Implantation and tracing of green fluorescent protein-expressing adipose-derived stem cells in peri-implant capsular fibrosis.

BACKGROUND: Adipose-derived stem cells (ASCs) have been reported to reduce fibrosis in various tissues. In this study, we investigated the inhibitory role of ASCs on capsule formation by analyzing the histologic, cellular, and molecular changes in a mouse model of peri-implant fibrosis. We also investigated the fate and distribution of ASCs in the peri-implant capsule. METHODS: To establish a peri-implant fibrosis model, customized silicone implants were inserted into the dorsal site of C57BL/6 wild-type mice. ASCs were harvested from the fat tissues of transgenic mice that express a green fluorescent protein (GFP-ASCs) and then injected into the peri-implant space of recipient mice. The peri-implant tissues were harvested from postoperative week 2 to 8. We measured the capsule thickness, distribution, and differentiation of GFP-ASCs, as well as the cellular and molecular changes in capsular tissue following ASC treatment. RESULTS: Injected GFP-ASCs were distributed within the peri-implant capsule and proliferated. Administration of ASCs reduced the capsule thickness, decreased the number of myofibroblasts and macrophages in the capsule, and decreased the mRNA level of fibrogenic genes within the peri-implant tissue. Angiogenesis was enhanced due to trans-differentiation of ASCs into vascular endothelial cells, and tissue hypoxia was relieved upon ASC treatment. CONCLUSIONS: We uncovered that implanted ASCs inhibit capsule formation around the implant by characterizing a series of biological alterations upon ASC treatment and the fate of injected ASCs. These findings highlight the value of ASCs for future clinical applications in the prevention of capsular contracture after implant-based reconstruction surgery.

Attenuation of UVB-Induced Photo-Aging by Polyphenolic-Rich Spatholobus Suberectus Stem Extract Via Modulation of MAPK/AP-1/MMPs Signaling in Human Keratinocytes.

It is well known that ultraviolet light activates mitogen-activated protein (MAP) kinase by increasing the reactive oxygen species (ROS) in the body, enhancing activating protein 1(AP-1) complexes (c-Jun and c-Fos), increasing matrix metalloproteinases (MMPs) and degrading collagen and elastin. In this study, we confirmed that polyphenolic rich Spatholobus suberectus (SS) stem extracts suppressed ultraviolet (UV)-induced photo-aging. The major active components of SS stem extracts were identified as gallic acid, catechin, vanillic acid, syringic acid and epicatechin. The aqueous and ethanolic extracts of the stem of SS (SSW and SSE, respectively) significantly reduced the elastase enzyme activity. Moreover, both extracts were suppressed the ROS generation and cellular damage induced by UVB in HaCaT cells. Our results also revealed that SSE could regulate the expression of MMPs, tissue inhibitor of matrix metalloproteinase (TIMP)-1, collagen type I alpha 1 (COL1A1), elastin (ELN) and hyaluronan synthase 2 (HAS2) at their transcriptional and translational level. Furthermore, SSE was blocked the UVB-induced phosphorylation of mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-κB) and c-Jun. Moreover, combination of syringic acid, epicatechin and vanillic acid showed strong synergistic effects on elastase inhibition activity, in which the combination index (CI) was 0.28. Overall, these results strongly suggest that the polyphenolics of SSE exert anti-ageing potential as a natural biomaterial to inhibit UVB-induced photo-aging.

Antioxidant mechanism of polyphenol-rich Nymphaea nouchali leaf extract protecting DNA damage and attenuating oxidative stress-induced cell death via Nrf2-mediated heme-oxygenase-1 induction coupled with ERK/p38 signaling pathway.

This study investigates the polyphenolic composition and antioxidant mechanism of an ethyl acetate fraction of Nymphaea nouchali leaves (NNLE). Various in vitro assays were performed using RAW 264.7 cells to assess the antioxidant effects of NNLE and to understand the underlying molecular mechanism. High-performance liquid chromatography analysis revealed the presence of gallic acid, catechin, epigallocatechin, epicatechin gallate, caffeic acid, luteolin, and kaempferol as the key polyphenolic composition of NNLE. NNLE had a potent ability to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation. In addition, NNLE prevented the damage of DNA and quenched t-BHP induced generation of ROS without showing toxicity. NNLE was found to combat oxidative stress by enhancing the transcription and translation of both primary antioxidant enzymes and phase-II detoxifying enzymes, especially heme-oxygenase-1 (HO-1). NNLE treatment enhanced Nrf2 accumulation in the nucleus and post-translational phosphorylation level of p38 kinase and extracellular signal-regulated kinase (ERK) in RAW 264.7 cells. Treatment with p38 and ERK inhibitors completely suppressed NNLE-induced Nrf2 and HO-1 expression. We also found that p38 and ERK inhibitors significantly antagonized the increase in cell viability and cellular ROS scavenging activity induced by NNLE. The findings of this study provide scientific evidence on the potential of NNLE as a cost-effective and readily available source of natural phytochemicals, along with the strategy to prevent diseases associated with oxidative stress through attenuating disease progression.

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38.

The aim of the present study was to examine the antioxidative activity of (+)-lariciresinol (LRSL), an optically active lignan isolated from Rubia philippinensis in several in vitro assays. LRSL was also subjected to evaluate its inhibitory effect against the generation of reactive oxygen species (ROS) in murine macrophage (RAW 264.7) cells. The results showed that LRSL possessed very strong radical scavenging activity and reducing power, as well as inhibited ROS generation in a dose-dependent manner without showing any cytotoxicity. The transcriptional and translational levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were markedly higher in the sample treated group. LRSL treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with a corresponding increase in the transcriptional and translational activities of the heme oxygenase-1 (HO-1). LRSL activated p38 and treatments with SB239063 (a p38 inhibitor) suppressed the LRSL-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Collectively, the data demonstrated that LRSL has potent antioxidative activity, decreasing ROS generation in RAW 264.7 cells and increasing the transcriptional and translational levels of antioxidant enzymes by activating Nrf2-mediated HO-1 induction via p38 signaling.

Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase-Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK-NRF2)-Mediated Antioxidant Pathway.

The leaves of Lannea coromandelica (Houtt.) Merr. are used in the Garo, Pahan, and Teli tribal communities of Bangladesh as a traditional medicinal plant to treat hepatitis, diabetes, ulcers, heart disease, and dysentery. However, there have been limited phytochemical and biological studies on the bark of L. coromandelica. This study aimed to investigate the antioxidant activities of L. coromandelica bark extract (LCBE) and the underlying mechanism using RAW 264.7 cells. The LCBE was analysed by high-pressure liquid chromatography (HPLC) to detect its key polyphenolic compounds. Various in vitro antioxidant assays were performed using RAW 264.7 cells to assess the antioxidant effects of the LCBE and to understand the underlying molecular mechanism. HPLC revealed the presence of gallic acid, (-)-epigallocatechin-3-gallate, catechin, chlorogenic acid, and caffeic acid in the LCBE. The extract showed a very potent capacity to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation and also quenched cellular reactive oxygen species (ROS) generation without showing any toxicity. The LCBE was found to combat the oxidative stress by enhancing the expression, at both transcriptional and translational levels, of primary antioxidant enzymes as well as phase II detoxifying enzymes, especially heme oxygenase 1, through the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated pathway in RAW 264.7 cells via the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK). The LCBE exhibited strong antioxidant activities and mitigated the cellular ROS production. These results provide scientific evidence of its potential as an ideal applicant for a cost-effective, readily available, and natural phytochemical, as well as a strategy for preventing diseases associated with oxidative stress and attenuating disease progress.