Yeokwisan, a Standardized Herbal Formula, Enhances Gastric Emptying via Modulation of the Ghrelin Pathway in a Loperamide-induced Functional Dyspepsia Mouse Model.

Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 µL) or diet of 5% charcoal (200 µL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues. Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor ß1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine. Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

The Interrelationships between Intestinal Permeability and Phlegm Syndrome and Therapeutic Potential of Some Medicinal Herbs.

The gastrointestinal (GI) tract has an intriguing and critical role beyond digestion in both modern and complementary and alternative medicine (CAM), as demonstrated by its link with the immune system. In this review, we attempted to explore the interrelationships between increased GI permeability and phlegm, an important pathological factor in CAM, syndrome, and therapeutic herbs for two disorders. The leaky gut and phlegm syndromes look considerably similar with respect to related symptoms, diseases, and suitable herbal treatment agents, including phytochemicals even though limitations to compare exist. Phlegm may be spread throughout the body along with other pathogens via the disruption of the GI barrier to cause several diseases sharing some parts of symptoms, diseases, and mechanisms with leaky gut syndrome. Both syndromes are related to inflammation and gut microbiota compositions. Well-designed future research should be conducted to verify the interrelationships for evidence based integrative medicine to contribute to the promotion of public health. In addition, systems biology approaches should be adopted to explore the complex synergistic effects of herbal medicine and phytochemicals on conditions associated with phlegm and leaky gut syndromes.

The Use of Microplates for Internal Fixation of Comminuted Mandibular Fractures.

BACKGROUND: Although clinical trials have successfully applied microplates for the internal fixation of single or double isolated mandibular fractures, the use of microplate systems in comminuted mandibular fractures is not widely accepted. This study aimed to evaluate the use of microplates for internal fixation of comminuted mandible fractures and to discuss their applicability. METHODS: Fourteen patients with comminuted mandibular fractures (10 at a single region, 3 at 2 regions, and 1 at 4 regions) were treated with open reduction and internal fixation using 0.5- or 0.6-mm-thick titanium microplates and 1.0-, 1.2-, or 1.3-mm monocortical microscrews. Three-level fixation at the lower border, upper border (as interdental wiring), and middle of the mandible was performed. Maxillomandibular fixation was applied only when premature occlusal contact was observed after fracture fixation. RESULTS: During the follow-up period (3-55 months), all fractures showed favorable and complete bone healing. Six patients experienced minor complications, including minimal malocclusion (n = 5) and a localized infection (n = 1). Most of these complications were managed with conservative treatment. No major complications that required further orthodontic treatment or reoperation occurred. CONCLUSIONS: These results suggest that 3-level fixation using microplates is appropriate for the reconstruction of comminuted mandibular fractures without bony defects. The small size and malleability of these devices facilitate accurate anatomical reduction for complete contact of the comminuted bony segments by multiple fixation. Furthermore, microplates allow for preservation of sufficient periosteal blood supply and restoration of premorbid occlusion (by occlusal self-adjustment) while providing sufficient stability.

Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS: DHP1401 (50µg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.

A Wrapping Method for Inserting Titanium Micro-Mesh Implants in the Reconstruction of Blowout Fractures.

Titanium micro-mesh implants are widely used in orbital wall reconstructions because they have several advantageous characteristics. However, the rough and irregular marginal spurs of the cut edges of the titanium mesh sheet impede the efficacious and minimally traumatic insertion of the implant, because these spurs may catch or hook the orbital soft tissue, skin, or conjunctiva during the insertion procedure. In order to prevent this problem, we developed an easy method of inserting a titanium micro-mesh, in which it is wrapped with the aseptic transparent plastic film that is used to pack surgical instruments or is attached to one side of the inner suture package. Fifty-four patients underwent orbital wall reconstruction using a transconjunctival or transcutaneous approach. The wrapped implant was easily inserted without catching or injuring the orbital soft tissue, skin, or conjunctiva. In most cases, the implant was inserted in one attempt. Postoperative computed tomographic scans showed excellent placement of the titanium micro-mesh and adequate anatomic reconstruction of the orbital walls. This wrapping insertion method may be useful for making the insertion of titanium micro-mesh implants in the reconstruction of orbital wall fractures easier and less traumatic.

Penicillipyrones A and B, meroterpenoids from a marine-derived Penicillium sp. fungus.

Penicillipyrones A (1) and B (2), two novel meroterpenoids, were isolated from the marine-derived fungus Penicillium sp. On the basis of the results of combined spectroscopic analyses, these compounds were structurally elucidated to be sesquiterpene γ-pyrones from a new skeletal class derived from a unique linkage pattern between the drimane sesquiterpene and pyrone moieties. Compound 2 elicited significant induction of quinone reductase.

Ohmyungsamycins A and B: cytotoxic and antimicrobial cyclic peptides produced by Streptomyces sp. from a volcanic island.

Ohmyungsamycins A and B (1 and 2), which are new cyclic peptides, were isolated from a marine bacterial strain belonging to the Streptomyces genus collected from a sand beach on Jeju, a volcanic island in the Republic of Korea. Based on the interpretation of the NMR, UV, and IR spectroscopic and MS data, the planar structures of 1 and 2 were elucidated as cyclic depsipeptides bearing unusual amino acid units, including N-methyl-4-methoxytrytophan, ß-hydroxyphenylalanine, and N,N-dimethylvaline. The absolute configurations of the α-carbons of the amino acid residues were determined using the advanced Marfey's method. The configurations of the additional stereogenic centers at the ß-carbons of the threonine, N-methylthreonine, and ß-hydroxyphenylalanine units were assigned by GITC (2,3,4,6-tetra-O-acetyl-ß-D-glucopyranosyl isothiocyanate) derivatization and the modified Mosher's method. We have developed a new method utilizing PGME (phenylglycine methyl ester) derivatization coupled with chromatographic analysis to determine the absolute configuration of N,N-dimethylvaline. Our first successful establishment of the absolute configuration of N,N-dimethylvaline using PGME will provide a general and convenient analytical method for determining the absolute configurations of amino acids with fully substituted amine groups. Ohmyungsamycins A and B showed significant inhibitory activities against diverse cancer cells as well as antibacterial effects.