Adiponectin Prevents Skin Inflammation in Rosacea by Suppressing S6 Phosphorylation in Keratinocytes.

Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared with nonlesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.

The impact of raw material form and starter culture inoculation on bacterial communities and metabolites in fermented anchovy sauce.

This study explored the dynamics of anchovy sauce fermentation and investigated how the raw material form and the use of starter cultures affect bacterial and metabolite profiles. Using a comprehensive approach, we examined the fermentation process using anchovies in two forms (whole and ground) and three different starter cultures. The use of ground anchovies resulted in an accelerated fermentation process for anchovy sauce; however, the increased diversity of bacterial phylotypes and altered accumulation of biogenic amines were observed. Inoculation of starter cultures resulted in a shift from spontaneous to controlled fermentation, highlighting their ability to regulate bacterial communities. Despite a slightly reduced fermentation rate, inoculation with Tetragenococcus halophilus was shown to be a potent method for reducing biogenic amines and affecting metabolite profiles. As the industry strives to balance fermentation speed and quality, our research could provide insights for improving the efficiency, safety, and quality of anchovy sauce production.

Momordica cochinchinensis extract alleviates oxidative stress and skin damage caused by fine particulate matter.

Momordica cochinchinensis (MC), commonly known as gac fruit, is a tropical fruit rich in antioxidants and bioactive compounds. This research aimed to elucidate the effect of MC on apoptosis induced by fine particulate matter with a diameter of less than 10 µm (< PM10) in epidermal keratinocyte HaCaT cells. We found that PM10 significantly diminish the viability of HaCaT cells through cytotoxic mechanisms. However, the treatment with MC at a concentration of 10 µg/mL notably restored the cellular viability decreased by PM10. MC reduced the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) by mainly preventing the generation of reactive oxygen species (ROS) in HaCaT cells subjected to PM10. Furthermore, MC exhibited a regulatory effect on the expression of genes associated with apoptosis, including B-Cell Lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and cleaved caspase-3 by inhibiting the activation of the transcription factor nuclear factor-kappa B (NF-κB). These findings demonstrate that MC aids in neutralizing the apoptotic signaling pathway of free radicals produced by environmental pollutants such as PM10, which have the potential to damage skin cells and accelerate the aging process.

Effectiveness of ceiling-mounted ultraviolet-C lamps: An experimental study in a biocontainment unit of a tertiary care hospital.

BACKGROUND: We aimed to evaluate the performance of ceiling-mounted UV-C lamps. METHODS: This study was conducted in an empty room with UV-C lamps in the biocontainment unit of a tertiary care hospital in South Korea. Each pathogen (Staphylococcus aureus, Escherichia coli, Candida krusei, Bacillus cereus, and Mycobacterium peregrinum) was inoculated on blood agar plates and placed in 20 selected places from the UV-C lamp, and irradiation was applied for 15 min. As a control group, the bacterial solution was diluted 10,000 times and UV was not applied. RESULTS: A mean ± SD of 5.95 ± 0.91 log reduction was observed with UV irradiation compared with the control. The log reduction was greatest for S. aureus [median, 7.05 (IQR, 6.49-7.26)] and least for M. peregrinum [median, 4.88 (IQR, 4.58-5.24)]. The degree of log reduction was inversely proportional to the square of the distance from the UV-C lamp (R2 = -0.12, P < .001). CONCLUSIONS: In this study, ceiling-mounted UV-C demonstrated effective disinfection of at least 4-log reduction of the test organisms within a 4-m distance. Mounted UV-C lighting is a considerable option for improving surface disinfection.

Effects of seasonal harvest of kimchi cabbage on microbial and metabolic profiles of kimchi.

Kimchi cabbage, the key ingredient in kimchi, is cultivated year-round to meet high production demands. This study aimed to examine the effects of seasonal harvesting (spring, summer, fall, and winter) on the microbial and metabolic profiles of kimchi during 30 days of fermentation. Lactic acid bacteria distribution is notably influenced by seasonal variations, with Latilactobacillus dominant in fall-harvested kimchi group and Weissella prevailing in spring, summer, and winter. The microbial communities of spring and fall group exhibited similar profiles before fermentation, whereas the microbial communities and metabolic profiles of spring and summer group were similar after 30 days of fermentation. Seasonal disparities in metabolite concentrations, including glutamic acid, serine, and cytosine, persist throughout fermentation. This study provides a comprehensive understanding of the substantial impact of seasonal harvesting of kimchi cabbage on the microbial and metabolic characteristics of kimchi, providing valuable insights into producing kimchi with diverse qualities.

Gene Expression and DNA Methylation Profiling Suggest Potential Biomarkers for Azacitidine Resistance in Myelodysplastic Syndrome.

Myelodysplastic syndrome/neoplasm (MDS) comprises a group of heterogeneous hematopoietic disorders that present with genetic mutations and/or cytogenetic changes and, in the advanced stage, exhibit wide-ranging gene hypermethylation. Patients with higher-risk MDS are typically treated with repeated cycles of hypomethylating agents, such as azacitidine. However, some patients fail to respond to this therapy, and fewer than 50% show hematologic improvement. In this context, we focused on the potential use of epigenetic data in clinical management to aid in diagnostic and therapeutic decision-making. First, we used the F-36P MDS cell line to establish an azacitidine-resistant F-36P cell line. We performed expression profiling of azacitidine-resistant and parental F-36P cells and used biological and bioinformatics approaches to analyze candidate azacitidine-resistance-related genes and pathways. Eighty candidate genes were identified and found to encode proteins previously linked to cancer, chronic myeloid leukemia, and transcriptional misregulation in cancer. Interestingly, 24 of the candidate genes had promoter methylation patterns that were inversely correlated with azacitidine resistance, suggesting that DNA methylation status may contribute to azacitidine resistance. In particular, the DNA methylation status and/or mRNA expression levels of the four genes (AMER1, HSPA2, NCX1, and TNFRSF10C) may contribute to the clinical effects of azacitidine in MDS. Our study provides information on azacitidine resistance diagnostic genes in MDS patients, which can be of great help in monitoring the effectiveness of treatment in progressing azacitidine treatment for newly diagnosed MDS patients.

UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice.

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.

Impact of essential and optional ingredients on microbial and metabolic profiles of kimchi.

This study aimed to examine the impacts of essential and optional ingredients on the microbial and metabolic profiles of kimchi during 100 days of fermentation, using a mix-omics approach. Kimchi manufactured without essential ingredients (e.g., red pepper, garlic, ginger, green onion, and radish) had lower lactic acid content. The absence of garlic was associated with a higher proportion of Latilactobacillus and Lactococcus, while the absence of red pepper was associated with a greater proportion of Leuconostoc than the control group. In addition, red pepper and garlic served as primary determinants of the levels of organic acids and biogenic amines. Sugar was positively correlated with the levels of melibiose, and anchovy sauce was positively correlated with the levels of amino acids such as methionine, leucine, and glycine. These findings contribute to a fundamental understanding of how ingredients influence kimchi fermentation, offering valuable insights for optimizing kimchi production to meet various preferences.

Enhancing Safety in Tumescent Liposuction: Managing Sedation-Related Respiratory Issues and Serious Complications Under Deep Sedation with the Propofol-Ketamine Protocol.

BACKGROUND: Over the past 4 years, aesthetic surgery, notably liposuction, has substantially increased. Tumescent liposuction, a popular technique, has two variants-true tumescent liposuction (TTL) and semi-tumescent liposuction. While TTL reduces risks, it has limitations. There is no literature reported on semi-tumescent liposuction under deep sedation using the propofol-ketamine protocol, which is proposed as a potentially safe alternative. METHODS: The retrospective analysis covered 8 years and included 3094 patients performed for tumescent liposuction under deep sedation, utilizing the propofol-ketamine protocol. The evaluation of patient safety involved an examination of potential adverse events with a specific focus on respiratory issues related to sedation, including instances of mask ventilation. RESULTS: Among the 3094 cases, no fatalities were recorded. Noteworthy events included 43 mask ventilation instances, primarily occurring in the initial 10 min. Twelve cases experienced surgery cancellation due to various factors, including respiratory issues. Three patients were transferred to upper-level hospitals, while another three required blood transfusions. Vigilant management prevented significant complications, and other adverse events like venous thromboembolism (VTE), fat embolism, severe lidocaine toxicity, and so on were not observed. CONCLUSIONS: The analysis of 3094 tumescent liposuction cases highlighted the overall safety profile of the propofol-ketamine protocol under deep sedation. The scarcity of severe complications underscores its viability. The study emphasizes the significance of thorough preoperative assessments, careful patient selection, and awareness of potential complications. Prompt interventions, particularly in addressing sedation-related respiratory issues, further contribute to positive outcomes for patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Insight into disparate nonradical mechanisms of peroxymonosulfate and peroxydisulfate activation by N-doped oxygen-rich biochar: Unraveling the role of active sites.

In this study, we first comprehensively studied peroxymonosulfate (PMS) and peroxydisulfate (PDS) activation mechanisms using N, O codoped sludge biochar (NOSB) to degrade organics from water. Among the catalysts, NOSB with a higher content of graphitic N, optimal edge nitrogen (pyridinic N and pyrrolic N), CO groups, sp2-hybridized C, and rich defects were demonstrated to be a superior catalyst. Therefore, by activating PDS and PMS, NOSB exhibited the highest rate of BPA degradation, which was 22-fold and 13-fold that of pristine sludge biochar, respectively. However, owing to different oxidation potentials and molecular structures, PMS and PDS show different degradation performances due to various catalytic mechanisms occurring, even with the same biochar. Due to the asymmetrical structure of PMS, electrons passed from PMS to NOSB and further generated singlet oxygen (1O2), which governs the degradation of bisphenol A with an auxiliary contribution of single electron transfer. Meanwhile, PDS is reduced at the Lewis basic sites of NOSB, forming inner-surface-bound {PDS-NOSB}, which was oxidizing around neighboring carbon and decomposed targets through transferring single and double electrons. NOSB is promising for practical applications because of its adaptation to a wide pH range, anions, high total organic carbon removal, tunable active sites, and re-usability for degrading organics via PMS/PDS activation. This study unveils knowledge about N, O codoped sludge biochar catalysts for activating PMS/PDS and advocates a great approach for organics' degradation in the environment.

Selective influence of garlic as a key ingredient in kimchi on lactic acid bacteria in a fermentation model system.

Garlic is an essential ingredient added to kimchi, a fermented vegetable, in small amounts owing to its sensory and antibacterial properties. This study aimed to elucidate the complex relationship between garlic and specific lactic acid bacteria (LAB) and the resulting metabolite changes in a controlled kimchi model system using nine strains as mixed and individual starters. The group without garlic using mixed starters showed the highest LAB growth activity, which influenced lactic acid production, pH, and titratable acidity. The group without garlic also showed differences in the composition of bacteria, such as Latilactobacillus sakei, Levilactobacillus brevis, unclassified Leuconostoc, and Weissella koreensis, during the fermentation period. In addition, the altering patterns of metabolites in the group without garlic during fermentation differed from those in the group with garlic. In addition, the metabolic profile of L. brevis group was mostly different from that of the other strains in the controlled model kimchi system using individual starters, suggesting that changes in LAB composition by garlic could subsequently affect metabolites during fermentation. This study provides valuable insights into the complex interactions among food ingredients, LAB succession, and metabolite production during fermentation.

Synergetic effect of nitrate on dissolved organic carbon attenuation through dissimilatory iron reduction during aquifer storage and recovery.

Aquifer storage and recovery (ASR) is a promising water management technique in terms of quantity and quality. During ASR, iron (Fe) (hydr)oxides contained in the aquifer play a crucial role as electron acceptors in attenuating dissolved organic carbon (DOC) in recharging water through dissimilatory iron reduction (DIR). Considering the preference of electron acceptors, nitrate (NO3⁻), possibly coexisting with DOC as the prior electron acceptor to Fe (hydr)oxides, might influence DIR by interrupting electron transfer. However, this phenomenon is yet to be clarified. In this study, we systematically investigated the potential effect of NO3⁻ on DOC attenuation during ASR using a series of sediment columns representing typical aquifer conditions. The results suggest that DOC attenuation could be enhanced by the presence of NO3⁻. Specifically, total DOC attenuation was notably higher than that from the stoichiometric calculation simply employing NO3⁻ as the additional electron acceptor to Fe (hydr)oxides, implying a synergetic effect of NO3⁻ in the overall reactions. X-ray photoelectron spectroscopy analyzes revealed that the Fe(II) ions released from DIR transformed the Fe (hydr)oxides into a less bioavailable form, inhibiting further DIR. In the presence of NO3⁻, however, no aqueous Fe(II) was detected, and another form of Fe (hydr)oxide appeared on the sediment surface. This may be attributed to nitrate-dependent Fe(II) oxidation (NDFO), in which Fe(II) is (re)oxidized into Fe (hydr)oxide, which is available for the subsequent DOC attenuation. These mechanisms were supported by the dominance of DIR-relevant bacteria and the growth of NDFO-related bacteria in the presence of NO3⁻.

Tools and tactics to define specificity of metabolic chemical reporters.

Metabolic chemical reporters (MCRs) provide easily accessible means to study glycans in their native environments. However, because monosaccharide precursors are shared by many glycosylation pathways, selective incorporation has been difficult to attain. Here, a strategy for defining the selectivity and enzymatic incorporation of an MCR is presented. Performing ß-elimination to interrogate O-linked sugars and using commercially available glycosidases and glycosyltransferase inhibitors, we probed the specificity of widely used azide (Ac4GalNAz) and alkyne (Ac4GalNAlk and Ac4GlcNAlk) sugar derivatives. Following the outlined strategy, we provide a semiquantitative assessment of the specific and non-specific incorporation of this bioorthogonal sugar (Ac4GalNAz) into numerous N- and O-linked glycosylation pathways. This approach should be generally applicable to other MCRs to define the extent of incorporation into the various glycan species.

Effects of ingredient size on microbial communities and metabolites of radish kimchi.

In this study, changes in physicochemical characteristics, microbial communities, and metabolites were investigated to identify the fermentation characteristics of radish kimchi according to the size of radish cubes used. The small-sized radish kimchi group showed the highest hardness value and glucose content in the early stages of fermentation. The relative abundance of major lactic acid bacteria, including Leuconostoc, Weissella, and Lactobacillus, was the highest in the small-sized radish kimchi group on day 5 of fermentation, which resulted in rapid production of lactic acid, thereby causing a decrease in pH and an increase in titratable acidity. The size of the radish in kimchi plays a pivotal role in determining various factors, most notably during the first 5 days of fermentation, leading to marked metabolic changes. A total of 17 metabolites, including glucose, sucrose, lactic acid, malic acid, citric acid, and GABA, exhibited significant differences in the small-size radish kimchi group. Interestingly, the sucrose content was higher in the large-sized radish group at the beginning of fermentation. This study revealed that ingredient size can selectively affect the growth of specific microorganisms in an environment where several microorganisms coexist, which could change the quality of radish kimchi.

Effects of sediment and temperature on the long-term aging process of rice wine: Microbial and metabolic insights.

Rice wine is low in alcohol content (6 %), rich in nutrients, and contains live microorganisms; therefore, it is generally produced without an aging process during manufacturing. In this study, we investigated the microbial and metabolic changes that occur during the long-term aging of undiluted rice wine with different amount of sediment and aging temperatures. Rice wine samples with higher amounts of sediment had higher yeast counts and alcohol content, indicating a crucial role of sediment in providing nutrients for yeast survival during aging. Furthermore, the rice wine samples that were aged at 12 °C exhibited a notable increase in the relative abundance of Lactobacillus after 100 days of aging. Metabolic profiling revealed that the production of metabolites during rice wine aging was greatly influenced by the amount of sediment and aging temperature, with most metabolites showing a strong correlation with these factors. This study provides valuable insights into the impact of sediment and temperature on the microbial and metabolic changes that occur during the long-term aging of rice wine.

Noggin contributes to brain metastatic colonization of lung cancer cells.

BACKGROUND: Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer. METHODS: We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice. RESULTS: Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal-epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial-mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells. CONCLUSIONS: Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.

Effects of saccharification agents on the microbial and metabolic profiles of Korean rice wine (makgeolli).

To brew rice wine, a saccharification agent is critical to provide sugars necessary for yeast to ferment alcohol. Nuruk, a traditional Korean saccharification agent, contains saccharification enzymes and various microorganisms, including fungi and lactic acid bacteria (LAB). To investigate the effect of saccharification agents on Korean rice wine (makgeolli), we analyzed makgeolli brewed with different saccharification agents, such as koji and nuruk. In contrast to koji makgeolli, nuruk makgeolli had a distinct microbial profile with higher proportion of LAB. Comparing the microbial profiles of the saccharification agents and makgeolli revealed that the dominant microorganisms in the makgeolli were possibly derived from the saccharification agents. Several metabolites also exhibited distinct profiles depending on the saccharification agent generating the total metabolic profile difference of makgeolli samples. Collectively, the saccharification agent could provide dominant microorganisms in the makgeolli microbiota, leading to a distinct microbial and metabolic profile of makgeolli depending on its type.

Nitrosylation of ß2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.