In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured ...epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting microRNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage microenvironment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection — all in the hopes of early detection of complications.
•Currently available wound dressings are mainly made of natural polymeric materials.•The carriers for the growth factors should be able to deliver them in a sustained manner.•New wound healing strategies are emerging including siRNA delivery and targeting mRNA molecules.•Stem cells derived from various tissues have a potential to heal acute and chronic wounds.•Sensors and actuators are being investigated to improve the management of wound healing.
Adult human articular cartilage harbors a population of CD166+ mesenchymal stem cell-like progenitors that become more numerous during osteoarthritis (OA). While their role is not well understood, ...here we report that they are indeed part of cellular clusters formed in OA cartilage, which is a pathological hallmark of this disease. We hypothesize that these cells, termed OA mesenchymal stem cells (OA-MSCs), contribute to OA pathogenesis. To test this hypothesis, we generated and characterized multiple clonally derived stable/immortalized human OA-MSC cell lines, which exhibited the following properties. Firstly, two mesenchymal stem cell populations exist in human OA cartilage. While both populations are multi-potent, one preferentially undergoes chondrogenesis while the other exhibits higher osteogenesis potential. Secondly, both OA-MSCs exhibit significantly higher expression of hypertrophic OA cartilage markers COL10A1 and RUNX2, compared to OA chondrocytes. Induction of chondrogenesis in OA-MSCs further stimulated COL10A1 expression and MMP-13 release, suggesting that they contribute to OA phenotypes. Finally, knocking down RUNX2 is insufficient to inhibit COL10A1 in OA-MSCs and also requires simultaneous knockdown of NOTCH1 thereby suggesting altered gene regulation in OA stem cells in comparison to chondrocytes. Overall, our findings suggest that OA-MSCs may drive pathogenesis of cartilage degeneration and should therefore be a novel cell target for OA therapy.
We study the rise of digital footprint (DF) users in the U.S. residential mortgage market. The proportion of lenders that use a borrower's DF has witnessed remarkable growth from 6% in 2013 to 34% in ...2018 in a short span – according to our analysis. We show that the use of DFs can significantly reduce a lender's overall risk and that the use of DFs can result in considerable societal benefits, by reducing the overall discriminatory forces. In sum, we provide evidence that the informational advantage associated with using a borrower's DF far outweighs that of existing traditional lending methods.
Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new ...antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of β-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.
Pancreatic adenocarcinoma (PDAC) persists as a malignancy with high morbidity and mortality that can benefit from new means to characterize and detect these tumors, such as radiogenomics. In order to ...address this gap in the literature, constructed a transcriptomic-CT radiogenomic (RG) map for PDAC.
In this Institutional Review Board approved study, a cohort of subjects (n = 50) with gene expression profile data paired with histopathologically confirmed resectable or borderline resectable PDAC were identified. Studies with pre-operative contrast-enhanced CT images were independently assessed for a set of 88 predefined imaging features. Microarray gene expression profiling was then carried out on the histopathologically confirmed pancreatic adenocarcinomas and gene networks were constructed using Weighted Gene Correlation Network Analysis (WCGNA) (n = 37). Data were analyzed with bioinformatics analyses, multivariate regression-based methods, and Kaplan-Meier survival analyses.
Survival analyses identified multiple features of interest that were significantly associated with overall survival, including Tumor Height (P = 0.014), Tumor Contour (P = 0.033), Tumor-stroma Interface (P = 0.014), and the Tumor Enhancement Ratio (P = 0.047). Gene networks for these imaging features were then constructed using WCGNA and further annotated according to the Gene Ontology (GO) annotation framework for a biologically coherent interpretation of the imaging trait-associated gene networks, ultimately resulting in a PDAC RG CT-transcriptome map composed of 3 stage-independent imaging traits enriched in metabolic processes, telomerase activity, and podosome assembly (P < 0.05).
A CT-transcriptomic RG map for PDAC composed of semantic and quantitative traits with associated biology processes predictive of overall survival, was constructed, that serves as a reference for further mechanistic studies for non-invasive phenotyping of pancreatic tumors.
Meniscus injuries are among the most common orthopedic injuries. Tears in the inner one‐third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized ...that progenitor cells from healthy human articular cartilage (chondroprogenitor cells C‐PCs) may be more suitable than bone‐marrow mesenchymal stem cells (BM‐MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C‐PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker activated leukocyte cell adhesion molecule (ALCAM) (CD166). Our findings revealed that healthy human C‐PCs are CD166+, CD90+, CD54+, CD106‐ cells with multilineage differentiation potential, and elevated basal expression of chondrogenesis marker SOX‐9. We show that, similar to BM‐MSCs, C‐PCs are responsive to the chemokine stromal cell‐derived factor‐1 (SDF‐1) and they can successfully migrate to the area of meniscal tissue damage promoting collagen bridging across inner meniscal tears. In contrast to BM‐MSCs, C‐PCs maintained reduced expression of cellular hypertrophy marker collagen X in monolayer culture and in an explant organ culture model of meniscus repair. Treatment of C‐PCs with SDF‐1/CXCR4 pathway inhibitor AMD3100 disrupted cell localization to area of injury and prevented meniscus tissue bridging thereby indicating that the SDF‐1/CXCR4 axis is an important mediator of this repair process. This study suggests that C‐PCs from healthy human cartilage may potentially be a useful tool for fibrocartilage tissue repair/regeneration because they resist cellular hypertrophy and mobilize in response to chemokine signaling. Stem Cells 2019;37:102–114
Using an explant model of meniscus repair, we demonstrate that progenitor cells from healthy human articular cartilage resist cellular hypertrophy and mediate meniscal fibrocartilage healing in a manner that is dependent of SDF‐1/CXCR4 chemokine signaling.
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