Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides.

Collagen is the most widespread extracellular matrix (ECM) protein in the body and is important in maintaining the functionality of organs and tissues. Studies have explored interventions using collagen-targeting tissue engineered techniques, using collagen hybridizing or collagen binding peptides, to target or treat dysregulated or injured collagen in developmental defects, injuries, and diseases. Researchers have used collagen-targeting peptides to deliver growth factors, drugs, and genetic materials, to develop bioactive surfaces, and to detect the distribution and status of collagen. All of these approaches have been used for various regenerative medicine applications, including neovascularization, wound healing, and tissue regeneration. In this review, we describe in depth the collagen-targeting approaches for regenerative therapeutics and compare the benefits of using the different molecules for various present and future applications

Three-dimensional culture system improves the yield of placentalmesenchymal stem cell-derived extracellular vesicles

Placental mesenchymal stem cell derived-extracellular vesicles (PMSC-EVs) triggercellular regeneration with less toxicity andimmunogenicity compared to cell-basedtherapy. Conventional monolayer cell culture has low yield of PMSC-EVs which limits currentapplications.The CELLine bioreactor, allows for a high-density 3D cell culture within a semipermeablemembrane. It has been utilized as a large-scaletissue culture method. The objective is to explore the application of the CELLine bioreactor as a novel approach to improve the production and yield of PMSC-EVs for regenerative medicine applications

Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering.

Prenatal stem cell-based regenerative therapies have progressed substantially and have been demonstrated as effective treatment options for fetal diseases that were previously deemed untreatable. Due to immunoregulatory properties, self-renewal capacity, and multilineage potential, autologous human placental chorionic villus-derived mesenchymal stromal cells (CV-MSCs) are an attractive cell source for fetal regenerative therapies. However, as a general issue for MSC transplantation, the poor survival and engraftment is a major challenge of the application of MSCs. Particularly for the fetal transplantation of CV-MSCs in the naturally hypoxic fetal environment, improving the survival and engraftment of CV-MSCs is critically important. Hypoxic preconditioning (HP) is an effective priming approach to protect stem cells from ischemic damage. In this study, we developed an optimal HP protocol to enhance the survival and proangiogenic capacity of CV-MSCs for improving clinical outcomes in fetal applications. Total cell number, DNA quantification, nuclear area test, and cell viability test showed HP significantly protected CV-MSCs from ischemic damage. Flow cytometry analysis confirmed HP did not alter the immunophenotype of CV-MSCs. Caspase-3, MTS, and Western blot analysis showed HP significantly reduced the apoptosis of CV-MSCs under ischemic stimulus via the activation of the AKT signaling pathway that was related to cell survival. ELISA results showed HP significantly enhanced the secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by CV-MSCs under an ischemic stimulus. We also found that the environmental nutrition level was critical for the release of brain-derived neurotrophic factor (BDNF). The angiogenesis assay results showed HP-primed CV-MSCs could significantly enhance endothelial cell (EC) proliferation, migration, and tube formation. Consequently, HP is a promising strategy to increase the tolerance of CV-MSCs to ischemia and improve their therapeutic efficacy in fetal clinical applications

In vitro and in vivo release studies of fluorouracil acetic acid-dextran conjugates

Fluorouracil acetic acid–dextran (FUD) conjugates were synthesized and its stability in buffer solution has been investigated previously in our laboratory. In this contribution, the in vitro and in vivo releases of FUD were investigated. The results revealed that no detectable 5-fluorouracil (5-FU, FU) found during in vitro and in vivo release studies. The in vitro release was dependent on both degree of substitution (DS) of 5-fluorouracil-1-acetic acid (5-FUA) in FUD and gastrointestinal tract section (GITs). 5- FUA can be completely released from the conjugates with DS of 10.3 % (wt/wt) in homogenates of cecum and colon content. After oral administration in rats, FUD with DS of 10.3 % showed colon specific delivery of 5-FUA compared with that of free 5-FUA. The target index (TI) of the conjugate was 1.93 in cecum contents and 2.09 in colon contents respectively within 24 h. The results indicated that the conjugates can be used as colon-specific delivery system of 5-FUA.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Changes of dendritic cells and fractalkine in type 2 diabetic patients with unstable angina pectoris: a preliminary report

<p>Abstract</p> <p>Background</p> <p>It has been shown that dendritic cells (DCs) and fractalkine play a role in accelerating progression of the inflamed atherosclerotic lesions and plaque rupture. We evaluated the numbers and functional changes of DCs and its subsets in human type 2 diabetes with or without unstable angina pectoris (UAP).</p> <p>Methods</p> <p>The study population consisted of 39 diabetic patients (DM:18 without CAD; DM + UAP: 21 with UAP), 18 non-diabetic UAP patients (UAP), and 15 healthy control (Normal). Peripheral blood DCs and its subsets were measured by three color flow cytometry. Serum levels of fractalkine, IL-12, and IFN-α were also measured. The functional status of the monocyte-derived DCs was analyzed by flow cytometry and allogeneic mixed T lymphocytes reaction.</p> <p>Results</p> <p>The percent and absolute numbers of DCs and mDC within the total leukocyte population was similar for Normal and DM, while significantly lower in DM + UAP. pDC numbers were not significantly altered. Serum fractalkine in DM + UAP was highest among the four groups (<it>p </it>= 0.04 vs. UAP, <it>p </it>= 0.0003 vs. DM, <it>p </it>< 0.0001 vs. Normal). Circulating mDC inversely correlated with serum fractalkine (r = -0.268, <it>p </it>= 0.01) level. Compared with DM and UAP, the costimulatory molecules CD86 and proliferation of T cells stimulated by DCs were significantly increased in DM + UAP group.</p> <p>Conclusions</p> <p>Our study suggested that increases in the fractalkine level and the number and functional changes of blood DCs might contribute to diabetic coronary atherosclerosis and plaque destabilization.</p

MAX-DOAS measurements of tropospheric NO2 and HCHO in Nanjing and a comparison to ozone monitoring instrument observations

In this paper, we present long-term observations of atmospheric nitrogen dioxide (NO2) and formaldehyde (HCHO) in Nanjing using a Multi-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) instrument. Ground-based MAX-DOAS measurements were performed from April 2013 to February 2017. The MAX-DOAS measurements of NO2 and HCHO vertical column densities (VCDs) are used to validate ozone monitoring instrument (OMI) satellite observations over Nanjing. The comparison shows that the OMI observations of NO2 correlate well with the MAX-DOAS data with Pearson correlation coefficient (R) of 0.91. However, OMI observations are on average a factor of 3 lower than the MAX-DOAS measurements. Replacing the a priori NO2 profiles by the MAX-DOAS profiles in the OMI NO2 VCD retrieval would increase the OMI NO2 VCDs by similar to 30% with correlation nearly unchanged. The comparison result of MAX-DOAS and OMI observations of HCHO VCD shows a good agreement with R of 0.75 and the slope of the regression line is 0.99. An age-weighted backward-propagation approach is applied to the MAX-DOAS measurements of NO2 and HCHO to reconstruct the spatial distribution of NO2 and HCHO over the Yangtze River Delta during summer and winter time. The reconstructed NO2 fields show a distinct agreement with OMI satellite observations. However, due to the short atmospheric lifetime of HCHO, the backward-propagated HCHO data do not show a strong spatial correlation with the OMI HCHO observations. The result shows that the MAX-DOAS measurements are sensitive to the air pollution transportation in the Yangtze River Delta, indicating the air quality in Nanjing is significantly influenced by regional transportation of air pollutants. The MAX-DOAS data are also used to evaluate the effectiveness of air pollution control measures implemented during the Youth Olympic Games 2014. The MAX-DOAS data show a significant reduction of ambient aerosol, NO2 and HCHO (30 %-50 %) during the Youth Olympic Games. Our results provide a better understanding of the transportation and sources of pollutants over the Yangtze River Delta as well as the effect of emission control measures during large international events, which are important for the future design of air pollution control policies

Local application of silver nitrate as an adjuvant treatment before deep lamellar keratoplasty for fungal keratitis poorly responsive to medical treatment

ObjectiveThe purpose of this study is to evaluate the efficacy and safety of the local application of silver nitrate (LASN) as an adjuvant treatment before deep lamellar keratoplasty (DLKP) for fungal keratitis responding poorly to medical treatment.MethodsA total of 12 patients (12 eyes) with fungal keratitis responding poorly to medical treatment (for at least 2 weeks) were included. LASN was performed using 2% silver nitrate, the ulcer was cleaned and debrided, and then, the silver nitrate cotton stick was applied to the surface of the ulcer for a few seconds. The effect of LASN was recorded. The number of hyphae before and after treatment was determined by confocal microscope. After the condition of the ulcer improved, DLKP was performed. Fungal recurrence, best-corrected visual acuity (BCVA), loose sutures, and endothelial cell density (ECD) were recorded in detail.ResultsClinical resolution of corneal infiltration and edema was observed, and the ulcer boundary became clear in all 12 patients after 7–9 days of LASN. Confocal microscopy showed that the number of hyphae was significantly reduced. Ocular pain peaked on days 1 and 2 after treatment, and 9 patients (75%, day 1) and 1 patient (8.3%, day 2) required oral pain medication. During the follow-up period after DLKP, no fungal recurrence and loose sutures were observed. After the operation, the BCVA of all patients improved. The mean corneal ECD was 2,166.83 ± 119.75 cells/mm2.ConclusionThe LASN was safe and effective and can be well tolerated by patients. Eye pain can be relieved quickly. LASN as an adjuvant treatment before DLKP might be a promising therapeutic strategy