ABSTRACT Rheumatoid arthritis (RA) is a major public health concern, which can cause serious outcomes. Low‐dose methotrexate (MTX) cornerstone in RA treatment, but there significant heterogeneity clinical response. To evaluate underlying sources of pharmacokinetic variability and response MTX, physiologically based pharmacodynamic (PBPK/PD) model was developed using PK‐sim Mobi (version 11.1). The PBPK included metabolism transportation by AXO1, FPGS, GGH, RFC, MRP2, with renal biliary...

We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells subcutaneous xenograft models. FA-OINPs were demonstrated to great potential as superb contrast agents enhance ultrasound photoacoustic (US/PA) imaging vitro vivo. Confocal laser scanning microscopy flow cytometry analysis verified that could specifically target SKOV3 be endocytosed with a remarkable...

Ultrasound-targeted microbubble destruction (UTMD) is a promising technique to facilitate the delivery of chemotherapy in cancer treatment. However, process typically uses nonspecific microbubbles, leading low tumor-to-normal tissue uptake ratio and adverse side effects. In this study, we synthesized LHRH receptor-targeted paclitaxel (PTX)-loaded lipid microbubbles (TPLMBs) for tumor-specific binding enhanced therapeutic effect at tumor site. An ovarian xenograft model was established by...

Photodynamic therapy (PDT), sonodynamic (SDT), and oxaliplatin (OXP) can induce immunogenic cell death (ICD) following damage-associated molecular patterns (DAMPs) exposure or release be united via the use of nanoplatforms to deliver drugs that impart anti-tumor effects. The aim this study was develop phase-transition nanoparticles (OI_NPs) loaded with perfluoropentane (PFP), indocyanine green (ICG), (OXP), augment efficacy immunological effects chemotherapy, photodynamic (PSDT).OI_NPs were...

We synthesized oxygen and paclitaxel (PTX) loaded lipid microbubbles (OPLMBs) for ultrasound mediated combination therapy in hypoxic ovarian cancer cells. Our experiments successfully demonstrated that induced OPLMBs destruction significantly enhanced the local release. also with (300 kHz, 0.5 W/cm(2), 15s) yielded anti-proliferative activities of 52.8 ± 2.75% cell apoptosis ratio 35.25 0.17% cells at 24h after treatment, superior to other treatment groups such as PTX only PTX-loaded MBs...

Photodynamic therapy and sonodynamic are developing, minimally invasive, site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic followed by therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen indocyanine green (OI-NPs) investigate the cytotoxic effects potential mechanisms of OI-NP-mediated on MH7A synoviocytes.The OI-NPs were...

Chemotherapy and photo-sonodynamic therapy (PSDT) can be combined through drug delivery nano-platforms to enhance the anti-tumor efficacy, however, which is limited by hypoxia in tumor, thereby causing chemotherapy resistance. Perfluoropentane (PFP) has ability carry oxygen ultrasound or photoacoustic imaging after vaporization. Herein, we constructed a kind of nanoparticles (PTX/ICG loaded PLGA (PIO_NPs)), had PFP core carrying shell indocyanine green (ICG) paclitaxel (PTX). PIO_NPs...

Although paclitaxel (PTX) is used with platinum as the first line chemotherapy regimen for ovarian cancer, its clinical efficacy often limited by severe adverse effects. Ultrasound-targeted microbubble destruction (UTMD) technique holds a great promise in minimizing side effects and maximizing therapeutic efficacy. However, typically uses nontargeted microbubbles suboptimal efficiency. We synthesized targeted PTX-loaded (MBs) UTMD mediated cancer cells. lipid MBs were coated luteinizing...

Nonviral gene transfer by ultrasound-targeted microbubble destruction (UTMD) is an promising technique for RNA interference (RNAi) therapy. Targeting silence survivin may provide important therapeutic option patients with ovarian cancer. However, UTMD mediated RNAi therapy typically uses nontargeted microbubbles suboptimal transfection efficiency. In this work, a LHRHa targeted agent and recombinant expression plasmid of shRNA targeting (pshRNA survivin) were constructed pshRNA in cancer...

The structural domains of human apolipoprotein B-100 in low density lipoproteins (LDL) and the conformational changes that accompany conversion very (VLDL) to LDL were investigated by limited proteolysis with 12 endoproteases various specificities, their cleavage sites determined.In LDL, we identified two peptide regions are highly susceptible proteolytic cleavage.One region encompassed about 40 amino acids (residues 1280-1320, designated as NH2-terminal region) other 100 3180-3280,...

Although brucea javanica oil liposomes (BJOLs) have been used clinically to treat ovarian cancer, its clinical efficacy is often limited by systemic side effects due non-specific distribution. Luteinizing hormone releasing receptor (LHRHR) overexpressed in most cancers but negligibly expressed of the other visceral organs. In this study, we aimed develop a novel LHRHa targeted and BJO-loaded (LHRHa-BJOLs), investigate characteristics, targeting ability anti-ovarian cancer efficiency both...

Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The (NP-Apt) were TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and prepared cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used determine the ability of TFO-NP-Apt inhibit...

This study aimed to assess the microbiological concordance between swab and soft tissue cultures, corresponding bone specimen cultures from patients with diabetic foot osteomyelitis (DFO). We analyze specimens' antimicrobial susceptibilities, improve clinical management of ulcer infections by using proper antibiotics.The microbial culture results swabs, specimens, susceptibility tests specimens DFO were analyzed in a single center.A total 60 three included. Staphylococcus aureus was most...

Nanomedicine has emerged as a novel therapeutic modality for cancer treatment and diagnosis. Lipid-polymer hybrid nanoparticles (LPHNPs) are core-shell nanoparticle (NP) structures comprising polymer cores lipid shells, which exhibit complementary characteristics of both polymeric NPs liposomes. However, it is difficult to wrap perfluoropentane (PFP) into in the existing preparation process, limits its application integration diagnosis treatment.The folate-targeted LPHNPs-loaded indocyanine...

Aims To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin‐like/kexin type 9 (PCSK9) inhibitors using the US Food Drug Administration Adverse Event Reporting System (FAERS). Methods We conducted a disproportionality analysis of PCSK9 in FAERS (01/2004–12/2021). The association between oAEs was evaluated information component (IC) reporting odds ratio (ROR), difference evolocumab alirocumab compared ROR. Different...

The low density lipoproteins (LDL) from patients with Tangier disease are enriched in triglycerides, 27% of LDL mass versus 7% for normal LDL. To study whether this unique core lipid composition affects the surface disposition apolipoprotein (apo) B-100, we analyzed by protease digestion and competitive radioimmunoassays. Limited proteolytic Staphylococcus aureus V8 generated a prominent fragment 120 kDa (cleavage site at residue 1076), which was not visible similarly digested In...