WGA-M001, a Mixture of Total Extracts of Tagetes erecta and Ocimum basilicum, Synergistically Alleviates Cartilage Destruction by Inhibiting ERK and NF-κB Signaling.

Tagetes erecta and Ocimum basilicum are medicinal plants that exhibit anti-inflammatory effects against various diseases. However, their individual and combined effects on osteoarthritis (OA) are unknown. Herein, we aimed to demonstrate the effects of T. erecta, O. basilicum, and their mixture, WGA-M001, on OA pathogenesis. The administration of total extracts of T. erecta and O. basilicum reduced cartilage degradation and inflammation without causing cytotoxicity. Although WGA-M001 contained lower concentrations of the individual extracts, it strongly inhibited the expression of pathogenic factors. In vivo OA studies also supported that WGA-M001 had protective effects against cartilage destruction at lower doses than those of T. erecta and O. basilicum. Moreover, its effects were stronger than those observed using Boswellia and Perna canaliculus. WGA-M001 effectively inhibited the interleukin (IL)-1ß-induced nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway and ERK phosphorylation. Furthermore, RNA-sequence analysis also showed that WGA-M001 decreased the expression of genes related to the IL-1ß-induced NF-κB and ERK signaling pathways. Therefore, WGA-M001 is more effective than the single total extracts of T. erecta and O. basilicum in attenuating OA progression by regulating ERK and NF-κB signaling. Our results open new possibilities for WGA-M001 as a potential therapeutic agent for OA treatment.

Neuroprotective effects of hydroponic ginseng fermented by Lactococcus lactis KC24 in oxidatively stressed SH-SY5Y cells.

BACKGROUND: Panax ginseng Meyer, a traditional herb in Asia, contains bioactive compounds such as polyphenolic compounds, flavonoids, and ginsenosides. Furthermore, fermentation with probiotics can promote the biofunctional activities of ginseng. This study's object was to investigate the neuroprotective effect of hydroponic ginseng against hydrogen peroxide (H2 O2 )-induced cytotoxicity and its effect on the fermentation time. RESULTS: Nonfermented hydroponic ginseng (HNF) was fermented with Lactococcus lactis KC24 at 37 °C for 12 h (H12F) or 24 h (H24F). As fermentation progressed, the content of ginsenosides Rd and F2 increased slightly. The viability of cells pretreated with H2 O2 -exposed nonfermented soil-cultivated ginseng (SNF), HNF, H12F, and H24F gradually improved. In addition, a similar cytotoxicity trend was observed for the level of lactate dehydrogenase released. Fermentation with L. lactis KC24 also enhanced the protective effect of HNF in all assays related to the neuroprotective pathway. In other words, superoxide dismutase and catalase messenger RNA (mRNA) expression levels were upregulated in H24F-treated cells. Similarly, H24F also upregulated the mRNA and protein expression of brain-derived neurotrophic factor to the highest observed concentration. Moreover, the Bax/Bcl-2 ratio was the lowest after H24F pretreatment in H2 O2 -induced SH-SY5Y cells. Attenuating the cytotoxicity in H2 O2 -induced SH-SY5Y cells, H24F markedly reduced caspase-3 and -9 mRNA expression and caspase-3 activity. CONCLUSION: These results suggest that HNF exhibited higher neuroprotection than SNF, which was enhanced after fermentation. This study demonstrates that H12F and H24F can be potential ingredients for developing healthy functional foods and pharmaceutical materials. © 2023 Society of Chemical Industry.

Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19).

The therapeutic benefits of curcuminoids in various diseases have been extensively reported. However, little is known regarding their preventive effects on extensive immunosuppression. We investigated the immunoregulatory effects of a curcuminoid complex (CS/M), solubilized with stevioside, using a microwave-assisted method in a cyclophosphamide (CTX)-induced immunosuppressive mouse model and identified its new pharmacological benefits. CTX-treated mice showed a decreased number of innate cells, such as dendritic cells (DCs), neutrophils, and natural killer (NK) cells, and adaptive immune cells (CD4 and CD8 T cells) in the spleen. In addition, CTX administration decreased T cell activation, especially that of Th1 and CD8 T cells, whereas it increased Th2 and regulatory T (Treg) cell activations. Pre-exposure of CS/M to CTX-induced immunosuppressed mice restored the number of innate cells (DCs, neutrophils, and NK cells) and increased their activity (including the activity of macrophages). Exposure to CS/M also led to the superior restoration of T cell numbers, including Th1, activated CD8 T cells, and multifunctional T cells, suppressed by CTX, along with a decrease in Th2 and Treg cells. Furthermore,CTX-injected mice pre-exposed to CS/M were accompanied by an increase in the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), which play an essential role against oxidative stress. Importantly, CS/M treatment significantly reduced viral loads in severe acute respiratory syndrome coronavirus2-infected hamsters and attenuated the gross pathology in the lungs. These results provide new insights into the immunological properties of CS/M in preventing extensive immunosuppression and offer new therapeutic opportunities against various cancers and infectious diseases caused by viruses and intracellular bacteria.

Colonial Research on Public Hygiene and its Postcolonial Legacy: Focusing on Hygiene Laboratory in Colonial Korea.

Previous studies on the history of Korean public health have shown that the public hygiene system in Korea under Japan's colonial rule relied heavily on the sanitary police, whose lack of expertise in hygiene reinforced the coercion and violence of the colonial public hygiene system. This view, however, has overlooked the existence and function of scientific knowledge, which underpinned the formulation and implementation of public hygiene policies. This paper explores the knowledge production in public hygiene by research institutes of Japan's colonial government in Korea, drawing on the Hygiene Laboratory as a case. The Hygiene Laboratory chiefly played three roles: first, providing advice on the sanitary police's crackdowns; second, quality inspection of food, beverage, and pharmaceuticals, and authorizing their production and distribution; third, investigating health resources such as conventional food ingredients, medicinal herbs, and drinking water to support the wartime public health policy of the colonial government in Korea. The third function in particular continued after the reorganization of the Hygiene Laboratory as the National Chemistry Laboratory in the postcolonial period. By tracing the Hygiene Laboratory's research activities, this paper highlights the complicated cooperation between expertise, practices, and institutions in the field of sanitation control in colonial Korea.

Tuning the sensing responses towards room-temperature hypersensitive methanol gas sensor using exfoliated graphene-enhanced ZnO quantum dot nanostructures.

A suitable and non-invasive methanol sensor workable in ambient temperature conditions with a high response has gained wide interest to prevent detrimental consequences for industrial workers from its low-level intoxication. In this work, we present a tunable and highly responsive ppb-level methanol gas sensor device working at room temperature via a bottom-up synthetic approach using exfoliated graphene sheet (EGs) and ZnO quantum dots (QDs) on an aluminum anodic oxide (AAO) template. It is verified that EGs-supported AAO with a vertical electrode configuration enabled high and fast-responsive methanol sensing. Moreover, the hydroxyl and carboxyl groups of the high surface area EGs and ZnO QDs with a 3.37 eV bandgap efficiently absorbing UV light led to 56 times high response due to the enhanced polarization on the sensor surface compared to non-UV-radiated EGs/AAO at 800 ppb of methanol. The optimal resonance frequency of methanol is determined to be 100 kHz, which could detect methanol with high response of 2.65% at 100 ppm. The limit of detection (LOD) concentration is obtained at 2 ppb level. This study demonstrates the potential of UV-assisted ZnO, EGs, and AAO-based capacitance sensor material for rapidly detecting hazardous gaseous light organic molecules at ambient conditions, and the overall approach can be easily expanded to a novel non-invasive monitoring strategy for light and hazardous volatile organic exposures.

Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antioxidant Activity and Inhibitory Effect on Nitric Oxide Production of Hydroponic Ginseng Fermented with Lactococcus lactis KC24.

Panax ginseng Meyer is used as a medicinal plant. The aim of this study was to ferment hydroponic ginseng with Lactococcus lactis KC24 and confirm its antioxidant activity and inhibitory effect on nitric oxide (NO) production. Flavonoid and phenol contents in fermented ginseng extracts were measured. Antioxidant activity was measured by DPPH, ABTS, reducing power, FRAP and ß-carotene assays. Additionally, inhibitory effects on NO production and toxicity of the fermented extract were determined using RAW 264.7 cells. Phenol and flavonoid contents increased as the fermentation time increased, and the contents were higher in hydroponic ginseng than in soil-cultivated ginseng. The DPPH assay revealed that the antioxidant activity of the 24 h fermented extract significantly increased from 32.57% to 41% (p < 0.05). The increase in antioxidant activity may be affected by an increase in phenol and flavonoid contents. At 1 mg/mL solid content, the 24 h fermented hydroponic ginseng extract inhibited NO production from 9.87 ± 0.06 µM to 1.62 ± 0.26 µM. In conclusion, the increase in antioxidant activity affects the inhibition of NO production, suggesting that fermented hydroponic ginseng may be used in the industries of functional food and pharmaceutical industry as a functional material with anti-inflammatory effects.

Statistics and Colonial Medicine: A Doubt and Controversy on Tuberculosis Statistics in Colonial Korea.

This paper focuses on the criticism of tuberculosis statistics published by the Japanese Government-general in colonial Korea and a research on the reality of tuberculosis prevalence by medical doctors from the Department of Hygiene and Preventive Medicine at Keijo Imperial University (DHPMK). Recent studies have shown that colonial statistics shape the image of colonial subjects and justify the control to them. Following this perspective, this paper explores the process of producing the statistical knowledge of tuberculosis by medical scientists from DHPMK. Their goal was to find out the resistance to tuberculosis as biological characteristics of Korean race/ethnicity. In order to do so, they demonstrated the existence of errors in tuberculosis statistics by the Korean colonial government and devised a statistical method to correct them based on the conviction that the Western modern medicine was superior than Korean traditional medicine as well as the racist bias against Korean. By analyzing how the statistical concepts reflected these prejudices, this paper argues that the statistical knowledge of tuberculosis created images that Japanese people was healthier and stronger than the Korean people and justified the colonial government's control over Korean.

Pharmacokinetic Analysis and Biomarker-Assisted Safety Assessment of Acetaminophen in Combination With Ojeok-san Compared With Acetaminophen Alone.

Acetaminophen and Ojeok-san are both frequently used analgesics. In this study, we evaluated acetaminophen pharmacokinetics (PK) and changes in microRNA-122 (miR-122) levels after multiple dosing of acetaminophen with or without Ojeok-san. An open-label, 1-sequence, 2-period, 2-treatment crossover study was conducted in 18 subjects. In period 1, 500 mg of acetaminophen was administered 3 times on day 1 and once on day 2. In period 2, after the administration of 14.47 g of Ojeok-san twice on day 2 and 3 times daily on days 3 to 7, Ojeok-san and acetaminophen were coadministered 3 times each on day 8 and once each on day 9. The geometric mean ratios (90% confidence intervals) of acetaminophen with Ojeok-san to acetaminophen alone were 0.98 (0.87 to 1.10) and 1.02 (0.98 to 1.05) for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during the dosing interval (AUC0-τ ), respectively, of acetaminophen at steady state. The alanine aminotransferase (ALT) levels were within the reference range in all the participants throughout the study period, although the mean fold changes in both serum miR-122 and ALT levels from baseline tended to increase on days 2 to 5. In conclusion, the PK properties of acetaminophen were not significantly affected by Ojeok-san coadministration. For osteoarthritis patients taking acetaminophen with or without Ojeok-san, monitoring potential liver toxicity using miR-122 as a biomarker may be useful.

Liquiritigenin inhibits hepatic fibrogenesis and TGF-ß1/Smad with Hippo/YAP signal.

BACKGROUND: Recent reports highlighted the possibility that Yes-associated protein (YAP) and transforming growth factor-ß1 (TGF-ß1) can act as critical regulators of hepatic stellate cells (HSCs) activation; therefore, it is natural for compounds targeting Hippo/YAP and TGF-ß1/Smad signaling pathways to be identified as potential anti-fibrotic candidates. PURPOSE: Liquiritigenin (LQ) is an aglycone of liquiritin and has been reported to protect the liver from injury. However, its effects on the Hippo/YAP and TGF-ß1/Smad pathways have not been identified to date. METHODS: We conducted a series of experiments using CCl4-induced fibrotic mice and cultured LX-2 cells. RESULT: LQ significantly inhibited liver fibrosis, as indicated by decreases in regions of hepatic degeneration, inflammatory cell infiltration, and the intensity of α-smooth muscle actin (α-SMA) staining in mice. Moreover, LQ blocked the TGF-ß1-induced phosphorylation of Smad 3, and the transcript levels of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-2 (MMP-2) in LX-2 cells, which is similar with resveratrol and oxyresveratrol (positive controls). Furthermore, LQ increased activation of large tumor suppressor kinase 1 (LATS1) with the induction of YAP phosphorylation, thereby preventing YAP transcriptional activity and suppressing the expression of exacerbated TGF-ß1/Smad signaling molecules. CONCLUSION: These results clearly show that LQ ameliorated experimental liver fibrosis by acting on the TGF-ß1/Smad and Hippo/YAP pathways, indicating that LQ has the potential for effective treatment of liver fibrosis.

Apoptosis and G2/M cell cycle arrest induced by a timosaponin A3 from Anemarrhena asphodeloides Bunge on AsPC-1 pancreatic cancer cells.

BACKGROUND: Timosaponin A3 (TA3), one of the active components of spirostanol saponin isolated from A. asphodeloides, is widely used as an anticancer agent in a variety of cancer cell lines. However, the research on the anticancer efficacy is very limited in human pancreatic cancer models. PURPOSE: In this study, we investigated the molecular targets in the active components of A. asphodeloides, which showed anti-cancer effects in human pancreatic cancer cells, and confirmed the pathways involved. STUDY DESIGN: The apoptotic effects of five solvent extracts of A. asphodeloides in human pancreatic cancer cells (AsPC-1) was studied, and the phytochemical leading to their effects identified. Next, we determined whether the phytochemical inhibit STAT3 and ERK1/2, and investigated the pathways involved. METHODS: Five solvent extracts of A. asphodeloides (100  µg/ml, 24  h) was investigated for their cytotoxicity against AsPC-1 cells. The active ingredient of the extract exhibiting the highest toxicity were analyzed by liquid chromatography-mass spectrometry. Next, we studied the mechanism of action of the phytochemical in pancreatic cancer. Cell cycle and annexin V/FITC assays were performed to assess cell growth and apoptosis capacity. The effects on apoptosis and proliferation-related pathways, STAT3, and MAPKs were confirmed at the protein level using immunoblotting. The factors regulated in the pathways were investigated using reverse transcription polymerase chain reaction. RESULTS: The results showed that the ethyl acetate extract of A. asphodeloides (EAA) induced apoptotic and anti-proliferative activities through the STAT3 and MAPKs pathways. We found that TA3, an active component of EAA, inhibits constitutive STAT3 and ERK1/2 proteins. EAA and TA3 decreased the viability of AsPC-1 cells, leading to cell cycle arrest at the sub-G1 and G2/M phases. Moreover, TA3 inhibited the expression of various genes encoding anti-apoptotic (Bcl-2, Bcl-xl), proliferative (Cyclin D1), metastatic (MMP-9), and angiogenic (VEGF-1) proteins. CONCLUSION: The results indicated that TA3, an active phytochemical from A. asphodeloides, could induce apoptosis and suppress cell proliferation by inhibiting the STAT3 and ERK1/2 pathways. Thus, TA3 is a candidate cancer chemotherapeutic agent instead to treat human pancreatic cancer.

In vivo evaluation of garlic (Allium sativum) supplementation to rice straw-based diet on mitigation of CH4 and CO2 emissions and blood profiles using crossbreed rams.

BACKGROUND: Two experiments were implemented using three cannulated crossbreed rams (Corriedale × Suffolk) fed rice straw-based diet. In vivo evaluation of garlic powder (GP) supplementation to rice straw-based diet on CH4 and CO2 emissions and blood profiles of the rams (body weight = 52 ± 3 kg) was performed. The design was a triplicate 3 × 3 Latin square. Groups were the control (no GP) and two GP groups, which were given supplementation for 0.1 (GP0.1) and 0.5% (GP0.5) of concentrate. The differences between two experiments were data missing of GP0.1 and uncontrolled environment in Experiment 1. Blood profiles were added in Experiment 2. RESULTS: In Experiment 1, supplementation of GP to the rams reduced CH4 production significantly (P < 0.05) by 38%. Dry matter intake was not different among the groups in both experiments. In Experiment 2, CH4 was lower in the GP0.5 group than the control group by 7%, whereas CO2 showed no difference among the groups. Serum glutamic oxaloacetic transaminase was significantly (P > 0.05) lower in the GP0.5 group than the control group, whereas glutamic pyruvic transaminase, total protein, urea N, total cholesterol, low-density lipoprotein, calcium, phosphorus, magnesium and non-esterified fatty acids were not significantly (P > 0.05) different. CONCLUSIONS: GP supplementation, particularly GP0.5, decreases CH4 emissions in rams fed rice straw-based diets. © 2018 Society of Chemical Industry.

Effects of Ojeok-san on the Pharmacokinetics of Celecoxib at Steady-state in Healthy Volunteers.

Ojeok-san is a frequently used herbal medication for the management of osteoarthritic pain. We evaluated the effect of Ojeok-san on the pharmacokinetics of celecoxib at steady-state in healthy individuals. An open-label, fixed-sequence, two-period, two-treatment cross-over study was conducted. In period I, the individuals received celecoxib capsule 200 mg once daily for 4 days. In period II, only Ojeok-san (14.47 g/pack, three times daily) was administered for 4 days, followed by co-administration with celecoxib for 4 days. On the fourth (final) day of administration, Ojeok-san was administered as a single dose. The blood samples for pharmacokinetic evaluation were collected for up to 48 hr after the administration of celecoxib in each study period. Of the 22 enrolled individuals, 20 individuals completed the study. In the presence of Ojeok-san, the systemic exposure of celecoxib was decreased. The geometric mean ratios ([celecoxib + Ojeok-san]/celecoxib) and the 90% confidence intervals for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during dosing interval (AUCτ ) of celecoxib at steady-state were 0.725 (0.620-0.848) and 0.885 (0.814-0.962), respectively. The changes in the mean of the Cmax and AUCτ of celecoxib were greater in intermediate metabolizers of cytochrome 2C9 (CYP2C9) than in normal metabolizers. Our results suggested that the Cmax and AUCτ of celecoxib were reduced by Ojeok-san co-administration. This finding may be beneficial to determine the required adjustment of celecoxib dosage when co-administered with Ojeok-san.

Anti-platelet effects of epigallocatechin-3-gallate in addition to the concomitant aspirin, clopidogrel or ticagrelor treatment.

BACKGROUND/AIMS: Although epigallocatechin-3-gallate (EGCG), which is found in high contents in the dried leaves of green tea, has been reported to have an anti-platelet effect, synergistic effects of EGCG in addition to current anti-platelet medications remains to be elucidated. METHODS: Blood samples were obtained from 40 participants who took aspirin (ASA, n = 10), clopidogrel (CPD, n = 10), ticagrelor (TCG, n = 10) and no anti-platelet medication (Control, n = 10). Ex vivo platelet aggregation and adhesion under various stimulators were analyzed by multiple electrode aggregometry (MEA) and Impact-R systems. PAC-1 and P-selectin expressions in human platelets were analyzed by flow cytometry. RESULTS: In MEA analysis, adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP)-induced platelet aggregations were lower in the CPD and the TCG groups; arachidonic acid (AA)-induced platelet aggregation was lower in the ASA group, whereas collagen (COL)-induced platelet aggregations were comparable among four groups. EGCG significantly reduced ADP- and COL-induced platelet aggregation in dose-dependent manner (ADP, p = 0.04; COL, p < 0.01). There were no additional suppressions of platelet aggregation stimulated by AA in the ASA group, and by ADP in the CPD and TCG groups. Moreover, EGCG suppressed shear stress-induced platelet adhesion on Impact-R, and had no effect on P-selectin and PAC-1 expressions. CONCLUSIONS: Ex vivo treatment of EGCG inhibited platelet adhesion and aggregation without changes in P-selectin and PAC-1 expression. There was no additional suppressions in platelet aggregation stimulated by AA in the ASA group and ADP in the CPD and TCG groups.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

Sialidase inhibitory activity of diarylnonanoid and neolignan compounds extracted from the seeds of Myristica fragrans.

Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from Myristica fragrans seeds. Of the isolated compounds (1-12), malabaricone C showed the most pneumococcal sialidases inhibition (IC50 of 0.3µM for NanA, 3.6µM for NanB, and 2.9µM for NanC). These results suggested that malabaricone C and neolignans could be potential agents for combating S. pneumoniae infection agents.

Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation. Ginkgo biloba has been tested clinical trials as a traditional medicine for asthma, bronchitis and cardiovascular disease. The effects of Ginkgolide A (GA), derived from the ginkgo biloba leaf, are still unknown in NAFLD. To determine the protective effects of GA in NAFLD, we examined the fatty liver disease condition in the non-esterified fatty acid (NEFA)-induced HepG2 cell line and in a high fat diet mouse model. The findings of this study suggest that GA is non-toxic at high concentrations in hepatocytes. Moreover, GA was found to inhibit cellular lipogenesis and lipid accumulation by causing mitochondrial oxidative stress. GA showed hepatoprotective efficacy by inducing cellular lipoapoptosis and by inhibiting cellular inflammation. The results demonstrated that GA may be feasible as a therapeutic agent for NAFLD patients.

Serial Ultrasound Findings After Laser Ablation for Benign Breast Lesions on Long-Term Follow-Up: Implications for Evaluation of Procedural Success.

OBJECTIVE: The purpose if this study was to describe the follow-up ultrasound (US) findings of percutaneous US-guided laser ablation for small benign breast lesions, and to define the procedural success. BACKGROUND DATA: There are limited reports on follow-up imaging after laser ablation, because the ablated tumors were generally resected by surgery. MATERIALS AND METHODS: US-guided laser ablation was performed on 19 benign breast lesions in 10 patients. The median size of the lesions was 7.8 mm (range, 3-11 mm). The lesions were diagnosed as image-pathology concordant benign by US-guided core biopsy. After ablation, we performed follow-up US with an interval of 3-12 months; the median follow-up period was 32 months (range, 30-36 months). We evaluated the morphologic and size changes by using serial follow-up US. RESULTS: US findings of the 13 cases followed within the first 6 months after ablation showed hypoechoic lesions having inner hyperechogenicity with or without a hypoechoic center. The size of these lesions during this period increased in comparison with the initial lesion size, and then decreased or became stable on serial follow-up US. On the last follow-up US examination, in 14 cases (73.6%), the lesions were invisible, 4 cases (21.1%) showed scar changes, and 1 case (5.3%) showed a hypoechoic remnant lesion. CONCLUSIONS: US findings within 6 months after laser ablation showed mixed echoic lesions with increased size, followed by gradual decrease in size. Therefore, the success of laser ablation may be evaluated by checking the changes in the lesions by comparing the size of the lesions with the first follow-up US within 6 months and not the original tumor.

Transcriptomic Analysis Reveals Wound Healing of Morus alba Root Extract by Up-Regulating Keratin Filament and CXCL12/CXCR4 Signaling.

Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA-mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real-time cell analysis and real-time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose-dependent manner on Kera-308 cell line, and up-regulated keratin expression including wound-induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up-regulated mRNA associated keratin filaments and toward a more up-regulated mRNA level of C-X-C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway.

Appropriate empirical antibiotic use and 30-d mortality in cirrhotic patients with bacteremia.

AIM: To analyze whether prompt and appropriate empirical antibiotic (AEA) use is associated with mortality in cirrhotic patients with bacteremia. METHODS: A total of 102 episodes of bacteremia in 72 patients with cirrhosis were analyzed. AEA was defined as a using or starting an antibiotic appropriate to the isolated pathogen at the time of bacteremia. The primary endpoint was 30-d mortality. RESULTS: The mortality rate at 30 d was 30.4% (31/102 episodes). Use of AEA was associated with better survival at 30 d (76.5% vs 46.9%, P = 0.05), and inappropriate empirical antibiotic (IEA) use was an independent factor associated with increased mortality (OR = 3.24; 95%CI: 1.50-7.00; P = 0.003, adjusted for age, sex, Child-Pugh Class, gastrointestinal bleeding, presence of septic shock). IEA use was more frequent when the isolated pathogen was a multiresistant pathogen, and when infection was healthcare-related or hospital-acquired. CONCLUSION: AEA use was associated with increased survival of cirrhotic patients who developed bacteremia. Strategies for AEA use, tailored according to the local epidemiological patterns, are needed to improve survival of cirrhotic patients with bacteremia.