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1.
[Bile Acid Diarrhea].
Kim, HJ, Kim, HJ
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi. 2024;(4):133-142
Abstract
Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.
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Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.
Kim, HJ, Lee, JH, Kwon, SY, Kwon, YJ, Park, MS, Kim, KH, Shin, CH, Joo, JC, Park, SJ
Nutrients. 2024;(13)
Abstract
The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.
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Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies.
Kim, HJ, Kim, YH
International journal of molecular sciences. 2024;(10)
Abstract
Acne vulgaris is a common dermatological condition that can present across different ages but predominantly affects adolescents and young adults. Characterized by various lesion types, the pathogenesis of acne is complex, involving genetic, hormonal, microbial, and inflammatory factors. This review comprehensively addresses current and emerging acne management strategies, emphasizing both topical and systemic treatments, procedural therapies, and dietary modifications. Key topical agents include retinoids, benzoyl peroxide, antibiotics, and other specialized compounds. Systemic options like antibiotics, hormonal therapies, and retinoids offer significant therapeutic benefits, particularly for moderate to severe cases. Procedural treatments such as laser devices, photodynamic therapy, chemical peels, and intralesional injections present viable alternatives for reducing acne symptoms and scarring. Emerging therapies focus on novel biologics, bacteriophages, probiotics, and peptides, providing promising future options. This review underscores the importance of personalized approaches to treatment due to the multifaceted nature of acne, highlighting the potential of innovative therapies for improving patient outcomes.
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4.
Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway.
Kang, YJ, Song, W, Lee, SJ, Choi, SA, Chae, S, Yoon, BR, Kim, HY, Lee, JH, Kim, C, Cho, JY, et al
Experimental & molecular medicine. 2024
Abstract
Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, β-hydroxy β-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-β-homoleucine (LβhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LβhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.
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5.
Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.
Chung, MK, Kim, DH, Park, JI, Lee, S, Park, HC, Kim, K, Kang, YS, Ko, K, Kim, J, Koo, H, et al
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2024;(1):47-57
Abstract
OBJECTIVE This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS Meal intervention statistically significantly stabilized serum phosphorus level (β = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.
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6.
Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.
Lambertini, M, Blondeaux, E, Agostinetto, E, Hamy, AS, Kim, HJ, Di Meglio, A, Bernstein Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, et al
JAMA. 2024;(1):49-59
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Abstract
IMPORTANCE Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. OBJECTIVE To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. DESIGN, SETTING, AND PARTICIPANTS International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. EXPOSURE Pregnancy after breast cancer. MAIN OUTCOMES AND MEASURES Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. RESULTS Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. CONCLUSIONS AND RELEVANCE In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03673306.
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Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus.
Han, JH, Joung, KH, Lee, JC, Kim, OS, Choung, S, Kim, JM, Kang, YE, Yi, HS, Lee, JH, Ku, BJ, et al
Diabetes & metabolism journal. 2024;(1):112-121
Abstract
BACKGRUOUND Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. METHODS A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. RESULTS The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. CONCLUSION Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.
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Magnetism-enhanced biomaterial Mg guide wire by MAP process for development of catheter insertion.
Chanchamnan, S, Kim, JS, Im, H, Kim, HJ, Heng, L, Mun, SD
Medical engineering & physics. 2024;:104098
Abstract
The surface topography of implant tools has indicated an interfacial contact in degradation still being discovered; however, the glossy texture of a tiny magnesium wire is important for absorbable medical devices. This paper investigated the alterations of surface quality by a magnetic abrasive polishing method using a rotational magnetic field-assisted system with input parameters of revolution, abrasive media, magnetic pole, flux density, vibration, and amplitude that could noticeably enhance asperities along a sample. Furthermore, the blood flow simulation is used to analyze flow within blood vessels while maintaining the surface roughness conditions of the guide wire. The results are compared and discussed. Magnetic field simulation is employed to investigate the magnetic field strength in the polishing zone. Scanning Electron Microscopy (SEM) provides visual aids for recognizing the differences between pre-and post-workpieces of magnesium wire. The experimental results reveal that a wire diameter of 0.50 mm predominantly achieves surface morphology from the initial roughness of 0.22 μm to 0.05 μm. The results corroborate that the distribution of blood in the circulatory system was relatively stable. Hence, this study establishes a crucial benchmark for the precision polishing of ultra-thin magnesium wires, which is vital for their use as high-precision biodegradable medical devices.
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International consensus guidelines on robotic pancreatic surgery in 2023.
Liu, R, Abu Hilal, M, Besselink, MG, Hackert, T, Palanivelu, C, Zhao, Y, He, J, Boggi, U, Jang, JY, Panaro, F, et al
Hepatobiliary surgery and nutrition. 2024;(1):89-104
Abstract
BACKGROUND With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. METHODS World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. RESULTS After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. CONCLUSIONS The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.
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10.
Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration.
Basyal, D, Lee, S, Kim, HJ
Antioxidants (Basel, Switzerland). 2024;(5)
Abstract
Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.
