Isoegomaketone exhibits potential as a new Mycobacterium abscessus inhibitor.

Although the incidence of Mycobacterium abscessus infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In particular, M. abscessus is often resistant to available macrolide antibiotics, so therapeutic options are extremely limited. Hence, there is a pressing demand to create effective drugs or therapeutic regimens for M. abscessus infections. The aim of the investigation was to assess the capability of isoegomaketone (iEMK) as a therapeutic option for treating M. abscessus infections. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of iEMK for both reference and clinically isolated M. abscessus strains. In addition to time-kill and biofilm formation assays, we evaluated iEMK's capability to inhibit M. abscessus growth in macrophages using an intracellular colony counting assay. iEMK inhibited the growth of reference and clinically isolated M. abscessus strains in macrophages and demonstrated effectiveness at lower concentrations against macrophage-infected M. abscessus than when used to treat the bacteria directly. Importantly, iEMK also exhibited anti-biofilm properties and the potential to mitigate macrolide-inducible resistance, underscoring its promise as a standalone or adjunctive therapeutic agent. Overall, our results suggest that further development of iEMK as a clinical drug candidate is promising for inhibiting M. abscessus growth, especially considering its dual action against both planktonic bacteria and biofilms.

Enzymatic hydrolyzation of Cordyceps militaris mushroom extracts and its effect on spent hen chicken.

Objective: This study was aimed to investigate the effect of fresh and dried hydrolyzed Cordyceps militaris (CM) mushroom with proteolytic enzymes; bromelain (CMB), flavorzyme (CMF), and mixture of bromelain: flavorzyme (CMBF) on quality properties of spent hen chicken. Methods: Mushroom extract (CME) were combined with three proteolytic enzyme mixtures that had different peptidase activities; stem bromelain (CMB), flavorzyme (CMF), and mixture of stem bromelain:flavorzyme (CMBF) at (1 : 1). The effect of these hydrolysates was investigated on spent hen breast meat via dipping marination. Results: Hydrolyzation positively alters functional properties of CM protease. in which bromelain hydrolyzed group (CMB) displayed the highest proteolytic activity at 4.57 unit/mL. The antioxidant activity had significant increment from 5.32% in CME to 61.79% in CMB. A significantly higher emulsion stability index (ESI) and emulsification activity index (EAI) compared to CME were another result from hydrolyzation (p<0.05). Texture properties along with the shear force value and myofibrillar fragmentation index (MFI) were notably improved under CMB and CMBF in fresh condition. Marination with CM mushroom protease that previously hydrolyzed with enzymes were proven to also increase the nucleotide compounds, indicated by higher AMP and IMP in hydrolysate groups (p<0.05). The concentration of both total and insoluble collagen remained unchanged, meaning less effect from CM protease. Conclusion: This study suggested the hydrolyzation of CM protease with bromelain or a mixture of bromelain:flavourzyme to significantly improve functional properties of protease and escalate the taste-related nucleotide compounds and texture profiles from spent hen breast meat.

Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of Mycobacterium peregrinum Infections.

Mycobacterium peregrinum (Mpgm) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. Mpgm is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on Mpgm, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) using macrophages and mouse bone marrow-derived cells. Mpgm has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in Mpgm-infected macrophages were measured using an extracellular flux analyzer. Mpgm-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to Mpgm-ATCC- and Mpgm-R-infected macrophages. Additionally, our findings revealed metabolic changes in Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon Mpgm-S infection. In summary, within the strains examined, Mpgm-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than Mpgm-ATCC and Mpgm-R. This study is the first to document distinct immune responses and metabolic reorganization following Mpgm infection. These findings lay a crucial foundation for further investigations into the pathogenesis of Mpgm.

Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition.

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Machine learning liquid chromatography retention time prediction model augments the dansylation strategy for metabolite analysis of urine samples.

Herein, a standalone software equipped with a graphic user interface (GUI) is developed to predict liquid chromatography mass spectrometry (LC-MS) retention times (RTs) of dansylated metabolites. Dansylation metabolomics strategy developed by Li et al. narrows down a vast chemical space of metabolites into the metabolites containing amines and phenolic hydroxyls. Combined with differential isotope labeling, e.g., 12C-reagent labeled individual samples spiked with a 13C-reagent labeled reference or pooled sample, LC-MS analysis of the dansylated samples enables accurate relative quantification of all labeled metabolites. Herein, the LC-RTs for dansylated metabolites are predicted using an artificial neural network (ANN) machine-learning model. For the ANN modeling, 315 dansylated urine metabolites obtained from the DnsID database are used. The ANN LC-RT prediction model was reliable, with a mean absolute deviation of 0.74 min for the 30 min LC run. In the RT model, a deviation of more than 2 min was observed in only 3.2% of the total 315 metabolites, while a deviation of 1.5 min or more was observed in 11% of the metabolites. Furthermore, it was found that the LC-RT prediction was also reliable even for metabolites containing both amine and phenolic functional groups that can undergo dansylation on either one of the two functional groups, resulting in the generation of two isomeric forms. This RT-prediction model is embedded into a user-friendly GUI and can be used for identifying nontargeted dansylated metabolites with unknown RTs, along with accurate mass measurements. Furthermore, it is demonstrated that the developed software can help identify metabolites from a urine sample of an anonymous healthy pregnant woman.

Genital tract infection and pelvic surgery contribute to the development of endometriosis.

Endometriosis is a multifactorial disease, and inflammation is considered a core pathology. Inflammation related to genital tract infection (GTI) and surgical injury may cause endometriosis. Therefore, we investigated the incidence of endometriosis in women with a recent history of GTI, pelvic surgery, or both. Using the Korean National Health Insurance Service-National Sample Cohort, 20- to 49-year-old women diagnosed with GTI or who underwent pelvic surgeries between 2002 and 2008 were collected and followed up for five years. After excluding women who had already been diagnosed with endometriosis or diseases that may affect endometriosis, a total of 30,336 women were diagnosed with GTI (Study 1), 2894 women who underwent pelvic surgery (Study 2), and 788 women who underwent GTI and pelvic surgery, both (Study 3) were enrolled for each study. The comparison groups in which sociodemographic factors matched for each group were collected. The incidence of endometriosis per 1000 person-year was 5.37, 5.17, and 20.81 in each case group and was significantly higher than each comparison group. A recent history of GTI increased an adjusted hazard ratio (aHR) of 2.29 (1.99-2.63, 95% confidence interval) for the development of endometriosis. The aHRs of pelvic surgery history and the history of both GTI and pelvic surgery were 2.10 and 7.82, respectively. In conclusion, the pelvic inflammation resulting from genital infection and pelvic surgical injury may play a role in developing endometriosis. Active treatment of genital infections and careful surgical procedures to minimize tissue injury may reduce the incidence of pelvic endometriosis.

Obesity enhances antiviral immunity in the genital mucosa through a microbiota-mediated effect on γδ T cells.

Obesity is detrimental to the immune system. It impairs lymphatics, T cell development, and lymphopoiesis; induces dysfunction of antitumor immunity; and also promotes tumor progression. However, direct evidence of the impact of obesity on viral infection is lacking. We report a protective role of obesity against herpes simplex virus 2 infection of the genital mucosa in mice. Although conventional antiviral immunity is comparable between obese mice and lean mice, obesity enhances the cytotoxic subset of γδ T cells. This effect is mediated by L-arginine produced by commensal microbiota in the genital mucosa, which induces "pseudonormoxia" of γδ T cells, resulting in increased natural killer (NK) group 2 D (NKG2D) expression of γδ T cells through the downregulation of hypoxia-inducible factor 1-alpha (HIF1A) by inducing nitric oxide (NO) production, thereby protecting mice from lethal genital herpes. Thus, our work illuminates one mechanism by which obesity-induced compositional changes in the vaginal microbiota can affect mucosal immune responses against viral infection.

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway.

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.

Physicochemical Characteristics and Flavor-Related Compounds of Fresh and Frozen-Thawed Thigh Meats from Chickens.

The physicochemical characteristics and flavor-related compounds of thigh meat derived from diverse Korean native chickens (KNC), namely Hanhyup No. 3 (HH3), Woorimatdag No 1 (WRMD 1), and Woorimatdag No 2 (WRMD 2), under fresh and frozen-thawed conditions were studied and compared with those of commercial broilers (CB). Regardless of the breed, KNC showed a higher (p < 0.05) percentage of linoleic and arachidonic acid. The highest proportion of docosahexaenoic acid was observed in WRMD 2. Despite having a higher collagen content, thigh meat derived from KNC maintained a similar texture profile in comparison to that of CB. The concentrations of most free amino acids (FAA), except for taurine, tryptophan, and carnosine, were higher in frozen-thawed meat than in fresh meat. Regarding volatile organic compounds (VOC), following freezing, the concentration of favorable VOCs increased in CB, but decreased in WRMD 1, suggesting a loss of pleasant flavor in frozen-thawed meat. This study indicated that changes in VOCs, including hydrocarbons (d-limonene, heptadecane, hexadecane, naphthalene, pentadecane, 3-methyl-, tridecane), esters (arsenous acid, tris(trimethylsilyl) ester, decanoic acid, ethyl ester, hexadecanoic acid, ethyl ester), alcohol (1-hexanol, 2-ethyl-), ketones (5,9-undecadien-2-one, 6,10-dimethyl-), and aldehydes (pentadecanal-, tetradecanal, tridecanal), may be a promising marker for distinguishing between fresh and frozen-thawed chicken thigh meat. These findings are of critical importance as preliminary data for developing high-quality chicken meat products.

The Effect of Hydrolysis Pre-Treatment by Flavourzyme on Meat Quality, Antioxidative Profiles, and Taste-Related Compounds in Samgyetang Breast Supplemented with Black Garlic.

This study aimed to carefully investigate the effect of hydrolysis using Flavourzyme on meat quality, antioxidative status, and taste-related compounds in breast of Samgyetang that was supplemented with black garlic (BG). Four different treatment groups were compared: (1) conventional Samgyetang (control), (2) Samgyetang hydrolyzed with Flavourzyme (1%, v/w) (FS), (3) Samgyetang made with the BG extract without hydrolysis (NBG), and (4) BG samgyetang pre-treated with Flavourzyme (1%, v/w) in a water bath at 55°C for 2.5 h and hydrolyzed before being processed (HBG). All the treatment groups were cooked by retorting at conditions 121°C and 1.5 kg/cm2 for 1 h. Improved umami profiles through the increase of umami-related nucleotides (5'-GMP, 5'-IMP) and free amino acids-aspartic acid and glumtamic acid, in Samgyetang breast was recorded following hydrolysis. The HBG group tended to impart stronger scavenging activity toward free radicals compared with the other two groups, while not differing with NBG group regarding suppressing malondialdehyde. Textural properties were improved through hydrolysis, wherein the shear force value decreased from 2.29 kgf in the control to 1.19 and 1.25 kgf in the FS and HBG group. Moisture percentages were highly retained, with the redness score increasing and the lightness color decreasing following hydrolysis. In conclusion, the results of this study can be a preliminary information of the effect of hydrolysis pre-treatment for BG samgyetang. Further experiments are required to compare various enzymes along with its organoleptic acceptances.

SIRT1 suppresses in vitro decidualization of human endometrial stromal cells through the downregulation of forkhead box O1 expression.

SIRT1 regulates survival, DNA repair, and metabolism in human cells and has pleiotropic effects on age-related diseases through either deacetylating target proteins or inhibiting gene transcription. Forkhead box O1 (FOXO1) is one of the most important transcription factors during decidualization. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) are well-known FOXO1-dependent genes in decidualizing cells. To determine whether SIRT1 plays a role in decidualization, we investigated morphological changes in cells following artificially stimulated decidualization and expression levels of PRL, IGFBP1, and FOXO1 in the immortalized non-neoplastic human endometrial stromal cell line T HESCs. SIRT1 expression decreased in the decidualization condition and SIRT1 inhibited morphological changes caused by decidualization of T HESCs. SIRT1 suppressed PRL, IGFBP1, and FOXO1 expression; inhibited FOXO1, PRL, and IGFBP1 promoter activity; and decreased histone protein acetylation of the FOXO1 promoter. We found that FOXO1 expression increased in the secretory phase compared with the proliferative phase, whereas SIRT1 expression decreased in the secretory phase in the human endometrium. We also revealed that SIRT1 may inhibit embryo implantation according to the blastocyst-like spheroid implantation assay. Collectively, these results indicate that SIRT1 suppresses decidualization of human endometrial stromal cells by inhibiting FOXO1 expression.

Effect of detoxified Rhus verniciflua extract on oxidative stability and quality improvement of raw chicken breast during cold storage.

This study investigated the utilization of detoxified Rhus verniciflua (RV) extract as a natural antioxidant to extend the shelf life of chicken breast meat during storage. Pre-heating at (35°C, 100°C, 120°C, and 140°C) was conducted on heartwood of RV prior to extraction to improve its antioxidant activity and remove the allergenic compound urushiol. The antioxidant activity was the highest when RV pre-heated at 120°C with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging activity observed at 62.29 EC50 µg/mL and 12.11 IC50 mg/mL, respectively. Pre-heating also significantly increased the total phenolic content (TPC), with the highest improvement was seen at 120°C, 100°C, and 140°C respectively, wherein 35°C shared no difference with the raw RV (RRV). Urushiol content was vanished following pre-heating at 120°C and 140°C. With respect to these result, pre-heating treatment at 120°C was applied before the extraction of the heartwood of RV. Prepared breast meat sample was dipped into distilled water as a negative control, 0.02% butylated hydroxytoluene (BHT) as positive control, and a solution containing detoxified RV extract (0.10%, 0.25%, 0.50%, 1.00%) at 4°C for 60 min. Treatment group with 0.50% and 1.00% addition increased the redness and yellowness value on day 6 and day 3 of storage respectively (p < 0.05). The pH value of breast meat was also increased in treatment of 0.50% and 1.00% on day 0, but subsequently lower until end of storge day compared to control negative (p < 0.05). Furthermore, 0.50% treatment exhibited a higher antioxidant activity, stronger inhibition of the microbial growth evaluated by total viable count and maintaining a lower total volatile basic nitrogen among treatments (p < 0.05), unless for BHT and 1.00% treatment groups (p > 0.05). It indicates a similar efficacy of detoxified RV extract with that of positive control treated with BHT. The results of this study suggested that dipping chicken breast meat into a solution containing 0.50% of previously pre-heated RV heartwood at 120°C could be a promising natural antioxidant for extending the shelf life, and at the same time improve its quality during storage.

Salicornia herbacea Aqueous Extracts Regulate NLRP3 Inflammasome Activation in Macrophages and Trophoblasts.

Salicornia herbacea L. (Chenopodiaceae), an edible salt marsh plant with anti-inflammatory effects, was examined in macrophages and trophoblasts whether it modulates NLRP3 inflammasome activity. Pretreatment and delayed treatment of S. herbacea extract (SHE) in bone marrow-derived macrophages (BMDMs) reduced the activity of NLRP3 inflammasome induced by lipopolysaccharide (LPS) and adenosine triphosphate stimulation and downregulated interleukin (IL)-1ß production. SHE also inhibited pyroptotic cell death, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), oligomerization, and speck by NLRP3 inflammasome activity in BMDM. Similarly, SHE decreased the mRNA expression of NLRP3, ASC, IL-1ß, and IL-6 in the LPS-stimulated human trophoblast cell line, Swan 71 cells. In addition, SHE inhibited the production of IL-6 and IL-1ß and decreased the expression of cyclooxygenase-2 and prostaglandin E2 in stimulated Swan 71 cells. Finally, 3,5-dicaffeoylquinic acid (3,5-DCQA), one of the components of S. herbacea, inhibited IL-1ß produced by NLRP3 inflammasome activity. In conclusion, SHE downregulated the activity of the NLRP3 inflammasome in macrophages and trophoblasts.

Fatty acid profiles and flavour-related compounds of retorted Korean ginseng chicken soup (Samgyetang) affected by pre-treated black garlic extract.

OBJECTIVE: This study aimed to characterize the effect of pre-treated black garlic (BG) extracts addition into retorted Korean ginseng chicken soup (Samgyetang) on the fatty acid composition and flavour-related indexes. METHODS: Four different treatments; Samgyetang made with a 5% (w/w) addition of garlic (G), fresh BG (FBG), oven-dried BG (DBG), or encapsulated BG (EBG) extracts were developed and compared to negative control (NC) without any extract addition. Prepared samples were cooked via retorting at 121.1°C, 1.5 kgf/cm2 for 1 h. RESULTS: The BG treated samples were higher in C18:3n3 and C18:2n6 fatty acids, with thrombogenic index was 18% to 20% lower than the NC. EBG yielded the highest umamirelated nucleotides (5'-guanosine monophosphate and 5'-inosine monophosphate) and modified some free amino acid (alyne, phenylalanine and leucine) thus possessed the highest equivalent umami concentration among samples. Some individual aldehydes (pentanal, hexanal, and heptanal) were lower, while furans and volatile sulfur compounds were higher than the NC and G treatment group, indicating a potential suppression of unpleasant flavour alongwith the intensificiation of favourable flavour from the addition of BG extracts into retorted Samgyetang. CONCLUSION: Taken together, the synergistic results of this study indicate that incorportating suitable pre-treatment of BG extract could be of critical importance for the development of the retorted Samgyetang with improved flavour and functionalities.

Aconitate Decarboxylase 1 Deficiency Exacerbates Mouse Colitis Induced by Dextran Sodium Sulfate.

Ulcerative colitis is a complex inflammatory bowel disorder disease that can induce rectal and colonic dysfunction. Although the prevalence of IBD in Western countries is almost 0.5% of the general population, genetic causes are still not fully understood. In a recent discovery, itaconate was found to function as an immune-modulating metabolite in mammalian immune cells, wherein it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. However, the association between the Acod1 (Aconitate decarboxylase 1)-itaconate axis and ulcerative colitis has rarely been studied. To elucidate this, we established a DSS-induced colitis model with Acod1-deficient mice and then measured the mouse body weights, colon lengths, histological changes, and cytokines/chemokines in the colon. We first confirmed the upregulation of Acod1 RNA and protein expression levels in DSS-induced colitis. Then, we found that colitis symptoms, including weight loss, the disease activity index, and colon shortening, were worsened by the depletion of Acod1. In addition, the extent of intestinal epithelial barrier breakdown, the extent of immune cell infiltration, and the expression of proinflammatory cytokines and chemokines in Acod1-deficient mice were higher than those in wild-type mice. Finally, we confirmed that 4-octyl itaconate (4-OI) alleviated DSS-induced colitis in Acod1-deficient mice and decreased the expression of inflammatory cytokines and chemokines. To our knowledge, this study is the first to elucidate the role of the Acod1-itaconate axis in colitis. Our data clearly showed that Acod1 deletion resulted in severe DSS-induced colitis and substantial increases in inflammatory cytokine and chemokine levels. Our results suggest that Acod1 may normally play an important regulatory role in the pathogenesis of colitis, demonstrating the potential for novel therapies using 4-OI.

Distinguishing Aroma Profile of Highly-Marbled Beef according to Quality Grade using Electronic Nose Sensors Data and Chemometrics Approach.

Fat deposition in animal muscles differs according to the genetics and muscle anatomical locations. Moreover, different fat to lean muscle ratios (quality grade, QG) might contribute to aroma development in highly marbled beef. Scientific evidence is required to determine whether the abundance of aroma volatiles is positively correlated with the amount of fat in highly marbled beef. Therefore, this study aims to investigate the effect of QG on beef aroma profile using electronic nose data and a chemometric approach. An electronic nose with metal oxide semiconductors was used, and discrimination was performed using multivariate analysis, including principal component analysis and hierarchical clustering. The M. longissimus lumborum (striploin) of QG 1++, 1+, 1, and 2 of Hanwoo steers (n=6), finished under identical feeding systems on similar farms, were used. In contrast to the proportion of monounsaturated fatty acids (MUFAs), the abundance of volatile compounds and the proportion of polyunsaturated fatty acids (PUFAs) decreased as the QG increased. The aroma profile of striploin from carcasses of different QGs was well-discriminated. QG1++ was close to QG1+, while QG1 and QG2 were within a cluster. In conclusion, aroma development in beef is strongly influenced by fat deposition, particularly the fat-to-lean muscle ratio with regard to the proportion of PUFA. As MUFA slows down the oxidation and release of volatile compounds, leaner beef containing a higher proportion of PUFA produces more volatile compounds than beef with a higher amount of intramuscular fat.

Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of Mycobacterium mucogenicum.

Mycobacterium mucogenicum (Mmuc), a rapidly growing nontuberculous mycobacterium (NTM), can infect humans (posttraumatic wound infections and catheter-related sepsis). Similar to other NTM species, Mmuc exhibits colony morphologies of rough (Mmuc-R) and smooth (Mmuc-S) types. Although there are several case reports on Mmuc infection, no experimental evidence supports that the R-type is more virulent. In addition, the immune response and metabolic reprogramming of Mmuc have not been studied on the basis of morphological characteristics. Thus, a standard ATCC Mmuc strain and two clinical strains were analyzed, and macrophages were generated from mouse bone marrow. Cytokines and cell death were measured by ELISA and FACS, respectively. Mitochondrial respiration and glycolytic changes were measured by XF seahorse. Higher numbers of intracellular bacteria were found in Mmuc-R-infected macrophages than in Mmuc-S-infected macrophages. Additionally, Mmuc-R induced higher levels of the cytokines TNF-α, IL-6, IL-12p40, and IL-10 and induced more BMDM necrotic death. Furthermore, our metabolic data showed marked glycolytic and respiratory differences between the control and each type of Mmuc infection, and changes in these parameters significantly promoted glucose metabolism, extracellular acidification, and oxygen consumption in BMDMs. In conclusion, at least in the strains we tested, Mmuc-R is more virulent, induces a stronger immune response, and shifts bioenergetic metabolism more extensively than the S-type. This study is the first to report differential immune responses and metabolic reprogramming after Mmuc infection and might provide a fundamental basis for additional studies on Mmuc pathogenesis.

Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. RESULTS: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. CONCLUSIONS: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

The Quality and Functional Improvement of Retorted Korean Ginseng Chicken Soup (Samgyetang) by Enzymolysis Pre-Treatment with Cordyceps militaris Mushroom Extract.

This study aimed to investigate the functional and quality improvement of retorted Korean ginseng chicken soup that was hydrolyzed using a single extract from Cordyceps militaris (CM) mushroom, or in combination with bromelain, flavorzyme, or a mix of both. A total of 36 fat-trimmed breast meat from commercial broilers were hydrolyzed with one of six treatments, (1) flavorzyme as a positive control (PC), (2) no addition as negative control (NC), (3) crude CM extract (CME), CM extract prepared with either (4) bromelain (CMB), (5) flavorzyme (CMF), or (6) bromelain:flavorzyme mixture (CMBF) in a water bath at 55 °C for 2.5 h, and subsequently retorted at 121.1 °C, 147.1 kPa for 1 h. The highest antioxidant activity was observed in the CMB treatment (40.32%), followed by CMBF (34.20%), and CME (32.97%). The suppression of malondialdehyde ranged between 28 and 83%. The water-holding-capacity of the treated samples increased, ranging between 59.69 and 62.98%, and significantly tenderized the meat. The shear force decreased from 23.05 N in negative control to 11.67 N in the CMB samples. The predominant nucleotides across the samples were 5'-IMP and hypoxanthine, and the lowest was adenosine. The intensification of the taste properties was due to the increase of umami substances, both by 5'-nucleotides (5'-IMP, 5'-GMP) and free amino acids (FAAs), whereas the highest improvement was observed in the CMB group. Therefore, the hydrolyzation of Korean ginseng chicken soup using CM extract, prepared using bromelain, improves functional and quality profiles.

Combined effects of processing method and black garlic extract on quality characteristics, antioxidative, and fatty acid profile of chicken breast.

The combined effects of pretreated black garlic (BG) extract and various cooking methods were investigated. The chicken breast was prepared at a uniform size of 5 × 5 × 1.5 cm and randomly allocated into 12 treatment groups that were placed in solutions containing fresh BG extract (1:4, w/v) (positive control), distilled water (negative control), oven-dried BG, and encapsulated BG extract. They were subjected to cooking via sous-vide (SV), boiling, and retorting, for 1 h. Both the BG extract and the different cooking methods modified the physicochemical, antioxidative, and fatty acid profiles of the chicken breast. The antioxidative value was 1.83 to 11.59 times higher than the negative control, with extensive protection from lipid oxidation observed in the oven-dried BG extract, compared the fresh BG treatment. The maltodextrin-encapsulated extract prolonged the protection of the antioxidant BG compounds under high-temperature cooking, and thus, produced the highest antioxidative values. The increase in SFA percentage is a consequence of high-temperature cooking, mainly from the increased proportion of palmitic and stearic acids. A higher percentage of monounsaturated fatty acids and polyunsaturated fatty acids was observed under the SV cooking treatments that had BG extract prepared at any pretreatments. The BG lightly protected the linoleic acid during the retorting process. The BG extract treatment improved meat quality by lowering cooking loss (CL), improving water holding capacity (WHC), and provided better visual attributes. This study suggests that an appropriate cooking method, together with the addition of oven-dried BG extract in an either raw or encapsulated form, can improve the functional quality of chicken breast.