A single-centre retrospective study of factors affecting steroid-free remission of immunoglobulin G4-related disease conducted in South Korea: A notable outcome after complete resection.

OBJECTIVES: Few studies have examined factors affecting steroid-free remission (SFR) in patients with immunoglobulin G4-related disease (IgG4-RD). The aim of this study was to investigate clinical factors affecting SFR in IgG4-RD. METHODS: The medical records of 68 patients who met the 2020 revised comprehensive diagnostic criteria for IgG4-RD were reviewed retrospectively. SFR was defined as remission maintained for at least 6 months without corticosteroids. Cox regression analysis was performed to examine the associations between SFR and various clinical factors. The relapse rate after SFR was examined using the log-rank test. RESULTS: After a median follow-up of 36 months, 30.9% (21/68) of patients with IgG4-RD achieved SFR. Multivariate Cox regression analysis revealed that IgG4-RD diagnosed by complete resection rather than by common diagnostic procedures was the only factor positively associated with SFR (hazard ratio, 7.41; 95% confidence interval, 2.23-24.60; P = .001). Furthermore, relapse after attainment of SFR was significantly less common in the group that underwent complete resection than in the group that did not undergo complete resection (log-rank P = .006). CONCLUSIONS: Patients with IgG4-RD diagnosed by complete resection had a higher likelihood of achieving SFR and a lower rate of relapse after attaining SFR.

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

Derhamnosylmaysin Inhibits Adipogenesis via Inhibiting Expression of PPARγ and C/EBPα in 3T3-L1 Cells.

We investigated the effects of derhamnosylmaysin (DM) on adipogenesis and lipid accumulation in 3T3-L1 adipocytes. Our data showed that DM inhibited lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Treatment of 3T3-L1 adipocytes with DM decreased the expression of major transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), the CCAAT-enhancer-binding protein (CEBP) family, and peroxisome proliferator-activated receptor gamma (PPARγ), in the regulation of adipocyte differentiation. Moreover, the expression of their downstream target genes related to adipogenesis and lipogenesis, including adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), stearyl-CoA-desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), was also decreased by treatment with DM during adipogenesis. Additionally, DM attenuated insulin-stimulated phosphorylation of Akt. These results first demonstrated that DM inhibited adipogenesis and lipogenesis through downregulation of the key adipogenic transcription factors SREBP-1c, the CEBP family, and PPARγ and inactivation of the major adipogenesis signaling factor Akt, which is intermediated in insulin. These studies demonstrated that DM is a new bioactive compound for antiadipogenic reagents for controlling overweight and obesity.

Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee.

Osteoarthritis (OA) is a degenerative and chronic joint disease characterized by clinical symptoms and distortion of joint tissues. It primarily damages joint cartilage, causing pain, swelling, and stiffness around the joint. It is the major cause of disability and pain. The prevalence of OA is expected to increase gradually with the aging population and increasing prevalence of obesity. Many potential therapeutic advances have been made in recent years due to the improved understanding of the underlying mechanisms, diagnosis, and management of OA. Embryonic stem cells and induced pluripotent stem cells differentiate into chondrocytes or mesenchymal stem cells (MSCs) and can be used as a source of injectable treatments in the OA joint cavity. MSCs are known to be the most studied cell therapy products in cell-based OA therapy owing to their ability to differentiate into chondrocytes and their immunomodulatory properties. They have the potential to improve cartilage recovery and ultimately restore healthy joints. However, despite currently available therapies and advances in research, unfulfilled medical needs persist for OA treatment. In this review, we focused on the contents of non-cellular and cellular therapies for OA, and briefly summarized the results of clinical trials for cell-based OA therapy to lay a solid application basis for clinical research.

Rotenoisin A is a novel anti-adipogenic compound.

The purpose of this study was to investigate the mechanisms underlying the inhibitory effects of rotenoisin A on adipogenesis in 3T3-L1 preadipocytes. 3T3-L1 cells were treated with rotenoisin A for 8 days after the induction of differentiation. Oil-red O staining showed that rotenoisin A significantly inhibited DMI-induced lipid accumulation and adipocyte differentiation. We found that rotenoisin A treatment of 3T3-L1 preadipocytes significantly reduced the mRNA and protein levels of the key adipocyte-specific transcription factors C/EBPß, C/EBPα, and PPARγ and markedly inhibited the expression of fatty acid-binding protein (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Furthermore, we observed that rotenoisin A substantially increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated acetyl CoA carboxylase (ACC). However, co-treatment with Compound C, an AMPK inhibitor, reversed the rotenoisin A-induced inhibition of the expression of the adipogenic transcription factors C/EBPα and PPARγ and decreased the levels of phosphorylated AMPK in differentiated 3T3-L1 cells. These results demonstrated that the anti-adipogenesis mechanism involves the down-regulation of critical adipogenic transcription factors, including C/EBPß, C/EBPα, and PPARγ, through activation of the AMPK signaling pathway by rotenoisin A.

Silk peptide treatment potentiates natural killer cell activity in vitro and induces natural killer cell maturation and activation in mouse splenocytes.

Context: Silk peptide from cocoons of silkworm (Bombyx mori L., Bombycidae) has been employed as a biomedical material and exhibits various bioactivities, including immune-modulating activity. Objective: We analyzed whether silk peptide exerts direct modulating effects on NK cells using an NK cell line in vitro and ex vivo splenocytes. We also attempted to delineate the mechanism underlying the modulation. Material and methods: In vitro activity of silk peptide on NK cells was determined by measurement of cytolytic activity against K562 cells at an effector-to-target ratio of 5:1 after incubation of NK-92MI cells with silk peptide (0-2000 µg/mL) for 48 and 72 h. Ex vivo activity of silk peptide on mouse splenic NK cells was determined similarly by using YAC-1 cells. Results: Treatment of NK-92MI NK cells with silk peptide (500-2000 µg/mL) significantly increased cytolytic activity on target cells by 2- to 4-fold. The same concentrations (500-2000 µg/mL) of silk peptide treatment also significantly enhanced the cytolytic activity of splenic NK cells against YAC-1 cells. Silk peptide treatment of IL-2-stimulated splenocytes induced enhanced expression of Th1, 2 and 17 cytokines including TNF-α, IFN-γ, IL-6, IL-4 and IL-17. Finally, ex vivo treatment with silk peptide on mouse splenocytes significantly enhanced the degree of NK cell maturation in a dose-dependent manner from 3.49 to 23.79%. Discussion and conclusions: These findings suggest that silk peptide stimulates NK cells, thereby influencing systemic immune functions and improving natural immunity. Thus, silk peptide could be useful as a complementary therapy in cancer patients.

Human ß-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity.

BACKGROUND: Antimicrobial peptides (AMPs) are primarily known for their innate immune defense against invading microorganisms, including viruses. In addition, recent research has suggested their modulatory activity in immune induction. Given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, AMPs are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses. RESULTS: In this study, we investigated the ability of human ß-defensin (HBD) 2 to promote antiviral immunity in vitro and in vivo using a receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen (Ag). When HBD 2-conjugated S RBD was used to treat THP-1 human monocytic cells, the expression levels of antiviral (IFN-ß, IFN-γ, MxA, PKR, and RNaseL) and primary immune-inducing (NOD2, TNF-α, IL-1ß, and IL-6) molecules were enhanced compared to those expressed after treatment with S RBD only. The expression of chemokines capable of recruiting leukocytes, including monocytes/macrophages, natural killer cells, granulocytes, T cells, and dendritic cells, was also increased following HBD 2-conjugated S RBD treatment. More important, immunization of mice with HBD 2-conjugated S RBD enhanced the immunogenicity of the S RBD and elicited a higher S RBD-specific neutralizing antibody response than S RBD alone. CONCLUSIONS: We conclude that HBD 2 activates the primary antiviral innate immune response and may also mediate the induction of an effective adaptive immune response against a conjugated Ag.

Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

CONTEXT: Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. OBJECTIVE: To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. MATERIALS AND METHODS: The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. RESULTS: Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. DISCUSSION AND CONCLUSION: Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

Application of an M-cell-targeting ligand for oral vaccination induces efficient systemic and mucosal immune responses against a viral antigen.

Oral mucosal vaccination is an alternative method to overcome the pitfalls of current injection-based vaccines, such as pain and high cost of vaccination. It is a feasible and economic vaccine application, especially in developing countries. However, achieving effective antigen delivery into mucosal lymphoid organs and efficient immune stimulation are prerequisites to successful oral mucosal vaccination. One promising approach for oral mucosal vaccine development is exploring the potential of M cells via M-cell-targeting ligands that have the potential to deliver ligand-conjugated antigens into mucosal lymphoid organs and evoke conjugated-antigen-specific systemic and mucosal immune responses. Here, we investigated the M-cell-targeting ligand, Co1, in inducing specific immune responses against a pathogenic viral antigen, envelope domain III (EDIII) of dengue virus, to provide the foundation for oral mucosal vaccine development against the pathogen. After oral administration of Co1-conjugated EDIII antigens, we observed efficient antigen delivery into Peyer's patches. We also report the elicitation of EDIII-specific immunity in systemic and mucosal compartments by Co1 ligand (located in the C-terminus of EDIII). Furthermore, the antibodies induced by the ligand-conjugated EDIII antigen showed effective virus-neutralizing activity. The results of this study suggest that the M-cell-targeting strategy using Co1 ligand as a mucosal adjuvant may be applicable for developing oral vaccine candidates against pathogenic viral antigen.

Suppression of lipopolysaccharide-induced expression of inflammatory indicators in RAW 264.7 macrophage cells by extract prepared from Ginkgo biloba cambial meristematic cells.

CONTEXT: Ginkgo biloba L. (Ginkgoaceae) leaves have been used as an herbal medicine that has a complex range of biological activities. However, when we consider that biological activity of plant extracts is highly variable according to the source, location, and harvest season, technology to obtain the natural products with homogeneity is extremely important. OBJECTIVE: We established the technology to obtain the cambial meristematic cells (CMCs) of Ginkgo biloba, which were expanded in vitro with homogeneity through a suspension culture and then determined the anti-inflammatory activity of fractionated samples prepared from the ethanol extract of CMCs. MATERIALS AND METHODS: We determined the anti-inflammatory activity of samples using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Especially, influence of sample treatment on the expression of various indicators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein (MAP) kinases, transcription factor, and cytokines, involved in inflammatory activity was assessed. RESULTS: A fractionated sample demonstrated 53.4% inhibition of LPS-induced NO production from the cells. Additionally, when fractionated samples were treated, iNOS and COX-2 expressions were almost completely suppressed. Fractionated samples also inhibited the phosphorylation of LPS-induced extracellular signal-regulated (ERK) and p38 MAP kinases more than 60%. IκB phosphorylation and subsequent nuclear factor (NF)-κB activation were also suppressed by fractionated samples. The expression of pro-inflammatory cytokines, IL-6 and tumor necrosis factor (TNF)-α, was significantly inhibited by the sample treatment. DISCUSSION AND CONCLUSION: Fractionated samples from the ethanol extract of Ginkgo biloba CMCs could potentially be the source of a powerful anti-inflammatory substance.

Protective effect of 17S­epoxy­docosapentaenoic acid against dextran sulfate sodium induced ulcerative colitis in BALB/c mice.

Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R­dihydroxy­16S,17S­epoxy­docosapentaenoic acid (diHEP­DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)­induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti­inflammatory effect of diHEP­DPA was confirmed by demonstrating that lipopolysaccharide­stimulated THP1 cells treated with diHEP­DPA decreased IL­6, TNF­α and nitrite levels by fluorescence­activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP­DPA at 20 µg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF­α, IL­6 and IL­1ß in the colon tissue and serum were significantly reduced in the diHEP­DPA + DSS­treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP­DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP­DPA + DSS­treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP­DPA+DSS­treated mice also exhibited decreased expression levels of phosporylated (p)­inhibitor κB protein, p­p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription­quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP­DPA against a severe colitis condition in vivo.

The Effects of a Death Preparation Education Program on Death Anxiety, Death Attitudes, and Attitudes toward End-of-Life Care among Nurses in Convalescent Hospitals.

Purpose: The purpose of this study was to examine the effects of a death preparation education program for nurses working in convalescent hospitals on death anxiety, death attitudes, and attitudes toward end-of-life care. Methods: This was a quasi-experimental study with a non-equivalent control group, pre-test and post-test design. Among 53 participants, 26 were assigned to the non-equivalent experimental group and 27 to the control group. The program was performed in the formats of lectures, video-watching, group discussions, and sharing, and consisted of 10 sessions held twice a week, for 5 weeks (90 minutes per session). Data were analyzed using descriptive statistics, the t-test, and the chi-square test in SPSS version 21.0. Results: Significant differences between the experimental and control groups were observed in death anxiety (t=7.62, P<0.001), death attitudes (t=-7.58, P<0.001), and attitudes to end-of-life care (t=-10.30, P<0.001). Conclusion: It was confirmed that the death preparation education program reduced death anxiety and had a positive effect on death attitudes and attitudes toward end-of-life care. Based on the results of this study, it is expected that specialized and systematic education that can increase the implementation and stability of death preparation education in various fields, including nursing, will have a positive effect on both hospice patients and members of society more broadly.

Urinary exosome microRNA signatures as a noninvasive prognostic biomarker for prostate cancer.

Predicting the risk of metastasis before starting prostate cancer (PCa) treatment can minimize the overtreatment of indolent cases and help choosing appropriate treatment. The levels of circulating microRNAs (miRNAs) from body fluids can be used as noninvasive prognostic biomarkers. In this study, urinary exosomal miRNA expression profiles of 149 PCas were determined and the miRNAs associated with metastasis were identified: miR-21, miR-16, miR-142-3p, miR-451, and miR-636. When evaluating clinical factors together, miR-21, miR-451, miR-636, and preoperative prostate-specific antigen (PSA) level remained significant in the multivariate analysis. Based on them, we developed a "Prostate Cancer Metastasis Risk Scoring (PCa-MRS)" model. The PCa-MRS showed superior stratification power (AUC = 0.925) to preoperative PSA or clinical Gleason score. Patients with high scores showed significantly poorer biochemical recurrence-free survival than those with low scores (P = 6.53 × 10-10). Our results showed the potential of urinary exosomal miRNAs as noninvasive markers for predicting metastasis and prognosis in PCa patients.

Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet.

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein ß (C/EBPß) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3ß (GSK3ß) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

Oral Administration of Silk Peptide Enhances the Maturation and Cytolytic Activity of Natural Killer Cells.

Silk peptide, the hydrolysate of silk protein derived from cocoons, has been employed as a biomedical material and is believed to be safe for human use. Silk peptide display various bioactivities, including anti-inflammatory, immune-regulatory, anti-tumor, anti-viral, and anti-bacterial. Although earlier investigations demonstrated that silk peptide stimulates macrophages and the production of pro-inflammatory cytokines, its effect on natural killer (NK) cell function has not yet been explored. In this study, we initially confirmed that silk peptide enhances NK cell activity in vitro and ex vivo. To assess the modulatory activity of silk peptide on NK cells, mice were fed various amounts of a silk peptide-supplemented diet for 2 months and the effects on immune stimulation, including NK cell activation, were evaluated. Oral administration of silk peptide significantly enhanced the proliferation of mitogen- or IL-2-stimulated splenocytes. In addition, oral silk peptide treatment enhanced the frequency and degree of maturation of NK cells in splenocytes. The same treatment also significantly enhanced the target cell cytolytic activity of NK cells, which was determined by cell surface CD107a expression and intracellular interferon-γ expression. Finally, oral administration of silk peptide stimulated T helper 1-type cytokine expression from splenic lymphocytes. Collectively, our results suggest that silk peptide potentiates NK cell activity in vivo and could be used as a compound for immune-modulating anti-tumor treatment.

Use of Novel Oral Anticoagulant to Treat Pulmonary Thromboembolism in Patient with Ulcerative Colitis Superinfected Cytomegalovirus Colitis.

Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm. We report a case of a 42-year-old female with ulcerative colitis who experienced an acute flare-up due to cytomegalovirus superinfection with pulmonary thromboembolism. She was treated with oral mesalamine, intravenous steroid and ganciclovir and low-molecular-weight heparin, followed by rivaroxaban, a novel oral anticoagulant. Her symptoms resolved after treatment, and no recurrence was noted during a 6-month post-treatment follow-up.

Annual Wormwood Leaf Inhibits the Adipogenesis of 3T3-L1 and Obesity in High-Fat Diet-Induced Obese Rats.

Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner. Consistently, AWL suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes through the downregulation of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin (DMI)-induced serine/threonine kinase protein kinase B (PKB/Akt) activation and the expression of adipogenic genes, including the CCAAT/enhancer binding protein-α (C/EBPα) and peroximal proliferator-activated receptor-γ (PPARγ). Moreover, the expression of adipocyte fatty acid-binding protein 4 (aP2), which is a known PPARγ-target gene, was downregulated by AWL treatment. Oral administration of AWL extracts significantly decreased the body weight gain, adipose tissue mass, adipocyte cell size, serum triglyceride (TG), and total cholesterol (TC) levels in HFD-induced obese rats. These results provide novel insight into the molecular mechanisms underlying the anti-obesity effects of AWL that are mediated by the downregulation of the expression of major adipogenic transcription factors, C/EBPα and PPARγ and Akt signalling.

Oral administration of red ginseng powder fermented with probiotic alleviates the severity of dextran-sulfate sodium-induced colitis in a mouse model.

Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product.

Rubus crataegifolius Bunge regulates adipogenesis through Akt and inhibits high-fat diet-induced obesity in rats.

BACKGROUND: Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death. The aim of this study was to determine the inhibitory effects of Rubus crataegifolius Bunge (RCB) on adipocyte differentiation in 3 T3-L1 cells and its anti-obesity properties in high fat diet (HFD)-induced obese rats. METHODS: 3 T3-L1 adipocytes and HFD-induced obese rats were treated with RCB, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. RESULTS: RCB treatment significantly inhibited adipocyte differentiation by suppressing the expression of C/EBPß, C/EBPα, and PPARγ in the 3 T3-L1 adipocytes. Subsequently, the expression of the PPARγ target genes aP2 and fatty acid synthase (FAS) decreased following RCB treatment during adipocyte differentiation. In uncovering the specific mechanism that mediates the effects of RCB, we demonstrated that the insulin-stimulated phosphorylation of Akt strongly decreased and that its downstream substrate phospho-GSK3ß was downregulated following RCB treatment in the 3 T3-L1 adipocytes. Moreover, LY294002, an inhibitor of Akt phosphorylation, exerted stronger inhibitory effects on RCB-mediated suppression of adipocyte differentiation, leading to the inhibition of adipocyte differentiation through the downregulation of Akt signaling. An HFD-induced obesity rat model was used to determine the inhibitory effects of RCB on obesity. Body weight gain and fat accumulation in adipose tissue were significantly reduced by the supplementation of RCB. Moreover, RCB treatment caused a significant decrease in adipocyte size, associated with a decrease in epididymal fat weight. The serum total cholesterol (TC) and triglyceride (TG) levels decreased in response to RCB treatment, whereas HDL cholesterol (HDL-C) increased, indicating that RCB attenuated lipid accumulation in adipose tissue in HFD-induced obese rats. CONCLUSION: Our results demonstrate an inhibitory effect of RCB on adipogenesis through the reduction of the adipogenic factors PPARγ, C/EBPα, and phospho-Akt. RCB had a potent anti-obesity effect, reducing body weight gain in HFD-induced obese rats.