Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Therapeutic strategy using novel RET/YES1 dual-target inhibitor in lung cancer.

Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR, MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.

Ultrasonic Nonlinearity Experiment due to Plastic Deformation of Aluminum Plate Due to Bending Damage.

The nonlinear ultrasonic evaluation technique is useful for assessing micro-defects and microstructure changes caused by fatigue or bending damage. In particular, the guided wave is advantageous for long-distance testing such as piping and plate. Despite these advantages, the study of nonlinear guided wave propagation has received relatively less attention compared to bulk wave techniques. Furthermore, there is a lack of research on the correlation between nonlinear parameters and material properties. In this study, the relationship between nonlinear parameters and plastic deformation resulting from bending damage was experimentally investigated using Lamb waves. The findings indicated an increase in the nonlinear parameter for the specimen, which was loaded within the elastic limit. Inversely, regions of maximum deflection in specimens with plastic deformation exhibited a decrease in the nonlinear parameter. This research is expected to be helpful for maintenance technology in the nuclear power plant and aerospace fields that require high reliability and accuracy.

Three cases of jejunal tumors detected by standard upper gastrointestinal endoscopy: A case series.

BACKGROUND: In patients with obscure gastrointestinal bleeding, re-examination with standard upper endoscopes by experienced physicians will identify culprit lesions in a substantial proportion of patients. A common practice is to insert an adult-sized forward-viewing endoscope into the second part of the duodenum. When the endoscope tip enters after the papilla, which is a marker for the descending part of the duodenum, it is difficult to endoscopically judge how far the duodenum has been traversed beyond the second part. CASE SUMMARY: We experienced three cases of proximal jejunal masses that were diagnosed by standard upper gastrointestinal endoscopy and confirmed with surgery. The patients visited the hospital with a history of melena; during the initial upper gastrointestinal endoscopy and colonoscopy, the bleeding site was not confirmed. Upper gastrointestinal bleeding was suspected; thus, according to guidelines, upper endoscopy was performed again. A hemorrhagic mass was discovered in the small intestine. The lesion of the first patient was thought to be located in the duodenum when considering the general insertion depth of a typical upper gastrointestinal endoscope; however, during surgery, it was confirmed that it was in the jejunum. After the first case, lesions in the second and third patients were detected at the jejunum by inserting the standard upper endoscope as deep as possible. CONCLUSION: The deep insertion of standard endoscopes is useful for the diagnosis of obscure gastrointestinal bleeding.

High impacts of cultivar and home-cooking practice on the content of free myo-inositol, a bioavailable health-promoting cyclitol, in sweet potato.

Free myo-inositol is a bioavailable form of a cyclitol having various health-promoting activities. The impact of cultivar and home-cooking practice on the content of free myo-inositol in sweet potatoes (12 cultivars grown in 2 different locations) was studied. A GC-MS/MS method following in situ trimethylsilylation was established and validated to determine free myo-inositol. The established analytical method was sensitive, precise, and accurate. It was found that free myo-inositol content in sweet potato varied greatly (sevenfolds) with cultivar, ranging from 377.1 to 2628.3 mg/kg dw. A cultivar Poongwon-mi was found to be an exceptionally rich source of free myo-inositol (2628.3 mg/kg dw). Home-cooking practice markedly increased free myo-inositol content (maximum 240%). Baking showed the highest impact on the increase in free myo-inositol, followed by steaming, microwave cooking, and boiling, in decreasing order. This represents the first report of the remarkably high impact of cultivar and home-cooking practice on the free myo-inositol content in sweet potato. PRACTICAL APPLICATION: The free myo-inositol content in sweet potato varied greatly with the cultivars. Poongwon-mi contained a surprisingly high content of free myo-inositol. Home-cooking dramatically increased the free myo-inositol content.

Bile Acids: Major Regulator of the Gut Microbiome.

Bile acids are synthesized from cholesterol and play an important role in regulating intestinal microflora. The different degrees of hydrophobicity and acidity of individual bile acids may affect their antimicrobial properties. We examined the antimicrobial effects of different bile acids on various microorganisms in vitro and confirmed whether these remain consistent in vivo. Using human bile acids, including ursodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, a disc diffusion test was performed, and a rodent model was created to determine the antimicrobial effects of each bile acid. The fecal bacterial population was analyzed using a real-time polymerase chain reaction. Each bile acid showed different microbial inhibitory properties. The inhibitory activity of bile acids against microbiota which normally resides in the gastrointestinal tract and biliary system, was low; however, normal flora of other organs was significantly inhibited. Changes in microbial counts after bile acid administration in a rodent model differed in the colon and cecum. The in vivo and in vitro results show that the antimicrobial effects of bile acids against intestinal microbiota were similar. In conclusion, bile acids could be a novel treatment strategy to regulate gut microbiota.

Numerical and Experimental Analysis of DVA on the Flexible-Rigid Rail Vehicle Carbody Resonant Vibration.

This paper examines the influence of the equipment considered as a DVA (Dynamic Vibration Absorber) upon the mode of vertical vibrations of the car body in high-speed vehicles. The car body is represented as an Euler-Bernoulli beam to minimize flexible vibration. The DVA approach is used to find the appropriate suspension frequencies for various types of equipment. A vertical mathematical model with a flexible car body and equipment is developed to investigate the effect of equipment mass, suspension stiffness, damping, and mounting location on car-body flexible vibrations. A three-dimensional, rigid-flexible coupled vehicle system dynamics model is developed to simulate the car body and equipment's response to track irregularities. The experimental result was considered to verify the theoretical analysis and dynamic simulation. The mathematical analysis demonstrates that the DVA theory can be used to design the suspension parameters of the equipment and that it is suitable and effective in reducing the flexible vibration of the car body in which the vertical bending mode is greatly affected. Heavy equipment should be mounted as close to the car body's center as possible to achieve significant flexible vibration reduction, whereas light equipment contributes very little flexible vibration reduction.

Pharmacokinetics of Ginsenoside Rb1, Rg3, Rk1, Rg5, F2, and Compound K from Red Ginseng Extract in Healthy Korean Volunteers.

Individual differences in ginsenoside pharmacokinetics following ginseng administration in humans are still unclear. We aimed to investigate the pharmacokinetic properties of various ginsenosides, including Rb1, Rg3, Rg5, Rk1, F2, and compound K (CK), after a single oral administration of red ginseng (RG) and bioconverted red ginseng extract (BRG). This was a randomized, open-label, single-dose, single-sequence crossover study with washout every 1 week, and 14 healthy Korean men were enrolled. All subjects were equally assigned to two groups and given RG or BRG capsules. The pharmacokinetic parameters of ginsenosides were measured from the plasma drug concentration-time curve of individual subjects. Ginsenosides Rg3, Rk1 + Rg5, F2, and CK in the BRG group showed a higher C max, AUC(0-t), and AUC(0-∞) and shorter T max (for CK) than those in the RG group. These results suggest that BRG may lead to a higher absorption rate of bioactive ginsenosides. This study provides valuable information on the pharmacokinetics of various bioactive ginsenosides, which is needed to enhance the therapeutic efficacy and pharmacological activity of ginseng.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes.

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Effects of Granulocyte Macrophage Colony-Stimulating Factor Inhibition on the Skin/Nerve Cell Model In Vitro.

The present study is based on the concept of neuro-aging and how it may affect surrounding skin cells. It has been shown that many factors play a significant role in skin homeostasis by interfering with various cytokines, either through activation or inhibition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine, and our previous study has shown its effects on neuronal senescence after ultraviolet (UV) irradiation of skin cells. Following our previous work, this study was performed to investigate the neuroprotective effects of a GM-CSF antagonist, and how it may play an essential role in mediating anti-senescence and anti-inflammatory effects in the keratinocyte/nerve aging model. When human blastoma cells (SH-SY5Y) were treated with 10 ng/ml of GM-CSF, the levels of regulatory RNAs associated with aging, such as matrix metalloproteinase-9 (MMP9), nuclear factor NF-kappa-B p50 subunit (NFKB), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1ß) increased, whereas GM-CSF inhibition caused their expression to decrease. A decrease in the antioxidant, glutathione (GSH) was observed after SH-SY5Y cells were treated with GM-CSF. This study confirms that this GM-CSF antagonist may play an important role in neural senescence, where inhibition may be a new target in the skin/nerve aging model.

A Combination of Korean Red Ginseng Extract and Glycyrrhiza glabra L. Extract Enhances Their Individual Anti-Obesity Properties in 3T3-L1 Adipocytes and C57BL/6J Obese Mice.

Anti-obesity activities of Korean red ginseng saponin fraction (RGS) and/or Glycyrrhiza glabra L. extract (GG) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice. RGS and GG extracts were mixed at a mass ratio of 3:1 (SG31), 1:1 (SG11), or 1:3 (SG13). SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts. SG31 showed higher inhibition efficiency on triglyceride (TG) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity. It also decreases the expression of adipogenic and lipogenic genes such as C/EBPα and SREBP-1c (sterol regulatory element-binding protein 1c). In the obese induced mouse model, SG31 significantly reduced white adipose tissue weight and body weight, attenuated dyslipidemia, and decreased serum TG levels. In some indices, the activity of SG31 was even higher compared with Garcinia Cambogia water extract, a positive control. The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase (AMPK) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance, inhibit TG formation, and promote ß-oxidation of fatty acids. Therefore, SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies.

Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research.

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%-65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies.

Synergistic action of Erigeron annuus L. Pers and Borago officinalis L. enhances anti-obesity activity in a mouse model of diet-induced obesity.

Prior studies show that Borago officinalis L. (BO) can suppress lipid accumulation in 3 T3-L1 adipocytes. Similarly, we recently revealed that Erigeron annuus L. Pers (EA) can significantly diminish both lipid accumulation and adipocyte differentiation in 3 T3-L1 cells through an AMPK (AMP-activated protein kinase)-dependent mechanism. Accordingly, the objective of this present study was to evaluate the anti-obesity activity of EA and/or BO using an animal model of obesity. Obesity was induced in C57BL/6 J mice by feeding a high-fat diet (HFD; 60 kcal% fat) for 3 weeks, followed by administration of EA and/or BO (100-200 mg/kg body weight) or positive control Garcinia Cambogia (GC) (100 mg/kg body weight) for an additional 8 weeks. The anti-obesity effect of EA and/or BO was assessed by measuring body weight, adipocyte size, lipid accumulation, and expression level of genes associated with adipogenesis. We found the administration of EA and/or BO significantly attenuated increases in body weight gain, adipocyte size, and lipid accumulation in obese mice induced by HFD. In addition, western blot analysis revealed that HFD-mediated increases in expressions levels of adipogenic genes such as PPARγ, C/EBPα, and SREBP-1c were diminished by EA and/or BO. Moreover, EA and/or BO significantly stimulated the production of adiponectin, a unique adipokine known to stimulate the breakdown of fat/lipids, whereas adiponectin levels were reduced in mice fed a HFD. Notably, a combination of EA and BO was more effective at modulating such parameters than EA or BO alone. Taken together, these results demonstrate that an anti-obesity effect of EA and/or BO can reduce adipocyte hypertrophy and modulate the expression of adipogenesis-associated genes.

Anti-Amyloidogenic Effects of Asarone Derivatives From Perilla frutescens Leaves against Beta-Amyloid Aggregation and Nitric Oxide Production.

Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aß) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aß aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of Perilla frutescens (L.) Britton (Lamiaceae) and its hexane fraction on Aß aggregation. Here, the hexane fraction of P. frutescens was subjected to diverse column chromatography based on activity-guided isolation methodology. This approach identified five asarone derivatives including 2,3-dimethoxy-5-(1E)-1-propen-1-yl-phenol (1), ß-asarone (2), 3-(2,4,5-trimethoxyphenyl)-(2E)-2-propen-1-ol (3), asaronealdehyde (4), and α-asarone (5). All five asarone derivatives efficiently reduced the aggregation of Aß and disaggregated preformed Aß aggregates in a dose-dependent manner as determined by a Thioflavin T (ThT) fluorescence assay. Furthermore, asarone derivatives protected PC12 cells from Aß aggregate-induced toxicity by reducing the aggregation of Aß, and significantly reduced NO production from LPS-stimulated BV2 microglial cells. Taken together, these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in AD.

Inhibitory effect of α-amyrin acetate isolated from Fraxinus rhynchophylla on Th17 polarization.

BACKGROUND: T helper 17 (Th17) cells, which are differentiated from CD4+ T cells, drive inflammation, leading to autoimmune diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Therefore, inhibiting Th17 polarization could be a therapeutic target for inflammatory diseases. PURPOSE: We investigated the inhibitory effect of Fraxinus rhynchophylla (Oleaceae) on Th17 differentiation and found its active component. STUDY DESIGN: The activity of F. rhynchophylla and its active constituent was verified using CD4+ cells extracted from C57BL/6 mice. METHODS: Micro-environment for Th17 polarization was provided to CD4+ cells and the effect of treatment with samples was measured by enzyme linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and Western blot. RESULTS: The extract of F. rhynchophylla Hance and its chemical constituent, α-amyrin acetate, which was isolated via bioassay-guided isolation, significantly inhibited Th17 polarization as revealed when interleukin (IL)-17, a characteristic cytokine produced by Th17 cells, was measured. Furthermore, the inhibitory effect of α-amyrin acetate was compared to the amyrin derivatives, α-amyrin and ß-amyrin. All displayed a suppressive effect on Th17 polarization and all reduced the expression of single transducer and activator of transcription 3 (STAT3) and retinoic acid receptor-related orphan receptor γt (RORγt), which are crucial transcription factors regulating Th17 differentiation. α-Amyrin acetate, however, exhibited the most prominent effects, which indicates that the functional group, acetate, might strengthen the inhibitory effect on Th17 differentiation. CONCLUSION: Taken together, these results suggest that the extract of F. rhynchophylla and its active constituent, α-amyrin acetate, could be applied as a potential therapeutic agent for autoimmune disorders such as rheumatoid arthritis.

A Study on Fatigue State Evaluation of Rail by the Use of Ultrasonic Nonlinearity.

Nonlinear ultrasonic testing has been accepted as a promising manner for evaluating material integrity in an early stage. Stress fatigue is the main threats to train safety, railways examinations for stress fatigue are more significant and necessary. A series of ultrasonic nonlinear wave experiments are conducted for rail specimens extracted from railhead with different degree of fatigue produced by three-point bent loading condition. The nonlinear parameter is the indicator of nonlinear waves for expressing the degree the fatigue. The experimental results show that the sensitivity of a third harmonic longitudinal wave is higher than second harmonic longitudinal wave testing. As the same time, collinear wave mixing shows strong relative with fatigue damages than a second longitudinal wave nondestructive testing (NDT) method and provides more reliable results than third harmonic longitudinal waves nonlinear testing method.

Comparative Biological Effects of Human Amnion and Chorion Membrane Extracts on Human Adipose-Derived Stromal Cells.

Although therapies with human amnion/chorion are used to ameliorate acute and chronic wounds, it is unclear which component of the amnion/chorion tissue promotes wound healing. To characterize the comparative effects of amnion and chorion in wound healing, we used human adipose-derived stromal cells to assess cell viability, migration, and gel contraction after treatment with amnion membrane extract (AME) or chorion membrane extract (CME). We then correlated the possible effectors via AME and CME protein profiling, and compared them by enzyme-linked immunosorbent assay (ELISA), western blotting, and immunocytochemistry. Cell viability was significantly increased with 50 and 100 µg/mL AME treatment, but with CME treatment, a significant increase was only observed with 100 µg/mL. With CME treatment, cell migration was 2.22-fold greater than the control, and collagen gels showed 20% greater contraction. Compared to control, the expression levels of α-smooth muscle actin (SMA) and smooth muscle protein 22-alpha (SM22α) increased both with AME and CME treatments, whereas calponin expression decreased. Protein profiling revealed significantly higher tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-8, exotoxin, and adiponectin levels in CME than in AME, and ELISA revealed 8-fold higher adiponectin levels in cells treated with CME than those treated with AME. Immunocytochemistry revealed that α-SMA, SM22α, and calponin were significantly higher in CME- than AME-treated cells; however, adiponectin treatment did not enhance α-SMA, SM22α, or calponin expression. In conclusion, amnion and chorion membrane extracts exerted differential effects on proliferation and contraction of human adipose-derived stromal cells. Amnion extract was superior at inducing cell proliferation and migration, whereas CME was superior at inducing cell contraction.

Effects of Granulocyte-Macrophage Colony-Stimulating Factor on Neuronal Senescence in Ultraviolet Irradiated Skin.

Ultraviolet (UV) irradiation affects neuronal structures of the skin and accelerates skin aging. Cytokine cascades in keratinocytes after UV irradiation may result in a paracrine inhibitory effect on nerve cells. The purpose of the present study was to determine the direct effect of cytokines induced by UV radiation on nerve cells in terms of neuronal senescence. Our group performed a preliminary study to determine cytokines induced in UV-irradiated keratinocytes. Among 40 cytokines studied, granulocyte-macrophage colony-stimulating factor (GM-CSF) was increased 4-fold in inflammation antibody array. The GM-CSF was added to cultured human neuroblastoma cells. To evaluate the effect of cellular senescence, the authors performed real-time polymerase chain reaction (RT-PCR), western blot, immunocytochemical, and phase-contrast microscopic evaluations. Expression levels of matrix metallopeptidase-9 (MMP-9), nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1), inducible nitric oxide synthase (iNOS), and interleukin ß1 (IL-ß1) were assessed by RT-PCR. Expression levels of AAP and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) related to formation of beta-amyloid were evaluated by western blot analysis. Expression levels of MMP-9, NF-κB1, iNOS, and IL-ß1 after treatment with GM-CSF were significantly higher than those in the control group. Enhanced expression of AAP and BACE1 was also observed in the treatment group. Thus, GM-CSF might have a provocative effect on nerve cells in terms of neuronal senescence.

Effects of Ultraviolet Irradiation on Cellular Senescence in Keratinocytes Versus Fibroblasts.

Aging is a biologic process characterized by time-dependent functional declines that are influenced by oxidative stress-induced inflammatory reactions. In particular, ultraviolet (UV) irradiation plays a key role in cellular senescence in photo-aged skin. However, the cellular senescence of epidermal keratinocytes and dermal fibroblasts by UV irradiation may differ depending on the exposure time and dosage of UV irradiation. Therefore, the purpose of the study was to evaluate and compare the effects of UV irradiation on cellular senescence in human epidermal keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). After cell viability test, 200 mJ/cm UV irradiation was used in this study. To evaluate the reactive oxygen species and reactive nitrogen species production, the levels of glutathione (GSH) and nitrite (NO2) were measured. We also performed reverse transcription-polymerase chain reaction, Western blot analysis, and senescence-associated beta-galactosidase assay. An overall decrease in GSH and an increase in NO2 were observed in the HaCaT and HDF cells. However, the time-line and dose-dependent effects varied. Higher expressions of tumor necrosis factor-α, inducible nitric oxide synthase, and interleukin-1ß than that of the control group were observed in both cells. The HDF cells showed high levels of matrix metallopeptidase 9 and neutral endopeptidase protein but low levels of SIRT1 and procollagen I. The expression of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) was increased in the HaCaT cells, but not in the HDF cells. The NF-κB peaked at 1 hour after UV irradiation in the HaCaT cells. The "turning-on" signal was faster in the irradiated HaCaT cells.