Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

BACKGROUND: Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. METHODS: A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0-4) followed by 4 weeks of follow-up (weeks 4-8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. DISCUSSION: This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

Benefits of Flavored Lactose-Free Milk for Korean Adults with Lactose Intolerance.

Although lactose-free dairy products for the clinical management of lactose intolerance (LI) are widely available, scientific evidence on their efficacy is still lacking. This study comparatively analyzed the efficacy of flavored lactose-free milk (LFM) and whole milk (WM) in reducing symptoms in South Korean adults with LI. This prospective study was conducted in adults suspected of LI. All screened participants underwent the hydrogen breath test (HBT) using 570 mL of chocolate-flavored WM (20 g of lactose) and responded to a symptom questionnaire. LI was confirmed when the ΔH2 peak exceeded 16 ppm above baseline values and with the occurrence of symptoms after WM consumption. The participants who were diagnosed with LI underwent the HBT again with 570 mL of chocolate-flavored LFM (0 g of lactose), followed by the symptom questionnaire survey after 1 week. After excluding 40 participants who did not meet the diagnostic criteria for LI and 2 who were lost to follow-up, a total of 28 lactose-intolerant individuals were enrolled in the study. The ΔH2 values in the first HBT were significantly higher than those in the second HBT (33.3 ± 21.6 ppm vs. 8.6 ± 6.3 ppm, P < .001). Similarly, there was a significant reduction in the total symptom score in the second HBT (4.18 ± 1.51 vs. 0.61 ± 0.98, P < .001). Flavored LFM is well tolerated in South Korean adults diagnosed with LI based on the HBT and symptom questionnaire results. Therefore, LFM may be a viable alternative to WM.

Herbal Therapies in Functional Gastrointestinal Disorders: A Narrative Review and Clinical Implication.

The pathophysiology of functional gastrointestinal disorders (FGIDs) is still unclear and various complex mechanisms have been suggested to be involved. In many cases, improvement of symptoms and quality of life (QoL) in patients with FGIDs is difficult to achieve with the single-targeted treatments alone and clinical application of these treatments can be challenging owing to the side effects. Herbal preparations as complementary and alternative medicine can control multiple treatment targets of FGIDs simultaneously and relatively safely. To date, many herbal ingredients and combination preparations have been proposed across different countries and together with a variety of traditional medicine. Among the herbal therapies that are comparatively considered to have an evidence base are iberogast (STW-5) and peppermint oil, which have been mainly studied and used in Europe, and rikkunshito and motilitone (DA-9701), which are extracted from natural substances in traditional medicine, are the focus of this review. These herbal medications have multi-target pharmacology similar to the etiology of FGIDs, such as altered intestinal sensory and motor function, inflammation, neurohormonal abnormality, and have displayed comparable efficacy and safety in controlled trials. To achieve the treatment goal of refractory FGIDs, extensive and high quality studies on the pharmacological mechanisms and clinical effects of these herbal medications as well as efforts to develop new promising herbal compounds are required.

Effects of probiotics or broccoli supplementation on Helicobacter pylori eradication with standard clarithromycin-based triple therapy.

BACKGROUND/AIMS: The eradication failure rate of standard triple therapy (proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has increased owing to antibiotic resistance in Korea. We assessed whether Saccharomyces boulardii probiotic or broccoli sprout extract sulforaphane supplementation could increase the H. pylori eradication rate and/or reduce antibiotic-associated adverse events. METHODS: A total of 217 patients with H. pylori-positive chronic gastritis or peptic ulcer disease were recruited. Clarithromycin resistance was assessed in all patients by testing for A2142G and A2143G point mutations in H. pylori 23S rRNA using a dual-priming polymerase chain reaction (PCR) oligonucleotide. Thirty-four patients (17.3%) were clarithromycin-resistant and were excluded from the study. Finally, 183 patients with infections not resistant to clarithromycin were randomly assigned to triple therapy only (group A, n = 61), triple therapy plus probiotics (group B, n = 61), or triple therapy plus sulforaphane (group C, n = 61) groups. CYP2C19 polymorphisms were examined at position G681A of exon 5 and G636A of exon 4 by PCR with restriction fragment length polymorphism (PCR-RFLP) analysis. H. pylori eradication was assessed by 13C-urea breath test 4 weeks after treatment completion. RESULTS: The eradication rates were similar among the groups both in the intention- to-treat (A = 85.2%, B = 89.6%, and C = 81.6%) and per-protocol (A = 89.2%, B = 86.8%, and C = 96.3%) analyses. The frequencies of overall adverse events in the groups also did not differ (A vs. B: p = 0.574; A vs. C: p = 1.000). CONCLUSION: Probiotic or sulforaphane with triple therapy for H. pylori infection neither increased the eradication rate nor reduced the occurrence of adverse events.

Structural and biochemical characterization of Rv0187, an O-methyltransferase from Mycobacterium tuberculosis.

Catechol O-methyltransferase (COMT) is widely distributed in nature and installs a methyl group onto one of the vicinal hydroxyl groups of a catechol derivative. Enzymes belonging to this family require two cofactors for methyl transfer: S-adenosyl-l-methionine as a methyl donor and a divalent metal cation for regiospecific binding and activation of a substrate. We have determined two high-resolution crystal structures of Rv0187, one of three COMT paralogs from Mycobacterium tuberculosis, in the presence and absence of cofactors. The cofactor-bound structure clearly locates strontium ions and S-adenosyl-l-homocysteine in the active site, and together with the complementary structure of the ligand-free form, it suggests conformational dynamics induced by the binding of cofactors. Examination of in vitro activities revealed promiscuous substrate specificity and relaxed regioselectivity against various catechol-like compounds. Unexpectedly, mutation of the proposed catalytic lysine residue did not abolish activity but altered the overall landscape of regiospecific methylation.

Medical Professionals' Review of YouTube Videos Pertaining to Exercises for the Constipation Relief.

BACKGROUND/AIMS: The primary aims of this study were to evaluate the content quality of YouTube videos on exercises to help relieve constipation and to assess whether the video source, exercise types, and popularity affected their quality. METHODS: Eight gastroenterologists independently evaluated the exercises presented in the constipation YouTube videos for seven items: image quality, usefulness in relieving constipation (quality 1), usefulness for general physical health (quality 2), difficulty in following, activity intensity, fun, and overall quality. Raters were asked open-ended questions to evaluate the strengths and weaknesses of the videos. Five-point ordinal scales were used to score each item aforementioned, with the exception of image quality and overall quality that used a six-point Likert scale. RESULTS: The 20 videos had a mean length of 268 seconds and a mean viewership of 32,694. The most common video source was commercial (n=10), and the most common type of physical activity was yoga (n=11). The median values of image quality, quality 1, quality 2, difficulty in following, activity intensity, fun, and overall quality were 3, 2, 2, 2, 2, 2, and 2, respectively. Yoga videos had significantly higher median quality 1 values (3) compared with massage videos (2, adjusted p=0.006) and 'others' videos (2, adjusted p<0.001). A lack of medical evidence was the most common answer to open-ended questions about the weaknesses of each video. CONCLUSIONS: Overall, YouTube exercise videos presented a low-quality content. This study highlights the need for evidence-based comprehensive educational videos addressing exercises for treating constipation.

Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification.

Enzyme-mediated modifications at the wobble position of tRNAs are essential for the translation of the genetic code. We report the genetic, biochemical and structural characterization of CmoB, the enzyme that recognizes the unique metabolite carboxy-S-adenosine-L-methionine (Cx-SAM) and catalyzes a carboxymethyl transfer reaction resulting in formation of 5-oxyacetyluridine at the wobble position of tRNAs. CmoB is distinctive in that it is the only known member of the SAM-dependent methyltransferase (SDMT) superfamily that utilizes a naturally occurring SAM analog as the alkyl donor to fulfill a biologically meaningful function. Biochemical and genetic studies define the in vitro and in vivo selectivity for Cx-SAM as alkyl donor over the vastly more abundant SAM. Complementary high-resolution structures of the apo- and Cx-SAM bound CmoB reveal the determinants responsible for this remarkable discrimination. Together, these studies provide mechanistic insight into the enzymatic and non-enzymatic feature of this alkyl transfer reaction which affords the broadened specificity required for tRNAs to recognize multiple synonymous codons.

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa.

BACKGROUND/AIMS: The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage. METHODS: The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (-) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a (13)C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay. RESULTS: BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups. CONCLUSIONS: BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.

Porcine SPARC: isolation from dentin, cDNA sequence, and computer model.

Genes encoding the major enamel matrix proteins and non-collagenous proteins of bone and dentin are members of the secretory calcium-binding phosphoprotein (SCPP) family, which originated from ancestral SPARC (secreted protein, acidic and rich in cysteine; BM-40/osteonectin). To better understand the role of SPARC in mineralizing systems, we isolated SPARC from developing pig teeth, deduced its primary structure from the cDNA sequence, and determined its quaternary structure by homology modelling with reference to human SPARC crystal structures. The guanidine/EDTA extract from porcine dentin was fractionated by anion-exchange and size-exclusion chromatography. Stains-all positive bands at 38 and 35 kDa gave the N-terminal sequences APQQEALPDETEV and DFEKNYNMYIFPV, which corresponded to the SPARC N terminus and an internal region of the protein. Porcine SPARC contains 300 amino acids, including the 17-amino acid signal peptide, and shares 96.2% amino acid sequence identity with human SPARC. Without post-translational modifications, the 283-amino acid secreted protein has a molecular mass of 32.3 kDa. The three-dimensional model revealed that porcine SPARC contains a single N-linked glycosylation at N113, seven intramolecular disulfide bridges, and assembles into dimers. SPARC is composed of three structural/functional domains: an acidic Ca2+-binding, a follistatin-like, and an extracellular calcium-binding domain.