Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway.

This study aims to investigate the wound-healing effectiveness of the phenolic compound, naringin, both in vitro and in vivo. Male mice were shaved on their dorsal skin under isoflurane, a biopsy punch was made in four symmetrical circular resection windows (6 mm) to induce a wound. These excision wounds were used to study the topical effects of naringin in terms of various biochemical, molecular, and histological parameters. We observed a significant recovery in the wound area. Increased levels of MMP-2, 9, 14, TIMP-2, VEGF-A, and VEGF-R1 were induced by naringin in the HaCaT cells. The time course experiments further revealed that levels of VEGF-A and B increased within 36 h; whereas levels of VEGF-C decreased. In line with this, VEGF-R3 levels, but not VEGF-R1 and 2 levels, increased soon after stimulation; although the increase subsided after 36 h. Additionally, naringin cream upregulated wound healing in vitro. The blockage of VEGF by Bevacizumab abolished the function of naringin cream on cell migration. Histological alterations in the wounded skin were restored by naringin cream, which accelerated wound healing via upregulated expression of growth factors (VEGF-A, B, and C and VEGF-R3), and thus increased MMP-2, 9, 14 expressions.

Activation of dynamin-related protein 1 - dependent mitochondria fragmentation and suppression of osteosarcoma by cryptotanshinone.

BACKGROUND: Discovering how to regulate mitochondrial function to reduce cancer growth holds great potential for future cancer therapy development. Here we explore the effects of cryptotanshinone (CPT), a natural product derived from Salvia miltiorrhiza, on mitochondria of osteosarcoma (OS) both in vitro and in vivo, and further elucidate the underlying molecular mechanisms. METHODS: Cytotoxicity in the CPT treated OS cells was analyzed by flow cytometry, CCK8, TUNEL assay and colony formation assays. Flow cytometric analysis was performed to evaluate the effect of CPT on cell cycle of OS cells. Mitochondrial morphology was examined by staining with the mitochondrial membrane potential -sensitive fluorochrome, MitoTracker Red (CMXRos). Immunoblotting, confocal-immunofluorescence staining, co-immunoprecipitation were used to examine the expression and interaction between CPT-mediated Drp1 and Bax. Finally, the synergistic effect of CPT on OS cells was validated using a mouse xenograft tumor model. RESULTS: In this study, we found CPT treatment induced S-phase arrest, apoptosis, and mitochondrial fragmentation in OS cells. CPT also effectively activated caspase-dependent apoptosis, which could be blocked by pan-caspase inhibitor Z-VAD-FMK. Moreover, we herein provide evidence that treatment with CPT resulted in mitochondrial fragmentation, which is mediated by dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission. Pursuing this observation, downregulation of Drp1 via silencing RNA could abrogate the induction of apoptosis and mitochondrial fragmentation induced by CPT. Finally, we demonstrate that CPT induced Drp1, which interacted directly with Bcl-2-associated X protein (Bax), which contributed to driving Bax translocation from the cytosol to the mitochondria. CONCLUSIONS: Our findings offer insight into the crosstalk between mitochondrial fragmentation and inhibition of osteosarcoma cell growth in response to CPT.

Gender-dependent effect of GSTM1 genotype on childhood asthma associated with prenatal tobacco smoke exposure.

It remains unclear whether the GSTM1 genotype interacts with tobacco smoke exposure (TSE) in asthma development. This study aimed to investigate the interactions among GSTM1 genotype, gender, and prenatal TSE with regard to childhood asthma development. In a longitudinal birth cohort in Taiwan, 756 newborns completed a 6-year follow-up, and 591 children with DNA samples available for GSTM1 genotyping were included in the study, and the interactive influences of gender-GSTM1 genotyping-prenatal TSE on childhood asthma development were analyzed. Among these 591 children, 138 (23.4%) had physician-diagnosed asthma at 6 years of age, and 347 (58.7%) were null-GSTM1. Prenatal TSE significantly increased the prevalence of childhood asthma in null-GSTM1 children relative to those with positive GSTM1. Further analysis showed that prenatal TSE significantly increased the risk of childhood asthma in girls with null-GSTM1. Furthermore, among the children without prenatal TSE, girls with null-GSTM1 had a significantly lower risk of developing childhood asthma and a lower total IgE level at 6 years of age than those with positive GSTM1. This study demonstrates that the GSTM1 null genotype presents a protective effect against asthma development in girls, but the risk of asthma development increases significantly under prenatal TSE.

Potential of probiotic strains to modulate the inflammatory responses of epithelial and immune cells in vitro.

Lactobacilli are important human commensal microbiota that are considered to be probiotic as they have been shown to reduce pathogenic infections and chronic inflammation. This study compared 4 strains of lactobacilli for their probiotic potential. These 4 strains showed varying capacities for adhesion and cytokine induction (interleukin [IL]-8 and IL-10) in different human epithelial cells, such as primary cultures of buccal cavity cells, and established cell lines derived from epithelia of the pharynx, intestine and cervix. After exposure to lactobacilli, secretion of cytokines (IL- 10, IL-12p70, interferon-?, and tumor necrosis factor-?) was induced at varying levels in different cultures of human immune cells, including dendritic cells, monocyte-depleted peripheral blood mononuclear cells, CD14+ cells, CD4+CD25- T cells, and regulatory T-cells. Growth inhibition of pathogenic strains was detectable in the presence of lactobacilli in vitro. Moreover, among the 4 strains tested, Lactobacillus salivarius sp. salicinius AP-32 was found to have the highest probiotic potential. This study highlights the complex host-pathogen-microbiota interactions and indicates that a combination of strains may have to be used to provide all the desirable probiotic benefits.

Role of certain trace minerals in oxidative stress, inflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients.

BACKGROUND: Asthma is associated with increased inflammation, oxidative stress and abnormal immune system function. We determined the distributions of several essential trace minerals and assessed their relationships to factors that are associated with the pathophysiological status of patients with mild/moderate asthma. METHODS: We enrolled 25 asthmatic patients and 25 healthy subjects. We measured: blood trace minerals, zinc (Zn), copper (Cu) and selenium (Se); oxidative stress markers thiobarbituric acid reactive substances (TBARS); antioxidant enzyme activities; percentages of CD4 and CD8 lymphocyte subsets; high-sensitivity C-reactive protein (hs-CRP); and a lung function index (FEV1/FVC%). RESULTS: Compared with healthy subjects, asthmatics had lower concentrations of Zn and Se; higher Cu concentrations, and Cu/Zn and Cu/Se ratios; and lower antioxidant enzyme glutathione peroxidase (GPx), glutathione reductase (GR) and catalase activities. Significantly increased concentrations of hs-CRP, TBARS and CD4/CD8 lymphocyte ratios were also observed. Furthermore, plasma TBARS or hs-CRP concentrations were negatively associated with Se concentrations, but were positively associated with Cu/Se ratios. CD4/CD8 lymphocyte ratios were inversely correlated with Se, while it was positively correlated with Cu/Se ratio. FEV1/FVC% was also significantly correlated with Se concentrations, and Cu/Se and Cu/Zn ratios. CONCLUSIONS: Abnormal distributions of these trace minerals may aggravate oxidative damage and inflammation, increased CD4/CD8 lymphocyte ratios and decreased lung function in asthma.

Aluminum accumulation induced testicular oxidative stress and altered selenium metabolism in mice.

Present work was carried out to investigate how testicular selenium (Se) metabolisms respond to oxidative stress induced by aluminum (Al). Mice were intraperitoneally exposed to 0, 7, or 35mg Al/kg/d for 14 days (CNL, LAL and HAL groups). Al administration significantly increased Al, reactive oxygen radical and malondialdehyde (MDA) levels, as well as decreased glutathione peroxidase (GPx) and glutathione reductase (GR) activities in serum and testes. The serum concentrations of Se were remarkably lower at LAL and HAL groups compared to the controls, whereas the testicular Se levels significantly reduced only in the HAL group. In addition, RT-PCR analysis revealed an increased testicular selenoprotein P (SelP) expression by Al treatment. Western blot analysis showed increased levels of SelP protein expression in the LAL group, but the expression levels were significantly reduced in HAL group. It was suggested that altered metabolism of Se, further stimulated testicular SelP transcription that may compensate for the loss of SelP protein resulted from Al-induced oxidative damage.