Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. MATERIALS AND METHODS: UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. RESULTS: Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. CONCLUSION: This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

A Series of Polymer-Supported Polyoxometalates as Heterogeneous Photocatalysts for Degradation of Organic Dye.

Photocatalytic degradation technology has developed rapidly in the treatment of organic pollutants due to its high efficiency, mild reaction conditions and easy control. In this paper, a series of heterogeneous photocatalysts, BWZ-en-R (BWZ = [BW11Z(H2O)O39]7-, Z = Zn, Cd, Mn, en = ethylenediamine, R = Merrifield resin), were prepared by using ethanediamine as a linker to immobilize Keggin-type transition elements substituting tungstoborates on Merrifield resin and characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. The photocatalytic properties of BWZ-en-R (Z = Zn, Cd, Mn) for the degradation of methyl red (MR) were investigated. The results show that the BWZ-en-R (Z = Zn, Cd, Mn) photocatalysts exhibited high photodegradation ability for MR under the irradiation of ultraviolet light, and were easily separated from the reaction media. The maximum degradation rate (%) of MR (40 mL, 25 µM, pH = 2) reached 96.4% for the BWMn-en-R photocatalyst (40 mg) after being irradiated for 30 min, making this a promising photocatalyst candidate for dye degradation. Moreover, the influences of some factors, such as the Z-substituted elements in the BWZ, the BWZ-en-R dosage and the MR initial concentration, on the photocatalytic degradation rate of MR were also examined.

Effects of DNA Immunoadsorption Combined with Medication on Immune Function and Renal Function in Patients with Systemic Lupus Erythematosus.

Objective. At present, glucocorticoids combined with cyclophosphamide are still used for the clinical treatment of systemic lupus erythematosus (SLE). However, long-term practice has shown that drug treatment currently has the phenomena of long treatment duration, uncontrollable conditions in a short period of time, and unsatisfactory efficacy. DNA immunoadsorption therapy is a newly developed therapy. The combination of drugs and DNA immunoadsorption has been reported for the treatment of SLEN in clinics for a long time. In this study, we observed the effects of DNA immunoadsorption combined with drug therapy on immune function and renal function in patients with systemic lupus erythematosus (SLE). The results showed that the DNA immunosorbent assay combined with medication in the treatment of SLE could quickly and specifically remove pathogenic substances from patients, improve renal function, immune function, and complement levels in patients, and help to relieve disease activity.

Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuwei Shexiang Pills (WWSX), a classic Tibetan medicine, consists of Chebulae Fructus (removed pit), Aucklandiae Radix, Moschus, Aconiti Fiavi Radix, and Acori Calami Rhizoma. It is used clinically in China to treat joint pain, swelling and other symptoms, and has the function of dispelling wind and relieving pain. However, to date, the mechanism of how it works against gout is still unclear. AIMS OF THE STUDY: Using network pharmacology, molecular docking and pharmacological verification to explore the potential anti-gout properties of WWSX. MATERIALS AND METHODS: With the use of UPLC-Q/TOF-MS, the main components of WWSX were obtained and screened for potential anti-inflammatory components by network pharmacology and molecular docking. The anti-inflammatory activity of the components screened from WWSX was also tested by in vitro assays. The anti-gout mechanism of WWSX was predicted by network pharmacology, and the pharmacological validation experiments using gouty arthritis model and mouse air pouch model were used to explore the multifaceted mechanism of WWSX to modify gout. RESULT: Thirty-eight active ingredients were obtained from the UPLC-Q/TOF-MS detection. The network pharmacology and molecular docking analysis showed that 104 co-targets were participated in the treatment of gout, and the main signaling pathways involved were NOD-like receptor pathway, NF-κB pathway and MAPK pathway. Pharmacological evaluation showed that WWSX could significantly improve gout in gouty arthritis models and mouse air pouch models by modulating the above pathways. CONCLUSION: This work has predicted and validated the anti-inflammatory material basis and predicted the anti-gout mechanism of WWSX which was verified by network pharmacology, molecular docking and in vitro cellular studies. The results reveal the mechanism of WWSX in the treatment of gout and provide a theoretical basis for its clinical application.

Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.

BACKGROUND AND PURPOSE: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. EXPERIMENTAL APPROACH: RNA-sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was evaluated, both in vivo and in vivo. KEY RESULTS: Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL-1ß. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS: These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.

Integrating network pharmacology and pharmacological validation to explore the effect of Shi Wei Ru Xiang powder on suppressing hyperuricemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Shi Wei Ru Xiang powder (SWR) is a traditional Tibetan medicinal formula with the effect of dispelling dampness and dispersing cold. In clinical practice, SWR is generally used for the treatment of hyperuricemia (HUA). However, its exact pharmacological mechanism remains unclear. AIMS OF THE STUDY: To preliminarily elucidate the regulatory effects and possible mechanisms of SWR on hyperuricemia using network pharmacology and experimental validation. MATERIALS AND METHODS: A mouse model of hyperuricemia was used to evaluate the alleviating effect of SWR on hyperuricemia. The major components of SWR were acquired by UPLC-Q/TOF-MS. The potential molecular targets and associated signaling pathways were predicted through network pharmacology. The mechanism of action of SWR in ameliorating hyperuricemia was further investigated by pharmacological evaluation. RESULTS: Mice with hyperuricemia and renal dysfunction were ameliorated by SWR. The 36 components of SWR included phenolic acids, terpenoids, alkaloids and flavonoids were identified. Network pharmacological analysis showed the involvement of the above compounds, and 115 targets were involved to treat hyperuricemia, involving multiple biological processes and different signaling pathways. Pharmacological experiments validated that SWR ameliorated hyperuricemic nephropathy in mice by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, nuclear factor kappaB (NF-κB) signaling pathway and NOD-like receptor signaling pathway. CONCLUSION: MAPK signaling pathway, NF-κB signaling pathway and NOD-like receptor signaling pathway play important roles in the therapeutic effects of SWR on hyperuricemia.

CT Combined with Multiparameter MRI in Differentiating Pathological Subtypes of Non-Small-Cell Lung Cancer before Surgery.

Objective: To investigate the diagnostic value of computed tomography (CT) combined with multiparametric magnetic resonance imaging (mpMRI) for preoperative differentiation of non-small-cell lung cancer (NSCLC). Methods: CT and MRI imaging data were collected from all patients with squamous lung cancer and adenocarcinoma admitted to our hospital from June 2019 to December 2020 (286 cases). ROC curves were plotted to evaluate the performance of CT, mpMRI, and CT combined with mpMRI to differentiate pathological subtypes of NSCLC. Univariate and multivariate regression were used to be independent predictors of pathological subtypes of NSCLC. Results: ROC curves showed that CT combined with mpMRI had the largest area under the curve, followed by mpMRI and CT successively. Univariate regression analysis showed that gender, smoking, tumor size, morphology, marginal lobulation, marginal burr, bronchial truncation sign, and vascular convergence sign were factors influencing the pathological subtype of NSCLC. Multivariate regression analysis suggested the fact that gender, tumor size, morphology, marginal lobulation, bronchial truncation, and vascular convergence sign are likely the independent predictors of NSCLC pathological subtypes. Conclusions: CT combined with mpMRI can effectively distinguish NSCLC pathological subtypes, which is worthy of clinical application.

Methyl Gallate Improves Hyperuricemia Nephropathy Mice Through Inhibiting NLRP3 Pathway.

Hyperuricemia nephropathy (HN) is a form of chronic tubulointerstitial inflammation, caused by the deposition of monosodium urate crystals (MSU) in the distal collecting duct and medullary interstitium, associated with a secondary inflammatory reaction. Numerous published reports indicated that NLRP3 inflammasome pathway play crucial roles in HN symptoms. The present study aims to investigate the protective effects of methyl gallate on HN mice and the underlying mechanisms. An HN model was established by intraperitoneal injection of potassium oxide (PO) to assess the effect of methyl gallate on renal histopathological changes, renal function, cytokine levels and expressions of NLRP3-related protein in HN mice. Moreover, in vitro models of lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs) were established to explore the mechanism of methyl gallate on NLRP3 inflammasome activation. The results showed that methyl gallate significantly ameliorated HN by inhibiting uric acid production and promoting uric acid excretion as well as ameliorating renal injury induced by NLRP3 activation. Mechanistically, methyl gallate is a direct NLRP3 inhibitor that inhibits NLRP3 inflammasome activation but has no effect on the activation of AIM2 or NLRC4 inflammasomes in macrophages. Furthermore, methyl gallate inhibited the assembly of NLRP3 inflammasomes by blocking the ROS over-generation and oligomerization of NLRP3. Methyl gallate was also active ex vivo against ATP-treated PBMCs and synovial fluid mononuclear cells from patients with gout. In conclusion, methyl gallate has a nephroprotective effect against PO-induced HN through blocking the oligomerization of NLRP3 and then exerting anti-inflammatory activity in the NLRP3-driven diseases.

Facet Engineered Interface Design of Plasmonic Metal and Cocatalyst on BiOCl Nanoplates for Enhanced Visible Photocatalytic Oxygen Evolution.

Integration of plasmonic metal and cocatalyst with semiconductor is a promising approach to simultaneously optimize the generation, transfer, and consumption of photoinduced charge carriers for high-performance photocatalysis. The photocatalytic activities of the designed hybrid structures are greatly determined by the efficiencies of charge transfer across the interfaces between different components. In this paper, interface design of Ag-BiOCl-PdOx hybrid photocatalysts is demonstrated based on the choice of suitable BiOCl facets in depositing plasmonic Ag and PdOx cocatalyst, respectively. It is found that the selective deposition of Ag and PdOx on BiOCl(110) planes realizes the superior photocatalytic activity in O2 evolution compared with the samples with other Ag and PdOx deposition locations. The reason was the superior hole transfer abilities of Ag-(110)BiOCl and BiOCl(110)-PdOx interfaces in comparison with those of Ag-(001)BiOCl and BiOCl(001)-PdOx interfaces. Two effects are proposed to contribute to this enhancement: (1) stronger electronic coupling at the BiOCl(110)-based interfaces resulted from the thinner contact barrier layer and (2) the shortest average hole diffuse distance realized by Ag and PdOx on BiOCl(110) planes. This work represents a step toward the interface design of high-performance photocatalyst through facet engineering.

Facet engineered interface design of NaYF4:Yb,Tm upconversion nanocrystals on BiOCl nanoplates for enhanced near-infrared photocatalysis.

The combination of upconversion nanocrystals with a wide-bandgap semiconductor is an efficient strategy to develop near-infrared (NIR)-responsive photocatalysts. The photocatalytic activity of the hybrid structures is greatly determined by the efficiency of the energy transfer on the interface between upconversion nanocrystals and the semiconductor. In this work, we demonstrate the interface design of a NaYF4:Yb,Tm-BiOCl hybrid structure based on the choice of suitable BiOCl facets in depositing NaYF4:Yb,Tm upconversion nanocrystals. It was found that the selective deposition of NaYF4:Yb,Tm nanocrystals on the BiOCl(110) facet can greatly enhance the photocatalytic performance in dye degradation compared with the sample with NaYF4:Yb,Tm nanocrystals loaded on the BiOCl(001) facet. Two effects were believed to contribute to this enhancement: (1) a stronger UV emission absorption ability of the BiOCl(110) facet from NaYF4:Yb,Tm in generating more photo-induced charge carriers resulted from the narrower bandgap; (2) a shorter diffusion distance of photogenerated charge carriers to the BiOCl(110) reactive facet for surface catalytic reactions owing to the spatial charge separation between different facets. This work highlights the rational interfacial design of an upconversion nanocrystal-semiconductor hybrid structure for enhanced energy transfer in photocatalysis.

Embedding Metal in the Interface of a p-n Heterojunction with a Stack Design for Superior Z-Scheme Photocatalytic Hydrogen Evolution.

The construction of a p-n heterojunction is an efficient strategy to resolve the limited light absorption and serious charge-carrier recombination in semiconductors and enhance the photocatalytic activity. However, the promotion effect is greatly limited by poor interfacial charge transfer efficiency as well as reduced redox ability of charge carriers. In this work, we demonstrate that the embedding of metal Pd into the interface between n-type C3N4 and p-type Cu2O can further enhance the interfacial charge transfer and increase the redox ability of charge carriers through the design of the C3N4-Pd-Cu2O stack nanostructure. The embedded Pd nanocubes in the stack structure not only trap the charge carriers from the semiconductors in promoting the electron-hole separation but also act as a Z-scheme "bridge" in keeping the strong reduction/oxidation ability of the electrons/holes for surface reactions. Furthermore, Pd nanocubes also increase the bonding strength between the two semiconductors. Enabled by this unique design, the hydrogen evolution achieved is dramatically higher than that of its counterpart C3N4-Cu2O structure without Pd embedding. The apparent quantum efficiency (AQE) is 0.9% at 420 nm for the designed C3N4-Pd-Cu2O. This work highlights the rational interfacial design of heterojunctions for enhanced photocatalytic performance.

Serum Levels of MDC and MMP-9 and the Relationship Between Serum Levels and Disease Activity in the Patients with Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is a complicated autoimmune disease. Although its pathogenesis is not clear, cytokine may be involved in it. So we investigated serum levels of macrophage-derived chemokine (MDC), and matrix metalloproteinase-9 (MMP-9), and to determine the relationship between serum levels and the disease activity of SLE. METHODS: Serum levels of MDC and MMP-9 were measured by enzyme-linked immuno sorbent assay (ELISA). RESULTS: Significantly decreased serum levels of MDC and MMP-9 were found in SLE as compared to those in controls (P<0.001 P<0.001), but serum levels of MDC and MMP-9 increased after treatment (P<0.001 P<0.05). Serum levels of MDC and MMP-9 were lower in patients with active disease than those with inactive disease (P<0.001 P<0.05). Significantly decreased serum levels of MDC and MMP-9 were found in patients with renal damage than those without the damage (P<0.001 P<0.05). Serum level of MDC was lower in patients with arthritis than those without the damage (P<0.001), but serum level of MMP-9 has no significant difference in two groups (P>0.05). CONCLUSION: The present data suggest that MDC and MMP-9 may be involved in the pathogenesis of SLE, and serum levels of MDC and MMP-9 could be markers of monitoring disease activity, renal damage, disease progression and improvement in SLE.

Preparation, electrochemical properties and electrocatalytic activity of Zn-substituted tungstoborate modified electrode.

3-Aminopropyltrimethoxysilane (APTMS) was covalently grafted on a glassy carbon electrode (GCE) by silicon-oxygen bonds formation. The APTMS-modified GCE was used as a suitable charged substrate to fabricate Keggin Zn-substituted tungstoborate (BW11Zn)-consisting monolayer film through layer-by-layer assembly based on the electrostatic attraction. This modification strategy is proven to be a general one suitable for anchoring many kinds of POMs on the APTMS-modified GCE. The APTMS/BW11Zn film obtained on GCE is electrochemically active in acid aqueous solutions and exhibited three pairs of well defined, stable and quasi-reversible cyclic voltammetry peaks in the pH range 0-2. The anodic and cathodic peak currents are linearly proportional to the scan rate in the 200-1000 mV s(-1), indicating a surface confined electrode process. The formal potentials of BW11Zn film, E0 versus saturated calomel electrode (SCE), are -0.27, -0.43, -0.55 V in pH 1 H2SO4 solution and changed linearly with the slope of 44, 63, and 60 mV/pH in the pH range 0-2, respectively. The BW11Zn/APTMS/GC electrode shows good catalytic activity for the reduction of BrO3-, NO2- and H2O2.

[Association between the synovial expression of cyclic citrullinated peptide and susceptibility variants of HLA-DRB1 shared epitope alleles and PADI 4 gene single nucleotide polymorphisms in patients with rheumatoid arthritis].

OBJECTIVE: To analyze the association between the synovial expression of cyclic citrullinated peptide (CCP) and susceptibility variants of HLA-DRB1 shared epitope (SE) alleles and/or peptidylarginine deiminase 4 (PADI4) gene single nucleotide polymorphisms (SNP) in patients with rheumatoid arthritis (RA). METHODS: From October 2008 to December 2011, 53 RA patients and 42 controls were enrolled. The expression of CCP in RA synovial tissues was detected by immunohistochemical assay with 6×His tagged anti-CCP single chain fragment V (ScFv) antibodies generated by pHEN2 phagemid recombinant antibodies display system. PADI4 SNP was genotyped by reverse transcription cDNA sequencing and heterozygote was DNA haplotype was mapped by TA clone sequencing. HLA-DRB1 SE alleles were analyzed by sequence specific primer-polymerase chain reaction (SSP-PCR). RESULTS: The prevalence of synovial CCP expression was significantly different between RA group and the control (76.9% and 11.4% respectively, P < 0.01). The frequencies of 2 SNPs (PADI4_89 G+ and PADI4_104 T+) varied significantly between the groups(P < 0.05). Compared with the major haplotypes, only these two minor alleles were associated with the increased RA susceptibility (OR = 3.67 and 2.53, P < 0.05). SE+ alleles was strongly associated with RA susceptibility (OR = 5.57, P < 0.01). The synovial expression of CCP in RA was strongly associated with SE+ alleles, only 2 minor SNPs (PADI4_89 G+ and PADI4_104T+) and the combination. Serum anti-CCP titers were significantly associated with SE+ alleles, PADI4_104T+, SE+/PADI4_89 G+ and SE+/PADI4_104T+ haplotype. CONCLUSION: The synovial expression of CCP and the generation of anti-CCP antibodies are strongly associated with SE alleles and/or certain PADI4 gene SNP in RA.

[Synthesis, spectroscopy and photocatalytic activity of II B elements substituted tungstoborate heteropoly complexes].

The Keggin II B element-monosubstitiuted heteropoly compounds with the stoichiometry of K7 [BW11 O39 M(H2O)] (M = Zn, Cd) were prepared by one-pot method and characterizated via elemental analyses, FTIR, UV and XRD. The photocatalytic activity of K7 [BW11O39M(H2O)] was tested vis degradation of the model molecule, methyl red (MR). After 60 min irradiation in the presence of K7 [BW11O39M(H2O)] (20 mg x L(-1)), the degradation rate of an aqueous MR (25 micromol X L(-1), pH 2) got to 95%.