Aurantiamide mitigates acute kidney injury by suppressing renal necroptosis and inflammation via GRPR-dependent mechanism.

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment.

[Risk factors for pancreatitis after endoscopic retrograde cholangiopancreatography in children]. / å„¿ç«¥ç»å† é•œé€†è¡Œèƒ°èƒ†ç®¡é€ å½±æœ¯åŽèƒ°è ºç‚Žå‘ç”Ÿçš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the application of endoscopic retrograde cholangiopancreatography (ERCP) in children and the risk factors for post-ERCP pancreatitis (PEP). METHODS: A retrospective analysis was conducted on the clinical data of 66 children, aged ≤16 years, who underwent ERCP for pancreaticobiliary diseases at the Gastrointestinal Endoscopy Center of the Second Affiliated Hospital of Kunming Medical University from September 2013 to September 2023. The incidence rate of PEP and the risk factors for the development of PEP were analyzed. RESULTS: A total of 78 ERCP procedures were performed on 66 children, with 5 diagnostic ERCPs, 69 therapeutic ERCPs, and 4 failed procedures. The success rate of ERCP operations was 95% (74/78). There were 17 cases of PEP in total, with an incidence rate of 22%. In the PEP group, the proportion of children with normal preoperative bilirubin and the proportion of guidewire insertion into the pancreatic duct during surgery were higher than in the non-PEP group (P<0.05). The multivariate logistic regression analysis showed that guidewire insertion into the pancreatic duct was an independent risk factor for PEP (P<0.05). CONCLUSIONS: With the increasing application of ERCP in children with pancreaticobiliary diseases, it is important to select an appropriate intubation technique during surgery to avoid blindly entering the guidewire into the pancreatic duct and reduce the occurrence of PEP.

Interruption of TRPC6-NFATC1 signaling inhibits NADPH oxidase 4 and VSMCs phenotypic switch in intracranial aneurysm.

Intracranial aneurysm (IA) is a frequent cerebrovascular disorder with unclear pathogenesis. The vascular smooth muscle cells (VSMCs) phenotypic switch is essential for IA formation. It has been reported that Ca2+ overload and excessive reactive oxygen species (ROS) are involved in VSMCs phenotypic switch. The transient receptor potential canonical 6 (TRPC6) and NADPH oxidase 4 (NOX4) are the main pathway to participate in Ca2+ overload and ROS production in VSMCs. Ca2+ overload can activate calcineurin (CN), leading to nuclear factor of activated T cell (NFAT) dephosphorylation to regulate the target gene's transcription. We hypothesized that activation of TRPC6-NFATC1 signaling may upregulate NOX4 and involve in VSMCs phenotypic switch contributing to the progression of IA. Our results showed that the expressions of NOX4, p22phox, p47phox, TRPC6, CN and NFATC1 were significantly increased, and VSMCs underwent a significant phenotypic switch in IA tissue and cellular specimens. The VIVIT (NFATC1 inhibitor) and BI-749327 (TRPC6 inhibitor) treatment reduced the expressions of NOX4, p22phox and p47phox and the production of ROS, and significantly improved VSMCs phenotypic switch in IA rats and cells. Consistent results were obtained from IA Trpc6 knockout (Trpc6-/-) mice. Furthermore, the results also revealed that NFATC1 could regulate NOX4 transcription by binding to its promoter. Our findings reveal that interrupting the TRPC6-NFATC1 signaling inhibits NOX4 and improves VSMCs phenotypic switch in IA, and regulating Ca2+ homeostasis may be an important therapeutic strategy for IA.

Toxicity effects of nanoplastics on soybean (Glycine max L.): Mechanisms and transcriptomic analysis.

Microplastic (MP) pollution has become a major concern in recent years. In agricultural production, MPs can not only affect the growth of crops but also affect yield. Compared with micron-sized MPs, nanoplastics (NPs) may be more harmful to plants. However, the effects of NPs on plant growth and development have attracted relatively little attention. As such, research has currently plateaued at the level of morphology and physiology, and the molecular mechanisms are still unclear. In this study, soybeans (Glycine max L.) were treated with polystyrene nanoplastics (PS-NPs) to observe phenotypic changes and measure the effects of PS-NPs on diverse aspects of soybeans. Compared to the control group, the soybean stem and root lengths were inhibited by 11.78% and 12.58%, respectively. The reactive oxygen species content and the antioxidant enzyme activities changed significantly (p < 0.05). The accumulation of manganese (Mn) and magnesium (Mg) in the roots revealed that root transmembrane transport was affected by PS-NPs stress. The content of salicylic acid 2-O-ß-glucoside was inhibited whereas the accumulation of l-tryptophan, the precursor of auxin synthesis, was significantly increased (p < 0.05) in leaves. Transcriptomic analysis showed that PS-NPs could affect soybean DNA repair, membrane protein transport, and hormone synthesis and response. This study revealed the toxicity of NPs to soybeans and that NPs affected a variety of biological processes through transcriptome and hormone metabolome analysis, which provides a theoretical basis to further study the molecular mechanism of the effects on plants.

Expression of serum miR-126 in patients with intracranial aneurysm and its relationship with postoperative cerebral vasospasm.

OBJECTIVE: To examine the expression of serum miR-126 in patients with intracranial aneurysm and to explore its relationship with postoperative cerebral vasospasm. METHODS: In this retrospective study, 85 patients with intracranial aneurysms diagnosed and treated in our hospital were enrolled into the research group (RG), and 83 healthy volunteers who came to our hospital for physical examination were selected as the control group (CG). The serum miR-126 expression in both groups was examined by RT-PCR, and the relationship between the diagnostic value of miR-126 for intracranial aneurysm and postoperative cerebral vasospasm was analyzed. The serum inflammatory related factors in the patients were tested, and their correlation with miR-126 was assessed. The risk factors of postoperative cerebral vasospasm were evaluated by multiple factors. RESULTS: The serum miR-126 expression in patients with intracranial aneurysm was obviously lower than that of participants in CG (P<0.05), and the AUC of miR-126 in diagnosing intracranial aneurysm was 0.945, which was of high diagnostic value. Serum inflammatory factors TNF-α and IL-6 were highly expressed in the serum of patients with intracranial aneurysm, which were positively correlated with the miR-126 level (P<0.05). After operation, the serum miR-126 level in patients with cerebral vasospasm was obviously higher than that of those without cerebral vasospasm, and the AUC of miR-126 for predicting cerebral vasospasm after operation was 0.859. Logistic regression analysis revealed that preoperative bleeding frequency, history of hypertension, Hunt-Hess grade and high expression of miR-126 were independent risk factors for cerebral vasospasm after operation in patients with intracranial aneurysm. CONCLUSION: miR-126 is highly expressed in the serum of patients with intracranial aneurysm, so it may be used as a potential biomarker for the diagnosis of patients with intracranial aneurysm and the prediction of cerebral vasospasm after operation.

SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in lipopolysaccharide-induced neuronal damage and Aß generation.

The level of lipopolysaccharide (LPS) is higher in the blood and brains of patients with Alzheimer's disease (AD), and this phenomenon is strongly linked to AD-related neuronal damage and ß-amyloid (Aß) generation. However, the mechanism by which LPS causes neuronal damage has still not been fully clarified. Oxidative stress, neuroinflammation, and Ca2+ overload are regarded as important factors influencing AD. NADPH oxidase 2 (NOX2) and the NOD-like receptor family protein 1 (NLRP1) inflammasome play important roles in promoting oxidative stress and inflammation in neurons. Ca2+ overload can activate calcineurin (CN), which further dephosphorylates nuclear factor of activated T cells (NFAT), leading to its translocation into the nucleus to regulate gene transcription. In the present study, LPS (250 µg/kg) exposure for 14 days was used to induce cognitive dysfunction in mice and LPS (20 µg/ml) exposure for 48 h was used to induce neuronal damage in HT22 cells. The results showed that LPS exposure activated phospholipase C (PLC), CN, and NFAT1; increased the expressions of NOX2- and NLRP1-related proteins; and promoted neuronal damage and Aß deposition in mice and HT22 cells. However, treatment with 2-APB (SOCE inhibitor), apocynin (NOX inhibitor), or tempol (reactive oxygen species scavenger) significantly reversed these LPS-induced changes, and improved neuronal damage and Aß deposition. Moreover, LPS exposure promoted PLC phosphorylation, increased the level of inositol-1,4,5-triphosphate, elevated the intracellular Ca2+ concentration ([Ca2+]i), and disrupted [Ca2+]i homeostasis in HT22 cells. These data indicated that the activation of SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in LPS-induced neuronal damage and Aß generation.

NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice.

BACKGROUND: Brain aging is an important risk factor in many human diseases, such as Alzheimer's disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process. METHODS: In this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice. RESULTS: The results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of ß-galactosidase (ß-gal), the levels of ROS and IL-1ß, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice. CONCLUSION: Our study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.

Ginsenoside Rg1 alleviates Aß deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice.

BACKGROUND: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. METHODS: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aß) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. RESULTS: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aß generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. CONCLUSIONS: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aß deposition by inhibiting NOX2 activation in APP/PS1 mice.

Ginsenoside Rg1 alleviates lipopolysaccharide-induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells.

Lipopolysaccharide (LPS) is a toxic component of cell walls of Gram-negative bacteria that are widely present in gastrointestinal tracts. Increasing evidence showed that LPS plays important roles in the pathogeneses of neurodegenerative disorders, such as Alzheimer's disease (AD). NADPH oxidase s2 (NOX2) is a complex membrane protein that contributes to the production of reactive oxygen species (ROS) in several neurological diseases. The NLRP1 inflammasome can be activated in response to an accumulation of ROS in neurons. However, it is still unknown whether LPS exposure can deteriorate neuronal damage by activating NOX2-NLRP1 inflammasomes. Ginsenoside Rg1 (Rg1) has protective effects on neurons, although whether Rg1 alleviates LPS-induced neuronal damage by inhibiting NOX2-NLRP1 inflammasomes remains unclear. In the present study, the effect of concentration gradients and different times of LPS exposure on neuronal damage was investigated in HT22 cells, and further observed the effect of Rg1 treatment on NOX2-NLPR1 inflammasome activation, ROS production and neuronal damage in LPS-treated HT22 cells. The results demonstrated that LPS exposure significantly induced NOX2-NLRP1 inflammasome activation, excessive production of ROS, and neuronal damage in HT22 cells. It was also shown that Rg1 treatment significantly decreased NOX2-NLRP1 inflammasome activation and ROS production and alleviated neuronal damage in LPS-induced HT22 cells. The present data suggested that Rg1 has protective effects on LPS-induced neuronal damage by inhibiting NOX2-NLRP1 inflammasomes in HT22 cells, and Rg1 may be a potential therapeutic approach for delaying neuronal damage in AD.

Molecular characterization of the Yp11.2 region deletion in the Chinese Han population.

The Y chromosome is male-specific and is important for spermatogenesis and male fertility. However, the Y chromosome is poorly characterized due to massive palindromes and inverted repeats, which increase the likelihood of genomic rearrangements, resulting in short tandem repeats on the Y chromosome or long fragment deletions. The present study reports a large-scale (2.573~2.648 Mb) deletion in the Yp11.2 region in a Chinese population based on the analysis of 34 selected Y-specific sequence-tagged sites and subsequent sequencing of the breakpoint junctions on the Y chromosome from 5,068,482-5,142,391 bp to 7,715,462-7,716,695 bp. The results of sequence analysis indicated that the deleted region included part or all of the following five genes: PCDH11Y, TSPY, AMELY, TBL1Y, and RKY. These genes are associated with spermatogenesis or amelogenesis and various other processes; however, specific physiological functions and molecular mechanisms of these genes remain unclear. Notably, individuals with this deletion pattern did not have an obvious pathological phenotype but manifested some degree of amelogenesis imperfecta.

Strain Engineering of a MXene/CNT Hierarchical Porous Hollow Microsphere Electrocatalyst for a High-Efficiency Lithium Polysulfide Conversion Process.

Tensile-strained Mxene/carbon nanotube (CNT) porous microspheres were developed as an electrocatalyst for the lithium polysulfide (LiPS) redox reaction. The internal stress on the surface results in lattice distortion with expanding Ti-Ti bonds, endowing the Mxene nanosheet with abundant active sites and regulating the d-band center of Ti atoms upshifted closer to the Fermi level, leading to strengthened LiPS adsorbability and accelerated catalytic conversion. The macroporous framework offers uniformed sulfur distribution, potent sulfur immobilization, and large surface area. The composite interwoven by CNT tentacle enhances conductivity and prevents the restacking of Mxene sheets. This combination of tensile strain effect and hierarchical architecture design results in smooth and favorable trapping-diffusion-conversion of LiPS on the interface. The Li-S battery exhibits an initial capacity of 1451 mAh g-1 at 0.2 C, rate capability up to 8 C, and prolonged cycle life.

Ginsenoside Rg1 ameliorates glomerular fibrosis during kidney aging by inhibiting NOX4 and NLRP3 inflammasome activation in SAMP8 mice.

Aging is closely related to the progress of renal fibrosis, which eventually results in renal dysfunction. Ginsenoside Rg1 (Rg1) has been reported to have an extensive anti-aging effect. However, the role and mechanism of Rg1 in aging-related renal fibrosis remain unclear. The present study aimed to evaluate the protective effect and mechanism of Rg1 in renal fibrosis during kidney aging in a model of SAMP8 mice. Taking SAMR1 mice as the control group, SAMP8 mice were administered Apocynin (50 mg/kg), Tempol (50 mg/kg), or Rg1 (5, 10 mg/kg) intragastrically for 9 weeks as treatment groups. The results showed that the elevated levels of blood urea nitrogen, serum creatinine and senescence-associated ß-galactosidase (ß-Gal) were markedly decreased, the glomerular mesangial proliferation was significantly alleviated and the increased levels of collagen IV and TGF-ß1 were significantly downregulated by Rg1 in SAMP8 mice. In addition, the generation of ROS and the expression of NADHP oxidase 4 (NOX4) in the renal cortex were significantly reduced by Rg1 treatment. The expression levels of NLRP3 inflammasome-related proteins and the inflammation-related cytokine IL-1ß were also inhibited by Rg1 treatment in the SAMP8 mice. These results suggested that Rg1 could delay kidney aging and inhibit aging-related glomerular fibrosis by reducing NOX4-derived ROS generation and downregulating NLRP3 inflammasome expression.

A Novel Hierarchically Porous Polypyrrole Sphere Modified Separator for Lithium-Sulfur Batteries.

The commercialization of Lithium-sulfur batteries was limited by the polysulfide shuttle effect, and modifying the routine separator was an effective method to solve this problem. In this work, a novel hierarchically porous polypyrrole sphere (PPS) was successfully prepared by using silica as hard-templates. As-prepared PPS was slurry-coated on the separator, which could reduce the polarization phenomenon of the sulfur cathode, and efficiently immobilize polysulfides. As expected, high sulfur utilization was achieved by suppressing the shuttle effect. When tested in the lithium-sulfur battery, it exhibited a high capacity of 855 mAh·g-1 after 100 cycles at 0.2 C, and delivered a reversible capacity of 507 mAh·g-1 at 3 C, showing excellent electrochemical performance.

Novel Sulfur/Ethylenediamine-Functionalized Reduced Graphene Oxide Composite as Cathode Material for High-performance Lithium-Sulfur Batteries.

Sulfur/ethylenediamine-functionalized reduced graphene oxide (S/EDA-RGO) nanocomposites were synthesized using a simple process. Ethylenediamine (EDA) was employed as both the reducing agent and the modification component. The morphologies, microstructures, and compositions of S/EDA-RGO composites were characterized by various detection techniques. The data indicated that EDA-RGO used as scaffolds for sulfur cathodes could enhance the electronic conductivity of the composites and strengthen the adsorbability of polysulfides. Meanwhile, the electrochemical properties of both S/EDA-RGO and S/RGO composites that were used as cathodes for lithium-sulfur (Li-S) batteries were investigated. The initial discharge capacity of S/EDA-RGO composites reached 1240 mAh g−1, with reversible capacity being maintained at 714 mAh g−1 after 100 cycles. The improvement in cycling stability of S/EDA-RGO composites was further verified at different current rates. These findings demonstrated that proper surface modification of RGO by EDA reducing agent might improve the electrochemical performances of Li⁻S batteries.

Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High Performance Lithium Sulfur Batteries.

An efficient, industry-accepted spray drying method was used to synthesize micro-spherical sulfur/graphene oxide (S/GO) composites as cathode materials within lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles, with wrinkled GO composites, was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The unique morphological design of this material enabled superior discharge capacity and cycling performance, demonstrating a high initial discharge capacity of 1400 mAh g-1 at 0.1 C. The discharge capacity remained at 828 mAh g-1 after 150 cycles. The superior electrochemical performance indicates that the S/GO composite improves electrical conductivity and alleviates the shuttle effect. This study represents the first time such a facile spray drying method has been adopted for lithium sulfur batteries and used in the fabrication of S/GO composites.

MeCP2 Regulates PTCH1 Expression Through DNA Methylation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, in which pathogenesis is not clear. Many research demonstrated that fibroblast-like synoviocytes (FLSs) play a key role in RA pathogenesis, join in the cartilage injury and hyperplasia of the synovium, and contribute to the release of inflammatory cytokines. We used adjuvant arthritis (AA) rats as RA animal models. The methyl-CpG-binding protein 2 (MeCP2) enables the suppressed chromatin structure to be selectively detected in AA FLSs. Overexpression of this protein leads to an increase of integral methylation levels. Some research has confirmed the hedgehog (Hh) signaling pathway plays an important role in RA pathogenesis; furthermore, patched 1 (PTCH1) is a negative fraction of Hh signaling pathway. We used 5-aza-2'-deoxycytidine (5-azadc) as DNA methylation inhibitor. In our research, we found MeCP2 reduced PTCH1 expression in AA FLSs; 5-azadc obstructed the loss of PTCH1 expression. 5-Azadc, treatment of AA FLSs, also blocks the release of inflammatory cytokines. In order to probe the potential molecular mechanism, we assumed the epigenetic participation in the regulation of PTCH1. Results demonstrated that PTCH1 hypermethylation is related to the persistent FLS activation and inflammation in AA rats. Knockdown of MeCP2 using small-interfering RNA technique added PTCH1 expression in AA FLSs. Our results indicate that DNA methylation may offer molecule mechanisms, and the reduced PTCH1 methylation level could regulate inflammation through knockdown of MeCP2. Graphical Abstract PTCH1 is an inhibitory protein of the Hedgehog signaling pathway. Increased expression of PTCH1 can inhibit the expression of Gli1 and Shh, thereby inhibiting the activation of Hedgehog signaling pathway. Inactivated Hedgehog signaling pathway inhibits the secretion of IL-6 and TNF-α. MeCP2 mediates hypermethylation of PTCH1 gene and decreases the expression of PTCH1 protein, thus activating Hedgehog signaling pathway and increasing secretion of IL-6 and TNF-α.

Hesperidin derivative-11 inhibits fibroblast-like synoviocytes proliferation by activating Secreted frizzled-related protein 2 in adjuvant arthritis rats.

Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has a multitude of pharmacological properties, which include antioxidant, anti-inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11), a HDN derivative with enhanced water-solubility and bioavailability, is effective on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated that administration of HDND-11 inhibited proliferation of fibroblast-like synoviocytes (FLS). Results of Western blot, Real-time quantitative PCR (RT-qPCR) analysis and Immunofluorescence staining demonstrated that HDND-11 was able to up-regulate the expression of Secreted frizzled-related proteins 2 (SFRP2) and diminish DNA methyltransferase 1(DNMT1) expression. We also identified that the effect of DNMT1 inhibition was completely similar to the effects of HDND-11 on SFRP2 gene expression. Furthermore, our results indicated that treatment with HDND-11 could suppress activation of Wnt pathway. Taken together, we found that the HDND-11diminished inhibitory effect of DNMT1 on SFRP2, thereby down-regulated ß-catenin expression and inhibited the activation of Wnt signaling pathways to inhibit FLS growth.

A numerical study of non-collinear wave mixing and generated resonant components.

Interaction of two non-collinear nonlinear ultrasonic waves in an elastic half-space with quadratic nonlinearity is investigated in this paper. A hyperbolic system of conservation laws is applied here and a semi-discrete central scheme is used to solve the numerical problem. The numerical results validate that the model can be used as an effective method to generate and evaluate a resonant wave when two primary waves mix together under certain resonant conditions. Features of the resonant wave are analyzed both in the time and frequency domains, and variation trends of the resonant waves together with second harmonics along the propagation path are analyzed. Applied with the pulse-inversion technique, components of resonant waves and second harmonics can be independently extracted and observed without distinguishing times of flight. The results show that under the circumstance of non-collinear wave mixing, both sum and difference resonant components can be clearly obtained especially in the tangential direction of their propagation. For several rays of observation points around the interaction zone, the further it is away from the excitation sources, generally the earlier the maximum of amplitude arises. From the parametric analysis of the phased array, it is found that both the length of array and the density of element have impact on the maximum of amplitude of the resonant waves. The spatial distribution of resonant waves will provide necessary information for the related experiments.

MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes.

OBJECTIVES: Rheumatoid arthritis (RA) is a heterogenic and systemic autoimmune disease characterized by synovitis and joint structural damage. However, the pathogenesis of RA is still obscure. It has been reported microRNA-20a (miRNA-20a) was significantly associated with the regulation of pro-inflammatory cytokines release in RA FLS. The purpose of this study was to explore the function and underlying mechanisms of miRNA-20a on NLRP3-inflammasome in adjuvant-induced arthritis (AA) fibroblast-like synoviocytes (FLSs) in vitro. METHODS: In this study, using a combination of Western blotting, Q-PCR, and ELISA analysis, we investigated the influence and function of miRNA-20a on NLRP3-inflammasome by targeting TXNIP in AA FLSs. RESULTS: In the present study, the expression of NLRP3-inflammasome was significant up-regulated in AA model in vitro. Our study indicated that silence of NLRP3 down-regulated the expression of NLRP3-inflammasome and the secretion of IL-1ß and MMP-1. Moreover, over-expression of miR-20a decreased formation of NLRP3-inflammasome, including NLRP3, ASC and caspase-1, and suppressed the secretion of IL-1ß and MMP-1, along with down-regulated the expressions of TXNIP in primary FLSs isolated from AA. With the combined use of prediction programs and luciferase assay, the rat TXNIP mRNA 3'UTR predicted to be targeted by miR-20a. Similarly, inhibitor TXNIP expression by TXNIP-siRNA markedly repressed formation of NLRP3-inflammasome and the secretion of IL-1ß and MMP-1. CONCLUSION: Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.