Efficacy of tracheostomy for respiratory management in patients with advanced oral cancer.

BACKGROUND: Many studies have been reported on tracheostomy to prevent upper airway obstruction after surgery. Among these, the scoring system proposed by Cameron et al. quantifies various factors that influence postoperative respiratory failure. This system provides a basis for surgeons to decide whether to perform an elective tracheostomy. In this study, the authors applied the Cameron scoring system retrospectively to patients undergoing severe oral cancer surgery to reevaluate the indications for elective tracheostomy and to investigate its clinical efficacy in airway management. In this study, a sample of 20 patients who underwent oral cancer surgery was selected and divided into two groups: 10 underwent tracheostomy and 10 did not. The Cameron scoring scores for each patient were extracted, to verify whether elective tracheostomy was performed in accordance with the threshold scores. Differences in scores and significant clinical impact factors between the two groups were analyzed and compared. RESULT: The 10 patients who underwent tracheostomy had an average Cameron score of 6.4, all scoring above the recommended threshold of 5 for tracheostomy. For the 10 patients who did not undergo tracheostomy, the average score was 2.5, with 8 out of these 10 patients scoring below 5. Significant clinical impact factors observed included the location and size of the tumor, the performance of mandibulectomy and neck dissection, and the type of reconstruction surgery. CONCLUSION: In planning surgery for oral cancer patients, it is essential to consider the use of elective tracheostomy based on preoperative assessment of the risk of postoperative airway obstruction using tools like the Cameron scoring system, and patients' condition. Research confirms that elective tracheostomy effectively enhances airway management in patients with severe oral cancer.

Liquid collagen from freshwater fish skin ameliorates hydration, roughness and elasticity in photo-aged skin: a randomized, controlled, clinical study.

BACKGROUND/OBJECTIVES: Collagen is commonly used in diverse forms as a functional component in skincare products. On the other hand, the effects of collagen on human skin are controversial. Dietary collagen hydrolysates from freshwater Pangasius hypophthalmus fish skin ameliorated photo-aged skin of hairless mice. This study conducted a randomized, double-blind, placebo-controlled clinical trial to determine if liquid fish collagen (Collagen-Tripep20™, Tripep20) as a drink strengthens skin health and quality. SUBJECTS/METHODS: In this clinical trial, 85 subjects aged 35-60 yrs were diagnosed with photo-aged skin. Eighty-five subjects were randomized to receive either Tripep20 (n = 44) or placebo (n = 41). Seventy-eight subjects fully participating for a 12-week period consumed 1,000 mg of Tripep20 (n = 41) or placebo (n = 37) in a 50-mL bottle as a daily drink. The intend-to-treat and per-protocol populations were 85 and 78, respectively. Skin hydration, wrinkles, and elasticity were assessed at 0 (baseline), 6, and 12 weeks during the study period. RESULTS: Skin hydration in the Tripep20 group was significantly higher from 6 weeks (P < 0.001) than the baseline. After 12 weeks, the Crow's-feet visual score and skin roughness (Ra, Rq, and Rmax) were significantly improved in the Tripep20 group than in the placebo group (P < 0.05). Consuming liquid collagen Tripep20 greatly enhanced skin elasticity (Gross R2, Net R5, and Biological elasticity R7) in 6 weeks compared to the placebo group. The Tripep20 group showed a significant increase in skin elasticity from the baseline after 6 and 12 weeks (P < 0.001). Neither abnormal symptoms nor adverse events were encountered during the study period in subjects ingesting Tripep20 or placebo. The changes in parameters related to hematology and clinical chemistry were within the normal ranges. CONCLUSION: Oral consumption of liquid collagen Tripep20 was safe and well-tolerated. The results of this study show that freshwater fish-derived liquid collagen Tripep20 can be used as a healthy functional food ingredient to improve skin moisturizing, anti-wrinkling, and elasticity in an aging population.

Improved weight initialization for deep and narrow feedforward neural network.

Appropriate weight initialization settings, along with the ReLU activation function, have become cornerstones of modern deep learning, enabling the training and deployment of highly effective and efficient neural network models across diverse areas of artificial intelligence. The problem of "dying ReLU," where ReLU neurons become inactive and yield zero output, presents a significant challenge in the training of deep neural networks with ReLU activation function. Theoretical research and various methods have been introduced to address the problem. However, even with these methods and research, training remains challenging for extremely deep and narrow feedforward networks with ReLU activation function. In this paper, we propose a novel weight initialization method to address this issue. We establish several properties of our initial weight matrix and demonstrate how these properties enable the effective propagation of signal vectors. Through a series of experiments and comparisons with existing methods, we demonstrate the effectiveness of the novel initialization method.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Recent Advances in Patterning Strategies for Full-Color Perovskite Light-Emitting Diodes.

Metal halide perovskites have emerged as promising light-emitting materials for next-generation displays owing to their remarkable material characteristics including broad color tunability, pure color emission with remarkably narrow bandwidths, high quantum yield, and solution processability. Despite recent advances have pushed the luminance efficiency of monochromic perovskite light-emitting diodes (PeLEDs) to their theoretical limits, their current fabrication using the spin-coating process poses limitations for fabrication of full-color displays. To integrate PeLEDs into full-color display panels, it is crucial to pattern red-green-blue (RGB) perovskite pixels, while mitigating issues such as cross-contamination and reductions in luminous efficiency. Herein, we present state-of-the-art patterning technologies for the development of full-color PeLEDs. First, we highlight recent advances in the development of efficient PeLEDs. Second, we discuss various patterning techniques of MPHs (i.e., photolithography, inkjet printing, electron beam lithography and laser-assisted lithography, electrohydrodynamic jet printing, thermal evaporation, and transfer printing) for fabrication of RGB pixelated displays. These patterning techniques can be classified into two distinct approaches: in situ crystallization patterning using perovskite precursors and patterning of colloidal perovskite nanocrystals. This review highlights advancements and limitations in patterning techniques for PeLEDs, paving the way for integrating PeLEDs into full-color panels.

Spatial integration framework of solar, wind, and hydropower energy potential in Southeast Asia.

Amid its massive increase in energy demand, Southeast Asia has pledged to increase its use of renewable energy by up to 23% by 2025. Geospatial technology approaches that integrate statistical data, spatial models, earth observation satellite data, and climate modeling can be used to conduct strategic analyses for understanding the potential and efficiency of renewable energy development. This study aims to create the first spatial model of its kind in Southeast Asia to develop multi-renewable energy from solar, wind, and hydropower, further broken down into residential and agricultural areas. The novelty of this study is the development of a new priority model for renewable energy development resulting from the integration of area suitability analysis and the estimation of the amount of potential energy. Areas with high potential power estimations for the combination of the three types of energy are mostly located in northern Southeast Asia. Areas close to the equator, have a lower potential than the northern countries, except for southern regions. Solar photovoltaic (PV) plant construction is the most area-intensive type of energy generation among the considered energy sources, requiring 143,901,600 ha (61.71%), followed by wind (39,618,300 ha; 16.98%); a combination of solar PV and wind (37,302,500 ha; 16%); hydro (7,665,200 ha; 3.28%); a combination of hydro and solar PV (3,792,500 ha; 1.62%); and a combination of hydro and wind (582,700 ha; 0.25%). This study is timely and important because it will inform policies and regional strategies for transitioning to renewable energy, with consideration of the different characteristics present in Southeast Asia.

Abnormal Seebeck Effect in Vertically Stacked 2D/2D PtSe2 /PtSe2 Homostructure.

When a thermoelectric (TE) material is deposited with a secondary TE material, the total Seebeck coefficient of the stacked layer is generally represented by a parallel conductor model. Accordingly, when TE material layers of the same thickness are stacked vertically, the total Seebeck coefficient in the transverse direction may change in a single layer. Here, an abnormal Seebeck effect in a stacked two-dimensional (2D) PtSe2 /PtSe2 homostructure film, i.e., an extra in-plane Seebeck voltage is produced by wet-transfer stacking at the interface between the PtSe2 layers under a transverse temperature gradient is reported. This abnormal Seebeck effect is referred to as the interfacial Seebeck effect in stacked PtSe2 /PtSe2 homostructures. This effect is attributed to the carrier-interface interaction, and has independent characteristics in relation to carrier concentration. It is confirmed that the in-plane Seebeck coefficient increases as the number of stacked PtSe2 layers increase and observed a high Seebeck coefficient exceeding ≈188 µV K-1 at 300 K in a four-layer-stacked PtSe2 /PtSe2 homostructure.

Deep-Learning-Based Algorithm for the Removal of Electromagnetic Interference Noise in Photoacoustic Endoscopic Image Processing.

Despite all the expectations for photoacoustic endoscopy (PAE), there are still several technical issues that must be resolved before the technique can be successfully translated into clinics. Among these, electromagnetic interference (EMI) noise, in addition to the limited signal-to-noise ratio (SNR), have hindered the rapid development of related technologies. Unlike endoscopic ultrasound, in which the SNR can be increased by simply applying a higher pulsing voltage, there is a fundamental limitation in leveraging the SNR of PAE signals because they are mostly determined by the optical pulse energy applied, which must be within the safety limits. Moreover, a typical PAE hardware situation requires a wide separation between the ultrasonic sensor and the amplifier, meaning that it is not easy to build an ideal PAE system that would be unaffected by EMI noise. With the intention of expediting the progress of related research, in this study, we investigated the feasibility of deep-learning-based EMI noise removal involved in PAE image processing. In particular, we selected four fully convolutional neural network architectures, U-Net, Segnet, FCN-16s, and FCN-8s, and observed that a modified U-Net architecture outperformed the other architectures in the EMI noise removal. Classical filter methods were also compared to confirm the superiority of the deep-learning-based approach. Still, it was by the U-Net architecture that we were able to successfully produce a denoised 3D vasculature map that could even depict the mesh-like capillary networks distributed in the wall of a rat colorectum. As the development of a low-cost laser diode or LED-based photoacoustic tomography (PAT) system is now emerging as one of the important topics in PAT, we expect that the presented AI strategy for the removal of EMI noise could be broadly applicable to many areas of PAT, in which the ability to apply a hardware-based prevention method is limited and thus EMI noise appears more prominently due to poor SNR.

Interface-Induced Seebeck Effect in PtSe2/PtSe2 van der Waals Homostructures.

The Seebeck effect refers to the production of an electric voltage when different temperatures are applied on a conductor, and the corresponding voltage-production efficiency is represented by the Seebeck coefficient. We report a Seebeck effect: thermal generation of driving voltage from the heat flowing in a thin PtSe2/PtSe2 van der Waals homostructure at the interface. We refer to the effect as the interface-induced Seebeck effect. By exploiting this effect by directly attaching multilayered PtSe2 over high-resistance PtSe2 thin films as a hybridized single structure, we obtained the highly challenging in-plane Seebeck coefficient of the PtSe2 films that exhibit extremely high resistances. This direct attachment further enhanced the in-plane thermal Seebeck coefficients of the PtSe2/PtSe2 van der Waals homostructure on sapphire substrates. Consequently, we successfully enhanced the in-plane Seebeck coefficients for the PtSe2 (10 nm)/PtSe2 (2 nm) homostructure approximately 42% compared to that of a pure PtSe2 (10 nm) layer at 300 K. These findings represent a significant achievement in understanding the interface-induced Seebeck effect and provide an effective strategy for promising large-area thermoelectric energy harvesting devices using two-dimensional transition metal dichalcogenide materials, which are ideal thermoelectric platforms with high figures of merit.

3D Printable concentrated liquid metal composite with high thermal conductivity.

Heat dissipation materials in which fillers are dispersed in a polymer matrix typically do not exhibit both high thermal conductivity (k) and processability due to a trade-off. In this paper, we fabricate heat dissipation composites which overcome the trade-off using liquid metal (LM). By exceeding the conventional filler limit, ten times higher k is achieved for a 90 vol% LM composite compared with k of 50 vol% LM composite. Further, an even higher k is achieved by introducing h-BN between the LM droplets, and the highest k in this study was 17.1 W m-1 K-1. The LM composite is processable at room temperature and used as inks for 3D printing. This combination of high k and processability not only allows heat dissipation materials to be processed on demand under ambient conditions but it also increases the surface area of the LM composite, which enables rapid heat dissipation.

PDE-guided reservoir computing for image denoising with small data.

While network-based techniques have shown outstanding performance in image denoising in the big data regime requiring massive datasets and expensive computation, mathematical understanding of their working principles is very limited. Not to mention, their relevance to traditional mathematical approaches has not attracted much attention. Therefore, we suggest how reservoir computing networks can be strengthened in combination with conventional partial differential equation (PDE) methods for image denoising, especially in the small data regime. Given image data, PDEs generate sequential datasets enhancing desired image features, which provide the network with a better guideline for training in reservoir computing. The proposed procedure, reservoir computing in collaboration with PDEs (RCPDE), offers a synergetic combination of data-driven network-based methods and mathematically well-established PDE methods. It turns out that RCPDE outperforms both the usual reservoir computing and existing PDE approaches in image denoising. Furthermore, RCPDE also excels deep neural networks such as a convolutional neural network both in quality and in time in the small data regime. We believe that RCPDE reveals the great potential of reservoir computing in collaboration with various mathematically justifiable dynamics for better performance as well as for better mathematical understanding.

Hydroxycoumarin Scopoletin Inhibits Bone Loss through Enhancing Induction of Bone Turnover Markers in a Mouse Model of Type 2 Diabetes.

Diabetes induces bone deterioration, which leads to increased risk of fracture, osteopenia, and osteoporosis. Thus, diabetes-associated bone fragility has been recognized as a diabetic complication. However, the pathophysiological effects of hyperglycemia on bone turnover remain unclear. Literature evidence demonstrates that anti-diabetic medications increase the risk of fractures in individuals with type 2 diabetes. Scopoletin is a naturally occurring hydroxycoumarin potentially exhibiting anti-inflammatory and antioxidant activities and ameliorating insulin resistance as an anti-diabetic agent. However, little is known regarding the effects of scopoletin on the impairment of bone remodeling that is caused by diabetes. The aim of this study was to identify that scopoletin was capable of inhibiting the impairment of bone remodeling and turnover in a mouse model of type 2 diabetes. Submicromolar scopoletin accelerated the formation TRAP-positive multinucleated osteoclasts (40.0 vs. 105.1%) and actin ring structures impaired by 33 mM glucose. Further, 1-20 µM scopoletin enhanced bone resorption and the induction of matrix-degrading enzymes in diabetic osteoclasts. The oral administration of 10 mg/kg scopoletin elevated serum RANKL/OPG ratio and osteocalcin level reduced in db/db mice along with an increase in BMD by ~6-14%; however, it was not effective in lowering blood glucose and hemoglobin glycation. In addition, the supplementation of scopoletin elevated the formation of trabecular bones and collagen fibers in femoral epiphysis and metaphysis with a thicker epiphyseal plate and cortical bones. Furthermore, 1-20 µM scopoletin enhanced ALP activity (4.39 vs. 7.02 nmol p-nitrophenyl phosphate/min/mg protein) and deposits of mineralized bone nodules in cultured osteoblasts reduced by 33 mM glucose. The treatment of diabetic osteoblasts with scopoletin stimulated the cellular induction of BMP-2 and osteopontin and Runx2 transcription. Accordingly, the administration of scopoletin protected mice from type 2 diabetes-associated bone loss through boosting bone remodeling via the robust induction of bone turnover markers of both osteoclasts and osteoblasts. These findings suggest that scopoletin could be a potential osteoprotective agent for the treatment of diabetes-associated bone loss and fractures.

Aesculetin Inhibits Airway Thickening and Mucus Overproduction Induced by Urban Particulate Matter through Blocking Inflammation and Oxidative Stress Involving TLR4 and EGFR.

Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs and blood streams, causing diverse respiratory diseases. Aesculetin, a coumarin derivative present in the Sancho tree and chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on PM-induced airway thickening and mucus hypersecretion is poorly understood. The current study examined whether naturally-occurring aesculetin inhibited airway thickening and mucus hypersecretion caused by urban PM10 (uPM10, particles less than 10 µm). Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 µg/mL uPM10 for 8 weeks. To further explore the mechanism(s) involved in inhibition of uPM10-induced mucus hypersecretion by aesculetin, bronchial epithelial BEAS-2B cells were treated with 1-20 µM aesculetin in the presence of 2 µg/mL uPM10. Oral administration of aesculetin attenuated collagen accumulation and mucus hypersecretion in the small airways inflamed by uPM10. In addition, aesculetin inhibited uPM10-evoked inflammation and oxidant production in lung tissues. Further, aesculetin accompanied the inhibition of induction of bronchial epithelial toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EFGR) elevated by uPM10. The inhibition of TLR4 and EGFR accompanied bronchial mucus hypersecretion in the presence of uPM10. Oxidative stress was responsible for the epithelial induction of TLR4 and EGFR, which was disrupted by aesculetin. These results demonstrated that aesculetin ameliorated airway thickening and mucus hypersecretion by uPM10 inhalation by inhibiting pulmonary inflammation via oxidative stress-stimulated TLR4 and EGFR. Therefore, aesculetin may be a promising agent for treating airway mucosa-associated disorders elicited by urban coarse particulates.

Astragalin Inhibits Cigarette Smoke-Induced Pulmonary Thrombosis and Alveolar Inflammation and Disrupts PAR Activation and Oxidative Stress-Responsive MAPK-Signaling.

Epidemiological evidence shows that smoking causes a thrombophilic milieu that may play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD) as well as pulmonary thromboembolism. The increased nicotine level induces a prothrombotic status and abnormal blood coagulation in smokers. Since several anticoagulants increase bleeding risk, alternative therapies need to be identified to protect against thrombosis without affecting hemostasis. Astragalin is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities of antioxidant and anti-inflammation. The current study investigated that astragalin attenuated smoking-induced pulmonary thrombosis and alveolar inflammation. In addition, it was explored that molecular links between thrombosis and inflammation entailed protease-activated receptor (PAR) activation and oxidative stress-responsive mitogen-activated protein kinase (MAPK)-signaling. BALB/c mice were orally administrated with 10-20 mg/kg astragalin and exposed to cigarette smoke for 8 weeks. For the in vitro study, 10 U/mL thrombin was added to alveolar epithelial A549 cells in the presence of 1-20 µM astragalin. The cigarette smoking-induced the expression of PAR-1 and PAR-2 in lung tissues, which was attenuated by the administration of ≥10 mg/kg astragalin. The oral supplementation of ≥10 mg/kg astragalin to cigarette smoke-challenged mice attenuated the protein induction of urokinase plasminogen activator, plasminogen activator inhibitor-1and tissue factor, and instead enhanced the induction of tissue plasminogen activator in lung tissues. The astragalin treatment alleviated cigarette smoke-induced lung emphysema and pulmonary thrombosis. Astragalin caused lymphocytosis and neutrophilia in bronchoalveolar lavage fluid due to cigarette smoke but curtailed infiltration of neutrophils and macrophages in airways. Furthermore, this compound retarded thrombin-induced activation of PAR proteins and expression of inflammatory mediators in alveolar cells. Treating astragalin interrupted PAR proteins-activated reactive oxygen species production and MAPK signaling leading to alveolar inflammation. Accordingly, astragalin may interrupt the smoking-induced oxidative stress-MAPK signaling-inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism.

Aesculetin Inhibits Osteoclastic Bone Resorption through Blocking Ruffled Border Formation and Lysosomal Trafficking.

For the optimal resorption of mineralized bone matrix, osteoclasts require the generation of the ruffled border and acidic resorption lacuna through lysosomal trafficking and exocytosis. Coumarin-type aesculetin is a naturally occurring compound with anti-inflammatory and antibacterial effects. However, the direct effects of aesculetin on osteoclastogenesis remain to be elucidated. This study found that aesculetin inhibited osteoclast activation and bone resorption through blocking formation and exocytosis of lysosomes. Raw 264.7 cells were differentiated in the presence of 50 ng/mL receptor activator of nuclear factor-κB ligand (RANKL) and treated with 1-10 µM aesculetin. Differentiation, bone resorption, and lysosome biogenesis of osteoclasts were determined by tartrate-resistance acid phosphatase (TRAP) staining, bone resorption assay, Western blotting, immunocytochemical analysis, and LysoTracker staining. Aesculetin inhibited RANKL-induced formation of multinucleated osteoclasts with a reduction of TRAP activity. Micromolar aesculetin deterred the actin ring formation through inhibition of induction of αvß3 integrin and Cdc42 but not cluster of differentiation 44 (CD44) in RANKL-exposed osteoclasts. Administering aesculetin to RANKL-exposed osteoclasts attenuated the induction of autophagy-related proteins, microtubule-associated protein light chain 3, and small GTPase Rab7, hampering the lysosomal trafficking onto ruffled border crucial for bone resorption. In addition, aesculetin curtailed cellular induction of Pleckstrin homology domain-containing protein family member 1 and lissencephaly-1 involved in lysosome positioning to microtubules involved in the lysosomal transport within mature osteoclasts. These results demonstrate that aesculetin retarded osteoclast differentiation and impaired lysosomal trafficking and exocytosis for the formation of the putative ruffled border. Therefore, aesculetin may be a potential osteoprotective agent targeting RANKL-induced osteoclastic born resorption for medicinal use.

Eucalyptol Inhibits Amyloid-ß-Induced Barrier Dysfunction in Glucose-Exposed Retinal Pigment Epithelial Cells and Diabetic Eyes.

Hyperglycemia elicits tight junction disruption and blood-retinal barrier breakdown, resulting in diabetes-associated vison loss. Eucalyptol is a natural compound found in eucalyptus oil with diverse bioactivities. This study evaluated that eucalyptol ameliorated tight junctions and retinal barrier function in glucose/amyloid-ß (Aß)-exposed human retinal pigment epithelial (RPE) cells and in db/db mouse eyes. RPE cells were cultured in media containing 33 mM glucose or 5 µM Aß for 4 days in the presence of 1-20 µM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Nontoxic eucalyptol inhibited the Aß induction in glucose-loaded RPE cells and diabetic mouse eyes. Eucalyptol reversed the induction of tight junction-associated proteins of ZO-1, occludin-1 and matrix metalloproteinases in glucose- or Aß-exposed RPE cells and in diabetic eyes, accompanying inhibition of RPE detachment from Bruch's membrane. Adding eucalyptol to glucose- or Aß-loaded RPE cells, and diabetic mouse eyes reciprocally reversed induction/activation of apoptosis-related bcl-2, bax, cytochrome C/Apaf-1 and caspases. Eucalyptol attenuated the generation of reactive oxygen species and the induction of receptor for advanced glycation end products in Aß-exposed RPE cells and diabetic eyes. Eucalyptol may ameliorate RPE barrier dysfunction in diabetic eyes through counteracting Aß-mediated oxidative stress-induced RPE cell apoptosis.

Linarin and its aglycone acacetin abrogate actin ring formation and focal contact to bone matrix of bone-resorbing osteoclasts through inhibition of αvß3 integrin and core-linked CD44.

BACKGROUND: Since enhanced bone resorption due to osteoclast differentiation and activation cause skeletal diseases, there is a growing need in therapeutics for combating bone-resorbing osteoclasts. Botanical antioxidants are being increasingly investigated for their health-promoting effects on bone. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. PURPOSE: This study aimed to determine whether linarin present in Cirsium setidens water extracts (CSE) and its aglycone acacetin inhibited osteoclastogenesis of RANKL-exposed RAW 264.7 murine macrophages for 5 days. METHODS: This study assessed the osteoprotective effects of CSE, linarin and acacetin on RANKL-induced differentiation and activation of osteoclasts by using MTT assay, TRAP staining, Western blot analysis, bone resorption assay actin ring staining, adhesion assay and immunocytochemical assay. This study explored the underlying mechanisms of their osteoprotection, and identified major components present in CSE by HPLC analysis. RESULTS: Linarin and pectolinarin were identified as major components of CSE. Nontoxic linarin and acacetin as well as CSE, but not pectolinarin attenuated the RANKL-induced macrophage differentiation into multinucleated osteoclasts, and curtailed osteoclastic bone resorption through reducing lacunar acidification and bone matrix degradation in the osteoclast-bone interface. Linarin and acacetin in CSE reduced the transmigration and focal contact of osteoclasts to bone matrix-mimicking RGD peptide. Such reduction was accomplished by inhibiting the induction of integrins, integrin-associated proteins of paxillin and gelsolin, cdc42 and CD44 involved in the formation of actin rings. The inhibition of integrin-mediated actin ring formation by linarin and acacetin entailed the disruption of TRAF6-c-Src-PI3K signaling of bone-resorbing osteoclasts. The functional inhibition of c-Src was involved in the loss of F-actin-enriched podosome core protein cortactin-mediated actin assembly due to linarin and acacetin. CONCLUSION: These observations demonstrate that CSE, linarin and acacetin were effective in retarding osteoclast function of focal adhesion to bone matrix and active bone resorption via inhibition of diffuse cloud-associated αvß3 integrin and core-linked CD44.

Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling.

Pulmonary fibrosis is a disease in which lung tissues become fibrous and thereby causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract, secreting inflammatory cytokines, which subsequently leads to the development of pulmonary fibrosis. Aesculetin, a major component of the sancho tree and chicory, is known to biologically have antioxidant and anti-inflammatory effects. Human alveolar epithelial A549 cells were cultured for 24 h in conditioned media of THP-1 monocyte-derived macrophages (mCM) with 1-20 µM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-α (TNF)-α and interleukin (IL)-8 as major cytokines. Aesculetin inhibited alveolar epithelial induction of the mesenchymal markers in mCM-exposed/IL-8-loaded A549 cells (≈47-51% inhibition), while epithelial markers were induced in aesculetin-treated cells subject to mCM/IL-8 (≈1.5-2.3-fold induction). Aesculetin added to mCM-stimulated A549 cells abrogated the collagen production and alveolar epithelial CXC-chemokine receptor 2 (CXCR2) induction. The production of matrix metalloproteinase (MMP) proteins in mCM-loaded A549 cells was reduced by aesculetin (≈52% reduction), in parallel with its increase in tissue inhibitor of metalloproteinases (TIMP) proteins (≈1.8-fold increase). In addition, aesculetin enhanced epithelial induction of tight junction proteins in mCM-/IL-8-exposed cells (≈2.3-2.5-fold induction). The inhalation of polyhexamethylene guanidine (PHMG) in mice accompanied neutrophil predominance in bronchoalveolar lavage fluid (BALF) and macrophage infiltration in alveoli, which was inhibited by orally administrating aesculetin to mice. Treating aesculetin to mice alleviated PHMG-induced IL-8-mediated subepithelial fibrosis and airway barrier disruption. Taken together, aesculetin may antagonize pulmonary fibrosis and alveolar epithelial barrier disruption stimulated by the infiltration of monocyte-derived macrophages, which is typical of PHMG toxicity, involving interaction of IL-8 and CXCR2. Aesculetin maybe a promising agent counteracting macrophage-mediated inflammation-associated pulmonary disorders.

Asaronic Acid Inhibited Glucose-Triggered M2-Phenotype Shift Through Disrupting the Formation of Coordinated Signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK.

Macrophage polarization has been implicated in the pathogenesis of metabolic diseases such as obesity, diabetes, and atherosclerosis. Macrophages responsiveness to polarizing signals can result in their functional phenotype shifts. This study examined whether high glucose induced the functional transition of M2 macrophages, which was inhibited by asaronic acid, one of purple perilla constituents. J774A.1 murine macrophages were incubated with 40 ng/mL interleukin (IL)-4 or exposed to 33 mM glucose in the presence of 1-20 µΜ asaronic acid. In macrophages treated with IL-4 for 48 h, asaronic acid further accelerated cellular induction of the M2 markers of IL-10, arginase-1, CD163, and PPARγ via increased IL-4-IL-4Rα interaction and activated Tyk2-STAT6 pathway. Asaronic acid promoted angiogenic and proliferative capacity of M2-polarized macrophages, through increasing expression of VEGF, PDGF, and TGF-ß. In glucose-loaded macrophages, there was cellular induction of IL-4, IL-4 Rα, arginase-1, and CD163, indicating that high glucose skewed naïve macrophages toward M2 phenotypes via an IL-4-IL-4Rα interaction. However, asaronic acid inhibited M2 polarization in diabetic macrophages in parallel with inactivation of Tyk2-STAT6 pathway and blockade of GLUT1-mediated metabolic pathway of Akt-mTOR-AMPKα. Consequently, asaronic acid deterred functional induction of COX-2, CTGF, α-SMA, SR-A, SR-B1, and ABCG1 in diabetic macrophages with M2 phenotype polarity. These results demonstrated that asaronic acid allayed glucose-activated M2-phenotype shift through disrupting coordinated signaling of IL-4Rα-Tyk2-STAT6 in parallel with GLUT1-Akt-mTOR-AMPK pathway. Thus, asaronic acid has therapeutic potential in combating diabetes-associated inflammation, fibrosis, and atherogenesis through inhibiting glucose-evoked M2 polarization.

Ultrasound Imaging of the Trunk Muscles in Acute Stroke Patients and Relations With Balance Scales.

OBJECTIVE: To examine the correlation between ultrasonographic trunk muscle parameters and balance scales in mild acute stroke patients. METHODS: A total of 55 stroke patients with hemiparesis and motor power grade ≥4 in the manual motor test were included. The Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and Trunk Control Test (TCT) were used to evaluate patient balance function. Ultrasonographic parameters were measured on both non-paretic and paretic sides of the rectus abdominis, external oblique, internal oblique, transversus abdominis, and erector spinae muscles. Resting thickness and contraction thickness were measured in all muscles, and contractility and contractility ratio were calculated based on measured thicknesses. The differences between paretic and non-paretic muscle parameters, and the correlation between ultrasonographic parameters and balance scales were analyzed. Stroke patients were divided into two groups according to their fall risk. Ultrasonographic measurements between the two groups were compared. RESULTS: All muscles' contraction thickness and contractility were significantly different between paretic and non-paretic sides (p<0.001). Contractility ratios of all trunk muscles showed a significant correlation with SARA, BBS, TUG, and TCT (p<0.05). Contractility ratios of all muscles were significantly different between high- and low-risk fall groups (p<0.05). CONCLUSION: The contractility ratio in stroke patients reflects their balance disturbance and fall risk and it may serve as a new parameter for ultrasound imaging of trunk muscles.