Article

Potent In Vitro Protection Against PM2.5-Caused ROS Generation and Vascular Permeability by Long-Term Pretreatment with Ganoderma tsugae

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Abstract

Epidemiological studies show increased particulate matter (PM2.5) particles in ambient air are correlated with increased myocardial infarctions. Given the close association of capillaries and alveoli, the dysfunction is caused when inhaled PM2.5 particles come in close proximity to capillary endothelial cells. We previously suggested that the inhalation of PM2.5 diesel exhaust particles (DEP) induces oxidative stress and upregulates the Nrf2/HO-1 pathway, inducing vascular permeability factor VEGFA secretion, which results in cell-cell adherens junction disruption and PM2.5 transmigratation into circulation. Here, we minimized the level that PM2.5 traveled in the bloodstream by pre-supplementing with a traditional Chinese medicine (TCM) Ganoderma tsugae DMSO extract (GTDE) prior to PM2.5 exposure. Our results show that PM2.5 caused alterations in enzyme activities and cellular anti-oxidant balance. We found decreased glutathione levels, a reduced cellular redox ratio, increased ROS generation and cytotoxicity in the cellular fractions. The oxidative stress caused DNA damage and apoptosis, likely causing downstream molecular events that trigger vasculature permeabilization and, eventually, cardiovascular disorders. Our results show long-term GTDE treatment increased endogenous glutathione level, while PM2.5-reduced glutathione levels and the cellular redox ratio. GTDE was protective against the genotoxic and apoptotic effects initiated by PM2.5 oxidative stress. Vascular permeability revealed that PM2.5 only accumulated on the surface of cells after GTDE treatment; no penetration was detected. After two weeks of GTDE treatment, VEGFA secretion was significantly reduced in human umbilical vein endothelial cells (HUVEC) and endothelial cell migration was blocked. Our results suggest GTDE prevents PM2.5 transmigration into the bloodstream, and the resultant dysfunction, by inhibiting oxidative stress production and endothelial permeability.

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... Dr. Hseu provided and authorized us to use the water extract for this study. The crude mixture contained 1.96% triterpenes and 3.93% polysaccharides [75]. The dried extract was further analyzed for the contents of total water-soluble polysaccharides, total triterpenoids, beta-Dglucans, and heavy metals. ...
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... Finally, they identified a major active ingredient in GTE, namely F5-2, which a peptidoglycan-like compound [72]. In addition, it has been reported that long-term GTE therapy upregulates GSH, SOD-1 and HO-1; decreases vascular permeability; and alleviates the genotoxicity and apoptosis caused by PM 2.5 in endothelial cells [73]. Korean red ginseng (KRG) is a food and drug with various pharmacological activities. ...
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... Macrophages were reported to promote angiogenesis, vascular permeability, and inflammatory cell recruitment via the activation of VEGFA, inducing human atherosclerotic plaque progression and rupture [38]. Furthermore, the oxidative stress induced vascular permeability factor VEGFA secretion, which was related to increased myocardial infarctions [39]. In our study, we observed that VEGFA was upregulated in MI patients, which was also supported by the above studies. ...
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... Many studies have confirmed that PM2.5 could increase ROS production. ROS increased in peripheral blood supernatants, lung and heart tissues in mice exposed to PM2.5 [6][7][8][9]. Excessive ROS could cause a series of damage to airway epithelial cells and alveolar cells, including structural damage, activation of inflammatory-related transcription factors, and the release of inflammatory mediators [10][11][12]. Frossi et al. found that oxidative stress increased Th2-mediated inflammatory response, the severity of asthma, the bronchial hyperresponsiveness, and promoted airway remodeling [13]. ...
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... A second physiological property of Ganoderma is the protection of cardiac capillary permeability against penetration of small particles that can damage underlying cardiac muscle and similar protection of the gut lining against increased permeability [127,128]. Urothelial permeability can be easily evaluated in our in vivo and in vitro bladder models using a variety of methodologies [129][130][131]. Thus, the rabbit urinary bladder is an excellent model to study the beneficial effects of GL on the response of organ system to oxidative stress. ...
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Thesis
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We compare the relative toxicity of various organic aerosol (OA) components identified by an Aerosol Mass Spectrometer (AMS) based on their ability to generate reactive oxygen species (ROS). Ambient fine aerosols were collected from urban (three in Atlanta, GA and one in Birmingham, AL) and rural (Yorkville, GA and Centerville, AL) sites in the Southeastern United States. The ROS generating capability of the water-soluble fraction of the particles was measured by the dithiothreitol (DTT) assay. Water-soluble PM extracts were further separated into the hydrophobic and hydrophilic fractions using a C-18 column, and both fractions were analyzed for DTT activity and water-soluble metals. Organic aerosol composition was measured at selected sites using a High-Resolution Time-of-Flight AMS. Positive matrix factorization of the AMS spectra resolved the organic aerosol into isoprene-derived OA (Isop_OA), hydrocarbon-like OA (HOA), less-oxidized oxygenated OA, (LO-OOA), more-oxidized OOA (MO-OOA), cooking OA (COA), and biomass burning OA (BBOA). The association of the DTT activity of water-soluble PM2.5 (WS_DTT) with these factors was investigated by linear regression techniques. BBOA and MO-OOA were most consistently linked with WS_DTT, with intrinsic water-soluble activities of 151±20 and 36±22 pmol/min/μg, respectively. Although less toxic, MO-OOA was most widespread, contributing to WS_DTT activity at all sites and during all seasons. WS_DTT activity was least associated with biogenic secondary organic aerosol. The OA components contributing to WS_DTT were humic-like substances (HULIS), which are abundantly emitted in biomass burning (BBOA) and include highly oxidized OA from multiple sources (MO-OOA). Overall, OA contributed approximately 60% to the WS_DTT activity, with the remaining probably from water-soluble metals, which were mostly associated with the hydrophilic WS_DTT fraction.
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Background: Urothelial cancer (UC) is a common cancer among males. Once metastatic or chemoresistant diseases develop, there is little effective treatment available. A fungal immunomodulatory protein, ganoderma tsugae (FIP-gts) possesses antitumor activity against solid tumors and inhibits telomerase activity. FIP-gts induces autophagy in cancer cells and may provide an alternative pathway against chemo-resistance. Materials and methods: Two UC cell lines were used to investigate the cytotoxicity effects and the autophagy regulation of FIP-gts using flow cytometry, acidic vesicular organelles (AVO) staining and western blotting. Results: MTT assay showed that FIP-gts and bafilomycin-A1 (Baf-A1) and or chloroquine (CQ) could enhance a significantly synergistic cytotoxicity. The treatment of UC cell lines with FIP-gts activated LC-3 II formation and AVO positive staining on western blot and flow cytometry. Interestingly, FIP-gts and Baf-A1 combined treatment was found to lead to enhancement of apoptosis along with inhibition of autophagy in parental and resistant UC cells. Conclusion: FIP-gts may have the potential to be utilized as a therapeutic adjuvant for the treatment of resistant UC cancer down-regulating Beclin-1 to activate autophagic cell death.
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Diesel exhaust has been classified as a potential carcinogen and associated with various health effects. A previous study showed that the doses for manifesting the mutagenetic effects of diesel exhaust could be reduced when co-exposed with ultraviolet-A (UVA) in a cellular system. However, the mechanisms underlying synergistic effects remain to be clarified, especially in an in vivo system. In the present study, using Caenorhabditis elegans (C. elegans) as an in vivo system we studied the synergistic effects of diesel particulate extract (DPE) plus UVA, and the underlying mechanisms were dissected genetically using related mutants. Our results demonstrated that though co-exposure of wild type worms at young adult stage to low doses of DPE (20 μg/ml) plus UVA (0.2, 0.5 and 1.0 J/cm2) did not affect the worm development (mitotic germ cells and brood size), it resulted in a significant induction of germ cell death. Using the strain of hus-1::gfp, distinct foci of HUS-1::GFP was observed in proliferating germ cells, indicating the DNA damage after worms were treated with DPE plus UVA. Moreover, the induction of germ cell death by DPE plus UVA was alleviated in single-gene loss-of-function mutations of core apoptotic, checkpoint HUS-1, CEP-1/p53 and MAPK dependent signaling pathways. Using a ROS probe, it was found that the production of ROS in worms co-exposed to DPE plus UVA increased as a time-dependent manner. In addition, employing a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron spin resonance analysis, the increased 1O2 production was demonstrated in worms co-exposed to DPE plus UVA. These results indicated that UVA could enhance the apoptotic induction of DPE at low doses through a DNA damage-trigged pathway, and the production of ROS, especially 1O2, played a pivotal role in initiating the synergistic process.
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Considerable evidence shows a key role for protein modification in the adverse effects of chemicals; however, the interaction of diesel exhaust particles (DEP) with proteins and the resulting biological activity remains unclear. DEP and carbon black (CB) suspensions with and without bovine serum albumin (BSA) were used to elucidate the biological effects of air pollutants. The DEP and CB samples were then divided into suspensions and supernatants. Two important goals of the interaction of DEP with BSA were as follows: (1) understanding BSA modification by particles and (2) investigating the effects of particles bound with BSA and the corresponding supernatants on cellular oxidative stress and inflammation. We observed significant free amino groups production was caused by DEP. Using liquid chromatography-mass spectrometry (LC-MS), we observed that BSA was significantly oxidised by DEP in the supernatants and that the peptides ETYGDMADCCEK, MPCTEDYLSLILNR and TVMENFVAFVDK, derived BSA-DEP conjugates, were also oxidised. In A549 cells, DEP-BSA suspensions and the corresponding supernatants reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) production and increased interleukin-6 (IL-6) levels when compared to DEP solutions without BSA. Our findings suggest that oxidatively modified forms of BSA caused by DEP could lead to oxidative stress and the activation of inflammation.
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Ganoderma mushrooms (Lingzhi in Chinese) have well-documented health benefits. Ganoderma tsugae (G. tsugae), one of the ganoderma species, has been commercially cultivated as a dietary supplement. Because G. tsugae has high antioxidant activity and because oxidative stress is often associated with cardiac injury, we hypothesized that G. tsugae protects against cardiac injury by alleviating oxidative stress. We tested the hypothesis using a work-overload-induced myocardial injury model created by challenging mice with isoproterenol (ISO). Remarkably, oral G. tsugae protected the mice from ISO-induced myocardial injury. Moreover, the triterpenoid fraction of G. tsugae, composed of a mixture of nine structurally related ganoderic acids (GAs), provided cardioprotection by inhibiting the ISO-induced expression of Fas/Fas ligand, oxidative stress, and apoptosis. The antioxidant activity of GAs was tested in cultured cardio-myoblast H9c2 cells against the insult of H2 O2 . GAs dissipated the cellular reactive oxygen species imposed by H2 O2 and prevented cell death. Our findings uncovered the cardioprotective activity of G. tsugae and identified GAs as the bioactive components against cardiac insults.
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Particulate pollution is a major public health concern because epidemiological studies have demonstrated that exposure to particles is associated with respiratory diseases and lung cancer. Diesel exhaust particles (DEP), which is classified as a human carcinogen (IARC, 2012), are considered a major contributor to traffic-related particulate matter (PM) in urban areas. DEP consists of various compounds, including PAHs and metals which are the principal components that contribute to the toxicity of PM. The present study aimed to investigate effects of PM on induction of oxidative DNA damage and inflammation by using lymphocytes in vitro and in human exposed to PM in the environment. Human lymphoblasts (RPMI 1788) were treated with DEP (SRM 2975) at various concentrations (25-100μg/ml) to compare the extent of responses with alveolar epithelial cells (A549). ROS generation was determined in each cell cycle phase of DEP-treated cells in order to investigate the influence of the cell cycle stage on induction of oxidative stress. The oxidative DNA damage was determined by measurement of 8-hydroxy-deoxyguanosine (8-OHdG) whereas the inflammatory responses were determined by mRNA expression of interleukin-6 and -8 (IL-6 and IL-8), Clara cell protein (CC16), and lung surfactant protein-A (SP-A). The results showed that RPMI 1788 and A549 cells had a similar pattern of dose-dependent responses to DEP in terms of particle uptake, ROS generation with highest level found in G2/M phase, 8-OHdG formation, and induction of IL-6 and IL-8 expression. The human study was conducted in 51 healthy subjects residing in traffic-congested areas. The effects of exposure to PM2.5 and particle-bound PAHs and toxic metals on the levels of 8-OHdG in lymphocyte DNA, IL-8 expression in lymphocytes, and serum CC16 were evaluated. 8-OHdG levels correlated with the exposure levels of PM2.5 (P<0.01) and PAHs (P<0.05), but this was not the case with IL-8. Serum CC16 showed significantly negative correlations with B[a]P equivalent (P<0.05) levels, but positive correlation with Pb (P<0.05). In conclusion, a similar pattern of the dose-dependent responses to DEP in the lymphoblasts and lung cells suggests that circulating lymphocytes could be used as a surrogate for assessing PM-induced oxidative DNA damage and inflammatory responses in the lung. Human exposure to PM leads to oxidative DNA damage whereas PM-induced inflammation was not conclusive and should be further investigated.
Article
To evaluate the effect of Chinese herbs decoction on endocrine therapy- associated hot flashes symptom in breast cancer patients. Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups, the control group received endocrine therapy alone, the other group is administered with Chinese herbs decoction besides the endocrine therapy: decoction was administered above 6 months per year for more than 2 years. Frequency of hot flashes per day was recorded, and the effect of decoction on hot flashes symptom being assessed with Kupperman Scoring Index. Sixty cases were analyzed, 32 cases in endocrine therapy combining Chinese herbs decoction group, 28 cases in mere endocrine therapy group. For hot flashes symptom, in Chinese herbs decoction administration group, 7 cases (21.9%) reported symptom disappeared, 22 cases (68.7%) reported symptom alleviated, 3 cases (9.4%) reported symptom not changed; in endocrine therapy alone group, 5 cases (17.9%) reported symptom disappeared, 13 cases (46.4%) reported symptom alleviated, 10 cases (10/28, 35.7%) reported symptom not changed. The difference between two groups was statistically significant (=0.013). For sleeping disorder, in Chinese herbs decoction administration group, 27 cases (84.4%) reported symptom improved, 5 cases (15.6%) reported no change; in endocrine therapy alone group, 16 cases (57.1%) symptom improved, 12 cases (42.9%) reported no change in sleeping disorder (=0.019), significance statistically. Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy, meanwhile without definite toxicity and influence on the risk of recurrence of tumor.
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Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells and acellullarly, whereas the exposure to urban dust did not generate ROS. ApoE(-/-) mice, which were exposed twice to 0.5 mg/kg of the particles by intratracheal instillation, had unaltered acetylcholine-elicited vasorelaxation in aorta segments. There was unaltered pulmonary expression level of Vcam-1, Icam-1, Hmox-1 and Ogg1. The levels of oxidatively damaged DNA were unchanged in lung tissue. The exposure to SWCNT significantly increased the expression of Ccl-2 in the lung tissue of the mice. The exposure to DEP and SWCNT was associated with elevated ROS production in cultured cells, whereas intratracheal instillation of the same particles had no effect on biomarkers of pulmonary oxidative stress and dilatory dysfunction in the aorta.
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Inhalation of diesel exhaust particles (DEPs) is associated with pulmonary and cardiovascular disease. One contributor to pathogenesis is inhaled particles reaching and injuring the lung capillary endothelial cells, and possibly gaining access to the blood stream. Using in vitro capillary tubes as a simplified vascular model system for this process, it was previously shown that DEPs induce the redistribution of vascular endothelial cell-cadherin (VE-Cad) away from the plasma membrane to intracellular locations. This allowed DEPs into the cell cytoplasm and tube lumen, suggesting the tubes may have become permeable (Chao et al., 2011). Here some of the mechanisms responsible for endothelial tube changes after DEP exposure were examined. The results demonstrate that endothelial tube cells mounted an oxidative stress response to DEP exposure. Hydrogen peroxide and oxidized proteins were detected after 24h of exposure to DEPs. Particles induced relocalization of Nrf2 from the cytoplasm to the nucleus, upregulating the expression of the enzyme heme oxygenase-1 (HO-1). Surprisingly, vascular endothelial cell growth factor-A (VEGF-A), initially termed "vascular permeability factor" (VPF), was found to be up-regulated in response to the HO-1 expression induced by DEPs. Similar to DEPs, applied VEGF-A induced relocalization of VE-Cadherin from the cell membrane surface to an intracellular location, and relocalization of VE-cadherin was associated with permeability. These data suggest that the DEPs may induce or contribute to the permeability of capillary-like endothelial tube cells via induction of HO-1 and VEGF-A.
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Particulate matter (PM) emissions involve a complex mixture of solid and liquid particles suspended in a gas, where it is noted that PM emissions from diesel engines are a major contributor to the ambient air pollution problem. While epidemiological studies have shown a link between increased ambient PM emissions and respiratory morbidity and mortality, studies of this design are not able to identify the PM constituents responsible for driving adverse respiratory health effects. This review explores in detail the physico-chemical properties of diesel PM (DPM) and identifies the constituents of this pollution source that are responsible for the development of respiratory disease. In particular, this review shows that the DPM surface area and adsorbed organic compounds play a significant role in manifesting chemical and cellular processes that if sustained can lead to the development of adverse respiratory health effects. The mechanisms of injury involved included inflammation, innate and acquired immunity, and oxidative stress. Understanding the mechanisms of lung injury from DPM will enhance efforts to protect at-risk individuals from the harmful respiratory effects of air pollutants.
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Extracts of Ganoderma tsugae, also known as the Hemlock varnish shelf mushroom, and related Reishi mushrooms are well documented in traditional Chinese medicine. Several Ganoderma sp. are currently cultivated for use in coffee, teas, and dietary supplements. We now report on the isolation and characterization of an unprecedented benzofuran, ganodone (1), from the fruiting bodies of mature growth G. tsugae. This discovery provides a key next step in evaluating the active components in their associated herbal supplements.
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15% of patients with severe endometriosis suffer from pain symptoms in spite of pharmacological and surgical treatments. In this retrospective study we aimed to assess the effectiveness of a combined therapy of Traditional Chinese medicine and hypnotherapy (systemic autoregulation therapy, SART) as a novel treatment for endometriosis-associated symptoms. 47 patients with severe endometriosis, which were treated with SART, were followed-up by standardized telephone interviews. Follow-up data were compared to baseline assessments. median follow-up time was 5 years. The median intensity of endometriosis-associated pain had decreased from 8 to 3 points on a 0-10 point visual analogue scale (p < 0.001). 18 patients (38%) were free of pain, and the number of patients using pain medication had decreased from 38 to 19 (from 81% to 40%). 17 out of the 31 women trying for a pregnancy (55%) showed a total of 21 births at follow-up. Exploratory analyses revealed that larger decreases in pain scores correlated significantly with longer treatment durations, suggesting a dose-response relationship. treatment of endometriosis with a holistic approach of Chinese medicine and hypnotherapy may result in a substantial reduction of pain as well as increased birth rates in patients with therapy-refractory endometriosis. Randomized controlled studies to further investigate the effectiveness of SART are highly warranted.
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Whether diesel exhaust particles (DEPs) potentially have a direct effect on capillary endothelia was examined by following the adherens junction component, vascular endothelial cell cadherin (VE-cadherin). This molecule is incorporated into endothelial adherens junctions at the cell surface, where it forms homodimeric associations with adjacent cells and contributes to the barrier function of the vasculature (Dejana et al., 2008; Venkiteswaran et al., 2002; Villasante et al., 2007). Human umbilical vein endothelial cells (HUVECs) that were pre-formed into capillary-like tube networks in vitro were exposed to DEPs for 24h. After exposure, the integrity of VE-cadherin in adherens junctions was assessed by immunofluorescence analysis, and demonstrated that increasing concentrations of DEPs caused increasing redistribution of VE-cadherin away from the cell-cell junctions toward intracellular locations. Since HUVEC tube networks are three-dimensional structures, whether particles entered the endothelial cells or tubular lumens was also examined. The data indicate that translocation of the particles does occur. The results, obtained in a setting that removes the confounding effects of inflammatory cells or blood components, suggest that if DEPs encounter alveolar capillaries in vivo, they may be able to directly affect the endothelial cell-cell junctions.
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Endothelial cells form cell-cell adhesive structures, called adherens and tight junctions, which maintain tissue integrity, but must be dynamic for leukocyte transmigration during the inflammatory response and cellular remodeling during angiogenesis. This review will focus on Vascular Endothelial (VE)-cadherin, an endothelial-specific cell-cell adhesion protein of the adherens junction complex. VE-cadherin plays a key role in endothelial barrier function and angiogenesis, and consequently VE-cadherin availability and function are tightly regulated. VE-cadherin also participates directly and indirectly in intracellular signaling pathways that control cell dynamics and cell cycle progression. Here we highlight recent work that has advanced our understanding of multiple regulatory and signaling mechanisms that converge on VE-cadherin and have consequences for endothelial barrier function and angiogenic remodeling.
Article
Ganoderma tsugae is a medicinal fungus with several biological activities. It has long been used as a folk remedy for the promotion of health and longevity in China and other oriental countries. Here, a bioactive fraction of G. tsugae was progressively purified to be enriched in the activity of cytoprotective enzymes. The highest bioactivity was detected in the 20% EtOH-precipitated fraction, which was prepared from submerged fermentation filtrate of G. tsugae. Following further purification by gel filtration chromatography and acetone extraction, the most bioactive fraction, F5-2, was identified as a peptidoglycan-like compound. Extracts of G. tsugae (F5-2) induced heme oxygenase-1 (HO-1) and thioredoxin reductase-1 (TrxR1) expression in endothelial cells by increasing NF-E2-related factor-2 (Nrf2) nuclear translocation. Pretreatment with F5-2 increased intracellular glutathione (GSH) and protected against H(2)O(2), suggesting that induction of these antioxidant enzymes is important in protection against oxidative stress. Hence the bioactive peptidoglycan-like compound from G. tsugae might protect endothelial cells.
Article
Heme oxygenase-1 apart from converting heme to carbon monoxide, iron and biliverdin has been shown to exert anti-inflammatory, antiapoptotic and antioxidant actions. The present review summarizes the most recent studies about heme oxygenase-1 involvement in atherosclerosis, neovascularization and endothelial progenitor cells biology. Heme oxygenase-1 has been shown to be protective against atherosclerosis via decreasing ROS generation and proinflammatory cytokine production resulting in diminished lipid uptake and foam cell formation. Moreover, heme oxygenase-1 role in neovascularization and its involvement in response of endothelial progenitor cells to stromal cell derived factor-1 as well as endothelial cells to vascular endothelial growth factor has been stressed, recently. The detailed mechanisms of heme oxygenase-1 action in the processes of vasculogenesis and angiogenesis as well as the involvement of Nrf2 and KLF2 transcription factors in heme oxygenase-1-dependent vascular protection are among the subjects most intensively studied, currently. Recent studies underscore the critical role of heme oxygenase-1 in neovascularization, implicating heme oxygenase-1 as an attractive therapeutic target for treatment of cardiovascular disease.
Article
This chapter discusses medicinal benefits of the Mushroom Ganoderma. Recently, the fruit body and liquid-cultured mycelium of Ganoderma have been reported to contain polysaccharides which inhibit the growth of tumors. Identified as glucans, one of the major constituents in the cell wall of fungi, they appear to increase bodily resistance against the growth of tumors, induce the production of interferon, enhance the immunity function, and kill tumor cells within the body. The role of medicinal mushrooms in metabolic regulation is gaining greater attention. Their use in the development and application of beneficial biological activities offers an advantage in that the active principle is safe and can be tolerated by humans. Cultivation of such mushrooms provides an adequate supply but is unnecessary if mycelial cultures grown in large-scale fermentations can produce the same active principle. Finally, the search for new uses for the traditional medicinal fungi continues and the public should be educated about their potential value.
Article
A systematic method of extraction, fractionation, and purification of polysaccharides from Songshan Lingzhi (Ganoderma tsugae) with antitumor activity was established. Seven glycans with strong antitumor activities were obtained from 14 water-soluble, and 15 water-insoluble fractions: FIo-a, FA-1, FII-1, FIII-2, and FIII-2-a, -b, and -c. FIo-a and FA-1 were protein-containing glucogalactans associated with mannose and fucose. FII-1 was a (1-->3)-beta-D-glucan having a lower protein content. The water-insoluble fractions FIII-2-a, -b, and -c were extracted with alkali, and were found to be protein-containing (1-->3)-beta-D-glucans showing the strongest activity. Chemical properties and structure of each antitumor polysaccharide were compared with three fungi of the Ganoderma family, Kofukitake (G. applanatum), Mannentake (G. lucidum), and Songshan Lingzhi (G. tsugae).
Article
Residents of the dense urban core neighborhoods of New York City (NYC) have expressed increasing concern about the potential human health impacts of diesel vehicle emissions. We measured concentrations of particulate matter [less than/equal to] 2.5 micro in aerodynamic diameter (PM(2.5)) and diesel exhaust particles (DEP) on sidewalks in Harlem, NYC, and tested whether spatial variations in concentrations were related to local diesel traffic density. Eight-hour (1000-1800 hr) air samples for PM(2.5 )and elemental carbon (EC) were collected for 5 days in July 1996 on sidewalks adjacent to four geographically distinct Harlem intersections. Samples were taken using portable monitors worn by study staff. Simultaneous traffic counts for diesel trucks, buses, cars, and pedestrians were carried out at each intersection on [Greater/equal to] 2 of the 5 sampling days. Eight-hour diesel vehicle counts ranged from 61 to 2,467 across the four sites. Mean concentrations of PM(2.5) exhibited only modest site-to-site variation (37-47 microg/m(3)), reflecting the importance of broader regional sources of PM(2.5). In contrast, EC concentrations varied 4-fold across sites (from 1.5 to 6 microg/m(3)), and were associated with bus and truck counts on adjacent streets and, at one site, with the presence of a bus depot. A high correlation (r = 0.95) was observed between EC concentrations measured analytically and a blackness measurement based on PM(2.5) filter reflectance, suggesting the utility of the latter as a surrogate measure of DEP in future community-based studies. These results show that local diesel sources in Harlem create spatial variations in sidewalk concentrations of DEP. The study also demonstrates the feasibility of a new paradigm for community-based research involving full and active partnership between academic scientists and community-based organizations.
Article
48 patients with liver fibrosis due to hepatitis B were treated for 2 years with the drugs for tonifying the kidney, supplementing qi, cooling and invigorating the blood and detoxification. The symptoms were markedly improved, and serum ALT and bilirubin were recovered and kept normal in most of the cases. The mean levels of serum hyaluronic acid, procollagen peptide III and circulating immune complex were decreased and returned to normal after the treatment. B-ultrasonography showed that the portal vein kept in normal size in 82% of the patients, the enlarged portal vein diminished in diameter, and the enlarged spleen reduced.
Article
Episodes of increased air pollution are associated with increases in hospital admissions for cardiovascular disease. Even modest acute phase responses are associated with increased risk of coronary heart disease. The study investigates whether induction of an acute phase response by exposure to air pollution may contribute to cardiovascular pathology. A prospective cohort study based on a survey in 1984/85 with a 3-year follow-up was conducted in 631 randomly selected men aged 45 to 64 years free of cardiovascular disease at entry 1984/85. Serum C-reactive protein concentrations were determined by a high sensitivity immunoradiometric assay. C-reactive protein concentration was increased in association with the 1985 air pollution episode. In multivariate analyses, elevated concentrations were independently associated with concentrations of total suspended particles and the sulphur dioxide episode. At ambient concentrations of pollution, as noted during the 1985 air pollution episode, the odds of observing C-reactive protein concentrations above 5.7 mg. l(-1)(>90th percentile) tripled, and increases of 26 microg. m(-3)total suspended particles (mean of 5 days) raised the odds of C-reactive protein levels 50% above the 90th percentile. Exposure to current levels of particulate matter in the atmosphere elicits an acute phase response in randomly selected healthy middle-aged men, which may contribute to the increased cardiovascular risk caused by air pollution.
Article
The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca(2+)/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.
Article
Two nationwide surveys were carried out using an electronic poll of 2,000 GPs and postal questionnaires were sent to 30,000 patients with osteoarthritis (OA). Both surveys found a high level of gastro-intestinal (GI) side-effects in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Almost every GP (97%) reported experience of patients suffering GI symptoms while on an NSAID, 38% reported patients who had been hospitalised and 4% reported patients who had died owing to NSAID-induced side-effects. Most GPs (92%) said they were concerned about GI safety when prescribing an NSAID and almost a third (32%) said they were concerned about litigation from patients who had experienced a bleed. Use of NSAIDs in OA remained high, with 44% of GPs prescribing conventional NSAIDs to at least three quarters of their patients, 57% of GPs using simple analgesia and just 12% using a cyclo-oxygenase-2 (COX-2) selective inhibitor in over 74% of patients. Some 45% of patients reported receiving NSAIDs compared with 43% on simple analgesia and 4% on COX-2 selective inhibitors. Most GPs (69%) stated that their main therapeutic objective in using an NSAID to treat OA was to control pain without GI side-effects. Almost a quarter (24%) said they used low-dose NSAIDs in the hope that this would control pain without GI side-effects. Dissatisfaction with treatment was the most common reason reported by GPs for patients on an NSAID to re-present, with 73% citing either breakthrough pain or incomplete pain relief as the most common reason for patient dissatisfaction. This mirrored the patients' perception, with 63% citing inadequate pain relief as their main reason for dissatisfaction with current painkillers compared to 17% who cited stomach upsets or irritation. Patient and GP appear to be united in their concern at the GI risks of NSAID treatment. In the light of this and recent data on the efficacy, safety profile and cost-effectiveness of COX-2 selective inhibitors, GPs should re-examine their medical management of OA.
Article
Particulate air pollution is associated with cardiorespiratory effects and ultrafine particles (UFPs, diameter < 100 nm) are believed to play an important role. We studied the acute (1 h) effect of intratracheally instilled unmodified (60 nm), negatively charged carboxylate-modified (60 nm), or positively charged amine-modified (60 or 400 nm) polystyrene particles on bronchoalveolar lavage (BAL) indices and on peripheral thrombosis in hamster. The latter was assessed by measuring the extent of photochemically induced thrombosis in a femoral vein via transillumination. Unmodified and negative UFPs did not modify thrombosis and BAL indices. Positive UFPs increased thrombosis at 500 microg per animal (+ 341 +/- 96%) and at 50 microg per animal (+ 533 +/- 122%), but not at 5 microg per animal. Neutrophils, lactate dehydrogenase, and histamine were increased in BAL at all these doses but protein concentration was increased only at 500 microg per animal. Positive 400-nm particles (500 microg per animal) did not affect thrombosis, although they led to a neutrophil influx and an increase in BAL proteins and histamine. Using the Platelet Function Analyser (PFA-100), the platelets of hamsters were activated by the in vitro addition of positive UFPs and 400-nm particles to blood. We conclude that intratracheally administered positive ultrafine and 400-nm particles induce pulmonary inflammation within 1 h. Positive UFPs, but not the 400-nm particles enhance thrombosis. Hence, particle-induced lung inflammation and thrombogenesis can be partially uncoupled.