Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring

Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing

The development of swimming power

The aim of this study was to study the effects of the transfer strength training method on swimming power. For this aim, twenty male swimmers “master“ were randomly allocated to strength (n= 10, ST) and swimming training (n=10, SW) groups. Both groups performed six-weeks training based on swimming training for SW and strength training which consisted in a weight training session immediately followed by the maximum swimming velocity. The performance in both groups was assessed by Maximal-Mechanical-External-Power (MMEP) before and after the six-weeks period, using a custom ergometer that provided force, velocity, and power measurement in water. A significant increased MMEP in ST group (5.73% with p< 0.05) was obtained by an increased strength (11.70% with p< 0.05) and a decreased velocity (4.99% with p> 0.05). Conversely, in the SW group there was a decreased in MMEP, force and velocity (7.31%, 4.16%, and 4.45%; respectively p> 0.05). This study showed that the transfer training method, based on combination of weight training (in dry condition) immediately followed by fast swim (in water) significantly improves swimming power in master

The development of swimming power

the aim of this study was to investigate the effects of the transfer strength training method on swimming power. METHODS: twenty male swimmers "master" were randomly allocated to strength (n= 10, ST) and swimming training (n=10, SW) groups. Both groups performed six-weeks training based on swimming training for SW and strength training which consisted in a weight training session immediately followed by the maximum swimming velocity. The performance in both groups was assessed by Maximal-Mechanical-External-Power (MMEP) before and after the six-weeks period, using a custom ergometer that provided force, velocity, and power measurement in water. RESULTS: a significant increased MMEP in ST group (5.73% with p 0.05). Conversely, in the SW group there was a decreased in MMEP (7.31%; p 0.05). CONCLUSION: this study showed that the transfer training method, based on combination of weight training (in dry condition) immediately followed by fast swim (in water) significantly improves swimming-power in master

The development of swimming power

Purpose: the aim of this study was to investigate the effects of the transfer strength training method on swimming powerMethods: twenty male swimmers “master“ were randomly allocated to strength (n= 10, ST) and swimming training (n=10, SW) groups. Both groups performed six-weeks training based on swimming training for SW and strength training which consisted in a weight training session immediately followed by the maximum swimming velocity. The performance in both groups was assessed by Maximal-Mechanical-External-Power (MMEP) before and after the six-weeks period, using a custom ergometer that provided force, velocity, and power measurement in water. Results: a significant increased MMEP in ST group (5.73% with p 0.05). Conversely, in the SW group there was a decreased in MMEP (7.31%; p 0.05)Conclusion: this study showed that the transfer training method, based on combination of weight training (in dry condition) immediately followed by fast swim (in water) significantly improves swimming-power in master

Modulation of metal-azolate frameworks for the tunable release of encapsulated glycosaminoglycans

Glycosaminoglycans (GAGs) are biomacromolecules necessary for the regulation of different biological functions. In medicine, GAGs are important commercial therapeutics widely used for the treatment of thrombosis, inflammation, osteoarthritis and wound healing. However, protocols for the encapsulation of GAGs in MOFs carriers are not yet available. Here, we successfully encapsulated GAG-based clinical drugs (heparin, hyaluronic acid, chondroitin sulfate, dermatan sulfate) and two new biotherapeutics in preclinical stage (GM-1111 and HepSYL proteoglycan) in three different pH-responsive metal-azolate frameworks (ZIF-8, ZIF-90, and MAF-7). The resultant GAG@MOF biocomposites present significant differences in terms of crystallinity, particle size, and spatial distribution of the cargo, which influences the drug-release kinetics upon applying an acidic stimulus. For a selected system, heparin@MOF, the released therapeutic retained its antithrombotic activity while the MOF shell effectively protects the drug from heparin lyase. By using different MOF shells, the present approach enables the preparation of GAG-based biocomposites with tunable properties such as encapsulation efficiency, protection and release.Miriam de J. Velásquez-Hernández, Efwita Astria, Sarah Winkler, Weibin Liang, Helmar Wiltsche, Arpita Poddar, Ravi Shukla, Glenn Prestwich, John Paderi, Pablo Salcedo-Abraira, Heinz Amenitsch, Patricia Horcajada, Christian J. Doonan and Paolo Falcar

The right place for me: A moderated mediation model to explain the involvement of employees aged over 50 years

Over the past decades, employment rates of older workers in most Western countries have rapidly increased. Hence, there is a growing interest in identifying the organizational dimensions that might impact the psychosocial adjustment of workers aged over 50 years. This study focuses on perceived organizational support (POS) and identity‐related measures (identification and authenticity) as key organizational components for workers at this stage of life. Furthermore, in the relationships discussed, we explore the moderating role of perceived age discrimination. In an ample sample of older workers (N = 4,563, aged 50–66 years), a moderated mediational model was tested where older workers' involvement was associated to POS. In the model, this relationship was mediated by organizational identification and authenticity, and the association between POS, identity‐related measures, and involvement was moderated by age‐based discrimination. Results showed that POS is associated with organizational involvement via organizational identification and authenticity and that high level of age discrimination decreased the positive association between POS, organizational identification, authenticity, and involvement

Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice

When replication forks collapse, Rad3 phosphorylates the checkpoint-clamp protein Rad9 in a manner that depends on Thr 225, a residue within the PCNA-like domain. The physiological function of Thr 225-dependent Rad9 phosphorylation, however, remains elusive. Here, we show that Thr 225-dependent Rad9 phosphorylation by Rad3 regulates DNA repair pathways. A rad9T225C mutant induces a translesion synthesis (TLS)-dependent high spontaneous mutation rate and a hyper-recombination phenotype. Consistent with this, Rad9 coprecipitates with the post-replication repair protein Mms2. This interaction is dependent on Rad9 Thr 225 and is enhanced by DNA damage. Genetic analyses indicate that Thr 225-dependent Rad9 phosphorylation prevents inappropriate Rhp51-dependent recombination, potentially by redirecting the repair through a Pli1-mediated sumoylation pathway into the error-free branch of the Rhp6 repair pathway. Our findings reveal a new mechanism by which phosphorylation of Rad9 at Thr 225 regulates the choice of repair pathways for maintaining genomic integrity during the cell cycle