Zaluzanin C Alleviates Inflammation and Lipid Accumulation in Kupffer Cells and Hepatocytes by Regulating Mitochondrial ROS.

Zaluzanin C (ZC), a sesquiterpene lactone isolated from Laurus nobilis L., has been reported to have anti-inflammatory and antioxidant effects. However, the mechanistic role of ZC in its protective effects in Kupffer cells and hepatocytes has not been elucidated. The purpose of this study was to elucidate the efficacy and mechanism of action of ZC in Kupffer cells and hepatocytes. ZC inhibited LPS-induced mitochondrial ROS (mtROS) production and subsequent mtROS-mediated NF-κB activity in Kupffer cells (KCs). ZC reduced mRNA levels of pro-inflammatory cytokines (Il1b and Tnfa) and chemokines (Ccl2, Ccl3, Ccl4, Cxcl2 and Cxcl9). Tumor necrosis factor (TNF)-α-induced hepatocyte mtROS production was inhibited by ZC. ZC was effective in alleviating mtROS-mediated mitochondrial dysfunction. ZC enhanced mitophagy and increased mRNA levels of fatty acid oxidation genes (Pparα, Cpt1, Acadm and Hadha) and mitochondrial biosynthetic factors (Pgc1α, Tfam, Nrf1 and Nrf2) in hepatocytes. ZC has proven its anti-lipid effect by improving lipid accumulation in hepatocytes by enhancing mitochondrial function to facilitate lipid metabolism. Therefore, our study suggests that ZC may be an effective compound for hepatoprotection by suppressing inflammation and lipid accumulation through regulating mtROS.

Spatiotemporal Expression of Anticoagulation Factor Antistasin in Freshwater Leeches.

Antistasin, which was originally discovered in the salivary glands of the Mexican leech Haementeria officinalis, was newly isolated from Helobdella austinensis. To confirm the temporal expression of antistasin during embryogenesis, we carried out semi-quantitative RT-PCR. Hau-antistasin1 was uniquely expressed at stage 4 of the cleavage and was strongly expressed in the late stages of organogenesis, as were other antistasin members. In order to confirm the spatial expression of antistasin, we performed fluorescence in situ hybridization in the late stages of organogenesis. The expression of each antistasin in the proboscis showed a similar pattern and varied in expression in the body. In addition, the spatial expression of antistasin orthologs in different leeches showed the possibility of different function across leech species. Hau-antistasin1 was expressed in the same region as hedgehog, which is a known mediator of signal transduction pathway. Hau-antistasin1 is probably a downstream target of Hedgehog signaling, involved in segment polarity signal pathway.

Comparative effects of artemisia vulgaris and charcoal moxa stimulating Zhongwan (CV 12) on body temperature in healthy participants: a cross-over single-blind randomized study.

OBJECTIVE: To evaluate the efficacy, safety, satisfaction, discomfort and patient preference of moxa cones of artemisia vulgaris and charcoal moxa. METHODS: This comparative study of moxibustion treatment with Artemisia vulgaris and charcoal moxa cone stimulating Zhongwan (CV 12) is a cross-over single-blinded, randomized clinical trial. A total of 40 healthy subjects (24 males and 16 females) participated in this study. Two subjects dropped out of the trial. Thirty-eight subjects were treated with Artemisia vulgaris and charcoal moxa cones for 30 min in a cross-over design. After treatment, the patients underwent a 30 minute waiting period, and then the temperatures at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4) were measured using digital infrared thermal imaging. RESULTS: After the use of Artemisia vulgaris moxa, the patients' body temperatures were slightly lowered at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After the use of charcoal moxa, the patients' body temperatures were somewhat increased at Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After Artemisia vulgaris moxa use, the body temperature difference between Zhongwan (CV 12) and Guanyuan (CV 4) was significantly increased. After charcoal moxa use, the body temperature difference between Tanzhong (CV 17) and Zhongwan (CV 12) was significantly decreased in males and in the whole group. This change was caused by the difference in the moxibustion type and by gender differences. CONCLUSION: This pilot study found that moxibustion did not raise the body temperature, but temperature differences between acupoints were affected. Further large-scale randomized controlled trials are needed for the effect of moxibustion on body temperature.

A 12-Week, Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial for the Evaluation of the Efficacy and Safety of Lactiplantibacillus plantarum SKO-001 in Reducing Body Fat.

There is growing evidence linking gut microbiota to overall health, including obesity risk and associated diseases. Lactiplantibacillus plantarum SKO-001, a probiotic strain isolated from Angelica gigas, has been reported to reduce obesity by controlling the gut microbiome. In this double-blind, randomised clinical trial, we aimed to evaluate the efficacy and safety of SKO-001 in reducing body fat. We included 100 participants randomised into SKO-001 or placebo groups (1:1) for 12 weeks. Dual-energy X-ray absorptiometry was used to objectively evaluate body fat reduction. Body fat percentage (p = 0.016), body fat mass (p = 0.02), low-density lipoprotein-cholesterol levels (p = 0.025), and adiponectin levels (p = 0.023) were lower in the SKO-001 group than in the placebo group after 12 weeks of SKO-001 consumption. In the SKO-001 group, the subcutaneous fat area (p = 0.003), total cholesterol levels (p = 0.003), and leptin levels (p = 0.014) significantly decreased after 12 weeks of SKO-001 consumption compared with baseline values. Additionally, SKO-001 did not cause any severe adverse reactions. In conclusion, SKO-001 is safe and effective for reducing body fat and has the potential for further clinical testing in humans.

Korean Red Ginseng Improves Oxidative Stress-Induced Hepatic Insulin Resistance via Enhancing Mitophagy.

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes-a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins' efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions.

KM110329 in adult patients with atopic dermatitis: a randomised, double-blind, placebo-controlled, multicentre trial--study protocol.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease with a high prevalence rate and a large socioeconomic cost. There are many treatments for atopic dermatitis, such as antihistamine, tacrolimus and corticosteroids. However, due to concern about the adverse effects, many patients seek alternative treatments. In this context, natural products are gaining interest. KM110329 is a functional food consisting of four herbs that are beneficial to skin health. The purpose of this study is to assess the efficacy and safety of KM110329 for atopic dermatitis. METHODS/DESIGN: This study is a randomised, double-blind, placebo-controlled and multicentre trial of KM110329. For this study, we will recruit 66 atopic dermatitis patients of both sexes, with ages ranging from 18 to 65, from three university hospitals. The participants will receive either KM110329 or a placebo twice a day for 8 weeks. The primary end point will be a change in the scoring atopic dermatitis (SCORAD) index. The secondary end points will include changes to the dermatology life quality index (DLQI) and transepidermal water loss (TEWL), among others. The outcomes will be measured at every visit. The study will be continued for 8 weeks and will include five visits with each subject (at screening and at 0, 1, 4 and 8 weeks). DISCUSSION: This trial will provide research methodologies for evaluate clinical efficacy and safety of KM110329 in adult patients with atopic dermatitis. In addition, we will evaluate the changes in the general skin health status and quality of life. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01692093.

The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases.

Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central to liver metabolism, mitochondria are essential for ATP production, gluconeogenesis, fatty acid oxidation, and heme synthesis. However, in diseases like NAFLD, ALD, and liver fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, and metabolic irregularities. This dysfunction, especially electron leakage, exacerbates the production of reactive oxygen species (ROS), augmenting liver damage. Amidst this, nuclear factor erythroid 2-related factor 2 (NRF2) emerges as a cellular protector. It not only counters oxidative stress by regulating antioxidant genes but also maintains mitochondrial health by overseeing autophagy and biogenesis. The synergy between NRF2 modulation and mitochondrial function introduces new therapeutic potentials for CLD, focusing on preserving mitochondrial integrity against oxidative threats. This review delves into the intricate role of oxidative stress in CLD, shedding light on innovative strategies for its prevention and treatment, especially through the modulation of the NRF2 and mitochondrial pathways.

T Cell Immunological Synaptosomes: Definition and Isolation.

In addition to microvilli's role as structural scaffold for TCR clustering, we recently discovered a novel function as message senders. We found that microvilli are separated from the T cell body shortly upon TCR stimulation and vesiculated to form T cell microvilli particles (TMPs), a new type of membrane vesicles. TMPs and synaptic ectosomes, which bud from the synaptic cleft, constitute "T cell immunological synaptosomes (TISs)" and act as conveyors of T cell messages or traits to cognate antigen-presenting cells. In practice, it is almost impossible to distinguish between TMPs and synaptic ectosomes. Here, we describe a newly developed protocol to isolate TISs from activated T cells using antibody-immobilized agarose beads and density gradient ultracentrifugation. We further describe the methods for TIS quantification with flow cytometry and to evaluate TIS efficacy on dendritic cells.

The Immunosuppressive Potential of Cholesterol Sulfate Through T Cell Microvilli Disruption.

Cholesterol (CL) is required for various biomolecular production processes, including those of cell membrane components. Therefore, to meet these needs, CL is converted into various derivatives. Among these derivatives is cholesterol sulfate (CS), a naturally produced CL derivative by the sulfotransferase family 2B1 (SULT2B1), which is widely present in human plasma. CS is involved in cell membrane stabilization, blood clotting, keratinocyte differentiation, and TCR nanocluster deformation. This study shows that treatment of T cells with CS resulted in the decreased surface expression of some surface T-cell proteins and reduced IL-2 release. Furthermore, T cells treated with CS significantly reduced lipid raft contents and membrane CLs. Surprisingly, using the electron microscope, we also observed that CS led to the disruption of T-cell microvilli, releasing small microvilli particles containing TCRs and other microvillar proteins. However, in vivo, T cells with CS showed aberrant migration to high endothelial venules and limited infiltrating splenic T-cell zones compared with the untreated T cells. Additionally, we observed significant alleviation of atopic dermatitis in mice injected with CS in the animal model. Based on these results, we conclude that CS is an immunosuppressive natural lipid that impairs TCR signaling by disrupting microvillar function in T cells, suggesting its usefulness as a therapeutic agent for alleviating T-cell-mediated hypersensitivity and a potential target for treating autoimmune diseases.

Current Research Status and Implication for Further Study of Real-World Data on East Asian Traditional Medicine for Heart Failure: A Scoping Review.

This study used real-world data (RWD) to explore the long-term effects of East Asian traditional medicine (EATM) on heart failure (HF). A comprehensive search was conducted across five databases to identify relevant studies, which were then reviewed using the Arksey and O'Malley scoping review framework. The analysis focused on a descriptive examination of the long-term outcomes associated with EATM intervention. Methodologically, the study explored various aspects, including study subjects, interventions, applied clinical outcomes, and statistical methods. Out of 258 studies, 12 were selected. Eight studies involved patients with HF, while the others used HF as an outcome. Datasets from the National Health Insurance Research Database were used in Taiwan, while electronic medical record data were used in China and Japan. EATM interventions have been found to be associated with lower mortality and readmission rates. One study indicated that an increased dose of Fuzi, a botanical drug, or prompt use of Fuzi after diagnosis led to a decreased mortality hazard ratio. In two studies examining readmission rates, a significant increase was observed in the non-exposed group, with odds ratios of 1.28 and 1.18. Additionally, in patients with breast cancer, the subdistribution hazard ratio for the occurrence of doxorubicin-induced HF was reduced to 0.69. Although cohort studies with survival analysis were common, methodological flaws, such as issues with statistical methods and HF diagnosis, were identified. Despite these challenges, the study observed an association between EATM and improved clinical outcomes in patients with HF, emphasizing the potential of RWD studies to complement randomized controlled trials, especially for longer-term follow-ups. These results provide foundational data for future RWD research.

T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells.

Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

Analysis of factors associated with the use of Korean medicine after spinal surgery using a nationwide database in Korea.

Many patients in Korea use Korean Medicine (KM) after spine surgery, but related research is lacking. Therefore, this retrospective cohort study aimed to analyze factors affecting the use and costs of KM using nationally representative data from the National Health Insurance Service-National Sample Cohort, South Korea. Patients who underwent spinal surgery for spinal diseases from 2011 to 2014 were followed up for 5 years, and their medical care was described. The association between patient and spinal surgery characteristics and the use of KM was analyzed. A two-part model was used to analyze factors affecting the use of KM in patients undergoing spinal surgery. Of 11,802 patients who underwent spinal surgery, 11,367 who met the inclusion criteria were included. Overall, 55.5% were female, 32.3% were aged ≥ 70 years, and 50.2% received KM treatment during the follow-up period. Open discectomy was the most common surgical procedure performed (58.6%), and 40.2% of surgeries were performed because of lumbar disc disorder. Female sex, older age, high Charlson Comorbidity Index score, and use of KM before surgery were associated with increased KM use and expenditure after surgery. In conclusion, patient characteristics, rather than surgical characteristics, appeared to be more strongly associated with the use of KM after surgery, particularly prior experience with KM use. This study is significant in that it analyzed the entire spine surgery to provide a comprehensive view of the use of KM after spine surgery and analyzed the impact of various factors related patients and surgical characteristics on KM use. The results of this study may be useful to patients with spinal diseases, clinicians, and policymakers.

Trogocytic molting of T cell microvilli upregulates T cell receptor surface expression and promotes clonal expansion.

Although T cell activation is known to involve the internalization of the T cell antigen receptor (TCR), much less is known regarding the release of TCRs following T cell interaction with cognate antigen-presenting cells. In this study, we examine the physiological mechanisms underlying TCR release following T cell activation. We show that T cell activation results in the shedding of TCRs in T cell microvilli, which involves a combined process of trogocytosis and enzymatic vesiculation, leading to the loss of membrane TCRs and microvilli-associated proteins and lipids. Surprisingly, unlike TCR internalization, this event results in the rapid upregulation of surface TCR expression and metabolic reprogramming of cholesterol and fatty acid synthesis to support cell division and survival. These results demonstrate that TCRs are lost through trogocytic 'molting' following T cell activation and highlight this mechanism as an important regulator of clonal expansion.

Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures.

Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. In this context, anti-diabetic agents such as rosiglitazone and glucagon-like peptide (GLP)-1 have been reported to reduce pathologies associated with AD, including tau hyperphosphorylation, suggesting that such agents might be used to treat AD. One such anti-diabetic agent is sitagliptin, which acts through inhibition of dipeptidyl peptidase (DPP)-IV to increase GLP-1 levels. Given this action, sitagliptin would be predicted to reduce AD pathology. Accordingly, we investigated whether sitagliptin is effective in attenuating AD pathologies, focusing on tau phosphorylation in the OLETF type 2 diabetic rat model. Unexpectedly, we found that sitagliptin was not effective against pathological tau phosphorylation in the hippocampus of OLETF type 2 diabetes rats, and instead aggravated it. This paradoxically increased tau phosphorylation was attributed to activation of the tau kinase, GSK3ß (glycogen synthase kinase 3ß). Sitagliptin also increased ser-616 phosphorylation of the insulin receptor substrate (IRS)-1, suggesting increased insulin resistance in the brain. These phenomena were recapitulated in primary rat cortical neurons treated with sitagliptin, further confirming sitagliptin's effects on AD-related pathologies in neurons. These results highlight the need for caution in considering the use of sitagliptin in AD therapy.

The Use of Artificial Intelligence in Complementary and Alternative Medicine: A Systematic Scoping Review.

Background: The development of artificial intelligence (AI) in the medical field has been growing rapidly. As AI models have been introduced in complementary and alternative medicine (CAM), a systematized review must be performed to understand its current status. Objective: To categorize and seek the current usage of AI in CAM. Method: A systematic scoping review was conducted based on the method proposed by the Joanna Briggs Institute. The three databases, PubMed, Embase, and Cochrane Library, were used to find studies regarding AI and CAM. Only English studies from 2000 were included. Studies without mentioning either AI techniques or CAM modalities were excluded along with the non-peer-reviewed studies. A broad-range search strategy was applied to locate all relevant studies. Results: A total of 32 studies were identified, and three main categories were revealed: 1) acupuncture treatment, 2) tongue and lip diagnoses, and 3) herbal medicine. Other CAM modalities were music therapy, meditation, pulse diagnosis, and TCM syndromes. The majority of the studies utilized AI models to predict certain patterns and find reliable computerized models to assist physicians. Conclusion: Although the results from this review have shown the potential use of AI models in CAM, future research ought to focus on verifying and validating the models by performing a large-scale clinical trial to better promote AI in CAM in the era of digital health.

Efficacy of Rubus coreanus Miq. and Astragalus membranaceus Bunge Extract for Postmenopausal Syndrome: A Randomised, Double-Blind, Placebo Comparative Clinical Trial.

OBJECTIVES: The most effective way to improve menopausal symptoms is to supplement deficient oestrogen; however, long-term administration of synthetic oestrogen increases the risk for breast and uterine cancers. Here, we report results from a clinical trial of Rubus coreanus Miq. and Astragalus membranaceus Bunge as agents for improving the menopause syndrome. METHODS: This study was a single-centre, double-blinded, parallel-group, placebo-controlled study. The efficacy of an extract of R. coreanus Miq. and A. membranaceus Bunge was investigated. Participants were females with postmenopausal syndrome in the menopausal or menopausal transition period. The primary endpoint of validation was improvement in the Kupperman index (KI) score of women. The secondary end point was change in the Menopause Rating Scale (MRS) and lipid profile. The participants were randomly allocated at a 1 : 1 ratio into R. coreanus Miq. and A. membranaceus Bunge extract (RCAM) or placebo groups and were administered 2000 mg of the extract or placebo, respectively, daily for 12 weeks. Outcomes were measured at visits 2 (day 0) and 5 (week 12). RESULTS: The RCAM group demonstrated decreased KI score and MRS compared with the placebo group after 12 weeks. In the safety evaluation, laboratory tests and vital signs demonstrated no clinically significant changes in subjects, and there was no difference in adverse reactions between the groups. The R. coreanus Miq. and A. membranaceus Bunge extract was effective in reducing postmenopausal symptoms in women. Moreover, the extract was found to be safe. CONCLUSIONS: For females with menopausal symptoms in the menopausal transitional and postmenopausal periods, ingestion of the R. coreanus Miq. and A. membranaceus Bunge extract for 12 weeks was effective, as demonstrated by a decrease in KI score and MRS relative to that in the placebo group, and significantly improved the menopausal symptoms.

Factors influencing use of conventional and traditional Korean medicine-based health services: a nationwide cross-sectional study.

BACKGROUND: In Korea, conventional medicine (CM) and traditional Korean medicine (KM) are run as a dual healthcare system; however, the backgrounds and characteristics of the users of both medical services have not yet been compared. This study aimed to identify the differences in factors determining the use of CM and KM health services. METHODS: A secondary data analysis of a nationwide cross-sectional survey was conducted in this study. The Survey on the Experience with Healthcare Services 2017 asked participants about their most recent outpatient visit to a health service. Initially, a descriptive analysis was performed on respondents who visited the CM or KM health service in the last 12 months. Then, logistic regression analysis using Andersen's behavioral model was performed, to identify the factors affecting health service selection, by classifying demographic variables into predisposing, enabling, and need factors. Respondents who replied they did not frequently use CM/KM and those with missing data were excluded. RESULTS: Of the total 11,098 respondents, 7,116 (64.1%) reported to have used CM/KM: 2,034 (18.3%), 4,475 (40.3%), and 607 (5.5%) for hospital CM, clinic CM, and KM, respectively. In logistic regression analysis, of the 2,723 (24.5%) respondents analyzed, 822 (7.4%) went to a hospital, 1,689 (15.2%) to a clinic, and 212 (1.9%) opted for KM service. Respondents with a higher number of chronic diseases were less likely to use KM (one disease, odds ratio: 0.52, 95% confidence interval: 0.36-0.76; two diseases: 0.51, 0.31-0.85; three to five diseases: 0.26, 0.10-0.69). Respondents with a high income were likely to go to the hospital (4Q vs. 1Q: 1.92, 1.35-2.72) and less likely to go to the clinic (4Q vs. 1Q: 0.49, 0.35-0.68). CONCLUSIONS: Significant differences were observed on the enabling factor (income) for CM and need factors (number of chronic diseases) for KM. Our analysis suggests that through the healthcare policy, we should consider stratifying user backgrounds and needs for each medical service.

Portable Cold Atmospheric Plasma Patch-Mediated Skin Anti-Inflammatory Therapy.

Although plasma is a promising technology in various fields, its clinical application is restricted by several limitations. A cold atmospheric plasma (CAP) patch is fabricated to help overcome hurdles, especially when treating skin diseases. This patch has surface dielectric barrier discharge, which generates reactive oxygen species (ROS) and reactive nitrogen species (RNS) on a flexible polymer film surface on which the embedded electrode induces a locally strong electric field. The effect of the CAP patch on psoriasis is also evaluated. The distinct characteristics of psoriasis between the lesion and non-lesion area allow the CAP patch to be suitable for only lesion area for its treatment. The CAP patch induces the opening of calcium channels in keratinocytes, thereby restoring abnormal keratinocyte differentiation and the collapse of the tight junction; thus, alleviating psoriatic symptoms. In addition, the favorable effect is due to the induction of ROS/RNS by the CAP patch, not the electric field generated during plasma generation. The findings indicate that the proposed portable CAP patch can help treat inflammatory skin disorders, especially psoriasis. As this can be used easily as a combination therapy with existing drugs, it may help reduce side effects caused by existing drugs.

Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice.

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.

Ubiquitin pathways regulate the pathogenesis of chronic liver disease.

Chronic liver disease (CLD) is considered the leading cause of global mortality. In westernized countries, increased consumption of alcohol and overeating foods with high fat/ high glucose promote progression of CLD such as alcoholic liver disease (ALD) and non-alcoholic liver disease (NAFLD). Accumulating evidence and research suggest that ubiquitin, a 75 amino acid protein, plays crucial role in the pathogenesis of CLD through dynamic post-translational modifications (PTMs) exerting diverse cellular outcomes such as protein degradation through ubiquitin-proteasome system (UPS) and autophagy, and regulation of signal transduction. In this review, we present the function of ubiquitination and latest findings on diverse mechanism of PTMs, UPS and autophagy which significantly contribute to the pathogenesis of alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cirrhosis, and HCC. Despite its high prevalence, morbidity, and mortality, there are only few FDA approved drugs that could be administered to CLD patients. The goal of this review is to present a variety of pathways and therapeutic targets involving ubiquitination in the pathogenesis of CLD. Further, this review summarizes collective views of pharmaceutical inhibition or activation of recent drugs targeting UPS and autophagy system to highlight potential targets and new approaches to treat CLD.