Morinda citrifolia Extract Prevents Alcoholic Fatty Liver Disease by Improving Gut Health.

Alcoholic liver disease (ALD) is a major chronic liver disease. Chronic alcohol consumption induces dysbiosis, disruption of gut barrier function, oxidative stress, inflammation, and changes in lipid metabolism, thereby leading to ALD. In this study, we investigated whether the commercial Morinda citrifolia extract Nonitri can ameliorate ALD symptoms through the gut-liver axis. We used mice chronically administered EtOH and found a marked increase in serum endotoxin levels and biomarkers of liver pathology. Moreover, the EtOH-treated group showed significantly altered gut microbial composition particularly that of Alistipes, Bacteroides, and Muribaculum and disrupted gut barrier function. However, Nonitri improved serum parameters, restored the microbial proportions, and regulated levels of zonula occludens1, occludin, and claudin1. Furthermore, Nonitri suppressed inflammation by inhibiting endotoxin-triggered toll-like receptor 4-signaling pathway and fat deposition by reducing lipogenesis through activating AMP-activated protein kinase in the liver. Furthermore, Pearson's correlation analysis showed that gut microbiota and ALD-related markers were correlated, and Nonitri regulated these bacteria. Taken together, our results indicate that the hepatoprotective effect of Nonitri reduces endotoxin levels by improving gut health, and inhibits fat deposition by regulating lipid metabolism.

Effectiveness and Safety of Combination Therapy with Herbal Medicine and Growth Hormone Compared to Growth Hormone Monotherapy for Short Stature Children: A Systematic Review and Meta-Analysis.

Introduction: Herbal medicines (HM) and growth hormones (GH) are widely used to treat short stature (SS) in children. This systematic review aimed to evaluate the effectiveness and safety of combination therapy with HM and GH (CHG) compared to those of GH monotherapy (GHM) in children with SS. Methods: We searched 17 electronic databases from inception to 1 April 2021. Only randomized controlled trials (RCTs) were included. Two authors independently performed the selection and quality assessment of the included studies using Cochrane Handbook criteria. Relative risk (RR) was used to measure dichotomous outcomes with a 95% confidence interval (CI). Mean difference (MD) or standard MD (SMD) was used to measure continuous outcomes with a 95% CI. Results: Seven RCTs involving 455 participants with SS were included. Standard deviations in height (MD = 0.31, 95% CI: 0.24-0.38, p < 0.00001), and insulin-like growth factor binding protein-3 (MD = 1.39, 95% CI: 0.93-1.85, p < 0.00001) were significantly higher in the CHG group than in the GHM group. Growth velocity (MD = 1.82, 95% CI: 1.34-2.31, p < 0.00001) and insulin-like growth factor-1 (MD = 61.85, 95% CI: 55.80-67.90, p < 0.00001) were significantly higher in the CHG group. Adverse events were significantly lower in the CHG group (risk ratio: 0.10, 95% CI: 0.02-0.54, p = 0.007). However, the level of evidence was low. Conclusions: CHG demonstrated significantly better efficacy than GHM for treating SS, with a low incidence of adverse events. However, since the level of evidence is low, methodologically standardized RCTs are required to verify these results.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

Inhibitory effect of sea buckthorn extracts on advanced glycation endproduct formation.

This study shows the inhibitory effect of sea buckthorn (Hippophae rhamnoides L.) extracts, sea buckthorn leaf (HRL) and berry (HRB), on the formation of advanced glycation endproducts (AGEs), closely linked to diverse disease. In vitro assay revealed the superior inhibitory effect of HRL on the AGEs formation and AGEs-induced collagen crosslinking compared with that of HRB. Ultra-performance liquid chromatography-mass spectrometry results revealed that HRL displays a higher inhibition efficiency on the AGEs formation at 30 AGEs binding sites in bovine serum albumin than HRB. The high concentration of 3-sophoroside-7-rhamnoside in HRL compared with that in HRB may result in the strong inhibitory effect of HRL compared with that of HRB. HRL also exhibited significantly higher ABTS and DPPH radical scavenging activities than HRB. Overall, this study demonstrated that HRL has excellent potential as a dietary agent for controlling various diseases mediated by AGEs and oxidative stress.

Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA.

Tristetraprolin (TTP), a well-characterized AU-rich element (ARE) binding protein, functions as a tumor suppressor gene. The purpose of this study was to investigate whether a bioactive substance derived from a natural medicinal plant affects the induction of TTP and to elucidate its mechanism. We examined the effects of natural bioactive materials including Resveratrol (RSV), thymoquinone (TQ) and curcumin on the expression of TTP in cancer cell. TQ derived from a natural plant Nigella sativa increased the expression levels of TTP mRNA and proteins in a dose-dependent manner in gastric and breast cancer cells. TQ-induced TTP increased the instability of MUC4 mRNA by direct binding of TTP to ARE in the 3'UTR of MUC4 mRNA. The induction of TTP by TQ also reduced the proliferation, migration and invasion of cancer cells. The expression of the epithelial-mesenchymal (EMT)-related genes, which were target genes of TTP, was also decreased by the TQ treatment. In the in vivo experiments using mouse melanoma cells, TQ-induced TTP inhibited metastasis of tumor cells. We have found that TQ-induced TTP might inhibit metastasis by reducing tumor cell migration and invasion through destabilization of MUC4 mRNA, which suggest the MUC4 as a novel target to TTP.

Hepatoprotective Effect of Kombucha Tea in Rodent Model of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.

Kombucha tea (KT) has emerged as a substance that protects the liver from damage; however, its mechanisms of action on the fatty liver remain unclear. Therefore, we investigated the potential role of KT and its underlying mechanisms on nonalcoholic fatty liver disease (NAFLD). db/db mice that were fed methionine/choline-deficient (MCD) diets for seven weeks were treated for vehicle (M + V) or KT (M + K) and fed with MCD for four additional weeks. Histomorphological injury and increased levels of liver enzymes and lipids were evident in the M + V group, whereas these symptoms were ameliorated in the M + K group. The M + K group had more proliferating and less apoptotic hepatocytic cells than the M + V group. Lipid uptake and lipogenesis significantly decreased, and free fatty acid (FFA) oxidation increased in the M + K, when compared with the M + V group. With the reduction of hedgehog signaling, inflammation and fibrosis also declined in the M + K group. Palmitate (PA) treatment increased the accumulation of lipid droplets and decreased the viability of primary hepatocytes, whereas KT suppressed PA-induced damage in these cells by enhancing intracellular lipid disposal. These results suggest that KT protects hepatocytes from lipid toxicity by influencing the lipid metabolism, and it attenuates inflammation and fibrosis, which contributes to liver restoration in mice with NAFLD.

Profiling of glucose-induced transcription in Sulfolobus acidocaldarius DSM 639.

Sulfolobus species can grow on a variety of organic compounds as carbon and energy sources. These species degrade glucose to pyruvate by the modified branched Entner-Doudoroff pathway. We attempted to determine the differentially expressed genes (DEGs) under sugar-limited and sugar-rich conditions. RNA sequencing (RNA-seq) was used to quantify the expression of the genes and identify those DEGs between the S. acidocaldarius cells grown under sugar-rich (YT with glucose) and sugar-limited (YT only) conditions. The functions and pathways of the DEGs were examined using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time PCR (qRT-PCR) was performed to validate the DEGs. Transcriptome analysis of the DSM 639 strain grown on sugar-limited and sugar-rich media revealed that 853 genes were differentially expressed, among which 481 were upregulated and 372 were downregulated under the glucose-supplemented condition. In particular, 70 genes showed significant changes in expression levels of ≥ twofold. GO and KEGG enrichment analyses revealed that the genes encoding components of central carbon metabolism, the respiratory chain, and protein and amino acid biosynthetic machinery were upregulated under the glucose condition. RNA-seq and qRT-PCR analyses indicated that the sulfur assimilation genes (Saci_2197-2204) including phosphoadenosine phosphosulfate reductase and sulfite reductase were significantly upregulated in the presence of glucose. The present study revealed metabolic networks in S. acidocaldarius that are induced in a glucose-dependent manner, improving our understanding of biomass production under sugar-rich conditions.

A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

Environmental asbestos exposure sources in Korea.

BACKGROUND: Because of the long asbestos-related disease latencies (10-50 years), detection, diagnosis, and epidemiologic studies require asbestos exposure history. However, environmental asbestos exposure source (EAES) data are lacking. OBJECTIVES: To survey the available data for past EAES and supplement these data with interviews. METHODS: We constructed an EAES database using a literature review and interviews of experts, former traders, and workers. Exposure sources by time period and type were visualized using a geographic information system (ArcGIS), web-based mapping (Google Maps), and OpenWeatherMap. The data were mounted in the GIS to show the exposure source location and trend. RESULTS: The majority of asbestos mines, factories, and consumption was located in Chungnam; Gyeonggi, Busan, and Gyeongnam; and Gyeonggi, Daejeon, and Busan, respectively. Shipbuilding and repair companies were mostly located in Busan and Gyeongnam. CONCLUSIONS: These tools might help evaluate past exposure from EAES and estimate the future asbestos burden in Korea.

Chemical composition and antimicrobial activity of the essential oil of apricot seed.

In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography-mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram-positive bacteria, Gram-negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram-positive bacteria, Gram-negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested.