Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees.

Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of Lactobacillus kunkeei culture supernatant (CSK), isolated from Apis mellifera Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control H2O2-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove H2O2-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.

Enhanced Photosynthetic Pigment Production Using a Scaled-Up Continuously Circulated Bioreactor.

Microalgae have gained attention as a promising source of chlorophylls and carotenoids in various industries. However, scaling up of conventional bubble columns presents challenges related to cell sedimentation and the presence of non-photosynthetic cells due to non-circulating zones and decreased light accessibility, respectively. Therefore, this study aimed to evaluate the newly developed continuously circulated bioreactor ROSEMAX at both laboratory and pilot scales, compared to a conventional bubble column. There was no significant difference in the biomass production and photosynthetic pigment content of Tetraselmis sp. cultivated at the laboratory scale (p > 0.05). However, at the pilot scale, the biomass cultured in ROSEMAX showed significantly high biomass (1.69 ± 0.11 g/L, dry weight, DW), chlorophyll-a (14.60 ± 0.76 mg/g, DW), and total carotene (5.64 ± 0.81 mg/g, DW) concentrations compared to the conventional bubble column (1.17 ± 0.11 g/L, DW, 10.67 ± 0.72 mg/g, DW, 3.21 ± 0.56 mg/g, DW, respectively) (p ≤ 0.05). Flow cytometric analyses confirmed that the proportion of Tetraselmis sp. live cells in the culture medium of ROSEMAX was 32.90% higher than that in the conventional bubble column, with a photosynthetic efficiency 1.14 times higher. These results support suggestions to use ROSEMAX as a bioreactor for industrial-scale applications.

A novel drying film culture method applying a natural phenomenon: Increased carotenoid production by Haematococcus sp.

Low productivity and high cost remain major bottlenecks for the large-scale production of Haematococcus sp. This study explored biomass production and carotenoid accumulation in Haematococcus sp. (KCTC 12348BP) using drying film culture. The broth-cultured strain (3.2 × 106 cells/mL, 0.83 ± 0.02 mg/mL for a 21 d culture) was cultured under various conditions (different inoculum volumes and mist feeding intervals) in waterless agar plates at 28 ± 0.5 °C, under fluorescent light (12 h light-dark cycle) for 1 month. The maximum biomass obtained was 17.60 ± 0.72 g/m2, while the maximum astaxanthin concentration was 8.23 ± 1.13 mg/g in the culture using 1 mL inoculum and 3 d feeding interval. Drought stress in drying film culture effectively induced the accumulation of carotenoids from ß-carotene, facilitating the production of canthaxanthin via the astaxanthin biosynthesis pathway. This cost-effective culture system can increase the biomass and carotenoid pigment production in Haematococcus sp.

Antioxidant Effects of Turbo cornutus By-Products Visceral Extract against Hydrogen Peroxide-Induced Oxidative Stress by Regulating MAPK and Akt Signaling Pathways in Vero Cells.

Turbo cornutus, a marine gastropod mollusk commonly called sea snail, is found along the southern coast of Korea and holds considerable importance as a marine food resource, particularly on Jeju Island, Korea. Data are scarce on the antioxidant activity of hot water extracts from T. cornutus visceral tissue. Therefore, this study was performed to evaluate the antioxidant activities of T. cornutus visceral tissue hot water extract (TVE) and the underlying mechanisms against hydrogen peroxide-induced oxidative stress in Vero cells. The amino acid composition and antioxidant effects of TVE were evaluated. Furthermore, the impact of TVE on the expression of proteins within the mitogen-activated protein kinase (MAPK) pathway is investigated. TVE showed a concentration-dependent enhancement in its scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (IC50 = 1.07 ± 0.06 mg/mL) and hydrogen peroxide (IC50 = 0.33 ± 0.03 mg/mL). TVE reduced intracellular reactive oxygen species (ROS) production and maintained cell viability under H2O2-induced oxidative stress by suppressing apoptosis in Vero cells. Additionally, TVE demonstrated regulatory effects on the MAPK and protein kinase B (Akt) signaling pathways activated by H2O2. In conclusion, the findings from our study propose that TVE holds potential as a bioactive component in the formulation of functional foods.

Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

Dysregulation of Lipid Droplet Protein Expression in Adipose Tissues and Association with Metabolic Risk Factors in Adult Females with Obesity and Type 2 Diabetes.

BACKGROUND: Adipocyte dysregulation of lipid droplet (LD) metabolism caused by altered expression of LD proteins contributes to obesity-related metabolic diseases. OBJECTIVES: We aimed to investigate whether expression levels of PLIN1, CIDEA, and CIDEC were altered in adipose tissues of women with obesity and type 2 diabetes and whether their alterations were associated with metabolic risk factors. METHODS: Normal-weight (NW; 18.5 kg/m2 < BMI ≤ 25 kg/m2; n = 43), nondiabetic obese (OB; BMI > 30 kg/m2; n = 38), and diabetic obese (OB/DM; BMI > 30 kg/m2, fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%; n = 22) women were recruited. Metabolic parameters were measured, and expressions of PLIN1, CIDEA, CIDEC, and obesity-related genes were quantified in abdominal subcutaneous (SAT) and visceral adipose tissues (VAT). Effects of proinflammatory cytokines, endoplasmic reticulum (ER) stress inducers, and metabolic improvement agents on LD protein gene expressions were investigated in human adipocytes. RESULTS: PLIN1, CIDEA, and CIDEC expressions were lower in SAT and higher in VAT in OB subjects relative to NW subjects; however, they were suppressed in both fat depots in OB/DM subjects relative to OB (P < 0.05). Across the entire cohort, whereas VAT PLIN1 (r = 0.349) and CIDEC expressions (r = 0.282) were positively associated with BMI (P < 0.05), SAT PLIN1 (r = -0.390) and CIDEA expressions (r = -0.565) were inversely associated. After adjustment for BMI, some or all of the adipose LD protein gene expressions were negatively associated with fasting glucose (r = -0.259 or higher) and triglyceride levels (r = -0.284 or higher) and positively associated with UCP1 expression (r = 0.353 or higher) (P < 0.05). In adipocytes, LD protein gene expressions were 55-70% downregulated by increased proinflammatory cytokines and ER stress but 2-4-fold upregulated by the metabolic improvement agents exendin-4 and dapagliflozin (P < 0.05). CONCLUSIONS: The findings suggest that reduction of adipose LD protein expression is involved in the pathogenesis of metabolic disorders in women with obesity and type 2 diabetes and that increasing LD protein expression in adipocytes could control development of metabolic disorders.

Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

The Effects of Spirulina maxima Extract on Memory Improvement in Those with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Spirulina maxima is a marine microalga that has been promoted worldwide as a super food. This study was conducted to evaluate its ability to improve memory in the older adults using Spirulina maxima 70% ethanol extract (SM70EE). This randomized, double-blind, placebo-controlled clinical trial comprised 80 volunteers recruited from Jeonbuk National University Hospital in Jeonju, Republic of Korea, who were randomly assigned to two groups. The participants received either 1 g/day of SM70EE or a placebo without otherwise changing their diet or physical activity. The participants were examined at baseline and after a 12-week interval to determine whether there were changes in their results for visual learning, visual working memory, and verbal learning tests from the Korean version of the Montreal Cognitive Assessment, brain-derived neurotrophic factor and beta-amyloid levels, and total antioxidant capacity. Compared to the placebo group, the treatment group showed a significant improvement in visual learning and visual working memory test results and enhanced vocabulary. SM70EE use was shown to improve memory, with no adverse effects. Its efficacy in alleviating Alzheimer's disease symptoms was verified for the first time through this clinical trial. SM70EE could play a role in the management of patients with dementia. This trial is registered with registration number of clinical research information service (CRIS: KCT0006161).

Malignant transformation of nevus sebaceous to basal-cell carcinoma: Case series, literature review, and management algorithm.

Nevus sebaceous (NS) is a common congenital hamartoma of the skin composed predominantly of sebaceous glands. Although most NS are benign skin tumors, malignant transformations have been reported. There is still controversy about the lifetime risk of malignant degeneration and precise surgical criteria. This study reports cases of malignant degeneration and suggests a surgical treatment algorithm. The medical records of patients with basal-cell carcinoma (BCC) arising from NS between January 2001 and January 2021 were retrospectively reviewed. Patient demographics including lesion location, and tumor size were investigated. The symptoms, histological findings before and after excision, complications, and recurrence during 2-year follow-up periods were investigated. Ten patients were identified with BCC arising from NS lesions. All patients were female and the mean age was 52.11 years. All patients complained of sudden morphological changes, the most common type being rapid color changes. Two cases had histological findings that showed a miss-match between punch biopsy and excisional biopsy results. No recurrence was detected 2 years after surgeries in any patients. Cases after third stage, especially in over 40 years who report morphologic changes, should undergo total surgical excision as the first approach, with strong suspicion of malignant degeneration.

Adipose tissue LECT2 expression is associated with obesity and insulin resistance in Korean women.

OBJECTIVE: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-upregulated hepatokine inducing skeletal muscle insulin resistance. The study's aim was to explore whether LECT2 is expressed in human adipose tissue and whether the expression is dysregulated during obesity and associated with obesity-related metabolic disorders. METHODS: This study measured metabolic parameters, serum LECT2, and expression of LECT2 and CD209, a gene encoding a putative receptor for LECT2, in abdominal subcutaneous and visceral adipose tissues in women with obesity (with or without type 2 diabetes) and women with normal weight. The expression/secretion of LECT2 and its putative effects were assessed in human adipocytes. RESULTS: Adipose tissue LECT2 mRNA and serum LECT2 were higher in women with obesity and were significantly correlated with parameters related to insulin resistance. LECT2 was mainly expressed by adipocytes. Both LECT2 and CD209 expression was higher in adipocytes from women with obesity. Incubating adipocytes with substances mimicking the microenvironment of obesity adipose tissue increased LECT2 expression/secretion. LECT2 treatment of adipocytes suppressed insulin-stimulated Akt phosphorylation; it reduced adiponectin (ADIPOQ) and increased leptin (LEP) expression in a CD209-dependent manner. CONCLUSIONS: This study demonstrates that LECT2 expression in adipose tissue is high in patients with obesity and associated with insulin resistance and suggests that adipocyte-derived LECT2 may contribute to adipose tissue dysfunction.

Prevention of postoperative adhesions after flexor tendon repair with acellular dermal matrix in Zones III, IV, and V of the hand: A randomized controlled (CONSORT-compliant) trial.

BACKGROUND: Various techniques have been attempted for preventing postoperative flexor tendon adhesion, such as modification of suture technique, pharmacological agents, and mechanical barriers. However, there is no evidence of the efficacy of these methods in clinical settings. In this study, we present the long-term outcomes of a randomized prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesions after tendon injury in the hand. METHODS: From January 2017 to January 2020, all patients with an acute single flexor tendon injury in hand Zones III, IV, or V were candidates. A single-digit, total tendon rupture repaired within 48 hours, from the index finger to the little finger, was included in the study. Patients were randomly allocated to either a control or ADM group. Complications and the range of movements were recorded. Functional outcomes and a patient satisfaction questionnaire were evaluated after 12 months following the tendon repair surgery. The present study is adhered to the CONSORT guidelines. RESULTS: A total of 25 patients was enrolled in the study: 13 patients in the ADM group and 12 in the control group. According to Buck-Gramcko II criteria, the postoperative functional outcome score was 14.38 ±â€Š1.71 in the ADM group and 13.08 ±â€Š1.82 in the control group (P value = .0485). Patient satisfaction was recorded at 8.38 ±â€Š1.44 in the ADM group and 7.08 ±â€Š1.58 in the control group (P value = .0309), a significant difference. There were no differences in complications between the 2 groups. CONCLUSION: The beneficial effects of ADM after tendon repair were confirmed by improved postoperative functional outcome at flexor Zones III, IV, and V, preventing peritendinous adhesions and acting effectively as an anti-adhesive barrier.

TRIB3 Is Highly Expressed in the Adipose Tissue of Obese Patients and Is Associated With Insulin Resistance.

CONTEXT: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVE: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSION: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.

Type I Interferons Are Involved in the Intracellular Growth Control of Mycobacterium abscessus by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.

Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-ß treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/ß receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-ß treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-ß before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-ß did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-ß gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-ß treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.

e-Learning for enhancement of medical student performance at the Objective Structured Clinical Examination (OSCE).

This study aimed to investigate the impact of student e-learning on the development of clinical competencies. The study participants were 3rd year students (n = 43) at a private mid-sized medical school located in a South Korean suburb on a four-year medical program. Educational intervention was implemented to enhance student clinical performance. Students engaged in learning activities that intended to promote their self-directed learning abilities and clinical performances using e-learning resources. Intervention was conducted for the duration of six months during the 3rd year and its effectiveness was investigated by comparing student performances in OSCEs in a pre- and post- comparison format and also by comparing them with national scores. In addition, student perceptions of the impact of e-learning on their OSCE performances were assessed using a questionnaire, which included 36 items that elicited student perceptions of their experiences of e-learning and readiness for e-learning. Student OSCE scores improved significantly after educational intervention in all domains of clinical competencies assessed and for total scores (p < 0.001). Furthermore, students achieved higher OSCE scores than national average scores in the post-test, whereas they had performed lower than national average scores in the pre-test. Students showed neutral or slightly positive responses to the effectiveness of e-learning, and their perceptions of e-learning were not associated with their e-learning readiness scores. The study shows student OSCE performance improved significantly after educational intervention, which indicate the effectiveness of e-learning to support student learning of clinical performance. Despite significant improvements in student OSCE scores after e-learning, their perceptions of its effectiveness were neutral. Furthermore, student perceptions of e-learning were not associated with their readiness for it. Suggestions are made to help students use e-learning more effectively to enhance their clinical competencies.

Year-Round Cultivation of Tetraselmis sp. for Essential Lipid Production in a Semi-Open Raceway System.

There is increasing demand for essential fatty acids (EFAs) from non-fish sources such as microalgae, which are considered a renewable and sustainable biomass. The open raceway system (ORS) is an affordable system for microalgae biomass cultivation for industrial applications. However, seasonal variations in weather can affect biomass productivity and the quality of microalgal biomass. The aim of this study was to determine the feasibility of year-round Tetraselmis sp. cultivation in a semi-ORS in Korea for biomass and bioactive lipid production. To maximize biomass productivity of Tetraselmis sp., f medium was selected because it resulted in a significantly higher biomass productivity (1.64 ± 0.03 g/L) and lower omega-6/omega-3 ratio (0.52/1) under laboratory conditions than f/2 medium (0.70/1). Then, we used climatic data-based building information modeling technology to construct a pilot plant of six semi-ORSs for controlling culture conditions, each with a culture volume of 40,000 L. Over 1 year, there were no significant variations in monthly biomass productivity, fatty acid composition, or the omega-6/omega-3 ratio; however, the lipid content correlated significantly with photosynthetic photon flux density. During year-round cultivation from November 2014 to October 2017, areal productivity was gradually increased by increasing medium salinity and injecting CO2 gas into the culture medium. Productivity peaked at 44.01 g/m2/d in October 2017. Throughout the trials, there were no significant differences in average lipid content, which was 14.88 ± 1.26%, 14.73 ± 2.44%, 12.81 ± 2.82%, and 13.63 ± 3.42% in 2014, 2015, 2016, and 2017, respectively. Our results demonstrated that high biomass productivity and constant lipid content can be sustainably maintained under Korean climate conditions.

Marine cyanobacterium Spirulina maxima as an alternate to the animal cell culture medium supplement.

Serum is a stable medium supplement for in vitro cell culture. Live cells are used in stem cell research, drug toxicity and safety testing, disease diagnosis and prevention, and development of antibiotics, drugs, and vaccines. However, use of serum in culture involves concerns such as an ethical debate regarding the collection process, lack of standardized ingredients, and high cost. Herein, therefore, we evaluated the possibility of using edible cyanobacterium (Spirulina maxima), which is a nutrient-rich, sustainable, and ethically acceptable source, as a novel substitute for fetal bovine serum (FBS). H460 cells were cultured to the 10th generation by adding a mixture of spirulina animal cell culture solution (SACCS) and FBS to the culture medium. Cell morphology and viability, cell cycle, apoptosis, proteomes, and transcriptomes were assessed. We observed that SACCS had better growth-promoting capabilities than FBS. Cell proliferation was promoted even when FBS was replaced by 50-70% SACCS; there was no significant difference in cell shape or viability. There were only slight differences in the cell cycle, apoptosis, proteomes, and transcriptomes of the cells grown in presence of SACCS. Therefore, SACCS has the potential to be an effective, low-cost, and eco-friendly alternative to FBS in in vitro culture.

The recurrence of well-differentiated liposarcoma from benign giant intramuscular lipoma: A case (CARE-compliant) report.

RATIONALE: Recurrent liposarcoma, previously confirmed as lipoma, has rarely been reported. However, the risk factors for recurrence and the correlation between benign lipoma and malignant liposarcoma remain unclear. In this case study, we suggest a precise diagnostic strategy to minimize recurrence and malignant transformation. PATIENT CONCERNS: A 60-year-old male patient with a history of left chest wall swelling without any symptoms underwent excisional surgery, and the mass was confirmed as a benign lipoma in 2015. In 2019, the patient returned to the hospital with symptoms of a palpable mass on the left chest wall. DIAGNOSIS: The mass was considered a recurrent lipomatous tumor with the possibility of malignant transformation. Magnetic resonance imaging (MRI) revealed a deep-seated, septate, intramuscular, irregular margin, and large lipomatous tumor invading the ribs, pleura, and adjacent muscle, suggestive of malignancy. The MRI findings were similar to those 4 years ago, except for margin irregularity and invasion to adjacent tissue. INTERVENTIONS: Wide en bloc excisions encompassing the 5th to 7th ribs, pleura, and adjacent muscle were followed by reconstruction with a pedicled latissimus dorsi muscle flap. OUTCOMES: The recurrent large lipomatous tumor was confirmed as well-differentiated liposarcomas through histological and MDM2-FISH immunohistochemical staining. Postoperatively, follow-up visits continued for 1.5 years without recurrence. LESSONS: We suggest that deep-seated, septate, and giant lipomatous tumors should be considered as risk factors for recurrence with the possibility of malignancy and misdiagnosis. It is important to inform patients of all these possibilities and plan close and long-term follow-up.

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.

PROBLEM: Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence of APOs. In this study, we evaluated whether receptor-interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide-binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against F. nucleatum. METHOD OF STUDY: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and Ripk2-deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme-linked immunosorbent assay, Western blot analysis, real-time PCR, and nitrite assay. RESULTS: Fusobacterium nucleatum-induced production of IL-6, but not of TNF-α and IL-10, was lower in Ripk2-deficient BMDMs than in WT cells. Western blotting revealed a decrease in F. nucleatum-induced p65 phosphorylation in Ripk2-deficient macrophages, whereas mitogen-activated protein kinases activation was comparable between WT and Ripk2-deficient cells. The production of nitric oxide (NO) in response to F. nucleatum and the gene and protein expression of inducible NO synthase was impaired in Ripk2-deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time-dependent manner. F. nucleatum also increased the production of IL-6, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2. CONCLUSIONS: In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum-induced immune response and can be a preventive and therapeutic target against APOs.

TLR2 and the NLRP3 inflammasome mediate IL-1ß production in Prevotella nigrescens-infected dendritic cells.

Prevotella nigrescens is an oral pathogen that is frequently observed in the subgingival plaque of periodontitis patients. Interleukin-1ß (IL-1ß) is known to be involved in the immunopathology of periodontal diseases and has been implicated in the destruction of bone. In this study, we investigated the mechanism of IL-1ß production by P. nigrescens in murine bone marrow-derived dendritic cells (BMDCs). Our results showed that a host receptor, Toll-like receptor 2 (TLR2), but not TLR4 is required for pro-IL-1ß induction and nucleotide-binding oligomerization domain like receptor pyrin domain containing 3 (NLRP3) priming in BMDCs in response to P. nigrescens and activation of the NLRP3 inflammasome is necessary for processing of pro-IL-1ß into mature IL-1ß. In addition, an inhibitor assay revealed that production of reactive oxygen species, P2X7R activity, and release of cathepsin B are involved in IL-1ß production in BMDCs in response to P. nigrescens.

The First Report to Evaluate Safety of Cyanobacterium Leptolyngbya sp. KIOST-1 for Use as a Food Ingredient: Oral Acute Toxicity and Genotoxicity Study.

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 µg/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.