraphy: there was no significant difference in left atrial strain or the strain rate between the LBBP and RVOP groups,but the absolute values of left atrial strain and strain rate in the LBBP group increased, while those in the RVOP group decreased. CONCLUSION: This study demonstrates that compared to RVOP, LBBP can increase left ventricular early diastolic function, improve BNP levels, and has a tendency to increase left atrial myocardial elasticity and left atrial strain capacity in the short term in pacemaker-dependent patients.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118988, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33065449

RESUMO

In this paper, a simple, rapid, low-cost and potential method was established for the simultaneous quantitative analysis of dabigatran etexilate (DABE) and dabigatran (DAB) in spiked biological fluids. It combined excitation-emission matrix fluorescence (EEMF) with different second-order calibration methods, including the self-weighted alternating normalized residue fitting (SWANRF) algorithm based on trilinear decomposition model, the multivariate curve resolution - alternating least-squares (MCR-ALS) based on bilinear decomposition model and the unfolded partial least-square coupled with residual bilinearization (U-PLS/RBL) based on latent variables model. The proposed method showed "second-order advantage", that is, satisfactory quantitative results were successfully obtained even in the presence of unknown interferences and serious spectral overlap. The recoveries of DABE and DAB in spiked biological fluids were 91.7%-101.7% for SWANRF, 95.9%-117.8% for MCR-ALS, 83.0%-109.6% for U-PLS/RBL, respectively. Figures of merit and other statistical parameters were also calculated to assess the performance of the proposed method. Moreover, the modeling procedures and characteristics of three different models in EEMF analysis were discussed and compared.

9.
J Neuroinflammation ; 17(1): 330, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153475

RESUMO

BACKGROUND: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated. METHODS: Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice. RESULTS: The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of Ldlr enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1ß and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in Ldlr-/- mice and cultured Ldlr-/- neuron after experimental stroke. CONCLUSIONS: These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.

10.
Cell Death Dis ; 11(11): 955, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159034

RESUMO

Programmed death ligand 1 (PD-L1, CD274) is an essential immune checkpoint protein that binds to programmed death 1 (PD-1) on T-lymphocytes. T cell plays a critical role in killing cancer cells while the cancer cell exhibits immune escape by the expression of PD-L1. The binding of PD-L1 to PD-1 inhibits T cell proliferation and activity, leading to tumor immunosuppression. Increasing evidence shows that PD-L1 protein undergoes degradation in proteasomes or lysosomes by multiple pathways, leading to enhanced immunotherapy for cancer. Although some specific drugs induce PD-L1 degradation and increase antitumor activity, the combination of these drugs with PD-L1/PD-1 blockade significantly enhances cancer immunotherapy. In this review, we have discussed the interaction of PD-L1 degradation with cancer immunotherapy.

11.
EClinicalMedicine ; : 100604, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33134901

RESUMO

Background: The current study aimed to determine the impact of SARS-CoV-2 infection on male fertility. Methods: This is a single-center, hospital-based observational study that included autopsied testicular and epididymal specimens of deceased COVID-19 male patients (n=6) and recruited recovering COVID-19 inpatients (n=23) with an equal number of age-matched controls, respectively. We performed histopathological examinations on testicular and epididymal specimens, and also performed TUNEL assay and immunohistochemistry. Whereas, we investigated the semen specimen for sperm parameters and immune factors. Findings: Autopsied testicular and epididymal specimens of COVID-19 showed the presence of interstitial edema, congestion, red blood cell exudation in testes, and epididymides. Thinning of seminiferous tubules was observed. The number of apoptotic cells within seminiferous tubules was significantly higher in COVID-19 compared to control cases. It also showed an increased concentration of CD3+ and CD68+ in the interstitial cells of testicular tissue and the presence of IgG within seminiferous tubules. Semen from COVID-19 inpatients showed that 39.1% (n=9) of them have oligozoospermia, and 60.9% (n=14) showed a significant increase in leucocytes in semen. Decreased sperm concentration, and increased seminal levels of IL-6, TNF-α, and MCP-1 compared to control males were observed. Interpretation: Impairment of spermatogenesis was observed in COVID-19 patients, which could be partially explained as a result of an elevated immune response in testis. Additionally, autoimmune orchitis occurred in some COVID-19 patients. Further research on the reversibility of impairment and developing treatment are warranted. Funding: This study was supported by Ministry of Science and Technology of China Plan, Hubei Science and Technology Plan, National Key Research and Development Program of China, HUST COVID-19 Rapid Response Call, China and National Natural Science Foundation of China; these funding bodies are public institutions, and they had no role in study conception, design, interpretation of results, and manuscript preparation.

12.
Opt Lett ; 45(21): 5941-5944, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137046

RESUMO

The converged vortex beam with a well-defined focal plane is an essential ingredient for trapping and rotating microparticles. Metasurfaces, two-dimensional metamaterials, provide an ultra-compact and flexible platform for designing a converged vortex by integrating the functions of a lens and vortex plate. A spin-defocused metasurface can further boost information capacity such as the multiplexing of helicity-dependent functionalities. Here we propose an approach to realize spin-defocused metalenses that can simultaneously focus terahertz (THz) waves with orthogonal spin states into helicity-dependent vortices based on pure geometric phases. Under the illumination of linearly polarized terahertz waves, all of the helicity-dependent vortices are observed, leading to helicity-multiplexing of converged vortices. Furthermore, the longitudinal multiplexing of converged cylindrical vector beams is demonstrated by superposition of helicity-dependent vortices. This unique approach for multiplexing converged vortices and cylindrical vector beams may open a window for designing future ultra-compact and multifunctional devices with potential applications in communications, optical trapping, and focusing.

13.
J Cell Mol Med ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135290

RESUMO

Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up-regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up-regulate the expression of CDK16 by sponging miR-584-5p. The expression of miR-584-5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR-584-5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR-584-5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR-584-5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment.

14.
Nucleic Acids Res ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219686

RESUMO

Within the tumour microenvironment, cells exhibit different behaviours driven by fine-tuning of gene regulation. Identification of cellular-specific gene regulatory networks will deepen the understanding of disease pathology at single-cell resolution and contribute to the development of precision medicine. Here, we describe a database, LnCeCell (http://www.bio-bigdata.net/LnCeCell/ or http://bio-bigdata.hrbmu.edu.cn/LnCeCell/), which aims to document cellular-specific long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) networks for personalised characterisation of diseases based on the 'One Cell, One World' theory. LnCeCell is curated with cellular-specific ceRNA regulations from >94 000 cells across 25 types of cancers and provides >9000 experimentally supported lncRNA biomarkers, associated with tumour metastasis, recurrence, prognosis, circulation, drug resistance, etc. For each cell, LnCeCell illustrates a global map of ceRNA sub-cellular locations, which have been manually curated from the literature and related data sources, and portrays a functional state atlas for a single cancer cell. LnCeCell also provides several flexible tools to infer ceRNA functions based on a specific cellular background. LnCeCell serves as an important resource for investigating the gene regulatory networks within a single cell and can help researchers understand the regulatory mechanisms underlying complex microbial ecosystems and individual phenotypes.

15.
Medicine (Baltimore) ; 99(45): e23014, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157947

RESUMO

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and alternative treatment for patients with FD. This study aimed to explore the effectiveness of EA for the treatment of FD. METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Cochrane Library) for randomized controlled trials of FD treated by EA from inception to February 3, 2020. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. The Cochrane Collaboration's risk of bias tool, RevMan 5.3 software were used for meta-analysis. Data were pooled to calculate relative risk and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data. RESULTS: Seven randomized clinical trials included 853 patients. This meta-analysis investigated the effectiveness of EA alone in the treatment of FD relative to sham-EA or pharmacologic medication (PM). The results showed that EA could significantly improve clinical symptoms. Compared with sham-EA, EA was more effective in reducing symptom scores (SMD -3.44, 95% CI -4.21 to -2.67) and increasing normal slow waves of electrogastrogram (SMD 0.93, 95% CI -0.30 to1.55). When EA was combined with PM, there was no significant difference in reducing symptom scores (SMD -0.18, 95% CI -0.51 to 0.16), increasing the effective rate of clinical symptoms (risk ratio 1.04, 95% CI 0.96 to 1.13), enhancing the level of plasma motilin (SMD 0.93, 95% CI -0.30 to1.55), and reducing gastric half-emptying time (SMD 0.02, 95% CI -0.16 to 0.20). The results also showed that there were very few adverse events reported. CONCLUSION: This meta-analysis suggests that EA is better than the placebo (sham-EA) in treating FD, and the therapeutic effect of EA on FD is equivalent to that of PM on FD. Compared with PM, EA for FD is safer and has fewer adverse reactions. Despite limitations due to the quality and number of the included studies, EA might be used as an effective and safe treatment for FD.


Assuntos
Dispepsia/fisiopatologia , Dispepsia/terapia , Eletroacupuntura/métodos , Terapia por Acupuntura/métodos , Estudos de Casos e Controles , Eletroacupuntura/efeitos adversos , Humanos , Motilina/sangue , Placebos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
Nat Commun ; 11(1): 5843, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203843

RESUMO

Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell-cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.

17.
Neurosci Lett ; : 135453, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186609

RESUMO

Alzheimer's disease (AD) is one of the common neurodegenerative illnesses in aging populations around the world. Recently, psychiatric symptoms are becoming increasingly important in recognizing the manifestations of AD in addition to cognitive impairment. Some studies suggest that the prefrontal cortex (PFC) is closely related to apathy/depression, and a network may exist between the CA1 of hippocampus and PFC. However, whether the injection of Aß2535 into hippocampi may result in PFC abnormalities in AD model rats is unclear. In this study, it was investigated the changes in the PFCs after the hippocampal injection via the P35/P25 - Cyclin-dependent kinase5 (CDK5) - Tau hyperphosphorylation signaling pathway. Our results demonstrated that rats injected with Aß25-35 showed decreased learning and memory ability, and increased depression-like behaviors compared with uninjected controls and saline-injected shams. P35/P25, CDK5, Tau[pS199], and Tau[pS202] are significantly elevated in the PFCs and hippocampi after Aß25-35 was injected into the hippocampi. Furthermore, P35/P25-CDK5 complexes were detected in vivo by immunofluorescence and co-immunoprecipitation. Therefore, the relative expression of proteins associated with the P35/P25-CDK5 pathway showed the same changes in the hippocampi and PFCs after Aß25-35 injection. These findings demonstrate a potential mechanism for prefrontal-mediated cognitive impairment and the psychiatric symptoms of AD.

18.
Stem Cell Res ; 49: 102052, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33130469

RESUMO

N-acetylneuraminic acid synthase (NANS), the gene encoding the synthase for N-acetylneuraminic acid (NeuNAc; sialic acid), is closely associated with infantile-onset severe developmental delay and skeletal dysplasia. However, the role and the involved mechanisms of NANS functioning have not been fully understood to date. Here, we generated a homozygous NANS-knockout human induced pluripotent stem cell (iPSC) line, NCCSEDi001-A-1, via the CRISPR/Cas9-based gene editing method. The NCCSEDi001-A-1 cell line does not express NANS protein, but maintains a normal karyotype, pluripotency, and trilineage differentiation potential.

19.
J Cell Biochem ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164261

RESUMO

Epidermal growth factor receptor (EGFR) induces peroxisome-proliferator-activated receptor-δ (PPARδ)-Y108 phosphorylation, while it is unclear the effect of phosphorylation of PPARδ on cancer cell metabolism. Here we found that EGF treatment increased its protein stability by inhibiting its lysosomal dependent degradation, which was reduced by gefitinib (EGFR inhibitor) treatment. PPARδ-Y108 phosphorylation in response to EGF recruited HSP90 (heat shock protein 90) to PPARδ resulting in increased PPARδ stability. In addition, PPARδ-Y108 phosphorylation promoted cancer cell metabolism, proliferation, and chemoresistance. Therefore, this study revealed a novel molecular mechanism of EGFR/HSP90/PPARδ pathway-mediated cancer cell metabolism, proliferation, and chemoresistance, which provides a strategy for cancer treatment.

20.
Mol Omics ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174576

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiological agent of the current rapidly growing outbreak of coronavirus disease (COVID-19), which is straining health systems around the world. Disrupting the intermolecular association of SARS-CoV-2 spike glycoprotein (S protein) with its cell surface receptor human angiotensin-converting enzyme 2 (hACE2) has been recognized as a promising therapeutic strategy against COVID-19. The association is a typical peptide-mediated interaction, where the hACE adopts an α1-helix, which can form a two-helix bundle with the α2-helix, to pack against a flat pocket on the S protein surface. Here, we demonstrate that the protein context of full-length hACE plays an essential role in supporting the hACE2 α1-helix recognition by viral S protein. Energetic analysis reveals that the α1-helical peptide (αHP) and also the two-helix bundle peptide (tBP) cannot bind effectively to S protein when they are split from the hACE protein. The context contributes moderately and considerably to the direct readout (DR) and indirect readout (IR) of peptide recognition, respectively. Dynamics simulation suggests that the two free peptides exhibit a large intrinsic disorder without the support of protein context, which would incur a considerable entropy penalty upon binding to S protein. To restore the IR effect lost by splitting peptides from hACE, we herein propose employing hydrocarbon stapling and cyclization strategies to constrain the free αHP and tBP peptides into their native ordered conformations, respectively. The stapling and cyclization are carefully designed in order to avoid influencing the peptide DR effect, which has been demonstrated to improve the peptide binding affinity (but not specificity) to S protein. The stapling/cyclization-imposed conformational constraint can effectively minimize the unfavorable IR effect (i) by reducing the peptide flexibility and entropy cost upon their binding to S protein, and (ii) by helping peptide pre-folding into their native state to facilitate the conformational selection by S protein.

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