Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact.
PurposeTo investigate the factors associated with the occurrence of and recovery from transient urinary incontinence (TUI) after holmium laser enucleation of the prostate (HoLEP).Materials and MethodsFrom March 2009 to December 2012, 391 consecutive patients treated with HoLEP for benign prostatic hyperplasia were enrolled. Information regarding age, prostate volume, International Prostate Symptom Score, Overactive Bladder Symptom Score, peak urinary flow rate, postvoid residual urine, and operation time was collected. TUI was defined as a patient complaint of urine leakage, regardless of type. Logistic regression was used to investigate the factors associated with the occurrence of TUI, and the Kaplan-Meier test was used to analyze the TUI recovery period.ResultsTUI after HoLEP occurred in 65 patients (16.6%), 52 patients of whom (80.0%) showed recovery within three months. Stress and urge urinary incontinence and postvoid dribbling occurred in 16 patients (4.1%), 29 patients (7.4%), and 33 patients (8.4%), respectively. Age (odds ratio [OR]=3.494; 95% confidence interval [CI]=1.565~7.803; p=0.002) and total operation time (OR=3.849; 95% CI=1.613~9.185; p=0.002) were factors that significantly affected the occurrence of TUI.ConclusionsTUI, defined as any type of urine leakage, occurred after HoLEP in some patients, most of whom recovered within three months. Stress urinary incontinence occurred in only 4% of patients after HoLEP. Age and total operation time were associated with the occurrence of postoperative TUI.
A 71-year-old man was referred for painless hematuria and a bladder tumor. Cystoscopy and computed tomography revealed a 3-cm oval nodular mass on the left lateral side of the bladder. The patient underwent a complete transurethral resection of the lesion and histology showed a proliferation of atypical spindle cells with inflammation consistent with a myofibroblastic tumor. After 4 and 7 months, follow-up cystoscopy demonstrated nodular mass lesions and transurethral resection of bladder tumor was done, which showed chronic cystitis and a recurred myofibroblastic tumor, respectively. Five months later, multiple lymph node, bone, and soft tissue metastases were found by positron emission tomography. The patient was treated first with palliative chemotherapy, including doxorubicin and cisplatin. After that, radiologic studies showed disease progression but the patient refused further treatment and died 6 months later.
In our previous study, the Kelch domain-containing 7B (KLHDC7B) was revealed to be hypermethylated at the promoter but upregulated in breast cancer. In this study, we identified a long non-coding RNA, ST8SIA6-AS1 (STAR1), whose expression was significantly associated with KLHDC7B in breast cancer (R2 = 0.3466, P < 0.01). Involvement of the two genes in tumorigenesis was examined via monitoring their effect on cellular as well as molecular events after each gene dysregulation in cultured mammary cell lines. Apoptosis of MCF-7 decreased by 49.5% and increased by 33.1%, while proliferation noted increase and decrease by up- and downregulation of KLHDC7B, respectively, suggesting its oncogenic property. STAR1, however, suppressed cell migration and increased apoptosis. Network analysis identified many target genes that appeared to have similar regulation, especially in relation to the interferon signaling pathway. Concordantly, expression of genes such as IFITs, STATs, and IL-29 in that pathway was affected by KLHDC7B and STAR1. Taken together, KLHDC7B and STAR1 are both overexpressed in breast cancer and significantly associated with gene modulation activity in the interferon signaling pathway during breast tumorigenesis.
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