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The progression of neurodegenerative diseases is associated with oxidative stress and inflammatory responses.

Previous studies have demonstrated that

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Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.

Diabetes in children and its complications are on the rise globally, which is accompanied by increasing in diabetes-related complications. Oxidative stress and inflammation induced by elevated blood sugar in diabetic patients are considered risk factors associated with the development of diabetes complications, including chronic kidney disease and its later development to end-stage renal disease. Microvascular changes within the kidneys of DM patients often lead to chronic kidney disease, which aggravates the illness. Sigesbeckia orientalis extract (SOE), reported to have strong antioxidative and excellent anti-inflammatory activities, is used in the modern practice of traditional Chinese medicine. Kidneys from three groups of control mice (CTR), mice with streptozotocin (STZ)-induced diabetes (DM), and mice with STZ-induced DM treated with SOE (DMRx) were excised for morphological analyses and immunohistochemical assessments. Only mice in the DM group exhibited significantly lower body weight, but higher blood sugar was present. The results revealed more obvious renal injury in the DM group than in the other groups, which appeared as greater glomerular damage and tubular injury, sores, and plenty of connective tissues within the mesangium. Not only did the DM group have a higher level of cytokine, tumor necrosis factor, and the oxidative stress marker, 8-hydroxyguanosine expression, but also factors of the nuclear factor pathway and biomarkers of microvascular status had changed. Disturbances to the kidneys in DMRx mice were attenuated compared to the DM group. We concluded that SOE is an effective medicine, with antioxidative and anti-inflammatory abilities, to protect against or attenuate diabetic nephropathy from inflammatory disturbances by oxidative stress and to cure vessel damage in a hyperglycemic situation.

Background Fatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD). Methods This study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. Results Patients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the pathogenesis of various vascular diseases, such as atherosclerosis and restenosis. Among the mediators of VSMC during atherosclerosis development, platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs and greatly contributes to the intimal accumulation of VSMCs. Glossogyne tenuifolia (GT, Xiang-Ru) is a traditional antipyretic and hepatoprotective herb from Penghu Island, Taiwan. This study evaluated the inhibitory effect of GT ethanol extract (GTE) and GT water extract (GTW) on proliferative and migratory activities in PDGF-BB-induced VSMCs. The experimental results demonstrated that GTE significantly inhibited the PDGF-BB-stimulated VSMC proliferation and migration, as shown by MTT, wound healing, and Boyden chamber assays. GTE was found to have a much more potent inhibitory activity than GTW. Based on the Western blot analysis, GTE significantly blocked the PDGF-BB-induced phosphorylation of NF-&kappa, B and mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), p38, and JNK, in VSMCs. In addition, GTE retarded the PDGF-BB-mediated migration through the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression in VSMCs. Three main ingredients of GT&mdash, chlorogenic acid, luteolin-7-glucoside, and luteolin&mdash, all showed significant anti-proliferative effects on PDGF-BB-induced VSMCs. As a whole, our findings indicated that GTE has the potential to be a therapeutic agent to prevent or treat restenosis or atherosclerosis.

Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 &deg, C or 11 &deg, C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-&alpha, IL-1&beta, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish&rsquo, s body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.

Glossogyne tenuifolia is a traditional antipyretic and hepatoprotective herb used in Taiwan. In this study, dehydrocostus lactone (DL, 6-hydroxy-guaia-4(15), 10(14), 11(13)-trien-12-oic acid lactone) and mokko lactone (ML, 4(15), 10(14)-guaiadien-12, 6-olide lactone) were isolated from the crude extract of G. tenuifolia. Structures of these two compounds were elucidated by spectroscopic evidence. These two sesquiterpene lactones were identified for the first time from G. tenuifolia. From cytotoxicity tests, DL inhibited the proliferation of human lung cancer A549 cells in a time-and dose-dependent manner, whereas the cytotoxicity of ML on A549 cells was unimportant. The cytometric analysis showed that the A549 cells were arrested at the sub-G1 phase by the treatment of DL. The evidence of the activation of caspase-9 and -3 verified that the death of A549 cells was through the apoptosis pathway. Other than A549 cells, DL also exhibited strong cytotoxicity on MDA-MB-231 (breast cancer) and Hep G2 (hepatoma) cells. Although DL is a known compound, to our knowledge, this work is the first to investigate its cytotoxicity on A549 cells.

The glucotoxicity caused by long-term exposure of β-cells to high glucose (HG) conditions may lead to the generation of more reactive oxygen species (ROS), reduce the activity of antioxidant enzymes, cause cell damage and apoptosis, and induce insulin secretion dysfunction. Siegesbeckia orientalis linne is a traditional folk herbal medicine used to treat snake bites, rheumatoid arthritis, allergies, and immune deficiencies. In this study, we evaluated the protective effect of S. orientalis ethanol extract (SOE) on cell death and oxidative stress in RIN-m5f pancreatic β-cells stimulated by two HG concentrations (50–100 mM). In the cell viability assay, SOE could significantly increase the survival rate of pancreatic β-cells under HG-induced conditions. For the oxidative stress induced by HG condition, the treatment of SOE effectively reduced the ROS formation, increased the content of intracellular glutathione, and up-regulated the expression of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase. As a result, the SOE treatment could decrease the glucotoxicity-mediated oxidative damage on RIN-m5F β-cells. Moreover, SOE had the function of regulating insulin secretion in pancreatic β-cells under different HG-mediated conditions. It could decrease the increasing intracellular insulin secretion under the low glucose concentration to normal level, while increase the decreasing intracellular insulin secretion under the relatively high glucose concentration to normal level. Taken together, this study suggests that SOE has a protective effect on pancreatic β-cells under the HG-stimulated glucotoxic environment.

Aims There is increasing evidence linking a shift work schedule with various adverse health effects. The present study aimed to examine the relationship between shift work and the metabolic syndrome (MetS) in male steel workers, and also the possible mechanism of shift work-related metabolic derangements. Methods A total of 1732 men aged 42 ± 8 years were enrolled in this cross-sectional study, including 862 day workers and 870 shift workers. Circulating levels of resistin were measured by ELISA using monoclonal specific antibodies. Results The shift workers had higher rates of MetS and its components (central obesity, hypertension, and hypertriglyceridemia) than the day workers. In multiple logistic regression analysis, shift work was independently associated with MetS. In further analysis, the shift workers had elevated circulating levels of resistin (13 ± 10 vs. 10 ± 7 ng/mL) and total white blood cell (WBC) count (6.865 ± 1.819 vs. 6.304 ± 1.547 109/L) than the day workers. In addition, both resistin level and total WBC count were significantly associated with shift work, MetS, and its components (body mass index, fasting glucose, triglyceride, and high-density lipoprotein-cholesterol levels), and plasma resistin levels were significantly associated with total WBC count (β = 0.34, p

Bulnesia sarmientoi (BS) has long been used as an analgesic, wound-healing and anti-inflammatory medicinal plant. The aqueous extract of its bark has been demonstrated to have anti-cancer activity. This study investigated the anti-proliferative and anti-metastatic effects of BS supercritical fluid extract (BSE) on the A549 and H661 lung cancer cell lines. The cytotoxicity on cancer cells was assessed by an MTT assay. After 72 h treatment of A549 and H661 cells, the IC50 values were 18.1 and 24.7 &mu, g/mL, respectively. The cytotoxicity on MRC-5 normal cells was relatively lower (IC50 = 61.1 &mu, g/mL). BSE arrested lung cancer cells at the S and G2/M growth phase. Necrosis of A549 and H661 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Moreover, the cytotoxic effect of BSE on cancer cells was significantly reverted by Nec-1 pretreatment, and BSE induced TNF-&alpha, and RIP-1 expression in the absence of caspase-8 activity. These evidences further support that BSE exhibited necroptotic effects on lung cancer cells. By wound healing and Boyden chamber assays, the inhibitory effects of BSE on the migration and invasion of lung cancer cells were elucidated. Furthermore, the chemical composition of BSE was examined by gas chromatography-mass analysis where ten constituents of BSE were identified. &alpha, Guaiene, (&minus, )-guaiol and &beta, caryophyllene are responsible for most of the cytotoxic activity of BSE against these two cancer cell lines. Since BSE possesses significant cytotoxicity and anti-metastatic activity on A549 and H661 cells, it may serve as a potential target for the treatment of lung cancer.

Graphical abstract, Highlights • The antioxidant and anti-inflammatory activities of the extracts of two species of Lonicera japonica were examined. • The extracts from three methods: water extraction, ethanol extraction, and supercritical-CO2 fluid extraction were compared. • The antioxidant activities of dry LJ (dLJ) extracts were superior to those of LJv extracts. • The SFE extracts of these two species all exhibited excellent anti-inflammatory activities. • The SFE extract prepared from fresh LJv flower buds exhibited the highest anti-inflammatory activity among all extracts., Lonicera japonica Thunberg (LJ) has long been used as an antipyretic, anti-inflammatory and anti-infectious agent in East Asia. The subspecies L. japonica Thunb. var. sempervillosa Hayata (LJv) is a variant that mainly grows in Taiwan. This study examined the antioxidant and anti-inflammatory activities of the extracts from the flower buds of these two species. The extracts were obtained by three extraction methods: water extraction, ethanol extraction, and supercritical-CO2 fluid extraction (SFE). The antioxidant activities of dry LJ (dLJ) extracts were superior to those of LJv extracts. Water extracts possessed higher activities than that prepared by ethanol or SFE. The total polyphenols content, total flavonoids content, and the amount of chlorogenic acid and luteolin-7-O-glucoside were all higher in the water extracts compared to the other two. The SFE extracts of these two species all exhibited excellent anti-inflammatory activities. Although the water and ethanol extracts of dLJ extracts had higher anti-inflammatory activity than that of LJv extracts, the SFE extracts prepared from fresh LJv flower buds (fLJv) exhibited the highest activity among all extracts. The SFE effectively isolates the bioactive components of L. japonica and can obtain the L. japonica extracts with high anti-inflammatory activity.

Background: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresylsulfate (PCS) are uremic toxins with similar protein binding, dialytic clearance, and proinflammatory features. Pruritus in CKD may correlate better with uremic toxins than the glomerular filtration rate (GFR), suggesting that uremic toxins either in the central nervous system or peripherally may play an important role in the pathophysiology. Objective: We sought to investigate the potential contribution of serum total IS and PCS to the pathogenesis of pruritus. Methods: The serum levels of total IS and PCS concentrations were measured in all patients by using the Ultra Performance LC System. The characteristics of pruritus were assessed using a visual analog scale score and an interview questionnaire. Results: Among the 320 CKD patients, 35% had pruritus. The patients with pruritus were older and had a higher frequency of diabetes mellitus, higher uric acid, calcium, phosphorus, creatinine, high-sensitivity C-reactive protein, and total IS and PCS levels, and lower albumin concentrations and estimated GFR (eGFR) than those without pruritus. Increasing concentrations of total PCS were independently and significantly associated with pruritus. Multiple logistic regression analysis revealed total PCS as an independent association factor for pruritus, even after full adjustment of known biomarkers. Furthermore, serum total PCS levels were positively associated with calcium, phosphorus, blood urea nitrogen, creatinine, and white blood cell count, and negatively associated with eGFR, hemoglobin, and hematocrit. Conclusion: Our results indicate that total PCS may play a role in the pathogenesis of pruritus.

Background Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. Methods Eighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Results Pearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 μg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 μg/ml was associated with LVH. Conclusions HA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients.

Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

In this study, the lignans in the seed of Schisandra chinensis were extracted by supercritical fluid extraction (SFE), and the lignans in the obtained seed oil were subsequently separated by simulated moving bed (SMB) chromatography with supercritical fluid as the desorbent (SF-SMB). Four lignans: Schisandrol A, Schisandrol B, Schisandrin A and Schisandrin B, in the seed oil are monitored to study the extraction and separation. Effects of the extraction temperature (40–60 °C), pressure (20–35 MPa) and the content of ethanol as a cosolvent (0–10.8 wt%) on the yield of seed oil were investigated. Sovova's equation was applied to fit the experimental results to investigate the extraction kinetics. A three-section SMB with six packed columns configured as 2/2/2 was employed to separate the lignans in the seed oil. Preparative silica gel was selected as the adsorbent, and 2-propanol was used as the cosolvent for supercritical carbon dioxide at 40 °C and 13.6 MPa. The separation of lignans by the SF-SMB was conducted by creating a slight concentration gradient of 2-propanol (14.8–15.5%) along the six packed columns. The experimental results showed that Schisandrol A with 42.9 wt% and Schisandrin B with 4.34 wt% can be individually separated from the seed oil, and the separation of Schisandrol A and B and Schisandrin A and B was successfully achieved. This study demonstrates that the extraction and separation of bioactive ingredients from herbs can be finished by solely using the supercritical fluid related technologies.

Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 μg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 ± 1.5 μg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC50 = 362.3 ± 9.2 μg/mL) and α-amylase (IC50 = 119.0 ± 17.7 μg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC50 = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC50 = 626.6 ± 15.0 μg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5–0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders.

Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) 65 years old (adjusted OR, 1.10; 95% CI, 1.00–1.20; p = 0.045), however, the association was not significant for those 65 years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65 years.

Additional file 4. Inhibitory proliferative effect of GTE on PHA-stimulated PBMCs from four individuals. Data are expressed as CPM of 3H-thymidine incorporation and represented as mean Âą SD.

Increased visfatin expression has been shown to increase gene expression, which promotes cell survival and increases SirT1 activity thereby promoting angiogenesis. Previous studies have shown that oral squamous cell carcinomas (OSCCs) express high levels of activated signal transducer and activator of transcription 3 (Stat3). Since visfatin expression is increased by Stat3, we hypothesized that visfatin protein may be highly expressed in OSCCs. Immunohistochemistry was the technique used to examine the expression of visfatin in 19 OSCCs and 4 hyperplastic lesions. The results indicated that visfatin was detected in the cytoplasm and nuclei of the OSCCs and epithelial hyperplasia as well as in the stromal tissues of patients with OSCC and oral hyperplasia. Furthermore, co-expression of visfatin and proliferating cell nuclear antigen proteins was noted in verrucous epithelial hyperplasia, and co-expression of visfatin and CD68 in the inflammatory cells of the stromal region was noted in the OSCCs. In addition, enzyme-linked immunosorbent assay showed that plasma visfatin concentrations were significantly increased in the patients with OSCC and oral hyperplasia compared to those of the control subjects. In conclusion, visfatin expression and concentrations were higher in OSCCs and oral hyperplasia, suggesting that visfatin may play a role in the pathogenesis of oral cancers.

Background The purpose of this study was to investigate whether the pretreatment total and differential leukocyte counts can predict the prognosis of patients with oral cavity cancer. Methods In a retrospective analysis of patients treated between 2004 and 2011, medical records of 202 patients with oral cavity cancer were evaluated. Results Patients with oral cavity cancer, the peripheral total white blood cell (WBC) count, monocyte, and neutrophil counts and neutrophil lymphocyte ratio increased with the advancement of clinical stage. In contrast, the lymphocyte count decreased. Further, total WBC, monocyte, and neutrophil counts were increased in those with pathologic stage T4 and poor tumor differentiation, and the monocyte count was also increased in those with lymph node metastasis. Moreover, the pretreatment circulating monocyte count was an independent prognostic factor for cancer-specific survival. Conclusion A higher pretreatment circulating monocyte count can be considered as a useful prognostic marker in patients with oral cavity cancer. © 2014 Wiley Periodicals, Inc. Head Neck 36: 947–953, 2014

Receptor activator of nuclear factor kappa B ligand (RANKL)-induced activation of NF-κB and MAPKs signaling pathways is critical to osteoclastogenesis. Glossogyne tenuifolia has been used as an antipyretic, detoxification and anti-inflammatory herb tea in Penghu Island, Taiwan. This study investigated the effects of G. tenuifolia ethanolic extract (GTE) on the formation of RANKL-activating osteoclasts and expression of signaling pathways using a RAW264.7 cells model. GTE significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts in a dose-dependent manner. GTE inhibited RANKL-induced activation of nuclear factor of activated T-cells (NFATc1) and suppressed the phosphorylation of NF-κB/p65 and JNK. Additionally, GTE reduced the phosphorylated forms of osteoclast survival-related signaling molecules, including NF-κB, JNK, p38 and Akt. Taken together, these results reveal that GTE may have potential in the development of health food against osteoclast-related diseases such as osteoporosis.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with limited therapeutic options, and high recurrence and mortality rates. In this study, the anti-tumorigenic properties of luteolin on GBM were examined in vitro. Luteolin was isolated from the whole plant of Glossogyne tenuifolia and the chemical structure was determined by its spectroscopic data. The inhibitory effect of luteolin on the proliferation of GBM 8401 and U87 human glioblastoma cells and the apoptotic effect of this compound on GBM 8401 cells were investigated. Luteolin inhibited the growth of GBM 8401 and U87 cells in a dose- and time-dependent manner. It significantly induced S and G2/M phase cell cycle arrest and apoptotic cell death by decreasing the expression of cyclin-dependent kinase (CDK1), cyclin B1, and anti-apoptotic proteins (Bcl-2, Mcl-1). In addition, luteolin increased the expression of pro-apoptotic proteins (Bid, Bak, Bax, Bad) and activated caspase-3, with a concomitant increased in the levels of cleaved poly-ADP-ribose polymerase (PARP). Moreover, luteolin reduced the cell migration of GBM 8401 cells. Combination treatment of luteolin with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an anticancer drug used in clinical GBM treatment, enhanced significantly the cytotoxic effect of BCNU in GBM 8401 cells. These results suggest that luteolin may be a potential candidate for GBM adjuvant therapy.

An immune-enhancing strain, Lactobacillus plantarum Pi06, isolated from a healthy infant was used for biomass production following optimization of the medium in shake-flask culture. Preliminary studies showed that commercial MRS medium and cultivation under static conditions generated higher biomass production than four other tested media with or without a shaking condition. The selected medium composition, consisting of glucose, yeast extract, soy peptone, ammonium citrate, and corn steep liquor, was further optimized using a systematic method that integrated the Taguchi array design and the Box-Behnken method. The response effects of these factors were first investigated using Taguchi design under an L 16 (45) array. The suggested medium composition, derived from Statistica 7.1 using the Taguchi design, was applied to cultivate cells and a biomass of 7.16 g dry cell weight (DCW)/L was obtained. Response surface methodology based on the Box-Behnken method for the three response variables of glucose, yeast extract, and corn steep liquor was then used to further increase the biomass level to 8.94 g DCW/L. The resulting optimum medium consisted of 35 g/L glucose, 35 g/L yeast extract, and 40 mL/L corn steep liquor. Compared with the initial medium, the biomass yield was improved from 4.31 to 8.94 g DCW/L, an enhancement of approximately 107%.

Our previous study has demonstrated that the ethyl acetate (EA) extract of Glossogyne tenuifolia has strong cytotoxicity toward several human cancer cells including lung cancer cells. In this work, a bioactive fraction (Fr. C) that exhibited significant antiproliferative activity on A549 human lung cancer cells (IC 50 = 18.2 μg/ml) and had less sensitive effect on MRC-5 normal lung fibroblast cells (IC 50 = 34.4 μg/ml) was obtained from the column chromatographic fractionation of EA extract. Cytometric analysis results indicated that the A549 cells were arrested at the G 0 /G 1 phase by treating this fraction. The Fr. C induced the apoptosis of A549 cells through the mitochondrial pathway by down-regulating Bcl-2 and Bcl-xL protein expression, up-regulating Bad and Bax protein expression and activating caspase-9 and caspase-3. From the GC–Mass spectrometric analysis, mokko lactone (4(15),10(14)-guaiadien-12,6-olide lactone), phytol (3,7,11,15-tetramethyl-2-hexadecen-1-ol), glossogin (1′-acetoxy-4-O-isovalyryleugenol), and dehydrocostus lactone (DL, 6-hydroxy-guaia-4(15),10(14),11(13)-trien-12-oic acid lactone) were the main components of Fr. C. The cytotoxic test demonstrated that DL (IC 50 = 6.3 μg/ml), phytol (IC 50 = 11.7 μg/ml) and glossogin (IC 50 = 48.5 μg/ml) are the major ingredients responsible for most of the cytotoxic activity on A549 cells of Fr. C.

Glossogyne tenuifolia (GT) is a traditional Chinese herb that possesses strong antioxidant activity and protects against endothelial cell (EC) injury by inhibition of free reactive oxygen species (ROS). The aim of this study was to elucidate the mechanisms by which GT prevents endothelial injury using a proteomics approach. We used a sensitive method to analyze the S- nitrosoproteins utilizing a modified biotin-switch method in order to detect the possible effects of GT on protein posttranslational modification. After treatment of vascular ECs with GT, two proteins HspA9 (IS1), beta-actin (IS2) were observed to have increased posttranslational S-nitrosylation, whereas seven proteins, vimentin (DS2, DS3 and DS5), tropomyosin 3, 4 (DS6 and DS7) and oxidative phosphorylation protein such as ATP synthase, F1 complex (DS1) and 80K-H protein (DS4), were found to have decreased posttranslational S-nitrosylation. Due to S-nitrosylation of HspA9 causing the reduction of intracellular ROS and S-nitrosylation of ATP synthase interfering with ATP production and ROS formation, our study may indicate a novel mechanism in which GT protects EC injury by the inhibition of oxidative reaction.