Chronic allergic asthma induces T-cell exhaustion and impairs virus clearance in mice.

BACKGROUND: Allergic asthma, one of the most common types of asthma, is thought to be highly susceptible to respiratory viral infections; however, its pathological mechanism needs to be elucidated. Recent studies have found impaired T-cell function in asthmatic mice. Therefore, we aimed to investigate the way by which asthma induction affects T-cell exhaustion in the lungs and assess the relationship between T-cell exhaustion and influenza viral infection. METHODS: Chronic allergic asthma mice were induced by intranasal injection of ovalbumin for 6 weeks and asthmatic features and T cell populations in lung or airway were assessed. To determine the influenza virus susceptibility, control and asthma mice were challenged with the human influenza virus strain A/Puerto Rico/8/1934 H1N1 and evaluated the survival rate, lung damage, and virus titer. RESULTS: Six weeks of OVA sensitization and challenge successfully induced chronic allergic asthma in a mouse model showing significant increase of sera IgE level and broncho-pathological features. A significant decrease in interferon-γ-producing T-cell populations and an increase in exhausted T-cell populations in the lungs of OVA-induced asthmatic mice were observed. Asthmatic mice were more susceptible to influenza virus infection than control mice showing lower survival rate and higher virus titer in lung, and a positive correlation existed between T-cell exhaustion in the lung and virus titer. CONCLUSIONS: Asthma induction in mice results in the exhaustion of T-cell immunity, which may contribute to the defective capacity of viral protection. This study demonstrates a correlation between asthma conditions and viral susceptibility by investigating the functional characteristics of T-cells in asthma. Our results provide insights into the development of strategies to overcome the dangers of respiratory viral disease in patients with asthma.

Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes.

In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca2+ ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER-anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid-like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51-VAPB interaction is mediated by the FFAT-like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM-tethering function.

Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis.

BACKGROUND. Risk stratification systems for evaluating thyroid nodules on ultrasound use varying approaches to classify levels of suspicion for malignancy, leading to variable performance. OBJECTIVE. The purpose of this study was to perform a network meta-analysis comparing six risk stratification systems used to evaluate thyroid nodules on ultrasound in terms of their diagnostic performance for the detection of thyroid cancer. EVIDENCE ACQUISITION. Five bibliometric databases were searched for studies published through August 31, 2022, that compared at least two of six ultrasound risk stratification systems (the American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi [AACE/ACE/AME] system; American College of Radiology Thyroid Imaging Reporting and Data System [ACR TI-RADS]; the American Thyroid Association [ATA] risk stratification system; European Thyroid Association Thyroid Imaging Reporting and Data System [EU-TIRADS]; the Korean Thyroid Imaging Reporting and Data System [K-TIRADS] endorsed by the Korean Thyroid Association and the Korean Society of Thyroid Radiology; and the Thyroid Imaging Reporting and Data System developed by Kwak et al. [Kwak TIRADS]) in terms of their diagnostic performance for the detection of thyroid cancer, with cytologic or histologic evaluation used as a reference standard. The studies' risk of bias was evaluated using the Newcastle-Ottawa Scale. A meta-analysis of each system was performed to identify the risk category threshold that had the highest accuracy as well as the highest sensitivity and specificity at this threshold. Network meta-analysis was used to perform hierarchic ranking and identify the systems having the highest sensitivities and specificities at each system's most accurate threshold. EVIDENCE SYNTHESIS. The analysis included 39 studies with 49,661 patients. All studies were of fair (n = 17) or good (n = 22) quality. The most accurate risk category thresholds were class 3 (high risk) for the AACE/ACE/AME system, TR5 (highly suspicious) for ACR TI-RADS, EU-TIRADS 5 (high risk) for EU-TIRADS, 4c (moderate concern but not classic for malignancy) for Kwak TIRADS, K-TIRADS 5 (high suspicion) for K-TIRADS, and high suspicion for the ATA system. At these thresholds, the systems had sensitivity of 64-77% and specificity of 82-90%. Network meta-analysis identified the highest sensitivity and highest specificity for ACR TI-RADS, followed by K-TIRADS. CONCLUSION. Of six risk stratification systems, ACR TI-RADS had the highest diagnostic performance for the detection of thyroid nodules on ultrasound. CLINICAL IMPACT. This network meta-analysis can inform decisions regarding implementation of the risk stratification systems and can aid future system updates.

Comparable Plasma Lipid Changes in Patients with High-Grade Cervical Intraepithelial Neoplasia and Patients with Cervical Cancer.

Cervical cancer is the fourth most prevalent cancer among women worldwide and usually develops from cervical intraepithelial neoplasia (CIN). In the present study, we compared alterations in lipids associated with high-grade CIN and cervical cancer with those associated with a normal status and low-grade CIN by performing global lipid profiling on plasma (66 healthy controls and 55 patients with CIN1, 44 with CIN2/3, and 60 with cervical cancer) using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. We identified 246 lipids and found 31 lipids with similar alterations in both high-grade CIN and cervical cancer. Among these 31 lipids, four lipid classes (phosphatidylcholine, phosphatidylethanolamine, diglyceride, and free fatty acids) were identified as the major lipid classes with significant differences in the patients with CIN2/3 and cervical cancer compared to the healthy controls and the patients with CIN1. Lipid metabolites belonging to the same classes were positively correlated with each other. High-grade CIN and cervical cancer induce comparable changes in lipid levels, which are closely related to the development of cervical tumors. These results suggest that lipid profiling is a useful method for monitoring progression to cervical cancer.

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker.

Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-α. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.

Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns.

Gut microbiota has emerged as an important regulator of bone homeostasis. In particular, the modulation of innate immunity and bone homeostasis is mediated through the interaction between microbe-associated molecular patterns (MAMPs) and the host pattern recognition receptors including Toll-like receptors and nucleotide-binding oligomerization domains. Pathogenic bacteria such as Porphyromonas gingivalis and Staphylococcus aureus tend to induce bone destruction and cause various inflammatory bone diseases including periodontal diseases, osteomyelitis, and septic arthritis. On the other hand, probiotic bacteria such as Lactobacillus and Bifidobacterium species can prevent bone loss. In addition, bacterial metabolites and various secretory molecules such as short chain fatty acids and cyclic nucleotides can also affect bone homeostasis. This review focuses on the regulation of osteoclast and osteoblast by MAMPs including cell wall components and secretory microbial molecules under in vitro and in vivo conditions. MAMPs could be used as potential molecular targets for treating bone-related diseases such as osteoporosis and periodontal diseases.

Tailoring a Dynamic Metal-Polymer Interaction to Improve Catalyst Selectivity and Longevity in Hydrogenation.

Controlling metal-support interactions is important for tuning the catalytic properties of supported metal catalysts. Here, premade Pd particles are supported on stable polymers containing different ligating functionalities to control the metal-polymer interactions and their catalytic properties in industrially relevant acetylene partial hydrogenation. The polymers containing strongly ligating groups (e.g., Ar-SH and Ar-S-Ar) can form a polymer overlayer on the Pd surface, which enables selective acetylene adsorption and partial hydrogenation to ethylene without deactivation. In contrast, polymers with weakly ligating groups (e.g., Ar-O-Ar) do not form an overlayer, resulting in non-selective hydrogenation and fast deactivation, similar to Pd catalysts on conventional inorganic supports. The results imply that tuning the metal-polymer interactions via rational polymer design can provide an efficient way of synthesizing selective and stable catalysts for hydrogenation.

Acinetobacter pullicarnis sp. nov. isolated from chicken meat.

A novel bacterial strain, named S23T, was isolated from chicken meat of local market in Korea. Cells were Gram-negative, milky-yellow colored, non-motile and coccobacillus. The strain was obligate aerobic and catalase-positive, oxidase-negative, optimum growth temperature and pH were 25 °C and pH 7.0, respectively. On the basis of 16S rRNA gene sequence analysis, strain S23T belongs to the genus Acinetobacter and is most closely related to Acinetobacter defluvii KCTC 52503 T (97.40%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) value between strain S23T and its closet phylogenetic neighbors was below 76% and 17%, respectively. The G + C content of genomic DNA of strain S23T was 41.53 mol%. The major respiratory quinone was Q-9. The major cellular fatty acids were summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c), C18:1ω9c, and C16:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanol-amine, and phosphatidylserine. The ANI and dDDH results and results of the genotypic analysis in combination with chemotaxonomic and physiological data demonstrated that strain S23T represented a novel species within the genus Acinetobacter, for which the name Acinetobacter pullicarnis sp. nov. is proposed. The strain type is S23T (= KACC 19921 T = JCM 33150 T).

Chryseobacterium vaccae sp. nov., isolated from raw cow's milk.

Strain CA7T, a Gram-stain-negative, non-motile, non-spore-forming, aerobic and rod-shaped bacterial strain, was isolated from raw cow's milk collected from a farm affiliated with Chung-Ang University, Anseong, Korea, and characterized by a polyphasic approach. Optimal growth of strain CA7T was observed on tryptic soy agar at 30 °C and pH 7.0 with 0 % NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain CA7T belonged to the genus Chryseobacterium. The most closely related strains (16S rRNA gene sequence similarity indicated in parentheses), based on the phylogenetic analysis, were Chryseobacterium rhizosphaerae KCTC 22548T (98.08 %), Chryseobacterium nakagawai CCUG 60563T (98.61 %), Chryseobacterium jejuense KACC 12501T (97.85 %) and Chryseobacterium aurantiacum KCTC 62135T (97.78 %). Whole genome sequencing indicated that the genome size was 5 125 723 bp and had a DNA G+C content of 37.4 mol%. Average nucleotide identity values for strain CA7T with C. rhizosphaerae, C. nakagawai, C. jejuense, C. aurantiacum, and the type species of the genus Chryseobacterium, C. gleum, were 80.2, 79.8, 79.8, 79.6 and 80.4 %, respectively. The digital DNA-DNA hybridization values of CA7T compared to C. rhizosphaerae, C. nakagawai, C. jejuense, C. aurantiacum and C. gleum were 24.1, 23.9, 23.9, 23.7 and 24.3 %, respectively. The major fatty acids were iso-C15 : 0, summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl), iso-C17 : 0 3-OH and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c). Menaquinone-6 was the only respiratory quinone. The major polar lipid was phosphatidylethanolamine. Based on this polyphasic taxonomic study, strain CA7T represents a novel species of the genus Chryseobacterium for which the name Chryseobacterium vaccae sp. nov. is proposed. The type strain is CA7T (=KACC 21402T=JCM 33749T).

Chryseobacterium mulctrae sp. nov., isolated from raw cow's milk.

A Gram-stain-negative bacterial strain, designated CA10T, was isolated from bovine raw milk sampled in Anseong, Republic of Korea. Cells were yellow-pigmented, aerobic, non-motile bacilli and grew optimally at 30 °C and pH 7.0 on tryptic soy agar without supplementation of NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain CA10T belonged to the genus Chryseobacterium, family Flavobacteriaceae, and was most closely related to Chryseobacterium indoltheticum ATCC 27950T (98.75 % similarity). The average nucleotide identity and digital DNA-DNA hybridization values of strain CA10T were 94.4 and 56.9 %, respectively, relative to Chryseobacterium scophthalmum DSM 16779T, being lower than the cut-off values of 95-96 and 70 %, respectively. The predominant respiratory quinone was menaquinone-6; major polar lipid, phosphatidylethanolamine; major fatty acids, iso-C15 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) and iso-C17 : 0 3-OH. The results of physiological, chemotaxonomic and biochemical analyses suggested that strain CA10T is a novel species of genus Chryseobacterium, for which the name Chryseobacterium mulctrae sp. nov. is proposed. The type strain is CA10T (=KACC 21234T=JCM 33443T).

Chryseobacterium aureum sp. nov., isolated from the Han River, Republic of Korea.

A Gram-stain-negative, yellow-pigmented, non-motile, non-spore-forming, aerobic and rod-shaped bacterial strain, designated 17S1E7T, was isolated from the Han River, Republic of Korea, and characterized by polyphasic taxonomy analyses. Strain 17S1E7T grew optimally on tryptic soy agar at 37 °C and pH 7.0 in the absence of NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain 17S1E7T belonged to the genus Chryseobacterium and was most closely related to Chryseobacterium culicis DSM 23031T (98.54 %). The average nucleotide identity value of strain 17S1E7T was 91.1 % to Chryseobacterium culicis DSM 23031T, which was lower than the cut-off of 95-96 %. The DNA G+C content of strain 17S1E7T was 37.4 mol%. Flexirubin-type pigments were produced. The predominant respiratory quinone was menaquinone 6. The major fatty acids of strain 17S1E7T were iso-C15 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), iso-C17 : 0 3-OH and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c). The predominant polar lipid was phosphatidylethanolamine. Based on polyphasic taxonomy data, strain 17S1E7T represents a novel species of the genus Chryseobacterium, for which the name Chryseobacterium aureum sp. nov. is proposed. The type strain is 17S1E7T (=KACC 19920T=JCM 33165T).

The Protective Effect of Exclusive Breastfeeding on Overweight/Obesity in Children with High Birth Weight.

BACKGROUND: A positive association between birth weight (BW) and body mass index (BMI) has been shown among children in many populations. The aim of this study was to investigate BMI trajectory according to BW status and the protective effect of breastfeeding on the prevalence of overweight/obesity in children 6 years of age. METHODS: A retrospective cohort study was conducted between January 1, 2008 and December 31, 2016 utilizing data from the National Health Information Database of Korea. The 38,049 subjects were followed until the end of 2016, providing that subjects were completely eligible for all health check-ups from birth to 6 years of age. At each check-up period, multiple logistic regressions were used to investigate the association between BW status (low birth weight [LBW], normal birth weight [NBW], high birth weight [HBW]) and growth development. RESULTS: HBW infants were highly likely to be overweight/obese compared to NBW infants (odds ratio [OR], 1.70-2.35) and LBW infants were highly likely to be underweight (OR, 1.69-2.20) through 6 years of age. The risk of overweight/obesity decreased significantly if HBW infants were breast-fed for 6 months (OR, 0.54-0.76). CONCLUSION: HBW status is associated with overweight/obesity during early childhood. Exclusive breastfeeding is a significant protective factor against overweight/obesity in children with HBW.

Metabolite profiling study on the toxicological effects of polybrominated diphenyl ether in a rat model.

Polybrominated diphenyl ethers (PBDEs) are commonly used to retard the combustion of materials such as foam padding, textiles, or plastics, and numerous studies have confirmed the accumulation thereof in the environment and in fish, mammals, and humans. In this study, we used metabolomics to conduct an environmental risk assessment of the PBDE-209. We profiled the urinary metabolites of control and PBDE-treated rats (exposed to PBDE-209) using nuclear magnetic resonance (NMR) and mass spectrometry (MS). Global metabolic profiling indicated that the effects of PBDE-209 on the urinary metabolic profile were not significant. However, targeted metabolic profiling revealed progressive effects of PBDE-209 over a 7-day PBDE-209 treatment. Moreover, despite the weak PBDE-209 effects, we observed that choline, acetylcholine, 3-indoxylsulfate, creatinine, urea, and dimethyl sulfone levels were decreased, whereas that of pyruvate was significantly increased. Furthermore, we suggest that the increased pyruvate level and decreased levels of choline, acetylcholine, and uremic toxins were suggestive of endocrine disruption and neurodevelopmental toxicity caused by PBDEs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1262-1272, 2017.

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery.

Bariatric surgery alleviates obesity and ameliorates glucose tolerance. Using metabolomic and proteomic profiles, we evaluated metabolic changes in serum and liver tissue after duodenal-jejunal bypass (DJB) surgery in rats fed a normal chow diet. We found that the levels of vitamin B12 in the sera of DJB rates were decreased. In the liver of DJB rats, betaine-homocysteine S-methyltransferase levels were decreased, whereas serine, cystathionine, cysteine, glutathione, cystathionine ß-synthase, glutathione S-transferase, and aldehyde dehydrogenase levels were increased. These results suggested that DJB surgery enhanced trans-sulfuration and its consecutive reactions such as detoxification and the scavenging activities of reactive oxygen species. In addition, DJB rats showed higher levels of purine metabolites such as ATP, ADP, AMP, and inosine monophosphate. Decreased guanine deaminase, as well as lower levels of hypoxanthine, indicated that DJB surgery limited the purine degradation process. In particular, the AMP/ATP ratio and phosphorylation of AMP-activated protein kinase increased after DJB surgery, which led to enhanced energy production and increased catabolic pathway activity, such as fatty acid oxidation and glucose transport. This study shows that bariatric surgery altered trans-sulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery.

Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR.

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation.

Using tyrosinase as a monophenol monooxygenase: A combined strategy for effective inhibition of melanin formation.

Tyrosinase is a binuclear copper-containing metalloprotein that leads the fast and regio-selective o-hydroxylation of monophenols to o-diphenols. However, the subsequent second oxidation to produce o-quinones, i.e., melanin precursors, from the o-diphenols has restricted its use to the production of functional o-diphenol derivatives. Herein, we present a combined strategy for the effective inhibition of melanin formation in tyrosinase reaction, which allows the use of tyrosinase as a monophenol monooxygenase. The o-diphenolic products were protected from being oxidized in the tyrosinase reaction by borate ions and L-ascorbic acid (LAA). Borate-o-diphenol complexes were favorable formed at high pH and consequentially protected the o-diphenolic products from the catecholase activity of tyrosinase. LAA not only directly reduced the byproduct, o-quinones, into o-diphenols but also assisted the completion of the tyrosinase reaction cycle by removing a hydroxyl group attached to the copper metal cluster at the active site of the met-form tyrosinase. The regio-selective o-hydroxylation of 7,4'-dihydroxyisoflavone (daidzein) to produce 7,3',4'-trihydroxyisoflavone (3'-ODI) was successfully carried out by whole E. coli cell biotransformation with heterologously expressed tyrosinase from Bacillus megaterium. The yield of this o-hydroxylation of 5 mM daidzein in one-pot 400 mL reaction was ca. 100% in 90 min and the productivity was 16.3 mg 3'-ODI · L(-1) · h(-1) · DCW mg(-1), which is considerably higher than that of other monooxygenases. The method effectively abolished melanin synthesis, so that the o-diphenolic product remained stable without enzyme inactivation. Other monophenolic phytochemicals such as resveratrol and genistein could be subjected to the same strategy. After 1 h, 1 mM of genistein and resveratrol were both converted to orobol and piceatannol, respectively, with ca. 95% conversion yield. These results support the strong potential of tyrosinase as a monooxygenase for regio-selective o-hydroxylation of various monophenolic compounds.

Secondary metabolite profiling of Curcuma species grown at different locations using GC/TOF and UPLC/Q-TOF MS.

Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

Monophosphoryl lipid A and poly I:C combination enhances immune responses of equine influenza virus vaccine.

Equine influenza is a contagious respiratory disease caused by H3N8 type A influenza virus. Vaccination against equine influenza is conducted regularly; however, infection still occurs globally because of the short immunity duration and suboptimal efficacy of current vaccines. Hence the objective of this study was to investigate whether an adjuvant combination can improve immune responses to equine influenza virus (EIV) vaccines. Seventy-two mice were immunized with an EIV vaccine only or with monophosphoryl lipid A (MPL), polyinosinic-polycytidylic acid (Poly I:C), or MPL + Poly I:C. Prime immunization was followed by boost immunization after 2 weeks. Mice were euthanized at 4, 8, and 32 weeks post-prime immunization, respectively. Sera were collected to determine humoral response. Bone marrow, spleen, and lung samples were harvested to determine memory cell responses, antigen-specific T-cell proliferation, and lung viral titers. MPL + Poly I:C resulted in the highest IgG, IgG1, and IgG2a antibodies and hemagglutination inhibition titers among the groups and sustained their levels until 32 weeks post-prime immunization. The combination enhanced memory B cell responses in the bone marrow and spleen. At 8 weeks post-prime immunization, the combination induced higher CD8+ central memory T cell frequencies in the lungs and CD8+ central memory T cells in the spleen. In addition, the combination group exhibited enhanced antigen-specific T cell proliferation, except for CD4+ T cells in the lungs. Our results demonstrated improved immune responses when using MPL + Poly I:C in EIV vaccines by inducing enhanced humoral responses, memory cell responses, and antigen-specific T cell proliferation.

Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: A biomechanical study.

Purpose: This study aims to compare the compressive and tensile strengths of bone cement mixed with various concentrations of vancomycin, tobramycin, and combinations of the two. Methods: 12 mm × 6 mm antibiotic bone cement samples were created by vacuum mixing 0-4 g of vancomycin, tobramycin, and combinations of the two in 0.5 g increments per one pouch (40 g) of Palacos LV cement. An Instron 3369 Universal Testing System was used to determine the compressive and tensile strengths. Results: Compressive and tensile strengths of the bone cement without antibiotics were 118 ± 4 MPa and 30.3 ± 12 MPa, respectively. 4 g of vancomycin alone decreased the compressive strength to 108 ± 4 MPa (p-value 0.001) and decreased the tensile strength beginning at 2 g which yielded a strength of 28.1 ± 12 MPa (p-value 0.016). Tobramycin alone decreased the tensile strength beginning at 1.5 g yielding a strength of 27.7 ± 7 MPa (p-value 0.003). Although it decreased compressive strength at 1 g to 117 ± 7 MPa (p-value 0.002), it demonstrated variable effects with increasing concentrations. A combination of vancomycin and tobramycin decreased both the compressive (111 ± 5 MPa, p-value 0.014) and tensile (27.9 ± 8 MPa, p-value 0.007) strengths beginning at 1 g each. Conclusions: Various combinations of vancomycin and tobramycin affect the compressive and tensile strengths of bone cement. Clinicians should be diligent when mixing these antibiotics in bone cement to prevent possible failure of the constructs.

A Comparison of Muscle Activities in the Lower Extremity between Flat and Normal Feet during One-leg Standing.

[Purpose] This study examined the differences in muscle activation between flat and normal feet in the one-leg standing position which delivers the greatest load to the lower extremity. [Subjects] This study was conducted with 23 adults, 12 with normal feet and 12 with flat feet, with ages ranging from 21 to 30 years old, who had no neurological history or gait problems. [Methods] The leg used for one leg standing was the dominant leg of the subjects. The experimenter instructed the subjects to raise the non-dominant leg with their eyes open, and the subjects maintained a posture with the non-dominant leg's knee flexed at 90° and the hip joint flexed at 45° for six seconds. In the position of one-leg standing, a horizontal rod was set at the height of the waist line of the subjects who lightly placed two fingers of each hand on the rod to prevent inclination of the trunk to one side. Measurements were taken three times and the maximum value was used. A surface electromyogram (TeleMyo 2400T, Noraxon Co., USA) was used to measure muscle activities. [Results] We compared muscle activities between flat and normal foot, and the results show a significant difference between normal and flat feet in the muscle activity of the abductor hallucis muscle. [Conclusion] The subjects with flat feet had relatively lower activation of the abductor hallucis muscle than those with normal feet during one leg standing. We infer from this that the abductor hallucis muscle of flat foot doesn't work as well as a dynamic stabilizer, compared to a normal foot, during one leg standing.