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1.
J Ethnopharmacol ; : 112262, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethanol extract of AOK stem showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

2.
J Exp Bot ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587070

RESUMO

An increased concentration of cytosolic Ca2+ is an early response of plant cells to heat shock (HS). Arabidopsis thaliana cyclic nucleotide-gated ion channel 6 (CNGC6) mediates heat-induced Ca2+ influx and is activated by cyclic adenosine monophosphate. However, it remains unclear how Ca2+ conductivity of the CNGC6 is negatively regulated under the elevated concentration of cytosolic Ca2+. In this study, A. thaliana CaM1/4, CaM2/3/5, CaM6 and CaM7 isoforms were found to bind to CNGC6 in varying degrees, and this binding was dependent on the presence of Ca2+ and IQ6, an atypical isoleucine glutamine motif in CNGC6. Knockout of CaM2, CaM3, CaM5 and CaM7 genes led to a marked increase in plasma membrane (PM) inward Ca2+ current under HS conditions; however, knockout of CaM1, CaM4 and CaM6 genes had no significant effect on PM Ca2+ current. Moreover, the deletion of the IQ6 from CNGC6 led to a marked increase in PM Ca2+ current under HS conditions. Taken together, the data presented here suggest that the CNGC6-mediated Ca2+ influx is likely to be negatively regulated by CaM2/3/5 and CaM7 isoforms under HS conditions, and the IQ6 plays important roles in CaM binding and the feedback regulation of the channel.

3.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3358-3364, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602895

RESUMO

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

4.
J Cell Physiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603255

RESUMO

Glioblastoma multiforme (GBM) is a highly proliferative cancer with generally poor prognosis and accumulating evidence has highlighted the potential of long noncoding RNAs (lncRNAs) in the biological behaviors of glioma cells. This study focused on the identification of lncRNAs to identify targets for possible GBM prognosis. Microarray expression profiling found that 1,759 lncRNAs and 3,026 messenger RNAs (mRNAs) were upregulated, and 1932s lncRNA and 2,979 mRNAs were downregulated in GBM. Bioinformatics analysis and experimental verification identified TCONS_00020456 (TCON) for further analysis. In situ hybridization, along with immunohistochemical and receiver operating characteristic analysis determined TCON (truncation value = 3.5) as highly sensitive and specific in GBM. Grade IV patients with glioma life span with different lncRNA staining scores were analyzed. TCON staining scores below 3.5 indicated poor prognosis (life span ranging from 0.25 to 7 months), even if the glioma was surgically removed. TCON decreased significantly in GBM, and showed a coexpressional relationship with Smad2 and protein kinase C α (PKCα). Overexpression of TCON reduced the proliferation on one hand and migration, invasion on the other. TCON also inhibited epithelial-mesenchymal transformation and glioma progression in vivo, based on a nude mouse tumorigenicity assay. In addition, we predicted a potential binding site and intersection that microRNAs targeting Smad2, PKCα, and TCON through RACE pretest and bioinformatics analysis. Taken together, TCON, regarded as oncosuppressor, targeting the Smad2/PKCα axis plays a novel role in inhibiting the malignant progression of glioma. Moreover, it also demonstrates that the level of TCON can be used as a prognostic and diagnostic biomarker for GBM.

5.
Biomed Chromatogr ; : e4701, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596954

RESUMO

Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. And, the present experiment use the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ anti-liver tumors. The results show that a total of 14 chemical components are identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, 7 prototypical components and 7 metabolic components are detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol, and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of anti-tumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and anti-tumor mechanism.

6.
Biosci Rep ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481528

RESUMO

Diabetic nephropathy (DN) is the common complications of diabetes mellitus, but the efficacy of available treatments for the prevention of DN is still unsatisfactory. In this study, we aimed to explore the effect of Danggui buxue tang (DGT) on the proliferation of high glucose (HG)-induced mesangial cells and accumulation of extracellular matrix in mesangial cells. We found DGT upregulated the expression of GAS5 and IKK dose-dependently in mouse mesangial cells (SV40 MES-13). We found DGT participated in the expression IKK and the activity of nuclear transcription factor-κB (NF-κB) via GAS5, and proved that lncRNA GAS5 was positively related with IKK. And we proved GAS5 regulated the expression of IKK and the activity of NF-κB. In addition, DGT inhibited viability of MES-13 cells and extracellular matrix related proteins (laminin, fibronectin and collagen IV) via GAS5. Moreover, we proved GAS5 regulated the viability of SV40 MES-13 cells and extracellular matrix related proteins through NF-κB pathway. DGT inhibited the proliferation of mesangial cells and accumulation of extracellular matrix via GAS5/NF-κB, therefore, DGT could be an effective treatment for the prevention of DN.

7.
Gastroenterology ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513797

RESUMO

BACKGROUND & AIMS: T-regulatory (Treg) cells suppress the immune response to maintain homeostasis. There are 2 main subsets of Treg cells: FOXP3-positive Treg cells, which do not produce high levels of effector cytokines, and type 1 Treg (Tr1) cells, which are FOXP3-negative and secrete interleukin 10 (IL10). IL10 is an anti-inflammatory cytokine, so Tr1 cells might be used in treatment of inflammatory bowel diseases. We aimed to develop methods to isolate and expand human Tr1 cells and define their functions. METHODS: We obtained blood samples and colon biopsies from patients with Crohn's disease or ulcerative colitis or healthy individuals (controls). CD4+ T cells were isolated from blood samples, stimulated with anti-CD3 and anti-CD28 beads, and Tr1 cells were purified using an IL10 cytokine-capture assay and cell sorting. FOXP3-positive Treg cells were sorted as CD4+CD25highCD127low cells from unstimulated cells. Tr1 and FOXP3-positive Treg cells were expanded, and phenotypes and gene expression profiles were compared. T cells in peripheral blood mononuclear cells from healthy donors were stimulated with anti-CD3 and anti-CD28 beads and the suppressive abilities of Tr1 and FOXP3-positive Treg cells were measured. Human colon organoid cultures were established, cultured with supernatants from Tr1 or FOXP3-positive cells, and analyzed by immunofluorescence and flow cytometry. T84 cells (human colon adenocarcinoma epithelial cells) were incubated with supernatants from Tr1 or FOXP3-positive cells and trans-epithelial electrical resistance was measured to determine epithelial cell barrier function. RESULTS: Phenotypes of Tr1 cells isolated from controls vs patients with Crohn's disease or ulcerative colitis did not differ significantly following expansion. Tr1 cells and FOXP3-positive Treg cells suppressed proliferation of effector T cells, but only Tr1 cells suppressed secretion of IL1beta (IL1B) and TNF from myeloid cells. Tr1 cells, but not FOXP3-positive Treg cells, isolated from healthy subjects and patients with Crohn's disease or ulcerative colitis secreted IL22, which regulated repair of the epithelium and promoted barrier function of human intestinal epithelial cells. Tr1 cell culture supernatants promoted differentiation of mucin-producing goblet cells in intestinal organoid cultures. CONCLUSIONS: Human Tr1 cells suppress proliferation of effector T cells (adaptive immune response) and production of IL1B and TNF by myeloid cells (inmate immune response). They also secrete IL22 to regulate repair of the epithelium and promote barrier function. They might be developed as a cell-based therapy for intestinal inflammatory disorders.

8.
Oncol Rep ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31545463

RESUMO

O­linked ß­N­acetylglucosamine (O­GlcNAc) modification is a dynamic post­translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling. This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O­GlcNAc transferase (OGT) and O­GlcNAcase (OGA), respectively. The present study aimed to determine the role of O­GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression. The results revealed that the expression of O­GlcNAc­modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry. Additionally, the level of endometrial O­GlcNAc modification increased gradually from the pre­receptive to the receptive phase, which was then decreased during the non­receptive phase. In endometrial cells, RNA interference was utilized to reduce the expression of two key O­GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O­GlcNAc modification. The results revealed that increasing the level of O­GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation. It is hypothesized that O­GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation. The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.

9.
Med Gas Res ; 9(3): 145-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552879

RESUMO

Hydrogen sulphide (H2S) has been considered as a toxic gas for a long time till new researches discovered the endogenous H2S effects on physiological and pathological processes. In virtue of H2S's effects on cellular redox imbalance and aspirin's good anticoagulation property, exogenous H2S donors, such as H2S-releasing aspirin (ACS14), have been explored to attenuate side effects of aspirin on gastrointestinal mucosal damage. However, existing researches mainly focus on the antithrombotic effects. Considering H2S role in angiogenesis and vascular-protection progress, we herein focused on if ACS14 further has the ability to attenuate oxidative lesion and inflammation in human umbilical vein endothelial cells (HUVECs) and macrophages. In this study, we synthesized ACS14 by 5-(4-methoxyphenyl)-1,2-dithiole-3-thione and o-acetylsalicylic acid (aspirin), and the obtained compounds showed the ability to release H2S. Our data illustrated that both aspirin and ACS14 had good cytocompatibility, and could support the proliferation of HUVECs. And, ACS14 was found to be able to promote 1.6 folds increase compared to aspirin. H2S released from ACS14 was detected inside cells, wherein H2S fluorescence intensity increased twofold in 5 µM and 10 µM ACS14 groups than 1 µM group. Owing to reactive oxygen species inside cells being obviously decreased in ACS14 group, the apoptosis rate of HUVEC herein was reduced as low as 1.6% from 60% of blank group. Meanwhile, the tumour necrosis factor alpha release in macrophage was also declined by 15% in ACS14 groups than the others. Basically, the ACS14 we obtained had the cyto-protective and anti-inflammatory capabilities. Potential applications for vascular intima repair in atherosclerosis are further expected.

10.
Sensors (Basel) ; 19(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491921

RESUMO

Short-term traffic speed prediction has become one of the most important parts of intelligent transportation systems (ITSs). In recent years, deep learning methods have demonstrated their superiority both in accuracy and efficiency. However, most of them only consider the temporal information, overlooking the spatial or some environmental factors, especially the different correlations between the target road and the surrounding roads. This paper proposes a traffic speed prediction approach based on temporal clustering and hierarchical attention (TCHA) to address the above issues. We apply temporal clustering to the target road to distinguish the traffic environment. Traffic data in each cluster have a similar distribution, which can help improve the prediction accuracy. A hierarchical attention-based mechanism is then used to extract the features at each time step. The encoder measures the importance of spatial features, and the decoder measures the temporal ones. The proposed method is evaluated over the data of a certain area in Hangzhou, and experiments have shown that this method can outperform the state of the art for traffic speed prediction.

11.
Biomaterials ; 224: 119490, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542515

RESUMO

Tumor ablation therapies provide a minimally invasive approach to treat cancer. However, inhibition of cancer metastasis and recurrence after ablation is still a challenge in clinical trials. Here, we propose a strategy using combinatorial thermal ablation, adjuvants and immune checkpoint blockade (ICB) to inhibit metastatic tumor and recurrence via antitumor immune responses post tumor thermal ablation, which are frequently used in the clinic. Furthermore, a strong immune memory against cancer was observed 80 days after the primary tumor was ablated. Considering that all components in our design are approved by Food and Drug Administration (FDA), we provide a strategy based on clinically used cancer treatment technique that is promising in clinical translation.

12.
Ying Yong Sheng Tai Xue Bao ; 30(9): 3019-3027, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529877

RESUMO

We examined the role of photosynthesis in regulating soil CO2 emission under nitrogen enrichment in Keerqin sandy grassland. Results showed that nitrogen (N) application could affect soil respiration rate by altering the allocation of photosynthetic products to the belowground. Gross ecosystem photosynthesis rate (GEP) was positively correlated with soil respiration rate (Rs). Nitrogen application reduced slope of the fitting function from 0.236 to 0.161, with the equation intercept difference (0.51 µmol·m-2·s-1) being similar to the nighttime soil respiration rate increment (0.52 µmol·m-2·s-1). From May to October, the difference of photosynthetic rate (differential ratio) caused by nitrogen application was significantly correlated with that of soil respiration (differential ratio). Results from partial correlation confirmed the essential role of photosynthetic rate difference (ΔGEP) in driving soil respiration rate difference (ΔRs) caused by nitrogen application. In the nighttime, soil respiration rate was affected by the aboveground vegetation activities in daytime. The daily mean GEP was an important factor affecting the nighttime soil respiration rate difference (ΔRs) (P<0.01). Photosynthesis, rather than soil temperature, was the main factor affecting soil respiration rate difference (ΔRs) under nitrogen application. Thus, the role of photosynthetic assimilation-regulating may provide a novel supplement for elucidating the responses of soil respiration to nitrogen enrichment.


Assuntos
Pradaria , Nitrogênio , Fotossíntese , Solo/química , Dióxido de Carbono , Ecossistema , Estações do Ano
13.
Food Res Int ; 125: 108619, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31554133

RESUMO

In this study, ferulic acid (FA) was covalently bound to one of the primary hydroxyls of ß-cyclodextrin (ß-CD) via an ester linkage to improve its stability and biological activity. Experiments using UV, FTIR, FS, NMR, MS and FE-SEM were performed to characterize the structure of the FA-ß-CD conjugate. Physicochemical properties such as solubility, crystallinity, thermal stability and photo-stability of the conjugate were also investigated, and the results revealed that the conjugate was in an amorphous form with improved thermal stability and photostability compared with the FA/ß-CD inclusion complex. Furthermore, in vitro cytotoxicity of the FA-ß-CD conjugate against HepG2 cell was enhanced with effective growth inhibition. Taken together, the present study indicates that the FA-ß-CD conjugate might be a novel and potential functional composition for application in food and medicine.

14.
EBioMedicine ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521609

RESUMO

BACKGROUND: Tumor mutations and tumor microenvironment are associated with resistance to cancer immunotherapies. However, peripheral T cell in effective anti-programmed death 1 (PD-1) antibody treatment is poorly understood. METHODS: Mass spectrometry and conventional flow cytometry were used to investigate peripheral blood cells isolated from patients. Furthermore, melanoma mouse model was performed to assess the role of CXCR3 signaling in anti-PD-1 antibody treatment. FINDINGS: We revealed a marked increase in the percentage of CXCR3+ T cells in the blood of cancer patients after the first pembrolizumab infusion. This percentage decreased after the second infusion in responsive patients, whereas a sustained high percentage of CXCR3+ T cells was observed in patients with progressive disease. A low percentage of CXCR3+ T cells presented in patients with stable disease or a partial response was confirmed by conventional flow cytometry. Intriguingly, blockade of CXCR3 signaling exacerbated tumor growth in mice. Intratumoral injection with recombinant CXCL9/10 plus intraperitoneal injection of anti-PD1 antibody inhibited the tumor growth in mice. INTERPRETATION: The dynamic changes in CXCR3+ T cells in blood may be a prognostic factor in anti-PD-1 immunotherapy, and promotion of CXCR3-mediated signaling may be beneficial to the anti-PD-1 therapy. FUND: This work was supported by the National Natural Science Foundation of China (Nos. 81722047, 81871944, 81670553, 81874317, 81572389, 81730100) and Jiangsu province key medical talents (Nos. ZDRCA2016026), The "Deng Feng" Distinguished Scholars Program, National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China (Number: 2018ZX09201002), and the Fundamental Research Funds for the Central Universities (020814380117).

15.
Adv Mater ; : e1904496, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512296

RESUMO

Single-atom catalysts (SACs) feature the maximum atom economy and superior performance for various catalysis fields, attracting tremendous attention in materials science. However, conventional synthesis of SACs involves high energy consumption at high temperature, complicated procedures, a massive waste of metal species, and poor yields, greatly impeding their development. Herein, a facile dangling bond trapping strategy to construct SACs under ambient conditions from easily accessible bulk metals (such as Fe, Co, Ni, and Cu) is presented. When mixing graphene oxide (GO) slurry with metal foam and drying in ambient conditions, the M0 would transfer electrons to the dangling oxygen groups on GO, obtaining Mδ+ (0 < δ < 3) species. Meanwhile, Mδ+ coordinates with the surface oxygen dangling bonds of GO to form MO bonds. Subsequently, the metal atoms are pulled out of the metal foam by the MO bonds under the assistance of sonication to give M SAs/GO materials. This synthesis at room temperature from bulk metals provides a versatile platform for facile and low-cost fabrication of SACs, crucial for their mass production and practical application in diverse industrial reactions.

16.
Clin Chim Acta ; 499: 75-80, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476304

RESUMO

Long noncoding RNAs (lncRNAs) can be over two hundred nucleotides in length and lack an obvious open reading frame (ORF). Interestingly, these RNAs form a group of nucleic acids involved in a variety of diverse cellular mechanisms involving proliferation, differentiation, apoptosis,and senescence. Given these characteristics, it is not unexpected that the aberrant expression of certain lncRNAs is strongly linked to oncogenesis and tumor advancement. OIP5-AS1, a prominent tumor-associated lncRNA, contributes to intricate cellular mechanisms during the evolution of malignant tumors. For example, it not only represses cyclin G-associated kinase (GAK) expression thus impacting mitosis, but also regulates cell proliferation and apoptosis in many cancers, including lung adenocarcinoma, breast, glioma and hepatoblastoma. In this paper, we review our current understanding of OIP5-AS1 in carcinogenesis and its potential application as a clinical biomarker or therapeutic target in malignancy.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31486254

RESUMO

The interaction of cytochrome c (Cyt c) with cardiolipin (CL) is believed to play an important role in the initial events of apoptosis. Herein, we investigate the structural changes of CL-bound Fe2+ Cyt c and the correlation with Cyt c release through surface-enhanced Raman spectroscopy (SERS) on nickel substrates. The SERS results together with molecular dynamics simulation reveal that Fe2+ Cyt c undergoes autoxidation and a relatively larger conformational alteration after binding with CL, inducing higher peroxidase activity of Cyt c and higher permeability of the CL membrane compared with those induced by the Fe3+ Cyt c. The proapoptotic activity and SERS effect of the Ni nanostructures allow the in situ study of the redox-state-dependent Cyt c release from isolated mitochondria, which reveals for the first time that the ferrous state of Cyt c most likely plays a more important role in triggering apoptosis.

18.
FEBS J ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31420997

RESUMO

The molecular bases of amyloid aggregation propensity are still poorly understood, especially for proteins that display a stable folded native structure. A prototypic example is human beta-2 microglobulin (ß2m), which, when accumulated in patients, gives rise to dialysis-related amyloidosis. Interestingly, although the physiologic concentration of ß2m in mice is five times higher than that found in human patients, no amyloid deposits are observed in mice. Moreover, murine ß2m (mß2m) not only displays a lower amyloid propensity both in vivo and in vitro but also inhibits the aggregation of human ß2m in vitro. Here, we compared human and mß2m for their aggregation propensity, ability to form soluble oligomers, stability, three-dimensional structure and dynamics. Our results indicate that mß2m low-aggregation propensity is due to two concomitant aspects: the low-aggregation propensity of its primary sequence combined with the absence of high-energy amyloid-competent conformations under native conditions. The identification of the specific properties determining the low-aggregation propensity of mouse ß2m will help delineate the molecular risk factors which cause a folded protein to aggregate.

19.
BMC Plant Biol ; 19(1): 367, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429697

RESUMO

BACKGROUND: Adaptation to abiotic stresses is crucial for the survival of perennial plants in a natural environment. However, very little is known about the underlying mechanisms. Here, we adopted a liquid culture system to investigate plant adaptation to repeated salt stress in Populus trees. RESULTS: We first evaluated phenotypic responses and found that plants exhibit better stress tolerance after pre-treatment of salt stress. Time-course RNA sequencing (RNA-seq) was then performed to profile changes in gene expression over 12 h of salt treatments. Analysis of differentially expressed genes (DEGs) indicated that significant transcriptional reprogramming and adaptation to repeated salt treatment occurred. Clustering analysis identified two modules of co-expressed genes that were potentially critical for repeated salt stress adaptation, and one key module for salt stress response in general. Gene Ontology (GO) enrichment analysis identified pathways including hormone signaling, cell wall biosynthesis and modification, negative regulation of growth, and epigenetic regulation to be highly enriched in these gene modules. CONCLUSIONS: This study illustrates phenotypic and transcriptional adaptation of Populus trees to salt stress, revealing novel gene modules which are potentially critical for responding and adapting to salt stress.


Assuntos
Adaptação Fisiológica/genética , Regulação da Expressão Gênica de Plantas , Populus/genética , Estresse Salino/genética , Transcrição Genética , Ontologia Genética , Redes Reguladoras de Genes , Genoma de Planta , Fenótipo , Populus/fisiologia , RNA de Plantas , Análise de Sequência de RNA , Transcriptoma , Árvores/genética , Árvores/fisiologia
20.
Med Sci Monit ; 25: 6436-6445, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454342

RESUMO

BACKGROUND The aim of this study was to review the efficacy and safety of intra-articular (IA) viscosupplementation (VS) for hip osteoarthritis (OA). MATERIAL AND METHODS We searched Medline, Clinical Trial Register Center, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing VS with placebo injection for hip OA. We included suitable studies, assessed the quality of studies, and extracted data on pain reduction, function improvement at different time points, and safety profiles. The comparisons of pain and function outcome were performed by meta-analysis. RESULTS Five high-quality randomized controlled studies trials (RCTs) with 591 patients with hip OA were identified. Although several trials demonstrated a significant decline in pain in VS groups during follow-up compared to baseline, without severe adverse events, the pooled analysis did not show VS was superior to placebo at any time windows [7-14 days: standardized mean difference (SMD): -0.18; 95% CI, -0.47 to 0.10, p=0.21; 28-30 days: 0.02 (-0.15, 0.19), p=0.82; or at final visit: -0.14 (-0.46, 0.18), p=0.38]. Similar results were also observed in the combined data of functional results. CONCLUSIONS IA VS does not reduce pain or improve function significantly better than placebo in a short-term follow-up. The benefits and safety of VS should be further assessed by sufficiently-sized, methodologically sound studies with validated assessment of more clinically relevant end-points.

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