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Abscisic acid (ABA) represses seed germination and postgerminative growth in Arabidopsis thaliana. Auxin and jasmonic acid (JA) stimulate ABA function; however, the possible synergistic effects of auxin and JA on ABA signaling and the underlying molecular mechanisms remain elusive. Here, we show that exogenous auxin works synergistically with JA to enhance the ABA-induced delay of seed germination. Auxin biosynthesis, perception, and signaling are crucial for JA-promoted ABA responses. The auxin-dependent transcription factors AUXIN RESPONSE FACTOR10 (ARF10) and ARF16 interact with JASMONATE ZIM-DOMAIN (JAZ) repressors of JA signaling. ARF10 and ARF16 positively mediate JA-increased ABA responses, and overaccumulation of ARF16 partially restores the hyposensitive phenotype of JAZ-accumulating plants defective in JA signaling in response to combined ABA and JA treatment. Furthermore, ARF10 and ARF16 physically associate with ABSCISIC ACID INSENSITIVE5 (ABI5), a critical regulator of ABA signaling, and the ability of ARF16 to stimulate JA-mediated ABA responses is mainly dependent on ABI5. ARF10 and ARF16 activate the transcriptional function of ABI5, whereas JAZ repressors antagonize their effects. Collectively, our results demonstrate that auxin contributes to the synergetic modulation of JA on ABA signaling, and explain the mechanism by which ARF10/16 coordinate with JAZ and ABI5 to integrate the auxin, JA, and ABA signaling pathways.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Ácidos Indolacéticos/metabolismo , Germinação , Proteínas de Arabidopsis/metabolismo , Sementes/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.
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Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.
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The non-Hermitian skin effect (NHSE) on the non-Hermitian Haldane model with gain and loss on the honeycomb lattice with the outline of a triangle is discussed. The NHSE only occurs on the edge of the lattice, transforming the edge modes into the higher-order corner modes. The NHSE can also occur on a lattice with only loss, which can be treated as a lattice with gain and loss as well as a global loss added to it. When the saturated gain is added to the three corner sites of the dissipative lattice, a single-mode laser system is obtained. When any one site is stimulated initially, the system will reach a saturated state depending on the distribution of the corner modes, and the stable laser light is emitted by sites at the corners.
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A nonlinear non-Hermitian topological laser system based on the higher-order corner states of the 2-dimensional (2D) Su-Schrieffer-Heeger (SSH) model is investigated. The topological property of this nonlinear non-Hermitian system described by the quench dynamics is in accordance with that of a normal 2D SSH model. In the topological phase, all sites belonging to the topological corner states begin to emit stable laser light when a pulse is given to any one site of the lattice, while no laser light is emitted when the lattice is in the trivial phase. Furthermore, the next-nearest-neighbor (NNN) couplings are introduced into the strong-coupling unit cells of the 2D SSH model, which open a band gap in the continuous band structure. In the topological phase, similar to the case of 2D SSH model without NNN couplings, the corner sites can emit stable laser light due to the robustness of the higher-order corner states when the NNN couplings are regarded as the perturbation. However, amplitude of the stimulated site does not decay to zero in the trivial phase, because the existence of the NNN couplings in the strong-coupling unit cells make the lattice like one in the tetramer limit, and a weaker laser light is emitted by each corner.
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We explore the influence of the artificial atomic chain on the input-output relation of the cavity. Specifically, we extend the atom chain to the one-dimensional Su-Schrieffer-Heeger (SSH) chain to check the role of atomic topological non-trivial edge state on the transmission characteristics of the cavity. The superconducting circuits can realize the artificial atomic chain. Our results show that the atom chain is not equivalent to atom gas, and the transmission properties of the cavity containing the atom chain are entirely different from that of the cavity containing atom gas. When the atom chain is arranged in the form of topological non-trivial SSH model, the atom chain can be equivalent to the three-level atom, in which the edge state contributes to the second level and is resonant with the cavity, while the high-energy bulk state contributes to form the third level and is greatly detuned with the cavity. Therefore, the transmission spectrum shows no more than three peaks. This allows us to infer the topological phase of the atomic chain and the coupling strength between the atom and the cavity only from the profile of the transmission spectrum. Our work is helping to understand the role of topology in quantum optics.
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PURPOSE: We conducted a systematic review and meta-analysis to evaluate the risk of early and late onset seizures following stroke mechanic thrombectomy (MT) compared with other systematic thrombolytic strategies. METHODS: A literature search was conducted to identify articles covering databases (PubMed, Embase, and Cochrane Library) published from 2000 to 2022. The primary outcome was the incidence of post-stroke epilepsy or seizures following MT or in combination with intravenous thrombolytics therapy. Risk of bias was assessed by recording study characteristics. The study was conducted according to the PRISMA guidelines. RESULTS: There were 1346 papers in the search results, and 13 papers were included in the final review.We identified 29,793 patients with stroke, of which 695 had seizures. Pooled incidence of post-stroke seizures had no significant difference between mechanic thrombolytic group and other thrombolytic strategy group (OR=0.95 (95%CI= 0.75-1.21); Z=0.43; p=0.67). In subgroup analysis, mechanic group have a lower risk of post-stroke early onset of seizures (OR=0.59 (95%CI=0.36-0.95); Z=2.18; p<0.05) but showed no significant difference in post-stroke late onset of seizures (OR=0.95 (95%CI= 0.68-1.32); Z=0.32; p=0.75). CONCLUSIONS: MT may be associated with a lower risk of post-stroke early onset of seizures, despite MT does not affect the pooled incidence of post-stroke seizures compared with other systematic thrombolytic strategies.
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PURPOSE: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. RESULTS: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-ß1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. CONCLUSION: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1ß, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.
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Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Cardiomegalia , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Fibrose , Glucose , Inflamassomos/metabolismo , Inflamação/complicações , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cofator PQQ/metabolismo , Cofator PQQ/farmacologia , Cofator PQQ/uso terapêutico , Piroptose , Transdução de SinaisRESUMO
Rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), displays a robust hypoglycemic action in patients with type 2 diabetes mellitus (T2DM) and elicits serious adverse reactions, especially hepatotoxicity and cardiotoxicity. Here, we aims to find a new natural PPAR-γ agonist with less adverse reactions than rosiglitazone in db/db mice. The method of virtual screening was used to identify a PPAR-γ agonist 18:0 Lyso PC from an in-house natural product library. We verified its pharmacological effects and adverse reactions comparing with rosiglitazone in vivo and in vitro. 18:0 Lyso PC exhibited pharmacological effects similar to those of rosiglitazone in db/db mice. Moreover, 18:0 Lyso PC showed a lower extent of liver injury and cardiotoxicity in db/db mice. The mechanism, by which this natural compound alleviates metabolic syndrome, involves a reduction in fatty acid synthesis mediated by activation of the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase-alpha (AMPKα) and acetyl-CoA carboxylase (ACC) and an increase expression of uncoupled protein 1 (UCP1) and PPAR-γ coactivator-1 alpha (PGC1-α). 18:0 Lyso PC, a natural compound, can show a similar hypoglycemic effect to rosiglitazone by activating PPAR-γ, while eliciting markedly fewer adverse reactions than rosiglitazone.
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Produtos Biológicos/química , Coração/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , Lisofosfolipídeos/química , PPAR gama/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP , Acetil-CoA Carboxilase/metabolismo , Animais , Cardiotoxicidade , Química Farmacêutica/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos/metabolismo , Lipídeos/química , Masculino , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , RosiglitazonaRESUMO
Multilayer neural networks are among the most powerful models in machine learning, yet the fundamental reasons for this success defy mathematical understanding. Learning a neural network requires optimizing a nonconvex high-dimensional objective (risk function), a problem that is usually attacked using stochastic gradient descent (SGD). Does SGD converge to a global optimum of the risk or only to a local optimum? In the former case, does this happen because local minima are absent or because SGD somehow avoids them? In the latter, why do local minima reached by SGD have good generalization properties? In this paper, we consider a simple case, namely two-layer neural networks, and prove that-in a suitable scaling limit-SGD dynamics is captured by a certain nonlinear partial differential equation (PDE) that we call distributional dynamics (DD). We then consider several specific examples and show how DD can be used to prove convergence of SGD to networks with nearly ideal generalization error. This description allows for "averaging out" some of the complexities of the landscape of neural networks and can be used to prove a general convergence result for noisy SGD.
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We show that an array of non-Hermitian particles can enable advanced manipulations of the scattering pattern, beyond what is possible with passive structures. Active linear elements are shown to provide zero forward scattering without sacrificing the total scattered power, and by adding more particles, it is possible to control the zero-scattering direction at will. We apply our theory to realistic implementations of scatterer arrays, using loaded dipole antennas in which we tune the load impedance and investigate the stability of these arrays based on a realistic dispersion model for the gain elements. Finally, we discuss the possibility of controlling multiple frequencies to enable broadband control of the scattering pattern.
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Partially defective fingerprint image (PDFI) with poor performance poses challenges to the automated fingerprint identification system (AFIS). To improve the quality and the performance rate of PDFI, it is essential to use accurate segmentation. Currently, most fingerprint image segmentations use methods with ridge orientation, ridge frequency, coherence, variance, local gradient, etc. This paper proposes a method of XFinger-Net for segmenting PDFIs. Based on U-Net, XFinger-Net inherits its characteristics. The attention gate with fewer parameters is used to replace the cascaded network, which can suppress uncorrelated regions of PDFIs. Moreover, the XFinger-Net implements a pixel-level segmentation and takes non-blocking fingerprint images as an input to preserve the global characteristics of PDFIs. The XFinger-Net can achieve a very good segmentation effect as demonstrated in the self-made fingerprint segmentation test.
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Dermatoglifia , Processamento de Imagem Assistida por Computador , HumanosRESUMO
Synthetic chiral helical polymers have achieved impressive progress in past few decades. Unfortunately, how to construct chiral helical polymer-derived functional materials still remains highly challenging. The present contribution reports an unprecedented, one-step strategy for judiciously combining chiral helical polymer with graphene to construct chiral hybrid foams. Graphene oxide (GO), ascorbic acid (L-AA), Rh catalyst, and an achiral acetylenic monomer bearing phenylboronic acid group are mixed in an aqueous dispersion. Under mild conditions, the monomer underwent polymerization; meanwhile GO transforms into reduced graphene oxide (RGO) which in situ self-assembles to construct a 3D porous structure. Herein, L-AA simultaneously plays double roles: 1) working as a chiral source for the monomer to undergo helix-sense-selective polymerization or transferring its chirality to the polymer chains via forming borate structure; and 2) working as a reducing agent for reducing GO. The preparation strategy combines four processes into one single step: monomer polymerization, chirality transfer, reduction of GO, and RGO's self-assembly. The eventually obtained chiral hybrid foams demonstrate advantages of porous structure, chirality, and reversible borate functional groups. The established preparation strategy promises a potent platform for conveniently constructing advanced chiral polymeric materials and even chiral hybrids starting from achiral monomers.
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Ácido Ascórbico/química , Grafite/química , Polímeros/química , Catálise , Polimerização , Rutênio/química , EstereoisomerismoRESUMO
PURPOSE: Little is known about the association between sleep duration and health status in Chinese university students. This study examined the association between sleep duration and self-rated health in university students in China. METHODS: Altogether, 2312 subjects (928 in Macao, 446 in Hong Kong, and 938 in mainland China) were recruited. Standardized measures of sleep and self-reported health were administered. Sleep duration was categorized in the following way: < 6 h/day, 6 to < 7 h/day, 7-9 h/day, and > 9 h/day. RESULTS: Overall, 71% of university students reported poor health, 53% slept 7-9 h/day, 14% slept less than 6 h/day, 32% slept 6 to < 7 h/day, and 1% slept > 9 h/day. Univariate analysis revealed that compared to students with medium sleep duration (7-9 h/day), those with short sleep duration (< 6 h/day and 6 to < 7 h/day) were more likely to report poor health. Multivariate logistic regression analysis found that after controlling for age, gender, body mass index, university location, being a single child, religious beliefs, interest in academic major, academic pressure, nursing major, pessimism about the future, and depression, sleep duration of less than 6 h/day (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.34-2.92, p < 0.01) was independently and significantly associated with poor self-reported health. CONCLUSIONS: Poor health status is common in Chinese university students, which appears to be closely associated with short sleep duration. Further longitudinal studies are warranted to gain a better understanding of the interaction between sleep patterns and health status in university students.
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Atitude Frente a Saúde , Nível de Saúde , Sono , Estudantes/psicologia , Adolescente , Adulto , China , Feminino , Hong Kong , Humanos , Macau , Masculino , Universidades , Adulto JovemRESUMO
Phosphatidylinositol 3-kinase delta (PI3Kδ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. In this study, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74- to >900-fold selectivity against other PI3K family members. In vitro and ex vivo studies using primary B cells, cell lines from B cell malignancies, and human whole blood show that INCB040093 inhibits PI3Kδ-mediated functions, including cell signaling and proliferation. INCB040093 has no significant effect on the growth of nonlymphoid cell lines and was less potent in assays that measure human T and natural killer cell proliferation and neutrophil and monocyte functions, suggesting that the impact of INCB040093 on the human immune system will likely be restricted to B cells. INCB040093 inhibits the production of macrophage-inflammatory protein-1ß (MIP-1beta) and tumor necrosis factor-ß (TNF-beta) from a B cell line, suggesting a potential effect on the tumor microenvironment. In vivo, INCB040093 demonstrates single-agent activity in inhibiting tumor growth and potentiates the antitumor growth effect of the clinically relevant chemotherapeutic agent, bendamustine, in the Pfeiffer cell xenograft model of non-Hodgkin's lymphoma. INCB040093 has a favorable exposure profile in rats and an acceptable safety margin in rats and dogs. Taken together, data presented in this report support the potential utility of orally administered INCB040093 in the treatment of B cell malignancies.
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Antineoplásicos/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL4/metabolismo , Cães , Feminino , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Linfoma não Hodgkin/metabolismo , Masculino , Camundongos , Camundongos SCID , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Neoplasias/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ratos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
We consider the non-horizontal distributions of orbital angular momentum biphotons through free-space atmospheric channels, in which case the non-Kolmogorov turbulent effects shall be considered. By considering the case of initial non-perfect resource, i.e., the orbital angular momentum biphotons are initially prepared in an extended Werner-like state, we investigate the non-Kolmogorov effects on the propagations of nonclassical correlations, including quantum entanglement and quantum discord. It is found that universal decay laws of entanglement and discord also exist for non-Kolmogorov turbulence but with their decay curves different from that of entanglement for Kolmogorov turbulence reported by Leonhard et al. [Phys. Rev. A91, 012345 (2015)PLRAAN1050-294710.1103/PhysRevA.91.012345]. We show that the universal decay laws are dependent on the power-law exponent of the non-Kolmogorov spectrum and compare the differences of decay properties between entanglement and discord caused by non-Kolmogorov turbulence.
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OBJECTIVE: The therapeutic effect and mechanism of total flavonoids in Isodon amethystoides (Ben-th) Cy Wu et Hsuan (TFIA) on adjuvant arthritis (AA) were investigated. METHODS: AA model rats were set and complete Freund's adjuvant injection,randomly divided into 4 groups: AA group,AA+TFIA 50 mg/kg group,AA+TFIA 100 mg/kg group,AA+TFIA 150 mg/kg group,and each group has 10 rats. Blank control group was set without modeling (n=10). Four days post-modeling rats in each TFIA groups were treated once a day with TFIA at 50 mg/kg,100 mg/kg and 150 mg/kg for 24 d,and rats in blank control and AA groups were given saline as control. At the 12th day,16th day,20th day and 24th day of treatment,the effect of TFIA on AA rats was evaluated by rat arthritis score. Then the rats were sacrificed on the 24th day of treatment,and the synovial tissue of rats was isolated and the fibroblast-like synoviocytes (FLS) were primary cultured. The expressions of IL-1 in FLS was detected by ELISA,the FLS proliferation activity was detected by MTT assay,and the expression of miR-152,ß-catenin and cyclin D1 gene (ccnd1) were detected by real time qPCR. MiR-152 mimics and NC mimics (control) were transfected into FLS in AA rats,and miR-152 inhibitors and NC inhibitors (control) were transfected into FLS in AA+TFIA 100 mg/kg group rats. The expressions of miR-152,ß-catenin, ccnd1, IL-1 and FLS proliferation were detected 36 h post-transfection. RESULTS: TFIA significantly inhibited the arthritis socre of rats and the expressions of ß-catenin, ccnd1, IL-1 and the proliferation of FLS in AA rats (P<0.05). There was no significant difference between the dose groups,all of which were significant when compared with the blank control group (P<0.05). Compared with the control group,the expression of miR-152 in AA group was significantly decreased (P<0.05). After transfection of miR-152 mimics into AA FLS,overexpression of miR-152 significantly inhibited the expressions of ß-catenin, ccnd1, IL-1 and the proliferation of FLS (P<0.05). After transfection of miR-152 inhibitors into FLS from AA+TFIA 100 mg/kg group,inhibition of miR-152 significantly promoted the expressions of ß-catenin, ccnd1, IL-1 and the proliferation of FLS. CONCLUSION: TFIA has a certain therapeutic effect on AA rats via the up-regulation of miR-152 expression,possibly affecting the classical Wnt signaling pathway.
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Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Sinoviócitos/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Proliferação de Células , MicroRNAs/genética , Ratos , Transfecção , Via de Sinalização WntRESUMO
OBJECTIVE: To study the effect of paeoniflorin (PF) on mTOR signal in synovial fibroblast-like synoviocytes (FLS) in rats with adjuvant arthritis. METHODS: AA model rats were prepared by complete Freun's adjuvant injection in foot-plantar, the PF was injected to rats in AA + PF 100 µg / mL group, AA + PF 200 µg / mL group and AA + PF 400 µg / mL group by the tail vein injection at the dose of 0.1 mL/200 g body mass, and the effects of three doses of PF on arthritis scores in AA rats were studied. The modeling rats and control rats were sacrificed at 28 d after modeling, then the synovium was separeated from rat articular, the FLS were cultured. The effect of PF on the expression of mTOR and MMP3 in AA FLS was detected by the real time qPCR. The effect on the cytokine IL-1, IL-6 was detected by ELISA, and the Western blot was used to investigate the role of PF in the mTOR phosphorylation. Furthermore, FLS were transfected with mTOR vectors, and the effect of mTOR overexpression on the PF roles was detected by real time qPCR and ELISA. RESULTS: The tail vein injection of PF can significantly reduce the AA rat arthritis score. Compared with AA group, the expression of mTOR in AA+PF 1 µg/mL, AA+PF 2 µg/mL, AA+PF 4 µg/mL was significantly decreased at 48 h after dosing. Compared with AA group, the relative expression of p-mTOR protein in PF 2 µg/mL group was also decreased. Compared with AA group at 48 h after dosing, the levels of IL-1, IL-6 and MMP3 in AA+PF 1 µg/mL, AA+PF 2 µg/mL, AA+PF 4 µg/ mL were significantly decreased, respectively. Compared with PF 2 µg/mL group, the relative expression of IL-1, IL-6 and MMP3 in PF 2 µg/mL+mTOR vectors was increased. CONCLUSION: PF can significantly inhibit the pathology of AA rats, and its mechanism may be related to the inhibition of mTOR signal in FLS of AA rats.
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Artrite Experimental/metabolismo , Fibroblastos/efeitos dos fármacos , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Células Cultivadas , Interleucinas/metabolismo , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/citologiaRESUMO
To assess the potential safety of lipid soluble green tea extract, also referred to as lipid soluble tea polyphenols (LSTP), a series of genotoxicity tests were conducted, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality test. The toxicity of LSTP was evaluated in 90- and 30-day feeding studies. LSTP did not show mutagenic activity in the Ames test and no genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). In the 90-day feeding study, LSTP was given in the diet at levels providing 0, 0.125, 0.25, or 0.50 g/kg bw/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The no-observed-adverse-effect level (NOAEL) was therefore considered to be 0.50 g/kg bw/day, the highest dose tested. Likewise, dosing of SD rats by gavage for 30 days also showed no adverse effects of growth, hematology, clinical chemistry, organ weights, or histopathology at doses of 0.58, 1.17, and 2.33 g/kg bw/day. The NOAEL in the 30-day study was considered to be the highest dose tested. These data provide evidence to support the safe use of LSTP in food.
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Extratos Vegetais/toxicidade , Polifenóis/toxicidade , Chá/toxicidade , Animais , Lipídeos , Camundongos , Testes de Mutagenicidade , Nível de Efeito Adverso não Observado , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Chá/químicaRESUMO
Our preliminary study showed that the total flavonoids in Isodon amethystoides(TFIA), a local medicinal herb in Suzhou, had a certain therapeutic effect on adjuvant arthritis, and this therapeutic effect may be achieved through the up-regulation of miR-152 expression. In this paper, the molecular mechanism of TFIA on the pathogenesis of adjuvant arthritis(AA) rats was further studied. AA rats were prepared with complete Freund's adjuvant, and then treated with TFIA by intragastric administration. Real-time qPCR was used to detect the effects of TFIA on the negative regulatory loop of miR-152, methylase DNMT1 and methyl-CpG binding protein MeCP2 in fibroblast like synoviocytes(FLS) of AA rats, as well as the effects of TFIA on the classic Wnt signaling pathway and the expression of fibronectin gene in AA rats. Intragastric administration of TFIA significantly inhibited the expression of DNMT1 and reversed the negative regulatory loop composed of miR-152, DNMT1 and MeCP2 in the pathology of AA rats. After transfection of miR-152 inhibitors into the FLS in treatment group, DNMT1 expression was significantly restored. TFIA significantly up-regulated the expression of SFRP4 and inhibited the expression of ß-catenin, C-myc and ccnd1, the key genes of canonical Wnt signaling pathway. TFIA also significantly inhibited the expression of fibronectin, an AA gene. The effect of TFIA on the expression of SFRP4, ß-catenin, C-myc, ccnd1 and fibronectin was reversed after transfection with miR-152 inhibitors in the treatment group FLS. TFIA may inhibit the DNMT1 expression, up-regulate the SFRP4 expression, inhibit the expression of classical Wnt signaling genes ß-catenin, C-myc, and ccnd1 as well as the RA gene fibronectin expression through the up-regulation of miR-152 expression.