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BACKGROUND: This retrospective study aimed to compare the efficacy of balloon angioplasty alone (BAA) with carotid artery stenting (CAS) for severe extracranial carotid artery stenosis. The primary outcomes assessed were restenosis requiring retreatment and symptomatic stroke occurrence within a 4-year follow-up period. METHODS: A total of 77 patients with 89 carotid artery stenoses undergoing endovascular carotid revascularization between January 2015 and December 2019 were included. Neuroradiologic evaluations, including computed tomography angiography or magnetic resonance angiography, were performed at defined intervals. Statistical analyses were conducted to compare patient characteristics, angiographic outcomes, and clinical outcomes between the BAA and CAS groups. RESULTS: The study demonstrated successful outcomes in both groups with low adverse event rates. The overall restenosis rate was 40.2%, but severe restenosis requiring retreatment occurred in only 10 cases (7 in BAA, and 3 in CAS). No significant difference was found in retreatment rates between the 2 groups (P = 0.53). Stroke occurrence within the 4-year follow-up period was observed in 3 patients, with no statistically significant difference between BAA and CAS groups. CONCLUSIONS: This study provides valuable insights into the comparative effectiveness of BAA and CAS for severe extracranial carotid artery stenosis. Despite slightly shorter intervals to restenosis in the BAA group, there was no significant difference in retreatment or stroke occurrence rates between the 2 procedures. BAA offers advantages in terms of retreatment options.
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Globally, the edible insect industry is emerging due to its potential contributions to food security and environmental sustainability. Edible insects are rapidly being integrated into the development of alternative foods and new pharmaceuticals. Silkworms, known for their high protein content, are not only a potential new source of human food and animal feed but have also been traditionally used for medicinal purposes. However, conventional silkworms are difficult to ingest. To address this, we have developed a steamed and freeze-dried mature silkworm larva powder (SMSP), and it is essential to investigate its potential toxicity and food safety for further studies and applications. Therefore, this study aimed to evaluate the toxicity of SMSP. A toxicity assessment of SMSP was conducted according to OECD guidelines. An oral repeat-administration study was performed on male and female SD rats at doses of 625, 1250, and 2500 mg/kg/day for 4 and 13 weeks. No toxicological changes were observed in clinical signs, body weight, water and food intake, urine tests, hematology, clinical biochemistry, gross findings, or histopathological examination. In conclusion, the no observed adverse effect level (NOAEL) of SMSP was 2500 mg/kg/day, with no target organs identified in either sex of the rats. These results suggest that SMSP is safe, is without side effects and has potential for use as an edible ingredient and in health functional food applications.
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PURPOSE: Several treatment options for acne vulgaris are limited by their associated adverse effects. An innovative approach involves introducing light-absorbing nanoparticles into sebaceous follicles before destroying the follicles using selective photothermolysis. We aimed to investigate efficient methods for introducing gold and platinum nanoparticles into sebaceous follicles and to identify suitable laser equipment and parameters for the effective destruction of these follicles. METHODS: We used porcine skin as the experimental model. We compared the efficacies of a thulium laser, ultrasound, and manual massage and evaluated the optimal method for delivering nanoparticles in close proximity to sebaceous follicles. Subsequently, a 1064-nm-wavelength neodymium-doped yttrium aluminum garnet (Nd: YAG) laser was employed to induce selective photothermolysis. We compared different parameters to identify the optimal pulse duration and fluence of the Nd: YAG laser. The extent of penetration and destruction of sebaceous follicles was assessed using hematoxylin and eosin (H&E) staining, and a numerical evaluation was conducted. RESULTS: H&E staining showed that irradiation with a long-pulsed Nd: YAG laser following a combination of thulium laser and sonophoresis effectively destroyed sebaceous follicles, with destruction rates exceeding 50%. These results were valid with a long pulse duration and a high fluence of the Nd: YAG laser. CONCLUSION: This study demonstrated that sebaceous follicles can be effectively destroyed through a mixture of gold and platinum nanoparticle delivery by a combination of microchanneling and sonophoresis, followed by selective thermal damage induced by a 1064-nm long-pulsed high-fluence Nd: YAG laser.
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Acne Vulgar , Ouro , Lasers de Estado Sólido , Nanopartículas Metálicas , Platina , Animais , Ouro/administração & dosagem , Suínos , Projetos Piloto , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Acne Vulgar/terapia , Lasers de Estado Sólido/uso terapêutico , Pele/efeitos da radiação , Glândulas Sebáceas/efeitos da radiação , Glândulas Sebáceas/efeitos dos fármacos , Glândulas Sebáceas/patologiaRESUMO
Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.
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Gastric mucosa is important to protect the gastric damage against external factors. We previously reported the gastro-protective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in ethanol-treated rats. However, the factors that promote mucosal formation still remain unclarified. In this study, we evaluated the effect of SMSP on the restoration and maintenance of gastric mucosal layer as well as anti-inflammatory response in ethanol-induced stomach injury in rats. A significant decrease of ulcer indexes, histopathological scores and pro-inflammatory cytokine levels was observed in SMSP-treated group. In addition, SMSP protected the mucosal layer from ethanol-induced gastric damage by increasing the expression of nitric oxide synthases and heat shock proteins, along with promoting genes related gastric mucosal protection and biosynthesis including mucin 5AC and trefoil factors. These results demonstrate that SMSP attenuates the pro-inflammatory responses and strengthens the gastric mucosal layer, thus exhibiting gastro-protective effect against ethanol-induced gastric injury in rats.
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Purpose: To assess normal CT scans with quantitative CT (QCT) analysis based on smoking habits and chronic obstructive pulmonary disease (COPD). Materials and Methods: From January 2013 to December 2014, 90 male patients with normal chest CT and quantification analysis results were enrolled in our study [non-COPD never-smokers (n = 38) and smokers (n = 45), COPD smokers (n = 7)]. In addition, an age-matched cohort study was performed for seven smokers with COPD. The square root of the wall area of a hypothetical bronchus of internal perimeter 10 mm (Pi10), skewness, kurtosis, mean lung attenuation (MLA), and percentage of low attenuation area (%LAA) were evaluated. Results: Among patients without COPD, the Pi10 of smokers (4.176 ± 0.282) was about 0.1 mm thicker than that of never-smokers (4.070 ± 0.191, p = 0.047), and skewness and kurtosis of smokers (2.628 ± 0.484 and 6.448 ± 3.427) were lower than never-smokers (2.884 ± 0.624, p = 0.038 and 8.594 ± 4.944, p = 0.02). The Pi10 of COPD smokers (4.429 ± 0.435, n = 7) was about 0.4 mm thicker than never-smokers without COPD (3.996 ± 0.115, n = 14, p = 0.005). There were no significant differences in MLA and %LAA between groups (p > 0.05). Conclusion: Even on normal CT scans, QCT showed that the airway walls of smokers are thicker than never-smokers regardless of COPD and it preceded lung parenchymal changes.
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Purpose: The present study was to evaluate the outcomes of Denali filter retrieval. Materials and Methods: We retrospectively reviewed 143 patients who received Denali filter insertion from September 2015 to April 2020. Ninety-seven patients who required removal of the filters were include in this study. Filters were retrieved with either standard or advanced techniques. Venography before and after retrieval was obtained to evaluate technical success, complications and duration of filter insertion. Results: All 97 filters were retrieved successfully without complications. Ninety-two (94.8%) were retrieved with standard technique and 5 filters (5.2%) required the advanced technique. There were two cases with a filter angle greater than 15 degrees. Inferior vena cava penetration was shown in 17 patients (17.5%) on venography but was not associated with contrast media extravasation after filter removal. Conclusion: The Denali filter showed a high rate of successful retrieval without complications. This study adds value to previous studies and trials showing that the Denali filter is a reliable and safe filter that can potentially improve retrieval rates, with increasing use of this device.
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BACKGROUND: Facial erythema is a common problem among patients visiting dermatologists. However, data on the clinical characteristics of facial erythema in healthy people are lacking. We aimed to compare and analyze the severity and pattern of facial vascularity in healthy subjects based on their age and gender. MATERIALS AND METHODS: This study included 198 Korean volunteers (126 females and 72 males) with Fitzpatrick skin types II, III, or IV. Fourteen different anatomical areas on the face were divided into facial erythema units. Each unit was scored from one (least erythematous) to five (most erythematous) according to the observed level of erythema on the red images implemented as hemoglobin content. We also evaluated the presence of facial telangiectatic macules. RESULTS: On average, the perinasal, nasal, and cheek units were the most hypervascular regions. In contrast, the degree of facial erythema was lowest in the labial (perioral), neck, and temporal regions. The average value of erythema was higher in males than in females. Additionally, the severity of erythema tended to increase with age. In both males and females, the number of telangiectatic macules increased with age. CONCLUSIONS: We analyzed the clinical characteristics of erythema in healthy subjects with Fitzpatrick skin types II, III, or IV in the Korean population. This study is expected to be used to identify the neurovascular pathogenesis of the most common regions of facial dermatosis in the future.
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Face , Dermatoses Faciais , Telangiectasia , Feminino , Humanos , Masculino , Povo Asiático , Eritema/patologia , República da Coreia/epidemiologia , Voluntários Saudáveis , Face/irrigação sanguíneaRESUMO
Purpose of this study was to compare the complication rates between reverse-tapered and nontapered peripherally inserted central catheters (PICCs). In total, 407 patients who had an inpatient clinic-based PICC insertion between September 2019 and November 2019 were retrospectively analyzed. Seven PICC types were used (4 reverse tapered: 4-Fr single-lumen (n = 75), 5-Fr single-lumen (n = 78), 5-Fr double-lumen (n = 62), and 6-Fr triple-lumen (n = 61); 3 nontapered: 4-Fr single-lumen (n = 73), 5-Fr double-lumen (n = 30), and 6-Fr triple-lumen (n = 23)). Complications such as periprocedural bleeding, delayed bleeding, inadvertent removal, catheter obstruction by thrombosis, infection, and leakage were investigated. The overall complication rate was 27.1%. The complication rate was significantly higher for nontapered PICCs than reverse-tapered PICCs (50.0% vs 16.7%, P < 0.001). The overall periprocedural bleeding rate was significantly higher for nontapered PICCs than for reverse-tapered PICCs (27.0% vs 6.2%, P <0.001). The overall inadvertent removal rate was significantly higher for nontapered PICCs than for reverse-tapered PICCs (15.1% vs 3.3%, P < 0.001). There were no other significant differences in complication rates. Nontapered PICCs were associated with higher rates of periprocedural bleeding and inadvertent removal than reverse-tapered PICCs.
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Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Trombose , Humanos , Estudos Retrospectivos , Fatores de Risco , Trombose/etiologia , Cateterismo Periférico/efeitos adversos , Catéteres , Cateteres Venosos Centrais/efeitos adversos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Cateteres de DemoraRESUMO
EC-IC bypasses have been performed to treat complex aneurysms or moyamoya disease or atherosclerotic steno-occlusive disease. We report the three cases that underwent EC-IC revascularization of the IMA-M2 bypass using the radial artery graft concurrently after the STA-MCA anastomosis to prevent potential ischemic damage during the operation and augment more flow in terminal internal carotid artery stenosis. All patients experienced neither perioperative complications nor further events for a 3-month follow-up. The double-barreled IMA-M2 and STA-MCA bypass is a good option for substantial amount of EC-IC revascularization with minimizing ischemic injury and maximizing flow amount in patients with severe hemodynamic compromise.
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Aneurisma , Revascularização Cerebral , Doença de Moyamoya , Humanos , Artéria Carótida Interna/cirurgia , Constrição Patológica , Doença de Moyamoya/cirurgia , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgiaRESUMO
BACKGROUND: Not many imaging techniques have been reported in Eustachian tube imaging. PURPOSE: To investigate the role of selective Eustachian tubography (SET) and Valsalva computed tomography (CT) in patients who underwent Eustachian tube balloon dilation (ETBD). MATERIAL AND METHODS: Eligible patients were aged 18 years and older with chronic Eustachian tube dysfunction who had failed medical treatment. On the day of the procedure, Valsalva CT and SET were performed. Participants underwent fluoroscopic ETBD with a 6×20-mm balloon catheter. Clinical examinations to check for the ability to perform the Valsalva maneuver and ETDQ-7 score change were conducted at one week and then at one, two, and six months. Follow-up Valsalva CT was performed in the one-month follow-up. RESULTS: A total of 30 ears in 23 patients (16 right ears, 14 left ears; 10 women, 13 men) underwent ETBD from August 2018 to November 2019. Positive CT patency was higher in follow-up Valsalva CT than baseline Valsalva CT (40% and 23.3%, respectively) (P = 0.006). In SET, positive patency was observed in 13 of 25 ears. Response to balloon dilation was observed in 18 of 25 patients. Clinical success was achieved in 16 of 27 ears. Response to balloon dilation was the only significant predictor of clinical success (P = 0.012). CONCLUSION: SET depicted the lumen of the Eustachian tube; thereby, it could be a potentially valuable tool in ETBD. Valsalva CT provides additional information about the cartilaginous portion of the Eustachian tube.
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Tuba Auditiva , Masculino , Humanos , Feminino , Tuba Auditiva/diagnóstico por imagem , Dilatação/métodos , Resultado do Tratamento , Cateterismo/métodos , Tomografia Computadorizada por Raios XRESUMO
Cinnamomum cassia (cassia) is a tropical aromatic evergreen tree of the Lauraceae family well known for its fragrance and spicy flavor and widely used in Asian traditional medicine. It has recently garnered attention for its diverse potential health benefits, including anti-inflammatory, anti-cancer, and anti-diabetic properties. However, the gastroprotective effect of C. cassia, particularly against ethanol-induced gastric damage, remains unclear. We investigated the potential gastroprotective property of C. cassia and the underlying mechanisms of action in a rat model of ethanol-induced gastric injury. To assess its effectiveness, rats were fed C. cassia for a 14-day period prior to inducing gastric damage by oral administration of ethanol. Our results indicated that pre-treatment with C. cassia mitigated ethanol-induced gastric mucosal lesions and bleeding. Reduced gastric acid secretion and expression of acid secretion-linked receptors were also observed. Additionally, pretreatment with C. cassia led to decreased levels of inflammatory factors, including TNF-α, p-p65, and IκBα. Notably, C. cassia upregulated the expressions of HO1 and HSP90, with particular emphasis on the enhanced expression of PAS and MUC, the crucial gastric mucosa defense molecules. These findings suggest that C. cassia has protective effects on the gastric mucosa and can effectively reduce oxidative stress and inflammation.
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Cinnamomum aromaticum , Animais , Ratos , Mucosa Gástrica , Estômago , Administração Oral , Etanol/toxicidadeRESUMO
Propolis, a natural resinous substance obtained from a variety of buds and plants, has been reported to possess various biological functions. Several recent studies have demonstrated the inhibitory effects of propolis on the growth of Helicobacter pylori (H. pylori) in vitro; however, current research efforts on Korean propolis (KP) remain insufficient especially in vivo. Our study aims to investigate the anti-inflammatory effect and molecular mechanism of KP on mouse gastric mucosa during H. pylori infection. We examined an in vivo H. pylori-induced gastric mucosal injury mice model. We found that KP inhibited the growth of H. pylori and attenuated the expression of H. pylori virulence factors such as cytotoxin-associated gene A, encoding urease A subunit, surface antigen gene and neutrophil-activating protein A. Moreover, KP reduced both gross lesions and pathological scores in H. pylori-challenged mice. In addition, KP markedly restrained the production of pro-inflammatory cytokines and nitric oxide levels compared with an untreated H. pylori-infected group. In particular, we found that KP repressed the phosphorylation of IκBα and NF-κB p65 subunit, and subsequently suppressed their downstream target genes. Taken together, these findings demonstrate the beneficial effects of KP on inflammation through the inhibition of NF-κB signaling as well as inhibition of H. pylori growth in a mouse model infected with H. pylori. This suggests the potential application of KP as a natural supplement for patient's suffering from gastric mucosal injury caused by H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Própole , Camundongos , Animais , Própole/farmacologia , Própole/uso terapêutico , NF-kappa B/metabolismo , Mucosa Gástrica , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Anti-Inflamatórios/uso terapêutico , República da CoreiaRESUMO
OBJECTIVES: To investigate the diagnostic accuracy of using 3D polylines (3DPs) to improve cone-beam CT (CBCT) virtual navigation (VN)-guided percutaneous transthoracic needle biopsies (PTNB) of pulmonary lesions. METHODS: From May 2021 to November 2021, patients (81 males and 41 females; age, 65 ± 12 years) who underwent CBCT VN with 3DPs for PTNB of pulmonary lesions were retrospectively reviewed. Fluoroscopic visibility of target lesions was evaluated using captured images from a Bull's eye view. Diagnostic accuracy was calculated, and complications were assessed. RESULTS: The mean size of biopsied lesions was 23 ± 13 mm (range: 6-75 mm). Overall, 13.9% (17/122) were small pulmonary nodules (diameter ≤1 cm), and 68.0% (83/122) of biopsied lesions were fluoroscopic visible. The overall diagnostic accuracy was 94.3%. The diagnostic accuracy for visible and invisible lesions was 94.0 and 94.9%, respectively (p = 0.843), and 100% for small pulmonary nodules. Major complications occurred in 8.2% (10/122; eight pneumothorax with chest tube insertion, one hemoptysis with transfusion, and one air embolism) of patients. CONCLUSION: CBCT VN with 3DP guidance provide a real-time outline of pulmonary lesions, thus enabling a reliable and accurate PTNB. ADVANCES IN KNOWLEDGE: 3DP guidance could be useful technique for CBCT-guided PTNB, especially in small pulmonary nodules.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Radiografia Intervencionista/métodos , Biópsia Guiada por Imagem/métodos , Nódulos Pulmonares Múltiplos/patologia , Biópsia por Agulha/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologiaRESUMO
This study aimed to report the specific methods and investigate the educational effects of diagnostic musculoskeletal ultrasound training and the Objective Structured Clinical Examination (OSCE) for traditional medicine students. Scanning volar wrist and diagnosing carpal tunnel syndrome were selected for musculoskeletal ultrasound to train students to use the basic functions of the ultrasound device and scan various structures including tendons, nerves, and arteries. The students were divided into two groups: one group had 8 weeks of training with mock OSCE experience and received feedback about their scan images, and the other group had 3 weeks of training with flipped learning. The OSCE was implemented on the last day of the training. The subjective learning outcomes were analyzed as students' evaluation with a 5-point scale, and the objective learning outcomes were analyzed using OSCE scores evaluated with a pre-validated checklist. Of the 111 students, 60 (54.1%) responded to the questionnaire. Overall satisfaction with this ultrasound training was high (4.5 ± 0.60). The average OSCE score in the 8-week group was significantly higher than that in the 3-week group. The students' self-assessment showed no significant differences between the two groups. Proficiency in using ultrasound is affected by the practice time and feedback. Ultrasound training should be further expanded as a required curriculum to meet students' needs and achieve learning objectives in the clinical skills education of Korean medicine colleges. Further studies are needed on ultrasound education, especially guided interventions for traditional medicine students.
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Purpose: The aim of this study was to evaluate the role of Pi10 in patients with fibrotic interstitial lung abnormality (fibrotic ILA) in a chest CT, according to cumulative cigarette smoking. Methods: We retrospectively assessed 54 fibrotic ILA patients and 18 healthy non-smokers (control) who underwent non-enhanced CT and pulmonary function tests. We quantitatively analyzed airway changes (the inner luminal area, airway inner parameter, airway wall thickness, Pi10, skewness, and kurtosis) in the chest CT of fibrotic ILA patients, and the fibrotic ILA patients were categorized into groups based on pack-years: light, moderate, heavy. Airway change data and pulmonary function tests among the three groups of fibrotic ILA patients were compared with those of the control group by one-way ANOVA. Results: Mean skewness (2.58 ± 0.36) and kurtosis (7.64 ± 2.36) in the control group were significantly different from those of the fibrotic ILA patients (1.89 ± 0.37 and 3.62 ± 1.70, respectively, p < 0.001). In fibrotic ILA group, only heavy smokers had significantly increased Pi10 (mean increase 0.04, p = 0.013), increased airway wall thickness of the segmental bronchi (mean increase 0.06 mm, p = 0.005), and decreased lung diffusing capacity for carbon monoxide (p = 0.023). Conclusion: Pi10, as a biomaker of quantitative CT in fibrotic ILA patients, can reveal that smoking affects airway remodeling.
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Fumar Cigarros , Doenças Pulmonares Intersticiais , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
AIMS: Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis. METHODS AND RESULTS: Specifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis. CONCLUSIONS: These results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.
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Aterosclerose , Placa Aterosclerótica , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Linhagem da Célula , Humanos , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica/metabolismo , Transdução de SinaisRESUMO
In the bone marrow, classical and plasmacytoid dendritic cells (DC) develop from the macrophage-DC precursor (MDP) through a common DC precursor (CDP) step. This developmental process receives essential input from the niche in which it takes place, containing endothelial cells (EC) among other cell types. Here we show that targeted deletion of serine/threonine kinase 11 (Stk11) encoding tumor suppressor liver kinase b1 (Lkb1) in mouse ECs but not DCs, results in disrupted differentiation of MDPs to CDPs, severe reduction in mature DC numbers and spontaneous tumorigenesis. In wild type ECs, Lkb1 phosphorylates polypyrimidine tract binding protein 1 (Ptbp1) at threonine 138, which regulates stem cell factor (Scf) pre-mRNA splicing. In the absence of Lkb1, exon 6 of Scf is spliced out, leading to the loss of Scf secretion. Adeno-associated-virus-mediated delivery of genes encoding either soluble Scf or the phosphomimetic mutant Ptbp1T138E proteins rescued the defects of MDP to CDP differentiation and DC shortage in the endothelium specific Stk11 knockout mice. In summary, endothelial Stk11 expression regulates DC differentiation via modulation of Scf splicing, marking the Stk11-soluble-Scf axis as a potential cause of DC deficiency syndromes.
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Proteínas Quinases Ativadas por AMP/genética , Diferenciação Celular/genética , Transformação Celular Neoplásica/genética , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Quinases Proteína-Quinases Ativadas por AMP/genética , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Células da Medula Óssea/metabolismo , Sobrevivência Celular/genética , Células Cultivadas , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Knockout , Camundongos Transgênicos , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismoRESUMO
Fibrosis has various biological processes and affects almost every organ, especially in patients with inflammatory bowel disease, including Crohn's disease, who experience discomfort caused by intestinal fibrosis, which is a problem that needs to be resolved. TGF-ß signaling is known to act as a key regulator of intestinal fibrosis, and its modulation could be an excellent candidate for fibrosis therapy. Xanthohumol (XN) has various effects, including anti-inflammation and anti-cancer; however, the detailed mechanism of TGF-ß signaling has not yet been studied. The purpose of this study was to investigate the mechanism underlying the anti-fibrotic effect of XN on TGF-ß1-induced intestinal fibrosis using primary human intestinal fibroblasts (HIFs). In this study, to check the anti-fibrotic effects of XN on intestinal fibrosis, we assessed the expression of fibrosis-related genes in TGF-ß1-stimulated HIFs by qPCR, immunoblotting, and immunofluorescence staining. As a result, XN showed the ability to reduce the expression of fibrosis-associated genes increased by TGF-ß1 treatment in HIFs and restored the cell shape altered by TGF-ß1. In particular, XN repressed both NF-κB- and Smad-binding regions in the α-SMA promoter, which is important in fibrosis. In addition, XN inhibited NF-κB signaling, including phosphorylated-IkBα and cyclooxygenase-2 expression, and TNF-α-stimulated transcriptional activity of NF-κB. XN attenuated TGF-ß1-induced phosphorylation of Smad2 and Smad3, and the transcriptional activity of CAGA. Particularly, XN interfered with the binding of TGF-Receptor I (TßRI) and Smad3 by binding to the kinase domain of the L45 loop of TßRI, thereby confirming that the fibrosis mechanism did not proceed further. In conclusion, XN has an inhibitory effect on TGF-ß1-induced intestinal fibrosis in HIFs, significantly affecting TGF-ß/Smad signaling.
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NF-kappa B , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , NF-kappa B/metabolismo , Fibrose , Transdução de SinaisRESUMO
Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal by long-term intervention, rejuvenating action, and no risk of bacterial resistance. Stimulated with finding that kimchi prevented H. pylori-gastric cancer, we compared the efficacy of cancer preventive kimchi (cpkimchi) and standard recipe kimchi (skimchi) and the efficacy between fermented kimchi and non-fermented kimchi (kimuchi) in H. pylori-initiated gastric cancer model and explored novel mechanisms hinted from RNAseq transcriptome analysis. Animal models assessing gastric pathology on 24 and 36 weeks after H. pylori initiated, salt diet-promoted gastric mutagenesis model showed fermented cpkimchi afforded the best outcome of either rejuvenating atrophic gastritis or inhibiting tumorigenesis compared to skimchi and kimuchi. Highest inhibition of atrophic gastritis was achieved with cpkimchi, while significantly lower in kimuchi. Transcriptomic analysis showed ameliorated-endoplasmic reticulum (ER) stress, -oxidative stress, and -apoptosis as major rejuvenating action of cpkimchi. Homogenates from animal model showed that elevated expressions of p-PERK, IRE, ATF6, p-elf, and XBP1 in control group, while significantly decreased with dietary intake of only cpkimchi. Significantly increased expressions of HO-1 and γ-GCS were only noted with cpkimchi. Conclusively, long-term dietary intervention of fermented cpkimchi can be potential way preventing H. pylori-associated carcinogenesis via rejuvenation of atrophic gastritis.