Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.     

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.

Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.

Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process.     

Computational pathology definitions,best practices,and recommendations for regulatory guidance: a white paper from the Digital Pathology Association

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

An investigation of vitamin D status in alopecia areata

Alopecia areata (AA) is a type of non-scarring, recurrent patchy loss of hair in hair-bearing areas and is mostly of autoimmune origin. Previous studies have suggested that some autoimmune diseases were found to be associated with vitamin D deficiency. The current study was designed to assess the levels of serum 25-hydroxy vitamin D and C-reactive protein in AA, as compared with controls and to further identify the association between vitamin D levels and disease severity in patients with AA. This cross-sectional study included 45 patients with AA and 45 healthy volunteers. Clinical and anthropometric parameters were recorded, according to a pre-designed proforma. Serum 25-hydroxy vitamin D and high-sensitivity C-reactive protein were estimated using ELISA kits. The severity of AA was determined using Severity of Alopecia Tool (SALT) score. We observed a significant rise in systemic inflammation as seen by elevated high-sensitive C-reactive protein levels and lowered 25-hydroxy vitamin D levels in patients with alopecia areata, compared to controls (p?=?0.001). The levels of 25-hydroxy vitamin D showed a significant negative correlation with disease severity, while hs-CRP levels showed a significant positive correlation with disease severity (ρ?=???0.714, p?=?0.001 and ρ?=?0.818, p?=?0.001). Our results suggest significant systemic inflammation and vitamin D deficiency in alopecia areata, more so with increasing disease severity. This gains particular importance in the treatment of alopecia areata in future, as supplementing vitamin D to AA patients would result in reducing the disease severity and inducing remission.