ABSTRACT
Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na/H exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.
ABSTRACT
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica [Sophora flavescens Ait.]. Possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor-kappa B [NF-[kappa]B] and mitogen-activated protein kinase [MAPK]-dependent inflammatory responses in lipopolysaccharide [LPS]-activated microglia. In this paper, BV2 microglia were pretreated with different concentrations of oxymatrine [1, 10 and 20 Microg/mL] for 30 min as followed by stimulation with LPS [1 Microg/mL] for different times [30 min, 1 h, 3 h, and 6 h]. Concentrations of nitric oxide [NO], prostaglandin E[2] [PGE[2]], tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta [IL-1beta] and interleukin-6 [IL-6] in supernatant, mRNA levels of inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2], cytosolic inhibitor of kappa B-alpha [I-[kappa]B alpha] and phospho- I-[kappa]B[alpha] and nuclear p65 protein levels, and the phosphorylations of MAPK molecules such as extracellular-signal-regulated kinase [ERK] 1/2, p38 MAPK and c-Jun N-terminal kinase [JNK] were determined. It was shown that oxymatrine inhibited the productions of NO, PGE2, TNF-alpha, IL-1beta and IL-6, attenuated the mRNA levels of iNOS and COX-2, suppressed the phosphorylation of I-[kappa]B[alpha] in cytosol, decreased the nuclear levels of p65, and also blocked ERK, p38 and JNK pathway in LPS-stimulated BV2 microglial cells in a dose-dependent manner. According to the results; it is suggested that oxymatrine may attenuate inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in the brain disorders
ABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical application characteristics of sural neurocutaneous island flaps.</p><p><b>METHODS</b>Sural neurocutaneous island flaps were used to repair the skin defect accompanied bone and tendon exposure in the lower leg, around the ankle and foot in 21 cases, including 4 cases to repair the foreside of the foot back . Direct flap was used in 5 cases and reverse flap in 16 cases. Meanwhile the coverage and formation of sural nerve were surveyed together with the starting point of peroneal perforator.</p><p><b>RESULTS</b>All the 21 sural flaps were survived, including sural nerve (18 cases) anastomose 12 cases, single trunk 4 cases, double trunk 2 cases. The anastomose site of medial sural cutaneous nerve and the communicating branch of lateral sural cutaneous nerve was at the point of 11 - 14 cm above the ankle in 12 cases. The lower was the anastomose site, the shorter was the sural nerve. The site is 4 - 7 cm above the ankle in 15 out of 18 sural nerve perforator branch cases, and the other 3 cases is 10, 11, 11.5 cm above the ankle respectively.</p><p><b>CONCLUSIONS</b>Sural neurocutaneous island flaps are easy to separate. Major arteries are not injured. It is the ideal flap to repair the skin defect accompanied by bone and tendon exposure in lower leg, around ankle and foot. The nerve must be anastomosed when repairing the heel.</p>