Repairing bone defects poses a major orthopedic challenge because current treatments are constrained by the limited regenerative capacity of human bone tissue. Novel therapeutic strategies, such as stem cell therapy and tissue engineering, have the potential to enhance bone healing and regeneration, and hence may improve quality of life for millions of people. However, the ex vivo expansion of stem cells and their in vivo delivery pose technical difficulties that hamper clinical translation and commercial development. A promising alternative to cell delivery-based strategies is to stimulate or augment the inherent self-repair mechanisms of the patient to promote endogenous restoration of the lost/damaged bone. There is growing evidence indicating that increasing the endogenous regenerative potency of bone tissues for therapeutics will require the design and development of new generations of biomedical devices that provide key signaling molecules to instruct cell recruitment and manipulate cell fate for in situ tissue regeneration. Currently, a broad range of biomaterial-based deployment technologies are becoming available, which allow for controlled spatial presentation of biological cues required for endogenous bone regeneration. This article aims to explore the proposed concepts and biomaterial-enabled strategies involved in the design of cell-free endogenous techniques in bone regenerative medicine.
A small library of heterocyclic-containing chalcones was developed and initial screening demonstrates modest activity against cancers, bacteria, and fungi.
The highly enantioselective preparation of pharmacologically interesting hexahydropyridazine derivatives based on a multicomponent cascade reaction is described. This one-pot approach utilizes an organocatalytic Michael reaction followed by intermolecular α-amination and intramolecular hemiaminalization to yield a chiral pyridazine backbone with contiguous stereogenic centers and multiple functional groups in good yield and with high stereoselectivity. Compounds synthesized by this method potently inhibited proliferation of MCF-7 breast cancer cells. Mechanistic studies suggest that compound 5 c exerts these anticancer effects by inducing apoptosis through extracellular signal related kinase (ERK)- and poly(adenosine diphosphate ribose) polymerase (PARP)-regulated pathways, as well as mitochondrial pathways.
Mercury is a highly toxic environmental pollutant that negatively affects human health. Thus, an in vivo method for noninvasive imaging of mercury(ii) and visualization of its accumulation within living systems would be advantageous. Herein, we describe a reaction-based bioluminescent probe for detection of mercury(ii) in vitro and accumulation in vivo. The application of this probe would help to shed light on the intricate contributions of mercury(ii) to various physiological and pathological processes.
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