17ß-estradiol activates SOX6 to balance the anabolism and catabolism via estrogen receptor 2 in chondrocyte.

We investigated the influence of 17ß-estradiol (17ß-E2) on cartilage extracellular matrix (ECM) homeostasis in postmenopausal women. We focused on the roles of estrogen receptors (ESR) and SOX6 in 17ß-E2-mediated stimulation of ECM metabolism during chondrocyte (CH) degeneration. We compared the expression of anabolic genes (collagen II and aggrecan) and catabolic genes (MMPs and TIMPs) in IL-1ß-induced CH degeneration in vitro, with and without 17ß-E2 supplementation. We separately silenced the SOX6, ESR1, and ESR2 genes in CHs to determine their impact on 17ß-E2 treatment. Additionally, we used Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and luciferase assays to investigate protein-DNA interactions within ESR2 and SOX6-promoter complexes. After three days of IL-1ß treatment, ESR1/2, SOX6, collagen II, aggrecan, and TIMP1/3 were decreased, while MMP3/9/13 were increased. The addition of 17ß-E2 partially reversed these effects, but silencing SOX6, ESR1, or ESR2 weakened the protective effects of 17ß-E2. Silencing ESR2, but not ESR1, abolished the upregulation of SOX6 induced by 17ß-E2. ESR2 was found to bind the SOX6 promoter and regulate SOX6 expression. 17ß-E2 upregulates SOX6 through ESR2 mediation, and the synergistic effect of 17ß-E2 and ESR2 on SOX6 balances ECM metabolism in CHs.

Heat shock protein-related diagnostic signature and molecular subtypes in ankylosing spondylitis: new pathogenesis insights.

Heat shock proteins (HSP) have been associated with a range of persistent inflammatory disorders; however, little research has been conducted on the involvement of HSP in the development of ankylosing spondylitis (AS). The research aims to identify a diagnostic signature based on HSP-related genes and determine the molecular subtypes of AS. We gathered the transcriptional data of patients with AS from the GSE73754 dataset and conducted a literature search for HSP-related genes (HRGs). The logistic regression model was utilized for the identification of hub HRGs associated with AS. Subsequently, these HRGs were employed in the construction of a nomogram prediction model. We employed a consensus clustering approach to identify novel molecular subgroups. Subsequently, we conducted functional analyses, encompassing GO, KEGG, and GSEA, to elucidate the underlying mechanisms between these subgroups. To assess the immunological landscape, we employed the xCell algorithm. Through logistic regression analysis, the four core HRGs (CCT2, HSPA6, DNAJB14, and DNAJC5) were confirmed as potential biomarkers for AS. Subsequent stratification revealed two distinct molecular phenotypes, designated as Cluster 1 and Cluster 2. Notably, Cluster 2 was characterized by the upregulation of pathways pertinent to immune response and inflammation. Our research suggests that the CCT2, HSPA6, DNAJB14, and DNAJC5 exhibit potential as effective blood-based diagnostic biomarkers for AS. These findings contribute to a deeper comprehension of the underlying mechanisms involved in the development of AS and offer potential targets for personalized therapeutic interventions.

Mn(II) Coordination Complex Loaded Hydrogel: Synthesis, Characterization, Fluorescence Properties, and Application in Treating Knee Arthritis.

Using a mixed-ligand approach, we successfully obtained two Mn(II)-based coordination compounds, namely [Mn2(L1)(TBIP)·H2O]n (1) and [Mn2(L2)(NPTA)·H2O]n (2) (where L1 and L2 are 1,4-bis(thiabenzimidazol-1-ylmethyl)benzene and 1,2-bis(thiabenzimidazol-1-ylmethyl)benzene, H2NPTA is 2-nitroterephthalic acid, and H2TBIP is 5-tert-butylisophthalic acid). Fluorescence performance testing of complexes 1 and 2 showed excellent green and blue fluorescence properties. Based on this, we further prepared HA/CMCS hydrogels using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials and studied their internal structural characteristics using scanning electron microscopy. Using "Duhuo Jisheng Decoction" as a drug model, two metal gel scaffolds loaded with "Duhuo Jisheng Decoction" were prepared, and their potential for treating knee osteoarthritis was evaluated.

Self-Powered and Self-Healable Extraocular-Muscle-Like Actuator Based on Dielectric Elastomer Actuator and Triboelectric Nanogenerator.

Although dielectric elastomer actuators (DEAs) are promising artificial muscles for use as visual prostheses in patients with oculomotor nerve palsy (ONP), high driving voltage coupled with vulnerable compliant electrodes limits their safe long-term service. Herein, a self-healable polydimethylsiloxane compliant electrode based on reversible imine bonds and hydrogen bonds is prepared and coated on an acrylic ester film to develop a self-healable DEA (SDEA), followed by actuation with a high-output triboelectric nanogenerator (TENG) to construct a self-powered DEA (TENG-SDEA). Under 135.9 kV mm-1 , the SDEA exhibits an elevated actuated strain of 50.6%, comparable to the actuation under DC power. Moreover, the mechanically damaged TENG-SDEA displays a self-healing efficiency of over 90% for 10 cycles. The TENG ensures the safe using of TENG-SDEAs and an extraocular-muscle-like actuator with oriented motion ability integrated by several TENG-SDEAs is constructed. Additionally, the SDEA is directly used as a flexible capacitive sensor for real-time monitoring of the patient's muscle movement. Accordingly, a medical aid system based on a conjunction of the extraocular-muscle-like actuator and a flexible capacitive sensor is manufactured to help the patients suffering from ONP with physical rehabilitation and treatment.

Long Non-Coding RNA AL928768.3 Promotes Rheumatoid Arthritis Fibroblast-Like Synoviocytes Proliferation, Invasion and Inflammation, While Inhibits Apoptosis Via Activating Lymphotoxin Beta Mediated NF-κB Signaling Pathway.

Our previous study using RNA sequencing and reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation identified a long non-coding RNA (lnc), lnc-AL928768.3, correlating with risk and disease activity of rheumatoid arthritis (RA), then the present study was conducted to further investigate the interaction of lnc-AL928768.3 with lymphotoxin beta (LTB) and their impact on proliferation, migration, invasion, and inflammation in RA-fibroblast-like synoviocytes (RA-FLS). Human RA-FLS was obtained and transfected with lnc-AL928768.3 overexpression, negative control overexpression, lnc-AL928768.3 short hairpin RNA (shRNA) and negative control shRNA plasmids. Then cell functions and inflammatory cytokine expressions were detected. Afterward, rescue experiments were conducted via transfecting lnc-AL928768.3 shRNA with or without LTB overexpression plasmids in RA-FLS. Lnc-AL928768.3 enhanced proliferation and invasion, inhibited apoptosis, while had little impact on migration in RA-FLS. In addition, lnc-AL928768.3 positively modulated interleukin-1ß (IL-1ß), IL-6 and IL-8 expressions in RA-FLS supernatant; moreover, it also positively regulated LTB mRNA expression, LTB protein expression, p-NF-κB protein expression, and p-IKB-α protein expression in RA-FLS. Furthermore, following experiment showed that lnc-AL928768.3 positively regulated LTB expression while LTB did not impact on lnc-AL928768.3 expression in RA-FLS. Furthermore, in rescue experiments, LTB overexpression curtailed the effect of lnc-AL928768.3 knock-down on regulating proliferation, invasion, apoptosis and inflammatory cytokine expressions in RA-FLS. Lnc-AL928768.3 promotes proliferation, invasion, and inflammation while inhibits apoptosis of RA-FLS via activating LTB mediated NF-κB signaling.

The First Discovery of a Microstructure in Black Plaster and Its Performance Characterization.

Background: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine. Methods: Methods for the morphological and quantitative characterization of black plaster's microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction. Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed "branched" soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8±59.5) µm2; after the 35 °C treatment, A2 = (259.7±52.8) µm2; after the 45 °C treatment, A3 = (408.0±57.7) µm2, and there were no significant differences in other pore parameters. Conclusion: The black plaster matrix's unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.

Preparation and Characterization of Aprepitant Solid Dispersion with HPMCAS-LF.

This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with HPMCAS-LF, the solvent evaporation method was applied. Based on dissolution analysis, the dissolution rate of SD increased by five times compared with aprepitant. In addition, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) results suggested the presence of amorphous-form aprepitant inside SD. According to Fourier transform infrared (FTIR) spectroscopy, intermolecular hydrogen bonds were detected between polymer and aprepitant. The Caco-2 cell experiment proved that SD did not lower the transepithelial electrical resistance (TEER) values but improved the permeation amount of aprepitant. Additionally, the SD of aprepitant displayed excellent stability.

Self-Powered Resilient Porous Sensors with Thermoelectric Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) and Carbon Nanotubes for Sensitive Temperature and Pressure Dual-Mode Sensing.

Portable and wearable dual-mode sensors that can simultaneously detect multiple stimuli are essential for emerging artificial intelligence applications, and most efforts are devoted to exploring pressure-sensing devices. It is still challenging to integrate temperature and pressure-sensing functions into one sensor without the requirement for complex decoupling processes. Herein, we develop a self-powered and multifunctional dual-mode sensor by dip-coating melamine sponge with both poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and carboxylated single-walled carbon nanotubes (CNTs). By integrating thermoelectric and conductive PEDOT:PSS/CNT components with the hydrophilic and resilient porous sponge, the resultant sensor is efficient in independently detecting temperature and pressure changes. The temperature and pressure stimuli can be independently converted to voltage and electrical resistance signals on the basis of the Seebeck and piezoresistive effects, respectively. The sensor exhibits a high Seebeck coefficient of 35.9 µV K-1 with a minimum temperature detection limit of 0.4 K and a pressure sensitivity of -3.35% kPa-1 with a minimum pressure detection limit of 4 Pa. Interestingly, the sensor can also be self-powered upon illumination. These multi-functionalities make the sensor a promising tool for applications in electronic skin, soft robots, solar energy conversion, and personal health monitoring.

Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability.

Aprepitant has been classified into BCS class IV, which has low permeability and poor water solubility, resulting in low bioavailability. This study focused on improving its permeability and solubility in order to improve the oral bioavailability of aprepitant. Hydroxypropyl chitosan (HPCS) was used as a stabilizer for the nanosuspension and wet milling was utilized for improving aprepitant's bioavailability and solubility. The resulting nanosuspension size was 151 ± 14.5 nm and its zeta potential was 63.5 ± 0.34 Mv. The spectral characteristics (XRPD, DSC, TEM) of the nanosuspension suggested that aprepitant existed in the crystalline form and that nanosuspension had 2-fold higher solubility than aprepitant. Hydroxypropyl chitosan can significantly reduce the TEER of Caco-2 cells and the Papp of the suspension in Caco-2 cells increased by 2.2 times compared with aprepitant. The relative bioavailability of the nanosuspension was 147.7% compared with the commercial capsule.

The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis.

BACKGROUND: Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. METHODS: After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. RESULTS: Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. CONCLUSION: CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

Video Desnowing and Deraining via Saliency and Dual Adaptive Spatiotemporal Filtering.

Outdoor vision sensing systems often struggle with poor weather conditions, such as snow and rain, which poses a great challenge to existing video desnowing and deraining methods. In this paper, we propose a novel video desnowing and deraining model that utilizes the salience information of moving objects to address this problem. First, we remove the snow and rain from the video by low-rank tensor decomposition, which makes full use of the spatial location information and the correlation between the three channels of the color video. Second, because existing algorithms often regard sparse snowflakes and rain streaks as moving objects, this paper injects salience information into moving object detection, which reduces the false alarms and missed alarms of moving objects. At the same time, feature point matching is used to mine the redundant information of moving objects in continuous frames, and a dual adaptive minimum filtering algorithm in the spatiotemporal domain is proposed by us to remove snow and rain in front of moving objects. Both qualitative and quantitative experimental results show that the proposed algorithm is more competitive than other state-of-the-art snow and rain removal methods.

A novel polymer micelle as a targeted drug delivery system for 10-hydroxycamptothecin with high drug-loading properties and anti-tumor efficacy.

A novel polyethylene glycol-polycaprolactone-poly-l-tyrosine (MPEG-PCL-PTyr) amphiphilic triblock copolymer micelle was synthesized for the first time. 10-hydroxycamptothecin (HCPT) was embedded in MPEG-PCL-PTyr nanomicelles using the emulsion solvent evaporation method. A series of was conducted to confirm the structure of the compound and to evaluate the physical properties of the MPEG-PCL-PTyr nanomicelles. Cellular uptake, cytotoxicity, and apoptosis were assessed using flow cytometry and MTT assays. Confocal microscopy and flow cytometry results demonstrated that the nanocapsules carrying HCPT had significantly increased anti-tumor activity against HepG2 cells and could target HepG2 cell lysosomes with obvious liver targeting. In addition, the drug-loaded nanomicelles could significantly block the S phase of cancer cells and induce apoptosis; thus, they could be potential carriers for future 10-HCPT delivery and cancer treatment.

Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer.

BACKGROUND: Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM: To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS: NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS: The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION: Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

How to use macrophages to realise the treatment of tumour.

Macrophages (Mø) are immune cells with natural phagocytic ability and play an important role in tumorigenesis, development and metastasis. Mø play a dual role of tumour inhibition and tumour promotion in tumour development due to their two different phenotypes. Mø in the tumour microenvironment have long been referred to as tumour-associated Mø (TAMs). Mø are mainly involved in tumour resistance, cancer metastasis and mediating immunosuppression. Nowadays, Mø and Mø membranes have been widely used in drug delivery systems (DDSs) because of their good biocompatibility, natural phagocytosis and their important role in tumour development. In this review, from the perspective of Mø's role in tumour development, we present strategies and drugs of Mø targeting and focusing on the several types of biomimetic nanoparticles constructed by Mø and Mø membranes in tumour therapy, and discuss the problem of this delivery system in present research and future directions.

Hyaluronic acid-coated nanostructured lipid carriers for loading multiple traditional Chinese medicine components for liver cancer treatment.

This study aimed to develop hyaluronic acid (HA)-coated nanostructured lipid carriers (NLC) loaded simultaneously with oleanolic acid (OA), ursolic acid (UA) and Ginsenoside Rg3 (Rg3), prepared by electrostatic attraction for delivering OA, UA and Rg3 (OUR), termed HA-OUR-NLC, to tumors over expressing cluster determinant 44(CD44). The dialysis method was used to assess the in vitro release of OUR. Parameters such as pharmacokinetics, biodistribution, fluorescence in vivo endo-microscopy (FIVE), optical in vivo imaging (OIVI) data, and in vivo antitumor effects were evaluated. The results showed a total drug loading rate of 8.76±0.95% for the optimized HA-OUR-NLC; total encapsulation efficiency was 45.67±1.14%; particle size was 165.15±3.84%; polydispersity index was 0.227±0.01; zeta potential was -22.87±0.97 mV. Drug release followed the Higuchi kinetics. Pharmacokinetics and tissue distribution, as well as antitumor effects were evaluated in nude mice in vivo. HA-OUR-NLC were better tolerated, with increased antitumor activity compared with 5-Fu. In in vivo optical imaging, we use 1,1'-dioctadecyl-3,3,3',3'-tetramethy(DiR) as a fluorescent dye to label the NLC. The DiR-OUR-NLC group showed bright systemic signals, while the tumor site was weak. The present findings indicated that HA-OUR-NLC accumulated in the tumor site, prolonging OUR duration in the circulation and enhancing tumoral concentrations. Therefore, NLC prepared by electrostatic attraction constitute a good system for delivering OUR to tumors.

A study of nanometre aggregates formation mechanism and antipyretic effect in Bai-Hu-Tang, an ancient Chinese herbal decoction.

BACKGROUND: Bai-Hu-Tang (BHT), a Chinese herbal decoction used as an antipyretic agent, results from the combination of Anemarrhena asphodeloides Bunge, Glycyrrhizae, Japonica rice, and Gypsum. In our previous study, we identified nanoaggregates in BHT. However, the present study aimed to analyze and elucidate the mechanism of nanoaggregate formation and to investigate its antipyretic effect. METHODS: A BHT decoction extract was split into 15 groups, and in each group, the extract was further separated into two solutions: Nano-phase and Decoction. The physicochemical properties of these solutions, such as particle size, salinity, conductivity, and surface tension were investigated, and analyzed the 15 groups of by transmission electron microscopy (TEM) and fingerprint chromatography. Furthermore, the antipyretic effect of nanoaggregates was evaluated through enzyme-linked immunosorbent assays, HE staining, Western Blot, and Real-time PCR. RESULTS: In the 15 groups, the salinity and conductivity results showed a promoting and stabilizing effect towards the Nano-phase formation. Analysis of the surface tension indicated good solubilization of Radix Glycyrrhizae. The TEM analysis of the BHT separated extracts revealed that only in the presence of Japonica rice the Nano-phase is formed. Sixteen common peaks were identified in the BHT fingerprint chromatogram, and the main chemical components were Neomangiferin, Mangiferin, Liquiritin, and Ammonium glycyrrhizinate. Furthermore, BHT and nanoaggregates from Bai-Hu-Tang (N-BHT) groups did not differ in the main chemical components. Additionally, the N-BHT group had the same antipyretic effect compared with the BHT group. However, the pathological analysis indicated that treatment with N-BHT could ameliorate the lung damage in the rat. At the same time, N-BHT group inhibited expression of several proteins, specifically IL-1ß, TRPV4, NF-κB, and TNF-α, which agreed with the Real-time PCR results. CONCLUSION: We identified the key factors that are involved in the nano-phase formation. Also, by Western blot and Real-time PCR methods, we investigated the N-BHT mechanism of antipyretic action. The discovery of the N-BHT formation would provide a new idea of studying traditional Chinese medicine decoction.

The Effect of Acupoint Application of Sinomenine for Rheumatoid Arthritis Measured by Microdialysis and UPLC-MS/MS.

OBJECTIVE: This study aimed to investigate the treatment effects of acupoint application of sinomenine in rheumatoid arthritis (RA). RA models were constructed using male New Zealand rabbits. METHODS: The rabbits were randomly divided into a blank control group and four experimental groups as follows: ST 36 group (acupoint application of sinomenine at Zusanli); GB 34 group (acupoint application of sinomenine at Yanglingquan); knee-joint group (application directly at the site of the knee joint); and oral administration group (sinomenine administered by gavage). In all rabbits, microdialysis was applied at the knee joint to obtain samples. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters were measured by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the PK/PD models were established according to the parameters derived. RESULTS: Sinomenine concentration was in the range of 0.832-208 ng/mL, and the peak area showed a good linear relationship with the regression equation of y = 539.64x + 953.81; r = 0.9998. Moreover, good specificity and precision were obtained for the LC-MS/MS method of sinomenine evaluation in the microdialysate samples. The PK analysis showed that the sinomenine effect time was longer in the ST 36 group (area under the time-concentration curve (AUC): 12683.81 h·ng/ml and T max: 6.21 h) than in the other groups. Arginine and citrulline were selected as the indices for PD, and in the analysis of parameters for PK/PD, the highest value of E max and the lowest value of k e0 were obtained in the ST 36 group. CONCLUSION: Acupoint application of sinomenine at ST 36 has potential for use in patients with RA by enabling enhanced and prolonged treatment effects.

Association between antiphospholipid antibodies and factor Bb in lupus nephritis patients with glomerular microthrombosis.

BACKGROUND AND PURPOSE: The mechanism of glomerular microthrombosis (GMT) in patients with lupus nephritis (LN) is largely unknown. The aim of this study is to investigate the association between antiphospholipid antibodies (aPLs) and factor Bb in LN patients with GMT. METHODS: Patients with biopsy-proven LN hospitalized from July 2015 to July 2018 in our hospital were selected for this study. Levels of lupus anticoagulant (LAC), anticardiolipin antibodies (aCLs), anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies and factor Bb were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS: A total of 25 LN patients with GMT and 76 LN patients without GMT were included in this study. In LN patients with GMT, the presence of anti-ß2GPI and LAC were both significantly higher than in those without GMT (P < .001 and P = .039, respectively). The level of factor Bb was also higher in LN patients with GMT than in those without GMT (P = .021). In the correlation analysis, Bb level was positively correlated with serum creatinine (r = 0.28, P = .014), activity index (r = 0.24, P = .021) GMT (r = 0.65, P < .001) and IgG-anti-ß2GPI (r = 0.771, P < .001). CONCLUSIONS: Our work suggests that aPLs, especially IgG-anti-ß2GPI, may play a role in the progress of GMT, and this process might involve alternative complement activation.

Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia.

Cerebral ischemia (CI) results from inadequate blood flow to the brain. The difficulty of delivering therapeutic molecules to lesions resulting from CI hinders the effective treatment of this disease. The inflammatory response following CI offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and penumbra. In the present study, neutrophils and monocytes were explored as cell carriers after selectively carrying cRGD liposomes, which effectively transmigrated the blood-brain barrier, infiltrated the cerebral parenchyma, and delivered therapeutic molecules to the injured sites and target cells. Our results showed the successful comigration of liposomes with neutrophils/monocytes and that both monocytes and neutrophils were important for successful delivery. Enhanced protection against ischemic injury was achieved in the CI/reperfusion model. The strategy presented here shows potential in the treatment of CI and other diseases related to inflammation.