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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.

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.

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., (Copyright © 2022. Published by Elsevier B.V.)

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 2 H 3 -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., Competing Interests: Conflicts of interest statement The authors whose name are listed below certify that we have NO affiliations with or involvement in any organization or entity with any financial interest(such as honoraria; educational grants; participation in speaker’s bureaus; membership, employments, consultancies, stockownership, or other equity interest; and expert testimony or patent-licensing arrangement), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

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.

Background: Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure., Methods: We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure × fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition., Results: A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28-29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p < 0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p < 0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p < 0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28-29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72., Conclusion: A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021. Published by Elsevier B.V.)

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 10 7 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 .

High hydrostatic pressure processing (HPP) is a non-thermal pasteurization technology which has already been applied in the food industries. Besides maintaining the food safety and quality, HPP also has potential applications in the enhancement of the health benefits of food products. This study examines the current progress of research on the use of HPP in the development of health foods. Through HPP, the nutritional value of food products can be enhanced or retained, including promotes the biosynthesis of γ-aminobutyric acid (GABA) in the food materials, retains immunoglobulin components in dairy products, increases resistant starch content in cereals, and reduces the glycemic index of fruit and vegetable products, which facilitates better control of blood glucose levels and decreases calorie intake. HPP can also be utilized as a hurdle technology in combination with existing processing technologies for the development of low-sodium food products and the maintenance of microbial safety, thereby lowering the risk of triggering cardiovascular disease. Additionally, HPP can be used to enhance the diversity of probiotic food products. Appropriate sporogenous probiotics can be screened and added to various high-pressure processed food products as a certain bacterial count is still retained in the products after HPP. As HPP causes physical damage to the structures of food products, it can also be used as a synergistic extraction technology to enhance the extraction efficiency of functional components, thereby reducing extraction time. By applying HPP in the extraction of functional components from food waste, the production costs of such components can be effectively reduced. This study provides a summary of the mechanisms by which HPP enhances the health benefits of food products and the current progress of relevant research. HPP possesses huge potential in the development of novel health foods and may provide an abundance of benefits to human health in the future., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

In the present study, we investigated the effects of Probiotic mix 1 (Pm1) with Lactobacillus plantarum subsp. plantarum, Lactobacillusparacasei subsp. paracasei, and Streptococcus salivarius subsp. thermophilus on preventing renal injury using a chronic kidney disease (CKD) minipig model previously developed in our lab using cisplatin-induced CKD in Lanyu pigs. The results indicated that the high dosage Pm1 (H.Pm1) group demonstrated lower incidence of lesions, including atrophy, mononuclear inflammation, cell infiltration, and interstitial fibrosis in renal tubules in hematoxylin and eosin (H&E) and Masson's trichrome stain. We further systematically investigated the preventing effect of Pm1. The H.Pm1 group decreased inflammatory cytokines production and increased the level of superoxide dismutase activity in plasma. The pigs fed with high dosage of Pm1 group also showed reduced both creatinine and blood urea nitrogen (BUN) when compared with the cisplatin group. Microbiota results indicated that Pm1-intervention not only reduced the abundance of Gram-negative bacteria but also affected the abundance of specific genera biomarkers, Anaerovibrio, possible&#95;genus&#95;SK018, Holdemanella, and Lachnospiraceae&#95;UCG&#95;010 in gut microbiota, leading to decreased inflammation and apoptosis in the kidney and further prevention/alleviation of the symptoms of CKD., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

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 E 2 . 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.

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 E 2 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.

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 (CO EC ). We aimed to trend CO EC 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 CO EC were compared. Both groups' baseline CO EC 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 CO EC 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 CO EC than the reference. Although there was no significant within-subject alteration of CO EC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher CO EC ., Conclusions: The changes of CO EC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline CO EC compared to those without PDA, and non-responders had higher CO EC especially at baseline compared to responders.

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., (© 2018 Society of Chemical Industry.)

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) [Fe 2 (μ-SR) 2 (NO) 4 ] (1) as a universal platform for the O 2 -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-βgal 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.

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.

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., (© 2016 Society of Chemical Industry.)

Background: Electrical cardiometry (EC) is an impedance-based monitoring that provides noninvasive cardiac output (CO) assessment. Through comparison to transthoracic echocardiography (Echo), the accuracy of EC has been verified. However, left-to-right patent ductus arteriosus (PDA) shunting is a concern because PDA shunts aortic flow to the pulmonary artery and may interfere with EC in measuring CO., Objective: To determine the agreement between EC and Echo in preterm infants with a hemodynamically significant PDA (hsPDA)., Methods: We reviewed our hemodynamic database in which simultaneous CO measurements by Echo and EC (Aesculon®) were recorded. Preterm infants with left-to-right shunting hsPDA were enrolled., Results: A total of 105 paired measurements in 36 preterm infants were compared. Infants' median (range) age and weight at measurement were 27+2 weeks (24+0-33+1) and 1,015 g (518-1,880), with mean (95% CI) ductal diameter 2.11 mm (1.99-2.22) or 2.15 mm/kg (2.00-2.30). Mean COEC and COEcho were 252 ± 32 and 258 ± 45 mL/kg/min, respectively, which demonstrated a moderate correlation and without a significant between-measurement difference. Bland-Altman analysis showed a bias, limits of agreement, and error percentage of -5.3 mL/kg/min, -78.3 to 67.7 mL/kg/min, and 28.6%, respectively. There was a trend of increased bias and error percentage of infants with high CO ≥280 mL/kg/min and supported with high-frequency ventilator., Conclusions: EC and Echo have a wide but clinically acceptable agreement in measuring CO in preterm infants with hsPDA. However, for infants with high CO or ventilated by high-frequency ventilation, interpretation of COEC should be approached with caution., (© 2017 S. Karger AG, Basel.)

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.

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.

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 β-strands β1 and β2 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.

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., (© 2013 Institute of Food Technologists®.)

BAG-1, an important regulatory protein associates with several signaling molecules and is capable of suppressing apoptosis. A 97-amino acid segment that includes the ubiquitin homology domain of mouse BAG-1 interacts with the cytoplasmic tail domain of proHB-EGF, and this interaction is likely to have functional significance. Here we report the backbone and side-chain resonance assignments for this 97-amino acid segment of mouse BAG-1. The assignment data has been deposited in the BMRB database under the accession number 18416.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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/β(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., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p < 0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.

In this study, the effects of phenolic acids [caffeic acid (CA), ferulic acid, m-coumaric acid, and chlorogenic acid] on methylglyoxal (MG)-induced protein glycation were investigated in vitro. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and advanced glycation end products (AGEs)-specific fluorescence showed that MG-mediated protein modification was enhanced dose-dependently by CA (P<.05), whereas α-lipoic acid, glutathione and EDTA inhibited these changes. Electron paramagnetic resonance spectra showed that CA increased reactive oxygen species (ROS) production during glycation, suggesting the proglycation mechanism of CA is associated with its pro-oxidative properties. Additionally, fetal bovine serum (FBS) was utilized as the source of target proteins for evaluating the effects of CA in cells. Differential glycation of FBS samples was performed by incubating FBS with MG, CA or aminoguanidine (AG, an AGE inhibitor). FBS incubated with MG and CA (MG/CA-FBS) evoked the greatest deleterious responses, as follows: (1) inducing proinflammatory tumor necrosis factor (TNF)-α and interleukin-1β expression and ROS production in monocytic THP-1 cells, (2) stimulating TNF-α secretion in RAW 264.7 macrophages and (3) causing oxidative DNA damage and inducing the expression of receptor for AGEs (RAGE), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, adhesion and transendothelial migration of monocytes were also significantly increased by MG/CA-FBS treatment compared to MG-FBS (P<.05). In conclusion, our data show that CA exhibits pro-oxidative and pro-glycative effects during the glycation process, suggesting a detrimental role for CA under high-glycotoxin conditions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Human epidermal growth factor (hEGF) induces the proliferation, differentiation and survival of various cell types including tumor-derived cells. Generally, hEGF performs its biological function by binding to a specific receptor (hEGFR) on the cell surface, thereby inducing signal transduction. Suramin, a polysulfonated naphthylurea that acts as a growth factor blocker, exhibits antiproliferative activity against non-small cell lung cancer (NSCLC) cells that overexpress EGFR on the cell surface. We determined the solution structure of hEGF under physiological conditions and investigated the interaction of suramin with hEGF using isothermal titration calorimetry and NMR spectroscopy techniques. The solution structure of hEGF presented in this paper is different from the bound form of hEGF present in the crystal structure of the 2:2 EGF-EGFR complex because its C-tail contains a hydrophobic core. This conformational difference supports the hypothesis that hEGF undergoes a conformational change when it binds to hEGFR and subsequently induces signal transduction. Based on the docking structure of the hEGF-suramin complex, we demonstrated how suramin blocks hEGF by binding to its receptor binding site (the C-terminal region around Arg45) and inhibits the crucial conformational change., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Scope: Hepatocellular carcinoma is the most common type of liver cancer and is highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Ginger is a natural dietary rhizome with anti-oxidative, anti-inflammatory, and anti-carcinogenic activities. The aims of this study were to evaluate the anti-invasion activity of 6-shogaol and 6-gingerol, two compounds found in ginger, on hepatoma cells., Methods and Results: The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with 6-shogaol and 6-gingerol. Upon incubation of PMA-treated HepG2 cells and PMA-untreated Hep3B cells with 6-shogaol and 6-gingerol, matrix metalloproteinase (MMP)-9 activity decreased, whereas the expression of tissue inhibitor metalloproteinase protein (TIMP)-1 increased in both cell types. Additionally, urokinase-type plasminogen activator activity was dose-dependently decreased in Hep3B cells after incubation with 6-shogaol for 24 h. Analysis with semi-quantitative reverse transcription-PCR showed that the regulation of MMP-9 by 6-shogaol and 6-gingerol and the regulation of TIMP-1 by 6-shogaol in Hep3B cells may on the transcriptional level., Conclusions: These results suggest that 6-shogaol and 6-gingerol might both exert anti-invasive activity against hepatoma cells through regulation of MMP-9 and TIMP-1 and that 6-shogaol could further regulate urokinase-type plasminogen activity.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is also highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues have been reported as candidates to prevent cancer growth and invasion. The bioactivity of resveratrol-related analogues could be altered due to the presence and positioning of methoxy groups on the basic resveratrol chemical structure. This study investigated the effects and mechanism of action of resveratrol and its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with resveratrol and 3,5,4'-trimethoxy-trans-stilbene (MR-3). Upon incubation of PMA-treated HepG2 cells with resveratrol (0-50 microM) or MR-3 (0-50 microM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose-dependent manner. With resveratrol (0-50 microM) or MR-3 (0-1 microM) treatment on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased but TIMP-2 protein increased in a dose-dependent manner. These results suggest that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be on the transcriptional level but on the translational or post-translational level for TIMP-1.

Transformations of dinitrosyl iron complex (DNIC) [(NO)(2)Fe(SEt)(2)](-) and the anionic Roussin's red ester (RRE) [(NO)(2)Fe(mu-SEt)(2)Fe(NO)(2)](-) into [2Fe-2S] clusters facilitated by HSCPh(3)/Me(2)S(3) and [Fe(SEt)(4)](-), respectively, via an intermediate anionic mixed thiolate-sulfide-bridged RRE [(NO)(2)Fe(mu-SEt)(mu-S)Fe(NO)(2)](-) through the reassembling process ([(NO)(2)Fe(SEt)(2)](-) (2)/[(NO)(2)Fe(mu-SEt)(2)Fe(NO)(2)](-) (4) --> [(NO)(2)Fe(mu-SEt)(mu-S)Fe(NO)(2)](-) (3-Et) --> [(NO)(2)Fe(mu-S)(2)Fe(NO)(2)](2-) (5) --> [(SEt)(2)Fe(mu-S)(2)Fe(SEt)(2)](2-) (1)) were demonstrated. The anionic mixed thiolate-sulfide-bridged RRE 3-Et was characterized by IR, UV-vis, electron paramagnetic resonance, (1)H NMR, cyclic voltammetry, and single-crystal X-ray diffraction. In contrast to the nucleophilicity displayed by complex 2, the inertness of [(NO)(2)Fe(SPh)(2)](-) toward HSCPh(3) implicates how the reducing ability of the coordinated thiolates of DNICs modulate the release of sulfide from HSCPh(3) via reduction and the conversion of DNICs into the anionic mixed sulfide-thiolate-bridged complex. The reversible interconversion between complex 3-Et and complex [(NO)(2)Fe(mu-SPh)(mu-S)Fe(NO)(2)](-) (3-Ph) via protonation and a bridged-thiolate exchange reaction, respectively, demonstrates that the [{Fe(NO)(2)}(9)-{Fe(NO)(2)}(9)] motif displays a preference for the stronger electron-donating alkylthiolate-bridged ligand over the phenylthiolate-bridged ligand. This study may signify that the anionic mixed thiolate-sulfide-bridged RREs act as a key intermediate in the transformation of DNICs into [2Fe-2S] clusters. Also, the thiolate-coordinate DNICs serve as not only the thiolate/electron carrier activating the incorporation of sulfide of HSCPh(3) (Me(2)S(3)) to assemble the [Fe(mu-S)(2)Fe] core but also the Fe source in the biosynthesis of the [2Fe-2S] and [4Fe-4S] iron-sulfur clusters.

Activation of circulating monocytes by hyperglycemia is bound to play a role in inflammatory and atherosclerosis. In this study, we examined whether flavonoids (catechin, EGCG, luteolin, quercetin, rutin) - phytochemicals that may possible belong to a new class of advanced glycation end products (AGEs) inhibitors - can attenuate high glucose (15 mmol/L, HG)-induced inflammation in human monocytes. Our results show that all flavonoids significantly inhibited HG-induced expression of proinflammatory genes and proteins, including TNF-alpha, interleukin-1beta (IL-1beta), and cyclooxygenase (COX)-2, at a concentration of 20 microM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and N(epsilon)-(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor-kappaB activation and may be supported by downregulation of the following: i) PKC-dependent NADPH oxidase pathway; ii) phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase, and iii) mRNA expression of receptor of AGEs. In addition, we found for the first time that lower levels of Bcl-2 protein under HG conditions could be countered by the action of flavonoids. Our data suggest that, along with their antioxidant activities, flavonoids possess anti-inflammatory properties and might therefore have additional protective effects against glycotoxin-related inflammation.

The anionic syn-/ anti-[Fe(mu-SEt)(NO) 2] 2 (-) ( 2a) were synthesized and characterized by IR, UV-vis, EPR, and X-ray diffraction. The geometry of the [Fe(mu-S) 2Fe] core is rearranged in going from [{Fe(NO) 2} (9)-{Fe(NO) 2} (9)] Roussin's red ester [Fe(mu-SEt)(NO) 2] 2 ( 1a) (Fe...Fe distance of 2.7080(5) A) to the [{Fe(NO) 2} (9)-{Fe(NO) 2} (10)] complex 2a (Fe...Fe distance of 2.8413(6) A) to minimize the degree of Fe...Fe interaction to stabilize complex 2a. On the basis of X-ray absorption (Fe K- and L-edge), EPR and SQUID, complex 2a is best described as the anionic [{Fe(NO) 2} (9)-{Fe(NO) 2} (10)] Roussin's red ester with the fully delocalized mixed-valence core. The complete bridged-thiolate cleavage yielded DNIC [(EtS) 2Fe(NO) 2] (-) ( 3a) in the reaction of 2 equiv of [EtS] (-) and complex 1a, whereas reaction of 2 equiv of [(t)BuS] (-) with [Fe(micro-S (t)Bu)(NO) 2] 2 (1b) gave DNIC [((t)BuS) 2Fe(NO) 2] (-) (3b) and the anionic Roussin's red ester [Fe(mu-S (t)Bu)(NO) 2] 2 (-) (2b) through bridged-thiolate cleavage in combination with reduction. In contrast to the inertness of DNIC 3b toward complex 1b, nucleophile DNIC 3a induces the reduction of complex 1a to produce the anionic Roussin's red ester 2a. Interestingly, dissolution of complex 3a in MeOH at 298 K finally led to the formation of a mixture of complexes 2a and 3a, in contrast to the dynamic equilibrium of complexes 3b and 1b observed in dissolution of complex 3b in MeOH. These results illustrate the aspect of how the steric structures of nucleophiles ([EtS] (-) vs [ (t)BuS] (-) and [(EtS) 2Fe(NO)2](-) vs [((t)BuS) 2Fe(NO)2] (-)) function to determine the reaction products.

The anionic {Fe(NO)2}(9) DNIC[(NO)2Fe(C3H3N2)2](-) (2) (C3H3N2 = deprotonated imidazole) containing the deprotonated imidazole-coordinated ligands and DNICs [(NO)2Fe(C3H3N2)(SR)](-) (R = (t)Bu(3), Et(4), Ph(5)) containing the mixed deprotonated imidazole-thiolate coordinated ligands, respectively, were synthesized by thiol protonation or thiolate(s) ligand-exchange reaction. The anionic {Fe(NO)2}(9) DNICs 2- 5 were characterized by IR, UV-vis, EPR, and single-crystal X-ray diffraction. The facile transformation among the anionic {Fe(NO)2}(9) DNICs 2- 5 and [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-) was demonstrated in this systematic study. Of importance, the distinct electron-donating ability of thiolates serve to regulate the stability of the anionic {Fe(NO)2}(9) DNICs and the ligand-substitution reactions of DNICs. At 298 K, DNIC 2 exhibits the nine-line EPR signal with g = 2.027 (aN(NO) = 2.20 and aN(Im-H) = 3.15 G; Im-H = deprotonated imidazole) and DNIC 3 displays the nine-line signals with g = 2.027 (aN(NO) = 2.35 and aN(Im-H) = 4.10 G). Interestingly, the EPR spectrum of complex 4 exhibits a well-resolved 11-line pattern with g = 2.027 (aN(NO) = 2.50, aN(Im-H) = 4.10 G, and aH = 1.55 G) at 298 K. The EPR spectra (the pattern of hyperfine splitting) in combination with IR nu NO spectra (DeltanuNO = the separation of NO stretching frequencies, DeltanuNO = approximately 62 cm (-1) for 2 vs approximately 50 cm(-1) for 3- 5 vs approximately 43 cm(-1) for [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-)) may serve as an efficient tool for the discrimination of the existence of the anionic {Fe(NO)2}(9) DNICs containing the different ligations [N,N]/[N,S]/[S,S].

Dinitrosyl iron complex [(-SC(7)H(4)SN)(2)Fe(NO)(2)](-) (1) was prepared by reaction of [S(5)Fe(NO)(2)](-) and bis(2-benzothiozolyl) disulfide. In synthesis of the analogous dinitrosyl iron compounds (DNICs), the stronger electron-donating thiolates [RS](-) (R = C(6)H(4)-o-NHCOCH(3), C(4)H(3)S, C(6)H(4)NH(2), Ph), compared to [-SC(7)H(4)SN](-) of complex 1, trigger thiolate-ligand substitution to yield [(-SC(6)H(4)-o-NHCOCH(3))(2)Fe(NO)(2)](-) (2), [(-SC(4)H(3)S)(2)Fe(NO)(2)](-) (3), and [(SPh)(2)Fe(NO)(2)](-) (4), respectively. At 298 K, complexes 2 and 3 exhibit a well-resolved five-line EPR signal at g = 2.038 and 2.027, respectively, the characteristic g value of DNICs. The magnetic susceptibility fit indicates that the resonance hybrid of {Fe(+)((*)NO)(2)}(9) and {Fe(-)((+)NO)(2)}(9) in 2 is dynamic by temperature. The IR nu(NO) stretching frequencies (ranging from (1766, 1716) to (1737, 1693) cm(-)(1) (THF)) of complexes 1-4 signal the entire window of possible electronic configurations for such stable and isolable {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-). The NO-releasing ability of {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) is finely tuned by the coordinated thiolate ligands. The less electron-donating thiolate ligands coordinated to {Fe(NO)(2)}(9) motif act as better NO-donor DNICs in the presence of NO-trapping agent [Fe(S,S-C(6)H(4))(2)](2)(2-). Interconversion between {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) and {Fe(NO)(2)}(10) [(Ph(3)P)(2)Fe(NO)(2)] was verified in the reaction of (a) [(RS)(2)Fe(NO)(2)](-), 10 equiv of PPh(3) and sodium-biphenyl, and (b) 2 equiv of thiol, [RS](-), and [(Ph(3)P)(2)Fe(NO)(2)], respectively. The biomimetic reaction cycle, transformation between {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) and {Fe(NO)(2)}(9) [(R'S)(2)Fe(NO)(2)](-), reversible interconversion of {Fe(NO)(2)}(9) and {Fe(NO)(2)}(10) DNICs, and degradation/reassembly of [2Fe-2S] clusters may decipher and predict the biological cycle of interconversion of {Fe(NO)(2)}(9) DNICs, {Fe(NO)(2)}(10) DNICs, and the [Fe-S] clusters in proteins.