Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Inhalable aerosol microparticles with low carrier dosage and high fine particle fraction prepared by spray-freeze-drying.

Co-suspension drug-loading technology, namely Aerosphere™, can improve fine particle fraction (FPF) and delivered dose content uniformity (DDCU). However, because of its poor drug-loading efficacy, the phospholipid carrier dosage in Aerosphere™ is usually dozens of times greater than that of the drug, resulting in a high material cost and blockage of the actuator. In this study, spray-freeze-drying (SFD) technology was used to prepare inhalable distearoylphosphatidylcholine (DSPC)-based microparticles for pressurized metered-dose inhalers (pMDI). Water-soluble, low-dose formoterol fumarate was used as an indicator to evaluate the aerodynamic performance of the inhalable microparticles. Water-insoluble, high-dose mometasone furoate was used to investigate the effects of drug morphology and drug-loading mode on the drug delivery efficiency of the microparticles. The results demonstrated that DSPC-based microparticles prepared using the co-SFD technology not only achieved higher FPF and more consistent delivered dose than those of drug crystal-only pMDI, but the amount of DSPC was also reduced to approximately 4% of that prepared using the co-suspension technology. This SFD technology may also be used to improve the drug delivery efficiency of other water-insoluble and high-dose drugs.

Structure-property relationship in the evaluation of xanthan gum functionality for oral suspensions and tablets.

The functional properties of xanthan gum (XG) in pharmaceutical preparations depend on its rheological properties, which inevitably rely on its molecular structure. Hence, this work investigated the relationship between the molecular structure of XG and its rheological properties and functional characteristics, and revealed the structural factors influencing the XG functionalities in oral suspensions and matrix tablets. Primarily, the molecular structures of four commercial XG products were characterized by infrared spectroscopy, differential scanning calorimetry and measuring the monosaccharide composition, average molecular weight, and pyruvate and acetyl contents. Furthermore, the flow behavior and viscoelasticity of XG solutions, the viscoelasticity of XG hydrogels, and XG combinations (XGC, aqueous solution containing XG, liquid glucose, and glycerin) were investigated. Finally, the dissolution time of XGC and the swelling and erosion properties of the XG matrix were studied to evaluate XG functionality in oral suspensions and matrix tablets, respectively. Results showed that the polydispersity of molecular weight and the pyruvate content affected the functionality and performance of XG in suspension and tablet forms. The higher polydispersity and pyruvate content of XG improved the hydrogel strength, which led to a longer dissolution time of XGC and a higher swelling extent of the XG matrix but a slower erosion rate.

Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (OGCs) of pancreas (UCOGCP) is a rare subtype of pancreatic ductal adenocarcinoma (PDAC), which had poorly described histopathological and clinical features. METHODS: In this study, single-cell RNA sequencing (scRNA-seq) was used to profile the distinct tumor microenvironment of UCOGCP using samples obtained from one UCOGCP patient and three PDAC patients. Bioinformatic analysis was carried out and immunohistochemical (IHC) staining was used to support the findings of bioinformatic analysis. After quality control of the raw data, a total of 18,376 cells were obtained from these four samples for subsequent analysis. These cells were divided into ten main cell types following the Seurat analysis pipeline. Among them, the UCOGCP sample displayed distinct distribution patterns from the rest samples in the epithelial cell, myeloid cell, fibroblast, and endothelial cell clusters. Further analysis supported that the OGCs were generated from stem-cell-like mesenchymal epithelial cells (SMECs). RESULTS: Functional analysis showed that the OGCs cluster was enriched in antigen presentation, immune response, and stem cell differentiation. Gene markers such as LOX, SPERINE1, CD44, and TGFBI were highly expressed in this SMECs cluster which signified poor prognosis. Interestingly, in myeloid cell, fibroblasts, and endothelial cell clusters, UCOGCP contained higher percentage of these cells and unique subclusters, compared with the rest of PDAC samples. CONCLUSIONS: Analysis of cell communication depicted that CD74 plays important roles in the formation of the microenvironment of UCOGCP. Our findings illustrated the genesis and function of OGCs, and the tumor microenvironment (TME) of UCOGCP, providing insights for prognosis and treatment strategy for this rare type of pancreatic cancer.

A lncRNA-immune checkpoint-related gene signature predicts metastasis-free survival in prostate adenocarcinoma.

Background: The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease biology. However, the role of immune checkpoint genes (ICGs) in PRAD remains unclear. Methods: Univariate and multivariate analyses were used to analyze genes associated with metastasis-free survival (MFS) in The Cancer Genome Atlas (TCGA)-PRAD dataset. The expressions of ADORA2A and TNFRSF18 were detected via immunohistochemical assay and real-time fluorescence quantitative PCR (RT-PCR) assay in our in-house cohort. The expression of long non-coding RNAs (lncRNAs) AL139287.1, SLC9A3-AS1, and SNHG12 were detected via RT-PCR assay in our in-house cohort. Stepwise regression, Cox regression, and nomogram analyses were used to evaluate the prognostic role of these genes in both the TCGA dataset and in-house cohort. The "pRRophetic" R package was used to evaluate drug sensitivity in the TCGA cohort according to the gene mRNA expression level. Results: In our study, univariate and multivariate analyses revealed that the mRNA expressions of two ICGs, ADORA2A and TNFRSF18, were independent factors affecting MFS in PRAD patients. A prognostic 2-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. The expressions of AL139287.1, SLC9A3-AS1, and SNHG12 were correlated with ADORA2A and TNFRSF18. A prognostic lncRNA-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. In addition, correlation analyses between the sensitivity of doxorubicin, erlotinib, gemcitabine, or vinorelbine and AL139287.1, SLC9A3-AS1, SNHG12, ADORA2A, and TNFRSF18 were conducted. Conclusions: Our results provide new targets for predicting tumor metastasis in PRAD and treating patients with metastatic PRAD.