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1.
BMC Musculoskelet Disord ; 25(1): 514, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961389

ABSTRACT

PURPOSE: Comminuted coronal shear fractures of the distal humerus represent rare injuries and are difficult to treat, especially comminuted capitellum and trochlear fractures (Dubberley Type III). The on-table reconstruction technique of comminuted articular fractures may be an option, although it has not been reported in the coronal shear fracture of the distal humerus. The aim of the present case series is to determine the functional and radiological outcomes of on-table reconstructed Dubberley III fractures. METHODS: A retrospective review was conducted of 10 patients with Dubberley type III fractures in coronal shear fractures of the capitellum and trochlea who underwent an 'on-table' reconstruction technique between January 2009 and October 2019. All patients were evaluated using the disabilities of the arm, shoulder, and hand (DASH) score, American Shoulder and Elbow Surgeons(ASES) score, Mayo Elbow Score Performance Index (MEPI) score and at least 4 years later. RESULTS: All cases achieved union. At the final follow-up, the mean range of elbow motion was 11.5°of flexion contracture and 131.9° of further flexion. The mean DASH score was 21.2 (5.7) points (range 13.3-32.5). The mean ASES score was 88.6 ± 7.4 (range, 77 to 100). The mean MEPI score was 87 (10) points (range 70-100). In complication, partial osteonecrosis of capitellum is developed in one patient. One patient had heterotopic ossification without functional impairment. CONCLUSION: The on-table reconstruction technique can be a reliable option in the surgical treatment of complex distal humerus fractures. This technique allows anatomical reduction of comminuted capitellum and trochlea, with a low risk of avascular necrosis over 4 years of follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.


Subject(s)
Elbow Joint , Fractures, Comminuted , Humeral Fractures , Range of Motion, Articular , Humans , Male , Retrospective Studies , Female , Humeral Fractures/surgery , Humeral Fractures/diagnostic imaging , Middle Aged , Adult , Treatment Outcome , Fractures, Comminuted/surgery , Fractures, Comminuted/diagnostic imaging , Elbow Joint/surgery , Elbow Joint/diagnostic imaging , Elbow Joint/physiopathology , Fracture Fixation, Internal/methods , Aged , Follow-Up Studies , Plastic Surgery Procedures/methods , Young Adult
2.
Environ Geochem Health ; 46(7): 216, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38941030

ABSTRACT

Iron phosphate-based coating and iron silicate-based coating were used to inhibit the oxidation of sulfide minerals in rainy and submerged environments. The inhibiting effectiveness of coating agents on the oxidation of iron sulfide minerals was investigated using pyrite and rock samples resulting from acid drainage. The film formed with both surface-coating agents was identified by pyrite surface analysis. It was also confirmed that the formation of coatings varies depending on the crystallographic orientation. The inhibitory effects under rainy and submerged conditions were investigated using column experiments. Submerged conditions accelerated deterioration compared to that under rainy conditions. Iron phosphate coating had a significantly better oxidation-inhibitory effect (84.86-98.70%) than iron silicate coating (56.80-92.36%), and at a concentration of 300 mM, H+ elution was inhibited by more than 90% throughout the experiment. Furthermore, methods for effective film formation were investigated in terms of producing Fe3+; (1) application of coating agents mixed with oxidant (H2O2), (2) application of coating agent after the use of the oxidant. In a rainy environment, applying iron phosphate-based coating using the sequential method showed oxidation inhibition effects for cycles 1-9, whereas applying the mixed material showed effects for cycles 9-13. The use of a surface-coating agent after applying an oxidant did not inhibit oxidation. The surface coating agent and the oxidizing agent should be applied as a mixture to form a film.


Subject(s)
Iron , Oxidation-Reduction , Phosphates , Silicates , Silicates/chemistry , Iron/chemistry , Phosphates/chemistry , Acid Rain , Sulfides/chemistry , Hydrogen Peroxide/chemistry , Ferric Compounds/chemistry
4.
Nutrients ; 16(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38931268

ABSTRACT

Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.


Subject(s)
Anti-Obesity Agents , Obesity , Peptides , Animals , Obesity/drug therapy , Mice , Male , Peptides/pharmacology , Anti-Obesity Agents/pharmacology , Protein Hydrolysates/pharmacology , Liver/drug effects , Liver/metabolism , Blood Glucose/drug effects , Blood Glucose/metabolism , Hypoglycemic Agents/pharmacology , Lipid Metabolism/drug effects , AMP-Activated Protein Kinases/metabolism , Mice, Inbred C57BL , Receptors, Leptin/metabolism , Receptors, Leptin/genetics , Adipogenesis/drug effects , Body Weight/drug effects
5.
Anim Biosci ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38938028

ABSTRACT

Objective: The improvement of carcass traits is essential for the Hanwoo industry because of the Hanwoo grade determination system, and Genome-Wide Association Study (GWAS) analysis is an instrumental tool for identifying the genetic factors that impact these traits. While GWAS analysis utilizing family data offers advantages in minimizing genetic bias, research on family-based GWAS in Hanwoo is currently lacking. Methods: This study classified Group A using both parental and offspring genetic information, and Group B based solely on offspring genetic information, to compare GWAS analysis results of Hanwoo carcass traits. Results: 16 significant SNP markers (carcass weight (CWT) 7, back fat thickness (BFT) 3, marbling score (MS) 6) were identified in Group A, and 7 significant SNP markers (CWT 3, eye muscle area (EMA) 1, BFT 1, MS 2) were identified in Group B. Functional annotation analysis revealed only one common function related to carcass traits between the groups, while Protein-protein interaction (PPI) analysis indicated more gene interactions in Group A. The reliability of estimated values for common SNP markers identified between the groups was higher in Group A. Conclusion: GWAS analysis utilizing parental genetic information holds greater potential for application, owing to its higher reliability of estimated values and the ability to explore numerous candidate genes.

6.
Gut ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724220

ABSTRACT

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

7.
Biomedicines ; 12(5)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38790898

ABSTRACT

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002-2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

8.
bioRxiv ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38746278

ABSTRACT

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB+FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNAseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 µm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 µm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor in vivo stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.

9.
Brain Tumor Res Treat ; 12(2): 132-140, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38742263

ABSTRACT

Giant cell tumors (GCTs) are locally aggressive primary bone tumors of osteoclast-like cells. Most GCTs occur within the long bones, and primary GCTs involving the clivus are extremely rare. We present the case of an 18-year-old boy with binocular horizontal diplopia with an insidious onset who was found to have a hypointense enhancing mass involving the clivus and left side dorsum sellae on magnetic resonance images. The tumor was completely resected via an endoscopic endonasal transclival approach, and histopathologic examination via immunohistochemistry indicated a GCT. The patient's left abducens nerve palsy improved slightly after surgery. Because of the rarity of GCTs, there is no consensus about the definitive treatment protocol. However, we suggest that gross total resection is the treatment of choice, and denosumab plays a critical role in patients with subtotal resection.

10.
J Gastroenterol ; 59(6): 528-529, 2024 06.
Article in English | MEDLINE | ID: mdl-38671285
11.
Nat Commun ; 15(1): 2983, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582860

ABSTRACT

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.


Subject(s)
Verrucomicrobia , beta Catenin , Male , Mice , Animals , beta Catenin/metabolism , Verrucomicrobia/metabolism , Intestines , Cadherins/metabolism , Akkermansia
12.
Endocrinol Metab (Seoul) ; 39(2): 334-343, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572536

ABSTRACT

BACKGRUOUND: Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. METHODS: This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. RESULTS: No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). CONCLUSION: Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.


Subject(s)
Iodine Radioisotopes , Neutrophils , Phenylurea Compounds , Quinolines , Thyroid Neoplasms , Humans , Phenylurea Compounds/therapeutic use , Female , Male , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/blood , Thyroid Neoplasms/mortality , Middle Aged , Retrospective Studies , Prognosis , Aged , Quinolines/therapeutic use , Iodine Radioisotopes/therapeutic use , Adult , Inflammation , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/blood , Lymphocytes , Aged, 80 and over , Republic of Korea , Biomarkers/blood
13.
Heliyon ; 10(8): e29666, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38655361

ABSTRACT

Additive manufacturing technology has advanced beyond creating optimized features, from strengthening materials to make them lightweight to fabricating multi-material combinations that offer functionalities beyond the capabilities of individual materials. In this study, a lamination method for laser-directed energy deposition (LDED) is developed to achieve dense multi-material features, and a design that combines different and dissimilar materials is developed. To evaluate these novel developments, two materials-AISI 316L stainless steel and Inconel 625-are introduced. Tensile specimens, fabricated via multi-material additive manufacturing using LDED, are subjected to tensile tests that are recorded on video for digital image correlation. After the tests, fracture surface analyses of the fractured specimens are performed via scanning electron microscopy, and optical monitoring analyses are performed on the specimens that are not subjected to the tensile tests. The results indicate that the specimens demonstrate varied mechanical properties due to the influence of lamination direction and order, which affect the formation of critical cracks and pores.

14.
J Pers Med ; 14(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38672983

ABSTRACT

While headaches frequently occur in individuals with chronic kidney disease (CKD), there are few statistical evaluations of their connection to migraines in population-based studies. In this nationwide longitudinal follow-up study of Korean health examination data (2002-2019), a total of 15,443 participants with CKD and 61,772 matched controls were enrolled. We applied overlap-weighted Cox proportional hazard regression models to assess hazard ratios, examining the correlation between CKD and the development of migraines. After accounting for various factors, we observed a modest reduction of approximately 11% in the likelihood of migraine occurrence among CKD patients (95% confidence intervals = 0.81-0.97) during the 16-year monitoring period. Subgroup analysis revealed a significant association among specific demographic and health conditions, including individuals aged 70 or older, females, overweight individuals, nonsmokers, and those without hypertension or diabetes. Our research may indicate a potential relationship between CKD and the onset of migraines in Korean adults, suggesting a slight reduction in the probability of the occurrence of migraines among those with CKD. These findings emphasize the need for attentive follow-up and preventive management in individuals without the identified protective factors, particularly in male CKD patients under the age of 70 with hypertension.

15.
Food Sci Biotechnol ; 33(7): 1697-1705, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38623440

ABSTRACT

Mast cells have a detrimental impact on coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Sambou Bamboo salt™ (BS) suppresses mast cell-mediated inflammatory response and enhances immunity. In this study, we investigated the regulatory effects of BS on expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2) in human mast cell line (HMC)-1 cells. BS resulted in significant reductions in expression levels of ACE2 and TMPRSS2 in activated HMC-1 cells. Levels of tryptase were reduced by BS. In addition, BS blocked activation of activator protein 1 (AP-1), c-Jun NH2-terminal kinases (JNK), p38, and phosphatidylinositide-3-kinase (PI3K) in activated HMC-1 cells. Therefore, these results show that BS reduces levels of ACE2, TMPRSS2, and tryptase by inhibiting AP-1/JNK/p38/PI3K signaling pathways in mast cells. These findings can serve as valuable foundational data for the development of therapeutic agents aimed at preventing SARS-CoV-2 infection.

16.
Biomedicines ; 12(4)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38672147

ABSTRACT

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson's disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

17.
Exp Mol Med ; 56(4): 975-986, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38609519

ABSTRACT

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.


Subject(s)
DNA Methylation , Ependymoglial Cells , Neurocytoma , Receptor, Fibroblast Growth Factor, Type 3 , Humans , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Neurocytoma/genetics , Neurocytoma/pathology , Neurocytoma/metabolism , Ependymoglial Cells/metabolism , Ependymoglial Cells/pathology , Gene Expression Regulation, Neoplastic
18.
Sci Rep ; 14(1): 6784, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38514670

ABSTRACT

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.


Subject(s)
Brain Neoplasms , Humans , Pilot Projects , Prospective Studies , Microscopy, Confocal/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Lasers
19.
Sci Rep ; 14(1): 6776, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38514712

ABSTRACT

Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically applying N-benzyl-N-methyldecan-1-amine (BMDA), derived from garlic, and its derivative [decyl-(4-methoxy-benzyl)-methyl-1-amine] (DMMA) could effectively alleviate AD-like skin lesions in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Administering these compounds to the irritated skin of DNCB-treated mice significantly reduced swelling, rash, and excoriation severity, alongside a corresponding decrease in inflamed epidermis and dermis. Moreover, they inhibited spleen and lymph node enlargement and showed fewer infiltrated mast cells in the epidermis and dermis through toluidine-blue staining. Additionally, they led to a lower IgE titer in mouse sera as determined by ELISA, compared to vehicle treatment. Analyzing skin tissue from the mice revealed decreased transcript levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6), IL-4, iNOS, and COX-2, compared to control mice. Simultaneously, the compounds impeded the activation of inflammation-related signaling molecules such as JNK, p38 MAPK, and NF-κB in the mouse skin. In summary, these findings suggest that BMDA and DMMA hold the potential to be developed as a novel treatment for healing inflammatory AD.


Subject(s)
Dermatitis, Atopic , Garlic , Maleic Anhydrides , Animals , Mice , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Dinitrochlorobenzene/toxicity , Skin/pathology , Cytokines , Amines/pharmacology , NF-kappa B/pharmacology , Mice, Inbred BALB C
20.
Front Pharmacol ; 15: 1268134, 2024.
Article in English | MEDLINE | ID: mdl-38533264

ABSTRACT

The gut microbiota and barrier function play important roles in bone health. We previously demonstrated that chronic glucocorticoid (GC)-induced bone loss in mice is associated with significant shifts in gut microbiota composition and impaired gut barrier function. Korean Red Ginseng (KRG, Panax Ginseng Meyer, Araliaceae) extract has been shown to prevent glucocorticoid-induced osteoporosis (GIO) in a subcutaneous pellet model in mice, but its effect on gut microbiota and barrier function in this context is not known. The overall goal of this study was to test the effect of KRG extract in a clinically relevant, oral model of GIO and further investigate its role in modulating the gut-bone axis. Growing male mice (CD-1, 8 weeks) were treated with 75 µg/mL corticosterone (∼9 mg/kg/day) or 0.4% ethanol vehicle in the drinking water for 4 weeks. During this 4-week period, mice were treated daily with 500 mg/kg/day KRG extract dissolved in sterile water or an equal amount of sterile water via oral gastric gavage. After 4 weeks of treatment, we assessed bone volume, microbiota composition, gut barrier integrity, and immune cells in the bone marrow (BM) and mesenteric lymph nodes (MLNs). 4 weeks of oral GC treatment caused significant distal femur trabecular bone loss, and this was associated with changes in gut microbiota composition, impaired gut barrier function and altered immune cell composition. Importantly, KRG extract prevented distal femur trabecular bone loss and caused significant alterations in gut microbiota composition but had only modest effects on gut barrier function and immune cell populations. Taken together, these results demonstrate that KRG extract significantly modulates the gut microbiota-bone axis and prevents glucocorticoid-induced bone loss in mice.

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