Euonymus alatus Leaf Extract Attenuates Effects of Aging on Oxidative Stress, Neuroinflammation, and Cognitive Impairment.

Our study aimed to explore the impact and mechanism of Euonymus alatus leaf extract on age-dependent oxidative stress, neuroinflammation, and progressive memory impairments in aged mice. Twenty-four-month-old mice received EA-L3 (300 mg/kg/day) or the reference drug, donepezil (DPZ, 5 mg/kg/day), for 6 weeks, and learning and memory functions were detected using the Passive Avoidance Test (PAT). As expected, cognitive function deficits were detected in aged mice compared with young mice, and these deficits were significantly mitigated by dietary treatments with EA-L3. In parallel, it upregulated the brain-derived neurotrophic factor (BDNF) and subsequently activated the extracellular-signal-regulated kinase (ERK)/cAMP response element-binding (CREB) signaling in the mouse hippocampus and scopolamine-induced B35 and SH-SY5Y neuroblastoma cells. EA-L3 showed strong anti-inflammatory effects with decreased NF-κBp65, cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α), increased interleukin (IL)-10, and doublecortin (DCX) protein expression in the hippocampus of aged mice. Similar results were also confirmed in LPS-induced BV-2 microglia and neuroblastoma cells upon treatment with EA-L3 extract. In addition, EA-L3 notably dose-dependently decreased ROS in BV2 cells after exposure to LPS. Taken together, EA-L3 might be used as a dietary supplement to alleviate oxidative stress, the deterioration of hippocampal-based memory tasks, and neuroinflammation in elderly people.

Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy.

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.

Deep learning algorithm for the automated detection and classification of nasal cavity mass in nasal endoscopic images.

Nasal endoscopy is routinely performed to distinguish the pathological types of masses. There is a lack of studies on deep learning algorithms for discriminating a wide range of endoscopic nasal cavity mass lesions. Therefore, we aimed to develop an endoscopic-examination-based deep learning model to detect and classify nasal cavity mass lesions, including nasal polyps (NPs), benign tumors, and malignant tumors. The clinical feasibility of the model was evaluated by comparing the results to those of manual assessment. Biopsy-confirmed nasal endoscopic images were obtained from 17 hospitals in South Korea. Here, 400 images were used for the test set. The training and validation datasets consisted of 149,043 normal nasal cavity, 311,043 NP, 9,271 benign tumor, and 5,323 malignant tumor lesion images. The proposed Xception architecture achieved an overall accuracy of 0.792 with the following class accuracies on the test set: normal = 0.978 ± 0.016, NP = 0.790 ± 0.016, benign = 0.708 ± 0.100, and malignant = 0.698 ± 0.116. With an average area under the receiver operating characteristic curve (AUC) of 0.947, the AUC values and F1 score were highest in the order of normal, NP, malignant tumor, and benign tumor classes. The classification performances of the proposed model were comparable with those of manual assessment in the normal and NP classes. The proposed model outperformed manual assessment in the benign and malignant tumor classes (sensitivities of 0.708 ± 0.100 vs. 0.549 ± 0.172, 0.698 ± 0.116 vs. 0.518 ± 0.153, respectively). In urgent (malignant) versus nonurgent binary predictions, the deep learning model achieved superior diagnostic accuracy. The developed model based on endoscopic images achieved satisfactory performance in classifying four classes of nasal cavity mass lesions, namely normal, NP, benign tumor, and malignant tumor. The developed model can therefore be used to screen nasal cavity lesions accurately and rapidly.

Treatment Outcome of Olfactory Neuroblastoma: A Multicenter Study by the Korean Sinonasal Tumor and Skull Base Surgery Study Group.

Objectives: Due to the rarity of olfactory neuroblastoma (ONB), there is an ongoing debate about optimal treatment strategies, especially for early staged or locally advanced cases. Therefore, our study aims to explore experiences from multiple centers, focusing on factors that influence the oncological outcomes of ONB. Methods: We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and the Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. Results: In our cohort, the 5-year overall survival rate (OS) was 78.6%, and the 5-year disease-free survival rate (DFS) was 62.4%. The Cox proportional hazards model revealed that the mKadish stage and Dulguerov T status were significant for DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though that result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Conclusion: Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Induction chemotherapy did not show a survival benefit, even after stage matching.

Predictors of surgical outcomes for limited palatal muscle resection in patients with obstructive sleep apnea.

OBJECTIVE: Limited palatal muscle resection (LPMR) is a modified palatal surgical technique to correct retropalatal obstruction without complications. This study aims to determine the associated factors affecting the success and cure rate of LPMR in patients with obstructive sleep apnea (OSA), thus guiding patient selection and improving surgical outcome. METHODS: Thirty-five OSA patients underwent LPMR were enrolled. All patients received routine physical examination, preoperative drug-induced sleep endoscopy (DISE), and polysomnography (PSG). Clinical, polysomnographic, cephalometric variables, and DISE findings were evaluated. These measurements were compared between the surgical success and failure group based on the results of preoperative and postoperative PSG. Furthermore, we compared the cured and non-cured groups in the surgical success group. RESULTS: Among 35 patients, the overall success rate was 57 % with a cure rate of 31.4 %. Patients with Friedman stage II had a significantly higher success rate (p = 0.032). According to DISE results, tongue base obstruction affected the surgical outcome (p < 0.001). The success rate was 100 % in the no tongue base obstruction during DISE, 72.2 % in the partial obstruction, and 9.1 % in the total obstruction. Tonsil size is also helpful in predicting surgical success rate (p = 0.041). Furthermore, patients with mild AHI were more likely to be surgical cures. when compared with patients with severe AHI (p = 0.044). CONCLUSION: Patients with larger tonsil size and no tongue base obstruction during DISE may have a higher chance of surgical success with LPMR. The lower AHI may be predictors of surgical cure after LPMR.

Single-Cell RNA Sequencing Reveals Immuno-Oncology Characteristics of Tumor-Infiltrating T Lymphocytes in Photodynamic Therapy-Treated Colorectal Cancer Mouse Model.

Photodynamic therapy (PDT) has shown promise in reducing metastatic colorectal cancer (CRC); however, the underlying mechanisms remain unclear. Modulating tumor-infiltrating immune cells by PDT may be achieved, which requires the characterization of immune cell populations in the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). Here, we determined the effect of Chlorin e6 (Ce6)-mediated PDT on tumor-infiltrating T cells using scRNA-seq analysis. We used a humanized programmed death-1/programmed death ligand 1 (PD-1/PD-L1) MC38 cell allograft mouse model, considering its potential as an immunogenic cancer model and in combination with PD-1/PD-L1 immune checkpoint blockade. PDT treatment significantly reduced tumor growth in mice containing hPD-1/PD-L1 MC38 tumors. scRNA-seq analysis revealed that the PDT group had increased levels of CD8+ activated T cells and CD8+ cytotoxic T cells, but decreased levels of exhausted CD8+ T cells. PDT treatment also enhanced the infiltration of CD8+ T cells into tumors and increased the production of key effector molecules, including granzyme B and perforin 1. These findings provide insight into immune-therapeutic modulation for CRC patients and highlight the potential of PDT in overcoming immune evasion and enhancing antitumor immunity.

Chlorin E6-Curcumin-Mediated Photodynamic Therapy Promotes an Anti-Photoaging Effect in UVB-Irradiated Fibroblasts.

Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy (Ce6-PDT), in addition to being the first-line treatment for malignancies, has been shown to lessen skin photoaging, while curcumin is well known for reducing the deleterious effects of ROS. In the current study, PDT with three novel Ce6-curcumin derivatives, a combination of Ce6 and curcumin with various linkers, including propane-1,3-diamine for Ce6-propane-curcumin; hexane-1,6-diamine for Ce6-hexane-curcumin; and 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) for Ce6-dipolyethylene glycol (diPEG)-curcumin, were studied for regulation of UVB-induced photoaging on human skin fibroblast (Hs68) and mouse embryonic fibroblast (BALB/c 3T3) cells. We assessed the antiphotoaging effects of Ce6-curcumin derivatives on cell viability, antioxidant activity, the mechanism of matrix metalloproteinase-1 and 2 (MMP-2) expression, and collagen synthesis in UVB-irradiated in vitro models. All three Ce6-curcumin derivatives were found to be non-phototoxic in the neutral red uptake phototoxicity test. We found that Ce6-hexane-curcumin-PDT and Ce6-propane-curcumin-associated PDT exhibited less cytotoxicity in Hs68 and BALB/c 3T3 fibroblast cell lines compared to Ce6-diPEG-curcumin-PDT. Ce6-diPEG-curcumin and Ce6-propane-curcumin-associated PDT showed superior antioxidant activity in Hs68 cell lines. Further, in UVB-irradiated in vitro models, the Ce6-diPEG-curcumin-PDT greatly attenuated the expression levels of MMP-1 and MMP-2 by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and tumor necrosis factor-α (NF-κB) signaling. Moreover, Ce6-diPEG-curcumin effectively inhibited inflammatory molecules, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while accelerating collagen synthesis. These results demonstrate that Ce6-diPEG-curcumin may be a potential therapy for treating skin photoaging.

Anti-Obesity Effect of Chlorin e6-Mediated Photodynamic Therapy on Mice with High-Fat-Diet-Induced Obesity.

This study aimed to evaluate the efficacy of Chlorin e6 (Ce6)-based photodynamic therapy (PDT) for anti-obesity activities in high-fat-diet (HFD)-induced obesity mouse models. We induced obesity in C57BL/6 mice by HFD and administered Ce6 (2.5 or 5 mg/kg) orally with 3 h of incubation. The mice were then exposed to light of high fluence rate (4.96 mW/cm2) or low fluence rate (2.56 mW/cm2) in the designed LED mouse chamber 2-3 days a week for up to 8 weeks. The study also analyzed the pharmacokinetics and optimization of the drug by evaluating the absorption, distribution, metabolism, and excretion (ADME) of Ce6 in the rat models. Both low doses (2.5 mg/kg) and high doses (5 mg/kg) of Ce6 with high irradiation dose showed better anti-obesity effects than other groups with decreased body weight. The lipid accumulation in the liver and adipocyte size in epididymal adipose tissues were found to be decreased by Ce6-PDT in comparison to vehicle-treated HFD groups. We also observed increased levels of the lipidomic biomarkers, such as leptin and LDL cholesterol, while observing decreasing levels of total cholesterol and adiponectin in the Ce6-PDT-treated mice. These findings may provide valuable insight into Ce6-PDT as an alternative and non-invasive therapeutic methodology for obesity and obesity-related diseases.

Novel Chlorin e6-Curcumin Derivatives as a Potential Photosensitizer: Synthesis, Characterization, and Anticancer Activity.

Novel series of chlorin e6-curcumin derivatives were designed and synthesized. All the synthesized compounds 16, 17, 18, and 19 were tested for their photodynamic treatment (PDT) efficacy against human pancreatic cancer cell lines: AsPC-1, MIA-PaCa-2, and PANC-1. The cellular uptake study was performed in the aforementioned cell lines using fluorescence-activated cell sorting (FACS). 17, among the synthesized compounds with IC50 values of 0.27, 0.42, and 0.21 µM against AsPC-1, MIA PaCa-2, and PANC-1 cell lines, respectively, demonstrated excellent cellular internalization capability and exhibited higher phototoxicity relative to the parent Ce6. The quantitative analyses using Annexin V-PI staining revealed that the 17-PDT-induced apoptosis was dose-dependent. In pancreatic cell lines, 17 reduced the expression of the anti-apoptotic protein, Bcl-2, and increased the pro-apoptotic protein, cytochrome C, which indicates the activation of intrinsic apoptosis, the primary cause of cancer cell death. Structure-activity relationship studies have shown that the incorporation of additional methyl ester moiety and conjugation to the enone moiety of curcumin enhances cellular uptake and PDT efficacy. Moreover, in vivo PDT testing in melanoma mouse models revealed that 17-PDT greatly reduced tumor growth. Therefore, 17 might be an effective photosensitizer for PDT anticancer therapy.

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model.

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied. Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats. Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed. Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

Risk factors for sialocele after parotidectomy: Does tumor size really matter?

OBJECTIVE: Sialocele that develops after parotid surgery often prolongs the treatment period and stresses both the surgeon and patient. The extent of surgery and tumor size are known to be associated with sialocele occurrence. We investigated the incidence of post-parotidectomy sialocele and the associated risk factors, with a focus on tumor size. METHODS: We retrospectively reviewed the medical records of 172 patients who underwent parotidectomy between January 2013 and May 2020 at Haeundae Paik Hospital, Inje University of Korea. We stratified patients into those with and without sialocele (fluid collection in the operative bed). We compared clinical data, patient demographics, and surgical details; we identified risk factors for sialocele development after parotid surgery. RESULTS: Seventeen patients were diagnosed with post-parotidectomy sialocele (9.88%; 17/172). Univariate logistic regression revealed that the male sex, deep lobe tumor location, and large tumor size were significantly associated with postoperative sialocele (p = 0.015, 0.009, and 0.016, respectively). We subjected these parameters to multivariate analyses; the odds ratios were 3.70, 3.58, and 2.34, respectively. Receiver operating characteristic curve analyses showed that a tumor size > 2.50 cm was the optimal cutoff in terms of predicting post-parotidectomy sialocele. CONCLUSION: Male sex, a tumor in the deep lobe, and large tumor size were strongly associated with increased risk for sialocele after parotidectomy. Tumor size > 2.50 cm serves as the cutoff identifying patients likely to experience sialocele after parotid surgery.

Chlorin e6-associated photodynamic therapy enhances abscopal antitumor effects via inhibition of PD-1/PD-L1 immune checkpoint.

We hypothesized that photodynamic therapy (PDT) with Chlorin e6 (Ce6) enhances antitumor abscopal effects via inhibition of the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint. By using syngeneic melanoma and pancreatic tumor mouse models, we studied the Ce6-PDT-induced immune responses in local and distant tumor microenvironments. In addition, the Ce6-PDT's target in the PD-1/PD-L1 interaction was analyzed in MC38-hPD-L1 colon cancer and PD-1 expressing Jurkat T cell coculture. The tumors in the irradiated and non-irradiated sites in the abscopal effective (Abseff) group of both mouse models were regressed, proving the abscopal effect. The immunogenic effect in the Abseff group was associated with an expansion of T cell and other immune cells infiltration without changes in the CD39+ population in either the right or left tumors compared to control group. Furthermore, the abscopal ineffective (Absineff) group demonstrated lesser increase of T cells, decreased immune cell infiltration, and increased CD39-expressing Treg cells without suppression of tumor growth. In the coculture with PD-1-expressing Jurkat T cell, Ce6-PDT efficiently suppressed the PD-1/PD-L1 interactions by increasing the proliferation and cytotoxic activity of CD8+ T cells while decreasing CD39-expressing Treg cells in a dose-dependent manner. Likewise, the inhibition of PD-1/PD-L1 interactions was also correlated with the increased production of IL-2 and Granzyme B. Our findings imply that Ce6-PDT is a promising immunotherapy with the potential to improve the abscopal effect.

Efficient Synthesis of Chlorin e6 and Its Potential Photodynamic Immunotherapy in Mouse Melanoma by the Abscopal Effect.

Photodynamic therapy (PDT) can eradicate not only cancer cells but also stimulate an antitumor immune response. Herein, we describe two efficient synthetic methodologies for the preparation of Chlorin e6 (Ce6) from Spirulina platensis and address the phototoxic effect of Ce6 in vitro along with antitumor activity in vivo. Melanoma B16F10 cells were seeded and phototoxicity was monitored by the MTT assay. The C57BL/6 mice were subcutaneously inoculated on the left and right flank with B16F10 cells. The mice were intravenously injected with Ce6 of 2.5 mg/kg and then exposed to red light (660 nm) on the left flank tumors 3 h after the injection. The immune response was studied by analyzing Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and Interleukin-2 (IL-2) of the right flank tumors through qPCR. Our results revealed that the tumor was suppressed not only in the left flank but also in the right flank, where no PDT was given. The upregulated gene and protein expression of IFN-γ, TNF-α, and IL-2 revealed antitumor immunity due to Ce6-PDT. The findings of this study suggest an efficient methodology of Ce6 preparation and the efficacy of Ce6-PDT as a promising antitumor immune response.

Effect of Photodynamic Therapy with Chlorin e6 on Canine Tumors.

This work aims to prepare pure Chlorin e6 (Ce6) and establish Ce6-mediated photodynamic therapy (Ce6-PDT) as a better therapy option for canine tumors as well as mouse tumor models. Five dogs suffering from various cancers were treated with Ce6-PDT from one to several times. After receiving the Ce6 (2.5 mg/kg) for 3 h, tumors were illuminated superficially or interstitially with 660 nm light. Two dogs underwent Ce6-guided fluorescence imaging by photodynamic diagnosis (PDD). Cell proliferation and apoptosis were detected by the 4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and western blot assay, respectively. Ce6-PDT efficacy was also determined using melanoma and pancreatic cancer mouse models. Two veterinary patients with mammary carcinoma and histiocytic sarcoma had their tumors significantly diminished and showed improved health after receiving Ce6-PDT. Moreover, in the cases of canine tumors, the adjunctive use of Ce6-PDD revealed cancers that were not visible with white light viewing and provided a visual contrast from surrounding tissues. Also, in vivo, Ce6-PDT remarkably reduced melanoma and pancreatic tumors in the mouse model. These findings could pave the way for a better understanding of the underlying processes of Ce6-PDT, making it an effective and safe candidate for use in human and veterinary applications to abolish various cancers.

DNA-cloaked nanoparticles for tumor microenvironment-responsive activation.

Although progress has been made in developing tumor microenvironment-responsive delivery systems, the list of cargo-releasing stimuli remains limited. In this study, we report DNA nanothread-cloaked nanoparticles for reactive oxygen species (ROS)-rich tumor microenvironment-responsive delivery systems. ROS is well known to strongly induce DNA fragmentation via oxidative stress. As a model anticancer drug, hydrophobic omacetaxine was entrapped in branched cyclam ligand-modified nanoparticles (BNP). DNA nanothreads were prepared by rolling-circle amplification and complexed to BNP, yielding DNA nanothread-cloaked BNP (DBNP). DBNP was unmasked by DNA nanothread-degrading ROS and culture supernatants of LNCaP cells. The size and zeta potential of DBNP were changed by ROS. In ROShigh LNCaP cells, but not in ROSlow fibroblast cells, the uptake of DBNP was higher than that of other nanoparticles. Molecular imaging revealed that DBNP exhibited greater distribution to tumor tissues, compared to other nanoparticles. Ex vivo mass spectrometry-based imaging showed that omacetaxine metabolites were distributed in tumor tissues of mice treated with DBNP. Intravenous administration of DBNP reduced the tumor volume by 80% compared to untreated tumors. Profiling showed that omacetaxine treatment altered the transcriptional profile. These results collectively support the feasibility of using polymerized DNA-masked nanoparticles for selective activation in the ROS-rich tumor microenvironment.

The Potential Anti-Photoaging Effect of Photodynamic Therapy Using Chlorin e6-Curcumin Conjugate in UVB-Irradiated Fibroblasts and Hairless Mice.

Photodynamic therapy (PDT) has been used to treat cancers and non-malignant skin diseases. In this study, a chlorin e6-curcumin conjugate (Ce6-PEG-Cur), a combination of chlorin e6 (Ce6) and curcumin via a PEG linker, was used as a photosensitizer. The in vitro and in vivo effects of PDT using Ce6-PEG-Cur were analyzed in UVB-irradiated fibroblasts and hairless mice. The UVB-induced expression of MMPs was reduced in Hs68 fibroblast cells, and procollagen type Ⅰ expression was enhanced by Ce6-PEG-Cur-mediated PDT on a Western blotting gel. Moreover, UVB-induced collagen levels were restored upon application of Ce6-PEG-Cur-mediated PDT. Ce6-PEG-Cur-mediated PDT inhibited the expression of phosphorylated p38 in the MAPK signaling pathway, and it reduced the expression of phosphorylated NF-κB. In animal models, Ce6-PEG-Cur-mediated PDT inhibited the expression of MMPs, whereas procollagen type Ⅰ levels were enhanced in the dorsal skin of UVB-irradiated mice. Moreover, UVB-induced dorsal roughness was significantly reduced following Ce6-PEG-Cur-mediated PDT treatment. H&E staining and Masson's trichrome staining showed that the thickness of the epidermal region was reduced, and the density of collagen fibers increased. Taken together, Ce6-PEG-Cur-mediated PDT might delay and improve skin photoaging by ultraviolet light, suggesting its potential for use as a more effective photo-aging treatment.

Euonymus alatus Twig Extract Protects against Scopolamine-Induced Changes in Brain and Brain-Derived Cells via Cholinergic and BDNF Pathways.

In the current study, the therapeutic and preventive effects of Euonymus alatus (EA) twig extract were investigated in a mouse model of cognitive deficit and B35 cells. Twig extract 1 was extracted with 70% ethanol and later twig extract 2 was extracted through liquid-liquid extraction with 70% ethanol and hexane. EA twig 2 (300 mg/kg) along with the standard drug donepezil (5 mg/kg) were orally administered to the mice for 34 days. Scopolamine was given intraperitoneally for 7 days. Administration of EA twig extract 2 significantly improved the passive avoidance test (PAT) in mice. EA twigs extract also restored the scopolamine-reduced brain-derived neurotrophic factor (BDNF)/extracellular regulated kinase (ERK)/cyclic AMP responsive element binding protein (CREB) signaling in B35 cells and the mouse hippocampus. In addition, EA twig extract significantly inhibited the acetylcholine esterase (AChE) activity in B35 cells in a dose-dependent manner. Chromatography and ESI MS analysis of EA twig extract revealed the presence of flavonoids; epicatechin, taxifolin, aromadendrin, and naringenin with catechin being the most abundant. These flavonoids exerted protective effects alone and had the possibility of synergistic effects in combination. Our work unmasks the ameliorating effect of EA twig extract 2 on scopolamine-associated cognitive impairments through the restoration of cholinergic systems and the BDNF/ERK/CREB pathway.

The Clinical and Radiologic Features Affecting the Ocular Symptoms in Patients With Paranasal Sinus Mucoceles Involving the Orbit.

INTRODUCTION: Paranasal sinus (PNS) mucoceles may involve orbit and have ophthalmic manifestations. The objective of this study was to investigate the clinical and radiological features affecting the ophthalmic manifestations in patients with PNS mucoceles involving the orbit. METHODS: Fifty-two patients underwent endoscopic sinus surgery for PNS mucoceles with orbital involvement were investigated. Ophthalmic manifestations included exophthalmos, ocular pain, diplopia, visual disturbance. The correlation between ocular symptoms and the mucocele volume, origin site of mucocele, and the involvement of extraocular muscles or optic nerve were evaluated. RESULTS: Ophthalmic manifestations were significantly higher in the anterior ethmoid and frontal sinus involvement. Exophthalmos was significantly increased in the involvement of anterior ethmoid sinus, frontal sinus, and superior group ocular muscles, but decreased in the mucocele of maxillary sinus. Ocular pain was significantly lower in the involvement of anterior ethmoid sinus, frontal sinus, and superior group ocular muscle. Diplopia showed no significant differences among clinical and radiological parameters. Visual disturbance was significantly higher in the involvement of posterior ethmoid sinus and sphenoid sinus. The volume of mucocele, relation to optic nerve, adjacent bony change, and duration of ocular symptom had no significant effect on ocular symptoms in patients with PNS mucoceles involving the orbit. CONCLUSION: The volume of mucocele did not affect the ophthalmic manifestations in patients with PNS mucoceles involving the orbit. Exophthalmos, ocular pain, and visual disturbance were significantly correlated with the involved sinus of PNS mucoceles.

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles.

BACKGROUND: Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. METHODS: C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 µg/50 µL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. RESULTS: Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. CONCLUSION: These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.