Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

The complexities of proanthocyanidin biosynthesis and its regulation in plants

Proanthocyanidins(PAs)are natural flavan-3-ol polymers that contribute protection to plants under biotic and abiotic stress,benefits to human health,and bitterness and astringency to food products.They are also potential targets for carbon sequestration for climate mitigation.In recent years,from model species to commercial crops,research has moved closer to elucidating the flux control and channeling,subunit biosynthesis and polymerization,transport mechanisms,and regulatory networks involved in plant PA metabolism.This review extends the conventional understanding with recent findings that provide new insights to address lingering questions and focus strategies for manipulating PA traits in plants.

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure.This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix.To this aim,the co-assembly behaviour of a carboxylated variant of xyloglucan(CXG)with a peptide amphiphile(PA-H3)has been investigated to generate hierarchical constructs with tuneable molecular composition,structure,and properties.Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks.At a higher concentration,CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by smallamplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios.A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

Rational design of hydrogels for immunomodulation

The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.

HLA-G and single nucleotide polymorphism(SNP)associations with cancer in African populations:Implications in personal medicine

The immune system plays an important role in protecting the body against malignancy.During cancer immunoediting,the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel molecules.However,the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming cells.Human Leukocyte Antigen G(HLA-G)is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against them.HLA-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound protein.HLA-G locus is highly polymorphic in the non-coding 3′untranslated region(UTR)and in the 5′upstream regulatory region(5′URR).HLA-G expression is controlled by polymorphisms located in these regions,and several association studies between these polymorphic sites and disease predisposition,response to therapy,and/or HLA-G protein expression have been reported.Various polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer biology.This review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer development.We highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis,prognosis and immunotherapy in the currently understudied African population.

Sustained adenosine release:Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe disabilities.Adenosine,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor activation.This study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone cells.The study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media.Insights into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways involved.Analysing gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC differentiation.Sustained adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic disorders.This study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone repair.Unveiling adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.