Background: Zinc homeostasis is essential for human health and is regulated by several zinc transporters including ZIP and ZnT. ZIP4 is expressed in the small intestine and is important for zinc absorption from the diet. We investigated in the present study the effects of Panax ginseng (P. ginseng) extract on modulating Zip4 expression and cellular zinc levels in mouse Hepa cells. Methods: Hepa cells were transfected with a luciferase reporter plasmid that contains metal-responsive elements, incubated with P. ginseng extract, and luciferase activity was measured. Using 65ZnCl2, zinc uptake in P. ginseng-treated cells was measured. The expression of Zip4 mRNA and protein in Hepa cells was also investigated. Finally, using a luciferase reporter assay system, the effects of several ginsenosides were monitored. Results: The luciferase activity in cells incubated with P. ginseng extract was significantly higher than that of control cells cultured in normal medium. Hepa cells treated with P. ginseng extract exhibited higher zinc uptake. P. ginseng extract induced Zip4 mRNA expression, which resulted in an enhancement of Zip4 protein expression. Furthermore, some ginsenosides, such as ginsenoside Rc and Re, enhanced luciferase activity driven by intracellular zinc levels. Conclusion: P. ginseng extract induced Zip4 expression at the mRNA and protein level and resulted in higher zinc uptake in Hepa cells. Some ginsenosides facilitated zinc influx. On the basis of these results, we suggest a novel effect of P. ginseng on Zip4-mediated zinc influx, which may provide a new strategy for preventing zinc deficiency.
Choi, Kyung Jin;Hwang, Jin Wook;Kim, Se Hoon;Park, Hyung Seo
The Korean Journal of Physiology and Pharmacology
/
v.26
no.3
/
pp.219-225
/
2022
Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca2+ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na+/Ca2+ exchanger (rNCX) in Ca2+ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca2+ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca2+ was ceased by substituting extracellular Na+ with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca2+ oscillation. Type 1 Na+/Ca2+ exchanger (NCX1) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca2+ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.
BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.
Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that produces attaching and effacing lesions on the large intestine and causes hemorrhagic colitis. It is primarily transmitted through the consumption of contaminated meat or fresh produce. Similar to other bacterial pathogens, antibiotic resistance is of concern for EHEC. Furthermore, since the production of Shiga toxin by this pathogen is enhanced after antibiotic treatment, alternative agents that control EHEC are necessary. This study aimed to discover alternative treatments that target virulence factors and reduce EHEC toxicity. The locus of enterocyte effacement (LEE) is essential for EHEC attachment to host cells and virulence, and most of the LEE genes are positively regulated by the transcriptional regulator, Ler. GrlA protein, a transcriptional activator of ler, is thus a potential target for virulence inhibitors of EHEC. To identify the GrlA inhibitors, an in vivo high-throughput screening (HTS) system consisting of a GrlA-expressing plasmid and a reporter plasmid was constructed. Since the reporter luminescence gene was fused to the ler promoter, the bioluminescence would decrease if inhibitors affected the GrlA. By screening 8,201 compounds from the Korea Chemical Bank, we identified a novel GrlA inhibitor named Grlactin [3-[(2,4-dichlorophenoxy)methyl]-4-(3-methylbut-2-en-1-yl)-4,5-dihydro-1,2,4-oxadiazol-5-one], which suppresses the expression of LEE genes. Grlactin significantly diminished the adhesion of EHEC strain EDL933 to human epithelial cells without inhibiting bacterial growth. These findings suggest that the developed screening system was effective at identifying GrlA inhibitors, and Grlactin has potential for use as a novel anti-adhesion agent for EHEC while reducing the incidence of resistance.
Objectives: The aim of this study is to modernize Nutrient Qi(營氣) and Defense Qi(衛氣) from the point of view of Visceral Body and Somatic Body. Methods: Investigate the areas of body and function of Nutrient Qi(營氣) and Defense Qi(衛氣) recorded in the 『HuangdiNeijing(黃帝內經)』 and 『Dongeuibogam(東醫寶鑑)』. And investigate Visceral Body and Somatic Body that anatomical structure is divided according to function based on the book 『Life and Rhythm』. Results: Nutrient Qi(營氣) works to nourish the body such as viscera and bowels in the meridian. Defense Qi(衛氣) works to protect the body such as skin, limb joint, eye outside the meridian. The human body is divided into Visceral Body called a vegetable organ and Somatic Body called an animal organ. Visceral body is the organ that manages "nutrition-reproductive" and is divided into the intestine(腸管), blood vessels(血管), and the nephridium(腎管). Somatic Body is an organ that manages 'sensory-motion' and is divided into a three-layer structure: the outer layer covering the body surface, the nerve layer connecting the outer layer and the muscle layer, and the muscle layer controling contraction and movement. Conclusions: It is estimated that Nutrient Qi(營氣) is similar to Visceral Body, and Defense Qi(衛氣) is similar to Somatic Body.
Objective : The purpose of this dissertation is to make a list of the Ceramiales growing naturally in the Korean coastal waters, and to carry out a survey on the current distribution status to investigate the Ceramiales which can be used as medicinal herbs. Methods : References and research papers about herbology published at home and abroad were examined. Results : The results of this study were as follows: 1. A total of 60 genera and 157 species of Ceramiales was found in the Korean coastal waters among which 5 genera and 6 species(approximately 4%) were medicinal plants. 2. Out of the 157 species of Ceramiales 67 species belonged to Rhodomelaceae, and out of the 6 species of medicinal plants 3 species belonged to Ceramiacera. 3. Among the medicinal parts 6 species belonged to algae. 2 species had flatness property, and 3 species had salty flavors. 4. As for the domestic distribution of medicinal plants, four species are distributed on the coast of the country, and Charmakji Caloglossa leprieuriii is distributed at the mouth of the Nakdonggang River and Goheung, Jeollanam-do. 5. 6 species had the efficacy of Spleen, stomach and large intestine meridian 2 species had the potency of remove phlegm, which helps to remove quench one's phlegm in human body. 6. None of the total medicinal Ceramiales were toxic. Conclusion : There were totaled to 60 genera and 157 species in Theaceae in Korea and among them medicinal plants are 5 genera, 9 species, some 4% in total.
Donghyun Lee;Jayun Joo;Hunseok Choi;Seonghyeon Son;Jonghyun Bae;Dong Wook Kim;Eun Jin Kim
Journal of Microbiology and Biotechnology
/
v.34
no.9
/
pp.1757-1768
/
2024
The expression of two major virulence factors of Vibrio cholerae, cholera toxin (CT) and toxin co-regulated pilus (TCP), is induced by environmental stimuli through a cascade of interactions among regulatory proteins known as the ToxR regulon when the bacteria reach the human small intestine. ToxT is produced via the ToxR regulon and acts as the direct transcriptional activator of CT (ctxAB), TCP (tcp gene cluster), and other virulence genes. Unsaturated fatty acids (UFAs) and several small-molecule inhibitors of ToxT have been developed as antivirulence agents against V. cholerae. This study reports the inhibitory effects of fatty acids and virstatin (a small-molecule inhibitor of ToxT) on the transcriptional activation functions of ToxT in isogenic derivatives of V. cholerae strains containing various toxT alleles. The fatty acids and virstatin had discrete effects depending on the ToxT allele (different by 2 amino acids), V. cholerae strain, and culture conditions, indicating that V. cholerae strains could overcome the effects of UFAs and small-molecule inhibitors by acquiring point mutations in toxT. Our results suggest that small-molecule inhibitors should be examined thoroughly against various V. cholerae strains and toxT alleles during development.
This paper was written in order to understand each constitutional symptoms and diseases with two aspects. The first was to trace the courses to accomplish constitutional symptoms and diseases from that of oriented medicine through "Dongyi Bogam" and the original writing such as "Shanghanlun". The second was to analyze the constitutional diseases with Lee Je-ma's own recognition on human being and the society which was based on the "Dongyi Suse Bowon". The original concepts of 'The Interior Disease' and 'The Exterior Disease' were based on the Nature and the Emotion, the Environmental Frames and the Human Affairs, the Ears Eyes Nose Mouth and the Lung Spleen Liver Kidney. The exterior disease were caused by the abilities of ears to listen, eyes to see, nose to smell, and mouth to taste on the environmental frames which were related one's recognition to society. The interior diseases were caused by the abilities of lung to study, spleen to ask, liver to think, kidney to judge on human affairs which were related the relationship between me and others. So the titles of constitutional diseases were named by these views on his first writing of "Dongyi Suse Bowon" in 1894. So the titles of Taeyangin diseases, 'The lumbar Vertebae Disease Induced by Exopathogen' and 'The Small Intestine Disease Induced by Endopathogen' were still remained as the first writing. But the titles of constitutional diseases were rewritten such as present titles in 1900. In order to express pathology and mechanism of constitutional diseases exactly, he rewrote titles which contained the manifestation sites of diseases, and the symptoms of febrile and cold, and the different congenital formations of organs. The exterior diseases and interior diseases had three characteristics. The first was that the exterior disease injured by the nature which had a tendency to progress slowly and the interior disease injured by the emotion which had a tendency to progress rapidly. The second was not that the interior disease and the exterior disease were separated, but that one influenced the other and these were revealed as a disease together when the diseases continued for a long time. The third was that even though the disease caught together it was included the beginning disease. The symptoms in ordinary times was the origin and clue to recognize the constitutional symptoms and diseases. It enabled to establish the constitutional medicine which treated by different ways according to constitution. It had two characteristics which were different from the Traditional Chinese Medicine in appearance of diseases. The first was that the disease was progressed to the next step from the symptoms in ordinary times. The second was that each constitution had different symptoms which were due to symptoms in ordinary times under the same disease, The third was the manifestation of disease were different from symptoms in ordinary times in the same constitution. But the most important thing was that Lee Je-ma recognized these symptoms in ordinary times as four categories and he presented constitutional symptoms and constitutional disease. The four categories were the method to recognize the human being and the diseases for him As the symptoms and diseases of Sasang Constitutional Medicine were compared to Traditional Chinese Medicine, the constitutional diseases of "Dongyi Suse Bowon" could be classified into two groups. The first group was the unique diseases and symptoms, which were not in the Traditional Chinese Medicine, and which were established by the Lee Je-ma. These contained the diseases of taeyangin, the exterior disease of taeumin, the exterior disease of soyangin. The second group used the unique methods to treat disease, which were not in Traditional Chinese Medicine, and which were established by Lee Je-ma. This contained the interior disease of taeumin, the delirium diseases from the MangYin of soyangin, the treatment to help the Yang-Qi ascend and to supplement the ql In the exterior disease of soeumin. Especially, the diseases of taeyangin and taeumin which were caused by the metabolism disorders of Qi-Yack(氣液) were the great achievement to establish constitutional symptoms and diseases. The discourse of taeyangin diseases presented his original thought to recognize the symptoms and diseases through the Shin Gi Hyul Jeong(神氣血精) and the Qi-Yack, the discourse of taeumin diseases presented the disperse of Qi-Yack through the forward and backward of sweat, the discourse of soyangin disease presented the sweat of hand and feet which was manifested that yin-qi of spleen descended to yin qi of kidney, and the bowel movement which was manifested that yang qi of large intestine ascend to head, face and four extremities, the discourse of soeumin disease presented the Jueyin syndrome without the abdominal pain and diarrhea as the exterior disease and made importance to the nervous mind And the classification of exterior diseases and interior diseases were not due to the pharmacology but due to the symptoms and diseases according to the constitution.
A growth trial and a digestibility trial were conducted to examine the effect of feed particle size on the performance, nutrient digestibility, gastric ulceration and intestinal morphology in pigs fed barley-based diets. Barley was processed through a hammer mill to achieve four diets varying in particle size (average particle $size{\pm}standard $deviation): coarse ($1,100{\pm}2.19\;{\mu}m$), medium ($785{\pm}2.23\;{\mu}m$), fine ($434{\pm}1.70\;{\mu}m$) and mixed (1/3 of coarse, medium and fine) ($789{\pm}2.45\;{\mu}m$). Sixty-four entire male pigs were used in the growth trial and the diets were fed ad libitum between 31 kg and 87 kg live weight. Following slaughter, stomach and ileal tissues were scored for integrity (ulceration or damage) and histological measurements taken. Twenty-four entire male pigs were used in the digestibility trial, which involved total faecal collection. Over the entire growth phase, there were no differences (p>0.05) in average daily gain and feed conversion ratio between pigs fed diets of different particle size. Pigs fed the coarse and medium diets had lower (p<0.05) stomach ulceration scores (0.20 and 0.25, respectively, on a scale from 0 to 3) than those fed the mixed (0.69) or the fine diets (1.87). The stomachs of all animals fed the fine diet had lesions and stomach ulcerations were present only in this group. Pigs fed the fine diet had thicker (p<0.001) ileal epithelial cell layer with no differences (p>0.05) being observed for villous height or crypt depth. Faecal digestibility coefficients of neutral and acid detergent fibre were the highest (p<0.05) for the mixed diet, intermediate for the fine and coarse diets and the lowest for the medium diet. A similar numerical trend (p = 0.103) was observed for the apparent faecal energy digestibility coefficient. It is concluded that, with barley based diets, a variation in average particle size between $400{\mu}m$ and $1,100{\mu}m$ had no effect on pig performance but the fine dietary particle size affected the integrity of the stomach, as well as the structure of the small intestine, thus compromising overall gut health. Our data also demonstrate that changes in particle size distribution during the digestion process, rather than average particle size or particle size variation, are related to apparent faecal digestibility.
This study was devised to elucidate whether soused shrimp exhibits a digestive action on boiled pork meats. and the mechanism by which sousing with a high concentration of sodium chloride preserves nutrients in foods for a prolonged pe\ulcornerriod. Protease was isolated from soused shrimp using a combination of ammonium sulfate fractionation. DEAE - cellulose ion exchange chromatography and gel filtra\ulcornertion. The isolated protease had specific activity of 1.560 units. 210 purification fo\ulcornerld with an yield of 38%. Its optimum pH and temperature were 8.0 and $43^{\circ}C$ respectively. The molecular weight of the enzyme was 35.000. The Km value of the enzyme for casein was 1.6 x $10^{-6}$ M The e=yme required the presence of cu\ulcornerpric ion to exhibit its full activity. Eighty eight percent of the enzyme activity was in\ulcornerhibited by 3.5M NaCI showing a reversibly linear decrease of the enzyme activity as NaCI concentration increased. The nature of the inhibition by NaCl was rever\ulcornersible and noncompetitive. The protease activity in soused shrimp was well preser\ulcornerved with the elapse of time at least in part due to NaCI induced suppression of autodigestion. The enzyme was denatured by acid easily. i.e. 1% of the original activity remained after staying at pH 2 for 10 minutes. which is within the norm\ulcorneral range of pH of the human stomach. Soused shrimp was observed to be one of those containing the highest protease activity compared with the other soused foo\ulcornerds such as soused oyster. squid. clam. and Pollack intestine with respect to spec\ulcornerific activities of dialized 1:4 whole homogenates(w/v) in 5 mM sodium phospha\ulcornerte - 2.4 mM j3 - mercaptoethanol buffer. pH 8.0. Casein and boiled meats including pork, beef, and chicken appeared to be the good substrates for the protease. Casein was the best. Therefore. the ingestion of boiled meats including pork together with soused sh\ulcornerrimp would help digestion of boiled pork in human not only by increasing appe\ulcornertite also by the direct proteolytic digestion of boiled meats by soused shrimp to\ulcorner some extent. And a high concentration of sodium chloride inhibited the protease activity reversibly in a remarkable degree, which ensued in a significant retardat\ulcornerion of autodigestion of protein in foods by proteases, and hereby contributed to the preservation of foods for an extended period.
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