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Exposure to particulate matter 2.5 (PM2.5) has been linked to ocular surface diseases, yet knowledge of the molecular mechanism impacted on retina pathogenesis is limited. Therefore, the purpose of this study was to explore the effects and involved factors of PM2.5 exposure in human retinal pigment epithelial APRE-19 cells. Our data revealed a decreased cell viability and an increased migratory ability in APRE-19 cells after PM2.5 stimulation. The MMP-2 and MMP-9 protein levels were markedly increased while the MMPs regulators TIMP-1 and TIMP-2 were significantly reduced in PM2.5-exposed APRE-19 cells. PM2.5 also increased pro-MMP-2 expression in the cell culture supernatants. Additionally, PM2.5 promoted the EMT markers through the activation of PI3K/AKT/mTOR pathway. Moreover, the ICAM-1 production was also remarkably increased by PM2.5 but reduced by PI3K/AKT inhibitor LY294002 in APRE-19 cells. Taken together, these results suggest that PM2.5 promotes EMT in a PI3K/AKT/mTOR-dependent manner in the retinal pigment epithelium.

Fine particulate matter (PM2.5) is the critical cause of lung cancer and can further promote tumor cell migration and invasion. This study investigated the effects of luteolin, an antiangiogenic flavonoid agent, on blocking aqueous extract PM2.5-prompted cancer progression. We observed that luteolin reduced cell migration and the expression of pro-metastatic factors pro-matrix metalloproteinase (MMP)-2 and intercellular adhesion molecule (ICAM)-1 in PM2.5-exposed H460 lung cancer cells. Luteolin treatment also reduced the transduction of PM2.5-induced epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) cascade signaling. Furthermore, the reduction of MMP-2 expression and ICAM-1 production by luteolin in PM2.5-stimulated H460 cells is EGFR-PI3K-AKT pathway dependent. These results suggest that luteolin exhibits antitumor progression by inhibiting EGFR-PI3K-AKT pathway.

Photodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach. We retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance. The base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p

This study examined the effect of the Flos Lonicerae Japonicae water extract (FLJWE), chlorogenic acid, and luteolin on pseudorabies virus (PRV)-induced inflammation in RAW264.7 cells and elucidated related molecular mechanisms. The results revealed that FLJWE and luteolin, but not chlorogenic acid, inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in PRV-infected RAW 264.7 cells. We found that the FLJWE and luteolin suppressed nuclear factor (NF)-κB activation by inhibiting the phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1 and STAT3, respectively). Moreover, the FLJWE significantly upregulated the expression of pNrf2 and its downstream target gene heme oxygenase-1 (HO-1). Our data indicated that FLJWE and luteolin reduced the expression of proinflammatory mediators and inflammatory cytokines, such as COX-2 and iNOS, through the suppression of the JAK/STAT1/3-dependent NF-κB pathway and the induction of HO-1 expression in PRV-infected RAW264.7 cells. The findings indicate that the FLJWE can be used as a potential antiviral agent.

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti-inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat Pseudomonas aeruginosa (P.a.) lipopolysaccharide- (LPS-) stimulated BV2 microglial cells. THC reduced P.a. LPS–induced mortality and the production of inflammatory mediators IL-6, TNF-α, MIP-2, IP-10, and nitrite. A further investigation revealed that THC decreased these inflammatory cytokines synergistically with JAK/STAT signaling inhibitors. THC also increased Nrf2/HO-1 signaling transduction which inhibits iNOS/COX-2/pNFκB cascades. Additionally, the presence of the HO-1 inhibitor Snpp increased the levels of IP-10, IL-6, and nitrite while THC treatment reduced those inflammatory factors in P.a. LPS–stimulated BV2 cells. In summary, we demonstrated that THC exhibits anti-inflammatory activities in P.a. LPS-induced inflammation in brain microglial cells by inhibiting STAT1/3-dependent NF-κB activation and inducing Nrf2-mediated HO-1 expression.

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti-inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (α-mangostin, α-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with α-MG (0, 3.75, 7.5, and 15 μM) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with α-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1α-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that α-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that α-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.

Oxidative damage of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Quercetin, a bioactive flavonoid compound, has been shown to have a protective effect against oxidative stress-induced cell apoptosis and inflammation in RPE cells, however, the detailed mechanism underlying this protective effect is unclear. Therefore, the aim of this study was to investigate the regulatory mechanism of quercetin in a sodium iodate (NaIO3)-induced retinal damage. The clinical features of the mice, the production of oxidative stress, and the activity of autophagy and mitochondrial biogenesis were examined. In the mouse model, NaIO3 treatment caused changes in the retinal structure and reduced pupil constriction, and quercetin treatment reversed the oxidative stress-related pathology by decreasing the level of superoxide dismutase 2 (SOD2) while enhancing the serum levels of catalase and glutathione. The increased level of reactive oxygen species in the NaIO3-treated ARPE19 cells was improved by treatment with quercetin, accompanied by a reduction in autophagy and mitochondrial biogenesis. Our findings indicated that the effects of quercetin on regulating the generation of mtROS were dependent on increased levels of deacetyl-SOD2 through the Nrf2-PGC-1α-Sirt1 signaling pathway. These results demonstrated that quercetin may have potential therapeutic efficacy for the treatment of AMD through the regulation of mtROS homeostasis.

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.

Kaempferol is a flavonoid with anticancer and anti-metastasis activity in different cancer-cell lines. However, the underlying mechanisms by which kaempferol acts on human retinal pigment epithelial (ARPE-19) cells remain unclear. In this study, we demonstrated that kaempferol inhibited migration and invasion in ARPE-19 cells at non-toxic dosages. We discovered that kaempferol obviously reduced the enzyme activity and protein expression of matrix metalloproteinase-2 by increasing the phosphorylated levels of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways. Additionally, ERK1/2-specific inhibitor PD98059 significantly reversed kaempferol's inhibitory effects on migration and expression of MMP-2 in ARPE-19 cells. Overall, our results are the first to demonstrate that kaempferol is capable of inhibiting cell migration by targeting ERK1/2 signaling in human retinal pigment epithelial cells.

This study examined the effect of the Flos Lonicerae Japonicae water extract (FLJWE), chlorogenic acid, and luteolin on pseudorabies virus (PRV)-induced inflammation in RAW264.7 cells and elucidated related molecular mechanisms. The results revealed that FLJWE and luteolin, but not chlorogenic acid, inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in PRV-infected RAW 264.7 cells. We found that the FLJWE and luteolin suppressed nuclear factor (NF)-κB activation by inhibiting the phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1 and STAT3, respectively). Moreover, the FLJWE significantly upregulated the expression of pNrf2 and its downstream target gene heme oxygenase-1 (HO-1). Our data indicated that FLJWE and luteolin reduced the expression of proinflammatory mediators and inflammatory cytokines, such as COX-2 and iNOS, through the suppression of the JAK/STAT1/3-dependent NF-κB pathway and the induction of HO-1 expression in PRV-infected RAW264.7 cells. The findings indicate that the FLJWE can be used as a potential antiviral agent.

Dihydromyricetin (DHM), a flavanonol compound in Ampelopsis grossedentata, possesses several biological activities. However, the molecular mechanism underlying the effects of DHM on human proliferative vitreoretinopathy (PVR) remains unclear. We explored the effects of DHM on cell migration and the metastasis-promoting proteins in human retinal pigment epithelial (RPE) cells (ARPE-19 cells). Our results revealed that DHM attenuated ARPE-19 cell invasion and migration by reducing matrix metalloproteinase-2 (MMP-2) expression. Furthermore, a Western blot analysis revealed that DHM significantly reduced levels of phosphorylated c-Jun N-terminal kinase 1/2, but not those of extracellular signal-regulated kinase 1/2 and p38. In conclusion, our findings shown that DHM inhibits human RPE cell migration through the inhibition of MMP-2 expression; therefore, DHM may have potential therapeutic value in treating PVR as adjuvant therapy.

Oxidative stress arising from life processes or environmental influences and its resultant cellular dysfunctions are major causes of neurodegenerative disorders. The objectives of this study were to investigate whether taurine (Tau) can prevent d-galactose-induced cognitive dysfunction and brain oxidative damage. Mice given with Tau supplementation (100 and 400 mg per kg BW per day) spent shorter (p < 0.05) time in searching target in d-galactose (100 mg per kg BW per day) treated mice in a water maze reference memory experiment. Moreover, Tau supplementation extended (p < 0.05) the searching period around the target quadrant in the probe test of the water maze, and neuronal degeneration and nucleus shrinkage in the hippocampus dentate gyrus area of d-galactose treated mice were observed to be attenuated. Tau also downregulated (p < 0.05) expression of the glial fibrillary acidic protein (Gfap) and of the cluster of differentiation marker Cd11b; meanwhile, it strengthened (p < 0.05) antioxidant capacity and lowered (p < 0.05) the accumulation of advanced glycation end-products (AGEs) in the brain. Therefore, Tau could be effective to ameliorate oxidative damage and inflammation in the brain, and apoptosis of brain cells, which further lessen the cognitive dysfunction.

Recent investigations have demonstrated that carotenoid extract of Dunaliella salina alga (Alga) contains abundant β-carotene and has good anti-inflammatory activities. Murine macrophage (RAW264.7 cells) was used to establish as an in vitro model of pseudorabies virus-induced reactive oxygen species (ROS) response. In this study, antioxidant activities of Alga were measured based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, trolox equivalent antioxidant capacity assays, reducing power, and virus-induced ROS formation in RAW264.7 cells. Anti-inflammatory activities of Alga were assessed by its ability to inhibit the production of interleukin-6 and nitric oxide (NO) using enzyme-linked immunosorbent assay, then the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was investigated by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (p50 and p65), JAK, STAT-1/3, and suppressor of cytokine signaling 3 (SOCS3) by Western blotting. In addition, Alga inhibited virus replication by plaque assay. Our results showed that the Alga had high antioxidant activity, significantly reduced the virus-induced accumulation of ROS, and inhibited the levels of nitric oxide and interleukin-6. Further studies revealed that Alga also downregulated the gene and protein expressions of iNOS, COX-2, nuclear factor-κB (p50 and p65), and the JAK/STAT pathway. The inhibitory effects of Alga were similar to pretreatment with specific inhibitors of JAK and STAT-3 in pseudorabies virus -infected RAW264.7 cells. Alga enhanced the expression of SOCS3 to suppress the activity of the JAK/STAT signaling pathway in pseudorabies virus-infected RAW264.7 cells. In addition, Alga has decreased viral replication (p

Background: Excessive reactive oxygen species (ROS) can result in inflammation and cytokine secretion in the liver, and then activate hepatic stellate cells that cause the accumulation of extracellular matrix proteins, especially collagen, in liver tissue. Naturally fermented noni juice (NJ; Morinda citrifolia) has been used for decades as a nutraceutical in humans. In this study, we intended to examine if NJ can ameliorate ROS-induced liver fibrosis via a thioacetamide (TAA)-induced rat model. Methods: The 50 rats used in this study were separated into five groups of 10 rats each for 8 weeks as follows: (1) control group; (2) TAA; (3) TAA + low-dose NJ (2.51 mL NJ/kg); (4) TAA + medium-dose NJ (5.02 mL NJ/kg); and (5) TAA + high-dose NJ (7.52 mL NJ/kg). Results: Treatment with TAA resulted in lower body weight and serum lipid levels (p

The protective efficacy of litchi (Litchi chinensis Sonn.) flower proanthocyanidin fraction (LFPF) composed of (-)-epicatechin and proanthocyanidin A2 against vascular endothelial growth factor (VEGF) generation induced by nickel (Ni) in hepatocellular carcinoma (Hep G2) cells was studied. VEGF is an angiogenic inducer, which promotes tumor angiogenesis, leading to rapid tumor growth and metastasis. VEGF could be substantially induced in the Ni-mediated Hep G2 cells. Through LFPF treatment, the Ni-induced VEGF generation could be suppressed significantly. The inhibition of HIF-1α expression by blocking phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways, and the suppression of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT 3), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)/mitogen-activated protein kinase (MEK1/2)/extracellular-signal-regulated kinase (ERK1/2) pathways are important molecular mechanisms for the LFPF action. LFPF should probably reduce the risk of liver cancer in Ni-contaminated environments by inhibiting VEGF expression. PRACTICAL APPLICATIONS: LFPF mainly contained (-)-epicatechin and proanthocyanidin A2. Our results demonstrated that LFPF considerably suppressed the Ni-induced VEGF expression through inhibition of JAK2/STAT 3 and RAF1/MEK1/2/ERK1/2 pathways and prohibited HIF-1α expression through blocking PI3K/AKT/mTOR pathway. Litchi flowers might have the potential to diminish the liver cancer risk in a Ni-contaminated environment through suitable treatment.

Prospective cohort studies have indicated that a highly nickel-polluted environment may severely affect human health, resulting in such conditions as respiratory tract cancers. Such exposure can trigger vascular endothelial growth factor (VEGF) expression. However, the signal transduction pathways leading to VEGF induction by nickel compounds are not well understood. This study revealed the occurrence of VEGF induction in human non-small-cell lung cancer H460 cells exposed to NiCl2 . Moreover, exposing H460 cells to NiCl2 activated extracellular signal-regulated protein kinase (ERK), nuclear factor kappa B (NFκB), and protein kinase B (Akt) as well as downregulated AMP activated protein kinase (AMPK) expression. The mitogen-activated protein kinase (MAPK) and ERK inhibitor significantly blocked NiCl2 -induced ERK activation and VEGF production. Pretreating H460 cells with a PI3K/Akt inhibitor substantially inhibited NiCl2 -induced VEGF expression and reduced Akt, ERK, and NFκB phosphorylation. Furthermore, 5-aminoimidazole-4-carboxamide ribonucleoside-induced AMPK activation improved VEGF expression in NiCl2 -treated H460 cells significantly. These results indicate that NiCl2 induces VEGF production through Akt, ERK, NFκB activation and AMPK suppression and mediates various types of pathophysiological angiogenesis.

Luteolin is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-virus inflammatory capacity of luteolin and its molecular mechanisms of action were analyzed. The cytotoxic effects of luteolin were assessed in the presence or absence of pseudorabies virus (PRV) via LDH and MTT assays. The results showed that luteolin (

The cytotoxic activity of litchi (Litchi chinensis Sonn.) flower ethanolic extract (LFEE) against A549 (human lung adenocarcinoma), KB (human nasopharyngeal carcinoma), MCF-7 (human breast adenocarcinoma) and HepG2 (human hepatocellular carcinoma) cells was evaluated. LFEE exhibited better anti-proliferative action against HepG2 cells, which induced G2/M phase arrest and apoptosis in HepG2 cells. HepG2 cells treated with LFEE (0.3 mg/mL) enhanced expressions of p53, tBid, Bad and Bax, along with decreased expressions of Bcl-2 and Bcl-xL, and induced the release of cytochrome c from mitochondria to cytosol. That also accompanied by activation of caspases-3, -8 and -9 and cleavage of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP); furthermore, down-regulations of phosphoinositide 3 kinase (PI3K), Akt, Akt phosphorylation and Bad phosphorylation could also be observed. Five flavonoids (total amount, 101.07 mg/g dried extract (g DE)), nine phenolic acids (total amount, 55.07 mg/ g DE) and proanthocyanidin A2 (81.20 mg/ g DE) could be determined in LFEE.

The cardiovascular and liver protection of carnitine (CNT) in a high-fat diet was investigated. Male C57BL/6 mice were divided randomly into four groups: 1) CON: Control, 2) HFD: high-fat diet, 3) CNTL: HFD + 500 mg CNT/kg BW, and 4) CNTH: HFD + 1500 mg CNT/kg BW. After a 25-week experimental period, CNT supplementation reduced (p

Curcumin (Cur), a polyphenolic compound extracted from spice and common food colourant turmeric, contains versatile bio-activities. Monoacetylcurcumin (MAC), a structural analogue of Cur, differs from Cur by acetyl modification, but retains enone groups. Comparative analysis revealed MAC effectively inhibited influenza virus infection (IAV) to a similar extent as, if not superior to, curcumin. Both compounds mildly reduced viral NA activity. Surprisingly, unlike Cur, the MAC inhibition of IAV did not occur through the blocking of HA activity. However, MAC strongly dampened Akt phosphorylation, the prerequisite signalling for efficient IAV propagation. A much stronger inhibition effect on IAV infection was observed when MAC treatment was in combination with Cur. Collectively, MAC demonstrated clear antiviral activity, and likely inhibited IAV via multiple mechanisms that were not identical to Cur. Importantly, Cur and MAC in combination synergistically inhibited IAV infection. Keywords: Curcumin, Influenza virus, Antiviral, Haemagglutinin, Synergic

Four flavonoids (epicatechin, rutin, diosmin and luteolin) and 11 phenolic acids (gallic acid, gentisic acid, p-hydroxybezoic acid, vanillic acid, caffeic acid, p-coumaric acid, ferulic acid, sinapic acid, syringic acid, p-anisic acid and rosmarinic acid) were determined in the ethanolic extract of M. calabura Linn. fruit gathered in Taiwan. The extract suppressed the lipopolysaccharide-stimulated expressions of inducible nitric oxide synthase and cyclooxygenase-2 as well as the productions of nitric oxide, prostaglandin E2 and pro-inflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1β and IL-6] in RAW264.7 macrophages. The extract modulated the inflammatory processes through inactivation of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs) p38 and c-Jun NH2-terminal kinase 1/2 (JNK1/2), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 1/3 (STAT1/3). Moreover, the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) followed by inducing the production of heme oxygenase-1 (HO-1) is also related to the anti-inflammatory effect of the extract.

Objective We have previously described the association of rheumatoid arthritis (RA) prevalence and two epidermal growth factor receptor (EGFR) SNPs (rs17337023 and rs2227983) among the Taiwanese population. This present study aimed to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA. Methods The cohort study included 366 Taiwan's Han Chinese RA patients and 326 age and gender matched healthy controls. Blood samples collected from the participants were analyzed to determine their serum EGFR levels and to identify EGFR SNPs from their genomic DNA. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. The relationship between EGFR SNP and the clinical manifestations of RA was evaluated. Results Our results showed that a statistically significant difference in genotype frequency distributions at rs17337023 SNP for RA patients and controls (p ˂ 0.05). In addition, compared with the haplotype frequencies between case and control groups, the RA patient with the GT haplotype appeared to be a significant "protective" haplotype compared with other haplotypes (OR: 0.73, 95% CI: 0.59-0.91; p = 0.005). Furthermore, the increased serum level of EGFR was also observed in RA patients (p ˂ 0.001). Conclusion Our study showed that RA is associated with rs17337023 SNP in EGFR gene and increased serum level of the EGFR protein. These findings suggest EGFR is worthy of further investigation as a therapeutic target for RA.

Previous reports have suggested that many constituents within various algal samples are able to attenuate LPS-induced inflammatory effects. To date no report has been published on the regulation of virus-induced inflammatory response of Dunaliella salina carotenoid extract. In the present study, the anti-inflammatory effect of D. salina carotenoid extract on pseudorabies virus (PRV)-infected RAW 264.7 macrophages was investigated. We evaluated the anti-inflammatory effect of D. salina carotenoid extract on PRV-infected RAW 264.7 cells by measuring cell viability, cytotoxicity, production of inflammatory mediators such as NO, iNOS, COX-2, pro-inflammatory cytokines and anti-virus replication by plaque assay. We found down-regulation of the expression of the iNOS, COX-2 and pro-inflammatory genes IL-1β, IL-6, TNF-α, and MCP-1 in a dose-dependent manner. Although there was no effect on viral replication, there were tendencies toward lower virus titer and tendencies toward higher cell survival. Most importantly, we found that inhibition of TLR9, PI3K and Akt phosphorylation plays a crucial role in the extract-mediated NF-κB regulation by modulating IKK-IκB signaling in PRV-infected RAW264.7 cells. These results indicate that D. salina carotenoid extracts inhibited inflammation by inhibition of NF-κB activation by TLR9 dependent via PI3K/Akt inactivation.

Background X-ray repair cross-complementing group 3 (XRCC3) plays a crucial role in mammalian DNA repair processes. The polymorphism of XRCC3, rs861539 (Thr > Met at codon 241), is common in populations worldwide. This study analyzed the relationship between this functional single nucleotide polymorphism and systemic lupus erythematosus (SLE) in the Han Chinese population in Taiwan (HC-TW). Methods Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism on 163 SLE patients and 191 healthy participants in the control group. Results The data showed that the genotype frequency at codon 241 did not differ significantly between the SLE patients and the healthy participants in the control group; however, the allele frequency analysis indicated a significant difference between these groups. In addition, we used the genotype and allele frequencies of 191 healthy HC-TW participants for comparison with HapMap populations. The results indicated a significant difference of XRCC3 Thr241Met allele and genotype frequencies between the HC-TW population and HapMap populations, except for the other Han Chinese populations. A prior study showed that Thr241 > Met substitution in XRCC3 protein was positive as damaging and functional consequences as well. Conclusion This is the first study to demonstrate the difference of XRCC3 Thr241 > Met variant between the HC-TW population and HapMap population.

The purpose of this study was to determine whether toll-like receptors 9 (TLR9) gene polymorphisms (rs352139 and rs352140) were markers of susceptibility to the development and progression of membranous nephropathy (MGN) in Taiwanese patients. The polymorphisms were investigated by polymerase chain reaction in 397 Taiwanese individuals (134 MGN patients and 263 controls). Patients with malignancy, chronic infectious diseases, lupus nephritis, or drug-induced secondary MGN were excluded from the study. Data showed AA genotype at rs352139 SNP or GG genotype at rs352140 SNP may indicate higher risk for MGN (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.02-2.35, at rs352139 SNP; OR = 1.57; 95% CI = 1.03-2.39, at rs352140 SNP). However, MGN patients with A-G haplotype were susceptible for decreased creatinine clearance rate and for seriously tubule-interstitial fibrosis. The result suggests for the first time that TLR9 (rs352139 and rs352140) polymorphisms may contribute to the development and progression of MGN.

The carotenoid extract from Dunaliella salina was used to evaluate the suppressive effects on lipopolysaccharide (LPS)-induced pro-inflammatory mediators in RAW264.7 cells. The extract composed all-trans forms of α-carotene (28.8 mg/g extract), β-carotene (471.1 mg/g extract), lutein (7.1 mg/g extract) and zeaxanthin (7.2 mg/g extract), 13- or 13′-cis-β-carotene (12.1 mg/g extract), 9- or 9′-cis-α-carotene (19.1 mg/g extract) and 9- or 9′-cis-β-carotene (440.3 mg/g extract) dose-dependently reduced the production of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-activated RAW264.7 cells. Its attenuation of LPS-induced inflammatory responses was closely related to inhibition of the nuclear NF-κB p50 subunit translocation by blocking inhibitor of κBα (IκB) phosphorylation and degradation correlated with suppressing IκB kinase (IKK) α/β phosphorylation, as well as down-regulation of the c-Jun NH2-terminal kinase (JNK) activation.

Background: Hepatic steatosis is defined as excessive amounts of triglyceride and other fats inside liver cells and has become an emergent liver disease in developed and developing countries. Methods: Deep seawater (DSW)300, DSW900, and DSW1500 drinking waters were formulated via a combination of reverse osmosis and electrodialysis. Hamsters on a high-fat diet were assigned to drink the following solutions: (1) normal distilled water, (2) DSW300, (3) DSW900, or (4) DSW1500. Serum, liver, and fecal biochemical values, expression of hepatic genes related to fatty-acid homeostasis, as well as liver antioxidative levels were measured after a 6-week feeding period. Additionally, hematoxylin and eosin staining was used to investigate the liver histopathology. Results: Serum/liver lipids, liver sizes, liver malondialdehyde content, and serum aspartate aminotransferase and alanine aminotransferase of high-fat diet hamsters were reduced (p 0.05) altered, DSW drinking water upregulated (p

Gentisic acid and epicatechin are two major compounds in phenolic acids and flavonoids of litchi-flower-water extracts (LFWEs), respectively. Increased (p

Ethnopharmacological relevance Antrodia camphorata is a functional fungus in Taiwan and owns several pharmacological functions. Antrosterol, a bioactive constitute of sterols in edible Antrodia camphorata submerged whole broth, can protect liver from CCl4 damage via enhancing antioxidant and anti-inflammatory capacities. Aim of the study The aim of this study was to investigate the hepatoprotection of antrosterol (named as EK100) against alcohol consumption. Materials and methods A Lieber-DeCarli regular EtOH diet (EtOH liquid diet, 5% (v/v) alcohol) was applied to induce alcoholic liver damage. Mice were randomly divided into 5 groups: (1) Control: control liquid diet; (2) EtOH: EtOH liquid diet; (3) EK100_1X: EtOH liquid diet and 1 mg EK100 (Antrosterol)/Kg body weight (bw); (4) EK100_5X: EtOH liquid diet and 5 mg EK100/Kg bw; (5) EK100_10X: EtOH liquid diet and 10 mg EK100/Kg bw. At the end of experiment, the livers were collected for histo-pathological analyses, RNA and protein extraction, and enzymatic activities. Results Antrosterol reduced serum/liver lipids of alcohol-diet fed mice which highly related to upregulated fatty acid β-oxidation and downregulated lipogenesis, and increased fecal lipid/bile-acid outputs. Antrosterol enhanced hepatic antioxidant capabilities in alcohol-diet fed mice while it also lowered serum alcohol level, as well as increased alcohol dehydrogenase (ADH) and catalase (CAT) activities and decreased CYP2E1 protein expression in livers of alcohol-diet fed mice. Besides, antrosterol lowered hepatic inflammation and fibrosis related gene expressions, as well as serum AST/ALT values and TNF-α/IL-1β contents in alcohol-diet fed mice. Conclusion Based on the results, hepatoprotection of antrosterol is mostly attributed to its regulations of lipid homeostasis, antioxidant capability, alcohol metabolism, and anti-inflammation.

Background We have previously described the association between rheumatoid arthritis (RA) prevalence and the two mutY Homolog (E. coli) (MUTYH) SNPs (rs3219463 and rs3219476) among the Taiwanese population. This present study will aim to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA. Methods The cohort study included 368 Taiwan’s Han Chinese RA patients and 364 healthy controls. Blood samples collected from the participants were analyzed to determine their serum MUTYH levels and to identify rs3219463 SNP of MUTYH from their genomic DNA. Results Our data resulted in a statistically significant difference in genotype frequency distributions at rs3219463 for RA patients and controls (p

The objective of this study was to investigate the anticancer activity of caffeate derivatives in human cancer cells. Our results demonstrate that caffeate derivatives decreased the population growth of COLO 205, assessed using the MTT assay. However, caffeate derivatives, at the concentrations used in this study (0–250 μM) did not affect the viability of HepG2, Huh7, PLC5, and SK-Hep-1 cells. Flow cytometric analysis of COLO 205 cells exposed to decyl caffeate showed that the number of apoptotic cells increased in a time- and dose-dependent manner. Western blot analysis revealed that decyl caffeate stimulated an increase in protein expression levels of p53, Fas, FasL, AIF, and Apaf-1. Additionally, treatment with decyl caffeate changed the expression levels of Bcl-2 family members and subsequently induced the activation of caspase-12, caspase-9, and caspase-3, which was followed by cleavage of PARP. Our findings highlight the chemopreventive potential of decyl caffeate.

Longan-flower-water-extract (LFWE) contains large amounts of phytochemicals where gentisic acid and epicatechin are the major compounds in phenolic acid and flavonoid compound, respectively. The objective of this study was to investigate if drinking LFWE could protect the liver from a hypercaloric dietary habit. Only rats fed the hypercaloric diet (HCD) with 25 g/L (w/v) LFWE solution (HCD_2X) group demonstrated lower (p

Purpose Herpes simplex virus type I (HSV-1) is capable of causing a wide array of human ocular diseases. Herpes simplex virus keratitis (HSK)-induced cytopathogenicity together with the chronic immune-inflammatory reaction can trigger stromal scarring, thinning, and neovascularization which may lead to permanent vision impairment. Lychee flower extract (LFE) is known for its antioxidant and anti-inflammatory effects. Therefore, in this study, we investigated the mechanism of the Statens Seruminstitut rabbit corneal (SIRC) epithelial cells infected by HSV-1 and examined the antiviral capabilities of LFE. Methods SIRC cells were pretreated with different concentrations of LFE (0.2, 0.1, and 0.05 μg/ml) and then infected with 1 MOI of HSV-1 for 24 h. The cell viability or morphology was evaluated in this study. In addition, the supernatants and cell extracts were collected for Cell Counting Kit-8 (CCK), plaque assay, and western blotting. Results We found that HSV-1-induced cell proliferation is regulated through inhibition of the mammalian target of rapamycin (mTOR) and p70s6k phosphorylation in response to the LFE. In addition, the LFE enhanced the autophagy protein expression (Beclin-1 and light chain 3, LC3) and decreased the viral titers. Conclusions These results showed the antiviral capabilities and the protective effects of LFE. Taken together, our data indicate that LFE has potential as an anti-HSK (herpes simplex keratitis) for HSV-1 infection.