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Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer worldwide. The epithelial-mesenchymal transition (EMT) is a critical process in cancer progression, contributing to increased malignancy. While Pleiotropic Regulator 1 (PLRG1) is upregulated in HCC and is associated with enhanced cell proliferation, its oncogenic role in EMT remains unclear. In this study, we demonstrate that PLRG1 promotes EMT in HCC cells. Knockdown of PLRG1 in Huh7 cells resulted in decreased expression of the EMT markers N-cadherin and Snail, and impaired cell migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase assays identified Y-box binding protein 1 (YBX1) as a direct regulator of PLRG1 transcription, binding to its promoter region. Overexpression of YBX1 in SNU-449 cells led to increased PLRG1 expression and subsequent EMT activation, as well as enhanced migration, and invasion. These effects were attenuated by PLRG1 knockdown. Our findings indicate that YBX1 drives EMT in HCC by upregulating PLRG1, offering novel insights into the molecular mechanisms underlying HCC progression.
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Carcinoma Hepatocelular , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas , Proteínas Nucleares , Proteína 1 de Ligação a Y-Box , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Proteínas Nucleares/genética , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Background: Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough. Methods: This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control. Results: The analysis of 341 patients (mean age: 55.5±15.1â years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated "need for cough rescue drug" notably higher than physicians. Conclusion: Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough.
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Pure laparoscopic living-donor right hepatectomy (PLDRH) has emerged as a significant advancement in liver transplantation, offering reduced donor morbidity and improved recovery times. However, PLDRH is still performed in only a limited number of centers. This retrospective study reports on the outcomes of 215 living donors who underwent PLDRH at Asan Medical Center in Seoul, Korea between November 2014 and December 2021. We reviewed donor and recipient demographics and anatomical characteristics of the donor grafts. Donor complications were classified and evaluated based on the Clavien-Dindo classification. The incidence of early donor complications within 30 days of surgery was 0.9% (n = 3), with minor complications in 0.3% (n = 1) patients and major complications in 0.6% (n = 2). No biliary complications were observed and no late complications had been reported by 30 days after surgery. The mean length of postoperative hospital stay was 7.2 days. PLDRH was a safe and feasible surgical technique characterized by a low complication rate and short hospital stays. PLDRH has the potential to become the standard procedure for the retrieval of right liver grafts from living donors.
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Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except "cough," were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P < 0.05). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 (P < 0.05) and anti-IL-4/IL-13 (P < 0.05) treatment groups with no significant difference between groups (P > 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.
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Cannabis (Cannabis sativa) is a versatile crop belonging to the Cannabaceae family, and is dioecious, typically with separate male and female plants. The flowers of female plants, especially the trichomes, accumulate relatively higher contents of cannabinoids compared with those of male plants. For this reason, to obtain seeds that are genetically female, it is desirable to induce the development of male flowers on a female plant that produces genetically female haploid gametes. Silver thiosulfate (STS) is a highly effective chemical for male flower induction. We investigated male flower induction in three commercial cultivars of female cannabis (Spectrum303, SuperwomanS1, and CBGambit) regarding the treatment frequency, stage of application, and concentration of STS applied as a foliar spray. All three cultivars showed adequate induction of male flowers in response to 1.5 mM STS applied at the early reproductive stage. In particular, SuperwomanS1 was most highly responsive to induction of male flowers, even when treated with 0.3 mM STS at the early reproductive stage. Treatment with three applications of STS was more effective compared with a single application, but a single application of 1.5 mM STS at the early reproductive stage was sufficient for male flower induction. A single STS application during the middle stage of reproductive growth was inadequate for induction of male flowers. However, 6 weeks after three applications of STS, CBGambit exhibited approximately 54% male flower induction at 0.3 mM STS, Spectrum303 showed approximately 56% induction at 3 mM STS, and SuperwomanS1 yielded approximately 26% induction at 1.5 mM (expressed as percentage of total number of individuals with the induced male flowers). Pollen stainability tests using KI-I2 solution and Alexander's staining showed high pollen viability with over 65% at different single STS concentrations, indicating that pollen grains induced by STS have sufficient viability for the self-pollination. This study demonstrated that different cultivars of cannabis respond diversely to different STS concentrations and highlighted the potential benefits of three STS applications during the middle reproductive stage for cannabis breeding.
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This study demonstrated a simple and innovative way of using the direct de novo synthesis to fabricate the mesoporous structure and diverse functionality of ZIF-8 for environmental cleanup and gas storage applications. By introducing different ligands, we have developed a version of ZIF-8 that could better capture carbon dioxide (CO2) and iodine. The ZIF-8 was successfully designed to have the hierarchical and mesoporous structure with the functional groups of amine and thiol groups by adjusting the pKa values (from 8 to 12) of ligand instead of original ligand, 2-methyl imidazole (Hmim, pKa~14.2). The modulation of ZIF-8 particle size, porosity, and functional characteristics was achieved through varied ligands and their concentrations, streamlined into a single and room-temperature synthesis condition. The resulting ZIF-8 materials exhibit intricate hierarchical architectures and a high density of functional groups, significantly enhancing molecular diffusion and accessibility. Among the developed materials, ZIF-8-AS, featuring both amine and thiol groups, demonstrates the fastest adsorption kinetics and a twofold increase in iodine adsorption capacity (qm = 1101.5 mg·g-1) compared to ZIF-8 (qm = 514.3 mg·g-1). Furthermore, the hierarchical mesoporosity of ZIF-8-A-10.1 improves CO2 adsorption to 1.0 mmol·g-1 at 298 K, which is 1.3 times higher than that of the microporous ZIF-8.
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Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-ß1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-ß1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.
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Bleomicina , Lipopolissacarídeos , Piridonas , Síndrome do Desconforto Respiratório , Transdução de Sinais , Animais , Piridonas/farmacologia , Piridonas/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Ratos , Masculino , Bleomicina/efeitos adversos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteína Smad2/metabolismo , Ratos Sprague-Dawley , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Modelos Animais de Doenças , Metaloproteinase 9 da Matriz/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Proteínas Smad/metabolismoRESUMO
Various treatment modalities are available for small solitary hepatocellular carcinoma (HCC), yet the optimal primary treatment strategy for tumors ≤ 3 cm remains unclear. This network meta-analysis investigates the comparative efficacy of various interventions on the long-term outcomes of patients with solitary HCC ≤ 3 cm. A systematic search of electronic databases from January 2000 to December 2023 was conducted to identify studies that compared at least two of the following treatments: surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), and transarterial chemoembolization (TACE). Survival data were extracted, and pooled hazard ratios with 95% confidence intervals were calculated using a frequentist network meta-analysis. A total of 30 studies, comprising 2 randomized controlled trials and 28 retrospective studies, involving 8,053 patients were analyzed. Surgical resection showed the highest overall survival benefit with a p-score of 0.95, followed by RFA at 0.59, MWA at 0.23, and TACE, also at 0.23. Moreover, SR provided the most significant recurrence-free survival advantage, with a p-score of 0.95, followed by RFA at 0.31 and MWA at 0.19. Sensitivity analyses, excluding low-quality or retrospective non-matched studies, corroborated these findings. This network meta-analysis demonstrates that SR is the most effective first-line curative treatment for single HCC ≤ 3 cm, followed by RFA in patients with preserved liver function. The limited data on MWA and TACE underscore the need for further studies.
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Background: While numerous studies have been conducted on sudden sensorineural hearing loss (SSNHL), research on how treatment outcomes and prognosis vary by age remains insufficient. This study aims to investigate the differences in recovery rates among SSNHL patients divided by age groups. Methods: A retrospective study was conducted on 177 patients diagnosed with SSNHL from 2020 to 2023. The patients were categorized into four age groups: under 20, 30-40, 50-60, and over 70. Recovery rates and associated symptoms were compared across these groups. Results: Significant recovery rates were observed in all age groups except for those over 70 (p = 0.006, p = 0.003, p = 0.009). No significant differences were found in recovery rates based on gender (p > 0.75) or symptoms such as tinnitus, ear fullness, and dizziness (p > 0.05). Conclusions: The study revealed that younger and middle-aged adults showed statistically significant improvements in recovery rates, while the elderly exhibited relatively lower recovery rates.
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OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.
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BACKGROUND: No studies to date have compared audiologic characteristics in patients with continuous and intermittent tinnitus. The present study classified tinnitus patients into continuous and intermittent groups based on tinnitus duration and compared their audiologic characteristics. METHODS: This study enrolled 604 patients with tinnitus from January 2019 to December 2022. Clinical manifestations, PTA results, the frequency and loudness of tinnitus, ABR, DPOAE, and TEOAE tests were compared in patients with continuous and intermittent tinnitus. RESULTS: Of the 604 patients, 231 (38.2%) had continuous and 373 (61.8%) had intermittent tinnitus. There were no significant between-group differences in otologic symptoms, tinnitus onomatopoeia. PTA showed that hearing thresholds, except at 125 Hz, were significantly higher in patients with continuous rather than intermittent tinnitus. The loudness of tinnitus was significantly greater in patients with continuous rather than intermittent tinnitus. ABR tests showed that the absolute latency of wave V was significantly longer in continuous than in intermittent tinnitus. Signal-to-noise ratios on TEOAE tests were significantly lower in patients with continuous rather than intermittent tinnitus at all frequencies tested (1, 1.5, 2, 3, and 4 kHz). Response rates to sound stimuli at all frequencies, except for 1 kHz, were significantly lower on DPOAE tests in patients with continuous rather than intermittent tinnitus. CONCLUSIONS: Continuous tinnitus is more common in males, more persistent over time, and is associated with a higher rate of hearing loss. In contrast, intermittent tinnitus is more common in women, appears acutely, and is associated with a relatively lower rate of hearing loss. Based on the findings of the current paper, it seems that audiologic characteristics may differ between patients with continuous and intermittent tinnitus.
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Rapeseed (Brassica napus L.) holds significant commercial value as one of the leading oil crops, with its agronomic features and oil quality being crucial determinants. In this investigation, 73,226 single nucleotide polymorphisms (SNPs) across 95 rapeseed mutant lines induced by gamma rays, alongside the original cultivar ('Tamra'), using genotyping-by-sequencing (GBS) analysis were examined. This study encompassed gene ontology (GO) analysis and a genomewide association study (GWAS), thereby concentrating on agronomic traits (e.g., plant height, ear length, thousand-seed weight, and seed yield) and oil traits (including fatty acid composition and crude fat content). The GO analysis unveiled a multitude of genes with SNP variations associated with cellular processes, intracellular anatomical structures, and organic cyclic compound binding. Through GWAS, we detected 320 significant SNPs linked to both agronomic (104 SNPs) and oil traits (216 SNPs). Notably, two novel candidate genes, Bna.A05p02350D (SFGH) and Bna.C02p22490D (MDN1), are implicated in thousand-seed weight regulation. Additionally, Bna.C03p14350D (EXO70) and Bna.A09p05630D (PI4Kα1) emerged as novel candidate genes associated with erucic acid and crude fat content, respectively. These findings carry implications for identifying superior genotypes for the development of new cultivars. Association studies offer a cost-effective means of screening mutants and selecting elite rapeseed breeding lines, thereby enhancing the commercial viability of this pivotal oil crop.
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PURPOSE: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT). METHODS: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center. RESULTS: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941). CONCLUSIONS: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC.
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Neoantigens are ideal targets for cancer immunotherapy because they are expressed de novo in tumor tissue but not in healthy tissue and are therefore recognized as foreign by the immune system. Advances in next-generation sequencing and bioinformatics technologies have enabled the quick identification and prediction of tumor-specific neoantigens; however, only a small fraction of predicted neoantigens are immunogenic. To improve the predictability of immunogenic neoantigens, we developed the in silico neoantigen prediction workflows VACINUSpMHC and VACINUSTCR: VACINUSpMHC incorporates physical binding between peptides and MHCs (pMHCs), and VACINUSTCR integrates T cell reactivity to the pMHC complex through deep learning-based pairing with T cell receptors (TCRs) of putative tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs). We then validated our neoantigen prediction workflows both in vitro and in vivo in patients with hepatocellular carcinoma (HCC) and in a B16F10 mouse melanoma model. The predictive abilities of VACINUSpMHC and VACINUSTCR were confirmed in a validation cohort of 8 patients with HCC. Of a total of 118 neoantigen candidates predicted by VACINUSpMHC, 48 peptides were ultimately selected using VACINUSTCR. In vitro validation revealed that among the 48 predicted neoantigen candidates, 13 peptides were immunogenic. Assessment of the antitumor efficacy of the candidate neoepitopes using a VACINUSTCR in vivo mouse model suggested that vaccination with the predicted neoepitopes induced neoantigen-specific T cell responses and enabled the trafficking of neoantigen-specific CD8 + T cell clones into the tumor tissue, leading to tumor suppression. This study showed that the prediction of immunogenic neoantigens can be improved by integrating a tumor-reactive TIL TCR-pMHC ternary complex.
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Antígenos de Neoplasias , Linfócitos do Interstício Tumoral , Receptores de Antígenos de Linfócitos T , Antígenos de Neoplasias/imunologia , Animais , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linhagem Celular Tumoral , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Complexo Principal de Histocompatibilidade/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Linfócitos T CD8-Positivos/imunologia , Feminino , Imunoterapia/métodosRESUMO
PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.
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Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.
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Fibrose , Piridonas , Ratos Sprague-Dawley , Bexiga Inativa , Bexiga Urinária , Micção , Animais , Piridonas/farmacologia , Piridonas/uso terapêutico , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Ratos , Micção/efeitos dos fármacos , Bexiga Inativa/tratamento farmacológico , Bexiga Inativa/fisiopatologia , Bexiga Inativa/etiologia , Modelos Animais de Doenças , Feminino , MasculinoRESUMO
Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 µL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.
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Colite Ulcerativa , Modelos Animais de Doenças , Mesalamina , Condicionamento Físico Animal , Animais , Mesalamina/uso terapêutico , Mesalamina/farmacologia , Colite Ulcerativa/terapia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Camundongos , Masculino , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Sulfato de Dextrana , NF-kappa B/metabolismo , Citocinas/metabolismo , Apoptose/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
BACKGROUND: Magnetically assisted capsule endoscopy (MACE) showed the feasibility for upper gastrointestinal examination. To further enhance the performance of conventional MACE, it is necessary to provide quality-improved and three-dimensional images. The aim of this clinical study was to determine the efficacy and safety of novel three-dimensional MACE (3D MACE) for upper gastrointestinal and small bowel examination at once. METHODS: This was a prospective, single-center, non-randomized, and sequential examination study (KCT0007114) at Dongguk University Ilsan Hospital. Adult patients who visited for upper endoscopy were included. The study protocol was conducted in two stages. First, upper gastrointestinal examination was performed using 3D MACE, and a continuous small bowel examination was performed by conventional method of capsule endoscopy. Two hours later, an upper endoscopy was performed for comparison with 3D MACE examination. The primary outcome was confirmation of major gastric structures (esophagogastric junction, cardia/fundus, body, angle, antrum, and pylorus). Secondary outcomes were confirmation of esophagus and duodenal bulb, accuracy for gastric lesions, completion of small bowel examination, 3D image reconstruction of gastric lesion, and safety. RESULTS: Fifty-five patients were finally enrolled. The examination time of 3D MACE was 14.84 ± 3.02 minutes and upper endoscopy was 5.22 ± 2.39 minutes. The confirmation rate of the six major gastric structures was 98.6% in 3D MACE and 100% in upper endoscopy. Gastric lesions were identified in 43 patients during 3D MACE, and 40 patients during upper endoscopy (Sensitivity 0.97). 3D reconstructed images were acquired for all lesions inspected by 3D MACE. The continuous small bowel examination by 3D MACE was completed in 94.5%. 3D MACE showed better overall satisfaction (3D MACE 9.55 ± 0.79 and upper endoscopy 7.75 ± 2.34, p<0.0001). There were no aspiration or significant adverse event or capsule retention in the 3D MACE examination. CONCLUSIONS: Novel 3D MACE system is more advanced diagnostic modality than the conventional MACE. And it is possible to perform serial upper gastrointestinal and small bowel examination as a non-invasive and one-step test. It would be also served as a bridge to pan-endoscopy.
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Endoscopia por Cápsula , Imageamento Tridimensional , Intestino Delgado , Humanos , Endoscopia por Cápsula/métodos , Endoscopia por Cápsula/efeitos adversos , Masculino , Feminino , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Pessoa de Meia-Idade , Imageamento Tridimensional/métodos , Estudos Prospectivos , Adulto , Idoso , Trato Gastrointestinal Superior/diagnóstico por imagem , Trato Gastrointestinal Superior/patologiaRESUMO
This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.