Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

Background and Objectives: Diabetes can cause various vascular complications. The Compounded Danshen-Dripping-Pill (CDDP) is widely used in China. This study aimed to analyze the effectiveness and safety of CDDP in the blood viscosity (BV) with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a systematic search of seven databases from their inception to July 2022 for randomized controlled trials that used CDDP to treat T2DM. To evaluate BV, we measured low shear rate (LSR), high shear rate (HSR), and plasma viscosity (PV). Homocysteine and adiponectin levels were also assessed as factors that could affect BV. Results: We included 18 studies and 1532 patients with T2DM. Meta-analysis revealed that CDDP significantly reduced LSR (mean difference [MD] -2.74, 95% confidence interval [CI] -3.77 to -1.72), HSR (MD -0.86, 95% CI -1.08 to -0.63), and PV (MD -0.37, 95% CI -0.54 to -0.19) compared to controls. CDDP also reduced homocysteine (MD -8.32, 95% CI -9.05 to -7.58), and increased plasma adiponectin (MD 2.72, 95% CI 2.13 to 3.32). Adverse events were reported less frequently in the treatment groups than in controls. Conclusions: CDDP is effective in reducing BV on T2DM. However, due to the poor design and quality of the included studies, high-quality, well-designed studies are required in the future.

Evaluation of clinical effectiveness of blood stasis leaflet in patients with blood stasis: A prospective, randomized, and crossover trial.

BACKGROUND: Blood stasis (BS) refers to a pattern of symptoms resulting from circulatory dysfunction or stagnation in the human body. Due to its historical origin and diverse interpretations, communication between patients and doctors of traditional Korean medicine (DKMs) presents challenges. Efforts to improve patients understanding in traditional Korean medicine (TKM) have led to the development of disease-specific standard clinical practice guidelines. However, there is a limited focus on creating clinical practice guidelines or informative leaflet specifically addressing BS, which is a frequently encountered pattern of symptoms in TKM. METHODS: This study aimed to bridge the gap between patients and DKMs by developing an informative leaflet focusing on BS for metabolic diseases. We assessed its appropriateness through expert advisory meetings and the Delphi process, and evaluated its clinical effectiveness. We conducted a prospective, randomized, crossover trial to compare the clinical effectiveness of using BS leaflets in TKM treatment. The hypothesis investigated whether the leaflet group would show higher scores in satisfaction of DKMs' explanations, understanding of DKMs' explanations, improving the reliability of TKM, satisfaction with treatment time, improvement in explanations compared to previous TKM experiences, and necessity of managing BS treatment, compared to the no-leaflet group. RESULTS: In a study involving 40 patients (mean age: 62.3 ±â€…7.8 years), symptoms persisted for an average of 16.75 ±â€…9.3 hours daily, with a severity rating of 2.53. The leaflet group exhibited significantly higher satisfaction scores than the no-leaflet group in all aspects (all P < .0001). After confirming the absence of sequence and period effects using a linear-mixed effect model, we were able to ascertain the presence of a treatment effect, as evidenced by statistically significant higher scores across all survey items in the leaflet group compared to the no-leaflet group (all P < .0001). CONCLUSION: Expert consensus on symptoms aligning with the BS pattern resulted in the development of an informative leaflet. Its utilization notably improved patient satisfaction, comprehension, and trust in TKM treatment, unaffected by temporal influences, thus demonstrating its clinical effectiveness. In summary, the BS leaflet significantly enhanced patient understanding and optimized treatment procedures.

Two case reports of tapering sedative-hypnotic drugs through classical conditioning using herbal medicine (CARE-compliant).

RATIONALE: Sedative-hypnotic drugs (SHDs) used for insomnia are recommended for short-term use owing to concerns regarding abuse and dependence. Nevertheless, drug discontinuation is challenging owing to rebound insomnia that occurs when the SHD is ceased. Therefore, a strategy is required to reduce or discontinue SHDs, while minimizing rebound insomnia. PATIENT CONCERNS: The present report discusses the cases of a 72-year-old man and 27-year-old man with insomnia. Both patients had been taking SHDs for more than 2 months. DIAGNOSES: Both patients were diagnosed with primary insomnia. INTERVENTIONS AND OUTCOMES: After 2 weeks of classical conditioning (CC) using Hwangryunhaedok-tang (HHT), both patients succeeded in tapering SHD; the Korean version of the insomnia severity index of patient 1 dropped from 14 to 5, and that of patient 2 dropped from 28 to 11. In the final follow-up, the index dropped to 2 and 3, respectively. LESSONS: The CC, a concept emerging in psychology, could be a new strategy for tapering drugs. In this case, SHDs, which had been taken for a long time, were successfully reduced or discontinued through CC using HHT. Herbal medicine such as HHT is selected as a neutral stimulus for CC because the risk of rebound phenomenon is low as the compounds of herbal medicine have high structural similarities with human metabolites. Both patients in this study reported no particular challenges when HHT was discontinued. However, further studies are needed that will assist in tapering anticonvulsants or steroids as well as SHDs.

Validity and Reliability of POM-Checker for Measuring Shoulder Range of Motion in Healthy Participants: A Pilot Single-Center Comparative Study.

BACKGROUND: The aim of this study was to compare shoulder movement measurements between a Kinect-based markerless ROM assessment device (POM-Checker) and a 3D motion capture analysis system (BTS SMART DX-400). METHODS: This was a single-visit clinical trial designed to evaluate the validity and reliability of the POM-Checker. The primary outcome was to assess the equivalence between two measurement devices within the same set of participants, aiming to evaluate the validity of the POM-Checker compared to the gold standard device (3D Motion Analysis System). As this was a pilot study, six participants were included. RESULTS: The intraclass correlation coefficient (ICC) and the corresponding 95% confidence intervals (CIs) were used to assess the reproducibility of the measurements. Among the 18 movements analyzed, 16 exhibited ICC values of >0.75, indicating excellent reproducibility. CONCLUSION: The results showed that the POM-checker is reliable and validated to measure the range of motion of the shoulder joint.

The clinical effects of Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) on patients with hyperlipidemia: A study protocol for a multicenter, double-blind, two-armed parallel, investigator-initiated, exploratory randomized controlled trial.

BACKGROUND: Hyperlipidemia, the most common form of dyslipidemia, is associated with an increased risk of atherosclerotic cardiovascular diseases. There is a constant demand for therapeutic agents with relatively few side effects that can be administered from the initial stage of hyperlipidemia, herbal medicines derived from natural products can be considered candidates for treating dyslipidemia. This study aims to explore the feasibility, preliminary effectiveness, and safety of Gyejibongnyeong-Hwan (GBH) in patients with hyperlipidemia. METHODS: This was a 2-armed, parallel, multicenter, and exploratory randomized controlled trial on dyslipidemia. We will recruit 90 patients aged 20 to 65 years with hyperlipidemia between November 2021 and December 2022. Eligible participants will be randomly assigned to receive GBH or placebo granules for 8 weeks and followed up for 4 weeks after 4 weeks of lifestyle modification. The primary outcome is the percentage changes in low-density lipoprotein cholesterol from baseline to week 8. The secondary outcomes are percentage changes in other blood lipid parameters, blood glucose parameters, and blood stasis scores. As an exploratory outcome measure, metabolite analysis will be conducted to observe changes in metabolic patterns. DISCUSSION: This is the first randomized controlled trial to explore the clinical effect and safety of GBH compared to placebo control in patients with hyperlipidemia, thereby potentially facilitating better management of hyperlipidemia. The results of this pilot study could form a foundation for future large-scale confirmatory clinical trials. ETHICS AND DISSEMINATION: This study was permitted by the Ministry of Food and Drug Safety on investigational new drug application on August 12, 2021 and approved by the Institutional Review Board of Kyung Hee University, Seoul, Republic of Korea (KOMCIRB202110012001) on November 26, 2021. The results will be published in a peer-reviewed journal and disseminated electronically and in print.

Characteristics of Gait Event and Muscle Activation Parameters of the Lower Limb on the Affected Side in Patients With Hemiplegia After Stroke: A Pilot Study.

Objectives: To confirm the characteristics of gait events and muscle activity in the lower limbs of the affected and unaffected sides in patients with hemiplegia. Design: Cross-sectional study. Setting: Motion analysis laboratory of the Wonkwang University Gwangju Hospital. Participants: Outpatients, diagnosed with ischemic stroke more than 3 months and less than 9 months before participating in the study (N=29; 11 men, 18 women). Interventions: Not applicable. Main Outcome Measures: The gait event parameters and time- and frequency-domain electromyogram (EMG) parameters of the lower limbs of the affected and unaffected sides was determined using BTS motion capture with the Delsys Trigno Avanti EMG wireless system. Results: The swing time, stance phase, swing phase, single support phase, and median power frequency of the gastrocnemius muscle showed a significant difference between the affected and unaffected sides. Using a logistic regression model, the swing phase, single support phase, and median frequency of the gastrocnemius muscle were selected to classify the affected side. Conclusion: The single support phase of the affected side is shortened to reduce load bearing, which causes a reduction in the stance phase ratio. Unlike gait-event parameters, EMG data of hemiplegic stroke patients are difficult to generalize. Among them, the logistic regression model with some affected side parameters expected to be set as the severity and improvement baseline of the affected side. Additional data collection and generalization of muscle activity is required to improve the classification model.

Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background/Aims: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. Methods: Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebo group (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. Results: Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological well-being (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. Conclusions: The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.

Fermented Whey Protein Supplementation Improves Muscular Strength, Muscle Parameters, and Physical Performance in Middle-Aged Korean Adults: An 8-Week Double Blind Randomized Controlled Trial.

The present study evaluated the effects of fermented whey protein using kimchi lactic acid bacteria Lactobacillus casei DK211 on skeletal muscle mass, muscle strength, and physical performance in healthy middle-aged males performing regular resistance exercises. Effective protein supplementation and regular exercise are two important factors for improving muscle health. Therefore, in this study, the effects of consuming fermented whey protein twice a day were investigated and compared with that of non-fermented supplementation. Forty-eight males (average age 44.8) were randomly assigned to two groups: Fermented whey protein supplementation (FWPS) and non-fermented whey protein concentration supplementation (WPCS) groups. Each group ingested 37 g of FWPS or WPCS twice a day for eight weeks. Body composition, muscle strength, and physical performance were assessed pre- and post-intervention. Independent t-tests or chi-square tests for the categorical variables were performed for analyzing the observations. FWPS was effective in promoting the physical performance in dynamic balance measurement and muscle health, indicated through the increment in grip strength (left), upper arm circumference, and flat leg circumference from the baseline. However, similar improvements were not observed in the WPCS group. These results imply that whey protein fermented by L. casei DK211 is an effective protein supplement for enhancing muscle health in males performing regular resistance exercises.

Comparison of Metabolites and Gut Microbes between Patients with Ulcerative Colitis and Healthy Individuals for an Integrative Medicine Approach to Ulcerative Colitis-A Pilot Observational Clinical Study (STROBE Compliant).

Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals. This was an observational case-control study. Blood and stool samples were collected from the participants, and metabolite and gut microbial studies were performed. Among metabolites, formate, glycolate, trimethylamine, valine, and pyruvate levels were significantly different between the two groups. Among gut microbes, the abundance of Bacteroidetes at the phylum level; Bacteroidia at the class level; Bacteroidales and Actinomycetales at the order level; Prevotellaceae, Acidaminococcaceae, and Leptotrichiaceae at the family level; and Prevotella, Roseburia, Paraprevotella, Phascolarctobacterium, Ruminococcus, Coprococcus, Clostridium_XIVB, Atopobium, and Leptotrichia at the genus level was also significantly different. Most of the metabolites and gut microbes significantly different between the two groups were involved in energy metabolism and inflammatory processes, respectively. The results of this study could be helpful for the identification of targets for integrative medicine approaches for UC.

Effect of herbal medicine (Jodeungsan) on migraine: A double-blind randomized clinical trial.

Background: Migraine is a relatively common disease that has a significant effect on the daily activities of affected individuals. The purpose of this study was to explore the effects of herbal medicine (Jodeungsan, JDS) on migraine. Methods: Sixty-four patients with migraine were recruited and randomized to either the JDS or placebo group at a 1:1 ratio. The subjects received JDS or placebo daily for four weeks. The primary outcome was a change in the number of headache attack days (HADs), and the secondary outcome measures were the headache impact test (HIT), migraine-specific quality of life (MSQoL), the deficiency and excess pattern identification questionnaire (DEPIQ), the cold and heat pattern identification questionnaire (CHPIQ), and the blood stasis pattern questionnaire (BSPQ). Results: In all, 61 of the 64 patients took the investigational drugs for four weeks. The number of HADs did not significantly differ between the JDS and placebo groups at the end of the study. However, the HIT and MSQoL results showed significant improvement over the baseline in both groups. Conclusion: JDS did not have a significant effect on chronic migraine. Larger studies are needed to confirm this result. Trial registration: Clinical Research Information Service (https://cris.nih.go.kr/): KCT0003121.

Comparison of Metabolites and Gut Microbes between Patients with Parkinson's Disease and Healthy Individuals-A Pilot Clinical Observational Study (STROBE Compliant).

INTRODUCTION: Even if levodopa, dopamine agonists, and others are used for patients with Parkinson's disease, the effect is not sustained, and side effects such as motor fluctuation and dyskinesia are more likely to appear as the dose increases. Thus, new approaches for managing Parkinson's disease are needed. This study aimed to compare the metabolites and gut microbes between patients with Parkinson's disease and healthy individuals. METHODS: This was an observational study with a case-control design. Metabolite and gut microbial analyses were performed using blood and stool samples collected from the subjects. RESULTS: Among the metabolites, the acetate, citrate, methionine, and trimethylamine levels were significantly different between the two groups. In the gut microbes, abundance of Bacteroidetes, Prevotella, Phascolarctobacterium, Pseudoflavonifractor, Eisenbergiella, and Gemella were also significantly different between the two groups. DISCUSSION: Metabolites are the products of gut microbes. Therefore, when the gut microbes change, the metabolites change accordingly. Metabolites and gut microbes that were significantly different between the two groups were mostly those involved in lipid and glucose metabolism. Our data may be helpful for the development of new drugs targeting metabolites and gut microbes through large-scale studies in the future.

An Observational Study Using Ultrasound to Assess Allowable Needle Insertion Range of Acupoint CV12.

BACKGROUND: Abdominal organ injuries are a rarely reported complication when deep acupuncture needling is applied to the abdomen. In order to ascertain the allowable needle insertion range (ANIR) of the abdomen region, we selected acupoint CV12, which is commonly used for treating gastric disease, and ANIR was measured with an ultrasound device. METHOD: Eighty-five healthy volunteers were recruited, of which 83 cases of ultrasound images were obtained. To investigate the prediction factor of ANIR, we also measured several anthropometric factors. RESULTS: The average ANIR was 25.3 ± 10.2; generally, the ANIRs of females were thicker than those of males; and the liver was observed in 62.7% subjects' ultrasound images. The non-observed group showed thicker ANIR and higher BMI than the liver-observed group. CONCLUSION: There are reliable variables that make it possible to predict the ANIR. It is advised to refer to anthropometric factors in needling acupoint CV12 to avoid complications with the acupuncture treatment. However, individual differences are not negligible when applying deep needling. Thus, if the risk is not judged before or during the procedure, practitioners could consider the patient's ANIR on CV12 when applying acupuncture by examining the individual anatomical structures using ultrasound and considering internal organ positions to prevent adverse events due to acupuncture.

Cupping Therapy for Migraine: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Migraine is a common reason for primary headache disorders. Cupping is a frequently used traditional intervention for controlling pain including migraine. There have been no systematic reviews on the clinical effects of cupping on migraine. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effectiveness of cupping therapy for migraine. The search strategy was built for the presence of related keywords, such as "migraine" and "cupping therapy", in the title and abstract of research articles indexed in the MEDLINE, EMBASE, CENTRAL, and other databases. The randomized controlled trials (RCTs) of cupping therapy for migraine were searched and selected from inception to May 2019. We searched eight databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials. The selection process and the quality assessment were performed by 2 authors independently. The meta-analysis was conducted and qualitative analysis was also performed. RESULTS: 218 studies were identified, and 6 RCTs were enrolled in this review. In comparison to drugs, wet cupping showed a higher total effective rate (TER). In the dry cupping plus acupuncture, the result of TER showed more effectiveness (RR 1.05, 95% CI 0.99 to 1.12, P=0.13) compared with acupuncture alone, but there was no statistically significant difference. In qualitative analysis, the results showed wet cupping plus drugs treatment could quickly relieve pain and significantly improve patients' quality of life and wet cupping could reduce headache pain. CONCLUSION: Cupping therapy could be effective for the treatment of migraine. However, the qualities of the evidence were low, so well-designed RCTs are needed to confirm the effectiveness of cupping. Systematic review registration: PROSPERO registration number is CRD42017054979.

Calcium Solubilization Ability and Anti-Inflammatory Effects of Hydrolyzed Casein.

This study performed to evaluate the applicability of functional dairy food materials by comparing the calcium solubilization ability and anti-inflammatory effects of hydrolyzed casein protein. Commercial enzyme (Alcalase®; Neutrase®; Protamex®; Flavourzyme®) was added to the 10% casein solution to prepare the casein hydrolysates. Samples obtained every hour [1:200 (w/v)]. According to results of measuring the degree of hydrolysis (DH), all of four enzymatic hydrolysates increased rapidly from 30 to 40 min, and after 150 min, there were no change. Protamex® and Neutrase® had the highest DH compared to others enzymatic hydrolysates. After that, peptides obtained throughout a preparative liquid chromatography system. In the calcium solubility experiments, neutrase fraction (NF) 4 and NF7 showed similar activities with casein phosphopeptide (CPP). In vitro cell experiments showed that no cytotoxicity except for NF6. Also, the production of nitric oxide (NO) inhibited as the concentration of fraction samples increased. The cytokine (IL-1α, IL-6, and TNF-α) production was lower than lipopolysaccharide (+) group significantly. Therefore, the possibility of anti-inflammatory activity found in the hydrolyzed samples. According to the above experiments, NF3 and Protamex Fraction (PF) 3 selected. Amino acids selected throughout an AccQ-Tag system. As a result, 17 species of amino acids and several species of unknown amino acids identified. Both fractions had the highest content of phenylalanine. This study identified the potential of biologically active and functional peptides derived from casein that affect the food and dairy industry.

Comparison of gait recovery patterns according to the paralyzed side in stroke patients: An observational study based on a retrospective chart review (STROBE compliant).

ABSTRACT: Gait rehabilitations have been abundantly performed for post-stroke patients, because gait is the most important factor for the return of post-stroke patients to daily life. However, conventional uniform gait rehabilitations tend to be tedious and reduce motivation. The aim of this study was to contribute to the development of personalized rehabilitation of gait by identifying differences in gait recovery pattern according to the paralyzed side of post-stroke patients.The gait analysis was performed on stroke patients who are right-handed and can walk independently. We retrospectively analyzed the results of pelvic movements and displacement of center of pressure (COP) during gait using corresponding equipments. To show the difference of gait recovery pattern according to the paralyzed side, we divided subjects into two groups, right (n = 19) and left (n = 20) hemiparesis group. The measured variables were as follows: tilt, obliquity, and rotation symmetries of pelvis; area, velocity, and lateral symmetry of COP.First, in the left hemiparesis group, obliquity (P < .01) and rotation (P < .01) symmetries of the movement of the pelvis were significantly improved in the follow-up compared to the initial gait analysis. In the right hemiparesis group, tilt (P < .001), obliquity (P < .001), and rotation (P < .05) symmetries were significantly improved in the follow-up compared to the initial gait analysis. Second, COP area and COP velocity values in the follow-up were significantly smaller than those in the initial gait analysis in the left (P < .001, P < .05) and right (P < .001, P < .01) hemiparesis groups. The positive value of lateral symmetry increased, although not a significant difference statistically, as walking ability improved in both groups. In the correlation analysis among variables obtained using Treadmill, there were significant positive linear relationships between the lateral symmetry and the COP area (P < .05), and between the COP velocity and the lateral symmetry (P < .001) of the follow-up gait analysis in the right hemiparesis group.It was confirmed that the gait recovery pattern differs according to the paralyzed side of post-stroke patients and the role of the intact side, such as moving the COP to the intact side, is important for the improvement of gait function in both groups.This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984) and was approved by the Institutional Review Board (IRB) of the WKUGH (WKIRB [2018-25], November 28, 2018).

Effect of Heat-killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome.

Non-viable bacteria, referred to as "paraprobiotics," have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.

Effect of a Synbiotic Containing Lactobacillus paracasei and Opuntia humifusa on a Murine Model of Irritable Bowel Syndrome.

The administration of a combination of probiotics and prebiotics is expected to be a promising strategy for improving irritable bowel syndrome (IBS) symptoms. This study aimed to investigate the efficacy of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa extract for symptomatic improvement of IBS in a murine model and to evaluate the mechanism underlying the beneficial effects of this synbiotic. A total of 20 male Wistar rats aged 8 weeks with IBS induced by restraint stress were assigned into four groups and administered L. paracasei as a probiotic and O. humifusa extract as a prebiotic for 4 weeks. The primary outcome was stool consistency at week 4. To evaluate the mechanism underlying the beneficial effects of the synbiotic, fecal microbial analysis was conducted, and the serum corticosterone levels, tumor necrosis factor-α (TNF-α) levels in the colon tissue, and expression of tight junction proteins were investigated. All three treatment groups showed significantly lower scores for stool consistency than the control group at week 4 (all p < 0.001). When compared with the control group, the synbiotic groups showed a significantly greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue, and higher expression of tight junction proteins. This novel synbiotic containing L. paracasei and O. humifusa extract can improve the stool consistency in a murine model of IBS. It may be a promising treatment option for IBS, and human studies are warranted.

Development of Integrative Medicine Therapy for Gastrointestinal Autoimmune Diseases: A study protocol for a registry study.

BACKGROUND: Although the incidence of AD, including gastrointestinal AD, increases every year, there is no effective therapy for it yet. This causes high medical costs to be spent on the management of autoimmune patients every year. The aim of this study is to identify the characteristics related to the causes and symptoms of gastrointestinal autoimmune disease (AD) by collecting patients' information and to further contribute to the development of an integrative medicine therapy for gastrointestinal AD. METHODS/DESIGN: This study is a registry study of patients diagnosed with gastrointestinal AD. Subjects who voluntarily sign a written consent form after receiving a sufficient explanation will be assessed for compliance with the inclusion and exclusion criteria through a screening process on their first visit. A total of 35 subjects will be recruited; 15 will be assigned to the patient group, 10 to the control group, 8 to the caregiver group, and 2 to the medical staff group. The clinical information of the subjects will be evaluated through statistical analyses. As this study is a registry study, it will not test specific hypotheses. DISCUSSION: If this study identifies the significant characteristics of gastrointestinal AD patients, the results will be useful for the development of integrative medicine methods for the treatment of gastrointestinal AD. STUDY REGISTRATION: This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0003976, date of registration: May 23, 2019).

Lactic Acid Bacteria Isolated From Korean Kimchi Activate the Vitamin D Receptor-autophagy Signaling Pathways.

BACKGROUND: Probiotic lactic acid bacteria (LAB) have been used in the anti-inflammation and anti-infection process of various diseases, including inflammatory bowel disease (IBD). Vitamin D receptor (VDR) plays an essential role in pathogenesis of IBD and infectious diseases. Previous studies have demonstrated that the human VDR gene is a key host factor to shape gut microbiome. Furthermore, intestinal epithelial VDR conditional knockout (VDRΔIEC) leads to dysbiosis. Low expressions of VDR is associated with impaired autophagy, accompanied by a reduction of ATG16L1 and LC3B. The purpose of this study is to investigate probiotic effects and mechanism in modulating the VDR-autophagy pathways. METHODS: Five LAB strains were isolated from Korean kimchi. Conditional medium (CM) from these strains was used to treat a human cell line HCT116 or intestinal organoids to measure the expression of VDR and autophagy. Mouse embryonic fibroblast (MEF) cells with or without VDR were used to investigate the dependence on the VDR signaling. To test the role of LAB in anti-inflammation, VDR+/+ organoids were treated with 121-CM before infection with Salmonella enterica serovar Enteritidis. In vivo, the role of LAB in regulating VDR-autophagy signaling was examined using LAB 121-CM orally administrated to VDRLoxp and VDRΔIEC mice. RESULTS: The LAB-CM-treated groups showed higher mRNA expression of VDR and its target genes cathelicidin compared with the control group. LAB treatment also enhanced expressions of Beclin-1 and ATG16L1 and changed the ratio of LC3B I and II, indicating the activation of autophagic responses. Furthermore, 121-CM treatment before Salmonella enterica serovar Enteritidis infection dramatically increased VDR and ATG16L1 and inhibited the inflammation. Administration of 121-CM to VDRLoxp and VDRΔIEC mice for 12 and 24 hours resulted in an increase of VDR and LC3B II:I ratio. Furthermore, we identified that probiotic proteins P40 and P75 in the LAB-CM contributed to the anti-inflammatory function by increasing VDR. CONCLUSIONS: Probiotic LAB exert anti-inflammation activity and induces autophagy. These effects depend on the VDR expression. Our data highlight the beneficial effects of these 5 LAB strains isolated from food in anti-infection and anti-inflammation.

Adjuvant effects of killed Lactobacillus casei DK128 on enhancing T helper type 1 immune responses and the efficacy of influenza vaccination in normal and CD4-deficient mice.

Lactic acid bacteria Lactobacillus casei DK128 isolated from fermented vegetable foods was suggested to stimulate innate immune responses. Here, we investigated whether heat-killed DK128 would exhibit adjuvant effects on enhancing the efficacy of influenza vaccination. Immunization of mice with split influenza virus vaccine in the presence of heat-killed DK128 induced significantly higher levels of both IgG1 and IgG2c isotype antibodies than those by vaccine only. A single dose DK128-adjuvanted influenza vaccination conferred higher efficacy of protection, as evidenced by intact lung function, less weight loss, enhanced clearance of lung viral loads, and lower levels of inflammatory cytokines and infiltrates. Immunization of CD4 T cell-knockout (CD4KO) mice with influenza vaccine and DK128, but not with vaccine alone, induced isotype-switched IgG antibodies and protection against lethal challenge in CD4KO mice. The results in this study suggest heat-killed DK128 as a potential vaccine adjuvant, promoting the induction of IgG isotype switching in CD4-deficient condition and enhancing protective efficacy of split influenza vaccination in immunocompromised and immune-competent subjects.