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1.
Phytomedicine ; 80: 153339, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33038868

RESUMO

BACKGROUND: As dysregulation of immunometabolism plays a key role in the immunological diseases, dyslipidemia frequently observed in rheumatoid arthritis (RA) patients (60%) is associated with the disease activity and has been considered as the potential target of anti-inflammatory strategy. However, targeting of metabolic events to develop novel anti-inflammatory therapeutics are far from clear as well as the mechanism of dyslipidemia in RA. PURPOSE: To explore the therapeutic potential and mechanisms of silybin again RA through the regulation of lipid metabolism. METHODS: Adjuvant-induced arthritis (AIA) rat model was used to examine the effects of silybin on modulating dysregulated lipid metabolism and arthritis. Metabolomics, docking technology, and biochemical methods such as western blots, qRT-PCR, immunofluorescence staining were performed to understanding the underlying mechanisms. Moreover, knock-down of LXRα and LXRα agonist were used on LO2 cell lines to understand the action of silybin. RESULTS: We are the first to demonstrate that silybin can ameliorate dyslipidemia and arthritis in AIA rats. Overexpression of LXRα and several key lipogenic enzymes regulated by LXRα, including lipoprotein lipase (LPL), cholesterol 7α and 27α hydroxylase (CYP7A, CYP27A), adipocyte fatty acid-binding protein (aP2/FABP4) and fatty acid translocase (CD36/FAT), were observed in AIA rats, which mostly accounted for dyslipidemia during arthritis development. Metabolomics, docking technology, and biochemical results indicated that anti-arthritis effects of silybin related to suppressing the up-regulated LXRα and abnormal lipid metabolism. Notably, activation of LXRα could potentiate cell inflammatory process induced by LPS through the regulation of NF-κB pathway, however, suppression of LXRα agonism by siRNA or silybin reduced the nuclear translocation of NF-κB as well as the induction of downstream cytokines, indicating LXRα agonism is the important factor for the arthritis development and could be a potential target. CONCLUSION: The up-regulation of LXRα can activate lipogenesis enzymes to worsen the inflammatory process in AIA rats as well as the development of dyslipidemia, therefore, rectifying lipid disorder via suppression of LXRα agonism pertains the capacity of drug target, which enables to discover and develop new drugs to treat rheumatoid arthritis with dyslipidaemia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33141452

RESUMO

Rational design of photocatalysts with multiple functions, including organic synthesis and water-splitting, is promising and challenging. Herein, we synthesized actiniae-like carbon nitride (ACN) bundles based on the pyrolysis of an asymmetric supramolecular precursor prepared from L-arginine (L-Arg) and melamine. ACN has adjustable band gaps (2.25 eV ~ 2.75 eV) and hollow microtubes with ultrathin pore walls, which enrich reaction sites, improve visible-light absorption and enhance charge separation. In the presence of phenylcarbinol, ACN exhibited excellent pure water-splitting ability (95.3 µmol/h) and in the meanwhile phenylcarbinol was selectively oxidized to benzaldehyde (conversion of 90.9%, selectivity of 99.7%) under solar irradiation. For the concurrent reactions, 2 D isotope labeling, separation and detection were conducted to confirm that the proton source of released hydrogen is water. Further, we theorized the mechanism of water splitting and phenylcarbinol oxidation and hope that it provides inspiration for simultaneous utilization of photogenerated electrons and holes in one system.

3.
Comput Biol Chem ; : 107358, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-33243703

RESUMO

BACKGROUND: In this study, the network pharmacological methods were used to predict the target of effective components of compounds in Zisheng Shenqi Decoction (ZSD, or Nourishing Kidney Qi Decoction) in the treatment of gouty arthritis (GA). METHOD: The main effective components and corresponding key targets of herbs in the ZSD were discerned through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP), Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) database. UniProt database and Swiss Target Prediction (STP) database was used to rectify and unify the target names and supply the target information. The targets related to GA were obtained by using GeneCards database. After we discovered the potential common targets between ZSD and GA, the interaction network diagram of "ZSD-component-GA-target" was constructed by Cytoscape software (Version 3.7.1). Subsequently, the Protein-protein interaction (PPI) network of ZSD effective components-targets and GA-related targets was constructed by Search Tool for the Retrieval of Interacting Genes Database (STRING). Bioconductor package "org.Hs.eg.db" and "cluster profiler" package were installed in R software (Version 3.6.0) which used for Gene Ontology analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. RESULTS: 146 components and 613 targets of 11 herbal medicines in the ZSD were got from TCMSP database and BATMAN-TCM database. 987 targets of GA were obtained from GeneCards database. After intersected and removed duplications, 132 common targets between ZSD and GA were screened out by Cytoscape software (Version 3.7.1). These common targets derived from 81 effective components of 146 components, such as quercetin, stigmasterol and kaempferol. They were closely related to anti-inflammatory, analgesic and anti oxidative stress and the principal targets comprised of Purinergic receptor P2X, ligand-gated ion channel 7 (P2x7R), Nod-like receptor protein 3 (NLRP3) and IL-1ß. GO enrichment analysis and KEGG pathway enrichment analysis by R software (Version 3.6.0) showed that the key target genes had close relationship with oxidative stress, reactive oxygen species (ROS) metabolic process and leukocyte migration in aspects of biological process, cell components and molecular function. It also indicated that ZSD could decrease inflammatory reaction, alleviate ROS accumulation and attenuate pain by regulating P2 × 7R and NOD like receptor signaling pathway of inflammatory reaction. CONCLUSION: A total of 81 effective components and 132 common target genes between ZSD and GA were screened by network pharmacology. The PPI network, GO enrichment analysis and KEGG pathway enrichment analysis suggested that ZSD can exerte anti-inflammatory and analgesic effects on the treatment of GA by reducing decreasing inflammatory reaction, alleviating ROS accumulation, and attenuating pain. The possible molecular mechanism of it mainly involved multiple components, multiple targets and multiple signaling pathways, which provided a comprehensive understanding for further study. In general, the network pharmacological method applied in this study provides an alternative strategy for the mechanism of ZSD in the treatment of GA.

4.
Transl Oncol ; 14(1): 100907, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217646

RESUMO

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer.

5.
Arch Microbiol ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112996

RESUMO

Germplasm of industrial brewing yeast of the worldwide have a richer diversity, and various successes in improving the performance of brewing yeasts. However, they are limited in that they have relatively low odds of combining desirable traits in a correct manner. To improve germplasm resource preservation, management, and utilization efficiency. In this study, the genetic diversity of 35 industrial brewing yeasts were analyzed based upon inter simple sequence repeat (ISSR) markers, in which 151 out of 167 SSR loci (90.42%) were polymorphic between two or more strains. Three preliminary core collections were established using ISSR data, and based on three different strategies as follows: an advanced maximization (M) strategy, an allele preferred sampling (A) strategy, and a random sampling (R) strategy. Comparison of genetic parameters, including polymorphic information content, Nei's genetic diversity (H), effective allele number, observed allele number, Shannon's index (I), and principal coordinate analyses, confirmed that all the core collections accurately recapitulated the diversity of the initial germplasm. Considering the loci retention ratio and trait coverage efficiency, Core1 was considered the best core collection.

6.
Plant J ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098697

RESUMO

Starch synthesis is an essential feature of crop filling, but knowledge of the molecular mechanisms regulating the expression of starch synthesis genes (SSGs) is currently limited to transcription factors (TFs). Here, we obtained transcriptome, small RNAome, and DNA methylome data from maize (Zea mays) endosperms during multiple developmental stages and established a regulatory network atlas of starch synthesis. Transcriptome analysis showed a sharp transition at 9-10 days after pollination, when genes involved in starch and sucrose metabolism are upregulated and starch accumulates rapidly. Expression pattern analysis established a comprehensive network between SSGs and TFs. During maize endosperm development, the miRNAs with preferential repression of the expression of TFs, particularly the TFs regulating SSG expression, were extensively downregulated. Specifically, ZmMYB138 and ZmMYB115 affected the transcriptional activities of Du1/Wx and Ae1/Bt2 genes at their respective promoter regions. Remarkably, the two TFs were negatively regulated by the copious expression of Zma-miR159k-3p at the post-transcriptional level. This suggests that miRNAs are important regulators of starch synthesis. Moreover, with the exclusion of the TFs, the expression of both SSGs and miRNAs was globally regulated by DNA methylation. Altogether, the present results (i) establish the regulatory functions of miRNAs and DNA methylation in starch synthesis and (ii) indicate that DNA methylation functions as a master switch.

7.
J Vet Med Sci ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32999131

RESUMO

Pseudorabies virus (PRV) infection leads to severe inflammatory responses and tissue damage, and many natural herbs exhibit protective effects against viral infection by modulating the inflammatory response. An ethyl acetate fraction of flavonoids from Polygonum hydropiper L. (FEA) was prepared through ethanol extraction and ethyl acetate fractional extraction. An inflammatory model was established in RAW264.7 cells with PRV infection to evaluate the anti-inflammatory activity of FEA by measuring cell viability, nitric oxide (NO) production, reactive oxygen species (ROS) release, and mRNA expression of inflammatory factors, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Its functional mechanism was investigated by analyzing the phosphorylation and nuclear translocation of key proteins in the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings indicate that PRV induced inflammatory responses in RAW264.7 cells, and the responses were similar to that in lipopolysaccharide (LPS)-stimulated cells. FEA significantly suppressed NO synthesis and down-regulated both expression and secretion of COX-2, iNOS, and inflammatory cytokines (P<0.05 or P<0.01). FEA also reduced NF-κB p65 translocation into the nucleus and decreased MAPK phosphorylation, indicating that the NF-κB/MAPK signaling pathway may be closely related to the inflammatory response during viral infection. The findings suggested the potential pharmaceutical application of FEA as a natural product that can treat viral infections due to its ability to mitigate inflammatory responses.

8.
Nanoscale Horiz ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063803

RESUMO

Compared with the highly active anatase TiO2, rutile TiO2 usually presents poor photocatalytic performance due to high electron-hole recombination. Herein, we propose a surface domain heterojunction (SDH) structure between adjacent micro-domains with and without chemisorbed chlorine on rutile TiO2, which utilizes the potential difference between these domains to form a built-in field that promotes charge separation. Single-crystal rutile TiO2 nanorods assembled into radial microspheres with SDHs were fabricated, and these exhibited excellent solar-driven photocatalytic hydrogen evolution, ∼8-fold higher than that of the pristine one. Experimental results and density functional theory calculations reveal that the exceptional photocatalytic performance can be attributed to the in situ formation of chemisorbed chlorine, which forms SDHs that separate electrons and holes efficiently and results in surface reconfiguration, exposing the tri-active sites, increasing the O-site active centers and enhancing the catalytic activity of the 4-coordinated (Ti4c) and 5-coordinated Ti sites (Ti5c). This SDH strategy can extend to other halogen elements and thus provides an universal approach for the rational design of high-efficiency TiO2 photocatalysts toward sustainable solar-fuel evolution.

9.
Elife ; 92020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107819

RESUMO

Brown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1l, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the Ucp1 promoter and other BAT genes. Through a direct interaction, Dot1l is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1l is induced during brown fat cell differentiation and by cold exposure and that Dot1l and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1l ablation in mice using Ucp1-Cre prevents activation of Ucp1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1l plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

10.
Math Biosci Eng ; 17(4): 2805-2819, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32987497

RESUMO

The present paper considers a fractional-order N species network, in which, the general functions are used for finding general theories. The existence, uniqueness, and non-negativity of the solutions for the considered model are proved. Moreover, the local and global asymptotic stability of the equilibrium point are studied by using eigenvalue method and Lyapunov direct method. Finally, some simple examples and numerical simulations are provided to demonstrate the theoretical results.

12.
Phytomedicine ; 79: 153342, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32992085

RESUMO

OBJECTIVE: Multidrug resistance (MDR) is the major barrier to the successful treatment of chemotherapy. Compounds from nature products working as MDR sensitizers provided new treatment strategies for chemo-resistant cancers patients. METHODS: We investigated the reversal effects of nuciferine (NF), an alkaloid from Nelumbo nucifera and Nymphaea caerulea, on the paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo, and explored the underlying mechanism by evaluating drug sensitivity, cell cycle perturbations, intracellular accumulation, function and protein expression of efflux transporters as well as molecular signaling involved in governing transporters expression and development of MDR in cancer. RESULTS: NF overcomes the resistance of chemotherapeutic agents included PTX, doxorubicin (DOX), docetaxel, and daunorubicin to HCT-8/T and A549/T cancer cells. Notably, NF suppressed the colony formation of MDR cells in vitro and the tumor growth in A549/T xenograft mice in vivo, which demonstrated a very strong synergetic cytotoxic effect between NF and PTX as combination index (CI) (CI<0.1) indicated. Furthermore, NF increased the intracellular accumulation of P-gp substrates included DOX and Rho123 in the MDR cells and inhibited verapamil-stimulated ATPase activity. Mechanistically, inhibition of PI3K/AKT/ERK pathways by NF suppressed the activation of Nrf2 and HIF-1α, and further reduced the expression of P-gp and BCRP, contributing to the sensitizing effects of NF against MDR in cancer. CONCLUSION: This novel finding provides a promising treatment strategy for overcoming MDR and improving the efficiency of chemotherapy by using a multiple-targets MDR sensitizer NF.

13.
PLoS One ; 15(8): e0238353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866964

RESUMO

OBJECTIVE: Our aim was to identify the patterns of multimorbidity among a group of patients who visited primary care in Singapore. METHODS: A cross-sectional study of electronic medical records was conducted on 437,849 individuals aged 0-99 years who visited National Healthcare Group Polyclinics from 1 Jul 2015 to 30 Jun 2016 for the management of chronic conditions. Patients' health conditions were coded with the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10), and patient records were extracted for analysis. Patients' diagnosis codes were grouped by exploratory factor analysis (EFA), and patterns of multimorbidity were then identified by latent class analysis (LCA). RESULTS: EFA identified 19 groups of chronic conditions. Patients with at least three chronic conditions were further separated into eight classes based on demographics and probabilities of various diagnoses. We found that older patients had higher probabilities of comorbid hypertension, kidney disease and ischaemic heart disease (IHD), while younger patients had a higher probability of comorbid obesity. Female patients had higher probabilities of comorbid arthritis and anaemia, while male patients had higher probabilities of comorbid kidney diseases and IHD. Indian patients presented with a higher probability of comorbid diabetes than Chinese and Malay patients. CONCLUSIONS: This study demonstrated that patients with multimorbidity in primary care could be classified into eight patterns. This knowledge could be useful for more precise management of these patients in the multiethnic Asian population of Singapore. Programmes for early intervention for at-risk groups can be developed based on the findings.


Assuntos
Múltiplas Afecções Crônicas/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Multimorbidade , Adulto Jovem
14.
Phys Rev Lett ; 125(10): 107001, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32955301

RESUMO

Recent experiments reported gate-induced superconductivity in the monolayer 1T^{'}-WTe_{2} which is a two-dimensional topological insulator in its normal state. The in-plane upper critical field B_{c2} is found to exceed the conventional Pauli paramagnetic limit B_{p} by one to three times. The enhancement cannot be explained by conventional spin-orbit coupling which vanishes due to inversion symmetry. In this Letter, we unveil some distinctive superconducting properties of centrosymmetric 1T^{'}-WTe_{2} which arise from the coupling of spin, momentum and band parity degrees of freedom. As a result of this spin-orbit-parity coupling (SOPC): (i) there is a first-order superconductor-metal transition at B_{c2} that is much higher than the Pauli paramagnetic limit B_{p}, (ii) spin-susceptibility is anisotropic with respect to in-plane directions and can result in possible anisotropic B_{c2}, and (iii) the B_{c2} exhibits a strong gate dependence as the spin-orbit-parity coupling is significant only near the topological band crossing points. The importance of SOPC on the topologically nontrivial inter-orbital pairing phase is also discussed. Our theory generally applies to centrosymmetric materials with topological band inversions.

15.
Colloids Surf B Biointerfaces ; 195: 111271, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32736122

RESUMO

Lipidated peptide amphiphiles exhibit high affinity for plasma cell membranes, good cell internalization and improved stability against degradation, which make them attractive as a drug delivery system. However, low drug loading capacity limits their application for drug delivery. Herein, we developed a gemini peptide amphiphile with enhanced membrane activity and endosomal escape, containing dodecanoic acid hydrophobic tails at the N-terminus, rhodamine on the pendant chain and an active targeting peptide sequence (GRGDS). The presence of rhodamine not only provides high drug loading capability due to the π-π stacking interaction between camptothecin (CPT) and rhodamine, but also promotes peptide amphiphiles to form compact spherical micelles, as well as allows for fluorescence imaging. Single-molecule total internal reflection fluorescence microscopy investigation reveals gemini peptide amphiphile has higher affinity for plasma cell membranes than single-tail peptide amphiphile. Meanwhile, better cell internalization of gemini peptide amphiphile was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, CPT-loaded gemini peptide amphiphile induced enhanced cytotoxicity in cancer cells when compared to free CPT, indicating that lipidated peptide amphiphile with π-conjugates on the pendant chain and two hydrophobic tails can serve as a highly efficient drug delivery vehicle.

16.
Sci Rep ; 10(1): 12785, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32733043

RESUMO

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice. Elafin improved leptin sensitivity via reduced interferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

17.
J Biol Chem ; 295(44): 14840-14854, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32848016

RESUMO

Candida albicans is a dimorphic fungus that converts from a yeast form to a hyphae form during infection. This switch requires the formation of actin cable to coordinate polarized cell growth. It's known that nucleation of this cable requires a multiprotein complex localized at the tip called the polarisome, but the mechanisms underpinning this process were unclear. Here, we found that C. albicans Aip5, a homolog of polarisome component ScAip5 in Saccharomyces cerevisiae that nucleates actin polymerization and synergizes with the formin ScBni1, regulates actin assembly and hyphae growth synergistically with other polarisome proteins Bni1, Bud6, and Spa2. The C terminus of Aip5 binds directly to G-actin, Bni1, and the C-terminal of Bud6, which form the core of the nucleation complex to polymerize F-actin. Based on insights from structural biology and molecular dynamic simulations, we propose a possible complex conformation of the actin nucleation core, which provides cooperative positioning and supports the synergistic actin nucleation activity of a tri-protein complex Bni1-Bud6-Aip5. Together with known interactions of Bni1 with Bud6 and Aip5 in S. cerevisiae, our findings unravel molecular mechanisms of C. albicans by which the tri-protein complex coordinates the actin nucleation in actin cable assembly and hyphal growth, which is likely a conserved mechanism in different filamentous fungi and yeast.

18.
Can J Gastroenterol Hepatol ; 2020: 8861854, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766176

RESUMO

Objective: To observe the effects of thalidomide on 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced experimental colitis in rats and to explore the possible mechanism of thalidomide in the treatment of CD. Methods: Forty SD rats were randomly assigned into a healthy control group and TNBS-induced colitis groups, including an untreated TNBS-induced colitis group, a low-dose thalidomide group, and a high-dose thalidomide group, with 10 rats in each. After 7 days, the disease activity index (DAI), colon macroscopic damage index (CMDI), and tissue damage index (TDI) were evaluated. The colonic protein and mRNA expression levels of interleukin-6 (IL-6), IL-17, IL-23, and retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) were determined using immunohistochemistry, western blot, and qRT-PCR. Results: Relative to the untreated TNBS-induced colitis group, the DAI, CMDI, and TDI were all reduced following the administration of thalidomide. Analytical testing (immunohistochemistry, western blot, and qRT-PCR) shows that IL-6, IL-17, IL-23, and RORγt protein and mRNA expression levels were significantly reduced by thalidomide (p < 0.05 for all) and that these levels were significantly lower in the high-dose thalidomide group than in the low-dose thalidomide group (p < 0.05 for all). Conclusions: Thalidomide effectively alleviated the symptoms and intestinal inflammatory injury induced by TNBS in rats, the effect of which was dose-dependent. The underlying mechanism may be a reduction in the expression levels of IL-6, IL-17, IL-23, and RORγt in colonic tissue and then subsequent inhibition of the differentiation and function of Th17 cells, thus further alleviating the intestinal inflammatory response.

19.
Mol Cell Biochem ; 475(1-2): 151-159, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32767228

RESUMO

More than 50% of colorectal cancer (CRC) deaths are attributed to metastasis, and the liver is the most common distant metastatic site of CRC. The molecular mechanisms underlying CRC liver metastasis are very complicated and remain largely unknown. Accumulated evidence has shown that non-coding RNAs (NcRNAs) play critical roles in tumor development and progression. Here we reviewed the roles and underlying mechanisms of NcRNAs in CRC liver metastasis.

20.
J Nat Med ; 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32761488

RESUMO

Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1ß, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1ß. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKß, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.

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