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Salted and fermented seafood (jeotgal) is known for its long shelf life and unique flavor. Despite the existence of various types of salted seafood, the factors influencing this quality have yet to be identified. These factors are essential for improving the quality of salted seafood, optimizing the fermentation process, and advancing the industrialization of fermented foods. Therefore, in this study, we explored microbial dynamics and changes in quality characteristics in three salted seafood items - salted anchovies (MJ), salted cutlass offal (GJ), and salted croakers (HJ), over a 24-month fermentation period. Distinct microbial community profiles, dominated by Tetragenococcus halophilus, Halanaerobium fermentans, and Chromohalobacter canadensis in MJ, GJ, and HJ, respectively, affect the metabolic pathways and the corresponding flavor profiles. The pH of all samples ranged from 5.7-6.0. The titratable acidity was highest in MJ at 1.4% and lowest in HJ at approximately 0.7%. Salinity was below 25% in all samples but slightly lower in MJ. Significant differences were observed in the amino acid, nucleotide, and overall metabolite profiles. MJ exhibited the highest amino acid and nitrogen-related factor levels, such as glutamic acid and hypoxanthine, enhancing flavor complexity. Correlation analysis revealed significant associations among the types, metabolites, and microbial communities. Microbial survival mechanisms in high-salt environments result in the production of unique metabolites, including umami and aroma components as well as precursors of biogenic amines, which can affect the overall quality of the final product. These differences were primarily influenced by the fish type rather than the fermentation time. Our findings provide foundational insights for enhancing fermentation strategies, improving product consistency, and advancing the industrial application of microbial management in seafood fermentation. This study not only fills a significant gap in the current understanding of fermented seafood but also outlines practical approaches for industry applications for the optimization of product quality.
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BACKGROUND: Hospitalized patients undergoing surgery or procedures may experience negative symptoms. Music is a nonpharmacological complementary approach and is used as an intervention to reduce anxiety, stress, and pain in these patients. Recently, music has been used conveniently in clinical situations with technology devices, and the mode of providing music is an important factor in technology-based music interventions. However, many reviews have focused only on the effectiveness of music interventions. OBJECTIVE: We aimed to review randomized controlled trials (RCTs) of technology-based music interventions for reducing anxiety and pain among patients undergoing surgery or procedures. We examined the clinical situation, devices used, delivery methods, and effectiveness of technology-based music interventions in primary articles. METHODS: The search was performed in the following 5 electronic databases: PubMed, MEDLINE (OvidSP), CINAHL complete, PSYCINFO, and Embase. This systematic review focused on technology-based music interventions. The following articles were included: (1) RCTs, (2) studies using interactive technology (eg, smartphones, mHealth, tablets, applications, and virtual reality), (3) empirical studies reporting pain and anxiety outcomes, and (4) English articles published from 2018 to 2023 (as of January 18, 2023). The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. RESULTS: Among 292 studies identified, 21 met the inclusion criteria and were included. Of these studies, 9 reported that anxiety scores decreased after music interventions and 7 reported that pain could be decreased before, during, and after procedures. The methodology of the music intervention was important to the results on anxiety and pain in the clinical trials. More than 50% (13/21, 62%) of the studies included in this review allowed participants to select themes themselves. However, it was difficult to distinguish differences in effects depending on the device or software used for the music interventions. CONCLUSIONS: Technology-based music interventions could help reduce anxiety and pain among patients undergoing surgery or procedures. The findings of this review could help medical teams to choose a practical methodology for music interventions. Future studies should examine the effects of advanced technology-based music interventions using smart devices and software that promote interactions between medical staff and patients.
Subject(s)
Anxiety , Music Therapy , Pain Management , Humans , Anxiety/psychology , Anxiety/prevention & control , Anxiety/therapy , Music Therapy/methods , Music Therapy/standards , Music Therapy/instrumentation , Pain Management/methods , Pain Management/standards , Pain Management/instrumentation , Pain Management/psychology , Pain/psychology , Pain/prevention & control , Surgical Procedures, Operative/psychology , Surgical Procedures, Operative/adverse effects , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). METHODS: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. RESULTS: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. CONCLUSIONS: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.
Subject(s)
Fasting , Lysosomes , Non-alcoholic Fatty Liver Disease , Animals , Mice , Humans , Lysosomes/metabolism , Fasting/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Mice, Inbred C57BL , Ribosomal Proteins/metabolism , Ribosomal Proteins/genetics , Male , Hepatocytes/metabolism , Protein Biosynthesis , Autophagy , Liver/metabolism , Mice, KnockoutABSTRACT
Rebaudioside A (Reb A) and neohesperidin dihydrochalcone (NHDC) are known as intense sweeteners. This study aimed to examine the anti-obesity effects of Reb A and NHDC. C57BL/6 J-ob/ob mice were supplemented with Reb A (50 mg/kg body weight [b.w.]), NHDC (100 mg/kg b.w.), or their combination (COMB) for 4 weeks. COMB-supplemented mice showed significant reduction in b.w. gain, food efficiency ratio, and fat mass. Additionally, mice in the COMB group showed suppressed levels of genes related to adipogenesis, lipogenesis, and lipolysis in the perirenal fat and the levels of hepatic triglyceride, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. The lipogenesis and pro-inflammatory gene expressions were also downregulated in the liver, whereas ß-oxidation related genes were upregulated in the COMB group. In addition, mice that received COMB showed distinct gut microbiota structure, enriched in Blautia and Parabacteroides, and depleted in Faecalibaculum and Mucispirillum, in relation to the control group. These results suggest that supplementation with Reb A and NHDC may be an effective treatment for obesity-related metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01391-1.
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Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. Using spatial transcriptomics in patient derived xenograft models, we capture clonal lineage evolution during treatment, finding the persister state to show increased oxidative phosphorylation, decreased proliferation, and increased invasive capacity, with central-to-peripheral gradients. Phylogenetic tracing identifies intrinsic- and acquired-resistance mechanisms (e.g. dual specific phosphatases, Reticulon-4, CDK2) and suggests specific temporal windows of potential therapeutic efficacy. Using deep learning to analyze histopathological slides, we find morphological features of specific cell states, demonstrating that juxtaposition of transcriptomics and histology data enables identification of phenotypically-distinct populations using imaging data alone. In summary, we define state change and lineage selection during melanoma treatment with spatiotemporal resolution, elucidating how choice and timing of therapeutic agents will impact the ability to eradicate resistant clones. Statement of Significance: Tumor evolution is accelerated by application of anti-cancer therapy, resulting in clonal expansions leading to dormancy and subsequently resistance, but the dynamics of this process are incompletely understood. Tracking clonal progression during treatment, we identify conserved, global transcriptional changes and local clone-clone and spatial patterns underlying the emergence of resistance.
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BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.
Subject(s)
Melanoma , Monocytes , Humans , Animals , Mice , Monocytes/metabolism , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Macrophages/metabolism , CD8-Positive T-Lymphocytes , Carcinogenesis/metabolism , Tumor Microenvironment , Signaling Lymphocytic Activation Molecule Family/metabolismABSTRACT
Protein translation is an energy-intensive ribosome-driven process that is reduced during nutrient scarcity to conserve cellular resources. During prolonged starvation, cells selectively translate specific proteins to enhance their survival (adaptive translation); however, this process is poorly understood. Accordingly, we analyzed protein translation and mRNA transcription by multiple methods in vitro and in vivo to investigate adaptive hepatic translation during starvation. While acute starvation suppressed protein translation in general, proteomic analysis showed that prolonged starvation selectively induced translation of lysosome and autolysosome proteins. Significantly, the expression of the orphan nuclear receptor, estrogen-related receptor alpha (Esrra) increased during prolonged starvation and served as a master regulator of this adaptive translation by transcriptionally stimulating 60S acidic ribosomal protein P1 (Rplp1) gene expression. Overexpression or siRNA knockdown of Esrra expression in vitro or in vivo led to parallel changes in Rplp1 gene expression, lysosome/autophagy protein translation, and autophagy. Remarkably, we have found that Esrra had dual functions by not only regulating transcription but also controling adaptive translation via the Esrra/Rplp1/lysosome/autophagy pathway during prolonged starvation.
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The purpose of this study is to confirm the effect of small, portable low-level laser therapy (light sources in square configuration: 830 nm GaAs diode 3.2 mW at the center, 4 × 650 nm InGaAIP diodes over the corners) treatment in reducing and enhancing hand function in patients with wrist pain. This study was a prospective, randomized, sham-controlled, and home-based self-therapy trial. A total of thirty subjects with wrist pain were enrolled. All participants received low-level laser therapy on painful area at the wrist. The experimental group (n = 15) received laser stimulation, while the control group (n = 15) received sham stimulation using identical equipment that generated only a red light without the laser output. Both groups self-treated for 30 min a day, 5 days per week for 3 weeks, total of 15 sessions. The primary outcome was assessed using a visual analogue scale (VAS) for wrist pain from 0 (painless) to 10 (extreme pain). The secondary outcomes were measured with patient-rated wrist evaluation (PRWE), grip strength, lateral, palmar, and tip pinch strength. Measures were taken before and after treatment. A total of thirty participants provided outcome data. After the intervention, both groups showed a significant decrease in VAS score, from 4.93 to 3.67 in experimental group, from 5.53 to 4.00 in control group (the experiment group: p = 0.020, the control group: p = 0.003). The experimental group showed a significant improvement in function scale score (p = 0.012), the control group did not. Lateral and pinch strength was significantly improved in the experimental group (p = 0.017) and in the control group (p = 0.034) respectively. There were no side effects in the patients. Medical laser irradiation is a portable and easy-to-use laser irradiator without side effects. Clinical Trial Registration number: KCT0006604.
Subject(s)
Low-Level Light Therapy , Wrist , Humans , Prospective Studies , Pain , Low-Level Light Therapy/adverse effects , Activities of Daily Living , Treatment OutcomeABSTRACT
PURPOSE: This study explored the work adjustment trajectory and its predictors and characteristics among newly registered nurses. METHODS: A total of 245 newly registered nurses working in a university hospital provided general baseline characteristics and completed a work adjustment questionnaire along with self-report measures of clinical competency, psychological capital, preceptor exchange, social support, and role conflict when they started working independently (baseline) and at 7 and 12 months after employment. Data were collected from July 2020 to August 2022. The collected data were subjected to a group-based trajectory model, χ2 test, F test, one-way ANOVA, and multiple logistic regression using SAS 9.4, and SPSS 25.0. RESULTS: Group-based trajectory modeling classified three newly registered nurse groups: nurses with a high work adjustment level in all subscales from the beginning of employment (early adjustment group, 16.1%), nurses with a moderate level of adjustment from beginning to end (standard adjustment group, 60.6%), and nurses with a low level of work adjustment from early to mid-term, rising later (delayed adjustment group, 23.3%). Higher hope, optimism, and emotional support predicted early and standard adjustments. CONCLUSIONS: Based on the trajectory characteristics, newly registered nurses need to improve their work adjustment. The early and standard adjustment groups should continuously monitor their levels of work adjustment while monitoring their hopes, optimism, and emotional support. In particular, the delayed adjustment group required customized educational programs and strengthened peer support.
Subject(s)
Employment , Nurses , Humans , Surveys and Questionnaires , Self Report , Role ConflictABSTRACT
OBJECTIVE: We investigated gender differences in psychosocial determinants that affect hand hygiene (HH) performance among physicians. DESIGN: The survey included a structured questionnaire with 7 parts: self-assessment of HH execution rate; knowledge, attitude, and behavior regarding HH; internal and emotional motivation for better HH; barriers to HH; need for external reminders; preference for alcohol gel; and embarrassment due to supervision. SETTING: The study was conducted across 4 academic referral hospitals in Korea. PARTICIPANTS: Physicians who worked at these hospitals were surveyed. METHODS: The survey questionnaire was sent to 994 physicians of the hospitals in July 2018 via email or paper. Differences in psychosocial determinants of HH among physicians were analyzed by gender using an independent t test or the Fisher exact test. RESULTS: Of the 994 physicians, 201 (20.2%) responded to the survey. Among them, 129 (63.5%) were men. Male physicians identified 4 barriers as significant: time wasted on HH (P = .034); HH is not a habit (P = .004); often forgetting about HH situations (P = .002); and no disadvantage when I do not perform HH (P = .005). Female physicians identified pain and dryness of the hands as a significant obstacle (P = .010), and they had a higher tendency to feel uncomfortable when a fellow employee performed inadequate HH (P = .098). Among the respondents, 26.6% identified diversifying the types of hand sanitizers as their first choice for overcoming barriers to improving HH, followed by providing reminders (15.6%) and soap and paper towels in each hospital room (13.0%). CONCLUSION: A significant difference in the barriers to HH existed between male and female physicians. Promoting HH activities could help increase HH compliance.
Subject(s)
Cross Infection , Hand Hygiene , Physicians , Humans , Male , Female , Sex Factors , Hospitals , Surveys and Questionnaires , Guideline Adherence , Infection Control , Hand DisinfectionABSTRACT
In this observational study conducted in 2022, 12.3% of patients who shared a room with a patient positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) also had a positive polymerase chain reaction (PCR) test, either at initial screening or during a 5-day quarantine. Therefore, screening and quarantine are still necessary within hospitals for close-contact inpatients during the SARS-CoV-2 omicron-variant dominant period.
Subject(s)
COVID-19 , Virus Diseases , Humans , SARS-CoV-2/genetics , Inpatients , COVID-19/diagnosis , Polymerase Chain Reaction , COVID-19 TestingABSTRACT
BACKGROUND: Ischemia reperfusion (IR) injury may result in rhabdomyolysis and compartment syndrome when blood supply returns after thrombectomy for patients with acute limb ischemia. OBJECTIVE: We highlight the value of early diagnosis and treatment in post-thrombectomy patients with IR injuries in their lower legs. CASE DESCRIPTION: Two patients received thrombectomy due to left superficial femoral artery occlusion. Both patients complained of left calf pain during ambulation at the 1- and 3-day follow up post-thrombectomy, as well as a heating sensation, swelling, weakness, and sensory changes in the affected leg. For early diagnosis musculoskeletal ultrasounds were performed and in both cases revealed swelling and change of echogenicity in the left calf. To further diagnosis, magnetic resonance imaging of the left leg revealed limb IR-induced muscular injury and rhabdomyolysis, respectively. In both cases, an electrodiagnostic study revealed peripheral nerve injury in the left leg. Medications were provided for neuropathic pain control and early rehabilitation was performed to improve function. In both cases, patients reported during their follow-up that their pain and muscle weakness had improved. CONCLUSION: When post-thrombectomy calf pain occurs early evaluation and treatment should be performed to identify any potential IR injury.
Subject(s)
Femoral Artery , Rhabdomyolysis , Humans , Femoral Artery/surgery , Femoral Artery/pathology , Lower Extremity , Thrombectomy/methods , Rhabdomyolysis/pathology , Pain , Treatment OutcomeABSTRACT
Fermentation of salted shrimp involves the interaction of multiple factors. However, studies of the effects of shrimp variety and fermentation temperature on metabolites generated during fermentation are limited. Therefore, we investigated the effects of the shrimp variety, fermentation temperature, and fermentation period on the composition of fermented salted shrimp. Four different varieties of salted shrimp, namely, Detteugijeot (SSA), Red shrimp jeot (SSB), Chujeot (SSC), and Yukjeot (SSD), were prepared and stored at 5 and 10 °C for 5 months. The pH values ranged from 6.71 to 6.99, with SSD showing the lowest pH at both temperatures. Although total nitrogen content remained relatively constant, amino nitrogen exhibited an upward trend after 2 months and was particularly increased at 10 °C. This increase was attributed to variations in microorganisms and enzymes in the salted shrimp. Except for proline, citrulline, and ornithine, amino acid levels increased during fermentation with the highest amounts detected in SSA. Additionally, the levels of glutamic acid and branched-chain amino acids were found to be sensitive to fermentation temperature. Amino acid levels were apparently affected by species-specific metabolic pathways of the microorganisms present in each salted shrimp. Compared to the other varieties, SSB had significantly higher contents of adenosine triphosphate and hypoxanthine. A high hypoxanthine content could contribute to increased bitterness and an umami taste profile. Furthermore, the correlation between salted shrimp and metabolites was unique in SSB, whereas partial clustering was observed between the SSA and SSC.
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PURPOSE: This study aimed to derive a conceptual definition and attributes for nursing students' rights in clinical practice in South Korea. METHODS: This concept-analysis study was conducted at a nursing school in South Korea. The participants were recruited using purposive sampling. The inclusion criteria were being a fourth-year nursing student and having two or more semesters of practical experience. The hybrid model used in this study had three stages. First, 12 studies were reviewed during the theoretical stage. Second, 10 in-depth interviews were conducted during the fieldwork stage. Third, in the analytical stage, the concept of nursing students' rights related to clinical practice was defined and the attributes were derived. RESULTS: The analysis established five attributes of nursing students' rights: the right to learn, the right to be protected from infections and accidents, the right to be cared for and supported, the right to be respected, and the right to be recognized as a member of a nursing team. A key theme that emerged from this study was having the right to learn in a safe and supportive environment. CONCLUSION: It is necessary to develop a measurement tool based on the above five attributes and to verify its effectiveness.
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Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. We investigate how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory, or cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk+, memory CD4+, γδ) and M2-like macrophages expand with age. Spatial transcriptomics reveal co-localization of aged immune and epithelial cells in situ. Lastly, transcriptional signatures of aging mammary cells are found in human breast tumors, suggesting mechanistic links between aging and cancer. Together, these data uncover that epithelial, immune, and stromal cells shift in proportions and cell identity, potentially impacting cell plasticity, aged microenvironment, and neoplasia risk.
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Food-borne bacteria have frequently been detected in kimchi, a representative and traditional fermented ethnic food of Korea. This study investigated the effect of atmospheric dielectric barrier discharge (DBD) plasma treatment (1.1 kV, 43 kHz, N2: 1.5 m/s, 5-60 min) on reduction of Yersinia enterocolitica and Staphylococcus aureus and on quality parameters in Geotjeroi, a non-fermented kimchi. A decrease of 0.12/0.09, 0.19/0.19, 0.34/0.45, 0.64/0.72, and 1.13/1.12 log10 CFU/g was observed by 5, 10, 20, 30, and 60 min of DBD plasma, respectively. D-value of 52.83 and 51.95 min was determined for Y. enterocolitica (R2 = 0.99) and S. aureus (R2 = 0.98) using the first order kinetics model. The quality parameters (pH, Brix, and hardness) were not significantly different (P > 0.05) between treated and untreated Geotjeori. Moreover, a decrease of >1 log10 CFU/g, for both bacteria was observed without any change in the quality of Geotjeori. These findings imply that DBD plasma treatment enhances Geotjeori safety and protects product from microbial risk.
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To the best of our knowledge, the upper age limit at which post-neonatal cerebral palsy (CP) can manifest remains uncertain. This uncertainty is attributed to the lack of objective parameters for assessing the developing brain. In a previous study, we reported that an ipsilateral corticospinal projection associated with brain injury, as manifested in the paretic hand of a CP patient, had never been observed in individuals aged > 2 years. In this case report, we present an instance of ipsilateral motor evoked potential (iMEP) in a girl whose traumatic brain injury occurred at the age of 4 years. This case is the oldest in which brain injury occurred and iMEP was maintained. In conclusion, iMEP can be a valuable indicator of motor system plasticity in the developing brain.
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Hypercholesterolemia and vascular inflammation are key interconnected contributors to the pathogenesis of atherosclerosis. How hypercholesterolemia initiates vascular inflammation is poorly understood. Here we show in male mice that hypercholesterolemia-driven endothelial activation, monocyte recruitment and atherosclerotic lesion formation are promoted by a crosstalk between macrophages and endothelial cells mediated by the cholesterol metabolite 27-hydroxycholesterol (27HC). The pro-atherogenic actions of macrophage-derived 27HC require endothelial estrogen receptor alpha (ERα) and disassociation of the cytoplasmic scaffolding protein septin 11 from ERα, leading to extranuclear ERα- and septin 11-dependent activation of NF-κB. Furthermore, pharmacologic inhibition of cyp27a1, which generates 27HC, affords atheroprotection by reducing endothelial activation and monocyte recruitment. These findings demonstrate cell-to-cell communication by 27HC, and identify a major causal linkage between the hypercholesterolemia and vascular inflammation that partner to promote atherosclerosis. Interventions interrupting this linkage may provide the means to blunt vascular inflammation without impairing host defense to combat the risk of atherosclerotic cardiovascular disease that remains despite lipid-lowering therapies.
Subject(s)
Atherosclerosis , Hypercholesterolemia , Male , Mice , Animals , Estrogen Receptor alpha/metabolism , Hypercholesterolemia/complications , Hypercholesterolemia/metabolism , Endothelial Cells/metabolism , Septins/metabolism , Cholesterol/metabolism , Atherosclerosis/metabolism , Macrophages/metabolism , Signal Transduction , Inflammation/pathologyABSTRACT
We developed a predictive growth model of Yersinia enterocolitica for fresh Kimchi cabbages as a function of storage temperature (5-20 °C). The Baranyi equation used for primary modeling at these storage temperatures was suitable as a model for obtaining lag time (LT) and specific growth rate (SGR) (R2 = 0.97-0.98). As the temperature increased, the growth of Y. enterocolitica tended to increase, with SGR values of 0.33, 0.40, 0.60 and 0.68 log colony-forming units/h at 8, 11, and 15 °C, and LT values of 5.63, 3.54, 2.23 and 1.09 h, respectively. The secondary model was determined by the non-linear regression analysis. The suitability of the modeling results for the SGR and LT value was verified by determining the mean square error (<0.01), bias factor (0.919-0.999), and accuracy factor (1.032-1.136). The predicted models can be used to predict the growth of Y. enterocolitica in Kimchi cabbage at various temperatures and as an effective tool for maintaining the safe level of Y. enterocolitica in the production, processing, and distribution of fresh agricultural products.
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This study aimed to identify which streptococcal species are closely associated with infective endocarditis (IE) and to evaluate risk factors for mortality in patients with streptococcal IE. We performed a retrospective cohort study of all patients with streptococcal bloodstream infection (BSI) from January 2010 to June 2020 in a tertiary hospital in South Korea. We compared clinical and microbiological characteristics of streptococcal BSIs according to the diagnosis of IE. We performed multivariate analysis to evaluate the risk of IE according to streptococcal species and risk factors for mortality in streptococcal IE. A total of 2,737 patients were identified during the study period, and 174 (6.4%) were diagnosed with IE. The highest IE prevalence was in patients with Streptococcus mutans BSI (33% [9/27]) followed by S. sanguinis (31% [20/64]), S. gordonii (23% [5/22]), S. gallolyticus (16% [12/77]), and S. oralis (12% [14/115]). In multivariate analysis, previous IE, high-grade BSI, native valve disease, prosthetic valve, congenital heart disease, and community-onset BSI were independent risk factors for IE. After adjusting for these factors, S. sanguinis (adjusted OR [aOR], 7.75), S. mutans (aOR, 5.50), and S. gallolyticus (aOR, 2.57) were significantly associated with higher risk of IE, whereas S. pneumoniae (aOR, 0.23) and S. constellatus (aOR, 0.37) were associated with lower risk of IE. Age, hospital-acquired BSI, ischemic heart disease, and chronic kidney disease were independent risk factors for mortality in streptococcal IE. Our study points to significant differences in the prevalence of IE in streptococcal BSI according to species. IMPORTANCE Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that Streptococcus sanguinis, S. mutans, and S. gallolyticus were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with S. mutans and S. gordonii bloodstream infection had a tendency of low performance in echocardiography. There are significant differences in the prevalence of infective endocarditis in streptococcal bloodstream infection according to species. Therefore, performing echocardiography in streptococcal bloodstream infection with a high prevalence of, and significant association with, infective endocarditis is desirable.