Gochujang, a traditional Korean fermented food, protects through suppressed inflammatory pathways and histological structure disruption in dextran sodium sulfate (DSS)-induced colitis mice.

The mechanisms underlying chronic inflammatory diseases remain unclear. Therefore, researchers have explored the mechanisms underlying colitis using diverse materials. Recently, there has been an increasing interest in fermented products and bioconversion materials, their potential efficacy is being actively studied. Gochujang, a traditional Korean fermented product, is crafted by blending fermented Meju powder, gochu (Korean chili) powder, glutinous rice, and salt. In our study, we explored the effectiveness of Gochujang (500 mg/kg; Cheongju and Hongcheon, Korea) in dextran sulfate sodium (DSS)-induced colitis mice model. Gochujang was orally administered for 2 weeks, followed by the induction of colitis using 3% DSS in the previous week. During our investigation, Gochujang variants (TCG22-25, Cheongju and TCG22-48, Hongcheon) did not exhibit significant inhibition of weight reduction (p = 0.061) but notably (p = 0.001) suppressed the reduction in large intestine length in DSS-induced colitis mice. In the serum from colitis mice, TCG22-48 demonstrated reduced levels of the inflammatory cytokines interleukin (IL)-6 (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.001). Additionally, it inhibited the phosphorylation of Erk (p = 0.028), p38, and NF-κB (p = 0.001) the inflammatory mechanism. In our study, TCG22-25 demonstrated a reduction in the IL-6 level (p = 0.001) in serum and inhibited the phosphorylation of p38 and NF-κB (p = 0.001). Histological analysis revealed a significant (p = 0.001) reduction in the pathological score of the large intestine from TCG22-25 and TCG22-48. In conclusion, the intake of Gochujang demonstrates potent anti-inflammatory effects, mitigating colitis by preventing the large intestine length reduction of animals with colitis, lowering serum levels of TNF-α and IL-6 cytokines, and inhibiting histological disruption and inflammatory mechanism phosphorylation.

Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging.

OBJECTIVES: Currently, no approved stem cell-based therapies for preserving ovarian function during aging. To solve this problem, we developed a long-term treatment for human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs). We investigated whether the cells retained their ability to resist ovarian aging, which leads to delayed reproductive senescence. MATERIALS AND METHODS: In a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs benefit the long-term maintenance of reproductive fecundity and ovarian reservoirs and how their transplantation regulates ovarian function. RESULTS: The number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice who underwent multiple introductions of hESC-MPCs compared to age-matched controls. The estradiol levels in the hESC-MPCs group were restored to those in the young and adult groups. Embryonic development and live birth rates were higher in the hESC-MPC group than in the control group, suggesting that hESC-MPCs delayed ovarian senescence. In addition to their direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via the suppression of myeloid-derived suppressor cells (MDSCs) produced in the bone marrow. CONCLUSIONS: Multiple introductions of hESC-MPCs could be a useful approach to prevent female reproductive senescence and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.

Protocol for differentiation of functional macrophages from human induced pluripotent stem cells.

Human induced pluripotent stem cell (hiPSC)-derived macrophages provide a valuable tool for disease modeling and drug discovery. Here, we present a protocol to generate functional macrophages from hiPSCs using a feeder-free hematopoietic differentiation technique. We describe steps for preparing hiPSCs, mesodermal differentiation, hematopoietic commitment, and macrophage differentiation and expansion. We then detail assays to characterize their phenotype, polarization, and phagocytic functions. The functional macrophages generated here could be used to generate organoids for disease modeling and drug discovery studies. For complete details on the use and execution of this protocol, please refer to Jeong et al.1 and Heo et al.2.

Successful Endoscopic Transsphenoidal Approach Treatment of Sphenoid Sinus Organized Hematoma Causing Visual Deficit: A Case Report.

Background: Organized hematoma in the sphenoid sinus is rare, but serious complications, such as visual deficits, can occur. Three such case reports have been published previously in the literature; however, none have achieved complete recovery of the vision. Case presentation: A 69-year-old male patient was referred to the ear, nose, and throat department with an expansile soft tissue mass filling the right sphenoid sinus and blurry vision in his right eye. Complete mass removal was achieved by a wide opening of the sphenoid sinus via an endoscopic transsphenoidal approach, followed by cauterization of the feeding artery and coverage by a nasoseptal flap. The patient's vision was restored after the operation, and he declared no visual symptoms until the latest follow-up (one year after the surgery). Conclusions: Complete excision with an endoscopic endonasal transsphenoidal approach can restore visual deterioration caused by a sphenoid sinus organized hematoma.

Comparison of the laxative effects of Korean Gochujang containing different microbiota on loperamide-induced constipation in ICR mice.

The prevalence of constipation, one of the common gastrointestinal (GI) diseases, has been gradually increasing. Gochujang, a traditional Korean fermented paste, has various microbiota and exerts diverse health beneficial effects. However, the ameliorative effect of Gochujang on constipation is unexplored. Seven-week-old ICR mice were divided into five groups: the normal group, the loperamide (LOP) group, the LOP + mosapride citrate (3 mg per kg BW, MOSA) treated group, the LOP + BMG Gochujang (2 g per kg BW) group, and the LOP + VMG Gochujang (2 g per kg BW) group. Gochujang alleviated constipation by increasing defecation frequency and water content in feces by reducing AQP3 mRNA expression. Additionally, Gochujang increased GI transit time and excitatory neurotransmitter levels and decreased inhibitory neurotransmitter levels. Moreover, Gochujang reduced mitogen-activated protein kinase (MAPK) activation and increased the c-Kit/SCF signaling pathway, suggesting that Gochujang regulates the enteric nervous system (ENS). Interestingly, BMG and VMG differently influenced the gut microbiota composition. Both Gochujang groups significantly decreased the Bacteroidetes and Firmicutes ratio compared to the LOP group. However, among Firmicutes genera, Acetatifactor was only reduced in BMG, and VMG only decreased Caproiciproducens and Acutalibacter. In summary, Gochujang effectively alleviated LOP-induced constipation outcomes regardless of their different microbial communities by ameliorating GI motility and changing the gut microbiota composition.

Protective Effect of Long-Term Fermented Soybeans with Abundant Bacillus subtilis on Glucose and Bone Metabolism and Memory Function in Ovariectomized Rats: Modulation of the Gut Microbiota.

We investigated the effects of different types of long-term fermented soybeans (traditionally made doenjang; TMD) on glucose and bone metabolism and memory function in ovariectomized (OVX) rats. The rats were categorized into six groups: Control, cooked unfermented soybeans (CSB), and four TMDs based on Bacillus subtilis (B. subtilis) and biogenic amine contents analyzed previously: high B. subtilis (HS) and high biogenic amines (HA; HSHA), low B. subtilis (LS) and HA (LSHA), HS and low biogenic amines (LA; HSLA), and LS and LA (LSLA). The rats in the CSB and TMD groups fed orally had a 4% high-fat diet for 12 weeks. Rats in the Control (OVX rats) and Normal-control (Sham-operated rats) groups did not consume CSB or TMD, although macronutrient contents were the same in all groups. Uterine weight and serum 17ß-estradiol concentrations were much lower in the Control than the Normal-control group, but CSB and TMD intake did not alter them regardless of B. subtilis and biogenic amine contents. HOMA-IR, a measure of insulin resistance, decreased with TMD with high B. subtilis (HSLA and HSHA) compared to the Control group. In OGTT and IPGTT, serum glucose concentrations at each time point were higher in the Control than in the Normal-control, and HSLA and HSHA lowered them. Memory function was preserved with HSHA and HSLA administration. Bone mineral density decline measured by DEXA analysis was prevented in the HSHA and HSLA groups. Bone metabolism changes were associated with decreased osteoclastic activity, parathyroid hormone levels, and osteoclastic activity-related parameters. Micro-CT results demonstrated that TMD, especially HSLA and HSHA, preserved bone structure in OVX rats. TMD also modulated the fecal bacterial community, increasing Lactobacillus, Ligalactobacillus, and Bacillus. In conclusion, through gut microbiota modulation, TMD, particularly with high B. subtilis content, acts as a synbiotic to benefit glucose, bone, and memory function in OVX rats. Further research is needed to make specific recommendations for B. subtilis-rich TMD for menopausal women.

Evaluation of Body Changes and the Anti-Obesity Effect after Consumption of Korean Fermented Food, Cheonggukjang: Randomized, Double-Blind Clinical Trial.

Cheonggukjang is a traditional Korean fermented soybean food with potential health benefits. For this reason, Cheonggukjang is consumed in the form of pills in addition to being used as a food ingredient. There are few clinical studies that have evaluated changes in various health indicators through blood and stool tests before and after consumption of Cheonggukjang. In this study, symptoms and hematological changes were analyzed before and after the intake of traditional Cheonggukjang pills containing high-dose (n = 19) or low-dose (n = 20) beneficial bacteria and commercial Cheonggukjang pills (n = 20). Anti-obesity effects and body composition changes were determined before and after Cheonggukjang consumption. Lastly, the changes in microorganisms and short-chain fatty acids in the stool were compared. No changes in obesity and inflammation-related indicators were observed before and after Cheonggukjang consumption. The Firmicutes/Bacteroidetes ratio, associated with obesity, decreased in all three groups after Cheonggukjang consumption, but no statistical significance was indicated. Cheonggukjang contained various BAs, but they did not adversely affect symptoms and hematological changes in the participants. BAs generated during the manufacturing process of Cheonggukjang did not have any adverse effects in this randomized, double-blind clinical trial. Further research is needed in future concerning the anti-obesity effect or regarding changes in the microbiome and short-chain fatty acids in feces.

Gochujang Ameliorates Hepatic Inflammation by Improving Dysbiosis of Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Abnormal fat accumulation with gut microbiota dysbiosis results in hepatic inflammation by upregulating the release of lipopolysaccharide (LPS) and inflammatory cytokine. Gochujang, a traditional fermented condiment, has beneficial effects, such as anti-colonic inflammatory effects. However, Gochujang has been controversial because of its high salt content (the Korean Paradox). Thus, the present study aimed to investigate the preventative effects of Gochujang on hepatic inflammation and related gut microbiota through discussing the Korean Paradox. The mice were divided into groups including a normal diet (ND), high-fat diet (HD), HD with salt (SALT), HD with a high percentage of beneficial microbiota Gochujang (HBM), and HD with diverse beneficial microbiota Gochujang (DBM). Gochujang markedly reduced lipid accumulation, hepatic injury, and inflammation response. Furthermore, Gochujang attenuated protein expression involved in the JNK/IκB/NF-κB pathway. Additionally, Gochujang regulated the gut microbiota-derived LPS production and Firmicutes/Bacteroidetes ratio. Gochujang regulated the levels of gut microbiota such as Bacteroides, Muribaculum, Lactobacillus, and Enterorhabdus, which were correlated with hepatic inflammation. Salt did not have foregoing effects, meaning that the salt content in Gochujang did not affect its anti-inflammatory effect. In conclusion, Gochujang showed anti-hepatic inflammation effects via reduced lipid accumulation, hepatic injury, and inflammatory response together with reorganization of gut microbiota dysbiosis regardless of salt content and the difference of micro bacteria composition.

Inverse association of daily fermented soybean paste ("Jang") intake with metabolic syndrome risk, especially body fat and hypertension, in men of a large hospital-based cohort.

Introduction: Jang is a fermented soybean paste containing salt and is traditionally used as a substitute for salt to enhance the flavor of foods in Korea. It has been speculated that regular consumption of Jang may lower the risk of metabolic syndrome (MetS). We hypothesized that Jang intake was associated with the risk of MetS and its components after adjusting for potential confounders, including sodium intake. The hypothesis was investigated according to gender in a large city hospital-based cohort (n = 58,701) in Korea. Methods: Jang intake, calculated as the sum of the intakes of Chungkookjang, Doenjang, Doenjang soup, and Ssamjang (a mixture of Doenjang and Kochujang), was included in the semi-quantitative food frequency questionnaire (SQFFQ) administered to the cohort, and the daily Jang intake was estimated. The participants were categorized into low-Jang and high-Jang groups by 1.9 g daily Jang intake. MetS was defined according to 2005 revised United States National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria modified for Asians. Results: The participants in the low-Jang and high-Jang groups consumed an average of 0.63 g and 4.63 g Jang daily; their total sodium intake was about 1.91 and 2.58 g/day, respectively. The participants in the high-Jang group had higher energy, fiber, calcium, vitamin C, vitamin D, and potassium intake than those in the low-Jang group. After adjusting for covariates, the participants with the highest sodium intake (≥3.31 g/day) were positively associated with MetS risk in the quintiles of men and women. Among the MetS components, waist circumference, fat mass, and hypo-high-density lipoprotein (HDL)-cholesterolemia were positively associated with sodium intake in all participants and women. Unlike the association seen with sodium intake, Jang intake (≥1.9 g/day) was inversely associated with MetS components, including waist circumference, fat mass, serum glucose concentrations, and hypo-HDL-cholesterolemia in all participants and men, after adjusting for covariates including sodium intake. Discussion: Substituting salt for Jang in cooking may be recommended to prevent and alleviate MetS incidence, and its efficacy for MetS risk was better in men than women. The results can be applied to sodium intake in Asian countries where salt is used to promote flavor.

Improvement of Estrogen Deficiency Symptoms by the Intake of Long-Term Fermented Soybeans (Doenjang) Rich in Bacillus Species through Modulating Gut Microbiota in Estrogen-Deficient Rats.

Traditionally made doenjang (TMD) produced by the long-term fermentation of soybeans with salt may improve symptoms of estrogen deficiency. We aimed to evaluate the effects of four TMD types, containing low and high amounts of Bacillus species and biogenic amines (HBHA, HBLA, LBHA, and LBLA), on energy, glucose, and lipid metabolism, by altering the gut microbiota in estrogen-deficient ovariectomized (OVX) rats. Their mechanisms were also examined. The OVX rats were divided into the control, cooked soybean (CSB), HBHA, LBHA, HBLA, and LBLA groups. Sham-operated rats were the normal control group. Serum 17ß-estradiol concentrations were similar among all OVX groups. Tail skin temperatures, which are indicative of hot flashes, were higher in the control than the HBHA and HBLA groups and were similar to the normal control group. Weight gain and visceral fat mass were lower in the TMD and CSB intake groups but not as low as in the normal control group. Lean body mass showed a trend opposite to that of visceral fat in the respective groups. The hepatic triglyceride content decreased with the TMD intake compared to the control and CSB groups. mRNA expressions of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and carnitine palmitoyltransferase-1 in the TMD and CSB groups were as high as in the normal control group, and the PPAR-γ mRNA expression was more elevated in the HBLA group than in the normal control group. The morphology of the intestines improved in the TMD groups compared to the control, and the HBHA and HBLA groups showed an enhanced improvement compared to the CSB group. The HBHA, HBLA, and LBHA groups increased the α-diversity of the cecal microbiota compared to the control. Akkermenia and Lactobacillus were higher in the HBLA and LBLA groups compared to the control. The expression of the estrogen, forkhead box proteins of the class-O subgroup, and insulin-signaling pathways were lower in the control group, and HBHA and HBLA prevented their decrement. In conclusion, long-term treatment with TMD containing high amounts of Bacillus potentially improves estrogen deficiency symptoms more than unfermented soybeans.

Effects of Cheonggukjang (Fermented Soybean) on the Development of Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is the third most common type of cancer and is caused by multiple factors. Chronic inflammation, known to cause inflammatory bowel disease (IBD), is closely associated with CRC. Cheonggukjang (CJ), a traditional Korean fermented soybean, is a functional food with anti-inflammatory effects in the intestines, but its anti-cancer effects have not yet been explored. In this study, we investigated the cancer-protective effects of cheonggukjang in an azoxymethane/DSS (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model. The CJ alleviated AOM/DSS-induced pathological symptoms such as colonic shortening, increased spleen weight, tumor formation, and histological changes. It also modulated pro-inflammatory and anti-inflammatory cytokine levels via the suppression of NF-κB and inflammatory mediator signaling pathways. Furthermore, the CJ improved intestinal integrity by regulating mucin-associated and tight junction proteins. In addition, it suppressed tumor growth by regulating apoptosis and proliferation. These results highlight the anti-tumor effects of CJ in an AOM/DSS-induced CAC mouse model.

Protective effect of traditional Korean fermented soybean foods (doenjang) on a dextran sulfate sodium-induced colitis mouse model.

Objective: The cause of ulcerative colitis (UC) is unknown, and the use of anti-inflammatory and immunosuppressive drugs with certain side effects is currently replacing treatment. Therefore, it is important to find new healthy foods or ingredients that exhibit potential protective and anti-inflammatory effects on UC. This study investigated the potential protective effect of doenjang on dextran sulfate sodium (DSS)-induced colitis in a mouse model. Materials and methods: Four doenjang samples (TCD21-51-1, TCD21-55-1, TMD21-16-1, and TFD21-1-1) were used. To examine the effects of the four doenjang samples on UC caused by DSS in a mouse model, the clinical symptoms of UC, such as body weight, disease activity index (DAI), and colon macroscopic damage index (CMDI) were analyzed. Moreover, immune-related blood cell counts, serum levels and protein expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and nitric oxide (NO) production were measured in DSS-induced UC in mice for analysis. Results: The four doenjang samples increased the colon length shortened by DSS, reduced DAI (diarrhea and hemoccult), CMDI (ulceration, inflammation, and hemorrhage) and the content of immune-related cells in the blood. Moreover, the levels of TNF-α, IL-6, and NO increased by DSS were decreased by doenjang, and tissue damage was significantly reduced. Conclusions: These findings confirmed that doenjang exerts protective effects against UC, suggesting its possible use in developing therapeutic strategies or functional products.

Anti-Obesity Effects of Traditional and Commercial Kochujang in Overweight and Obese Adults: A Randomized Controlled Trial.

Kochujang shows anti-obesity effects in cell and animal models. Kochujang is traditionally prepared via slow fermentation or commercially using Aspergillus oryzae. We analyze the anti-obesity effects of two types of Kochujang in overweight and obese adults. The analyses included the following groups: traditional Kochujang containing either a high-dose (HTK; n = 19), or a low-dose of beneficial microbes (LTK; n = 18), and commercial Kochujang (CK; n = 17). Waist circumference decreased significantly in the HTK and CK groups. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels decreased in the HTK and LTK groups. Visceral fat is significantly reduced in the HTK group. The population of beneficial microorganisms in stool samples increased in all groups. Consumption of Kochujang reduces visceral fat content and improves the lipid profile, which can be enhanced by enrichment with beneficial microbes. These results suggest that Kochujang has the potential for application in obesity prevention.

Alleviation of Metabolic Disturbance by Substituting Kanjang High in Bacillus for Salt through Modulation of Gut Microbiota in Estrogen-Deficient Rats.

A high salt intake may exacerbate menopausal symptoms and substituting for different types of traditionally made kanjang (TMK; soy sauce) may prevent it. This study examined whether substituting salt with lyophilized TMK containing low and high Bacillus and biogenic amines in a high-fat diet might modulate the menopausal symptoms and the energy, glucose, and lipid metabolism in ovariectomized (OVX) rats. They were categorized into salt (Control), TMK with high Bacillus and low biogenic amines (HBLB), TMK with high Bacillus and high biogenic amines (HBHB), TMK with low Bacillus and low biogenic amines (LBLB), and TMK with low Bacillus and high biogenic amines (LBHB). Sham-operated rats consumed the same diet as the Control. HBLB, HBHB, and LBHB prevented increased tail skin temperature compared to the Control. HBHB and HBLB partially inhibited the increased weight gain and abdominal fat mass by reducing the food efficiency without changing the serum 17ß-estradiol concentrations. Serum glucose and insulin concentrations and the insulin resistance index by the homeostatic model assessment for insulin resistance showed a positive association for weight gain. HBLB and HBHB decreased the serum malondialdehyde and tumor-necrosis factor-α levels. Hepatic triglyceride storage was lower in all TMK groups than in the Control, while hepatic glycogen accumulation was higher in the HBLB, HBHB, and LBHB groups than in the Control and LBLB groups. Accordingly, the mRNA expression of peroxisome proliferator-activated receptors-γ(PPAR-γ) was higher in the HBLB and HBHB groups compared to the Control, and that of fatty acid synthase was opposite to PPAR-γ expression. However, HBLB and HBHB improved dyslipidemia and insulin resistance compared to the Control, but their improvement did not reach that of the Normal-control. The acetic acid concentrations in the portal vein were lower in the LBLB than in the Control, while the butyric acid contents were higher in the LBHB and HBLB groups than in the Control. HBHB, HBLB, and LBHB elevated Akkermansia and Lactobacillus, and HBLB and LBLB increased Bacteroides and Ruminococcus compared to the Control. Polycyclic aromatic hydrocarbon degradation, bile acid synthesis, and unsaturated fatty acid biosynthesis were significantly higher in the HBLB group than in the Control group. In conclusion, substituting salts to TMK with a high Bacillus content regardless of the bioamine contents partially improved the menopausal symptoms and metabolic disturbance in estrogen-deficient animals.

Protective Effects of Fermented Soybeans (Cheonggukjang) on Dextran Sodium Sulfate (DSS)-Induced Colitis in a Mouse Model.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, and the incidence of IBD is increasing every year owing to changes in dietary structure. Although the exact pathogenesis of IBD is still unclear, recent evidence suggests that gut dysbiosis is closely associated with IBD pathogenesis. Cheonggukjang is a traditional Korean fermented soybean paste produced using traditional and industrial methods, and contains probiotics, which affect the gut microbiota composition. However, the protective effect of Cheonggukjang against IBD is unknown. In this study, we investigated the bacterial community structure of traditional and commercial Cheonggukjang samples, as well as the protective effect of Cheonggukjang on a dextran sulfate sodium (DSS)-induced colitis mouse model. Traditional and commercial Cheonggukjang were found to contain various type of useful probiotics in their bacterial community structure. Cheonggukjang reduced the progression of DSS-induced symptoms, such as body weight loss, colonic shortening, disease activity index, and histological changes. Further, Cheonggukjang improved the intestinal epithelial barrier integrity on DSS-induced colitis mice. In addition, Cheonggukjang suppressed the expression of proinflammatory cytokines and inflammatory mediators through the inactivation of NF-κB and MAPK signaling pathways. These results indicate that Cheonggukjang exerts protective effects against DSS-induced colitis, suggesting its possible application as a functional food for improving inflammatory diseases.

Biosorption of arsenite (As[III]) using Saccharomyces cerevisiae SRCM 501804 isolated from Korean turbid rice wine.

The potentiality of Saccharomyces cerevisiae SRCM 501804 to remove arsenite (As[III]) in an aqueous solution was investigated in this study. The S. cerevisiae SRCM 501804 was isolated from Korean turbid rice wine (Makgeolli). The S. cerevisiae SRCM 501804 was characterized by phylogenetic analysis, Fourier transform infrared (FT-IR) spectroscopy, visual minerals technologies (MINTEQ) model, and point of zero charge (pHpzc). The relationship between the factors (pH, biosorbent dosage, contact time, and concentration) and biosorption capacity was investigated. The S. cerevisiae SRCM 501804 was removed 31.1-90.1% of the As(III) depending on the initial biomass dosage within 1 h. Co-existing anions in aqueous solution showed a negative influence on the biosorption performance of As(III) in the order Cl- > NO3- > SO42- > CO32-. The results of isotherms and kinetics suggested the Langmuir (R2 > 0.95) and Pseudo-second order (R2 > 0.99) models fit well with the equilibrium experimental data. The maximum biosorption capacity (qm) of S. cerevisiae SRCM 501804 biomass for As(III) was found to be 113.9 mg/g from Langmuir isotherm. Based on the results, it can be concluded that the biomass of S. cerevisiae SRCM 501804 could be used as an effective bio-sorbent for As(III) biosorption in an aqueous solution.

Bacterial Community and Anti-Cerebrovascular Disease-Related Bacillus Species Isolated from Traditionally Made Kochujang from Different Provinces of Korea.

Traditionally made Kochujang (TMK) is a long-term fermented soybean and rice mixture with red pepper and salts. The ambient bacteria in rice straw and nutrient components of Kochujang influence the bacteria community. We aimed to investigate the bacterial composition and quality of TMK from different provinces of Korea: Chungcheung (CC), Jeolla (JL), Kyungsang (KS), and GeongGee plus Kangwon (GK) provinces, and Jeju island (JJ). Furthermore, Bacillus spp. isolated from TMK were studied to have anti-cerebrovascular disease activity and probiotic properties. Seventy-three TMK samples from different regions were collected to assess the biogenic amine contents, bacteria composition using next-generation methods, and bacterial functions using Picrust2. Bacillus spp. was isolated from the collected TMK, and their antioxidant, fibrinolytic, and angiotensin I conversion enzyme (ACE) inhibitory activities and probiotic properties were examined. KS TMK had lower sodium contents than the other TMK. There were no significant differences in histamine and tyramine contents among the TMK samples in different provinces. The predominant bacteria in TMK was Bacillus spp., but KS included much less Bacillus spp. and higher Enterococcus and Staphylococcus than the other TMK. Gene expression related to lipopolysaccharide biosynthesis was higher in KS TMK than the other TMK in Picrust2. The predominant Bacillus spp. isolated from TMK was B. subtilis and B. velezensis. B. subtilis SRCM117233, SRCM117245, and SRCM117253 had antioxidant activity, whereas B. subtilis had higher fibrinolytic activity than other Bacillus spp. Only B. velezensis SRCM117254, SRCM117311, SRCM117314, and SRCM117318 had over 10% ACE inhibitory activity. In conclusion, KS had less Bacillus related to lower sodium contents than the other TMK. The specific strains of B. subtilis and B. velezensis had antioxidant, fibrinolytic, and ACE inhibitory activity, and they can be used as a starter culture to produce better quality controlled Kochujang with anti-cerebrovascular disease activities.

Bacterial Distribution, Biogenic Amine Contents, and Functionalities of Traditionally Made Doenjang, a Long-Term Fermented Soybean Food, from Different Areas of Korea.

Since doenjang quality depends on the bacterial composition, which ambient bacteria in the environment and production conditions influence, a complete understanding of the bacteria community in traditionally madetraditionally made doenjang (TMD) from different regions is needed. We aimed to investigate the bacteria composition and quality of TMD in the following areas: Chonbuk (CB), Chonnam (CN), Kyungsang (KS), Kangwon (KW), Chungchung (CC) provinces, and Jeju island (JJ) of Korea. Twenty-nine TMD samples from different regions were used to assess biogenic amine contents, bacteria composition using next-generation methods, and metabolic functions of the bacteria using Picrust2. Bacillus spp. were isolated, and their antioxidant and fibrinolytic activities were determined. Most TMD contained high amounts of beneficial bacteria (Bacillus, Lactobacillus, Pediococcus and Weissella). However, some KS samples contained harmful bacteria (Cronobacter, Proteus and Acinetobacter) and less beneficial B. velezensis bacteria. There was no similarity among the regional groups, and each TMD showed a different bacteria composition. Shannon index, α-diversity index, was lower in TMD from JJ and CB than the other areas, but there was no ß-diversity among TMD from the six area groups. Picrust2 analysis revealed that the functional potential for arachidonic acid metabolism was lowest in JJ and CN, that for supporting insulin action was highest in KS and JJ, and that for carbohydrate digestion and absorption was lowest in CB and JJ among all groups (p < 0.05) according to the Kyoto Encyclopedia of Genes and Genomes Orthology. Histamine contents were lower in CN and CC, and tyramine contents did not differ significantly. B. velezensis, B. subtilis, B. licheniformis, B. siamensis, and B. amyloliquefaciens were isolated from TMD. None of the isolated Bacillus spp. contained the B. cereus gene. B. subtilis from CN had the highest fibrinolytic activity, and B. velezensis from CB had the highest antioxidant activity. In conclusion, TMD mainly contained various Bacillus spp., and the predominant one was B. velezensis, which had antioxidant and fibrinolytic activity regardless of the regional origin.

BMP4 and perivascular cells promote hematopoietic differentiation of human pluripotent stem cells in a differentiation stage-specific manner.

The efficient and reproducible derivation and maturation of multipotent hematopoietic progenitors from human pluripotent stem cells (hPSCs) requires the recapitulation of appropriate developmental stages and the microenvironment. Here, using serum-, xeno-, and feeder-free stepwise hematopoietic induction protocols, we showed that short-term and high-concentration treatment of hPSCs with bone morphogenetic protein 4 (BMP4) strongly promoted early mesoderm induction followed by increased hematopoietic commitment. This method reduced variations in hematopoietic differentiation among hPSC lines maintained under chemically defined Essential 8 medium compared to those maintained under less-defined mTeSR medium. We also found that perivascular niche cells (PVCs) significantly augmented the production of hematopoietic cells via paracrine signaling mechanisms only when they were present during the hematopoietic commitment phase. A protein array revealed 86 differentially expressed (>1.5-fold) secretion factors in PVC-conditioned medium compared with serum-free control medium, of which the transforming growth factor-ß inducible gene H3 significantly increased the number of hematopoietic colony-forming colonies. Our data suggest that BMP4 and PVCs promote the hematopoietic differentiation of hPSCs in a differentiation stage-specific manner. This will increase our understanding of hematopoietic development and expedite the development of hPSC-derived blood products for therapeutic use.

CD1d is a novel cell-surface marker for human monocytic myeloid-derived suppressor cells with T cell suppression activity in peripheral blood after allogeneic hematopoietic stem cell transplantation.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR-CD14+ monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we identified, using high-throughput screening, a set of surface markers that are strongly expressed in HLA-DR-CD14+ monocytic MDSCs isolated from the peripheral blood (PB) of patients receiving allo-HSCT. Subsequent experiments showed the consistent dominant expression of CD1d in monocytic MDSCs of allo-HSCT PB in comparison with granulocytic MDSCs. In addition, CD1d-expressing cells isolated from PB of allo-HSCT patients showed the suppressive activity of T cell proliferation and higher expression of MyD88 and IDO compared with CD1d- cells. Our results suggest that CD1d could be a valuable marker for further therapeutic evaluation of human monocytic MDSCs for immune-related diseases, including GVHD.