Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E(2) by hypoxia-inducible factor-1α up-regulation in human periodontal ligament cells

Kim Y‐S, Shin S‐I, Kang K‐L, Herr Y, Bae W‐J, Kim E‐C. Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E₂ by hypoxia‐inducible factor‐1α up‐regulation in human periodontal ligament cells. J Periodont Res 2012; 47: 719–728. © 2012 John Wiley & Sons A/S Background and Objective: Although hypoxia‐inducible factor 1α (HIF‐1α) is up‐regulated in the periodontal pockets of periodontitis patients, the expression and precise molecular mechanisms of HIF‐1α remain unknown in human periodontal ligament cells (PDLCs). The aim of this study was to explore the effects, as well as the signaling pathway, of nicotine and lipopolysaccharide (LPS) on the expression of HIF‐1α and on the production of its target genes, including cyclooxygenase‐2 (COX‐2)‐derived prostaglandin E₂ (PGE₂), MMP‐2 and MMP‐9 in PDLCs. Material and Methods: The expression of COX‐2 and HIF‐1α proteins was evaluated using western blotting. The production of PGE₂ and MMPs was evaluated using enzyme immunoassays and zymography, respectively. Results: LPS and nicotine synergistically induced the production of PGE₂, MMP‐2 and MMP‐9, and increased the expression of MMP‐2, MMP‐9, COX‐2 and HIF‐1α proteins. Inhibition of HIF‐1α activity by chetomin or knockdown of HIF1α gene expression by small interfering RNA markedly attenuated the production of LPS‐ and nicotine‐stimulated PGE₂ and MMPs, as well as the expression of COX‐2 and HIF‐1α. Furthermore, pretreatment with inhibitors of COX‐2, p38, extracellular signal‐regulated kinase, Jun N‐terminal kinase, protein kinase C, phosphatidylinositol 3‐kinase and nuclear factor‐kappaB decreased the expression of nicotine‐ and LPS‐induced HIF‐1α and COX‐2, as well as the activity of PGE₂ and MMPs. Conclusion: These data demonstrate novel mechanisms by which nicotine and LPS promote periodontal tissue destruction, and provide further evidence that HIF‐1α is a potential target in periodontal disease associated with smoking and dental plaque.     

Effects of Schisandra chinensis Baillon (Schizandraceae) on lipopolysaccharide induced lung inflammation in mice

Aim of the study

This study was aimed to evaluate the neuroprotective and anti-aging activity of extracts in Caenorhabditis elegans from the roots and leaves of Damnacanthus officinarum Huang to provide the pharmacological basis in traditional medicine.

Materials and methods

Investigations on the neuroprotective and lifespan activity were carried out, which were observed by utilizing the following models: observing the worms’ chemosensory behavior test based on the aversion index in the assay plate, neuroprotective activity of nematode by evaluating the ASH neuron survival and lifespan test in C. elegans.

Results

It has been shown that the ethanol, n-butanol and aqueous extracts in the roots possessed significantly neuroprotective effect both in chemosensory behavior test and ASH neuron survival model. The same extracts in the leaves showed similar activities in two models, but have less potency revealing by the data. Four candidate extracts, possessing excellent neuroprotective activity, extend lifespan in C. elegans. The n-butanol extracts in the root part showed best efficacy among them.

Conclusion

The results show the n-butanol and aqueous extracts are the major pharmacological plant extracts. Moreover, the neuroprotective and lifespan-extension activity effects of root extracts are superior to leave extracts, supporting the traditional application of above-ground parts of DOH in treating various diseases associated with brain disorders and anti-aging.     

Intracranial hemorrhage after carotid angioplasty: a pooled analysis.

PURPOSE: To use a pooled analysis of the literature to find the incidence of and characteristics common to intracranial hemorrhage (ICH) associated with carotid artery stenting (CAS). METHODS: A search of the English-language literature (1996-2005) was performed in PubMed to find cases of CAS-associated ICH. Information was derived from the identified case studies in 5 categories and 19 aspects: (1) incidence of CAS-associated ICH; (2) demographic data (sex, age, symptom presentation, and presence of preexisting hypertension); (3) imaging data (side of lesion, degree of maximal stenosis, lesion location, status of the contralateral carotid artery, collateral circulation, and preprocedural imaging features); 4) procedure-related characteristics (antithrombotic medication, use of cerebral protection devices, residual stenosis, symptoms, interval from the procedure to ICH, type of ICH, and blood pressure changes); and (5) clinical outcome. RESULTS: Fifty-four cases of CAS-associated ICH were reviewed: 51 cases from 36 published articles and our own 3 cases. The incidence of CAS-associated ICH was 0.63% (95% CI 0.38% to 0.97%) in studies consisting of >100 cases, which was significantly lower (p<0.0001) than that of case series consisting of <100 cases (2.69%, 95% CI 1.75% to 3.94%). Distinctive features included symptomatic lesions, severe stenosis (> or =90%), maximal stenosis in the internal carotid artery (ICA) distal to the bifurcation, and preexisting cerebral infarction. CONCLUSION: The incidence of CAS-associated ICH was significantly lower in series consisting of >100 cases. More caution should be directed toward patients with symptomatic lesions, severe stenosis, maximal ICA stenosis distal to the carotid bifurcation, and preexisting cerebral infarction.     

Homogeneity and tolerance to heat of monolayer MoS2 on SiO2 and h-BN

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy. For MoS₂ on SiO₂, the PL spectra of the basal plane differ from those of the edge, but MoS₂ on hexagonal boron nitride (h-BN) was electron-depleted with a homogeneous PL spectra over the entire area. Annealing at 450 °C rendered MoS₂ on SiO₂ homogeneously electron-depleted over the entire area by creating numerous defects; moreover, annealing at 550 °C and subsequent laser irradiation on the MoS₂ monolayer caused a loss of its inherent crystal structure. On the other hand, monolayer MoS₂ on h-BN was preserved up to 550 °C with its PL spectra not much changed compared with MoS₂ on SiO₂. We performed an experiment to qualitatively compare the binding energies between various layers, and discuss the tolerance of monolayer MoS₂ to heat on the basis of interlayer/interfacial binding energy.

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy.     

Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-β, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-β.Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120–127; http://dx.doi.org/10.1289/ehp.1408094     

Clinical significance of intrahepatic biliary stricture in efficacy of hepatic resection for intrahepatic stones

In the Far East, hepatic resection is the definitive treatment for complicated intrahepatic stones (IHS). However, many investigators have reported that the associated intrahepatic biliary stricture is the main cause of treatment failure. A retrospective comparative study was undertaken to clarify the long-term efficacy of hepatic resection for treatment of IHS and to investigate the clinical significance of intrahepatic biliary stricture in treatment failure after hepatic resection performed in 44 patients with symptomatic IHS. The patients were divided into two study groups: group A, with intrahepatic biliary stricture (n = 28) and group B, without stricture (n = 16). Residual or recurrent stones, recurrence of intrahepatic biliary stricture, late cholangitis, and final outcomes were analyzed and compared statistically between the two groups. The patients were followed up for a median duration of 65 months after hepatectomy. The overall incidence of residual or recurrent stones was 36% and 11%, respectively, in groups A and B. The initial treatment failure rate was 50% in group A and 31% in group B. Intrahepatic biliary stricture recurred in 46% of patients in group A, while none of the group B patients had biliary stricture recurrence (P = 0.001). More than two-thirds of the restrictures in group A were identified at the primary site. The incidence of late cholangitis was higher in group A (54%) than in group B (6%) (P = 0.002). Three-quarters of the patients with cholangitis in group A had severe cholangitis, that was recurrent, and related to stones and strictures (n = 11). They and 2 asymptomatic patients in group B required secondary procedures done at a median of 12 months after hepatectomy. Final outcomes after hepatectomy with or without secondary management were good in 80%, fair in 16%, and poor in 4% of our 44 patients. Most recurrent cholangitis after hepatectomy in patients with IHS was related to recurrent intrahepatic ductal strictures. Therefore, to be effective, hepatic resection should include the strictured duct. However, with hepatectomy alone it is difficult to clear the IHS or relieve the ductal strictures completely, particularly in patients with bilateral IHS, so perioperative team approaches that include both radiologic and cholangioscopic interventions should be combined for the effective management of IHS.