Non-surgical periodontal treatment can effectively improve periodontal and circulating inflammatory status. Despite a lack of strong evidence, trends in some results support improved glycemic control after periodontal treatment in patients with diabetes.
Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines) that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF),vascular endothelial growth factor A (VEGF-A) interleukin 6 (IL-6) and interleukin 8 (IL-8) under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM) vs. normoxic BM-MSC-derived conditioned medium (norCM) or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.
Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enzyme, O6-methylguanine-DNA-methyltransferase (MGMT), which counteracts chemotherapy-induced DNA alkylation and is a key component of chemoresistance. MGMT repairs TMZ-induced DNA lesions, O6-meG, by transferring the alkyl group from guanine to a cysteine residue. This review provides an overview of recent advances in the field, with particular emphasis on the inhibitors of MGMT and underlying mechanisms. Literature search was performed through PubMed and all relevant articles were reviewed, with particular attention to MGMT, its role in TMZ-resistant gliomas, effects of MGMT inhibitors and the underlying mechanisms. Several strategies are currently being pursued to improve the therapeutic efficacy of TMZ via inhibition of MGMT to reduce chemoresistance and improve overall survival. MGMT may be a promising target for the treatment of TMZ-resistant gliomas.
A novel hydrogel (HA-az-F127 hydrogel) formed by reacting hydrazide modified hyaluronic acid (HAAD) and benzaldehyde terminated F127 triblock copolymers (BAF127) was developed in this work. The hydrogel with dynamic covalent chemically and micellar physically double-cross-linked networks exhibited rapid gelation and shear thinning properties. Besides, the hydrogel possessed functions, such as adaptable mechanical strength, self-healability, liquid-absorption, or drainage and tissue adhesion, which are important for wound treatment. Studies on cytocompatibility and histopathology by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide tests, live/death staining, and cell counting kit 8 assay demonstrated excellent biocompatibility of the hydrogels. After it was applied in the deep partial-thickness burn model, the hydrogel contributed effectively in promoting burn wound repair. Therefore, the HA-az-F127 hydrogel combined multiple functions in one system, demonstrating potential application in promoting burn wound healing.
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