The ethanol extract of Cyperus exaltatus var. iwasakii exhibits cell cycle dysregulation, ERK1/2/p38 MAPK/AKT phosphorylation, and reduced MMP-9-mediated metastatic capacity in prostate cancer models in vitro and in vivo.

BACKGROUND: Prostate cancer is the second most common cause of cancer death worldwide in men. The development of novel and highly efficient therapeutic strategies is strongly recommended to treat prostate cancer. Cyperaceae are an ecologically and economically important family of plants with several pharmacological effects. However, the biological efficacy of Cyperus exaltatus var. iwasakii (CE) is unknown. PURPOSE: This study aimed to investigate the antitumor effect of the ethanol extract of CE against prostate cancer. METHODS: In vitro antitumor efficacy of CE was explored by the MTT assay, cell counting assay, FACS analysis, immunoblot, wound-healing migration, invasion assay, zymographic assay, and EMSA in prostate cancer cells, DU145 and LNCaP. For in vivo experiments, xenograft mice were injected with LNCaP cells. Histology (H&E and Ki-67) and biochemical enzyme assay were then performed. The toxicity test was evaluated by an acute toxicity assay. The phytochemical constituents of CE were identified by spectrometric and chromatographic analyses. RESULTS: CE exerted a significant antiproliferative effect against prostate cancer cells. CE-induced antiproliferative cells were associated with cell cycle arrest at G0/G1 (cyclin D1/CDK4, cyclin E/CDK2, p21Waf1) in DU145 cells, but G2/M (ATR, CHK1, Cdc2, Cdc25c, p21Waf1, and p53) in LNCaP cells. CE stimulated the phosphorylation of ERK1/2, p38 MAPK, and AKT in DU145 cells, but only p38 MAPK phosphorylation was increased in LNCaP cells. CE treatment suppressed migration and invasion in the two types of prostate cancer cells by inhibiting MMP-9 activity through the regulation of transcription factors, such as AP-1 and NF-κB. In vivo experiments showed a reduction in tumor weight and size following oral CE administration. Histochemistry confirmed that CE inhibited tumor growth in the mouse LNCaP xenograft model. The administration of CE had no adverse effects on body weight, behavioral patterns, blood biochemistry, and histopathology findings of vital organs in mice. Finally, a total of 13 phytochemical constituents were identified and quantified in CE. The most abundant secondary metabolites in CE were astragalin, tricin, and p-coumaric acid. CONCLUSION: Our results demonstrated the antitumor efficacy of CE against prostate cancer. These findings suggest that CE might be a potential candidate for prostate cancer prevention or treatment.

Ethyl Acetate Fraction from a Catalpa ovata G. Don Extract Inhibits ɑ-MSH-Induced Melanogenesis through the cAMP/CREB Pathway.

The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.

Plasma amyloid-beta oligomer is related to subjective cognitive decline and brain amyloid status.

BACKGROUND: Subjective cognitive decline (SCD) is a target for Alzheimer's disease prediction. Plasma amyloid-beta oligomer (AßO), the pathogenic form of Aß in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aß deposition. The relationship between plasma AßO, brain Aß deposition, and SCD in individuals with normal objective cognition has not been investigated. METHODS: In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma AßO level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain Aß deposition was assessed by [18F] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma AßO levels or SUVR were analyzed in multiple linear regression models. The association between plasma AßO level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. RESULTS: Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma AßO levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs (p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma AßO levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma AßO presented area under the curves of 0.789 (ratio) and 0.783 (concentration). CONCLUSIONS: Our findings indicate that the high plasma AßO level could serve as a potential surrogate biomarker of severe SCD and the presence of brain Aß deposition in individuals with normal objective cognition.

Structural properties and anti-dermatitis effects of flavonoids-loaded gold nanoparticles prepared by Eupatorium japonicum.

Recently, green synthesis-based nanoformulations using plants or microorganisms have attracted great interest because of their several advantages. Nanotechnology-based biological macromolecules are emerging materials with potential applications in cosmetics and medications for ameliorating and treating inflammatory skin diseases (ISDs). Eupatorium japonicum (EJ), a native Korean medicinal plant belonging to the family Asteraceae, has been traditionally used to prepare prescriptions for the treatment of various inflammatory diseases. EJ-based gold nanoparticles (EJ-AuNPs) were biosynthesized under optimal conditions and characterized their physicochemical properties using various microscopic and spectrometric techniques. Additionally, the effects of EJ-AuNPs on ISDs as well as their underlying mechanisms were investigated in the tumor necrosis factor-α/interferon-γ (T+I)-induced skin HaCaT keratinocytes. The MTT and live/dead cell staining assays showed that EJ-AuNP treatment was considerably safer than EJ treatment alone in HaCaT cells. Moreover, EJ-AuNP treatment effectively suppressed the production of T+I-stimulated inflammatory cytokines (RANTES, TARC, CTACK, IL-6, and IL-8) and intracellular reactive oxygen species, and such EJ-driven anti-inflammatory effects were shown to be associated with the downregulation of intracellular mitogen-activated protein kinase and nuclear factor-κB signaling pathways. The present study provides preliminary results and a valuable strategy for developing novel anti-skin dermatitis drug candidates using plant extract-based gold nanoparticles.

Biologically Synthesized Rosa rugosa-Based Gold Nanoparticles Suppress Skin Inflammatory Responses via MAPK and NF-κB Signaling Pathway in TNF-α/IFN-γ-Induced HaCaT Keratinocytes.

Nanotechnology-applied materials and related therapeutics have gained attention for treating inflammatory skin diseases. The beach rose (Rosa rugosa), belonging to the family Rosaceae, is a perennial, deciduous woody shrub endemic to northeastern Asia. In this study, R. rugosa-based gold nanoparticles (RR-AuNPs) were biologically synthesized under optimal conditions to explore their potential as anti-inflammatory agents for treating skin inflammation. The synthesized RR-AuNPs were analyzed using field emission-transmission electron microscopy, energy-dispersive X-ray spectrometry, selected-area electron diffraction, and X-ray diffraction. The uniformly well-structured AuNPs showed near-spherical and polygonal shapes. Cell viability evaluation and optical observation results showed that the RR-AuNPs were absorbed by human keratinocytes without causing cytotoxic effects. The effects of RR-AuNPs on the skin inflammatory response were investigated in human keratinocytes treated with tumor necrosis factor-α/interferon-γ (T + I). The results showed that T + I-stimulated increases in inflammatory mediators, including chemokines, interleukins, and reactive oxygen species, were significantly suppressed by RR-AuNP treatment in a concentration-dependent manner. The western blotting results indicated that the RR-AuNP-mediated anti-inflammatory effects were highly associated with the suppression of inflammatory signaling, mitogen-activated protein kinase, and nuclear factor-κB. These results demonstrate that plant extract-based AuNPs are novel anti-inflammatory candidates for topical application to treat skin inflammation.

Effects of a High-Molecular-Weight Polysaccharides Isolated from Korean Persimmon on the Antioxidant, Anti-Inflammatory, and Antiwrinkle Activity.

Persimmon (Diospyros kaki), a familiar and widespread fruit worldwide, is known to exhibit several physiological effects because of the presence of pharmacologically active compounds called phytochemicals. However, its high-molecular-weight compounds, particularly polysaccharides, have not been extensively studied. In this study, D. kaki extract (DK) was fractionated into low- and high-molecular-weight fractions (DK-L and DK-H, respectively) through ethanol fractionation, and their effects on antioxidant, anti-inflammatory, and antiwrinkle activities were investigated by an in vitro system. DK-H contained significantly higher contents of neutral sugar, uronic acid, and polyphenols compared to DK and DK-L. Furthermore, DK-H exhibited significantly improved pharmacological activities, such as antioxidant, anti-inflammatory, and antiwrinkle properties, compared to those of DK and DK-L, demonstrating that DK-H may play an important role in mediating the beneficial effects of persimmon. Sugar composition analysis and molecular characterization indicated that DK-H consisted of a galacturonic acid (GalA)-rich polysaccharide with a molecular weight of >345 kDa that mainly comprised GalA and small amounts of neutral sugar and polyphenol residues. These results suggest that the bioactive fraction DK-H is likely to be a GalA-rich pectic polysaccharide containing a small number of polyphenol residues, which may be a novel candidate in the pharmaceutical and cosmeceutical industries.

Benzodiazepine-Related Cognitive Impairment or Dementia: A Signal Detection Study Using a Case/Non-Case Approach.

OBJECTIVE: The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a case/non-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. METHODS: Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). RESULTS: Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66-4.38). Higher ROR estimates were shown in female (2.33, 1.48-3.67) and in those with polypharmacy (2.20, 1.35-3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. CONCLUSION: These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

Anti-inflammatory action of herbal medicine comprised of Scutellaria baicalensis and Chrysanthemum morifolium.

Various mixtures were prepared depending on the mixing ratio of Scutellaria baicalensis hot water extract (SB-HW), and Chrysanthemum morifolium ethanol extract (CM-E) and their anti-inflammatory activity were compared. Among them, SB-HW (80 µg/mL)/CM-E (120 µg/mL) or SB-HW (40 µg/mL)/CM-E (160 µg/mL) significantly inhibited LPS-stimulated NO and IL-6 levels in RAW 264.7 cells. The SB-HW (80 µg/mL)/CM-E (120 µg/mL) mixture, which was determined as active mixture, significantly reduced MUC5AC secretion in PMA and LPS-induced NCI-H292 cells. The active mixture also reduced the production of PGE2 and IL-8 in PMA-induced A549 cells. LC-MS/MS analysis showed that the active mixture was composed of high contents of flavone glycosides, such as baicalin and cynaroside. Western blot analysis indicated that the active mixture suppressed phosphorylation of ERK, JNK, and p38, associating with the inhibition of MAPK signaling. Taken together, our results suggest that the active mixture could be applied as a new anti-inflammatory herbal medicine. ABBREVIATIONS: JNK: c-Jun N-terminal kinases; COPD: chronic obstructive pulmonary disease; CM: Chrysanthemum morifolium; COX-2: cyclooxygenase-2; ERK: extracellular-signal-regulated kinase; IL-6: interleukin-6; IL-8: interleukin-8; IL-12: interleukin-12; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; NO: nitric oxide; NK- κB: nuclear factor kappa B; p38: p38 mitogen-activated protein kinases; PBS: phosphate buffered saline; PMA: phorbol-12-myristate-13-acetate; SB: Scutellaria baicalensis; PGE2: prostaglandin E2; TBST: Tris-buffered saline containing 0.1% Tween 20; TIC: total ion chromatogram; TNF-α: tumor necrosis factor-alpha.

Benzodiazepine Use and Risk of Acute Angle-Closure Glaucoma: A Population-Based Case-Crossover Study.

INTRODUCTION: Theoretically, benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG). However, little evidence exists regarding this association. OBJECTIVE: The objective of this study was to assess whether the use of BZDs is associated with the risk of AACG. METHODS: We conducted a population-based case-crossover study using the nationwide claims database of the National Health Insurance Service in Korea. Patients with newly diagnosed AACG-between 1 January 2013 and 31 December 2016-who had received at least one BZD prescription prior to AACG diagnosis were enrolled. The date of AACG diagnosis was set as the index date. We assessed BZD use by each patient during a 30-day case period prior to the index date and three consecutive control periods that preceded this date. We used conditional logistic regression that adjusted for concomitant medications to determine the odds ratio for the use of BZDs in the case period compared with that in the control period in patients with incident AACG. RESULTS: Of the 11,093 patients with incident AACG, 6709 received a prescription for BZD prior to diagnosis. BZD use was associated with an increased risk of AACG [adjusted odds ratio (aOR) = 1.40; 95% confidence interval (CI) 1.27-1.54]. AACG risk was similar for short-acting (aOR = 1.40, 95% CI 1.24-1.57) and long-acting BZDs (aOR = 1.33, 95% CI 1.18-1.50). CONCLUSION: We found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients.

Benzylideneacetone Derivatives Inhibit Osteoclastogenesis and Activate Osteoblastogenesis Independently Based on Specific Structure-Activity Relationship.

(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 µM (IC50 of alendronate, 3.7 µM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 µM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 µM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.

Inhibition of ß-site amyloid precursor protein cleaving enzyme 1 and cholinesterases by pterosins via a specific structure-activity relationship with a strong BBB permeability.

We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer's disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC50 of 29.6, 16.2 and 48.1 µM, respectively. The Ki values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC50 values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure-activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (Pe) of 60.3×10-6 cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of Aß peptides from neuroblastoma cells that overexpressed human ß-amyloid precursor protein at 500 µM. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics.

Population-based dementia prediction model using Korean public health examination data: A cohort study.

The early identification and prevention of dementia is important for reducing its worldwide burden and increasing individuals' quality of life. Although several dementia prediction models have been developed, there remains a need for a practical and precise model targeted to middle-aged and Asian populations. Here, we used national Korean health examination data from adults (331,126 individuals, 40-69 years of age, mean age: 52 years) from 2002-2003 to predict the incidence of dementia after 10 years. We divided the dataset into two cohorts to develop and validate of our prediction model. Cox proportional hazards models were used to construct dementia prediction models for the total group and sex-specific subgroups. Receiver operating characteristics curves, C-statistics, calibration plots, and cumulative hazards were used to validate model performance. Discriminative accuracy as measured by C-statistics was 0.81 in the total group (95% confidence interval (CI) = 0.81 to 0.82), 0.81 in the male subgroup (CI = 0.80 to 0.82), and 0.81 in the female subgroup (CI = 0.80 to 0.82). Significant risk factors for dementia in the total group were age; female sex; underweight; current hypertension; comorbid psychiatric or neurological disorder; past medical history of cardiovascular disease, diabetes mellitus, or hypertension; current smoking; and no exercise. All identified risk factors were statistically significant in the sex-specific subgroups except for low body weight and current hypertension in the female subgroup. These results suggest that public health examination data can be effectively used to predict dementia and facilitate the early identification of dementia within a middle-aged Asian population.

Low Molecular Weight Mannogalactofucans Derived from Undaria pinnatifida Induce Apoptotic Death of Human Prostate Cancer Cells In Vitro and In Vivo.

Low molecular weight mannogalactofucans (LMMGFs) prepared by enzymatic degradation of high molecular weight Undaria galactofucan (MF) were evaluated for their anti-cancer effects against human prostate cancer. Correlation NMR and linkage analyses confirmed that LMMGFs consist mainly of α-fucose and ß-galactose units: α-fucose units are 1,3-linked; ß-galactose units are terminal, 1,3- and/or 1,6-linked; both sugars are partially sulphated, fucose at positions O-2 and/or O-4 and galactose at O-3. Mannose residue, as a minor sugar, presents as the 1,4-linked terminal units. LMMGFs more significantly induced cell cycle arrest at the G0/G1 phase and cell death via suppression of the Akt/GSK-3ß/ß-catenin pathway than MF in human PC-3 prostate cancer cells. LMMGFs upregulated mRNA expression of death receptor-5 (DR-5), the ratio of Bax to Bcl-2, the cleavage of caspases and PARP, the depolarisation of mitochondrial membrane potential, and ROS generation. LMMGFs (200-400 mg/kg) effectively reduced both tumour volume and size in a xenografted mouse model. These results demonstrated that LMMGFs attenuate the growth of human prostate cancer cells both in vitro and in vivo, suggesting that LMMGFs can be used as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat androgen-independent human prostate cancer. Graphical Abstract.

Anti-melanogenic activity of schaftoside in Rhizoma Arisaematis by increasing autophagy in B16F1 cells.

Skin pigmentation involves multiple processes, including melanin synthesis, transport, and melanosome release. Melanin content determines skin color and protects against UV radiation-induced damage. Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular components and organelles. In the present study, B16F1 cells were treated with Rhizoma Arisaematis extract (RA) and assessed for pigmentation and autophagy regulation. RA treatment suppressed the α-MSH-stimulated increase of melanogenesis and down-regulated the expression of tyrosinase and TRP1 proteins in B16F1 cells. In addition, autophagy was activated in RA-treated cells. Inhibition of autophagy reduced the anti-melanogenic activity of RA in α-MSH-treated B16F1 cells. We identified schaftoside as an effector molecule by LC-MS analysis of RA. Consistently, treatment of schaftoside showed anti-melanogenic effect and induced autophagy activation in B16F1 cells. Inhibition of autophagy by 3 MA treatment reduced the anti-melanogenic effect of the schaftoside and recovered expression level of melanogenesis regulators in α-MSH-treated B16F1 cells. Taken together, our results suggest that schaftoside from RA inhibits skin pigmentation through modulation of autophagy.

Photodynamic therapy inhibits melanogenesis through paracrine effects by keratinocytes and fibroblasts.

Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In this study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in vivo. Exposure of MCs to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing MCs to conditioned media of PDT-treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due to a decreased release of melanocyte-stimulating cytokines such as Kit ligand and hepatocyte growth factor from these cells. Furthermore, we observed that PDT reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting the clinical importance of skin whitening by PDT.

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 µM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1ß, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1ß secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1ß and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

Factors Associated with Insomnia among the Elderly in a Korean Rural Community.

OBJECTIVE: Sleep disturbance is common in the elderly, which is result from multi-factorial causes encompassing socio-demographic, behavioral, and clinical factors. We aimed to identify factors associated with insomnia among the elderly in a rural community in South Korea, a country with a rapidly growing aged population. METHODS: This cross-sectional study used the data from the second wave of the Korean Social life, Health and Ageing Project, which is a cohort study of individuals living in a typical rural community in South Korea. Socio-demographic, behavioral, and clinical characteristics were obtained through face-to-face interviews. Various factors suspected to be associated with insomnia were compared between elderly participants with and without insomnia, and multiple logistic regression analyses were conducted to identify independent risk factors for insomnia. RESULTS: We found that 32.4% of 509 participants (72.8±7.7 years old) had insomnia. Female sex [odds ratio (OR)=2.19], low education level (OR=2.44), current smoking (OR=2.26), number of chronic diseases (OR=2.21 for 2-3 chronic diseases; OR=2.06 for 4 or more chronic diseases), and depression (OR=2.53) were independently associated with insomnia. CONCLUSION: We found that sex, education, chronic disease, and depression independently increase the risk of insomnia of the elderly in a Korean rural community. To overcome the elderly's insomnia, interventions should target modifiable factors such as depression. To promote active aging, longitudinal studies of factors associated with insomnia among the elderly should be performed in different regions and communities.

Development of Epidural and Paraspinal Abscesses after Insufficient Evaluation and Treatment of Acute Pyelonephritis Caused by Staphylococcus aureus.

Diagnoses of pyelonephritis caused by Staphylococcus aureus should be accompanied by investigations of concomitant bladder obstruction and metastatic infections, especially to the spine or heart. Complicated pyelonephritis due to S. aureus requires more than 2 weeks of antibiotics, which is the typically recommended treatment duration for pyelonephritis. We describe a patient who was diagnosed with complicated epidural and paraspinal abscesses after insufficient evaluation and treatment of acute pyelonephritis due to S. aureus. A 62-year-old man with type 2 diabetes was admitted with fever, increased urinary frequency, and left flank pain. He was diagnosed with acute pyelonephritis caused by S. aureus. His fever and flank pain subsided after 3 days of intravenous antibiotics. Evaluation of bladder obstruction and metastatic infection were not performed, as he declined further evaluation. The patient was discharged with oral antibiotics and was requested to attend weekly appointments but was lost to follow-up. One month later, the patient presented at the outpatient clinic with similar symptoms. Computed tomography showed recurrent pyelonephritis and a distended bladder. His flank pain persisted despite administration of an opioid agent. Therefore, magnetic resonance imaging was performed, revealing epidural and paraspinal abscesses. Ultrasound-guided aspiration of the paraspinal muscle layer was performed, and blood and percutaneous aspirated fluid cultures revealed S. aureus growth. The pattern of antimicrobial sensitivity was identical to that at his first admission. Following more than 4 weeks of antibiotics, magnetic resonance imaging showed the abscesses had decreased in size. The patient was discharged without neurologic sequelae and was provided with oral antibiotics.