Thymosin Beta 4 Inhibits LPS and ATP-Induced Hepatic Stellate Cells via the Regulation of Multiple Signaling Pathways.

Risk signals are characteristic of many common inflammatory diseases and can function to activate nucleotide-binding oligomerization (NLR) family pyrin domain-containing 3 (NLRP3), the innate immune signal receptor in cytoplasm. The NLRP3 inflammasome plays an important role in the development of liver fibrosis. Activated NLRP3 nucleates the assembly of inflammasomes, leading to the secretion of interleukin (IL)-1ß and IL-18, the activation of caspase-1, and the initiation of the inflammatory process. Therefore, it is essential to inhibit the activation of the NLRP3 inflammasome, which plays a vital role in the immune response and in initiating inflammation. RAW 264.7 and LX-2 cells were primed with lipopolysaccharide (LPS) for 4 h and subsequently stimulated for 30 min with 5 mM of adenosine 5'-triphosphate (ATP) to activate the NLRP3 inflammasome. Thymosin beta 4 (Tß4) was supplemented to RAW264.7 and LX-2 cells 30 min before ATP was added. As a result, we investigated the effects of Tß4 on the NLRP3 inflammasome. Tß4 prevented LPS-induced NLRP3 priming by inhibiting NF-kB and JNK/p38 MAPK expression and the LPS and ATP-induced production of reactive oxygen species. Moreover, Tß4 induced autophagy by controlling autophagy markers (LC3A/B and p62) through the inhibition of the PI3K/AKT/mTOR pathway. LPS combined with ATP significantly increased thee protein expression of inflammatory mediators and NLRP3 inflammasome markers. These events were remarkably suppressed by Tß4. In conclusion, Tß4 attenuated NLRP3 inflammasomes by inhibiting NLRP3 inflammasome-related proteins (NLRP3, ASC, IL-1ß, and caspase-1). Our results indicate that Tß4 attenuated the NLRP3 inflammasome through multiple signaling pathway regulations in macrophage and hepatic stellate cells. Therefore, based on the above findings, it is hypothesized that Tß4 could be a potential inflammatory therapeutic agent targeting the NLRP3 inflammasome in hepatic fibrosis regulation.

3',4'-Dihydroxyflavone mitigates inflammatory responses by inhibiting LPS and TLR4/MD2 interaction.

BACKGROUND: We previously reported the potential inhibitory activity of 3',4'-dihydroxyflavone (DHF) on nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated macrophages. PURPOSE: We investigated the underlying molecular mechanisms of DHF in LPS-activated macrophages and evaluated its effect on LPS-induced septic shock in mice. METHODS: To explore the anti-inflammatory effect of DHF, nitrite, PGE2, and cytokines were measured in vitro and in vivo experiments. In addition, to verify the molecular signaling pathway, quantitative real time-PCR, luciferase assay, nuclear extraction, electrophoretic mobility shift assay, immunocytochemistry, immunoprecipitation, molecular docking analysis, and myeloid differentiation 2 (MD2)-LPS binding assay were conducted. RESULTS: DHF suppressed the LPS-induced expression of proinflammatory mediators through nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) inactivation pathways in RAW 264.7 macrophages. Importantly, molecular docking analysis and in vitro binding assays showed that DHF interacts with the hydrophobic pocket of MD2 and then interferes with the interaction between LPS and toll-like receptor 4 (TLR4). DHF inhibited LPS-induced oxidative stress by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). Treatment of LPS-induced endotoxemia mice with DHF reduced the expression levels of pro-inflammatory mediators via the inactivation of NF-κB, AP-1, and signal transducer and activator of transcription 1 (STAT1) in the lung tissue, thus increasing the survival rate. CONCLUSION: Taken together, our data first time revealed the underlying mechanism of the DHF-dependent anti-inflammatory effect by preventing LPS from binding to the TLR4/MD2 complex. Therefore, DHF may be a possible anti-inflammatory agent for the treatment of LPS-mediated inflammatory diseases.

Anti-Inflammatory Activity of a Medicinal Herb Extract Mixture, HM-V, on an Animal Model of DNCB-Induced Chronic Skin Inflammation.

Chronic inflammatory skin diseases, such as atopic dermatitis, are caused by the accumulation of immune cells and the overproduction of chemokines, including CCL17 and CCL22, due to the activation of pro-inflammatory cytokines secreted from keratinocytes. In the present study, the inhibitory activity of HM-V on tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-induced pro-inflammatory cytokines was examined in human keratinocytes (HaCaTs) and 2,4-dinitrofluorobenzene (DNCB)-induced chronic skin contact dermatitis animal models. Traditional Asian medicinal herb extracts mixture (HM-V), which have been extensively used in Asian medicine, were utilized. In TNF-α/IFN-γ-induced HaCaTs, HM-V strongly inhibited mRNA and protein expression of CCL17 and CCL22 in a concentration-dependent manner. The expression of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 was also inhibited. Therefore, localized administration of HM-V in the DNCB-induced animal model alleviated immune cell deposition and skin inflammation. The results indicate that HM-V exerts inhibitory effects on keratinocyte production of CCL17 and CCL22. Furthermore, HM-V may be a useful anti-inflammatory agent for the prevention and treatment of inflammatory skin diseases.

Bakuchiol, main component of root bark of Ulmus davidiana var. japonica, inhibits TGF-ß-induced in vitro EMT and in vivo metastasis.

Cancer is a second leading cause of death worldwide, and metastasis is the major cause of cancer-related mortality. The epithelial-mesenchymal transition (EMT), known as phenotypic change from epithelial cells to mesenchymal cells, is a crucial biological process during development. However, inappropriate activation of EMT contributes to tumor progression and promoting metastasis; therefore, inhibiting EMT is considered a promising strategy for developing drugs that can treat or prevent cancer. In the present study, we investigated the anti-cancer effect of bakuchiol (BC), a main component of Ulmus davidiana var. japonica, in human cancer cells using A549, HT29 and MCF7 cells. In MTT and colony forming assay, BC exerted cytotoxicity activity against cancer cells and inhibited proliferation of these cells. Anti-metastatic effects by BC were further confirmed by observing decreased migration and invasion in TGF-ß-induced cancer cells after BC treatment. Furthermore, BC treatment resulted in increase of E-cadherin expression and decrease of Snail level in Western blotting and immunofluorescence analysis, supporting its anti-metastatic activity. In addition, BC inhibited lung metastasis of tail vein injected human cancer cells in animal model. These findings suggest that BC inhibits migration and invasion of cancers by suppressing EMT and in vivo metastasis, thereby may be a potential therapeutic agent for treating cancers.

Amentoflavone, active compound of Selaginella tamariscina, inhibits in vitro and in vivo TGF-ß-induced metastasis of human cancer cells.

Epithelial mesenchymal transition (EMT) is a well-known and important step in metastasis and thus can be a key target in cancer treatment. Here, we tested the EMT inhibitory actions of Selaginella tamariscina and its active component, amentoflavone (AF). EMT was examined in vitro using wound-healing and invasion assays and by monitoring changes in the expression of the EMT-related proteins, E-cadherin, Snail, and Twist. Metastasis was examined in vivo using SCID mice injected with luciferase-labeled A549 cells. We confirmed that aqueous extracts of S. tamariscina (STE) and AF inhibited EMT in human cancer cell lines. We found that STE and AF at nontoxic concentrations exerted remarkable inhibitory effects on migration (wound healing assay) and invasion (Transwell assay) in tumor necrosis factor (TGF)-ß-treated cancer cells. Western blotting and immunofluorescence imaging show that AF treatment also restored E-cadherin expression in these cells compared to cells treated with TGF-ß only. Suppression of metastasis by AF was investigated by monitoring migration of tail-vein-injected, circulating A549-luc cells to the lungs in mice. After 3 wk, fewer nodules were observed in mice co-treated with AF compared with those treated with TGF-ß only. Our findings indicate that STE and AF are promising EMT inhibitors and, ultimately, potentially potent antitumor agents.

Co-immunomodulatory Activities of Anionic Macromolecules Extracted from Codium fragile with Red Ginseng Extract on Peritoneal Macrophage of Immune-Suppressed Mice.

In this study we investigated the immune effects of oral administration of anionic macromolecules extracted from Codium fragile (CFAM) and red ginseng extract mixture on the peritoneal macrophage cells in immune-suppressed mice. Cyclophosphamide (CY) induces the immune-suppressed condition. CY-treated mice were orally fed with different concentrations of CFAM supplemented with red ginseng extract and the peritoneal macrophages collected. CY treatment significantly decreased the immune activities of peritoneal macrophages, compared to the normal mice. The administration of CFAM mixed with red ginseng extract significantly boosted the viability of macrophage cells and nitric oxide production of peritoneal macrophages. Further, the oral administration of CFAM mixed with red ginseng extract up-regulated the expression of iNOS, COX-2, and TLR-4 as well as cytokines such as IL-1ß, IL-6, TNF-α, and IFN-γ more than the red ginseng-treated group. This study showed that CFAM enhanced the immune activity of red ginseng extract in the peritoneal macrophage cells of immune-suppressed mice. Furthermore, CFAM might be used as a co-stimulant of red ginseng extract through the regulation of macrophage cells for the enhancement of human health and immunity.

Pregnant women with IBD are more likely to be adherent to biologic therapies than other medications.

BACKGROUND: There are differences in the efficacy and safety profiles of medications used to treat IBD that may impact a woman's perceived risk of medication exposure during pregnancy, potentially leading to medication non-adherence, poor disease-control and adverse pregnancy outcomes. AIM: To assess whether medication adherence patterns differ by drug class during pregnancy and influence birth outcomes for women with IBD. METHODS: Of 143 491 women, a validated case definition was used to identify 370 women with IBD in five administrative health databases in Alberta, Canada (2012-2015). Women who had ≥2 consecutive medications prescription for maintenance therapy for IBD in the year prior to pregnancy were included (n = 230). Prescription-based medication possession ratio ≥0.8 defined adherence. Chi-squared tests were used to compare adherence patterns by drug class and outcomes. RESULTS: Of the 159/230 women who were adherent during the year prior to pregnancy, 20 (12.6%; 95% CI: 8.2%, 18.8%) were not adherent and 21 (13.2%; 95% CI: 8.7%, 19.5%) discontinued their medications during pregnancy. Medication adherence during pregnancy differed significantly by drug class. A greater proportion of women on biologics (41.5%; 95% CI 32.9%, 50.7%) were adherent during pregnancy than women on thiopurines (22.9%; 95% CI 16.1%, 31.5%; P = 0.006); adherence was not significantly different for 5-aminosalicylates (35.6%; 95% CI 27.4%, 44.8%; P = 0.204). Women were more likely to be adherent to biologics (49.3%, 95% CI 37.3%, 61.3%) than thiopurines (20.9%; 95% CI 12.6%, 32.6%; P = 0.014) and 5-aminosalicylates (29.9%; 95% CI 19.9%, 42.1%; P = 0.030) in the first trimester. This was similar in the third trimester. In the second trimester, adherence pattern did not significantly differ by drug class (biologics vs thiopurines: P = 0.348; biologics vs 5-aminosalicylate: P = 0.999). Infants born to women with IBD (adherent: RR 1.58. 95% CI 1.02, 2.27; non-adherent: RR 1.32, 95% CI 0.97, 1.81) were more likely to be admitted into the neonatal intensive care unit than the general obstetric population, but this was not significantly different between women who were adherent or not adherent to their IBD medication (P = 0.711). CONCLUSION: Almost a quarter of women with IBD who were previously adherent to medical therapy were not adherent during pregnancy. Adherence pattern differed by drug class.

Immune Enhancement Effects of Codium fragile Anionic Macromolecules Combined with Red Ginseng Extract in Immune-Suppressed Mice.

Codium fragile is an edible seaweed in Asian countries that has been used as a thrombolytic, anticoagulant, antioxidant, anti-inflammatory, and immune-stimulatory agent. Ginseng has also been known to maintain immune homeostasis and to regulate the immune system via enhancing resistance to diseases and microorganisms. In this study, anionic macromolecules extracted from C. fragile (CFAM) were orally administered with red ginseng extract (100 mg/kg body weight) to cyclophosphamide-induced immunosuppressed male BALB/c mice to investigate the immune-enhancing cooperative effect of Codium fragile and red ginseng. Our results showed that supplementing CFAM with red ginseng extract significantly increased spleen index, T- and B-cell proliferation, NK cell activity, and splenic lymphocyte immuneassociated gene expression compared to those with red ginseng alone, even though a high concentration of CFAM with red ginseng decreased immune biomarkers. These results suggest that CFAM can be used as a co-stimulant to enhance health and immunity in immunosuppressed conditions.

Augmented Mechanical Forces of the Surface-Modified Nanoporous Acupuncture Needles Elicit Enhanced Analgesic Effects.

Over the past several decades, clinical studies have shown significant analgesic effects of acupuncture. The efficacy of acupuncture treatment has improved with the recent development of nanoporous needles (PN), which are produced by modifying the needle surface using nanotechnology. Herein, we showed that PN at acupoint ST36 produces prolonged analgesic effects in an inflammatory pain model; the analgesic effects of PN acupuncture were sustained over 2 h, while those using a conventional needle (CN) lasted only 30 min. In addition, the PN showed greater therapeutic effects than CN after 10 acupuncture treatments once per day for 10 days. We explored how the porous surface of the PN contributes to changes in local tissue, which may in turn result in enhanced analgesic effects. We showed that the PN has greater rotational torque and pulling force than the CN, particularly at acupoints ST36 and LI11, situated on thick muscle layers. Additionally, in ex vivo experiments, the PN showed greater winding of subcutaneous connective tissues and muscle layers. Our results suggest that local mechanical forces are augmented by the PN and its nanoporous surface, contributing to the enhanced and prolonged analgesic effects of PN acupuncture.

Toxicity of dietary selenomethionine in juvenile steelhead trout, Oncorhynchus mykiss: tissue burden, growth performance, body composition, hematological parameters, and liver histopathology.

The steelhead trout (Oncorhynchus mykiss) is the species most at risk from selenium (Se) exposure in the San Francisco Bay Delta (SFBD). However, although steelhead trout are usually exposed to environmental Se in the juvenile stage, data to test their sensitivity to excess Se, especially its organic form, in the juvenile stage are scarce. Therefore, the objective of the current study was to assess the sensitivity of juvenile steelhead trout to ecologically relevant forms of Se using integrated sensitive endpoints. Fish (mean weight: 22.3 g) were fed one of five diets containing 1.1 (control), 8.8, 15.4, 30.8, and 61.6 µg Se/g diet dw (Se1.1, Se8.8, Se15.4, Se30.8, and Se61.6, respectively) in the form of selenomethionine for 4 weeks. After 4 weeks, Se significantly accumulated in a dose-dependent manner in all tissues at different rates. The growth rate and plasma cholesterol were significantly depressed in fish fed diets containing Se30.8 and above. Hematological parameters and mortality were significantly elevated in fish fed the Se61.6 diet. Marked histopathological alterations were observed in fish fed the Se8.8 diet (the lowest observed effect concentration, LOEC) and above. The current results suggest that the steelhead trout is more sensitive to excess Se than nonanadromous rainbow trout used in previous studies because of its lower LOEC despite the use of selenomethionine and the shorter experimental duration. Additionally, it should be noted that the current Se levels found in the SFBD are already a threat to the threatened population of steelhead trout on the central California coast.

Effect of sulfation and partial hydrolysis of polysaccharides from Polygonatum sibiricum on immune-enhancement.

The aqueous polysaccharide from Polygonatum sibiricum was extracted and fractionated using anion-exchange chromatography to obtain F1 fraction. The F1 was chemically sulfated and partially acid-hydrolyzed for the production of its over-sulfated (OS1,2,3) and hydrolyzed (HP1,2,3) derivatives, in which the sulfate content of OS1,2,3 was 7.5-17.1%, and the Mw of HP1,2,3 ranged from 18.2 × 103 to 57.3 × 103 g/mol. Considerable RAW264.7 cell activation was observed by HP1,2,3 with NO production of 34.9, 44.3 and 42.7 µM, respectively, as well as the mRNA expression of cytokines (IL-1ß, IL-6, IL-10 and IL-12). NK cell cytotoxicity against HT-29 cell was facilitated by OS1,2,3 treatment with the increased gene expressions of INF-γ, Granzyme-B, perforin, NKG2D, and FasL. RAW264.7 cells appeared to be activated via MR and TLR4 mediated signaling pathway, but CR3 and TRL2 might play a main role in stimulating NK cells. Overall, the present study suggests the potential application of polysaccharides from P. sibiricum in functional foods and pharmacological industries.

Bone Tissue Engineering Strategies in Co-Delivery of Bone Morphogenetic Protein-2 and Biochemical Signaling Factors.

Administration of bone morphogenetic protein-2 (BMP-2), which is commercially approved by the food and drug administration to damaged bone sites has been investigated for the purpose of bone tissue regeneration. BMP-2 can promote osteoblastic differentiation of mesenchymal stem cells as well as regeneration of bone formation in early phase. This review highlights various factors such as vitamin D, dexamethasone, platelet-derived growth factor, placental growth factor, BMP-7, and NEL-like protein-1 that enhance and stimulate angiogenesis, cell differentiation, and bone regeneration. These biochemical signals and growth factors (GFs) accelerate bone repair and remodeling either synergistically or individually. Delivery systems and scaffolds are used for sustained release of these cargo molecules and support at damaged bone sites. Compared with direct administration of BMP-2, current studies have demonstrated that a combination of multiple GFs and/or therapeutic chemical factors with delivery platforms synergistically facilitates bone regeneration. Therefore, in the future, multiple combinations of various GFs, chemicals, and materials could provide patients and surgeons with non-invasive treatment options without secondary surgery and pain. To the end, this review summarizes the biological functions and synergistic effects of dual administration modalities involving BMP-2 as well as recent developments in bone tissue engineering applications.

Association of the loudness dependence of auditory evoked potentials with clinical changes to repetitive transcranial magnetic stimulation in patients with depression.

BACKGROUND: Although the application of repetitive transcranial magnetic stimulation (rTMS) for treatment of depression has been well investigated, there are few biological predictors of clinical outcomes to rTMS treatment. Previous studies have suggested that the loudness dependence of auditory evoked potentials (LDAEP) can be used as a predictor of response to antidepressant treatment. However, little is known about the association between rTMS and LDAEP. The present study aimed to investigate whether baseline LDAEP is associated with clinical changes to rTMS treatment in patients with major depressive disorder (MDD), and to explore the effect of high-frequency rTMS on LDAEP. METHODS: Thirty patients were randomized to receive 15 sessions of active (n = 15) or sham rTMS (n = 15). LDAEP and clinical measures of depression were assessed before and after 10 Hz rTMS treatment for 15 days. RESULTS: Baseline LDAEP was associated with changes in scores on the Hamilton Rating Scale for Depression. There were no significant effects of rTMS on LDAEP. Patients with high LDAEP exhibited more favorable clinical changes than those with low LDAEP following treatment with rTMS. LIMITATIONS: The sample was relatively small, and the participants were not divided into responders and non-responders group due to small sample. An influence of medication has not been controlled. CONCLUSIONS: Our findings suggest that high baseline LDAEP may be associated with favorable clinical changes to rTMS treatment in patients with MDD. Further studies are required to replicate and validate the potential use of LDAEP as a predictor of clinical changes to rTMS treatment.

Pregnant Women with Inflammatory Bowel Disease Are at Increased Risk of Vitamin D Insufficiency: A Cross-Sectional Study.

BACKGROUND AND AIMS: Vitamin D insufficiency is prevalent in individuals with inflammatory bowel disease [IBD], as well as in pregnant women; however, the prevalence of vitamin D insufficiency in pregnant women with IBD is unknown. This study assessed the prevalence of vitamin D insufficiency in pregnant women with IBD and the adequacy of recommended supplementation. METHODS: A cross-sectional study was conducted in pregnant women with inflammatory bowel disease [Crohn's disease = 61, ulcerative colitis = 41] and without inflammatory bowel disease [n = 574]. Chi square tests and log binomial regression were used to examine the prevalence of vitamin D insufficiency. Covariates included ethnicity and season. Adequacy of vitamin D supplementation during pregnancy was also assessed. RESULTS: The prevalence of vitamin D insufficiency [25-OHD ≤75 nmol/L] in those with Crohn's disease was 50.8% (95% confidence interval [CI]: 38.4%-63.2%) and 60.9% [95% CI: 45.3%-74.7%] with ulcerative colitis compared with 17.4% [95% CI: 14.6%-20.8%] without inflammatory bowel disease. Women with inflammatory bowel disease were more likely to be vitamin D insufficient after adjusting for ethnicity and season (Crohn's disease-adjusted relative risk [aRR] = 2.98,;: 2.19-4.04; ulcerative colitis-aRR = 3.61; 95% CI: 2.65-4.93). Despite vitamin D supplementation, 32.3% [95% CI: 17.8%-51.2%] of those with Crohn's disease, 58.3% [95% CI: 37.1%-76.9%] of those with with ulcerative colitis, and 10.8% [95% CI: 6.9%-16.6%] of those without inflammatory bowel disease were still vitamin D insufficient. CONCLUSIONS: Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency compared with those without inflammatory bowel disease. The current guidelines for vitamin D supplementation may be inadequate for pregnant women with inflammatory bowel disease.

Effects of Dietary Inclusion of Astaxanthin on Growth, Muscle Pigmentation and Antioxidant Capacity of Juvenile Rainbow Trout (Oncorhynchus mykiss).

This study was designed to investigate the effects of dietary astaxanthin levels on growth performance, feed utilization, muscle pigmentation, and antioxidant capacity in juvenile rainbow trout. Four experimental diets were formulated to contain 0, 50, 75, and 100 mg/kg astaxanthin (designed as AX0, AX50, AX75, and AX100). Each diet was fed to triplicate groups of fish (18.5 g/fish) for 10 weeks. Growth performance and muscle composition of fish were not affected by dietary astaxanthin levels. Total carotenoid concentration in the muscle of fish fed the AX50 diet was higher than that of fish fed the AX0 diet, but no significant differences were observed between these fish and those fed the AX75 and AX100 diets. Muscle astaxanthin content increased with increased astaxanthin in the diet. Deposition of astaxanthin in the flesh resulted in a decrease in lightness and an increase in redness and yellowness. The fillets from trout fed the AX75 diet had significantly lower lightness than trout fed the AX50 and AX100 diets. Fish fed the AX50 and AX75 diets showed significantly lower catalase activity than those fed the control diet. Total antioxidant status increased significantly in all astaxanthin supplemented groups when compared to the control group. Superoxide dismutase activity was significantly decreased in fish fed the AX50 diet compared to fish fed the AX0 diet. These findings suggest that while fillet pigmentation increased with increasing dietary astaxanthin concentration, indices of fish antioxidant capacity may not be affected in a dose dependent manner.

Effect of Hyaluronidase Addition to Lidocaine for Trigger Point Injection in Myofascial Pain Syndrome.

INTRODUCTION: This randomized, double-blind study compared the efficacy of hyaluronidase co-injection with that of local anesthesia alone on the degree of pain and quality of life in patients with myofascial pain syndrome (MPS). METHODS: Sixty-one adults, aged 25 to 75 years, with MPS affecting both trapezius muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL). Patients were followed for 14 days (pre- and post-TPI days 0, 1, 4, 7, and 14) with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS on day 7. Also, we evaluated the neck disability index (NDI) and the short form of brief pain inventory (BPI-SF) on pre- and post-TPI day 14. RESULTS: In both groups, VNRS decreased on days 4, 7, and 14 compared to the pre-TPI. However, in group H, VNRS decreased on day 1 also. There were no significant differences of VNRS between the 2 groups during 14 days. NDI and BPI-SF scores also significantly decreased after TPI in both groups. CONCLUSIONS: There were no significant differences between groups in terms of VNRS, NDI, or BPI-SF scores. However, TPI consisting of lidocaine mixed with hyaluronidase worked more effectively than lidocaine alone on post-TPI day 1. Further, hyaluronidase showed a tendency to reduce TPI-related soreness.

Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways.

The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity.

Red ginseng extract promotes the hair growth in cultured human hair follicles.

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

Light-controlled biphasic current stimulator IC using CMOS image sensors for high-resolution retinal prosthesis and in vitro experimental results with rd1 mouse.

Retinal prosthetic devices stimulate retinal nerve cells with electrical signals proportional to the incident light intensities. For a high-resolution retinal prosthesis, it is necessary to reduce the size of the stimulator pixels as much as possible, because the retinal nerve cells are concentrated in a small area of approximately 5 mm × 5 mm. In this paper, a miniaturized biphasic current stimulator integrated circuit is developed for subretinal stimulation and tested in vitro. The stimulator pixel is miniaturized by using a complementary metal-oxide-semiconductor (CMOS) image sensor composed of three transistors. Compared to a pixel that uses a four-transistor CMOS image sensor, this new design reduces the pixel size by 8.3%. The pixel size is further reduced by simplifying the stimulation-current generating circuit, which provides a 43.9% size reduction when compared to the design reported to be the most advanced version to date for subretinal stimulation. The proposed design is fabricated using a 0.35 µm bipolar-CMOS-DMOS process. Each pixel is designed to fit in a 50 µ m × 55 µm area, which theoretically allows implementing more than 5000 pixels in the 5 mm × 5 mm area. Experimental results show that a biphasic current in the range of 0 to 300 µA at 12 V can be generated as a function of incident light intensities. Results from in vitro experiments with rd1 mice indicate that the proposed method can be effectively used for retinal prosthesis with a high resolution.