Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.

Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1LSH/HELLS), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.1. In ddm1 mutants, DNA methylation is partly restored by loss of the H3.3 chaperone HIRA, while the H3.1 chaperone CAF-1 becomes essential. The single-particle cryo-EM structure at 3.2 Å of DDM1 with a variant nucleosome reveals engagement with histone H3.3 near residues required for assembly and with the unmodified H4 tail. An N-terminal autoinhibitory domain inhibits activity, while a disulfide bond in the helicase domain supports activity. DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1Dnmt1, but is blocked by H4K16 acetylation. The male germline H3.3 variant MGH3/HTR10 is resistant to remodeling by DDM1 and acts as a placeholder nucleosome in sperm cells for epigenetic inheritance.

Pasteurella Infections in South Korea and Systematic Review and Meta-analysis of Pasteurella Bacteremia.

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018‒2022. We also conducted a collaborative systematic review and meta-analysis of the global burden of Pasteurella bacteremia. The study included 283 cases found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01-1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%-18.6%) and of mortality 8.4% (95% CI 2.7%-16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management.

Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma.

Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.

Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Fitness costs of Tn1546-type transposons harboring the vanA operon by plasmid type and structural diversity in Enterococcus faecium.

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.

Anticoagulants Are a Risk Factor for Delayed Bleeding after Colorectal Endoscopic Submucosal Dissection: A HASID Multicenter Study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3%). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Pulmonary Foreign Body Granulomatosis after Cosmetic Injection.

INTRODUCTION: We occasionally encounter irregular marginated masses discovered incidentally in young individuals. In most cases, further investigations are conducted to assess the presence of a primary malignancy, as these masses often raise suspicions of malignancy. However, rare exceptional cases leave us perplexed. Granulomas arising from common lung infections and those induced by foreign substances can often pose challenge in distinguishing them from lung cancer. Therefore, we aimed to present a case of multiple pulmonary granulomatosis following cosmetic procedure. CASE PRESENTATION: A 55-year-old woman visited the hospital after an incidental discovery of an abnormal chest radiograph during a routine health check-up. Subsequent computed tomography (CT) scans showed worrisome lung nodules, leading to biopsies and positron emission tomography CT scans. Histological examination of the biopsied specimens revealed a chronic inflammatory reaction surrounded by multinucleated foreign body giant cells. Upon sharing the biopsy results with the patient and conducting additional history-taking, she had undergone various cosmetic procedures (botox injection, dermal filler treatments, and thread lifts) around the face and neck, approximately 5-6 months ago. It was hypothesized that these cosmetic materials might have led to the observed pulmonary granulomatosis. After 3 months of conservative care, a follow-up CT showed no change in the lesions. CONCLUSION: We present this case to underscore the importance of considering pulmonary foreign body granulomatosis as a potential differential diagnosis, especially when it closely resembles lung cancer, particularly following cosmetic injections.

Antibacterial and Immunosuppressive Effects of a Novel Marine Brown Alga-Derived Ester in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin condition that is characterized by dysregulated immune responses and a heightened risk of Staphylococcus aureus infections, necessitating the advancement of innovative therapeutic methods. This study explored the potential of (6Z,9Z,12Z,15Z)-(2R,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl octadeca-6,9,12,15-tetraenoate (HSN-S1), a compound derived from the marine alga Hizikia fusiformis, which shows anti-inflammatory, antimicrobial, and immunomodulatory properties. HSN-S1 was isolated and characterized using advanced chromatographic and spectroscopic methods. Its efficacy was evaluated via in vitro assays with keratinocytes, macrophages, and T cells to assess cytokine suppression and its immunomodulatory effects; its antibacterial activity against S. aureus was quantified. The in vivo effectiveness was validated using a 2,4-dinitrochlorobenzene-induced AD mouse model that focused on skin pathology and cytokine modulation. HSN-S1 significantly reduced pro-inflammatory cytokine secretion, altered T-helper cell cytokine profiles, and showed strong antibacterial activity against S. aureus. In vivo, HSN-S1 alleviated AD-like symptoms in mice and reduced skin inflammation, transepidermal water loss, serum immunoglobulin-E levels, and Th2/Th17 cytokine outputs. These findings suggest HSN-S1 to be a promising marine-derived candidate for AD treatment, as it offers a dual-target approach that could overcome the limitations of existing therapies, hence warranting further clinical investigation.

Effect of Ishige okamurae Extract on Osteoclastogenesis In Vitro and In Vivo.

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.

Assessment of phthalate exposure at a fire site in Korean firefighters.

To determine phthalate exposure in 32 firefighters, the concentrations of urinary phthalate metabolites, immediately (exposure day) and three weeks (control day) after fire suppression, were compared. Mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-n-butyl phthalate (MBP), mono-n-benzyl phthalate (MBzP), and total phthalates (∑phthalates) levels, and creatinine-adjusted levels of MBP, MBzP, and ∑phthalates were significantly higher on exposure day than on control day. Phthalate concentration was significantly higher in firefighters who performed the fire extinguishing tasks (geometric mean [GM], 149.9 µg/L) than in those who performed other tasks (GM 70.8 µg/L) (p = .012). The GM concentration of firefighters who were active ≤ 50 m from the fire was 119.0 µg/L, and 37.6 µg/L for those who were > 50 m away (p = .012). The GM concentration was significantly different (p = .039) in firefighters with subjective symptoms after fire suppression (151.9 µg/L) compared to those without symptoms (81.6 µg/L). This study showed that firefighters were exposed to phthalate.

Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

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.

Effect of Ishophloroglucin A Isolated from Ishige okamurae on In Vitro Osteoclastogenesis and Osteoblastogenesis.

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the bone remodeling process. This study aimed to investigate the effect of Ishophloroglucin A (IPA) isolated from Ishige okamurae on the function of osteoclasts and osteoblasts in vitro. First, we demonstrated the effect of IPA on osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW 264.7 cells. IPA inhibited the tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation in RANKL-induced RAW 264.7 cells. Moreover, it inhibited the RANKL-induced osteoclast-related factors, such as TRAP, matrix metalloproteinase-9 (MMP-9), and calcitonin receptor (CTR), and transcription factors, such as nuclear factor of activated T cells 1 (NFATc1) and c-Fos. IPA significantly suppressed RANKL-activated extracellular signal-regulated kinase (ERK), and NF-κB in RAW 264.7 cells. Our data indicated that the ERK and NF-κB pathways were associated with the osteoclastogenesis inhibitory activity of IPA. Next, we demonstrated the effect of IPA on osteoblastogenesis in MG-63 cells. IPA significantly promoted alkaline phosphatase (ALP) activity in MG-63 cells, along with the osteoblast differentiation-related markers bone morphogenetic protein 2 (BMP2), type 1 collage (COL1), p-Smad1/5/8, and Runx2, by activating the MAPK signaling pathways. Taken together, the study indicated that IPA could be effective in treating bone diseases, such as osteoporosis.

WT1 Pulsed Human CD141+ Dendritic Cell Vaccine Has High Potential in Solid Tumor-Targeted Immunotherapy.

Dendritic cells (DC) are powerful cells that play critical roles in anti-tumor immunity, and their use in cancer immunotherapy unlocks hidden capabilities as an effective therapeutic. In order to maximize the full potential of DC, we developed a DC vaccine named CellgramDC-WT1 (CDW). CDW was pulsed with WT1, an antigen commonly expressed in solid tumors, and induced with zoledronate to aid DC maturation. Although our previous study focused on using Rg3 as an inducer of DC maturation, problems with quality control and access led us to choose zoledronate as a better alternative. Furthermore, CDW secreted IL-12 and IFN-γ, which induced the differentiation of naïve T cells to active CD8+ T cells and elicited cytotoxic T lymphocyte (CTL) response against cancer cells with WT1 antigens. By confirming the identity and function of CDW, we believe CDW is an improved DC vaccine and holds promising potential in the field of cancer immunotherapy.

Angiotensin I-Converting Enzyme (ACE) Inhibition and Molecular Docking Study of Meroterpenoids Isolated from Brown Alga, Sargassum macrocarpum.

Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum, and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC50 value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Sargassum horneri Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay.

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-ß1 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-ß1-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-ß1 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-ß1-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.

Two vs One Forward View Examination of Right Colon on Adenoma Detection: An International Multicenter Randomized Trial.

BACKGROUND & AIMS: Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection. METHODS: Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR. RESULTS: Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection. CONCLUSIONS: In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.

Does para-aortic lymphadenectomy improve survival in pathologically diagnosed early-stage grade 3 endometrioid and non-endometrioid endometrial cancers? A retrospective cohort study in Korea and Taiwan.

PURPOSE: The therapeutic effect of para-aortic lymphadenectomy in early-stage high-grade endometrial cancer remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared to pelvic lymphadenectomy alone in patients with pathologically diagnosed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. METHODS: We retrospectively reviewed the medical records of 281 patients with histologically confirmed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers who underwent pelvic lymphadenectomy alone or combined pelvic and para-aortic lymphadenectomy in staging surgery at two tertiary centers in Korea and Taiwan. Prognostic factors to predict outcomes in these cases were also analyzed. RESULTS: Among 281 patients, 144 underwent pelvic lymphadenectomy alone and 137 underwent combined pelvic and para-aortic lymphadenectomy. Within a median follow-up of 45 months, there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In multivariable analysis, age at diagnosis ≥60 years (HR = 2.20, 95% CI 1.25-3.87, p = 0.006) and positive lymph-vascular space invasion (LVSI) (HR = 2.79, 95% CI 1.60-4.85, p < 0.001) were associated with worse RFS, and only non-endometrioid histology was associated with worse OS (HR = 3.18, 95% CI 1.42-7.12, p = 0.005). In further subgroup analysis, beneficial effects of combined pelvic and para-aortic lymphadenectomy on RFS and OS were not observed. CONCLUSIONS: In this study, combined pelvic and para-aortic lymphadenectomy could not improve survival compared to pelvic lymphadenectomy alone in patients with FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. Therefore, para-aortic lymphadenectomy may be omitted for these cases.