With more and more engineered nanoparticles (NPs) being designed renal clearable for clinical translation, fundamental understanding of their transport in the different compartments of kidneys ...becomes increasingly important. Here, we report noninvasive X‐ray imaging of renal clearable gold NPs (AuNPs) in normal and nephropathic kidneys. By quantifying the transport kinetics of the AuNPs in cortex, medulla and pelvis of the normal and injured kidneys, we found that ureteral obstruction not just blocked the NP elimination through the ureter but also slowed down their transport from the medulla to pelvis and enhanced the cellular uptake. Moreover, the transport kinetics of the NPs and renal anatomic details can be precisely correlated with local pathological lesion. These findings not only advance our understandings of the nano‐bio interactions in kidneys but also offer a new pathway to noninvasively image kidney dysfunction and local injuries at the anatomical level.
Imaging of nanoparticle transport: High‐contrast noninvasive X‐ray imaging of the transport process of renal clearable gold nanoparticles makes it possible to quantitatively understand the interactions between the nanoparticles and both a normal and an injured kidney at the anatomical level. The transport kinetics of the nanoparticles and renal anatomic details can be precisely correlated with local pathological lesion.
Primary cilium is a microtubule-based organelle that projects from the surfaces of most mammalian cell types and protrudes into the extracellular milieu as an antenna-like sensor to senses ...extracellular physical and biochemical signals, and then transmits signals into cytoplasm or nucleus to regulate numerous physical and developmental processes. Therefore, loss of primary cilia is associated to multiple cancer progression, including skin, breast, pancreas, ovarian, prostate, and kidney cancers. Our previous studies demonstrate that high prevalent loss of DAB2 Interacting Protein (DAB2IP) is associated with renal cell carcinoma, and we found a kinesin-like protein, kinesin family member 3A (KIF3a), was significantly increased in DAB2IP-interacting protein fraction. KIF3 is one of the most abundant kinesin-2 family proteins expressed in cells, and it is necessary for ciliogenesis. In this study, we observed that loss of DAB2IP in normal kidney epithelial cell significantly impair primary cilia formation. We unveiled a new mechanism of primary cilia stability via DAB2IP and KIF3a physical interaction at DAB2IP-PH domain. Furthermore, we found that KIF3a also act as a tumor suppressor in renal cell carcinoma, affect tumor development and patient survival.
Rationale Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food reaction typically occurring in young infants that resolves over time, and the oral food challenge (OFC) ...remains the gold standard for evaluating its resolution.
Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently ...downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment.
Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA.
ubiquitination assay was used to test PARP-1 degradation. Furthermore,
mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR.
We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model.
In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.
A subpopulation of cancer stem cells (CSCs) plays a critical role of cancer progression, recurrence, and therapeutic resistance. Many studies have indicated that castration-resistant prostate cancer ...(CRPC) is associated with stem cell phenotypes, which could further promote neuroendocrine transdifferentiation. Although only a small subset of genetically pre-programmed cells in each organ has stem cell capability, CSCs appear to be inducible among a heterogeneous cancer cell population. However, the inductive mechanism(s) leading to the emergence of these CSCs are not fully understood in CRPC. Tumor cells actively produce, release, and utilize exosomes to promote cancer development and metastasis, cancer immune evasion as well as chemotherapeutic resistance; the impact of tumor-derived exosomes (TDE) and its cargo on prostate cancer (PCa) development is still unclear. In this study, we demonstrate that the presence of Cav-1 in TDE acts as a potent driver to induce CSC phenotypes and epithelial-mesenchymal transition in PCa undergoing neuroendocrine differentiation through NFκB signaling pathway. Furthermore, Cav-1 in mCRPC-derived exosomes is capable of inducing radio- and chemo-resistance in recipient cells. Collectively, these data support Cav-1 as a critical driver for mCRPC progression.
Passive IgE-mediated anaphylaxis i.v. injection of anti-IgE (EM95, 20μg), passive oral antigen-induced IgE anaphylaxis i.v. anti-trinitrophenyl (TNP)-IgE (20μg), followed by oral gavage with ...TNP-ovalbumin (TNP-OVA, 50mg), and active oral antigen-induced anaphylaxis i.p. 50μg OVA / 1mg alum followed by repeated oral gavage challenge of OVA (50mg) were induced in BALB/c mice. ...passive and active IgE-mediated oral antigen-induced shock (Temperature Change (oC) -2.98 ± 0.76 and -2.63 ± 0.47), were not associated with increased platelet activation compared to control groups (% positive CD62p ± SD; active oral: 33.4 ± 13.8 vs 17.2 ± 3.6, p = 0.1; passive oral: 12.8 ± 0.8 vs 15.1 ± 0.4, p = 0.017).
...workup revealed a positive urine Histoplasmosis test and a new lesion at the lower pole of the right kidney, identified as an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue ...(MALT) on biopsy.
Key Clinical Message
Consider the differential of Epstein–Barr virus (EBV) reactivation in pregnant women who develop progressive meningoencephalitis and transverse myelitis. EBV nucleic acid ...amplification should be considered in immunosuppressed patients.
A 32‐year‐old G10P6M3K22 pregnant female presented to a regional hospital with progressive severe neurological and behavioral deficits. Magnetic resonance revealed cervical transverse myelitis. Lumbar puncture confirmed Epstein–Barr virus (EBV) DNA on a background of IgG‐positive EBV serology. A diagnosis of EBV reactivation‐related meningoencephalitis with transverse myelitis in pregnancy was concluded.
Although oral food challenge (OFC) is an important clinical procedure for diagnosing food allergy, there is a paucity of literature on the outcome of the procedure and specifically the patients on ...whom the procedure is performed from the aspects of their age, sex, race/ethnicity, health insurance status, and serum specific IgE to the food tested.
We aimed to review results of OFC and determine the impact of patient age, sex, race/ethnicity, insurance status, private or public, and food specific serum IgE on the outcome of OFC.
A retrospective chart review was performed of patients undergoing OFCs at a children's hospital outpatient allergy clinic over a two-year period. The outcome of OFC was allergic or non-allergic based on determination and documentation by the treating physician. A logistic regression model was built to determine the association between the OFC outcomes, age, and symptoms at the time of OFC. A Chi-square analysis was performed to check for any significant relationship between the OFC outcome and age when stratified by insurance status.
Five hundred and eight children underwent 641 OFCs. Twenty nine percent of OFCs had an allergic outcome with the most commonly challenged foods being peanuts, eggs, and milk. Patient age and gender, when stratified by insurance status, did not have a significant effect on OFC outcomes. Serum IgE to peanuts and egg was significantly different between allergic OFC and non-allergic outcome. Vomiting and urticaria/angioedema correlated with an allergic OFC outcome.
OFCs confirm the food allergy diagnosis in about one-third of patients tested, and they should continue to be used when possible for an accurate diagnosis. Age, sex, and insurance status do not have a significant association with the outcome of OFC and cannot be added as predictive factors.
PDF
