Rutin alleviates bisphenol A-glycidyl methacrylate-induced generation of proinflammatory mediators through the MAPK and NF-κB pathways in macrophages.

Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 µM for 30 min before being incubated with BisGMA at 0 or 3 µM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.

Fine Particulate Matter Exposure Levels in Patients with Normal-Tension Glaucoma and Primary Open-Angle Glaucoma: A Population-Based Study from Taiwan.

Patients with NTG or POAG with more than one outpatient or discharge diagnosis from the ophthalmology department were included in the study. These data were merged with the PM2.5 data from the Air Quality Monitoring Network for analysis. This was a case−control study, with 1006 participants in the NTG group and 2533 in the POAG group. To investigate fine particulate matter (PM2.5) exposure levels in patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG), patient data were obtained from Taiwan's Longitudinal Health Insurance Database 2000 for the 2008 to 2013 period. We used a multivariate logic regression model to assess the risk for each participant. The PM2.5 exposure levels were divided into four groups: <25th percentile (Q1), <617 µg/mm3; 25th to 50th percentile (Q2), 617 to 1297 µg/mm3; 50th to 75th percentile (Q3), 1297 to 2113 µg/mm3; and >75th percentile (Q4), >2113 µg/mm3. The results are expressed in terms of odds ratio (OR) and 95% CI. A multiple logistic regression was used to compare the results of the NTG group with those of the POAG group. Compared with the PM2.5 Q1 level, the OR of the PM2.5 Q2 level was 1.009 (95% CI 0.812−1.254), the PM2.5 Q3 level was 1.241 (95% CI 1.241−1.537, p < 0.05), and the PM2.5 Q4 level was 1.246 (95% CI 1.008−1.539, p < 0.05). Our research reveals that compared with POAG, the risk of developing NTG is more closely related with PM2.5 exposure, and PM2.5 has a concentration−dose effect. It is hoped that in the future, in the clinical judgment of NTG and POAG, the level of PM2.5 in the environment can be taken as a risk factor.

1-Nitropyrene Induced Reactive Oxygen Species-Mediated Apoptosis in Macrophages through AIF Nuclear Translocation and AMPK/Nrf-2/HO-1 Pathway Activation.

1-Nitropyrene (1-NP), one of the most abundant nitropolycyclic aromatic hydrocarbons (nitro-PAHs), is generated from the incomplete combustion of carbonaceous organic compounds. 1-NP is a specific marker of diesel exhaust and is an environmental pollutant and a probable carcinogen. Macrophages participate in immune defense against the invasive pathogens in heart, lung, and kidney infection diseases. However, no evidence has indicated that 1-NP induces apoptosis in macrophages. In the present study, 1-NP was found to induce concentration-dependent changes in various cellular functions of RAW264.7 macrophages including cell viability reduction; apoptosis generation; mitochondrial dysfunction; apoptosis-inducing factor (AIF) nuclear translocation; intracellular ROS generation; activation of the AMPK/Nrf-2/HO-1 pathway; changes in the expression of BCL-2 family proteins; and depletion of antioxidative enzymes (AOE), such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) These results indicate that 1-NP induced apoptosis in macrophages through AIF nuclear translocation and ROS generation due to mitochondrial dysfunction and to the depletion of AOE from the activation of the AMPK/Nrf-2/HO-1 pathway.

Protective Effects of Kirenol against Lipopolysaccharide-Induced Acute Lung Injury through the Modulation of the Proinflammatory NFκB Pathway and the AMPK2-/Nrf2-Mediated HO-1/AOE Pathway.

Acute lung injury (ALI) is an acute and life-threatening inflammatory disease of the lung parenchyma that is associated with high mortality worldwide. No therapeutic strategies have been developed for the mitigation of the proinflammatory response that characterizes ALI. Kirenol has anti-inflammatory, antiarthritic, and immunoregulatory effects. In the present study, we investigated the protective effects of kirenol against lipopolysaccharides (LPS)-induced ALI in mice. Kirenol reduced the LPS-induced histopathology changes involving edema and thickening of the interstitial or alveolar walls, infiltration of leukocytes, formation of hyaline membrane. Pretreatment with kirenol reduced leukocytes infiltration in bronchoalveolar lavage fluid (BALF), the alveolar-capillary barrier disruption and lipid peroxidation in lung tissues induced by LPS. Kirenol significantly inhibited the secretion of cytokines, IL-1ß, IL6, and TNFα, into the BALF of the mice with LPS-induced ALI through NFκB activation. Moreover, kirenol attenuated the downregulation of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and catalase that was induced by LPS. HO-1 expression and the phosphorylation of Nrf2 and AMPK2 were also induced by kirenol. The results indicate that kirenol can be developed as a treatment strategy for ALI, and its effects are induced through the inhibition of the NF-κB proinflammatory pathway and promotion of AMPK2/Nrf2-mediated HO-1 and antioxidant enzymes (AOE) activation.

Rutin-protected BisGMA-induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes.

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.

Safrole-induced expression of proinflammatory responses is associated with phosphorylation of mitogen-activated protein kinase family and the nuclear factor-κB/inhibitor of κB pathway in macrophages.

OBJECTIVE: Safrole, also called shikimol and Sassafras, is the carcinogenic and phenylpropanoid compound extracted from Sassafras tree and anise, betel, and camphor. Moreover, a high concentration of safrole can be occur in the saliva because of betel nut or areca quid chewing which a common habit observed in Southern and Southeastern Asia. Notably, macrophages are crucial phagocytic cells of the immune system. Nonetheless, to date, no evidence has been reported regarding safrole-induced proinflammatory response and the corresponding mechanism in macrophages. MATERIALS AND METHODS: In the present study, the cytokines expression, NO generation, protein phosphorylation, and expression were assessed by enzyme-linked immunosorbent assay, Griess reagent, and Western blot assay, respectively. RESULTS: In this study, we determined that safrole induces the generation of nitric oxide and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and IL-6 in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, inhibitor of κB (IκB) degradation was caused by safrole in a concentration-dependent manner. In addition, the phosphorylation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) family, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was induced by safrole began to increase at 10 µM and attained a plateau at 100 µM. CONCLUSION: These results indicated that safrole induces the expression of proinflammatory responses in macrophages through the NF-κB/IκB pathway and its upstream factor, MAPK family phosphorylation.

Toxic Effects of Urethane Dimethacrylate on Macrophages Through Caspase Activation, Mitochondrial Dysfunction, and Reactive Oxygen Species Generation.

Urethane dimethacrylate (UDMA) is a dimethacrylate-based resin monomer that can react with other related monomers and inorganic particles, causing hydrophobic polymerization through cross-linking upon light activation. UDMA polymers are commonly used for the reconstruction and reinforcement of teeth and bones. UDMA can become unbound and be released from light-cured polymer resins. Thus far, no evidence exists on the toxic effects of UDMA and its related working mechanisms for macrophages. Therefore, in the present study, we investigated the cytotoxicity, mode of cell death, DNA damage, caspase activities, mitochondrial dysfunction, and reactive oxygen species (ROS) generation in RAW264.7 macrophages treated with UDMA using the lactate dehydrogenase (LDH) assay kit, Annexin V-FITC and PI assays, micronucleus formation and comet assay, caspase fluorometric assay, JC-1 assay, and 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay, respectively. Our results show that UDMA induced cytotoxicity; apoptosis and necrosis; genotoxicity, which is also called DNA damage; increased caspase-3, -8, and -9 activities; mitochondrial dysfunction; and intracellular ROS generation in a concentration-dependent manner in RAW264.7 macrophages. Thus, based on the observed inhibited concentration parallel trends, we concluded that UDMA induces toxic effects in macrophages. Furthermore, UDMA-induced intracellular ROS generation, cytotoxicity, and DNA damage were reduced by N-acetyl-L-cysteine.

Evaluation of cytotoxicity, apoptosis, and genotoxicity induced by indium chloride in macrophages through mitochondrial dysfunction and reactive oxygen species generation.

Due to rapid advances in the era of electronic technologies, indium has played the important material for the production of liquid crystal display screens in the semiconductor and optoelectronic industries. The present study focuses on evaluating the toxic effects and related mechanisms of indium chloride (InCl3) on RAW264.7 macrophages. Cytotoxicity was induced by InCl3 in a concentration- and time-dependent manner. InCl3 had the ability to induce macrophage death through apoptosis rather than through necrosis. According to the cytokinesis-block micronucleus assay and alkaline single-cell gel electrophoresis assay, InCl3 induced DNA damage, also called genotoxicity, in a concentration-dependent manner. Cysteine-dependent aspartate-directed protease (caspase)-3, -8, and -9 were activated by InCl3 in a concentration-dependent manner. Mitochondria dysfunction and cytochrome c release from the mitochondria were induced by InCl3 in a concentration-dependent manner. Downregulation of BCL2 and upregulation of BAD were induced by InCl3 in a concentration-dependent manner. More, we proposed that InCl3 treatment generated reactive oxygen species (ROS) in a concentration-dependent manner. In conclusion, the current study revealed that InCl3 induced macrophage cytotoxicity, apoptosis, and genotoxicity via a mitochondria-dependent apoptotic pathway and ROS generation.

Vaginal wellness: whose turf is it?

Dermatologists were the pioneers in the development of laser technology and have the most experience using these lasers to treat the external genitalia for many cutaneous disorders. Dermatologists who have experience and expertise using lasers and devices, are already using them to treat the external genitalia, and are comfortable performing female gynecologic exams may want to explore the wide range of options that are available to treat the functional and aesthetic needs of the female population. Dermatologists should work with obstetricians and gynecologists to ensure that patients are proper candidates for the procedures.

Novel 3-in-1 wavelength light source for photorejuvenation.

The objective of this study was to evaluate a novel flashlamp emitting light device which represents the first light-based device for skin rejuvenation with the ability to shift the wavelength spectrum depending on the application. Three distinct programs adjust the wavelengths to accommodate the melanin and hemoglobin absorption, and also adjust the pulse width and cooling depending on the needs of the patient. Patients received treatment on the left side of the face or other body part; the untreated side served as the control.

The image feature analysis for microscopic thyroid tissue classification.

Thyroid diseases are prevalent among endocrine diseases. Observation and examination of histological tissue images can help in understanding the cause and pathogenesis of the tumor. The aim of this study was to quantify the histological image features of microscopic thyroid images in order to classify varying tissue types. Five typical histological thyroid tissues were characterized using seven image features including hue, brightness, standard deviation of brightness, entropy, energy, regularity, and fractal analysis. Statistical stepwise selection and multiple discriminant analysis were then used to classify the features. The results show all of the features are significant and our algorithm has the capability of differentiating histological tissue types. The algorithm is applied utilizing quad-tree based region splitting methods to segment the tissue regions from the heterogeneous microscopic image. The preliminary results show the system has good performance for tissue segmentation.

Combination 532-nm and 1064-nm lasers for noninvasive skin rejuvenation and toning.

BACKGROUND: Noninvasive techniques for skin rejuvenation are quickly becoming standard in the treatment of mild rhytids and overall skin toning. Multiple laser wavelengths and modalities have been used with varying degrees of success, including 532-nm, 585-nm, 1064-nm, 1320-nm, 1450-nm, and 1540-nm wavelengths. OBJECTIVES: To evaluate a combination technique using a long-pulsed, 532-nm potassium titanyl phosphate (KTP) laser and a long-pulsed 1064-nm Nd:YAG laser, separately and combined, for noninvasive photorejuvenation and skin toning and collagen enhancement and to establish efficacy and degree of success. DESIGN: Prospective nonrandomized study with longitudinal follow-up. SETTING: Private dermatologic surgery and laser practice. METHODS: A total of 150 patients, with skin types I through V, were treated with long-pulsed KTP 532-nm and long-pulsed Nd:YAG 1064-nm lasers, separately and combined. For the KTP 532-nm laser, the fluences varied between 7 to 15 J/cm2 at 7- to 20-millisecond pulse durations with a 2-mm handpiece and 6 to 15 J/cm2 at 30- to 50-millisecond pulses with a 4-mm handpiece. The 1064-nm Nd:YAG laser fluences were set at 24 to 30 J/cm2 for a 10-mm handpiece. These energies were delivered at 30- to 65-millisecond pulse durations. All subjects were treated at least 3 times and at most 6 times, depending on patient satisfaction level, at monthly intervals and were observed for up to 18 months after the last treatment. MAIN OUTCOME MEASURES: All patients were asked to fill out a "severity scale" on which redness, pigmentation, rhytids, skin tone/tightness, texture, and patient satisfaction were noted before and after each treatment. Redness, pigmentation, rhytids, skin tone/tightness, and texture were also evaluated by the physician and another observer. RESULTS: After 3 to 6 treatments, 50 patients treated with the 532-nm KTP laser alone showed improvement of 70% to 80% in redness and pigmentation, 30% to 50% in skin tone/tightening, 30% to 40% in skin texture, and 20% to 30% in rhytids. Another 50 patients treated with the 1064-nm Nd:YAG laser alone showed improvement of 10% to 20% in redness, 0% to 10% in pigmentation, 10% to 30% in skin tone/tightening, 20% to 30% in skin texture, and 10% to 30% in rhytids. The third group of 50 patients treated with both KTP and Nd:YAG lasers showed improvement of 70% to 80% in redness and pigmentation, 40% to 60% in skin tone/tightening, 40% to 60% in skin texture, and 30% to 40% in rhytids. Skin biopsy specimens taken at 1-, 2-, 3-, and 6-month intervals demonstrated new collagen formation. CONCLUSIONS: All 150 patients exhibited mild to moderate improvement in the appearance of rhytids, moderate improvement in skin toning and texture, and great improvement in the reduction of redness and pigmentation. The KTP laser used alone produced results superior to those of the Nd:YAG laser. Results from combination treatment with both KTP and Nd:YAG lasers were slightly superior to those achieved with either laser alone.

Combination visible and infrared lasers for skin rejuvenation.

Noninvasive techniques for skin rejuvenation are quickly being established as a new standard in the treatment of mild rhytides and overall skin toning. Multiple laser wavelengths and modalities have been tried for this procedure with varying degrees of success. These lasers include 532 nm, 585 nm, 1064 nm, 1320 nm, 1450 nm, and 1540 nm wavelengths. This study evaluates a combination technique by using a long-pulsed 532 nm potassium titanyl phosphate (KTP) laser and a long-pulsed 1064 nm Neodynium:yttrium aluminum garnet (Nd:YAG) laser, both separately and combined, for noninvasive photorejuvenation and skin toning/collagen enhancement, and establishes efficacy and degree of success. A total of 150 patients were treated with the long-pulsed KTP 532 nm (Aura; Laserscope, San Jose, CA) and long-pulsed Nd:YAG 1064 nm (Lyra; Laserscope) lasers both separately and combined. Patients included skin types I through V. The fluences varied between 7 and 15 J/cm2 at 7 to 20 ms pulse duration with a 2-mm handpiece, and 6 to 15 J/cm2 and 30 to 50 ms with a 4-mm handpiece for KTP. The Nd:YAG fluences were set at 24 to 30 J/cm2 for a 10-mm handpiece and 30 J/cm2 for a SmartScan Plus scanner (Laserscope, San Jose, CA). These energies were delivered at 30 to 65 ms pulse durations. All patients were treated at least 3 times and at most 6 times at monthly intervals, and were observed for up to 18 months after the last treatment. All 150 patients exhibited a mild to moderate degree of improvement in the appearance of rhytides, moderate degree of improvement in skin toning and texture, and great improvement in the reduction of redness and pigmentation. The KTP used alone was superior to the Nd:YAG laser in terms of results. The KTP and Nd:YAG laser combination was superior to either laser used alone.