Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Pharmaceutics, MDPI AG, Vol. 15, No. 7 ( 2023-06-28), p. 1842-
    Abstract: As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm2. Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches ( 〉 200 μg/cm2/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Cells, MDPI AG, Vol. 12, No. 16 ( 2023-08-12), p. 2053-
    Abstract: Fatal familial insomnia (FFI) is a rare autosomal-dominant inherited prion disease with a wide variability in age of onset. Its causes are not known. In the present study, we aimed to analyze genetic risk factors other than the prion protein gene (PRNP), in FFI patients with varying ages of onset. Whole-exome sequencing (WES) analysis was performed for twenty-five individuals with FFI (D178N-129M). Gene ontology enrichment analysis was carried out by Reactome to generate hypotheses regarding the biological processes of the identified genes. In the present study, we used a statistical approach tailored to the specifics of the data and identified nineteen potential gene variants with a potential effect on the age of onset. Evidence for potential disease modulatory risk loci was observed in two pseudogenes (NR1H5P, GNA13P1) and three protein coding genes (EXOC1L, SRSF11 and MSANTD3). These genetic variants are absent in FFI patients with early disease onset (19–40 years). The biological function of these genes and PRNP is associated with programmed cell death, caspase-mediated cleavage of cytoskeletal proteins and apoptotic cleavage of cellular proteins. In conclusions, our study provided first evidence for the involvement of genetic risk factors additional to PRNP, which may influence the onset of clinical symptoms in FFI.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Agronomy, MDPI AG, Vol. 12, No. 2 ( 2022-02-15), p. 481-
    Abstract: The phototaxis of insects is closely related to light source factors, such as spectrum and light intensity. The cane grub, Exolontha castanea Chang (Coleoptera: Melolonthidae), is an important underground pest of sugarcane in Guangxi province of China. To clarify the effect of spectral sensitivity and light intensity response on the phototactic behavior of E. castanea, the phototactic behavior responses of male and female adults to 13 monochromatic lights in the wavelength range of 365–630 nm and different light intensities were measured. We found that both male and female adults had positive phototaxis to 13 monochromatic lights. The phototactic response rate of males and females at ultraviolet and violet light was the highest in the wavelength range of 365–420 nm. Among them, the most sensitive spectrum of females and males was at 365 nm and 420 nm, respectively. From the intensity response of phototactic behavior to different spectrum, the G1 (strong phototaxis) response rates of females at 365 nm and males at 420 nm were the highest. In addition, the phototactic response rate of females and males increased with the light intensity, showing a significant positive correlation. This study showed that the spectrum and light intensity were the key factors affecting the phototactic behavior of E. castanea. The sensitive spectrum of males and females were different, with a similar trend in phototaxis.
    Type of Medium: Online Resource
    ISSN: 2073-4395
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2607043-1
    SSG: 23
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Membranes, MDPI AG, Vol. 11, No. 12 ( 2021-11-24), p. 919-
    Abstract: Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).
    Type of Medium: Online Resource
    ISSN: 2077-0375
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2614641-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Cells, MDPI AG, Vol. 10, No. 9 ( 2021-09-16), p. 2440-
    Abstract: Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Cells, MDPI AG, Vol. 11, No. 8 ( 2022-04-07), p. 1254-
    Abstract: Dysregulation of platelet function is causally connected to thrombus formation and cardiovascular diseases. Therefore, assessing platelet reactivity is crucial. However, current platelet function tests come with pitfalls, limiting clinical use. Plasma miRNA signatures have been suggested as novel biomarkers for predicting/diagnosing cardiovascular diseases and monitoring antiplatelet therapy. Here, we provide results from a comprehensive study on the feasibility of using circulatory platelet miRNAs as surrogate markers of platelet activation. We performed small RNA-Seq on different blood cell types to confirm known and identify novel platelet-enriched miRNAs and validated a panel of 16 miRNAs using RT-qPCR. To identify the main carrier of these blood-based platelet miRNAs, we enriched and analyzed distinct microvesicle populations. Platelets were stimulated with GPVI and P2Y12 agonists in vitro to monitor the release of the selected miRNAs following activation. Finally, the miRNA panel was also measured in plasma from mice undergoing the Folts intervention (recurrent thrombus formation in the carotid artery). Applying an unbiased bioinformatics-supported workflow to our NGS data, we were able to confirm a panel of previously established miRNA biomarker candidates and identify three new candidates (i.e., miR-199a-3p, miR-151a-5p, and miR-148b-3p). Basal levels of platelet-derived miRNAs in plasma were mainly complexed with proteins, not extracellular vesicles. We show that changes in miRNA levels due to platelet activation are detectable using RT-qPCR. In addition, we highlight limitations of studying the in vitro release of miRNAs from platelets. In vivo thrombosis resulted in significant elevations of platelet-derived miRNA levels in mice. In conclusion, we provide in-depth evidence that activated platelets release miRNAs, resulting in measurable changes in circulatory miRNA levels, rendering them promising biomarker candidates.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-18), p. 608-
    Abstract: In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 10 ( 2022-05-15), p. 5519-
    Abstract: Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H2S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined. Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H2S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H2S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia. Results: Both inhalative and intravenously delivered H2S reduced retinal ganglion cell death with a better result from inhalative application. H2S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H2S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H2S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H2S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase. Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H2S and intravenous GYY 4137 administrations can improve neuronal cell survival.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 17 ( 2022-08-31), p. 9902-
    Abstract: Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 17 ( 2023-09-01), p. 13567-
    Abstract: Dystrophinopathies are the most common muscle diseases, especially in men. In women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare due to X-chromosomal inheritance. We present two young girls with severe muscle weakness, muscular dystrophies, and creatine kinase (CK) levels exceeding 10,000 U/L. In the skeletal muscle tissues, dystrophin staining reaction showed mosaicism. The almost entirely skewed X-inactivation in both cases supported the possibility of a dystrophinopathy. Despite standard molecular diagnostics (including multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) gene panel sequencing), the genetic cause of the girls’ conditions remained unknown. However, whole-genome sequencing revealed two reciprocal translocations between their X chromosomes and chromosome 5 and chromosome 19, respectively. In both cases, the breakpoints on the X chromosomes were located directly within the DMD gene (in introns 54 and 7, respectively) and were responsible for the patients’ phenotypes. Additional techniques such as Sanger sequencing, conventional karyotyping and fluorescence in situ hybridization (FISH) confirmed the disruption of DMD gene in both patients through translocations. These findings underscore the importance of accurate clinical data combined with histopathological analysis in pinpointing the suspected underlying genetic disorder. Moreover, our study illustrates the viability of whole-genome sequencing as a time-saving and highly effective method for identifying genetic factors responsible for complex genetic constellations in Duchenne muscular dystrophy (DMD).
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages