Molecular networking-guided isolation strategy of a new C-glycosyl flavone rotamer from Stellaria alsine and evaluation of anti-inflammatory and antioxidant activities.

INTRODUCTION: Stellaria alsine has traditionally been used as both a famine relief food and an alternative medicine in East Asia. Modern pharmacological studies have revealed that S. alsine has various biological effects such as anticancer, anti-hepatoma, anti-inflammatory, and antioxidative effects. However, the anti-inflammatory properties of chemical constituents derived from this plant have not been studied well. OBJECTIVES: To identify potential therapeutic candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD). METHODS: The distribution of chemical compounds was investigated by Global Natural Product Social (GNPS)-based molecular networking (MN) analysis using UPLC-Orbitrap tandem mass spectrometry. The anti-inflammatory and antioxidative effects of S. alsine extracts and fractions were evaluated by measuring interleukin (IL)-8 and reactive oxygen species (ROS) productions. RESULTS: The active EA layer of S. alsine showed the highest percentage of major compounds by feature-based molecular networking. The top candidate structures of EA fraction were rapidly annotated as flavone C- or O-glycosides via an advanced analysis tool, Network Annotation Propagation (NAP). With the GNPS molecular networking-guided isolation strategy, a new C-glycosyl flavone rotamer (1) was isolated. The structures of the major (1a) and minor (1b) rotational isomers were determined by extensive NMR analysis and MS/MS fragmentation. Finally, the anti-inflammatory activity of 1 was predicted by molecular docking simulations with IL-8 protein. CONCLUSION: These results suggested that the compound 1 is a potential therapeutic candidate for inflammatory bowel disease (IBD).

Multicomponent-Loaded Vesosomal Drug Carrier for Controlled and Sustained Compound Release.

Liposomes have been extensively adopted in drug delivery systems with clinically approved formulations. However, hurdles remain in terms of loading multiple components and precisely controlling their release. Herein, we report a vesosomal carrier composed of liposomes encapsulated inside the core of another liposome for the controlled and sustained release of multiple contents. The inner liposomes are made of lipids with different compositions and are co-encapsulated with a photosensitizer. Upon induction of reactive oxygen species (ROS), the contents of the liposomes are released, with each type of liposome displaying distinct kinetics due to the variance in lipid peroxidation for differential structural deformation. In vitro experiments demonstrated immediate content release from ROS-vulnerable liposomes, followed by sustained release from ROS-nonvulnerable liposomes. Moreover, the release trigger was validated at the organismal level using Caenorhabditis elegans. This study demonstrates a promising platform for more precisely controlling the release of multiple components.

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

Refining the online health information searcher typology: Applying the patient health engagement model.

BACKGROUND: Despite numerous quantitative findings on online health information seeking, little is known about the process of online health information seeking itself. OBJECTIVES: The study aimed to learn about how adults search for health information online, whether Macias et al.'s Online Health Searcher Typology applies to a broader, non-university sample, and to better identify and understand online health searchers by employing the Patient Health Engagement (PHE) model. METHODS: This study examined the role of engagement in online health information search processes using think-aloud qualitative interviews with 11 participants in their 30s to 70s. The research applied both thematic analysis and a quantitative coding scheme based on the PHE model to analyse the qualitative data that consists of 500 pages of think-aloud verbatim transcripts. RESULTS: This study found that four (flounderer, skimmer, digester and devourer) out of five types emerged as distinct search styles. Insights into engagement helped distinguish online health searcher types in this sample. CONCLUSION: The dynamics of the engagement dimension indicate that the online health information search process is multi-dimensional. It is comprised of different levels of cognitive, emotional, and conative responses, further extending the PHE model. Health science librarians and health professionals have a unique opportunity to help individuals better navigate online health search.

Association between Stroke Quality Assessments and Mortality within 30 Days among Patients Who Underwent Hemorrhagic Stroke Surgeries in South Korea.

INTRODUCTION: In South Korea, to improve the quality of medical services provided to stroke patients, stroke quality assessments have been implemented since 2006. To further promote improvement of care, financial incentives were introduced since 2012. This study aims to examine the association between stroke quality assessments and mortality within 30 days among South Korean adults who underwent hemorrhagic stroke surgeries to provide evidence of the importance of such assessments. METHODS: Data from 45,741 patients from 374 healthcare organizations, derived from the 2013-2016 claims data of the Korean Health Insurance Review and Assessment Service, were examined. To ensure homogeneity, only patients who underwent hemorrhagic stroke surgeries were selected. Healthcare organizations were classified based on whether stroke quality assessments were conducted. The dependent variable of this study was death within 30 days of hospitalization. A generalized linear mixed model was constructed to analyze the association between variables. RESULTS: Healthcare organizations without stroke quality assessments exhibited a higher risk of mortality than those that did (adjusted odds ratio [OR] = 1.53, 95% confidence interval [CI] = 1.16-2.01). Among healthcare organizations with the lowest volume, those without stroke quality assessments had a higher risk of mortality than those that did (tertile 1 [low], adjusted OR = 1.38, 95% CI = 1.04-1.84). Among rural healthcare organizations, those without assessments had a higher risk of mortality than did those that did (adjusted OR = 1.61, 95% CI = 1.06-2.43). CONCLUSIONS: The study identified a significant relationship between stroke quality assessments and 30-day mortality. Healthcare organizations without stroke quality assessments may exhibit a comparatively higher risk of mortality. Future interventions to minimize mortality and provide evidence for policymakers and healthcare leaders could involve expanding the scope of stroke quality assessment.

Cyclohumulanoid Sesquiterpenes Induced by the Noncompetitive Coculture of Phellinus orientoasiaticus and Xylodon flaviporus.

Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitive interactions between test strains. During our LC-MS-based chemical screening of randomized cocultures of Basidiomycetous fungi, we discovered that the coculture of Phellinus orientoasiaticus (Hymenochaetaceae) and Xylodon flaviporus (Schizoporaceae) induces multiple metabolites, although they did not show any competitive morphology. Targeted isolation yielded three new sesquiterpenes (1-3) along with five known analogues (4-8). The structures of the isolates were determined by MS and NMR experiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-, sterpurane-, and tremulane-type scaffolds (1-7) were produced by P. orientoasiaticus, whereas a drimane-type sesquiterpene (8) was produced by X. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds 1-7 exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 µM.

Successful delayed delivery of the second twin by evacuating the cord prolapsed first fetus and emergent cerclage: a report of 2 cases.

BACKGROUND: In twin pregnancies, the cord prolapse of either fetus during the pre-viable period leads to fetal death but can also cause an intrauterine infection, leading to death or prematu-re birth of the remaining fetus. However, there are no validated protocols to prolong the gestational period or decrease the morbidity and mortality of the remaining fetus. CASE PRESENTATION: The present cases were PPROM and cord prolapse very early during the second trimester (around 17 weeks in the first case and 19 weeks in the second case). The first fetus was evacuated, and cervical cerclage was performed at 23 and 20 weeks in the two cases, respectively. After maintaining the pregnancy, the second baby was born around 27 and 39 weeks in the first and second cases, respectively. The delivery interval between the first and second fetuses was 46 days in the first case and 126 days in the second case. CONCLUSION: If cord prolapse is identified at a pre-viable time in twin fetuses, evacuation and cerclage should be performed as soon as possible after the cord prolapse to reduce intrauterine infection and increase the survival chances of the remaining fetus.

Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. METHODS: Clinical parameters and postpartum complications were reviewed in all participants. Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4+ T, CD8+ T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. RESULTS: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4+ T and CD8+ T cells than the control group. Interestingly, senescent CD4+ T cells tended to increase and CD8+ T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274+) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. CONCLUSION: This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Impact of subjective dizziness on motor and non-motor symptoms in patients with early stages of Parkinson's disease.

Clinicians sometimes encounter patients with Parkinson's disease complaining of dizziness in real clinical settings. We sought to identify the relationship between self-perceived dizziness and motor or non-motor symptoms, especially in Parkinsonian patients in the early stages. Eight-six patients with less than five years of Parkinson's disease duration were recruited. We used the dizziness handicap inventory to access self-reported dizziness in patients with early Parkinson's disease. Parkinsonian motor symptoms such as postural instability and gait difficulty and non-motor features for global cognitive function, depressive mood, anxiety state, fatigue state, and autonomic dysfunction were measured using representative scales. Linear regression analysis demonstrated that the dizziness handicap inventory score was significantly related to postural instability and gait difficulty, anxiety, gastrointestinal, and cardiovascular domain of dysautonomia. In addition, the dizziness handicap inventory score was positively correlated with scores for postural instability and gait difficulty, anxiety, gastrointestinal, and cardiovascular dysautonomia. We found that self-reported dizziness was highly linked to postural instability and gait difficulty, anxiety, gastrointestinal and cardiovascular dysfunctions in patients with early Parkinson's disease. Further follow-up studies on the association between dizziness and the pathophysiology of Parkinson's disease are needed.

Heminiphilus faecis gen. nov., sp. nov., a member of the family Muribaculaceae, isolated from mouse faeces and emended description of the genus Muribaculum.

The novel strain AM35T was isolated from the faeces of C57BL/6 mice. These cells are strictly anaerobic, gram negative, oxidase negative, catalase positive, rod-shaped and non-motile. The strain produced creamy yellowish colonies on brain heart infusion (BHI) agar with hemin. Growth was investigated at 30-41 °C in the presence of 0.5-1.5% (w/v) NaCl at pH 6.5-8.5. Taxonomic analysis based on 16S rRNA gene sequencing revealed that strain AM35T is affiliated with the family Muribaculaceae and closely related to the genus Muribaculum. The genomic DNA G + C content of strain AM35T was 47.8 mol%. We detected the whole-cell sugars ribose and galactose; meso-2,6-diaminopimelic acid was absent. The major fatty acids (> 10%) were anteiso-C15:0 and iso-C15:0; the major polar lipid was phosphatidylethanolamine. The major respiratory quinones were MK-10 and MK-11. Based on our phylogenetic, phenotypic and chemotaxonomic analyses, strain AM35T represents a novel genus within the family Muribaculaceae, for which we propose the name Heminiphilus faecis gen. nov., sp. nov. The type strain of Heminiphilus faecis gen. nov., sp. nov. is AM35T (= KCTC 15907 T = DSM 110151 T).

Recent glycemic control can predict the progressive motor deficits of acute subcortical infarction with diabetes or prediabetes.

BACKGROUND AND PURPOSE: The predictors of progressive motor deficits in acute subcortical infarctions are still controversial. It is not known whether glycemic control influences on stroke progression. METHODS: A total of 268 consecutive patients with diabetes or prediabetes who had acute (< 24 h) subcortical infarction were enrolled. (1) All patients were divided into 4 groups by quartile of glycated hemoglobin (HbA1c). (2) Only the patients with diabetes were divided by effective glycemic control. Progressive motor deficits were prospectively captured and defined as an increase of motor score ≥ 1 on the upper or lower limb items of the National Institute of Health Stroke Scale within 72 h from stroke onset. RESULTS: Progressive motor deficits occur in 8/78 (10.3%) for ≤ 5.9, 15/61 (24.6%) for 6.0-6.4, 16/62 (25.8%) for 6.5-7.4, and 30/67 (44.8%) for ≥ 7.5. In diabetic patients alone, those occur in 5/37 (13.5%) for ≤ 6.5, 10/42 (23.8%) for 6.6-7.0, 12/42 (28.6%) for 7.1-8.0, and 24/50 (48.0%) for ≥ 8.1. An adjusted OR of progressive motor deficits was 2.61 (95% confidence interval [CI] 0.98-7.00, P = .056) for 6.0-6.4, 3.42 (95% CI 1.27-9.18, P = .015) for 6.5-7.4, and 6.65 (95% CI 2.38-18.62, P < .001) for ≥ 7.5. In diabetic patients alone, those were 3.15 (95% CI 0.89-11.15, P = .075) for 6.6-7.0, 2.90 (95% CI 0.79-10.61, P = .107) for 7.1-8.0, and 4.17 (95% CI 1.07-16.25, P = .038) for ≥ 8.1. The optimal cutoff value of HbA1c was 6.65% in discriminating progressive motor deficits. CONCLUSION: Increased HbA1c was associated with higher incidence of progressive motor deficits in acute subcortical infarction with diabetes and prediabetes.

Ring-shaped replicative helicase encircles double-stranded DNA during unwinding.

Ring-shaped replicative helicases are hexameric and play a key role in cellular DNA replication. Despite their importance, our understanding of the unwinding mechanism of replicative helicases is far from perfect. Bovine papillomavirus E1 is one of the best-known model systems for replicative helicases. E1 is a multifunctional initiator that senses and melts the viral origin and unwinds DNA. Here, we study the unwinding mechanism of E1 at the single-molecule level using magnetic tweezers. The result reveals that E1 as a single hexamer is a poorly processive helicase with a low unwinding rate. Tension on the DNA strands impedes unwinding, indicating that the helicase interacts strongly with both DNA strands at the junction. While investigating the interaction at a high force (26-30 pN), we discovered that E1 encircles dsDNA. By comparing with the E1 construct without a DNA binding domain, we propose two possible encircling modes of E1 during active unwinding.

Unmet needs related to the quality of life of advanced cancer patients in Korea: a qualitative study.

BACKGROUND: It has recently been emphasized that the unmet needs of cancer patients should be evaluated more holistically, for example, by exploring caregivers' perspectives and cross cultural differences. This study explored additional domains or items of unmet needs among Korean cancer patients in reference to the Sheffield Profile for Assessment and Referral to Care (SPARC). METHODS: We conducted four focus group discussions (FGDs) with 15 cancer patients, following a semi-structured format to elicit participants' health perceptions, comments on SPARC, and opinions on the roles of medical professionals to improve the health-related quality of life of cancer patients. We analyzed the verbatim transcripts using a content analysis method. RESULTS: The following themes were derived: living as a cancer patient, striving to overcome cancer, changing attitudes toward life after the cancer diagnosis, and ways to live a better life as a cancer patient. The participants asserted the significance of providing adequate treatment information that is easily understood by cancer patients during the conversation between patients and medical professionals. Besides the physical symptoms identified by SPARC, the participants struggled with numbness in their hands and feet and hair loss. Korean cancer patients prominently wished to avoid burdening their family or others in their daily life. They considered the improvement of health behaviors, such as diet and exercise, as part of the treatment, which was not limited to drugs. Furthermore, it was essential to evaluate the value of cancer patients' lives, as they desired to be helpful members of their families and society. CONCLUSIONS: This study identified additional domains and items of unmet needs of Korean cancer patients and broadened the understanding of unmet needs among cancer patients.

Antioxidant Compounds, Kirenol and Methyl ent-16α, 17-dihydroxy-kauran-19-oate Bioactivity-Guided Isolated from Siegesbeckia glabrescens Attenuates MITF-Mediated Melanogenesis via Inhibition of Intracellular ROS Production.

Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation.

Diterpenoids Isolated from Podocarpus macrophyllus Inhibited the Inflammatory Mediators in LPS-Induced HT-29 and RAW 264.7 Cells.

Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest pain, arthritis, rheumatism, and sexually transmitted diseases. To identify natural products having efficacy against inflammatory bowel disease (IBD), we identified a new, 16-hydroxy-4ß-carboxy-O-ß-D-glucopyranosyl-19-nor-totarol (4) together with three known diterpenoids from P. macrophyllus. Furthermore, all the extracts, fractions, and isolates 1-4 were investigated for their anti-inflammatory effects by assessing the expression on nitric oxide (NO) production and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 and HT-29 cells. Among them, nagilactone B (2) exhibited a potent anti-inflammatory effect against NO production on RAW 264.7 cells; therefore, nagilactone B was further assessed for anti-inflammatory activity. Western blot analysis revealed that nagilactone B significantly decreased the expression of LPS-stimulated protein, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated extracellular regulated kinase (pERK)1/2. In addition, nagilactone B downregulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels in LPS-induced macrophages and colonic epithelial cells. To our best knowledge, this is the first report on the inhibitory effect of nagilactone B (pure state) and rakanmakilactone G against NO production in LPS-stimulated RAW 264.7 cells. Thus, diterpenoids isolated from P. macrophyllus could be employed as potential therapeutic phytochemicals for IBD.

The barriers to using modern contraceptive methods among rural young married women in Moshi Rural District, the Kilimanjaro region, Tanzania.

The relationship between the rate of modern contraception and unintended pregnancy is complicated in Tanzania. Although the contraception rate has been slightly increased; the unintended pregnancy rate has remained at 22~24% since 1999. In addition, married women in rural areas use less modern contraceptive methods than those in urban areas. Young women are at a higher risk of mistimed and unintended pregnancy compared to older females. Various barriers to using contraceptive methods have been reported, including fear of side effects, lack of knowledge, misconception, accessibility of the methods, and limited health workers' skills. This study was aimed to invest the barriers to using modern contraceptive methods among rural young married. A qualitative study was carried out in Moshi rural district in northeast Tanzania between June 2019 and July 2019. 22 in-depth interviews (9 key informants and 13 young married women aged 19-34) were conducted. Thematic analysis was used and data transcripts were coded. As a result, all participants were familiar with modern contraceptive methods and experienced at least one of them. Fear of side effects and prefer inappropriate birth control methods especially superstitious methods were major barriers to use. Also, rumours and misleading concerns have arisen from peers and village members. Condoms were not used among them, and males and the elderly still perceived family planning negatively. Additionally, although long-term modern contraceptive methods have been increased and preferred, IUCD is inaccessible due to the lack of skilled workers and facilities. In conclusion, community-based reproductive education is required to increase awareness of safe and reliable modern contraceptive methods. And frequent outreach services of the field are essential to provide more contraception's benefits to the village members so that barriers to using contraception and unwanted pregnancy could be reduced in rural Tanzania. In order to do that, more interventions, such as NGOs and strengthened government systems of reproductive health, should be enhanced.

Effects of various genetic polymorphisms on thiopurine treatment-associated outcomes for Korean patients with Crohn's disease.

AIMS: This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea. METHODS: A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia). RESULTS: The median duration of thiopurine treatment was 47.0 months (range 6.0-153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti-tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6-thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05). CONCLUSION: The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients.

Detailed visual assessment of striatal dopaminergic depletion in patients with idiopathic normal pressure hydrocephalus: unremarkable or not?

BACKGROUND: Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. METHODS: In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. RESULTS: Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. CONCLUSION: Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.

Serratane triterpenoids isolated from Lycopodium clavatum by bioactivity-guided fractionation attenuate the production of inflammatory mediators.

Lycopodium clavatum has been used in traditional medicine for the treatment of kidney disorders, rheumatic arthritis, cystitis, and gastritis. We isolated a new serratane triterpenoid (2), and five known triterpenoids (1, 3-6) from the ethyl acetate fraction of L. clavatum by bioactivity-guided fractionation based on their suppression of inflammatory cytokines. Two different cell lines, RAW 264.7 and HT-29 were used to determine the anti-inflammatory activity of the isolated compounds. Among them, compounds 1, 2, 4, and 5 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. Compounds 1, 2, 4, and 5 reduced inducible nitric oxide (iNOS) expression in RAW 264.7 cells and compounds 1 and 6 downregulated COX-2, which correlated with the reduced expression of PGE2. Compounds 1, 2, 4, and 5 downregulated pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) in macrophages, and additionally suppressed the levels of IL-8 in HT-29 cells. To determine the signaling pathways involved in the suppression of NO production by these compounds, we investigated ERK1/2 and nuclear factor-kappa B (NF-κB) expression by western blot analysis. We observed that these compounds downregulated the expression of LPS-induced NF-κB and pERK 1/2 in RAW 264.7 cells. Our results demonstrate that serratane triterpenoids isolated from L. clavatum may be used as potential candidates for treating inflammatory bowel disease (IBD) due to their anti-inflammatory effects.

Multiple RPAs make WRN syndrome protein a superhelicase.

RPA is known to stimulate the helicase activity of Werner syndrome protein (WRN), but the exact stimulation mechanism is not understood. We use single-molecule FRET and magnetic tweezers to investigate the helicase activity of WRN and its stimulation by RPA. We show that WRN alone is a weak helicase which repetitively unwind just a few tens of base pairs, but that binding of multiple RPAs to the enzyme converts WRN into a superhelicase that unidirectionally unwinds double-stranded DNA more than 1 kb. Our study provides a good case in which the activity and biological functions of the enzyme may be fundamentally altered by the binding of cofactors.