Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

BACKGROUND:Pathological cardiac hypertrophy is a risk factor for various heart diseases,but its pathogenesis remains unclear.Circular RNAs are strongly associated with cardiac hypertrophy.However,the role of circular RNA CHACR in cardiac hypertrophy and its regulatory mechanisms have not been clarified.OBJECTIVE:To investigate the role of circular RNA CHACR in pressure overload-induced cardiac hypertrophy and the underlying mechanisms.METHODS:(1)Transverse aortic constriction was used to induce cardiac hypertrophy in vivo after in situ injection of cyclic RNA CHACR overexpressing lentivirus into the heart for 1 week.Heart mass/tibia length ratio and lung mass/tibia length ratio were calculated;cardiomyocyte surface area was measured;hypertrophic marker gene expression levels were detected;myocardial fibrosis degree was detected,and cardiac function was assessed.(2)H9c2 cardiomyocytes were treated with circular RNA CHACR overexpressing lentivirus for 72 hours,and then treated with 1 μmol/L angiotensin Ⅱ for 24 hours to induce hypertrophy of cardiomyocytes.The hypertrophy was assessed by measuring the surface area of cardiomyocytes,the expression level of hypertrophic marker genes,and the protein/DNA ratio.Oxidative stress damage was assessed by detecting reactive oxygen species levels and mitochondrial membrane potential.RESULTS AND CONCLUSION:(1)The expression level of circular RNA CHACR was significantly decreased in both in vivo and in vitro myocardial hypertrophy models(P＜0.01).(2)The overexpression of circular RNA CHACR significantly inhibited the cardiac hypertrophy induced by transverse aortic constriction,including reducing the enlarged heart volume,significantly decreasing the increased heart mass/tibia length ratio(P＜0.05),lung mass/tibia length ratio(P＜0.05),and cardiomyocyte surface area(P＜0.05),and decreasing the upregulated expression levels of hypertrophic markers atrial natriuretic peptide(P＜0.05)and brain natriuretic peptide(P＜0.05).(3)Cardiac fibrosis induced by transverse aortic constriction in mice was significantly inhibited by enforcing expression of circular RNA CHACR,as evidenced by reduced fibrotic area(P＜0.01)and decreased expression levels of the fibrosis marker gene Acta1(P＜0.05).(4)Overexpression of circular RNA CHACR significantly improved cardiac function in mice,including significantly increased ejection fraction(P＜0.05)and fractional shortening(P＜0.01).(5)Enforced expression of circular RNA CHACR significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including a significant reduction in cardiomyocyte surface area(P＜0.05),downregulation of atrial natriuretic peptide(P＜0.05),and brain natriuretic peptide(P＜0.05)expression levels,and a significant decrease in protein/DNA ratio(P＜0.05).(6)Overexpression of circular RNA CHACR significantly inhibited the elevation of reactive oxygen species levels(P＜0.001)and the decrease in mitochondrial membrane potential(P＜0.05)induced by angiotensin Ⅱ.These results confirm that the expression level of circular RNA CHACR is significantly decreased in cardiac hypertrophy at both in vivo and in vitro myocardial hypertrophy models,and overexpression of circular RNA CHACR significantly inhibits cardiac hypertrophy,alleviates cardiac fibrosis,improves cardiac function,and significantly attenuates angiotensin Ⅱ-induced oxidative stress damage.

BACKGROUND:Pathological cardiac hypertrophy is a risk factor for various heart diseases,but its pathogenesis remains unclear.Circular RNAs are strongly associated with cardiac hypertrophy.However,the role of circular RNA CHACR in cardiac hypertrophy and its regulatory mechanisms have not been clarified.OBJECTIVE:To investigate the role of circular RNA CHACR in pressure overload-induced cardiac hypertrophy and the underlying mechanisms.METHODS:(1)Transverse aortic constriction was used to induce cardiac hypertrophy in vivo after in situ injection of cyclic RNA CHACR overexpressing lentivirus into the heart for 1 week.Heart mass/tibia length ratio and lung mass/tibia length ratio were calculated;cardiomyocyte surface area was measured;hypertrophic marker gene expression levels were detected;myocardial fibrosis degree was detected,and cardiac function was assessed.(2)H9c2 cardiomyocytes were treated with circular RNA CHACR overexpressing lentivirus for 72 hours,and then treated with 1 μmol/L angiotensin Ⅱ for 24 hours to induce hypertrophy of cardiomyocytes.The hypertrophy was assessed by measuring the surface area of cardiomyocytes,the expression level of hypertrophic marker genes,and the protein/DNA ratio.Oxidative stress damage was assessed by detecting reactive oxygen species levels and mitochondrial membrane potential.RESULTS AND CONCLUSION:(1)The expression level of circular RNA CHACR was significantly decreased in both in vivo and in vitro myocardial hypertrophy models(P＜0.01).(2)The overexpression of circular RNA CHACR significantly inhibited the cardiac hypertrophy induced by transverse aortic constriction,including reducing the enlarged heart volume,significantly decreasing the increased heart mass/tibia length ratio(P＜0.05),lung mass/tibia length ratio(P＜0.05),and cardiomyocyte surface area(P＜0.05),and decreasing the upregulated expression levels of hypertrophic markers atrial natriuretic peptide(P＜0.05)and brain natriuretic peptide(P＜0.05).(3)Cardiac fibrosis induced by transverse aortic constriction in mice was significantly inhibited by enforcing expression of circular RNA CHACR,as evidenced by reduced fibrotic area(P＜0.01)and decreased expression levels of the fibrosis marker gene Acta1(P＜0.05).(4)Overexpression of circular RNA CHACR significantly improved cardiac function in mice,including significantly increased ejection fraction(P＜0.05)and fractional shortening(P＜0.01).(5)Enforced expression of circular RNA CHACR significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including a significant reduction in cardiomyocyte surface area(P＜0.05),downregulation of atrial natriuretic peptide(P＜0.05),and brain natriuretic peptide(P＜0.05)expression levels,and a significant decrease in protein/DNA ratio(P＜0.05).(6)Overexpression of circular RNA CHACR significantly inhibited the elevation of reactive oxygen species levels(P＜0.001)and the decrease in mitochondrial membrane potential(P＜0.05)induced by angiotensin Ⅱ.These results confirm that the expression level of circular RNA CHACR is significantly decreased in cardiac hypertrophy at both in vivo and in vitro myocardial hypertrophy models,and overexpression of circular RNA CHACR significantly inhibits cardiac hypertrophy,alleviates cardiac fibrosis,improves cardiac function,and significantly attenuates angiotensin Ⅱ-induced oxidative stress damage.

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker initially identified from colorectal cancer cell lines and is currently widely used in the diagnosis and monitoring of pancreatic and biliary tract cancers. Although CA 19-9 is not routinely screened in general checkups, increasing its screening has led to the frequent detection of elevated CA 19-9 levels in asymptomatic individuals. Patients with elevated CA 19-9 levels often visit clinics for concerns about malignancy, making cancer exclusion essential to exclude cancers through detailed medical history taking, physical examination, and imaging studies. However, many cases of elevated CA 19-9 levels result from benign causes, such as pancreatobiliary diseases, hepatic diseases, pulmonary diseases, or gynecologic conditions. Thus, to avoid unnecessary tests, clinicians must understand the various causes and mechanisms of CA 19-9 elevation. Integrating the patient’s symptoms and medical and family history facilitates appropriate test selection and minimizes unnecessary procedures.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker initially identified from colorectal cancer cell lines and is currently widely used in the diagnosis and monitoring of pancreatic and biliary tract cancers. Although CA 19-9 is not routinely screened in general checkups, increasing its screening has led to the frequent detection of elevated CA 19-9 levels in asymptomatic individuals. Patients with elevated CA 19-9 levels often visit clinics for concerns about malignancy, making cancer exclusion essential to exclude cancers through detailed medical history taking, physical examination, and imaging studies. However, many cases of elevated CA 19-9 levels result from benign causes, such as pancreatobiliary diseases, hepatic diseases, pulmonary diseases, or gynecologic conditions. Thus, to avoid unnecessary tests, clinicians must understand the various causes and mechanisms of CA 19-9 elevation. Integrating the patient’s symptoms and medical and family history facilitates appropriate test selection and minimizes unnecessary procedures.

Background/Aims: This study aimed to compare the safety of the double-guidewire technique (DGT) with that of the conventional single-guidewire technique (SGT) in real-world situations. Methods: A total of 240 patients with naïve papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) at Daegu Catholic University Medical Center between January 2021 and December 2021 were included. The primary outcome was the rate of post-ERCP pancreatitis (PEP) in the SGT and DGT groups. Results: A total of 163 patients (67.9%) belonged to the SGT group, and 77 (32.1%) belonged to the DGT group. The rates of successful biliary cannulation were 95.7% and 83.1% in the SGT and DGT groups, respectively (p=0.002). In the study group, PEP occurred in 14 patients (5.8%). The PEP rates were not significantly different between the SGT and DGT groups (4.3% vs. 9.1%, p=0.150). In the multivariate analysis, the age of <50 years (odds ratio [OR], 9.305; 95% confidence interval [CI], 1.367–63.358; p=0.023) and hyperlipidemia (OR, 7.384; 95% CI, 1.103–49.424; p=0.039) were significant risk factors for PEP in the DGT group. Conclusions DGT did not increase the PEP rate in patients with naïve papilla. In addition, the age of <50 years and hyperlipidemia were significant risk factors for PEP in the DGT group.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker initially identified from colorectal cancer cell lines and is currently widely used in the diagnosis and monitoring of pancreatic and biliary tract cancers. Although CA 19-9 is not routinely screened in general checkups, increasing its screening has led to the frequent detection of elevated CA 19-9 levels in asymptomatic individuals. Patients with elevated CA 19-9 levels often visit clinics for concerns about malignancy, making cancer exclusion essential to exclude cancers through detailed medical history taking, physical examination, and imaging studies. However, many cases of elevated CA 19-9 levels result from benign causes, such as pancreatobiliary diseases, hepatic diseases, pulmonary diseases, or gynecologic conditions. Thus, to avoid unnecessary tests, clinicians must understand the various causes and mechanisms of CA 19-9 elevation. Integrating the patient’s symptoms and medical and family history facilitates appropriate test selection and minimizes unnecessary procedures.