Search

Numerous studies have explored the welfare rearing conditions of broilers; however, studies on the level of metabolisable energy (ME) in feed, which is a key factor in broiler growth, are lacking. Accordingly, this study investigated the appropriate ME levels for broilers under welfare rearing environments. A total of 980 one-day-old male chickens (Ross 308) were allocated to each group according to the environment and dietary ME as follows: conventional environment fed a standard ME program (conventional control; CC), welfare environment with a standard ME (welfare control; WC) and welfare groups with 200 kcal/kg lower (WL200), 100 kcal/kg lower (WL100), 100 kcal/kg higher (WH100) and 200 kcal/kg higher (WH200) than standard ME. The experiment lasted 5 weeks. The productivity, meat quality, blood and intestinal characteristics, nutrient digestibility and welfare indicators were analysed, whose results are as follows: WH200 had the highest body weight and low feed conversion ratio, whereas CC had the lowest feed intake (p

Abstract Transcriptional silencing by RNAi paradoxically relies on transcription, but how the transition from transcription to silencing is achieved has remained unclear. The Cryptic Loci Regulator complex (CLRC) in Schizosaccharomyces pombe is a cullin-ring E3 ligase required for silencing that is recruited by RNAi. We found that the E2 ubiquitin conjugating enzyme Ubc4 interacts with CLRC and mono-ubiquitinates the histone H3K9 methyltransferase Clr4SUV39H1, promoting the transition from co-transcriptional gene silencing (H3K9me2) to transcriptional gene silencing (H3K9me3). Ubiquitination of Clr4 occurs in an intrinsically disordered region (Clr4IDR), which undergoes liquid droplet formation in vitro, along with Swi6HP1 the effector of transcriptional gene silencing. Our data suggests that phase separation is exquisitely sensitive to non-coding RNA (ncRNA) which promotes self-association of Clr4, chromatin association, and di-, but not tri- methylation instead. Ubc4-CLRC also targets the transcriptional co-activator Bdf2BRD4, down-regulating centromeric transcription and small RNA (sRNA) production. The deubiquitinase Ubp3 counteracts both activities.

Abstract Astronauts wear liquid perfused garments inside their outer spacesuits for regulating body temperature. The present study explored relationships between local heat production from the upper arm and body morphology while wearing liquid perfused sleeve. Heat extraction from the upper arm of 19 subjects (8 males and 11 females) during three different exercise modes (running at 6–8 km∙h−1, cycling at 40–55 W, and arm ergometer at 10–20 W) and rest has been investigated. The total body fat (27.5 ± 7.2%), body mass index (24.4 ± 2.7 kg·m−2), arm surface area (589 ± 90 cm2), and arm volume (1300 ± 300 mL) were considered as covariates. Subjects wore a liquid perfused sleeve over the upper arm (left) with the water inlet temperature of 24.0 ± 0.3 °C and the heat extraction was calculated using the water flow rate and temperature differences. Heat extraction from the upper arm showed no significant differences among the three exercises. During cycling, there was a negative relationship between heat extraction and total body fat (r = − 0.527, P

Abstract Garnet-type Li6.1Ga0.3La3Zr2O12 (LGLZO) exhibits high ionic conductivity and extremely low electronic conductivity. The electrochemical properties strongly depend on the characteristics of the grain boundaries and pores in the oxide–ceramic electrolyte. Currently, the main issue of LGLZO is its large grain boundary resistance due to high-temperature sintering. Herein, we propose an effective method for reinforcing the chemical and structural characteristics of the grain boundaries using a Li2O-B2O3-Al2O3 (LBA) sintering aid. In this study, the LBA sintering aid is critical because it fills grain boundaries and void spaces. As a result, LGLZO solid-state electrolytes with sintering aids significantly enhance the ionic conductivity and reduce the activation energy, especially in the grain boundary region. Another crucial issue is the formation of Li dendrites in LGLZO. Since dendritic Li propagates along the grain boundaries, the optimized LGLZO solid-state electrolyte demonstrates excellent stability against Li metals. Overall, the LGLZO electrolyte with the LBA sintering aid exhibits stable long-term cycling performance due to the well-designed grain boundaries.

Hypertension is a significant risk factor for cardiovascular disease and heart damage. Stichopus japonicus (S. japonicus) is a red sea cucumber with antioxidant and anti-hypertensive activities. However, its anti-hypertensive mechanism remains unclear. In this study, we evaluated the inhibitory effects of angiotensin-converting enzyme (ACE) of α-chymotrypsin-assisted hydrolysate of S. japonicus (α-chy) and its ultrafiltrate fractions (>10 kDa [α-chy-I], 5–10 kDa [α-chy-II], and

This study aimed to screen peptides with antihypertensive effects from the α-chymotrypsin hydrolysate of Sebastes schlegelii (SSA). SSA demonstrated ACE inhibitory activity with an IC50 value of 0.062 ± 0.001 mg/mL. The SSA significantly reduced body weight and systolic blood pressure in the SHR spontaneously hypertensive rat (SHR) model and improved hypertension-induced vasopathy and interstitial fibrosis in heart and vascular tissues, indicating the presence of ACE inhibitory peptides contributing to cardiovascular health. Peptide composition analysis identified fractions of SSA with potent ACE inhibitory activity, particularly those with molecular weights of 5 kDa or less. Further evaluation of ACE activity using Sephadex G-10 separated SSA fractions led to the amino acid sequence analysis of the most effective fraction (SSA-F1). Molecular docking simulations predicted that peptides from SSA-F1 inhibit ACE activity by binding to its active sites. This research suggests the potential of peptides from S. schlegelii for clinical hypertension treatment.

Abstract A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Abstract Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image–based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model’s decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Abstract Background/aims Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. Methods This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. Results Significant differences were observed in each bile acid level in the three endoscopic BR groups (P

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Background: A sea cucumber (Stichopus japonicus) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry. Methods: Bioactive peptides were isolated from Stichopus japonicus through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity. Results: Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC50 values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril. Conclusions: These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods.

Abstract Background Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). Methods We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. Results By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. Conclusions The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. Trial registration NCT04080726 ( https://classic.clinicaltrials.gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits.

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet’s disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p

Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session. Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.

Abstract Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time‐consuming, labor‐intensive, and prone to intra‐ and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four‐step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.

Background/Aims: Gastrointestinal (GI) bezoars are relatively rare diseases with clinical characteristics and treatment modalities that depend on the location of the bezoars. This study evaluated the clinical characteristics and treatment outcomes in patients with GI bezoars. Methods: Seventy-five patients diagnosed with GI bezoars were enrolled in this study. Data were collected on the demographic and clinical characteristics and the characteristics of the bezoars, such as type, size, location, treatment modality, and clinical outcomes. Results: Among the 75 patients (mean age 71.2 years, 38 males), 32 (42.6%) had a history of intra-abdominal surgery. Hypertension (43%) and diabetes (30%) were common morbidities. The common location of the bezoars was the stomach in 33 (44%) and the small intestine in 33 (44%). Non-surgical management, including adequate hydration, chemical dissolution, and endoscopic removal, was successful in 2/2 patients with esophageal bezoars, 26/33 patients with gastric bezoars, 7/9 patients with duodenal bezoars, and 20/33 patients with small intestinal bezoars. The remaining patients had undergone surgical management. Conclusions: The management of GI bezoars requires multidisciplinary approaches, including the appropriate correction of fluid and electrolyte imbalances, chemical dissolution, and endoscopic and surgical treatments.

Abstract The association between ulcerative colitis (UC) and uterine cervical cancer is still unclear. To investigate cervical cancer risk in South Korean women with UC, we analyzed the Korean National Health Insurance claims data. UC was defined using both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases of UC diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios were calculated using multivariate Cox proportional hazard regression, and the event was defined as occurrence of cervical cancer. A total of 12,632 women with UC and 36,797 women without UC were enrolled. The incidence of cervical cancer was 38.8 per 100,000 women per year in UC patients and 25.7 per 100,000 women per year in controls, respectively. The adjusted HR for cervical cancer was 1.56 (95% CI 0.97–2.50) in the UC group with reference to the control group. When stratified by age, the adjusted HR for cervical cancer was 3.65 (95% CI 1.54–8.66) in elderly UC patients (≥ 60 years) compared to elderly control group (≥ 60 years). Within UC patients, increased age (≥ 40 years) and low socioeconomic status were associated with an increased risk of cervical cancer. The incidence of cervical cancer was found to be higher among elderly patients (≥ 60 years) with newly diagnosed UC in South Korea, compared to age-matched controls. Therefore, regular cervical cancer screening is recommended for elderly patients who have recently been diagnosed with UC.

This study was conducted to efficiently produce virus-like particles (VLPs) of enterovirus 71 (EV71), a causative virus of hand, foot, and mouth disease (HFMD). The expression level of the P1 precursor, a structural protein of EV71, was modified to increase VLP production, and the optimal expression level and duration of the 3CD protein for P1 cleavage were determined. The expression level and duration of 3CD were controlled by the p10 promoter, which was weakened by repeated burst sequence (BS) applications, as well as the OpIE2 promoter, which was weakened by the insertion of random untranslated region sequences of various lengths. The cleavage and production efficiency of the P1 precursor were compared based on the expression time and level of 3CD, revealing that the p10-BS5 promoter with four repeated BSs was the most effective. When P1 and 3CD were expressed using the hyperexpression vector and the p10-BS5 promoter, high levels of structural protein production and normal HFMD-VLP formation were observed, respectively. This study suggests that the production efficiency of HFMD-VLPs can be significantly enhanced by increasing the expression of the P1 precursor and controlling the amount and duration of 3CD expression.

Background/aimsColonic diverticular bleeding (CDB) is a common cause of acute lower gastrointestinal bleeding. Patients with CDB are at increased risk for recurrence. Here, we aimed to evaluate the clinical course of patients with CDB and identify risk factors for recurrent CDB (rCDB).MethodsWe included patients who were hospitalized at a single tertiary center for management of CDB between January 2005 and March 2020. A Cox proportional hazards regression analysis was performed to evaluate the risk factors of patients with rCDB as follows: model 1 adjusted by age, Charlson comorbidity index (CCI), and presence of bilateral colon diverticula; model 2 adjusted by age, CCI, and presence of left side colon diverticula; model 3 adjusted by age, CCI, and presence of sigmoid colon diverticula.ResultsAmong 219 patients (mean age, 68.0 years; 55 females), 56 and 163 had definite and presumptive CDB, respectively. During the median period of 506 days, 62 patients (28.3%) experienced rCDB. CCI score ≥ 4 was independently associated with rCDB in models 1, 2 and 3 (all p

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p

Brown adipose tissue (BAT) is a specialized thermogenic organ that undergoes high demands of protein synthesis during thermogenic adaptation. Here, the authors show that the cold responsive phosphatase Ssu72 is required for mRNA translation that affects thermogenic adaptation in BAT.

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 μg/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. The potential cytotoxicity of NO and PGE2 was first examined, confirming no toxicity at concentrations ranging from 10-100 μg/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 μg/mL S. linearis extract, respectively; and PGE2 production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 μg/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE2 production. The cellular production of reactive oxygen species, measured using 2′,7′-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 μg/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 μg/mL extract and against Bacillus cereus with a MIC of 1,024 μg/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-β1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-β1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-β1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-β1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, metallopeptidase-9 (MMP-9), the calcitonin receptor (CTR), and cathepsin K (CTK). IOE treatment suppressed the expression of activated T cell cytoplasmic 1 and activator protein-1, thus controlling the expression of osteoclast-related factors. Moreover, IOE significantly reduced RANKL-phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). It also reduced the RANKL-induced phosphorylation of NF-κB and nuclear translocation of p65. IOE inhibited Dex-induced bone loss and osteoclast-related gene expression in zebrafish larvae. HPLC analysis shows that IOE consists of 3.13% and 3.42% DPHC and IPA, respectively. Our results show that IOE has inhibitory effects on osteoclastogenesis in vitro and in vivo and is a potential therapeutic for osteoporosis.

The World Health Organization Classification of Tumors of the Central Nervous System recently incorporated histological features, immunophenotypes, and molecular characteristics to improve the accuracy of glioblastoma (GBM) diagnosis. FGFR3::TACC3 (F3T3) fusion has been identified as an oncogenic driver in IDH-wildtype GBMs. Recent studies have demonstrated the potential of using FGFR inhibitors in clinical trials and TACC3-targeting agents in preclinical models for GBM treatment. However, there is limited information on the clinicopathological and genetic features of IDH-wildtype GBMs with F3T3 fusion. The aim of this study was to comprehensively investigate the clinical manifestations, histological features, and mutational profiles of F3T3-positive GBMs. Between September 2017 and February 2023, 25 consecutive cases (5.0%) of F3T3-positive GBM were extracted from 504 cases of IDH-wildtype GBM. Clinicopathological information and targeted sequencing results obtained from 25 primary and 4 recurrent F3T3-positive GBMs were evaluated and compared with those from F3T3-negative GBMs. The provisional grades determined by histology only were distributed as follows: 4 (26/29; 89.7%), 3 (2/29; 6.9%), and 2 (1/29; 3.4%). Grade 2–3 tumors were ultimately diagnosed as grade 4 GBMs based on the identification of the TERT promoter mutation and the combined gain of chromosome 7 and loss of chromosome 10 (7+/10−). F3T3-positive GBMs predominantly affected women (2.6 females per male). The mean age of patients with an F3T3-positive GBM at initial diagnosis was 62 years. F3T3-positive GBMs occurred more frequently in the cortical locations compared to F3T3-negative GBMs. Imaging studies revealed that more than one-third (12/29; 41.4%) of F3T3-positive GBMs displayed a circumscribed tumor border. Seven of the seventeen patients (41.2%) whose follow-up periods exceeded 20 months died of the disease. Histologically, F3T3-positive GBMs more frequently showed curvilinear capillary proliferation, palisading nuclei, and calcification compared to F3T3-negative GBMs. Molecularly, the most common alterations observed in F3T3-positive GBMs were TERT promoter mutations and 7+/10−, whereas amplifications of EGFR, PDGFRA, and KIT were not detected at all. Other genetic alterations included CDKN2A/B deletion, PTEN mutation, TP53 mutation, CDK4 amplification, and MDM2 amplification. Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.

Dedifferentiation is a very rare phenomenon in uterine leiomyosarcoma (LMS). The aim of this study was to comprehensively analyze the clinicopathological characteristics of uterine dedifferentiated LMS (DDLMS). We reviewed electronic medical records and pathology slides from five patients with uterine DDLMS and performed immunostaining. The mean age of the patients was 56 years. Two patients presented with abdominal discomfort, while in three cases the uterine tumors were detected on routine medical examination. The mean size of the tumors was 17.0 cm. Four patients underwent hysterectomy. The initial stages were distributed as IB (2/5), IIIC (2/5), and IVC (1/5). Post-operative concurrent chemoradiation therapy, radiation therapy, and chemotherapy were administered in one, one, and two patients, respectively. Despite post-operative treatment, three patients developed metastatic recurrences in the abdominal and pelvic organs. Recurrence-free survival time ranged between 4 and 30 months. Histologically, the differentiated areas demonstrated the classic morphology of malignant smooth muscle differentiation, whereas the dedifferentiated areas resembled undifferentiated pleomorphic sarcoma and were characterized by large pleomorphic tumor cells admixed with haphazardly arranged atypical cells with marked nuclear pleomorphism. All cases also exhibited heterologous components, including chondrosarcoma (CSA; 3/5) and rhabdomyosarcoma (2/5). In two cases, the heterologous components were initially detected in primary tumors. In three cases, the primary tumors did not exhibit any dedifferentiated or heterologous components. Instead, more than half of the recurrent tumors consisted of heterologous components. Three cases showed a sharp demarcation between the LMS and CSA components, while in two cases the dedifferentiated area imperceptibly merged with the differentiated component. Immunostaining revealed that the dedifferentiated components exhibited a lack of desmin immunoreactivity in three of the four examined cases. A subset of uterine LMS represents various amounts and types of dedifferentiation and heterologous components in both primary and recurrent tumors. Routine recognition of DDLMS and distinction from its mimickers are required for accurate diagnosis and further characterization of these rare tumors.

Background/Aims: Golimumab has been used for patients with ulcerative colitis (UC) since 2013. However, there is limited data on the effectiveness and safety of the real-world use of golimumab in Asian patients. Methods: This was a multicenter, prospective, observational study. We enrolled patients with moderate-to-severe UC who were administered subcutaneous golimumab at 46 medical centers between May 2014 and November 2019. The primary outcome was the effectiveness and safety of golimumab at week 22. Clinical outcomes and adverse events were assessed according to partial Mayo score at weeks 0, 2, 6, 14, and 22. Results: A total of 130 patients were included (mean age: 45.7±16.0 years). The clinical response/ remission rates at weeks 2, 6, 14, and 22 were 40.4%/22.9%, 56.0%/35.8%, 70.6%/49.5%, and 67.9%/48.6%, respectively. Based on full Mayo score at week 14, clinical response and remission rates were 84.2% and 39.5%, respectively. Mucosal healing rate was 65.8%. In multivariate analysis with logistic regression, longer disease duration was significantly associated with a higher clinical response rate (adjusted odds ratio [aOR], 1.136; 95% confidence interval [CI], 1.006 to 1.282; p=0.040 at week 6; aOR, 1.256; 95% CI, 1.049 to 1.503; p=0.013 at week 22). A higher baseline Mayo endoscopic subscore was significantly associated with a lower clinical response rate at week 6 (aOR, 0.248; 95% CI, 0.089 to 0.692; p=0.008). The incidence of adverse drug reactions was 4.6% (6/130, nine events). No serious unexpected adverse drug reactions or deaths were reported. Conclusions: Golimumab was effective and safe as an induction and maintenance treatment for Korean patients with moderate-to-severe UC.

This study investigated the effects of light intensity on growth performance, blood components, eye condition, and carcass characteristics of broiler chickens. Three hundred and fifty-two 1-day-old male chicks were assigned to one of four treatments (four repetitions per treatment, 22 birds per repetition) and reared in a floor pen for 5 weeks. From the second week, chicks were reared under four different levels of light intensity (5, 20, 35, and 50 lx) and the lighting duration was maintained at 18-hours light : 6-hours dark (18L : 6D). The feed intake and body weight were measured weekly. At 35 days of age, 12 birds per treatment were randomly selected for blood sampling, eye measurement, and carcass analysis. There were no significant differences in body weight gain, feed intake, and feed conversion ratio among treatments. Triglyceride levels in the serum were significantly higher in the 5 lx treatment, and creatinine was significantly lower in the 5 lx treatment (p < 0.05). The heterophil : lymphocyte ratios decreased significantly as light intensity increased (p < 0.05); however, other blood cell compositions were not affected by light intensity. Interleukin-6 content was significantly higher in the 5 lx treatment than in other treatments (p < 0.05), but the content of tumor necrosis factor-α was not significantly different among treatments. Serum corticosterone concentration was significantly higher at 5 lx than at 20, 35, and 50 lx (p < 0.05). The corneal diameter was the highest in 5 lx treatment (p < 0.05), and tended to increase as the light intensity decreased. Other eye parameters were not significantly different among treatments, but displayed a tendency to increase as the light intensity decreased. Carcass yield and part yields were not affected by light intensity. Meat quality parameters (pH, color, cooking loss, and water-holding capacity) did not show significant difference among the treatments. The results indicate that a light intensity of 5 lx may increase physiological stress or have a negative effect on broiler welfare, even if the performance and carcass characteristics are not affected. Therefore, a light intensity of 20 lx or above is recommended considering both the growth performance and welfare of broilers.

Background/Aims: Inflammatory bowel disease (IBD) is associated with the occurrence of venous thromboembolism (VTE). However, to date, there have been few studies on the risk of VTE in Asian IBD patients. We aimed to estimate the incidence of VTE in Asian IBD patients and to determine if IBD is related to increased VTE risk. Methods: We performed a population-based cohort study between 2004 and 2015 using Korean National Health Insurance data. IBD and VTE were defined by ICD-10 codes. Incidence rates of VTE were calculated among patients with IBD and among age- and sex-matched controls. Hazard ratios were estimated using Cox regression with adjustment for multiple variables. We performed additional analyses stratifying by age, sex, Charlson comorbidity index (CCI) score, and disease type. Results: Among the 45,037 patients with IBD (IBD cohort) and 133,019 matched controls (non-IBD cohort) included in our analysis, 411 IBD patients and 641 controls developed VTE. The IBD cohort had a higher incidence rate ratio and risk of VTE than the non-IBD cohort (incidence rate ratio: 1.92 and hazard ratio: 1.93). Older age, female sex, higher CCI scores, cardiovascular disease, chronic kidney disease, use of steroids, and hospitalization were significant risk factors for VTE in patients with IBD. Conclusions: The IBD patients in this study were approximately two times more likely to develop VTE than the non-IBD individuals. Our findings support the need for thromboprophylaxis in Asian IBD patients with various factors that further increase the risk of VTE.

Background/Aims This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). Methods A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. Results A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P

IntroductionUnderwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions.MethodsThis prospective, observational, single-center study included consecutive patients with intermediate-sized (10–20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications.ResultsForty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42–607) and 50 mL (30–130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized 15 mm in size.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients ( n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Alginate is a prominent food component extensively employed in developing functional food items and a dietary supplement with significant anti-inflammatory potential. Globally, rising air pollution by particulate matter (PM) has become a significant threat to humans, causing collateral lung tissue damage by inflammation. Therefore, the present study aimed to evaluate the anti-inflammatory potential of alginate isolated from Ecklonia maxima stipes (EMSA) against lung inflammation due to PM exposure. Initial results from cell viability, nitric oxide, prostaglandin E-2, and pro-inflammatory cytokine production assays showed that EMSA has potential anti-inflammatory activity against PM-induced inflammation. Western blot and qPCR results revealed the anti-inflammatory potential of EMSA through inflammatory signaling pathways, further confirmed by in vivo results and inductively coupled plasma-optical emission spectrometry. Therefore, EMSA can produce low-cost and high-quality alginate for several fields, such as functional foods using E. maxima stipes, a natural source such as functional foods, pharmaceuticals, and nutraceuticals.

Abstract Background Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. Methods Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2–3 weeks), and group 3 (interval >3 weeks). Results Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. Conclusions A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Marine resources have various biological activities and their constituents are more novel than those of land organisms. Several biologically active constituents have been found in marine organisms. Recently, many studies have reported that marine animals (MAs) can be used as functional ingredients in functional foods or nutraceutical due to their health benefits. However, no studies have extensively investigated the cosmeceutical activities of MAs extracts. Here, 70% ethanol extracts of 38 MAs were investigated for their activities of whitening and anti-aging properties for use as materials in novel cosmeceuticals. Anti-aging activities were determined by skin aging-related enzyme activities (anti-collagenase, anti-elastase, anti-hyaluronidase) and whitening activities (anti-tyrosinase, anti-3,4-dihydroxyl-L-phenylalanine [DOPA] oxidation) evaluated by colorimetric method. Among the 38 MAs, we found that Urechis unicinctus and Petrosia corticata extracts showed the strongest inhibitory effects against tyrosinase and DOPA oxidation, respectively. Our results additionally showed that Protankyra bidentata extract might provide a major source of anti-hyaluronidase and anti-elastase; meanwhile, anti-collagenase effects were similar in most MAs. Overall, these results suggest that extracts of marine animals have potential as a tyrosinase, collagenase, elastase, and hyaluronidase inhibitors. Taken together, MA resources could be considered as a novel cosmeceutical agent to be applied in cosmetic industry.

Abstract In this study, we present a method for synthesizing Ni-rich LiNi0.93Co0.04Al0.03O2 (NCA) with a high-energy cathode material by the solid-phase method. The sintering temperature plays a very important role in the electrochemical performance of the LiNi0.93Co0.04Al0.03O2 since it affects the crystallinity and structural stability. Therefore, various sintering temperatures (660 °C/690 °C/720 °C/750 °C/780 °C/810 °C) are studied to get optimum electrochemical performances. The electrochemical performance of LiNi0.93Co0.04Al0.03O2 sintered at 720 °C shows the highest discharge capacity of 217.48 mAh g−1 with excellent Coulombic efficiency of 87.84% at 0.1 C. Moreover, the LiNi0.93Co0.04Al0.03O2 sintered at 720 °C exhibits excellent rate-capability (181.1 mAh g−1 at 2.0 C) as well as superior cycle stability (95.4% after 80 cycles at 0.5 C). This is because optimized sintering temperature leads to good structural stability with low cation disorder and residual lithium content.

Background/Aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form. Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

Background/Aims: Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods: A multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results: In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p

The gastrointestinal tract microbiome is essential for regulating nutrient absorption, gut immune function, and host growth and development. In the present study, we characterized the development of ileum and cecum microbiota in pullets throughout the rearing period, encompassing a period from the day of hatching to 18 weeks of age. The growth performance and intestinal microbiome (ileum and cecum) of pullets were analyzed at 1, 5, 11, and 18 weeks of age. The richness of the ileum and cecum bacterial communities (alpha diversity) was higher in pullets at 18 weeks of age than in those at 1 and 5 weeks of age. Microbiota from weeks 1, 5, 11, and 18 were distinctly grouped in a NMDS plot, representing beta diversity within the ileum. However, the results for cecum microbiota did not reveal evident separation among the different age groups in the weighted UniFrac. In conclusion, our findings demonstrate variations and diversification in ileum and cecum microbiota across different rearing stages in pullets. These insights have the potential to inform the development of nutritional strategies that promote gut health and contribute to the improved development of pullets.

Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze the clinicopathological characteristics of EAC showing MELF pattern. We collected the clinicopathological information of 10 cases of EAC with the MELF pattern and conducted polymer-based immunostaining for Ki-67 (dilution 1:200, clone MIB-1) on these cases. Ki-67 expression was assessed using the average estimation within the hotspot method. All tumors were human papillomavirus-associated EAC with Silva pattern C. All except one tumor exceeded 3 cm in size. Five tumors involved the entire thickness of the cervical stroma, and four tumors extended into the parametrium. Lymphovascular space invasion was identified in six cases. Two patients developed metastatic recurrences in the para-aortic lymph nodes and lungs, respectively. The MELF area showed significantly lower Ki-67 labelling index than that of a conventional tumor area. We confirmed our previous observation that the MELF area displayed lower proliferative activity than the conventional tumor area of EAC. We also demonstrated that patients with EAC showing MELF pattern had several adverse clinicopathological characteristics reflecting aggressive behavior. On the other hand, since the frequencies of post-operative recurrence and disease-related mortality that occurred during the follow-up period were relatively low, further investigations are warranted to clarify the prognostic value of MELF pattern in EAC patients.

Abstract Ovarian carcinoma (OC) is the most lethal gynecological malignancy due to frequent recurrence resulting from cisplatin-resistance. ARL6IP5 is a novel gene implicated to suppress cisplatin-resistance by activating apoptosis and inhibiting DNA repair through XRCC1 and PARP1. We investigated the clinicopathological and prognostic significance of the immunohistochemical ARL6IP5 expression on 79 post-chemotherapy OC patient tissue samples; in vitro, the effect of ARL6IP5 overexpression (OE) and knockdown (KD) on cancer hallmark functions and the effect of ARL6IP5 on the expression of DNA repair and apoptosis-related proteins were observed in OC cells and their cisplatin-resistant (CisR) counterparts. ARL6IP5 expression was significantly associated with chemotherapeutic response and was an independent prognosticator of progression-free and overall survival of high-grade serous OC patients. ARL6IP5-OE decreased cellular proliferation, invasion, migration, adhesion, and increased apoptosis (p

Background/Aims: Endoscopic submucosal dissection (ESD) is a curative treatment modality for early gastric neoplasms; however, ESD can be a time-consuming process. To overcome this pitfall, we developed the one-step knife (OSK) approach, which combines an endoscopic knife and injection needle on a single sheath. We aimed to evaluate whether this approach could reduce the ESD procedure time.Methods: This single-blinded randomized multicenter trial at four tertiary hospitals from June 2019 to June 2020 included patients aged 19 to 85 years undergoing ESD. Patients were randomly assigned to two groups (OSK or conventional knife [CK]). The injection time, total procedure time, resected specimen size, submucosal fluid amount, degree of device satisfaction, and adverse events were evaluated and compared between groups.Results: Fifty-one patients were analyzed (OSK: 25 patients and CK: 26 patients). No baseline differences were observed between groups, with the exception of a higher portion of males in the OSK group. The mean injection time was significantly reduced in the OSK group (39.0 seconds) compared to that in the CK group (87.5 seconds, p

BackgroundTailored therapy has been widely used for patients with Helicobacter pylori (H. pylori) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori.MethodsWe enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed.ResultsAmong 460 patients (164 women, median age 63.0 years), 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin (TT-half CLA). The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA (P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA (P = 0.436).ConclusionFor patients with H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted.

The aim of this study was to isolate and identify secondary metabolites from Sonchus brachyotus and evaluate their antioxidant and anti-inflammatory activities. In this study, we isolated three flavonoids from a 70% EtOH extract by Medium Pressure Liquid Chromatography (MPLC) and prep-High-Performance Liquid Chromatography (HPLC). To evaluate the biological activities (an-tioxidant and anti-inflammatory) of these flavonoids, their in vitro inhibitory activities against lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation, nitric oxide (NO) production, and prostaglandin E2 (PGE2) secretion were determined. We successfully identified three flavonoids, namely luteolin (1), luteolin-7-O-β-D-glucoside (2), and luteolin-7-O-β-D-glucuronide (3) by spectral analyses. Luteolin (1) at 20 μg/mL inhibited ROS generation, NO production, and PGE2 secretion by 48.6%, 61.28% and 12.10%, respectively, and luteolin-7-O-β-D-glucoside (2) inhibited NO and PGE2 generation by 67.03% and 20.82%, respectively. Luteolin (1) and luteolin-7-O-β-D-glucoside (2) showed similar anti-inflammatory activities; however, luteolin (1) was observed to be a stronger antioxidant. Besides antioxidant and anti-inflammatory activities, S. brachyotus extract containing luteolin (1) and lu-teolin-7-O-β-D-glucoside (2) is considered to possess diverse biological activities. The results indicate that S. brachyotus is an edible medicinal plant, which is believed to be significant resource of functional foods.

Background/Aims: The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of MucostaⓇ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. Methods: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or MucostaⓇ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; MucostaⓇ, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; MucostaⓇ, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. Results: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 MucostaⓇ-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. Conclusions: The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (MucostaⓇ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.

Abstract As the second wave of COVID-19 hits South Asia, an increasing deadly complication ‘fungal infections (such as Mycosis, Candida and Aspergillus) outbreak’ has been raised concern about the insufficient technologies and medicals for its diagnosis and therapy. Biosilica based nano-therapy can be used for therapeutic efficacy, yet their direct role as antibiotic agent with biocompatibility and stability remains unclear. Here, we report that a diatomaceous earth (DE) framework semiconductor composite conjugated DE and in-house synthesized zinc oxide (DE-ZnO), as an antibiotic agent for the enhancement of antibiotic efficacy and persistence. We found that the DE-ZnO composite had enhanced antibiotic activity against fungi (A. fumigatus) and Gram-negative bacteria (E. coli, S. enterica). The DE-ZnO composite provides enhancing large surface areas for enhancement of target pathogen binding affinity, as well as produces active ions including reactive oxygen species and metal ion for breaking the cellular network of fungi and Gram-negative bacteria. Additionally, the toxicity of DE-ZnO with 3 time less amount of dosage is 6 times lower than the commercial SiO2-ZnO. Finally, a synergistic effect of DE-ZnO and existing antifungal agents (Itraconazole and Amphotericin B) showed a better antifungal activity, which could be reduced the side effects due to the antifungal agents overdose, than a single antibiotic agent use. We envision that this DE-ZnO composite can be used to enhance antibiotic activity and its persistence, with less-toxicity, biocompatibility and high stability against fungi and Gram-negative bacteria which could be a valuable candidate in medical science and industrial engineering.

This study aimed to examine the effect of probiotics containing Bacillus subtilis and oregano essential oil on the growth performance, intestinal morphology, and cecal microbial composition in pullets aged 0–18 weeks. A total of 324 day-old Hy-Line Brown chicks were randomly assigned to three treatment groups, with six replicates per group and 18 birds per pen. The experimental treatments consisted of the following: a control group receiving a basal diet (Con), a group receiving a basal diet supplemented with 1 g/kg (3 × 108 cfu/kg) of Bacillus subtilis (BS), and a group receiving a basal diet supplemented with 0.3 g/kg of oregano essential oil (ORO). The groups supplemented with BS and ORO demonstrated significantly higher villus height/crypt depth ratios than the Con group. Microbial richness was significantly higher in groups supplemented with BS (p = 0.0317) and ORO (p = 0.00794) than in the Con group. These findings revealed a distinct separation between gut microbial communities of the Con group and those supplemented with ORO, based on unweighted and weighted UniFrac indices. Therefore, supplementation with Bacillus subtilis and oregano oil improved the composition of the microbiota, suggesting their positive effects on the gut health of pullets.

Data on genetic and immunophenotypical characteristics of uterine mesonephric-like adenocarcinoma (MLA) remain limited. Therefore, we aimed to investigate the clinicopathological, immunohistochemical, and molecular features of uterine MLA. We performed targeted sequencing, array comparative genomic hybridization, and immunostaining in 17, 13, and 17 uterine MLA cases, respectively. Nine patients developed lung metastases. Eleven patients experienced disease recurrences. The most frequently mutated gene was Kirsten rat sarcoma viral oncogene homolog (KRAS; 13/17). Both the primary and matched metastatic tumors harbored identical KRAS (3/4) and phosphatase and tensin homolog deleted on chromosome 10 (1/4) mutations, and did not harbor any additional mutations. A total of 2 of the 17 cases harbored tumor protein 53 (TP53) frameshift insertion and deletion, respectively. Chromosomal gains were detected in 1q (13/13), 10 (13/13), 20 (10/13), 2 (9/13), and 12 (6/13). Programmed cell death-ligand 1 overexpression or mismatch repair deficiency was not observed in any of the cases. Initial serosal extension and lung metastasis independently predicted recurrence-free survival with hazard ratios of 6.30 and 7.31, respectively. Our observations consolidated the clinicopathological and molecular characteristics of uterine MLA. Both clinicians and pathologists should consider these features to make an accurate diagnosis of uterine MLA and to ensure appropriate therapeutic management of this rare entity.