Transcriptome dataset of two Pistacia species: Pistacia chinensis and Pistacia weinmannifolia.

Pistacia chinensis and Pistacia weinmannifolia are small trees and are distributed in East Asia, in particular China. The data on P. chinensis presented in this article is associated with the research article, "DOI: 10.5010/JPB.2019.46.4.274" [1]. Both P. chinensis and P. weinmannifolia have long been used as ethnobotanical plants to treat various illnesses, including dysentery, inflammatory swelling, rheumatism, liver diseases, influenza, lung cancer, etc. Many studies have been carried out to delve into the pharmaceutical properties of these Pistacia species using plant extracts, but genomic studies are very rarely performed to date. To enrich the genetic information of these two species, RNA sequencing was conducted using a pair-end Illumina HiSeq2500 sequencing system, resulting in 2.6 G of raw data from P. chinensis (Accession no: SRR10136265) and 2.7 G bases from P. weinmannifolia (Accession no: SRR10136264). Transcriptome shotgun assembly using three different assembly tools generated a total of 18,524 non-redundant contigs (N50, 1104 bp) from P. chinensis and 18,956 from P. weinmannifolia (N50, 1137 bp). The data is accessible at NCBI BioProject: PRJNA566127. These data would be crucial for the identification of genes associated with the compounds exerting pharmaceutical properties and also for molecular marker development.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Closed-Loop Auditory Stimulation to Guide Respiration: Preliminary Study to Evaluate the Effect on Time Spent in Sleep Initiation during a Nap.

Various stimulation systems to modulate sleep structure and function have been introduced. However, studies on the time spent in sleep initiation (TSSI) are limited. This study proposes a closed-loop auditory stimulation (CLAS) to gradually modulate respiratory rhythm linked to the autonomic nervous system (ANS) activity directly associated with sleep. CLAS is continuously updated to reflect the individual's current respiratory frequency and pattern. Six participants took naps on different days with and without CLAS. The average values of the TSSI are 14.00 ± 4.24 and 9.67 ± 5.31 min in the control and stimulation experiments (p < 0.03), respectively. Further, the values of respiratory instability and heart rate variability differ significantly between the control and stimulation experiments. Based on our findings, CLAS supports the individuals to gradually modulate their respiratory rhythms to have similar characteristics observed near sleep initiation, and the changed respiratory rhythms influence ANS activities, possibly influencing sleep initiation. Our approach aims to modulate the respiratory rhythm, which can be controlled intentionally. Therefore, this method can probably be used for sleep initiation and daytime applications.

Anti-Inflammatory Effects of Lagerstroemia ovalifolia Teijsm. & Binn. in TNFα/IFNγ-Stimulated Keratinocytes.

Ethnopharmacological Relevance. Atopic dermatitis is a chronic inflammatory skin disease. Lagerstroemia ovalifolia Teijsm. & Binn. (LO) has traditionally been used as an herbal medicine for anti-inflammatory diseases. The effect of LO on atopic dermatitis has not been verified scientifically. We investigated the effects of CHCl3 fraction number 5 of LO (LOC) on atopic dermatitis through cell-based experiments. HaCaT cells were treated with tumor necrosis factor-alpha (TNFα)/interferon-gamma (IFNγ) to induce an inflammatory reaction. Proinflammatory cytokines, interleukin- (IL-) 6, IL-8, and IL-1ß and chemokines such as thymus and activation-regulated chemokine (TARC/CCL17), monocyte chemoattractant protein 1 (MCP1/CCL2), and macrophage-derived chemokine (MDC/CCL22) were measured by RT-PCR and ELISA. In addition, the degree of phosphorylation and activation of JAK/STAT1, PI3K/AKT, and nuclear factor-kappa B (NF-κB) were measured by western blot and luciferase assays. The production of inflammatory cytokines and chemokines and activation of the JAK/STAT1, PI3K/AKT, and NF-κB pathways were induced by TNFα/IFNγ in HaCaT cells. Under these conditions, LOC treatment inhibited the production of targeted cytokines and chemokines and decreased the phosphorylation and activation of JAK/STAT1, PI3K/AKT, and NF-κB. These results suggest that LOC reduces the production of proinflammatory cytokines and chemokines by suppressing the JAK/STAT1, PI3K/AKT, and NF-κB pathways. Therefore, LOC may have potential as a drug for atopic dermatitis.

A Longitudinal Study of Adult Patients with Staphylococcus aureus Bacteremia over 11 Years in Korea.

BACKGROUND: The temporal changes in the Staphylococcus aureus genotypes causing S. aureus bacteremia (SAB) and the corresponding clinical changes over the last decade in South Korea are rarely investigated. METHODS: A longitudinal study of adult SAB patients was conducted in a large referral hospital in Seoul, South Korea. Adult monomicrobial SAB patients were enrolled between August 2008 and December 2018. Genotyping was performed by multilocus sequence typing (MLST) and staphylococcal protein A (spa) typing. Trends in changes were identified by linear regression analysis. RESULTS: Of 1782 adult SAB patients, the blood isolates of 1,778 (99.8%) and 1,634 (91.7%) were determined to be MLST and spa type, respectively. ST5 (-2.626%/year) and ST239 (-0.354%/year) decreased during the study period (P < 0.001 for both), but ST72 (2.009%/yr)-and ST8 (0.567%/yr) increased (P < 0.001 for both). The most common genotype was changed from ST5 in 2008 (44.9%) to ST72 in 2018 (36.3%). Panton-Valentine leukocidin-positive spa-t008-MRSA (USA300) was found in 28.6%. Central venous catheter (CVC)-related SAB (-2.440%/yr) and persistent SAB (-1.016%/yr) decreased, but mortality and recurrence rates were unchanged. CONCLUSION: Over the last decade, the hospital clones ST5 and ST239 have been replaced by community genotype ST72. This was associated with decreased CVC-related and persistent SAB. Increased USA300 was observed in community and hospital settings. Further research is required to identify the reasons for the ST72 epidemic and predict the impending epidemic of ST8 strains, including USA300.

Estrogenic properties of Prunus cerasoides extract and its constituents in MCF-7 cell and evaluation in estrogen-deprived rodent models.

Prunus cerasoides (PC) products contain relatively high levels of flavones and isoflavones and may be potential sources of phytoestrogens for postmenopausal symptom relief. We assessed the PC extract (PCE) and its representative constituents in vitro with assays for estrogen receptor alpha binding, estrogen response element transcriptional activity, cell proliferation, and gene expression changes for pS2 in MCF-7 cells. PCE and its compounds showed strong estrogen receptor binding affinities and estrogen response element induction. A previously undescribed compound (designated as compound 18), now identified as being gentisic acid, 5-O-ß-D-(6'-O-trans-4-coumaroyl)-glucopyranoside, also showed potent estrogenic properties and induced proliferation of MCF-7 cells. PCE was evaluated for its in vivo uterotrophic effects in immature female rats as well as for its lipid lowering effects in estrogen-deprived animals. For ovariectomized rats and aged female mice, PCE-treated groups had lower plasma triglyceride levels compared with control and, for the same comparison, had reduced serum levels of liver stress/damage markers. Our results point to strong estrogenic activities and beneficial metabolic effects for PCE, with properties that put PC and its extracts as promising sources of phytoestrogens for symptom relief in menopausal and postmenopausal cases.

Selection of an appropriate empiric antibiotic regimen in hematogenous vertebral osteomyelitis.

BACKGROUND: Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. METHOD: We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. RESULTS: In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). CONCLUSIONS: Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Estrogenic effects of phytoestrogens derived from Flemingia strobilifera in MCF-7 cells and immature rats.

Phytoestrogen (PE) has received considerable attention due to the physiological significance of its estrogenicity. Flemingia strobilifera (FS) has been used as a folk medicine in Asia for the treatment of inflammation, cancer, and infection; however, the estrogenic effects and chemical components of FS have not yet been reported. We aimed to uncover the estrogenic properties and PEs derived from FS using phytochemical and pharmacological evaluation. PEs from FS extract (FSE) were analyzed by NMR, HPLC, and MS. To evaluate estrogenic activity, FSE and its compounds were evaluated by in vitro and in vivo assays, including human estrogen receptor alpha (hERα) binding, estrogen response element (ERE)-luciferase reporter assays, and uterotrophic assays. FSE and its compounds 1-5 showed binding affinities for hERα and activated ERE transcription in MCF-7 cells. Additionally, FSE and compounds 1-5 induced MCF-7 cell proliferation and trefoil factor 1 (pS2) expression. In immature female rats, significant increases in uterine weight and pS2 gene were observed in FSE-treated groups. We identified estrogenic activities of FSE and its bioactive compounds, suggesting their possible roles as PEs via ERs. PEs derived from FSE are promising candidates for ER-targeted therapy for post-menopausal symptoms.

Dipterocarpus obtusifolius attenuates the effects of lipopolysaccharide­induced inflammatory response in RAW264.7 macrophages.

Dipterocarpus obtusifolius has been traditionally used as a herbal medicine and is considered to have anticancer properties. The biological activity of D. obtusifolius in inflammation and the underlying mechanisms of its activity remain to be elucidated. The present study investigated the effects of D. obtusifolius methanolic extract (DOME) on lipopolysaccharide (LPS)­stimulated inflammation in RAW264.7 cells. The effects of DOME on the production of nitric oxide, prostaglandin E2 and pro­inflammatory cytokines were assessed by ELISA, western blot analysis and reverse transcription­quantitative polymerase chain reaction. It was demonstrated that expression of inducible nitric oxide synthase, cyclooxygenase­2, interleukin­1ß and tumor necrosis factor­α was suppressed by DOME in LPS­stimulated cells. Furthermore, treatment with DOME suppressed phosphorylation of mitogen activated protein kinase (MAPK) molecules, including extracellular signal­regulated kinase, c­Jun N­terminal kinase and p38 MAPK. Translocation of the nuclear factor­κB p65 subunit into the nucleus was additionally inhibited by DOME. Phosphorylation of MAPK promoter activity was inhibited by treatment with DOME, PD98059, SB202190 and SP600125. These results demonstrated that DOME inhibits LPS­induced inflammatory responses. Therefore, DOME may be a potential therapeutic approach for the treatment of inflammatory diseases.

Impact of immune status on the clinical characteristics and treatment outcomes of nocardiosis.

Nocardiosis occurs in both immunocompromised and immunocompetent patients. We aimed to assess how its characteristics differ depending on patients' immune status. Of a total of 54 patients with culture-proven nocardiosis diagnosed over 13 years, 18 (33%) were immunocompetent. Half of immunocompetent patients had chronic lung disease and were not receiving systemic corticosteroid. There were no significant differences in clinical, radiographic, and microbiologic characteristics, and treatment outcomes according to immune status, except that pulmonary cavitation (47% vs. 8%) and coexisting infections (17% vs. 0%) were more frequent in immunocompromised hosts. Nocardia farcinica, the most commonly identified isolates at the species level (51%), was highly susceptible to trimethoprim-sulfamethoxazole (100%) and highly resistant to ceftriaxone (94%). Nocardiosis should be considered in differential diagnosis of pneumonia, brain abscess, or soft tissue infection that does not respond to conventional antibiotic therapy such as ceftriaxone, regardless of whether the patient is immunocompromised or not.

Clausena anisata-mediated protection against lipopolysaccharide-induced acute lung injury in mice.

Clausena anisata (Willd.) Hook.f. ex Benth. (CA), which is widely used in traditional medicine, reportedly exerts antitumor, anti-inflammatory and other important therapeutic effects. The aim of the present study was to investigate the potential therapeutic effects of CA in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and in LPS-stimulated RAW 264.7 cells. Male C57BL/6 mice were administered treatments for 3 days by oral gavage. On day 3, the mice were instilled intranasally with LPS or PBS followed 3 h later by oral CA (30 mg/kg) or vehicle administration. In vitro, CA decreased nitric oxide (NO) production and pro-inflammatory cytokines, such as interleukin (IL)-6 and prostaglandin E2 (PGE2), in LPS-stimulated RAW 264.7 cells. CA also reduced the expression of pro-inflammatory mediators, such as cyclooxygenase-2. In vivo, CA administration significantly reduced inflammatory cell numbers in the bronchoalveolar lavage fluid (BALF) and suppressed pro-inflammatory cytokine levels, including tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß, as well as reactive oxygen species production in the BALF. CA also effectively reduced airway inflammation in mouse lung tissue of an LPS-induced ALI mouse model, in addition to decreasing inhibitor κB (IκB) and nuclear factor-κB (NF-κB) p65 phosphorylation. Taken together, the findings demonstrated that CA inhibited inflammatory responses in a mouse model of LPS-induced ALI and in LPS-stimulated RAW 264.7 cells. Thus, CA is a potential candidate for development as an adjunctive treatment for inflammatory disorders, such as ALI.

Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7­TIPRL in human hepatocellular carcinoma cells.

Induction of apoptosis through activation of the TRAIL pathway is considered to be a promising anticancer strategy due to its ability to selectively induce apoptosis in cancer cells. However, the ability of cancer cells to acquire TRAIL resistance has limited the clinical translation of this approach. We previously reported that the TOR signaling pathway regulator-like (TIPRL) protein contributes to the resistance to TRAIL-induced apoptosis by inhibiting the MKK7-c-Jun N-terminal kinase (JNK) pathway via MKK7­TIPRL interaction. In the present study, we identified Tussilago farfara L. (TF) as a novel TRAIL sensitizer among 500 natural products using an ELISA system that specifically detects the MKK7-TIPRL interaction, and we validated candidates by GST-pull down assay. Co-treatment of Huh7 cells with TF and TRAIL induced apoptosis via inhibition of the MKK7-TIPRL interaction and an increase in MKK7/JNK phosphorylation. This is the first report to describe TF as a novel TRAIL sensitizer, unveiling a potentially novel therapeutic strategy in cancer therapy.

Efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVE: We evaluated the efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent (≥7 days) methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B). METHODS: All patients with MRSA-B during 2-year period at a tertiary-care hospital were prospectively enrolled. Linezolid-based salvage therapy was classified if patients switched glycopeptides to linezolid with/without carbapenem due to persistent MRSA-B. Covariate adjustment using the propensity score and inverse probability of treatment weighting (IPTW) using the propensity score were performed to control for bias in treatment assignment. RESULTS: Of 377 patients with MRSA-B, 90 with persistent MRSA-B were included. Of these, 38 (42%) were classified as linezolid-based salvage group and the remaining 52 (58%) as glycopeptide-based therapy group. The duration of persistent bacteremia (median 16 days vs. 10 days; P = 0.008) was longer in linezolid-based salvage group than in the comparator. However, the 30-day mortality (11% vs. 25%; P = 0.08) had a trend toward being lower in linezolid-based salvage group than those in the comparator. Logistic regression models with covariate adjustment and IPTW using propensity scores also revealed that linezolid-based salvage showed a trend toward having better outcome than the comparator, although this did not reach any statistically significance (OR 0.31; 95% CI 0.03-2.95 and OR 0.19; 95% CI 0.01-3.39, respectively). CONCLUSIONS: While having worse prognostic factors compared with glycopeptide-based therapy, linezolid-based salvage therapy revealed a trend toward better outcomes than the comparator. Our data suggest that linezolid-based salvage therapy would be considered in patients with persistent MRSA-B despite the use of glycopeptides therapy.

Novel lipolytic enzymes identified from metagenomic library of deep-sea sediment.

Metagenomic library was constructed from a deep-sea sediment sample and screened for lipolytic activity. Open-reading frames of six positive clones showed only 33-58% amino acid identities to the known proteins. One of them was assigned to a new group while others were grouped into Families I and V or EstD Family. By employing a combination of approaches such as removing the signal sequence, coexpression of chaperone genes, and low temperature induction, we obtained five soluble recombinant proteins in Escherichia coli. The purified enzymes had optimum temperatures of 30-35°C and the cold-activity property. Among them, one enzyme showed lipase activity by preferentially hydrolyzing p-nitrophenyl palmitate and p-nitrophenyl stearate and high salt resistance with up to 4 M NaCl. Our research demonstrates the feasibility of developing novel lipolytic enzymes from marine environments by the combination of functional metagenomic approach and protein expression technology.

Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC beta-lactamase: implications for antibiotic use.

Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii are characterized by chromosomally encoded AmpC beta-lactamases and possess the ability to develop resistance upon exposure to broad-spectrum cephalosporins. To determine the incidences of the emergence of resistance during antimicrobial therapy for infections caused by these organisms and the effect of the emergence of resistance on patient outcomes, all patients who were admitted to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June 2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C. freundii, or M. morganii were monitored prospectively. The main end point was the emergence of resistance during antimicrobial therapy. A total of 732 patients with infections were included for analysis. The overall incidence of the emergence of antimicrobial resistance during antimicrobial therapy was 1.9% (14/732). Resistance to broad-spectrum cephalosporins, cefepime, extended-spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0% (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%, 10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M. morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct invasion was significantly associated with the emergence of resistance to broad-spectrum cephalosporins (P = 0.024 at a significance level of 0.042, by use of the Bonferroni correction). Only 1 of the 14 patients whose isolates developed resistance during antimicrobial therapy died. The emergence of resistance was more frequently associated with broad-spectrum cephalosporins than with the other antimicrobial agents tested, especially in Enterobacter spp. However, the emergence of resistance was associated with a low risk of mortality.

Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer cells through dephosphorylation of Akt.

Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.

Korean mistletoe lectin-induced apoptosis in hepatocarcinoma cells is associated with inhibition of telomerase via mitochondrial controlled pathway independent of p53.

The extract of European mistletoe (Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coloratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisms for these effects. We showed that VCA induced apoptosis in both SK-Hep-1 (p53-positive) and Hep 3B (p53-negative) cells through p53- and p21-independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondrial controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.