Tongue feature dataset construction and real-time detection.

BACKGROUND: Tongue diagnosis in traditional Chinese medicine (TCM) provides clinically important, objective evidence from direct observation of specific features that assist with diagnosis. However, the current interpretation of tongue features requires a significant amount of manpower and time. TCM physicians may have different interpretations of features displayed by the same tongue. An automated interpretation system that interprets tongue features would expedite the interpretation process and yield more consistent results. MATERIALS AND METHODS: This study applied deep learning visualization to tongue diagnosis. After collecting tongue images and corresponding interpretation reports by TCM physicians in a single teaching hospital, various tongue features such as fissures, tooth marks, and different types of coatings were annotated manually with rectangles. These annotated data and images were used to train a deep learning object detection model. Upon completion of training, the position of each tongue feature was dynamically marked. RESULTS: A large high-quality manually annotated tongue feature dataset was constructed and analyzed. A detection model was trained with average precision (AP) 47.67%, 58.94%, 71.25% and 59.78% for fissures, tooth marks, thick and yellow coatings, respectively. At over 40 frames per second on a NVIDIA GeForce GTX 1060, the model was capable of detecting tongue features from any viewpoint in real time. CONCLUSIONS/SIGNIFICANCE: This study constructed a tongue feature dataset and trained a deep learning object detection model to locate tongue features in real time. The model provided interpretability and intuitiveness that are often lacking in general neural network models and implies good feasibility for clinical application.

Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.

Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.

Andrographolide Inhibits Lipotoxicity-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages.

Andrographolide is the major bioactive component of the herb Andrographis paniculata and is a potent anti-inflammatory agent. Obesity leads to an excess of free fatty acids, particularly palmitic acid (PA), in the circulation. Obesity also causes the deposition of ectopic fat in nonadipose tissues, which leads to lipotoxicity, a condition closely associated with inflammation. Here, we investigated whether andrographolide could inhibit PA-induced inflammation by activating autophagy, activating the antioxidant defense system, and blocking the activation of the NLRP3 inflammasome. Bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and then activated with PA. LPS/PA treatment increased both the mRNA expression of NLRP3 and IL-1[Formula: see text] and the release of IL-1[Formula: see text] in BMDMs. Andrographolide inhibited the LPS/PA-induced protein expression of caspase-1 and the release of IL-1[Formula: see text]. Furthermore, andrographolide attenuated LPS/PA-induced mtROS generation by first promoting autophagic flux and catalase activity, and ultimately inhibiting activation of the NLRP3 inflammasome. Our results suggest that the mechanisms by which andrographolide downregulates LPS/PA-induced IL-1[Formula: see text] release in BMDMs involve promoting autophagic flux and catalase activity. Andrographolide may thus be a candidate to prevent obesity- and lipotoxicity-driven chronic inflammatory disease.

14-Deoxy-11,12-Didehydroandrographolide Ameliorates Glucose Intolerance Enhancing the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 Signaling Pathway and Inducing GLUT4 Expression in Myotubes and Skeletal Muscle of Obese Mice.

14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive component of Andrographis paniculata, has antidiabetic activity. AMP-activated protein kinase (AMPK) regulates glucose transport and ameliorates insulin resistance. The aim of the present study was to investigate whether activation of AMPK is involved in the mechanism by which deAND ameliorates insulin resistance in muscles. deAND amounts up to 40 [Formula: see text]M dose-dependently activated phosphorylation of AMPK[Formula: see text] and TBC1D1 in C2C12 myotubes. In addition, deAND significantly activated phosphorylation of LKB1 at 6 h after treatment, and this activation was maintained up to 48 h. deAND increased glucose uptake at 18 h after treatment, and this increase was time dependent up to 72 h. Compound C, an inhibitor of AMPK, suppressed deAND-induced phosphorylation of AMPK[Formula: see text] and TBC1D1 and reversed the effect on glucose uptake. In addition, the expression of GLUT4 mRNA and protein in C2C12 myotubes was up-regulated by deAND in a time-dependent manner. Promotion of GLUT4 gene transcription was verified by a pGL3-GLUT4 (837 bp) reporter assay. deAND also increased the nuclear translocation of MEF-2A and PPAR[Formula: see text]. After 16 weeks of feeding, the high-fat diet (HFD) inhibited phosphorylation of AMPK[Formula: see text] and TBC1D1 in skeletal muscle of obese C57BL/6JNarl mice, and deactivation of AMPK[Formula: see text] and TBC1D1 by the HFD was abolished by deAND supplementation. Supplementation with deAND significantly promoted membrane translocation of GLUT4 compared with the HFD group. Supplementation also significantly increased GLUT4 mRNA and protein expression in skeletal muscle compared with the HFD group. The hypoglycemic effects of deAND are likely associated with activation of the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 signaling pathway and stimulation of MEF-2A- and PPAR[Formula: see text]-dependent GLUT4 gene expression, which account for the glucose uptake into skeletal muscle and lower blood glucose levels.

Inhibitory Effects of Digoxin and Digitoxin on Cell Growth in Human Ovarian Cancer Cell Line SKOV-3.

BACKGROUND: Cardiac glycosides (CGs) possess a chemical structure similar to steroids, and are inhibitors of the sodium potassium pump. An anti-tumor effect of CGs in breast and prostate cancers has been reported, but the effect of CGs on ovarian cancer is still unclear. AIMS: In this study, the effects of CGs on proliferation, cytotoxicity and cell cycle of ovarian cancer cell line (SKOV-3) have been investigated. PROCEDURE: The cell proliferation and cytotoxicity were detected by MTT assay and LDH activity assay, respectively. CGs, at concentrations higher than IC50, decreased cell proliferation and showed increased cytotoxicity toward SKOV-3 cells. The colony-formation ability was reduced after treatment with digoxin and digitoxin for 10 days. Furthermore, we explored the effect of digoxin and digitoxin on the distribution of cell cycle by flow cytometry. RESULTS: Results revealed that both digoxin and digitoxin led to cell cycle arrest in G0/G1 phase with 24 or 48 hours, but the arrest of G0/G1 phase was not observed at 72 hours. We evaluated the percentage of hypodiploid cell population as an index of the cellular fragments through flow cytometry. The data indicated that cellular fragments were significantly increased by treating with digitoxin at the concentrations of IC50 and 10-6 M for 72 hours. CONCLUSION: Taken together, these data suggest that CGs decreased cell proliferation and increased cytotoxicity through cell cycle arrest at the G0/G1 phase. CGs have anti-tumor effect in SKOV-3 cells and might be a potential therapeutic drug for ovarian cancer. Since this study is a preliminary investigation of CGs on SKOV-3 cells, more experiments might be performed in the future. Furthermore, more ovarian cancer cell lines might also be employed in the future studies to confirm the effect of CGs in ovarian cancer.

Andrographis paniculata Improves Insulin Resistance in High-Fat Diet-Induced Obese Mice and TNFα-Treated 3T3-L1 Adipocytes.

Pro-inflammatory cytokines interfere with blood glucose homeostasis, which leads to hyperglycemia. Andrographis paniculata (AP) has been shown to possess anti-inflammatory activity and to reduce blood glucose levels in diabetes. The two major bioactive diterpenoids in AP, andrographolide (AND) and 14-deoxy-11,12-didehydroandrographolide (deAND), have potent anti-inflammatory activity. We studied whether APE (an ethanolic extract of AP), AND, and deAND could improve a high-fat diet (HFD)-induced hyperglycemia in vivo and TNF[Formula: see text]-induced impairment of insulin signaling in vitro. Male C57BL/6JNarl mice were fed a normal diet (ND) or the HFD, and the fatty mice were treated with APE, deAND, or AND for 16 weeks. 3T3-L1 cells were used to study the underlying mechanisms by which APE, deAND, or AND attenuated TNF[Formula: see text]-induced insulin resistance. The HFD significantly induced obesity, hyperglycemia, insulin resistance, and inflammation, whereas APE and deAND significantly ameliorated HFD-induced obesity, hyperglycemia, insulin resistance, and TNF[Formula: see text] production. The HFD significantly impaired insulin signaling by decreasing the protein expression of p-IRS1 tyr632 and p-AKT ser473, as well as the membrane translocation of GLUT4 in response to insulin stimulation in epididymal adipose tissue. HFD-impaired the membrane translocation of GLUT4 was significantly reversed by deAND and APE. In addition, deAND and APE markedly reversed the detrimental effect of TNF[Formula: see text] on the insulin signaling pathway and glucose uptake in 3T3-L1 cells. Despite no significant positive effect on p-AS160, a trend for recovery by deAND and APE was observed. These results suggest that deAND and APE protect against HFD-induced insulin resistance by ameliorating inflammation-driven impairment of insulin sensitivity.

The Antinociceptive Effect of Light-Emitting Diode Irradiation on Incised Wounds Is Correlated with Changes in Cyclooxygenase 2 Activity, Prostaglandin E2, and Proinflammatory Cytokines.

Background. Light-emitting diode (LED) phototherapy has been reported to relieve pain and enhance tissue repair through several mechanisms. However, the analgesic effect of LED on incised wounds has never been examined. Objectives. We examined the analgesic effect of LED therapy on incision pain and the changes in cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2), and the proinflammatory cytokines interleukin 6 (IL-6), IL-1ß, and tumor necrosis factor α (TNF-α). Methods. Rats received LED therapy on incised skin 6 days before incision (L-I group) or 6 days after incision (I-L group) or from 3 days before incision to 3 days after incision (L-I-L group). Behavioral tests and analysis of skin tissue were performed after LED therapy. Results. LED therapy attenuated the decrease in thermal withdrawal latency in all the irradiated groups and the decrease in the mechanical withdrawal threshold in the L-I group only. The expression levels of COX-2, PGE2, and IL-6 were significantly decreased in the three LED-treated groups, whereas IL-1ß and TNF-α were significantly decreased only in the L-I group compared with their levels in the I groups (p < 0.05). Conclusions. LED therapy provides an analgesic effect and modifies the expression of COX-2, PGE2, and proinflammatory cytokines in incised skin.

Effect of flow characteristics on ultrafine particle emissions from range hoods.

In order to understand the physical mechanisms of the production of nanometer-sized particulate generated from cooking oils, the ventilation of kitchen hoods was studied by determining the particle concentration, particle size distribution, particle dimensions, and hood's flow characteristics under several cooking scenarios. This research varied the temperature of the frying operation on one cooking operation, with three kinds of commercial cooking oils including soybean oil, olive oil, and sunflower oil. The variations of particle concentration and size distributions with the elevated cooking oil temperatures were presented. The particle concentration increases as a function of temperature. For oil temperatures ranging between 180°C and 210°C, a 5°C increase in temperature increased the number concentration of ultrafine particles by 20-50%. The maximum concentration of ultrafine particles was found to be approximately 6 × 10(6) particles per cm(3) at 260°C. Flow visualization techniques and particle distribution measurement were performed for two types of hood designs, a wall-mounted range hood and an island hood, at a suction flow rate of 15 m(3) min(-1). The flow visualization results showed that different configurations of kitchen hoods induce different aerodynamic characteristics. By comparing the results of flow visualizations and nanoparticle measurements, it was found that the areas with large-scale turbulent vortices are more prone to dispersion of ultrafine particle leakage because of the complex interaction between the shear layers and the suction movement that results from turbulent dispersion. We conclude that the evolution of ultrafine particle concentration fluctuations is strongly affected by the location of the hood, which can alter the aerodynamic features. We suggest that there is a correlation between flow characteristics and amount of contaminant leakage. This provides a comprehensive strategy to evaluate the effectiveness of kitchen hoods in capturing cooking oil fumes, which is based on an assessment of the entire hood face exposure instead of on breathing-zone sampling alone.

Camptothecin-Loaded Liposomes with α-Melanocyte-Stimulating Hormone Enhance Cytotoxicity Toward and Cellular Uptake by Melanomas: An Application of Nanomedicine on Natural Product.

In this study, we attempted to develop functional liposomes loaded with camptothecin and attached to α-melanocyte-stimulating hormone (α-MSH) to target melanoma cells. The liposomes were mainly composed of phosphatidylcholine, cholesterol, and stearylamine, and were characterized by the vesicle size, zeta potential, camptothecin encapsulation efficiency, and release behavior. Results revealed that α-MSH liposomes possessed an average size of approximately 250 nm with a surface charge of 60 mV. Camptothecin was successfully entrapped by the targeted liposomes with an encapsulation percentage of nearly 95%. The liposomes provided sustained and controlled camptothecin release. Non-targeted liposomes with the drug exerted superior cytotoxicity against melanomas compared to the free control. Cell viability was reduced from 48% to 32% compared to conventional liposomes. Peptide ligand conjugation further promoted cytotoxicity to 18% viability, which was a 2.7-fold decrease versus the free control. According to the images of fluorescence microscopy, α-MSH liposomes exhibited greater cell endocytosis than did non-targeted liposomes and the free control. α-MSH liposomes were predominantly internalized in the cytoplasm. These findings demonstrate that α-MSH liposomes could enhance the anti-melanoma activity of camptothecin owing to their targeting ability and controlled drug delivery.

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions.

The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216-256 and 18-125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm(2)/h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 µm to ∼140 µm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA.

Suspended onion particles and potential corneal injury in onion harvesters.

The authors suspected that suspended onion particles contributed to corneal ulcers in onion harvesters in southern Taiwan. In the present study, the authors used manikins to study suspended onion particles in fields in an effort to simulate typical conditions experienced by onion harvesters. An animal eye-exposure simulation study was also performed by the authors, who impacted suspended soil grains or onion particles onto the corneas of guinea pigs via aerosol generated from the Palas dispersion nozzle. The average size of 25.9 pm for suspended particles collected during the digging of onions was the largest one of those for various harvesting activities. Some onion skin flakes were found in samples obtained from gathering and packing activities; the typical flake size was approximately 3.5 x 2.5 mm2. The results of the animal study indicated that the size of soil grains has a demonstrable effect on the severity of corneal injury (p = .009). With respect to onion skin flakes, wind velocity was also associated significantly with the occurrence of corneal injury (p = .0004). A wind velocity threshold of 7 m/sec is recommended for the maintenance of safety, and if the wind speed exceeds this threshold level, workers should not engage in harvesting activities. Furthermore, use of appropriately designed goggles is necessary for the protection of onion harvesters who work in high-wind conditions.