Efficacy and Safety of WCFA19 (Weissella confusa WIKIM51) in Reducing Body Fat in Overweight and Obese Adults.

Background: WCFA19 (Weissella confusa WIKIM51), found during the fermentation of kimchi, is known for its inhibitory effects on body weight and body fat. This study looked at the impact of WCFA19 isolated from dandelion kimchi on weight loss in overweight and obese adults that are otherwise healthy. Methods: This study was conducted as a multicenter, double-blind, randomized, placebo-controlled study with 104 overweight and obese subjects. Subjects were randomized evenly into the test group (WCFA19, 500 mg, n = 40) or control group (n = 34) for 12 weeks from 14 June 2021 to 24 December 2021. Effects were based on DEXA to measure changes in body fat mass and percentage. Results: Among the 74 subjects analyzed, WCFA19 oral supplementation for 12 weeks resulted in a significant decrease in body fat mass of 633.38 ± 1396.17 g (p = 0.0066) in overweight and obese individuals in the experimental group. The control group showed an increase of 59.10 ± 1120.57 g (p = 0.7604), indicating a statistically significant difference between the two groups. There was also a statistically significant difference (p = 0.0448) in the change in body fat percentage, with a decrease of 0.41 ± 1.22% (p = 0.0424) in the experimental group and an increase of 0.17 ± 1.21% (p = 0.4078) in the control group. No significant adverse events were reported. Conclusions: Oral supplementation of 500 mg of WCFA19 for 12 weeks is associated with a decrease in body weight, particularly in body fat mass and percentage.

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.

Using (S)-decursinol isolated from root of AGN, we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited JAK1 and STAT3 phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.

Mechanism of Z-Selective Allylic Functionalization via Thianthrenium Salts.

A detailed mechanistic study of the Z-selective allylic functionalization via thianthrenium salts is presented. Kinetic analyses, deuterium labeling experiments, and computational methods are used to rationalize the observed reactivity and selectivity. We find that the reaction proceeds via a rate-determining and stereodetermining allylic deprotonation of an alkenylthianthrenium species. The Z-configuration of the resultant allylic ylide is translated into the Z-allylic amine product through a sequence of subsequent fast and irreversible steps: protonation to form a Z-allylic thianthrenium electrophile and then regioselective substitution by the nucleophile. In the stereodetermining deprotonation step, computational studies identified a series of stabilizing nonbonding interactions in the Z-alkene-forming transition state that contribute to the stereoselectivity.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression.

BACKGROUND AND PURPOSE: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1ß, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.

Pediatric mandibular chronic nonbacterial osteomyelitis: A case report with 12 years of radiologic follow-up.

Chronic nonbacterial osteomyelitis (CNO) is histologically characterized by nonspecific osteitis. This inflammatory disorder, which lacks an infectious origin, typically presents with chronic pain and swelling at the affected site that can persist for months or even years. However, it is rare for CNO to affect the mandible. A 10-year-old girl presented with a primary complaint of pain in her left mandible. She had no significant medical or dental history. On examination, swelling was visible on the left buccal side, and imaging revealed radiolucent bone deterioration within the left mandible. This case report presents the radiological changes observed over a 12-year follow-up period. Variations in radiopacity, radiolucency, and periosteal reactions were noted periodically. This case highlights the radiological characteristics and findings that are crucial for the diagnosis of CNO, a condition for which no clear diagnostic criteria are currently available.

Risk factors of reattempt among suicide attempters in South Korea: A nationwide retrospective cohort study.

This study aimed to identify underlying demographic and clinical characteristics among individuals who had previously attempted suicide, utilizing the comprehensive Health Insurance Review and Assessment Service (HIRA) database. Data of patients aged 18 and above who had attempted suicide between January 1 and December 31, 2014, recorded in HIRA, were extracted. The index date was identified when a suicide attempt was made within the year 2014. The medical history of the three years before the index date and seven years of follow-up data after the index date were analyzed. Kaplan-Meier estimate was used to infer reattempt of the suicide attempters, and Cox-proportional hazard analysis was used to investigate risk factors associated with suicide reattempts. A total of 17,026 suicide attempters were identified, of which 1,853 (10.9%) reattempted suicide; 4,925 (28.9%) patients had been diagnosed with depressive disorder. Of the reattempters, 391 (21.1%) demonstrated a history of suicide attempts in the three years before the index date, and the mean number of prior attempts was higher compared to that of the non-reattempters (1.7 vs.1.3, p-value < 0.01). Prior psychiatric medication, polypharmacy, and an increase in the number of psychotropics were associated with suicide reattempt in overall suicide attempters. (Hazard ratio (HR) = 3.20, 95% confidence interval [CI] = 2.56-4.00; HR = 2.42, 95% CI = 1.87-3.14; HR = 19.66, 95% CI = 15.22-25.39 respectively). The risk of reattempt decreased in individuals receiving antidepressant prescriptions compared to those unmedicated, showing a reduction of 78% when prescribed by non-psychiatrists and 89% when prescribed by psychiatrists. Similar risk factors for suicide reattempts were observed in the depressive disorder subgroup, but the median time to reattempt was shorter (556.5 days) for this group compared to that for the overall attempters (578 days). Various risk factors including demographics, clinical characteristics, and medications should be considered to prevent suicide reattempts among suicide attempters, and patients with depressive disorder should be monitored more closely.

Inpatient Transition from Methadone to Buprenorphine-Naloxone Using a Microdosing Strategy in a Postoperative Cancer Patient: A Case Report.

Background: Buprenorphine initiation in opioid-tolerant patients usually requires decreasing the total opioid intake per day due to its potential for precipitating withdrawal. However, this strategy may not be tolerated in patients who require higher amounts of opioids, such as those with cancer pain. Case Presentation: We utilized a buprenorphine microdosing strategy for a postoperative cancer patient who was previously taking buprenorphine-naloxone for chronic noncancer pain, then initiated on methadone for uncontrolled cancer-related pain. He had a planned cancer resection in the hospital. He subsequently underwent a successful transition from methadone to buprenorphine-naloxone through microdosing in one week with close monitoring in the inpatient setting. Conclusions: Using a microdosing strategy to transition from methadone to buprenorphine-naloxone in a span of days was achieved in this case report. More research regarding the feasibility and tolerability of microinductions is needed, especially in the setting of chronic pain or cancer-related pain.

Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

A Case of Esophageal MALT Lymphoma Mimicking a Subepithelial Tumor.

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is a low-grade B-cell lymphoma that can develop in the mucosal layer of various organs, including the gastrointestinal tract, salivary glands, lungs, and skin. The most common site is the gastrointestinal tract, particularly the stomach. On the other hand, primary esophageal lymphomas are extremely rare. MALT lymphomas can undergo histological transformation into more aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma, resulting in a poor prognosis. This paper reports a rare case of primary esophageal MALT lymphoma mimicking a subepithelial tumor located in the lower esophagus that was treated successfully with radiotherapy. MALT lymphoma should be included in a differential diagnosis when subepithelial tumors are found in the esophagus, particularly if endoscopic ultrasonography reveals the tumor to be located in the deep mucosal and submucosal layers. Following the precise diagnosis, accurate staging and appropriate treatment are crucial. Regular follow-up is necessary to assess the possibility of recurrence or transformation to high-grade lymphoma.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Prognostic Effect of Tertiary Lymphoid Structures in Epstein-Barr Virus-associated Gastric Carcinomas measured by Digital Image Analysis.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent tumor-infiltrating lymphocytes (TIL) and has a favorable prognosis. Tertiary lymphoid structures (TLS), characterized by ectopic aggregated lymphocytes with high endothelial venules (HEV), are associated with favorable outcomes in various solid tumors. We hypothesized that EBVaGC, characterized by intense TIL, may be closely associated with TLS or HEV. To test this hypothesis, we digitally analyzed the TLS, HEV, and TIL in 73 surgically resected advanced EBVaGCs. For HEV, dual MECA-79 and CD31 dual immunohistochemistry were performed, and the ectopic expression of MECA-79 in tumor cells was measured. In 73 patients with EBVaGC, a high TLS ratio was found in 29 (39.7%) cases, high tumor-associated HEV density in 44 (60.3%) cases, and high CD8+ TIL density in 38 (52.1%) cases. Ectopic tumor expression of MECA-79 was observed in 36 patients (49.3%) cases. A low TLS ratio and tumor-associated HEV density were significantly associated with lymph node metastasis (p=0.005 and 0.042, respectively). Ectopic MECA-79 expression was significantly associated with lymph node metastasis (p=0.003). Patients with a low TLS ratio (p=0.038), low HEV density (p=0.042), and ectopic tumor MECA-79 expression (p=0.032) had significantly worse prognoses. In conclusion, the TLS ratio and HEV density affect the survival of patients with EBVaGC and may be related to the immune response that interrupts lymph node metastasis.

Ancistrocladus tectorius Extract Inhibits Obesity by Promoting Thermogenesis and Mitochondrial Dynamics in High-Fat Diet-Fed Mice.

Root extracts of Ancistrocladus tectorius (AT), a shrub native to China, have been shown to have antiviral and antitumor activities, but the anti-obesity effects of AT aerial parts, mainly the leaves and stems, have not been investigated. This study is the first to investigate the anti-obesity effects and molecular mechanism of AT 70% ethanol extract in 3T3-L1 adipocytes and high-fat diet (HFD)-fed C57BL/6J mice. Treatment with AT extract inhibited lipid accumulation in 3T3-L1 cells and decreased the expression of adipogenesis-related genes. AT extract also upregulated the mRNA expression of genes related to mitochondrial dynamics in 3T3-L1 adipocytes. AT administration for 12 weeks reduced body weight and organ weights, including liver, pancreas, and white and brown adipose tissue, and improved plasma profiles such as glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and total cholesterol in HFD-fed mice. AT extract reduced HFD-induced hepatic steatosis with levels of liver TG and lipogenesis-related genes. AT extract upregulated thermogenesis-related genes such as Cidea, Pgc1α, Ucp1, Prdm16, Adrb1, and Adrb3 and mitochondrial dynamics-related genes such as Mff, Opa1, and Mfn2 in brown adipose tissue (BAT). Therefore, AT extract effectively reduced obesity by promoting thermogenesis and the mitochondrial dynamics of BAT in HFD-fed mice.

Augmentation of NK-cell activity and immunity by combined natural polyphenols and saccharides in vitro and in vivo.

Curcuma longa and Sargassum coreanum are commonly used in traditional pharmaceutical medicine to improve immune function in chronic diseases. The present study was designed to systematically elucidate the in vitro and in vivo immuno-enhancing effects of a combination of C. longa and S. coreanum extracts (CS) that contain polyphenols and saccharides as functional molecules in a cyclophosphamide (Cy)-induced model of immunosuppression. In primary splenocytes, we observed the ameliorative effects of CS on a Cy-induced immunosuppression model with low cytotoxicity and an optimal mixture procedure. CS treatment enhanced T- and B-cell proliferation, increased splenic natural killer-cell activity, and restored cytokine release. Wistar rats were orally administered low (30 mg/kg), intermediate (100 mg/kg), or high (300 mg/kg) doses of CS for four weeks, followed by oral administration of Cy (5 mg/kg) for four weeks. Compared with the vehicle group, low-, intermediate-, and high-dose CS treatment accelerated dose-dependent recovery of the serum level of tumor necrosis factor-α, interferon-γ, interleukin-2, and interleukin-12. These results suggest that CS treatment accelerates the amelioration of immune deficiency in Cy-treated primary splenocytes and rats, which supports considering it for immunity maintenance. Our findings provide experimental evidence for further research and clinical application in immunosuppressed patients.

Epidemiological and Genetic Characterization of Coxsackievirus A6-Associated Hand, Foot, and Mouth Disease in Gwangju, South Korea, in 2022.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Clinical implication of neck dissection for metastatic lymph nodes originating from non-head and neck regions.

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.

CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment.

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment. Given this context, our study aimed to target the GBM TME, with a special focus on pericytes expressing CD19, to evaluate the potential effectiveness of CD19 CAR-iNK cells against GBM. We performed CD19 CAR transduction in induced pluripotent stem cell-derived NK (iNK) cells. To determine whether CD19 CAR targets the TME pericytes in GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing GBM spheroids with blood vessel organoids. When co-cultured with GBVA, CD19 CAR-iNK cells migrated towards the pericytes surrounding the GBM. Using a microfluidic chip, we demonstrated CD19 CAR-iNK cells' targeted action and cytotoxic effects in a perfusion-like environment. GBVA xenografts recapitulated the TME including human CD19-positive pericytes, thereby enabling the application of an in vivo model for validating the efficacy of CD19 CAR-iNK cells against GBM. Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.

Introduction: The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature on AOPs but summarizes and maps biological knowledge and diseases represented by the already developed AOPs (with OECD endorsed status or under validation). Methods: Knowledge from the AOP-Wiki database were extracted and prepared for analysis using a multi-step procedure. An automatic mapping of the existing information on AOPs (i.e., genes/proteins and diseases) was performed using bioinformatics tools (i.e., overrepresentation analysis using Gene Ontology and DisGeNET), allowing both the classification of AOPs and the development of AOP networks (AOPN). Results: AOPs related to diseases of the genitourinary system, neoplasms and developmental anomalies are the most frequently investigated on the AOP-Wiki. An evaluation of the three priority cases (i.e., immunotoxicity and non-genotoxic carcinogenesis, endocrine and metabolic disruption, and developmental and adult neurotoxicity) of the EU-funded PARC project (Partnership for the Risk Assessment of Chemicals) are presented. These were used to highlight under- and over-represented adverse outcomes and to identify and prioritize gaps for further research. Discussion: These results contribute to a more comprehensive understanding of the adverse effects associated with the molecular events in AOPs, and aid in refining risk assessment for stressors and mitigation strategies. Moreover, the FAIRness (i.e., data which meets principles of findability, accessibility, interoperability, and reusability (FAIR)) of the AOPs appears to be an important consideration for further development.

Fe-Porphyrin Cross-Linked Hydrogel for Reactive Oxygen Species Scavenging and Oxygen Generation in Diabetic Wounds.

Healing chronic diabetic wounds is challenging because of excessive reactive oxygen species (ROS) and hypoxia in the wound microenvironment. To address this issue, we propose a hydrogel wound dressing composed of polyethylene glycol (PEG) cross-linked with a biomimetic catalase, Fe-containing porphyrin (FeP) (i.e., FeP hydrogel). The immobilized FeP can serve as a catalyst for both ROS scavenging and O2 generation. The properties of the hydrogels were optimized by varying the composition ratios of the two constituent materials based on their mechanical properties and catalytic activity. Our in vitro cell experiments revealed that the FeP-80 hydrogel enhanced the proliferation and migration of keratinocytes and dermal fibroblasts and promoted the expression of angiogenic growth factors in keratinocytes. When tested with an in vivo diabetic chronic wound model, the FeP-80 hydrogel promoted wound healing by facilitating re-epithelialization, promoting angiogenesis, and suppressing inflammation, compared with other control groups.