Monotropein promotes angiogenesis and inhibits oxidative stress-induced autophagy in endothelial progenitor cells to accelerate wound healing.

Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM-EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury-related wounds.

Endoplasmic Reticulum Stress and NF-[Formula: see text]B Pathway in Salidroside Mediated Neuroprotection: Potential of Salidroside in Neurodegenerative Diseases.

Microglial activation leads to increased production of proinflammatory enzymes and cytokines, which is considered to play crucial role in neurodegenerative diseases, however there are only a few drugs that target microglia activation. Recent studies have indicated that the Traditional Chinese Medicine, salidroside (Sal), exerted anti-inflammatory effects. According to this evidence, our present study aims to explore the effect of the Sal (a phenylpropanoid glycoside compound which is isolated from rhodiola), on microglia activation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Our results showed that Sal could significantly inhibit the excessive production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) in LPS-stimulated BV2 cells. Moreover, Sal treatment could suppress the mRNA and protein expressions of inflammatory enzymes, including Inducible Nitric Oxide Synthase (iNOS) and Cyclooxygenase-2 (COX-2). The mechanisms may be related to the inhibition of the activation of Nuclear Factor-kappaB (NF-[Formula: see text]B) and endoplasmic reticulum stress. Our study demonstrated that salidroside could inhibit lipopolysaccharide-induced microglia activation via the inhibition of the NF-[Formula: see text]B pathway and endoplasmic reticulum stress, which makes it a promising therapeutic agent for human neurodegenerative diseases.

Piceatannol inhibits the IL-1ß-induced inflammatory response in human osteoarthritic chondrocytes and ameliorates osteoarthritis in mice by activating Nrf2.

Osteoarthritis (OA) is a complex process, to which an inflammatory environment contributes markedly. Piceatannol exerts anti-inflammatory effects on several diseases. In the current study, we explored the protective effects of piceatannol on the progression of OA and investigated its molecular target. In vitro, piceatannol not only attenuated the over-production of inflammatory mediators and cytokines-such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6)-but also suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the mRNA and protein levels. Piceatannol also decreased the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which mediate extracellular matrix degradation. Mechanistically, we found that piceatannol inhibited IL-1ß-induced nuclear factor kappa B (NF-κB) activation by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Furthermore, piceatannol exerted protective effects in a mouse model of OA. Taken together, these findings indicate that piceatannol may be a potential therapeutic agent for OA.

Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation.

Impacts of human lysozyme transgene on the microflora of pig feces and the surrounding soil.

The rapid development of genetic engineering and extensive applications of genetically engineered (GE) animals have provided many research benefits, but concerns have been raised over the potential environmental impact of transgenic animals. We investigated the effects of human lysozyme (hLZ) transgenic pigs which can express hLZ in their mammary glands on the surrounding environment from the angle of the changes of pig feces and the surrounding soil, including the probability of horizontal gene transfer (HGT), the impact on microbial communities in pig gastrointestinal (GI) tracts and soil, and the influence on the total nitrogen (TN) and total phosphorus (TP) content of pig excrement and surrounding soil. Results showed that hLZ gene was not detected by polymerase chain reaction (PCR) or quantitative real-time PCR (Q-PCR) in gut microbial DNA extracts of manure or microbial DNA extracts of topsoil. PCR-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) analysis and 16S rDNA sequence analysis showed that hLZ gene had no impact on the microflora structure of pig guts or soil. Finally, TN and TP contents were not significantly different in pig manure or soils taken at different distances from the pig site (P>0.25).