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These ex vivo results contradict previous in vitro and in vivo reports of how MSC and their secretome may affect the microenvironment of the spinal cord after injury and highlight the importance of a careful comparison of the different experimental conditions used to assess the potential of cell therapies for the treatment of spinal cord injury.Hepatocyte growth factor (HGF) is a neurotrophic factor and its role in peripheral nerves has been relatively unknown. In this study, biological functions of HGF and its receptor c-met have been investigated in the context of regeneration of damaged peripheral nerves. Axotomy of the peripheral branch of sensory neurons from embryonic dorsal root ganglia (DRG) resulted in the increased protein levels of HGF and phosphorylated c-met. When the neuronal cultures were treated with a pharmacological inhibitor of c-met, PHA665752, the length of axotomy-induced outgrowth of neurite was significantly reduced. On the other hand, the addition of recombinant HGF proteins to the neuronal culture facilitated axon outgrowth. In the nerve crush mouse model, the protein level of HGF was increased around the injury site by almost 5.5-fold at 24 h post injury compared to control mice and was maintained at elevated levels for another 6 days. The amount of phosphorylated c-met receptor in sciatic nerve was also observed to be higher than control mice. When PHA665752 was locally applied to the injury site of sciatic nerve, axon outgrowth and injury mediated induction of cJun protein were effectively inhibited, indicating the functional involvement of HGF/c-met pathway in the nerve regeneration process. When extra HGF was exogenously provided by intramuscular injection of plasmid DNA expressing HGF, axon outgrowth from damaged sciatic nerve and cJun expression level were enhanced. Taken together, these results suggested that HGF/c-met pathway plays important roles in axon outgrowth by directly interacting with sensory neurons and thus HGF might be a useful tool for developing therapeutics for peripheral neuropathy.Several attempts have been made over the past decade to explore the concept of prodrug strategies that exploit PSA as a molecular target for the release of anticancer drugs in prostate tumors using various prostate specific antigen (PSA)-cleavable peptide linkers, but the desired antitumor and antimetastatic efficacy has not yet been fully achieved. We set out to look for new PSA-cleavable peptide substrates that could be cleaved more rapidly and efficiently than the previously used peptides. To look for the most susceptible PSA-cleavable peptide substrates, we used the so-called spot technology. With the following general formula, we designed 25 different fluorogenic heptapeptides; Cellulose-P5-P4-P3-P2-P1-P1′-P2′ (Fluorophore). The increase of the fluorescence in the supernatant of the reaction mixture was monitored using a 96-well fluorometric plate reader with excitation of λ ex 485 nm and λ em 535 nm. Three sequences showed a high fluorogenic liberation after incubation with PSA, i.e., Arg-Arg-Leu-His-Tyr-Ser-Leu (7), Arg-Arg-Leu-Asn-Tyr-Ser-Leu (8) and Arg-Ser-Ser-Tyr-Arg-Ser-Leu (23). Future incorporation of these optimized substrates in the PSA-cleavable prodrug formulations could further optimize the cleavage pattern and so the release characteristics of these prodrugs to rapidly and efficiently liberate the free cytotoxic agents inside the tumor tissues.Monoclonal antibodies can acquire the property of engagement of a second antigen via fusion methods or modification of their CDR loops, but also by modification of their constant domains, such as in the mAb2 format where a set of mutated amino acid residues in the CH3 domains enables a high-affinity specific interaction with the second antigen. We tested the possibility of introducing multiple binding sites for the second antigen by replacing the Fab CH1/CL domain pair with a pair of antigen-binding CH3 domains in a model scaffold with trastuzumab variable domains and VEGF-binding CH3 domains. Such bispecific molecules were produced in a “Fab-like” format and in a full-length antibody format. Novel constructs were of expected molecular composition using mass spectrometry. They were expressed at a high level in standard laboratory conditions, purified as monomers with Protein A and gel filtration and were of high thermostability. Their high-affinity binding to both target antigens was retained. Finally, the Her2/VEGF binding domain-exchanged bispecific antibody was able to mediate a potentiated surface Her2-internalization effect on the Her2-overexpressing cell line SK-BR-3 due to improved level of cross-linking with the endogenously secreted cytokine. To conclude, bispecific antibodies with Fabs featuring exchanged antigen-binding CH3 domains offer an alternative solution in positioning and valency of antigen binding sites.Diabetic patients usually avoid germinated endosperm of sugar palm (GESP) and elephant foot yam tuber (EFYT), fearing that these may further deteriorate existing hyperglycemia. In the present study, this suspicion was investigated by analyzing the nutrients and following the animal experiments by supplementary feeding powder of GESP, EFYT, and their mixture in addition to the regular diet for the six consecutive weeks. Next three weeks, the powder was withdrawn, and fasting blood glucose (FBG) levels were recorded from the beginning. The results clearly showed that these foodstuffs significantly (P less then 0.001) reduced FBG levels of alloxan-induced diabetic rats. The mixture of GESP & EFYT showed the maximum antidiabetic effects followed by GESP and EFYT, respectively. GESP, as well as the mixture, returned the FBG levels of diabetic rats within the normal range by the end of the 6th week, even after withdrawing the powder, but not by the EFYT. These results suggested that the foodstuffs may restore the damaged pancreatic β-cell functions by the end of the 6th week. Nutrient contents like fiber, zinc, as well as antidiabetogenic phytochemicals present in these foodstuffs, could perform these functions.

To investigate primary infant caregiver awareness of the current national public health safe sleep messages and the associations of awareness with care practices.

A cross-sectional survey in Queensland, Australia. All families with live babies birthed during April-May 2017 were eligible. HIF modulator Questionnaires were distributed when infants were approximately 3 months old.

Of the 10 200 eligible families, 3341 (33%) primary caregivers participated.

Participants were asked to recall key safe sleeping messages they were aware of (unprompted); questions about their infant care practices; and to select the current, national six safe sleeping messages (prompted multi-choice).

Overall, the majority of families are aware of sleep-related infant mortality and sudden infant death (3178/3317, 96%); however, approximately one in four caregivers (867/3292, 26%) could not identify the current six messages to promote safer infant sleep in a multi-choice question. Despite being aware of the six key messages, some caregiver practices did not always align with advice (336/2423, 14% were not smoke-free; 349/2423, 14% were not usually supine for sleep; 649/2339, 28% employed practices which may increase risk of head or face covering; 426/2423, 18% were not receiving breastmilk).