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1.
Foodborne Pathog Dis ; 18(2): 123-130, 2021 02.
Article in English | MEDLINE | ID: mdl-33544050

ABSTRACT

This study investigated the inactivation mechanism of Aspergillus flavus conidia by high hydrostatic pressure (HHP). Activity counts, scanning electron microscopic (SEM) analysis, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to study the effects of the HHP treatment on the morphology and protein composition of A. flavus spores. The results showed that that a 3-min-lasting 600 MPa treatment could completely abolish 107 colony-forming units/mL of live fungi. Furthermore, we also observed that lower spore viability corresponded to a higher Propidium Iodide absorption rate. The SEM images revealed that HHP disrupted the spore morphology and resulted in pore formation that led to the release of intracellular molecules, such as nucleic acids and proteins. The nucleic acid and protein concentration in the spore suspension increased in parallel with the increasing treatment pressure. The SDS-PAGE analysis showed that there were differences in the protein bands between the HHP-treated and untreated A. flavus spores, as the HHP treatment caused partial protein degradation and extracellular release. Therefore, the results of this study proved that high pressure could induce a morphological disruption in the internal and external cellular structures and degrade intracellular and extracellular proteins leading to an inactive state in A. flavus.


Subject(s)
Aspergillus flavus/physiology , Food Microbiology/methods , Hydrostatic Pressure , Microbial Viability , Spores, Fungal/physiology , Colony Count, Microbial , Electrophoresis, Polyacrylamide Gel , Microscopy, Electron, Scanning
2.
BMC Pediatr ; 19(1): 179, 2019 06 05.
Article in English | MEDLINE | ID: mdl-31167645

ABSTRACT

BACKGROUND: Infants with hemodynamically significant patent ductus arteriosus (PDA) may physiologically compensate with a supranormal cardiac output (CO). As such, a supranormal CO may be a surrogate marker for a significant PDA or indicate a failed response to PDA closure by ibuprofen. Electrical cardiometry (EC) is an impedance-based monitor that can continuously and non-invasively assess CO (COEC). We aimed to trend COEC through ibuprofen treatment for PDA in preterm infants. METHODS: We reviewed our database of preterm infants receiving ibuprofen for PDA closure. Response to ibuprofen was defined as no ductal flow in echocardiography ≤24 h after treatment. Responders were compared with gestational age (GA) and postnatal age matched non-responders and their trends of COEC were compared. Both groups' baseline COEC were further compared to the reference infants without PDA. RESULTS: Eighteen infants (9 responders and 9 non-responders) with median (interquatile range) GA 27.5 (26.6-28.6) weeks, birthweight 1038 (854-1218) g and age 3.5 (3.0-4.0) days were studied. There were positive correlations between COEC and ductal diameter and left atrium/ aortic root ratio (r = 0.521 and 0.374, p < 0.001, respectively). Both responders and non-responders had significantly higher baseline COEC than the reference. Although there was no significant within-subject alteration of COEC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher COEC. CONCLUSIONS: The changes of COEC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline COEC compared to those without PDA, and non-responders had higher COEC especially at baseline compared to responders.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cardiac Output/drug effects , Ductus Arteriosus, Patent/drug therapy , Ibuprofen/therapeutic use , Analysis of Variance , Cardiac Output/physiology , Cardiography, Impedance/methods , Case-Control Studies , Cyclooxygenase Inhibitors/therapeutic use , Ductus Arteriosus, Patent/diagnostic imaging , Ductus Arteriosus, Patent/physiopathology , Echocardiography , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Male , Treatment Outcome
3.
J Food Sci Technol ; 56(9): 3988-3997, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31477970

ABSTRACT

The aim of this study was to use high hydrostatic pressure treatment to enhance the extraction efficiency of the active components from the fruiting bodies of Antrodia cinnamomea, and compare with those obtained by shake and ultrasonic extraction methods. The conditions of high pressure extraction (HPE) at 600 MPa, a liquid/solid ratio of 40:1, and 3 min of treatment yielded triterpenoids and adenosine concentrations of 410.41 mg/100 mL and 0.47 mg/100 mL, respectively, which did not differ significantly from those with the two other treatments-shake extraction at 180 rpm for 8 h and ultrasonic extraction at 50 Hz for 60 min. The HPE extracts significantly attenuated reactive oxygen species, nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated RAW 264.7 cells than shake extracts did. SEM micrographs revealed that high-pressure caused physical morphological damage to the mycelium of fruiting bodies, such as distortion and disruption of mycelial cells, and increased the mass-transfer effectiveness of the solvent and solute. HPE can be employed as an efficient extraction technique for production of bioactive ingredients that might have a potential application in food and related industries.

4.
J Food Sci Technol ; 56(9): 4016-4024, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31477973

ABSTRACT

The hulls of Djulis (Chenopodium formosanum) are a type of agricultural waste. Using 70% ethanol as the extraction solvent, this study compared the extraction yields of high-pressure-assisted extraction (HPE) and conventional oscillation extraction (CE) for Djulis hulls (DH). The total phenolic and flavonoid contents, and antioxidant, anti-inflammatory and anti-tyrosinase activities were also compared. Our findings indicated that 600 MPa/5 min of HPE resulted in higher total phenolic (567-642 mg GAE/g) and flavonoid (47.2-57.2 mg QU/g) concentrations; gallic acid (44.5-53.2 µg/g) and rutin (26.8-34.2 µg/g) were the main phenolic and flavonoid compounds. When the extraction pressure was greater than 450 MPa, HPE extracts showed stronger antioxidant capacity and anti-tyrosinase activity than CE extracts. In a LPS-induced RAW 264.7 cell model of inflammation, HPE extracts had significant inhibitory effects on the cumulative concentrations of nitric oxide and prostaglandin E2. These results indicate that HPE had a better extraction yield, and required a shorter time for the extraction of functional ingredients from DH. Hence, DH could be a potential source for natural antioxidants for the food and biotechnology industries.

5.
J Biol Inorg Chem ; 23(5): 775-784, 2018 07.
Article in English | MEDLINE | ID: mdl-29858679

ABSTRACT

The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)2] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe2(µ-SR)2(NO)4] (1) as a universal platform for the O2-triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-ßgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology.


Subject(s)
Caenorhabditis elegans/physiology , Iron/chemistry , Longevity , Nitric Oxide/administration & dosage , Nitrogen Oxides/chemistry , Adenylate Kinase/metabolism , Animals , Caenorhabditis elegans/genetics , Half-Life , Kinetics , Molecular Structure , Nitric Oxide/chemistry , Sequence Analysis, RNA , Signal Transduction , Spectrum Analysis/methods
6.
J Sci Food Agric ; 98(15): 5625-5631, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29700833

ABSTRACT

BACKGROUND: The aim of this study was to investigate the influence of high-pressure processing (HPP) on γ-aminobutyric acid (GABA) content, glutamic acid (Glu) content, glutamate decarboxylase (GAD) activity, growth of Aspergillus fresenii, and accumulated ochratoxin A (OTA) content in coffee beans. RESULTS: The results indicated that coffee beans subjected to HPP at pressures ≥50 MPa for 5 min increased GAD activity and promoted the conversion of Glu to GABA, and showed a significantly doubling of GABA content compared with unprocessed coffee beans. Additionally, investigation of the influence of HPP on A. fresenii growth on coffee beans showed that application ≥400 MPa reduced A. fresenii concentrations to <1 log. Furthermore, during a 50-day storage period, we observed that a processing pressure of 600 MPa completely inhibited A. fresenii growth, and on day 50 the OTA content of coffee beans subjected to processing pressures of 600 MPa was 0.0066 µg g-1 , which was significantly lower than the OTA content of 0.1143 µg g-1 in the control group. CONCLUSION: This study shows that HPP treatment can simultaneously increase GABA content and inhibit the growth of A. fresenii, thereby effectively reducing the production and accumulation of OTA and maintaining the microbiological safety of coffee beans. © 2018 Society of Chemical Industry.


Subject(s)
Coffea/chemistry , Food Handling/methods , gamma-Aminobutyric Acid/analysis , Aspergillus ochraceus/growth & development , Aspergillus ochraceus/metabolism , Coffea/microbiology , Coffee/chemistry , Coffee/microbiology , Food Contamination/analysis , Food Handling/instrumentation , Food Safety , Glutamic Acid/analysis , Ochratoxins/analysis , Ochratoxins/metabolism , Pressure , Seeds/chemistry , Seeds/microbiology
7.
J Food Sci Technol ; 55(5): 1716-1725, 2018 May.
Article in English | MEDLINE | ID: mdl-29666524

ABSTRACT

This study validated high hydrostatic pressure processing (HPP) for achieving greater than 5-log reductions of Escherichia coli O157:H7 in carambola juice and determined shelf life of processed juice stored at 4 °C. Carambola juice processed at 600 MPa for 150 s was identified capable of achieving greater than 5.15-log reductions of E. coli O157:H7, and the quality was compared with that of high temperature short time (HTST)-pasteurized juice at 110 °C for 8.6 s. Aerobic, psychrotrophic, E. coli/coliform, and yeasts and moulds in the juice were reduced by HPP or HTST to levels below the minimum detection limit (< 1.0 log CFU/mL), and showed no outgrowth after refrigerated storage of 40 days. There were no significant differences in pH and titratable acidity between the untreated, HPP, and HTST juices. However, HTST treatment significantly changed the color of juice, while no significant difference was observed between the control and HPP samples. HPP and HTST treatments reduced the total soluble solids in the juice, but maintained higher sucrose, glucose, fructose, and total sugar contents than untreated juice. The total phenolic and ascorbic acid contents were higher in juice treated with HPP than untreated and HTST juice, but there was no significant difference in the flavonoid content. Aroma score analysis showed that HPP had no effect on aroma, maintaining the highest score during cold storage. The results of this study suggest that appropriate HPP conditions can achieve the same microbial safety as HTST, while maintaining the quality and extending the shelf life of carambola juice.

8.
J Sci Food Agric ; 97(10): 3166-3172, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27885688

ABSTRACT

BACKGROUND: The aim of this study was to investigate the microbial levels, physicochemical and antioxidant properties and polyphenol oxidase (PPO) and peroxidase (POD) activities as well as to conduct a sensory analysis of white grape juice treated with high-pressure processing (HPP) and thermal pasteurization (TP), over a period of 20 days of refrigerated storage. RESULTS: HPP treatment of 600 MPa and TP significantly reduced aerobic bacteria, coliform and yeast/mold counts. At day 20 of storage, HPP-600 juice displayed no significant differences compared with fresh juice in terms of physicochemical properties such as titratable acidity, pH and soluble solids, and retained less than 50% PPO and POD activities. Although significant differences were observed in the color, antioxidant contents and antioxidant capacity of HPP-treated juice, the extent of these differences was substantially lower than that in TP-treated juice, indicating that HPP treatment can better retain the quality of grape juice. Sensory testing showed no significant difference between HPP-treated juice and fresh juice, while TP reduced the acceptance of grape juice. CONCLUSION: This study shows that HPP treatment maintained the overall quality parameters of white grape juice, thus effectively extending the shelf life during refrigerated storage. © 2016 Society of Chemical Industry.


Subject(s)
Food Handling/methods , Fruit and Vegetable Juices/analysis , Vitis/chemistry , Antioxidants/analysis , Food Handling/instrumentation , Fruit/chemistry , Hot Temperature , Pasteurization , Polyphenols/analysis
9.
Crit Rev Food Sci Nutr ; 56(4): 527-40, 2016.
Article in English | MEDLINE | ID: mdl-25629307

ABSTRACT

High hydrostatic pressure is an emerging non-thermal technology that can achieve the same standards of food safety as those of heat pasteurization and meet consumer requirements for fresher tasting, minimally processed foods. Applying high-pressure processing can inactivate pathogenic and spoilage microorganisms and enzymes, as well as modify structures with little or no effects on the nutritional and sensory quality of foods. The U.S. Food and Drug Administration (FDA) and the U.S. Department of Agriculture (USDA) have approved the use of high-pressure processing (HPP), which is a reliable technological alternative to conventional heat pasteurization in food-processing procedures. This paper presents the current applications of HPP in processing fruits, vegetables, meats, seafood, dairy, and egg products; such applications include the combination of pressure and biopreservation to generate specific characteristics in certain products. In addition, this paper describes recent findings on the microbiological, chemical, and molecular aspects of HPP technology used in commercial and research applications.


Subject(s)
Food Handling/methods , Food Microbiology/methods , Foodborne Diseases/prevention & control , Hydrostatic Pressure , Alcoholic Beverages/standards , Animals , Dairy Products/microbiology , Dairy Products/standards , Eggs/microbiology , Eggs/standards , Food Handling/standards , Food Microbiology/standards , Food Microbiology/trends , Food Quality , Freezing , Fruit/microbiology , Fruit/standards , Humans , Meat Products/microbiology , Meat Products/standards , Nutritive Value , Pasteurization , Pigmentation , Seafood/microbiology , Seafood/standards , Sterilization , Taste , Vegetables/microbiology , Vegetables/standards
10.
Foodborne Pathog Dis ; 12(2): 139-44, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25514674

ABSTRACT

The aim of this work was to investigate the mechanisms underlying the inactivation of Listeria monocytogenes in raw milk under high hydrostatic pressure (HHP). The results showed that a 450-MPa treatment for 5 min could completely eliminate 108 colony-forming units/mL of viable bacteria, as indicted by increased uptake of propidium iodide. Morphological damage to the cell wall, cell membrane, and cytoplasmic components by HHP treatments was observed on scanning and transmission electron micrographs. The protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels differed between HHP-treated and untreated L. monocytogenes, in that HHP decreased the protein content and caused partial protein degradation. Therefore, our results indicate that HHP inactivates L. monocytogenes by causing morphological changes in the internal and external cellular structures, as well as through membrane damage, cell wall rupture, and membrane protein degradation.


Subject(s)
Cell Membrane/ultrastructure , Cell Wall/ultrastructure , Listeria monocytogenes/ultrastructure , Milk/microbiology , Pasteurization , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Cell Membrane/metabolism , Cell Wall/metabolism , Colony Count, Microbial , Hydrostatic Pressure , Listeria monocytogenes/growth & development , Listeria monocytogenes/isolation & purification , Listeria monocytogenes/metabolism , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Microbial Viability , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Stability , Proteolysis , Taiwan , Time Factors
11.
Biochemistry ; 53(12): 1935-46, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24628338

ABSTRACT

The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF and a membrane-anchored cytoplasmic tail (proHB-EGF-CT), which may be targeted to the nuclear membrane after a shedding stimulus. Bcl-2-associated athanogene 1 (BAG-1) accumulates in the nuclei and inhibits apoptosis in adenoma-derived cell lines. The maintenance of high levels of nuclear BAG-1 enhances cell survival. However, the ubiquitin homology domain of BAG-1 from Mus musculus (mBAG-1-UBH) is proposed to interact with proHB-EGF-CT, and this interaction may enhance the cytoprotection against the apoptosis inducer. The mechanism of the synergistic anti-apoptosis function of proHB-EGF-CT and mBAG-1-UBH is still unknown. We offer a hypothesis that proHB-EGF-CT can maintain high levels of nuclear BAG-1. In this study, we first report the three-dimensional nuclear magnetic resonance structure of proHB-EGF-CT complexed with mBAG-1-UBH. In the structure of the complex, the residues in the C-terminus and one turn between ß-strands ß1 and ß2 of mBAG-1-UBH bind to two terminals of proHB-EGF-CT, which folds into a loop with end-to-end contact. This end-to-end folding of proHB-EGF-CT causes the basic amino acids to colocalize and form a positively charged groove. The dominant forces in the binding interface between proHB-EGF-CT and mBAG-1-UBH are charge-charge interactions. On the basis of our mutagenesis results, the basic amino acid cluster in the N-terminus of proHB-EGF-CT is the crucial binding site for mBAG-1-UBH, whereas another basic amino acid in the C-terminus facilitates this interaction. Interestingly, the mBAG-1-UBH binding region on the proHB-EGF-CT peptide is also involved in the region found to be important for nuclear envelope targeting, supporting the hypothesis that proHB-EGF-CT is most likely able to trigger the nuclear translocation of BAG-1 in keeping its level high.


Subject(s)
DNA-Binding Proteins/chemistry , Intercellular Signaling Peptides and Proteins/chemistry , Magnetic Resonance Spectroscopy , Transcription Factors/chemistry , Ubiquitin/chemistry , Amino Acid Sequence , Animals , Binding Sites/genetics , Cell Survival/genetics , Cytoplasm/chemistry , Cytoplasm/genetics , Cytoplasm/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Genes, bcl-2 , Heparin-binding EGF-like Growth Factor , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Magnetic Resonance Spectroscopy/methods , Mice , Molecular Sequence Data , Sequence Homology, Amino Acid , Transcription Factors/genetics , Transcription Factors/metabolism , Ubiquitin/genetics , Ubiquitin/metabolism
12.
Compr Rev Food Sci Food Saf ; 13(1): 78-90, 2014 Jan.
Article in English | MEDLINE | ID: mdl-33412689

ABSTRACT

High-pressure processing (HPP) technology is a novel, nonthermal processing technology for food. This special processing method can inactivate microorganisms and enzymes in food at room temperature using ultra-high pressures of above 100 MPa, while the original flavor and nutritional value of the food are maintained, with an extended refrigerated shelf-life of the food in distribution. In recent years, because of the rising prevalence of food allergies, many researchers have actively sought processing methods that reduce the allergenicity of food allergens. This study describes the effects of the current HPP technology on allergen activity. Our main goal was to provide an overview of the current research achievements of the application of HPP to eliminate the allergenicity of various foods, including legumes, grains, seafood, meat, dairy products, fruits, and vegetables. In addition, the processing parameters, principles, and mechanisms of HPP for allergen destruction are discussed, such as the induction of protein denaturation, the change in protein conformation, allergen removal using the high-pressure extraction technology, and the promotion of enzymatic hydrolysis to alter the sensitization of the allergens. In the future, the application of HPP technology as a pretreatment step for raw food materials may contribute to the development of food products with low or no allergenic ingredients, which then can effectively reduce the concern for consumers with allergies, reduce the risk of mistaken ingestion, and reduce the overall incidence of allergic reactions from food.

13.
J Agric Food Chem ; 72(15): 8347-8364, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38571475

ABSTRACT

Gut dysbiosis contributes to deterioration of chronic kidney disease (CKD). Probiotics are a potential approach to modulate gut microbiota and gut-derived metabolites to alleviate CKD progression. We aim to provide a comprehensive view of CKD-related gut dysbiosis and a critical perspective on probiotic function in CKD. First, this review addresses gut microbial alterations during CKD progression and the adverse effects associated with the changes in gut-derived metabolites. Second, we conduct a thorough examination of the latest clinical trials involving probiotic intervention to unravel critical pathways via the gut-kidney axis. Finally, we propose our viewpoints on limitations, further considerations, and future research prospects of probiotic adjuvant therapy in alleviating CKD progression. Enhancing our understanding of host-microbe interactions is crucial for gaining precise insights into the mechanisms through which probiotics exert their effects and identifying factors that influence the effectiveness of probiotics in developing strategies to optimize their use and enhance clinical outcomes.


Subject(s)
Gastrointestinal Microbiome , Probiotics , Renal Insufficiency, Chronic , Humans , Dysbiosis , Kidney , Renal Insufficiency, Chronic/therapy , Probiotics/therapeutic use
14.
Animals (Basel) ; 14(4)2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38396596

ABSTRACT

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease (CKD). Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxin (GDUT), indoxyl sulfate (IS), were potential clinical significance in IS after Lm treatment (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, metabolic functional pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious GDUTs. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

15.
Biochem Biophys Res Commun ; 431(1): 86-91, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23277101

ABSTRACT

BAG-1 (Bcl-2-associated athanogene 1), a multifunctional anti-apoptotic protein known to interact with various cellular proteins, was isolated using its interaction with the anti-apoptotic protein, Bcl-2. A 97-amino acid segment that includes the ubiquitin homology (UBH) domain of mouse BAG-1 (mBAG-1) interacts with a peptide corresponding to the cytoplasmic tail (CT) domain of proHB-EGF. This protein-peptide interaction is likely to have functional significance, as the two species exhibit a synergistic cytoprotective effect. In this study, we determined the solution structure of mBAG-1-UBH and investigated its interaction with the proHB-EGF-CT peptide using isothermal titration calorimetry and NMR spectroscopy. The solution structure of mBAG-1-UBH was shown to be similar to the previously reported structure of hBAG-1-UBH (PDB code 1WXV). However, their electrostatic potential maps demonstrated some differences in the UBH motifs that may be important for protein-peptide interaction. An NMR titration experiment demonstrated that residues 23-26 and residues 89-94 of mBAG-1-UBH are important for its molecular interaction with the peptide proHB-EGF-CT. BAG-1-UBH shares some biological functions with ubiquitin including the formation of polyubiquitin chain and the proteasomal protein degradation. The unique cytoprotective activity suggests mBAG-1-UBH to be an interesting ubiquitin-like protein with distinct biological functions. Here, we first reported the solution structure of mBAG-1-UBH and the growth factor precursor-interacting motif on the protein. For detail understanding about the binding interface and the mechanism of interaction, the study on mBAG-1-UBH/proHB-EGF-CT complex structure is necessary.


Subject(s)
DNA-Binding Proteins/chemistry , Transcription Factors/chemistry , Ubiquitin/chemistry , Amino Acid Sequence , Animals , Heparin-binding EGF-like Growth Factor , Humans , Intercellular Signaling Peptides and Proteins/chemistry , Mice , Molecular Sequence Data , Nuclear Magnetic Resonance, Biomolecular , Protein Interaction Mapping , Protein Structure, Tertiary , Solutions
16.
J Allergy Clin Immunol ; 129(6): 1562-9.e5, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22322005

ABSTRACT

BACKGROUND: Increasing studies have revealed that HLA alleles are the major genetic determinants of drug hypersensitivity; however, the underlying molecular mechanism remains unclear. OBJECTIVE: We adopted the HLA-B∗1502 genetic predisposition to carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) as a model to study the pathologic role of HLA in delayed-type drug hypersensitivity. METHODS: We in vitro expanded CBZ-specific cytotoxic T lymphocytes (CTLs) from patients with CBZ-induced SJS/TEN and analyzed the interaction between HLA-B and CBZ analogs based on CTL response, surface plasmon resonance, peptide-binding assay, site-directed mutagenesis, and computer modeling. RESULTS: The endogenous peptide-loaded HLA-B∗1502 molecule presented CBZ to CTLs without the involvement of intracellular drug metabolism or antigen processing. The HLA-B∗1502/peptide/ß(2)-microglobulin protein complex showed binding affinity toward chemicals sharing 5-carboxamide on the tricyclic ring, as with CBZ. However, modifications of the ring structure of CBZ altered HLA-B∗1502 binding and CTL response. In addition to HLA-B∗1502, other HLA-B75 family members could also present CBZ to activate CTLs, whereas members of the HLA-B62 and HLA-B72 families could not. Three residues (Asn63, Ile95, and Leu156) in the peptide-binding groove of HLA-B∗1502 were involved in CBZ presentation and CTL activation. In particular, Asn63 shared by members of the B75 family was the key residue. Computer simulations revealed a preferred molecular conformation of the 5-carboxamide group of CBZ and the side chain of Arg62 on the B pocket of HLA-B∗1502. CONCLUSIONS: This study demonstrates a direct interaction of HLA with drugs, provides a detailed molecular mechanism of HLA-associated drug hypersensitivity, and has clinical correlations for CBZ-related drug-induced SJS/TEN.


Subject(s)
Carbamazepine/adverse effects , Carbamazepine/immunology , Drug Hypersensitivity/immunology , HLA-B15 Antigen/chemistry , Lymphocyte Activation/immunology , Stevens-Johnson Syndrome/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Antigen Presentation/immunology , Carbamazepine/chemistry , Cell Line , Child , Drug Hypersensitivity/genetics , Female , HLA-B15 Antigen/genetics , HLA-B15 Antigen/metabolism , Humans , Male , Middle Aged , Models, Molecular , Peptides/immunology , Protein Binding/immunology , Stevens-Johnson Syndrome/chemically induced , Stevens-Johnson Syndrome/genetics , T-Lymphocytes, Cytotoxic/immunology , Young Adult
17.
J Microbiol Immunol Infect ; 56(2): 337-343, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36210318

ABSTRACT

BACKGROUND/PURPOSE: The rapid emergence of Pseudomonas aeruginosa resistance made selecting antibiotics more challenge. Antimicrobial stewardship programs (ASPs) are urging to implant to control the P. aeruginosa resistance. The purpose of this study is to evaluate the relationship between antimicrobial consumption and P. aeruginosa resistance, the impact of ASPs implemented during the 14-year study period. METHODS: A total 14,852 P. aeruginosa isolates were included in our study. The resistant rate and antimicrobial consumption were investigated every six months. Linear regression analysis was conducted to examine the trends in antibiotics consumption and antimicrobial resistance over time. The relationship between P. aeruginosa resistance and antimicrobial consumption were using Pearson correlation coefficient to analysis. The trend of resistance before and after ASPs implanted is evaluated by segment regression analysis. RESULTS: P. aeruginosa resistance to ceftazidime, gentamicin, amikacin, ciprofloxacin and levofloxacin significantly decreased during the study period; piperacillin/tazobactam (PTZ), cefepime, imipenem/cilastatin and meropenem remained stable. The P. aeruginosa resistance to ciprofloxacin and levofloxacin increasing initial then decreased after strictly controlled the use of levofloxacin since 2007. As the first choice antibiotic to treat P. aeruginosa, the consumption and resistance to PTZ increase yearly and resistance became stable since extended-infusion therapy policy implant in 2009. CONCLUSION: Our ASP intervention strategy, which included extended infusion of PTZ and restrict use of levofloxacin, may be used to control antimicrobial resistance of P. aeruginosa in medical practice.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Pseudomonas Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas aeruginosa , Levofloxacin , Hospitals, Teaching , Ciprofloxacin , Microbial Sensitivity Tests , Pseudomonas Infections/drug therapy
18.
Forensic Sci Int ; 339: 111413, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35994985

ABSTRACT

Modern rectified spirit is distilled ethanol (EtOH) containing only a tiny amount of methanol (MeOH), as opposed to former industrial alcohol, and is frequently used by perpetrators to adulterate or counterfeit Scotch whiskies in Taiwan. As a result, MeOH level presents an obvious discrepancy between adulterated whiskies and authentic Scotch whiskies. In this study, 54 authentic single malt Scotch whisky samples and 30 authentic blended Scotch whisky samples were comparatively analyzed. Instead of various analog internal standards often spiked for GC/MS quantitative analyses, the isotope-labeled internal standard 2H3-MeOH was employed for optimizing the Scotch whisky analysis to achieve a limit of quantitation (LOQ) of 5 ppm for MeOH. The resulting data were further analyzed by a distribution fitting method and showed that the distribution of MeOH levels corresponded to a lognormal distribution for both authentic single malt Scotch whiskies and authentic blended Scotch whiskies. Based on the statistical characteristics of the lognormal distribution, 99.7% of the MeOH concentrations would lie between 13.4 and 44.2 ppm for authentic single malt Scotch whiskies and between 7.87 and 74.9 ppm for authentic blended Scotch whiskies, suggesting that the MeOH level might serve as a marker for the authentication of the seized Scotch whiskies in Taiwan.


Subject(s)
Alcoholic Beverages , Methanol , Alcoholic Beverages/analysis , Ethanol/analysis , Gas Chromatography-Mass Spectrometry , Methanol/analysis , Taiwan
19.
Nutrients ; 14(16)2022 Aug 12.
Article in English | MEDLINE | ID: mdl-36014816

ABSTRACT

Exercise causes changes in the gut microbiota, and in turn, the composition of the gut microbiota affects exercise performance. In addition, the supplementation of probiotics is one of the most direct ways to change the gut microbiota. In recent years, the development and application of human-origin probiotics has gradually attracted attention. Therefore, we obtained intestinal Lactiplantibacillus plantarum "Tana" from a gold-medal-winning weightlifter, who has taken part in various international competitions such as the World Championships and the Olympic Games, to investigate the benefits of Tana supplementation for improving exercise performance and promoting antifatigue effects in mice. A total of 40 male Institute of Cancer Research (ICR) mice were divided into four groups (10 mice/group): (1) vehicle (0 CFU/mice/day), (2) Tana-1× (6.15 × 107 CFU/mice/day), (3) Tana-2× (1.23 × 108 CFU /mice/day), and (4) Tana-5× (3.09 × 108 CFU/mice/day). After four weeks of Tana supplementation, we found that the grip strength, endurance exercise performance, and glycogen storage in the liver and muscle were significantly improved compared to those in the vehicle group (p < 0.05). In addition, supplementation with Tana had significant effects on fatigue-related biochemical markers; lactate, ammonia, and blood urea nitrogen (BUN) levels and creatine kinase (CK) activity were significantly lowered (p < 0.05). We also found that the improved exercise performance and antifatigue benefits were significantly dose-dependent on increasing doses of Tana supplementation (p < 0.05), which increased the abundance and ratio of beneficial bacteria in the gut. Taken together, Tana supplementation for four weeks was effective in improving the gut microbiota, thereby enhancing exercise performance, and had antifatigue effects. Furthermore, supplementation did not cause any physiological or histopathological damage.


Subject(s)
Physical Conditioning, Animal , Probiotics , Animals , Fatigue , Glycogen , Humans , Male , Mice , Mice, Inbred ICR , Muscle Fatigue , Physical Conditioning, Animal/physiology , Probiotics/pharmacology , Swimming
20.
Microorganisms ; 10(10)2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36296158

ABSTRACT

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease accompanied with severe itching and skin lesions. Current studies have demonstrated that probiotics can exert an immunomodulatory effect, improve epithelial barrier function, and normalize the composition of gut microbiota. Thus, the aim of this study was to investigate the effect of probiotics on the immune balance of AD in vivo. We first screened two lactic acid bacteria strains, which were Lactococcus lactis subsp. cremoris MP01 and Lactobacillus paracasei subsp. paracasei MP02, from 10 strains isolated from traditional fermented milk with inflammation regulating activities in vitro. In the house dust mite (HDM) extraction-induced AD mouse model, mice were assigned randomly to four groups: control group (PC), HDM-induced AD group (NC), HDM-induced AD mice with administration of a mixture of heat-killed MP01 and MP02 at a low concentration (LD), and high concentration (HD) groups. Compared with the NC group, the probiotic treatments could relieve the AD symptoms. Moreover, the LD group significantly decreased total and HDM-specific IgE concentration. These results indicated that a combination of heat-killed MP01 and MP02 strains modulated the proportion of IL4+CD4+ T cells and IFNγ+CD4+ T cells in the spleen of HDM extraction-induced AD mice. In conclusion, administration of the heat-killed MP01 and MP02 mixtures appeared to relieve the classic AD signs, decrease serum IgE concentration, and rebalance the population of Th1/Th2 cells in HDM extraction-induced AD mice. The immunomodulatory activities of a combination of heat-killed MP01 and MP02 provided a potential new therapeutic strategy against AD.

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