The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis.

Background: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy. Methods: We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity. Results: A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression. Conclusion: PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea.

BACKGROUND: Intrahepatic duct (IHD) stones are among the most important risk factors for cholangiocarcinoma (CCC). Approximately 10% of patients with IHD stones develop CCC; however, there are limited studies regarding the effect of IHD stone removal on CCC development. AIM: To investigate the association between IHD stone removal and CCC development. METHODS: We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020. RESULTS: CCC occurred in 36 of the 397 enrolled patients. In univariate analysis, chronic hepatitis B infection (11.1% vs 3.0%, P = 0.03), carbohydrate antigen 19-9 (CA19-9, 176.00 vs 11.96 II/mL, P = 0.010), stone located in left or both lobes (86.1% vs 70.1%, P = 0.042), focal atrophy (52.8% vs 26.9%, P = 0.001), duct stricture (47.2% vs 24.9%, P = 0.004), and removal status of IHD stone (33.3% vs 63.2%, P < 0.001) were significantly different between IHD stone patients with and without CCC. In the multivariate analysis, CA19-9 > upper normal limit, carcinoembryonic antigen > upper normal limit, stones located in the left or both lobes, focal atrophy, and complete removal of IHD stones without recurrence were independent factors influencing CCC development. However, the type of removal method was not associated with CCC risk. CONCLUSION: Complete removal of IHD stones without recurrence could reduce CCC risk.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer.

BACKGROUND: Currently, there is no standard adjuvant therapy for patients with resected ampulla of Vater (AoV) cancer. AIM: To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy (CCRT) in patients with advanced AoV cancer who underwent curative resection. METHODS: This single-centered, retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018. The impact of CCRT on advanced AoV cancer was analyzed. RESULTS: The 1-, 3-, and 5-yr recurrence-free survival (RFS) rates for patients with advanced AoV cancer were 82.8%, 48.3%, and 40.8%, respectively, and the overall survival (OS) rates were 89.7%, 62.1%, and 51.7%, respectively. Lymphovascular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis, whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis. Compared to the patients who did not receive adjuvant CCRT, those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS, although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio. CONCLUSION: Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer. These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Sphingomonas flavescens sp. nov., isolated from soil.

An aerobic bacterium, designated as PT-12T, was isolated from soil collected from agriculture field, and its taxonomic position was validated through a comprehensive polyphasic methodology. The strain was identified as Gram-stain-negative, non-motile, rod-shaped, and catalase- and oxidase-positive. The yellow-colored colonies showed growth ability at temperature range of 18-37 °C, NaCl content of 0-1.0% (w/v), and at a pH of 6.0-8.0. The 16S rRNA gene and phylogenetic analysis showed that strain PT-12T affiliated with the genus Sphingomonas in the family Sphingomonadaceae, and displayed the highest 16S rRNA nucleotide sequence similarity with Sphingomonas limnosediminicola 03SUJ6T (98.4%). The genome size of strain PT-12T was 2,656,862 bp and the DNA G + C content estimated from genome was 63.5%. The highest values of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were observed between strain PT-12T and Sphingomonas segetis YJ09T, accounting to 76.2% and 20.2%, respectively. In addition, both ANI and dDDH values between strain PT-12T and other phylogenetically related neighbors ranged between 69.6% and 76.2% and 18.4% and 20.2%, respectively. Chemotaxonomic features exhibited Q-10 as the only ubiquinone; homospermidine as the major polyamine; summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, and 10-methyl C18:0 as the notable fatty acids; and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, and sphingoglycolipid as dominating polar lipids. Overall, the comprehensive polyphasic data supported that strain PT-12T represents a novel bacterial species within the genus Sphingomonas. Accordingly, we propose the name Sphingomonas flavescens sp. nov. The type strain is PT-12T (= KCTC 92114T = NBRC 115717T).

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining.

BACKGROUND: The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS: Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS: Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS: Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells.

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Metastatic pancreatic solitary fibrous tumor: A case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that is most commonly found in the pleura but can also originate from non-pleural sites. Among the non-pleural localizations, the pancreas is extremely rare. In particular, metastasis to the pancreas from the central nervous system (CNS) is extremely rare, with only two cases reported so far. We report a case of recurrence in the pancreas 14 years after the initial complete surgical removal of a tumor in the CNS. CASE SUMMARY: A 68-year-old man with a past medical history of recurrent meningeal hemangiopericytoma, currently referred to as SFT, presented to the hospital with jaundice. The patient was first diagnosed with an 8cm-sized meningeal hemangiopericytoma fourteen years ago and underwent osteoplastic craniotomy. After 16 mo, imaging showed recurrence and he underwent gamma knife radiosurgery (GKRS). 2 years later, imaging showed recurrence again leading to a second GKRS. 5 years later, recurrence was again suspected leading to a second craniotomy. Since then 3 years had passed, and imaging showed a 3.5cm-sized mass lesion on the pancreatic head with obstruction of the pancreatic and bile ducts. Endosonography with fine-needle aspiration biopsy was done preoperatively and aided in the diagnosis of SFT. The patient underwent pylorus-preserving pancreaticoduodenectomy. Pathologic findings of the resected pancreatic specimen, consistent with the previously resected brain specimen, confirmed the diagnosis of SFT. CONCLUSION: The rarity and lack of knowledge about SFTs make suspecting and diagnosing this disease challenging. We believe that a report of metastatic pancreatic SFT from the CNS will contribute to a better understanding of this rare disease.

Paenibacillus silvisoli sp. nov. and Paenibacillus humicola sp. nov., isolated from forest soil.

During the study of microbial ecology of forest soil, two circular, white-colored bacterial colonies were isolated and labeled as strains TW38T and TW40T. Both strains were catalase positive and oxidase negative. Strains TW38T and TW40T demonstrated growth within a temperature range of 10-37 °C and 18-37 °C, respectively, and thrived within a pH range of 5.5-9.0 and 6.0-8.0, respectively. Both strains grew at 0-2.0% (w/v) NaCl concentrations. The phylogenetic analysis indicated that strains TW38T and TW40T affiliated to the genus Paenibacillus, with the closest neighbors being Paenibacillus montanisoli RA17T (98.6%) and Paenibacillus arachidis E3T (95.4%), respectively. In both strains, the sole respiratory quinone was MK-7, the signature fatty acid was antiso-C15:0, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine. The digital DNA-DNA hybridization and the average nucleotide identity values between TW38T, TW40T, and closest reference strains were < 29.0% and < 85.0%, respectively. The DNA G+C content of TW38T and TW40T was 54.5% and 57.1%, respectively. In general, the phylogenetic, genomics, chemotaxonomic, and phenotypic data support the differentiation of TW38T and TW40T from other closest members of the genus Paenibacillus. Thus, we conclude both strains TW38T and TW40T represent novel species of the genus Paenibacillus, for which the name Paenibacillus silvisoli sp. nov. and Paenibacillus humicola sp. nov. are proposed, respectively. The type strain of Paenibacillus silvisoli is TW38T (= KCTC 43468T = NBRC 116015T) and type strain of Paenibacillus humicola is TW40T (= KCTC 43469T = NBRC 116016T).

Mucosal distribution of somatostatin-secreting gastric Delta cells in children with gastrointestinal reflux diseases.

Introduction: Gastric delta cells (D-cells) secrete somatostatin, which is the primary paracrine suppressor of acid secretion. The number and distribution of D-cells were investigated in children exhibiting endoscopic findings of duodenogastric and gastroesophageal reflux. This study aimed to determine whether the number of D-cells in the gastric body differs from that in the gastric antrum in children using endoscopic findings. Methods: We retrospectively used immunohistochemical assessments to determine the number of D-cells in the gastric body and antrum in 102 children who presented with abdominal symptoms. The number and distribution of D-cells were investigated according to symptoms, endoscopic findings of gastroesophageal reflux and duodenogastric reflux, and Helicobacter pylori infection status. Results: The average age of the patients was 13.3 ± 3.3 years, and the male-to-female ratio was 1:1.68. The mean number of D-cells per high-power field in the antrum and body did not significantly differ by symptoms. However, these values were significantly lower in the gastric body than in the antrum for all symptoms (p < 0.05). Children with reflux had a higher mean number of D-cells (9.6 ± 8.8) in the gastric body than did those without reflux (4.3 ± 3.4) (p = 0.007). Furthermore, the number of D-cells in the gastric body was marginally significantly lower in Helicobacter pylori-positive children (4.9 ± 6.5) than in Helicobacter pylori-negative children (8.5 ± 8.2) (p = 0.053). Conclusion: The number of D-cells in the gastric body decreased in Helicobacter pylori-positive children but significantly increased in children with duodenogastric reflux. Therefore, somatostatin peptide secretion by D-cells may be a major pathophysiological pathway in gastrointestinal reflux disease.

Paenibacillus caseinilyticus sp. nov., isolated forest soil.

A milky-white-coloured, aerobic, Gram-stain-positive, rod-shaped and motile bacterial strain (GW78T) was isolated from forest soil. GW78T was catalase-positive and oxidase-negative. The strain was able to grow optimally at 37 °C and at pH 7.0 in Reasoner's 2A media. The phylogenetic and 16S rRNA gene sequence analysis of GW78T showed its affiliation with the genus Paenibacillus. The 16S rRNA gene sequence of GW78T revealed 98.3 % similarity to its nearest neighbour Paenibacillus mucilaginosus VKPM B-7519T. Its chemotaxonomic properties included MK-7 as the sole menaquinone, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine as major polar lipids, and anteiso-C15 : 0, C16 : 1 ω11c and anteiso-C17 : 0 as predominant fatty acids. Digital DNA-DNA hybridization and average nucleotide identity results with its closest relatives were <74.0 % and <14.0 %, respectively. Overall, 16S rRNA gene sequence comparisons, phylogenetic and genomic evidence, and phenotypic and chemotaxonomic data allow the differentiation of GW78T from other members of the genus Paenibacillus. Thus, we propose that strain GW78T represents a novel species of the genus Paenibacillus, with the name Paenibacillus caseinilyticus sp. nov. The type strain is GW78T (=KCTC 43430T=NBRC 116023T).

Toward Practical Multivalent Ion Batteries with Quinone-Based Organic Cathodes.

Multivalent ion batteries have emerged as promising solutions to meet the future demands of energy storage applications, offering not only high energy density but also diverse socio-economic advantages. Among the various options for cathodes, quinone-based organic compounds have gained attention as suitable active materials for multivalent ion batteries due to their well-aligned ion channels, flexible structures, and competitive electrochemical performance. However, the charge carriers associated with anions that are often exploited in multivalent ion battery systems operate by way of a "non-rocking-chair" mechanism, which requires the use of an excess amount of electrolyte and results in a significant decrease in the energy density. In this review, by categorizing the various charge carriers exploited in previous studies on multivalent ion batteries, we summarize recently reported quinone-based organic cathodes for multivalent ion batteries and emphasize the importance of accurately identifying the charge carriers for calculating the energy density. We also propose potential future directions toward the practical realization of multivalent ion batteries, in link with their efficient energy storage applications.

Clinicopathological characteristics of extrahepatic biliary neuroendocrine neoplasms in the gallbladder, extrahepatic biliary tract, and ampulla of Vater: A single-center cross-sectional study.

Backgrounds/Aims: In 2019, the grading and staging system for neuroendocrine neoplasms (NENs) was significantly changed. In this study, we report the clinicopathological characteristics and surgical outcomes of patients with extrahepatic biliary NENs who underwent curative resection with or without adjuvant treatment. Methods: We retrospectively reviewed a database of 16 patients who developed NENs, neuroendocrine carcinoma (NEC), and mixed endocrine non-endocrine neoplasms (MiNENs) after curative resection. Among them, eight patients had ampulla of Vater (AoV) tumors, and eight patients had non-AoV tumors. Results: G1 and G2 were more frequently observed in the AoV group than in the non-AoV group (12.5% and 62.5%, respectively). In contrast, NEC and MiNEN were more common in the non-AoV group (50.0%). High Ki-67 index (> 20%) and perineural invasion (PNI) were more frequently observed in the non-AoV group. Advanced age (> 65 years), mitotic count > 20 per 2 mm2, and Ki-67 index > 20% were strongly correlated with patient survival (p = 0.018, 0.009, and 0.044, respectively). Advanced age (> 65 years) and mitotic count > 20 per 2 mm2 were significantly correlated with disease recurrence (p = 0.033 and 0.010, respectively). Conclusions: AoV and non-AoV tumors had significant differences in the histologic grade, Ki67, and PNI. Patients with non-AoV tumors had an increased risk for survival and recurrence than those in the AoV group. For extrahepatic biliary NENs, early detection of tumors, adequate surgery, and aggressive adjuvant treatment for high-risk patients are important to achieve long-term survival and prevent disease recurrence.

Spiral-phase-objective for a compact spiral-phase-contrast microscopy.

Spiral-phase-contrast imaging, which utilizes a spiral phase optical element, has proven to be effective in enhancing various aspects of imaging, such as edge contrast and shadow imaging. Typically, the implementation of spiral-phase-contrast imaging requires the formation of a Fourier plane through a 4f optical configuration in addition to an existing optical microscope. In this study, we present what we believe to be a novel single spiral-phase-objective, integrating a spiral phase plate, which can be easily and simply applied to a standard microscope, such as a conventional objective. Using a new hybrid design approach that combines ray-tracing and field-tracing simulations, we theoretically realized a well-defined and high-quality vortex beam through the spiral-phase-objective. The spiral-phase-objective was designed to have conditions that are practically manufacturable while providing predictable performance. To evaluate its capabilities, we utilized the designed spiral-phase-objective to investigate isotropic spiral phase contrast and anisotropic shadow imaging through field-tracing simulations, and explored the variation of edge contrast caused by changes in the thickness of the imaging object.

Guggulsterone protects against lipopolysaccharide-induced inflammation and lethal endotoxemia via heme oxygenase-1.

Guggulsterone (GS) is a phytosterol used to treat inflammatory diseases. Although many studies have examined the anti-inflammatory activities of GS, the detailed mechanisms of GS in lipopolysaccharide (LPS)-induced inflammation and endotoxemia have not yet been examined. Therefore, we investigated the anti-inflammatory effects of GS on LPS-induced inflammation. In murine peritoneal macrophages, the anti-inflammatory activity of GS was primarily mediated by heme oxygenase-1 (HO-1) induction. HO-1 induction by GS was mediated by GSH depletion and reactive oxygen species (ROS) production. The ROS generated by GS caused the phosphorylation of GSK3ß (ser9/21) and p38, leading to the translocation of nuclear factor erythroid-related factor 2 (Nrf2), which ultimately induced HO-1. In addition, GS pretreatment significantly inhibited inducible nitric oxide synthase (iNOS), iNOS-derived NO, and COX-2 protein and mRNA expression, and production of COX-derived prostaglandin PGE2, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α). In a mouse model of endotoxemia, GS treatment prolonged survival and inhibited the expression of inflammatory mediators, including IL-1ß, IL-6, and TNF-α. GS treatment also inhibited LPS-induced liver injury. These results suggest that GS-induced HO-1 could exert anti-inflammatory effects via ROS-dependent GSK (ser21/9)-p38 phosphorylation and nuclear translocation of Nrf2.

Catechin hydrate ameliorates cerulein­induced chronic pancreatitis via the inactivation of TGF­ß/Smad2 signaling.

Chronic pancreatitis (CP) is a pancreatic inflammatory disease associated with histological changes, including fibrosis, acinar cell loss and immune cell infiltration, and leads to damage of the pancreas, which results in pain, weight loss and loss of pancreas function. Catechin or catechin hydrate (CH) has antioxidant, anticancer and immune­regulatory effects. However, unlike other catechins, the antifibrotic effects of (+)­CH have not been widely studied in many diseases, including CP. Therefore, the anti­fibrotic effects of (+)­CH against CP were evaluated in the present study. To assess the prophylactic effects of CH, (+)­CH (1, 5 or 10 mg/kg) or ethanol was administered 1 h before first cerulein (50 µg/kg) injection. To assess the therapeutic effects, (+)­CH (5 mg/kg) or ethanol was administered after cerulein injection for one or two weeks. In both methods, cerulein was injected intraperitoneally into mice once every hour, six times a day, four times a week, for a total of three weeks, to induce CP. The data showed that (+)­CH markedly inhibited glandular destruction and inflammation during CP. Moreover, (+)­CH prevented pancreatic stellate cell (PSC) activation and the production of extracellular matrix components, such as fibronectin 1 and collagens, which suggested that it may act as a novel therapeutic agent. Furthermore, the mechanism and effectiveness of (+)­CH on pancreatic fibrosis were investigated in isolated PSCs. (+)­CH suppressed the activation of Smad2 and fibrosis factors that act through transforming growth factor­ß (TGF­ß) or platelet­derived growth factor. These findings suggest that (+)­CH exhibits antifibrotic effects in cerulein­induced CP by inactivating TGF­ß/Smad2 signaling.

An all-in-one platform to deplete pathogenic bacteria for rapid and safe enrichment of plant-derived extracellular vesicles.

Plant-derived extracellular vesicles (PDEVs) have exhibited several advantages, such as high biocompatibility, improvement of skin conditions, and the prevention of skin aging. However, traditional methods of extraction for plant substances, such as heating under reflux or solvent extraction, are complicated, time-consuming, and low in purity. Accordingly, a simple and efficient platform is necessary for purely isolating natural substances from plants. In this study, we report a newly designed platform for removing impurities to purify PDEVs. The proposed platform comprises three parts: (i) inflow of samples, (ii) depletion of impurities, and (iii) collection of PDEVs. The platform is designed to flow from top to bottom using gravity without the need for electric components. The platform allows the delimitation of impurities, such as the pathogenic bacteria in PDEVs, by capturing magnetic beads coated with Concanavalin A (Con A). We validate the practicality of our platform using extracellular vesicles derived from liquorice (LdEVs). Notably, the LdEVs purified using the Con A-coated magnetic beads provide better cell uptake and wound recovery than the commercialized extract LdEVs. This highlights the therapeutic potential of fresh LdEVs purified using our platform, particularly in preventing skin aging. The findings of this study hold significant practical implications for the cosmeceutical and therapeutic field, providing a promising approach for the extraction and purification of natural substances from plants to harness their benefits effectively.

Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.

OBJECTIVES: We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO). METHODS: Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome. RESULTS: Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99). CONCLUSIONS: During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.