No abstract

Background: Omalizumab (OMA) is an effective anti-immunoglobulin E (IgE) treatment for moderateto-severe asthma. However, predicting an individual's response is difficult. Monitoring change of total serum IgE may be useful for predicting the response to OMA. The purpose of this study was to determine if measuring the change in total IgE level could predict the response to OMA in patients with moderate-tosevere asthma. Methods: This study included 25 patients (11 females and 14 males; mean age =46.1 years; mean prebronchodilator FEV1% =67.8%) with moderate-to-severe asthma. All patients were treated with OMA, and total IgE serum concentrations were measured at baseline before treatment (median baseline total serum IgE =210 IU/mL) and at 4 weeks after beginning treatment. Patients were divided into responders (i.e., excellent or good response) and non-responders (i.e., moderate or poor response) using the global treatment effectiveness (GETE) response method after 16 weeks of treatment. The characteristics of responders and non-responders were compared, and receiver operating characteristic (ROC) curve analysis was used to determine the ability of change in IgE level to predict treatment response. Results: There were 20 responders (80%) and 5 non-responders (20%), and responders demonstrated better improvements of asthma control test (ACT) and asthma control questionnaire (ACQ) scores, and reduction of oral corticosteroid use as compared with non-responders. Twenty-one patients had a total serum IgE 4-week-to-baseline ratio ≥2, and 20 of the patients responded to OMA. The area under the ROC curve (AUC) for baseline IgE level for predicting treatment response was 0.53 (95% CI: 0.18-0.88), and that of the week 4 IgE level was 0.69 (95% CI: 0.42-0.96). Using a cutoff value of 2, the 4-week: baseline IgE ratio achieved the highest AUC of 0.87 (95% CI: 0.64-1), with a sensitivity and specificity of 100% and 80%, respectively, for predicting treatment response. Conclusions: A total week 4 serum IgE level:baseline level ratio ≥2 can predict the response to OMA in patients with moderate-to-severe asthma after 16 weeks of treatment with high likelihood. Monitoring changes of total IgE level in asthma patients treated OMA may be useful for predicting clinical response.

No abstract

No abstract

Unusual clinical course Background:Lupus nephritis (LN) is the most common and serious complication of systemic lupus erythematosus (SLE). Minimal change disease (MCD) and primary membranous nephropathy (PMN) are the 2 most common causes of primary nephrotic syndrome. Our purpose in publishing this case report is to introduce an unusual clinical course and initial renal biopsy revealed MCD and then PMN in second renal biopsy. Subsequently, a third renal biopsy resulted in a final diagnosis of LN. To the best of our knowledge, this is the first such report. Case Report:The 31-year-old male patient was initially diagnosed with MCD after the first renal biopsy in 2004. He improved with initial management and had a complete remission for 9 years. After 9 years, the patient again presented with heavy proteinuria without systemic lupus erythematous finding and he was diagnosed with MN following the second renal biopsy. Seven years later, he again developed proteinuria alone with concurrent systemic symptoms of systemic lupus erythematosus, and a third biopsy was performed, leading to final diagnosis as LN. He was well managed with the methylprednisolone and cyclophosphamide (CTX) regimen, which improved renal function and spared the patient from continuous hemodialysis. Conclusions:In rare case, MCD may represent an early phase of lupus nephritis, which may subsequently develop into severe lupus nephritis.

Background Exposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that the receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma. Histone deacetylase (HDAC) has been reported to be important in asthmatic pathogenesis. However, its effect on TDI-induced asthma is not known. The aim of this study was to determine the role of RAGE and HDAC in regulating airway inflammation using a TDI-induced murine asthma model. Methods BALB/c mice were sensitized and challenged with TDI to establish an asthma model. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitors) were administered intraperitoneally before each challenge. In vitro, the human bronchial epithelial cell line 16HBE was stimulated with TDI-human serum albumin (TDI-HSA). RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was also used in the experiments. Results In TDI-induced asthmatic mice, the expression of RAGE, HDAC1, and p-AKT/t-AKT was upregulated, and these expressions were attenuated by FPS-ZM1. Airway reactivity, Th2 cytokine levels in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by JNJ-26482585 and romidepsin. In addition, JNJ-26482585 and romidepsin ameliorated the redistribution of E-cadherin and β-catenin in TDI-induced asthma. In TDI-HSA-stimulated 16HBE cells, knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT). Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. Conclusions These findings indicate that RAGE modulates HDAC1 expression via the PI3K/AKT pathway, and that inhibition of HDAC prevents TDI-induced airway inflammation.

Hydroxyapatite nanoparticles (HAP) have been widely used in various fields because of their natural biological origin and functional properties. The emerging evidence on their toxicities has attracted research interest. HAP-induced vascular smooth muscle cell (VSMC) damage is a key step in vascular calcification (VC), particularly in patients with chronic kidney disease. However, the injury effects and mechanism of action of HAP on VSMCs have not been extensively investigated. This study comprehensively characterized commercially available HAP and investigated its adverse biological effects in cultured A7R5 cells. In vitro experiments revealed that internalized HAP was localized in lysosomes, followed by the release of Ca2+ owing to the low pH microenvironment. Upon Ca2+ homeostasis, Ca2+ enters the mitochondria, leading to the simultaneous generation of reactive oxygen species (ROS). ROS subsequently attack mitochondrial transmembrane potentials, promote mitochondrial ROS production, and oxidize mitochondrial DNA (Ox-mtDNA). Mitochondrial permeability-transition pores open, followed by the release of more Ox-mtDNA from the mitochondria into the cytosol due to the redox imbalance. This activates NLRP3/caspase-1/gasdermin D-dependent pyroptosis and finally excretes inflammatory factors to induce VC; an antioxidant could rescue this process. It has been suggested that HAP could induce an imbalance in intracellular Ca2+ homeostasis in A7R5 cells, followed by the promotion of mitochondrial dysfunction and cell pyroptosis, finally enhancing VC. To detect the in vivo toxicity of HAP, mice were treated with Cy7-labelled HAP NPs for 24 h. In vivo results also demonstrated that HAP accumulated in the kidneys, accompined with increased Ca concentration, upregulated oxidative stress-related factor and kidney damage. Overall, our research elucidates the mechanism of calcium homeostasis and redox imbalance, providing insights into the prevention of HAP-induced cell death.

Severe acute respiratory disease coronavirus 2 is currently causing the coronavirus disease 2019 (COVID-19) pandemic, placing extreme strain on the global health system. Vaccination is the main measure for preventing the COVID-19 epidemic, especially for high-risk groups including patients with chronic kidney disease (CKD). However, CKD patients receiving dialysis or kidney transplant may be characterized by decreased renal function and immune disorders, which may have uncertainties in their health. This overview aims to introduce the possible impact of the COVID-19 vaccine on kidney disease and its application in patients with CKD to provide evidence for the COVID-19 vaccine in patients with CKD. The data for this study were collected from PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI). The following keywords were used: “COVID-19”, “COVID-19 vaccine,” and “CKD”. The publication time of the papers was set from the establishment of the databases to September 2021. A total of 47 studies were included, and patients with CKD are a high-risk group for COVID-19 infection and severe illness. Vaccination is a powerful tool for preventing CKD patients from COVID-19. Because of possible side effects, the recurrence or deterioration of kidney disease may occur in CKD patients after vaccination. Although vaccination for patients with CKD remains a problem, with the advantages outweighing the disadvantages, stable CKD patients should complete a vaccination plan, and doctors should be aware of the recurrence or deterioration of kidney disease and close monitoring.Data access statement:Research data supporting this publication are available from the electronic databases of PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI).