Individual Micron-Sized Aerosol Qualitative Analysis-Combined Raman Spectroscopy and Laser-Induced Breakdown Spectroscopy by Optical Trapping in Air.

The attribution of single particle sources of atmospheric aerosols is an essential problem in the study of air pollution. However, it is still difficult to qualitatively analyze the source of a single aerosol particle using noncontact in situ techniques. Hence, we proposed using optical trapping to combine gated Raman spectroscopy with laser-induced breakdown spectroscopy (LIBS) in a single levitated micron aerosol. The findings of the spectroscopic imaging indicated that the particle plasma formed by a single particle ablation with a pulsed laser within 7 ns deviates from the trapped particle location. The LIBS acquisition field of view was expanded using the 19-bundle fiber, which also reduces the fluctuation of a single particle signal. In addition, gated Raman was utilized to suppress the fluorescence and increase the Raman signal-to-noise ratio. Based on this, Raman can measure hard-to-ionize substances with LIBS, such as sulfates. The LIBS radical can overcome the restriction that Raman cannot detect ionic chemicals like fluoride and chloride in halogens. To test the capability of directly identifying distinctive feature compounds utilizing spectra, we detected anions using Raman spectroscopy and cations using LIBS. Four typical mineral aerosols are subjected to precise qualitative evaluations (marble, gypsum, baking soda, and activated carbon adsorbed potassium bicarbonate). To further validate the application potential for substances with indistinctive feature discrimination, we employed machine learning algorithms to conduct a qualitative analysis of the coal aerosol from ten different origin regions. Three data fusion methodologies (early fusion, intermediate fusion, and late fusion) for Raman and LIBS are implemented, respectively. The accuracy of the late fusion model prediction using StackingClassifier is higher than that of the LIBS data (66.7%) and Raman data (86.1%) models, with an average accuracy of 90.6%. This research has the potential to provide online single aerosol analysis as well as technical assistance for aerosol monitoring and early warning.

Self-absorption correction method for one-point calibration laser-induced breakdown spectroscopy.

As an important variant of calibration-free laser-induced breakdown spectroscopy (CF-LIBS), one-point calibration LIBS (OPC-LIBS) corrects the Boltzmann plot of the unknown sample by using one known sample and obtains higher quantitative accuracy than CF-LIBS. However, the self-absorption effect restricts its accuracy. In this work, a new self-absorption correction (SAC) method for OPC-LIBS is proposed to solve this problem. This method uses an algorithm to correct the self-absorption and does not require the calculation of the self-absorption coefficient. To verify the effectiveness of this SAC method, Ti, V, and Al elements in two titanium alloys were determined by classical OPC-LIBS and OPC-LIBS with SAC. The average relative errors (AREs) of all elements in the two samples were decreased from 8.78% and 9.28% to 8.07% and 7.56%, respectively. The results demonstrated the effectiveness of this SAC method for OPC-LIBS.

Role of Omega-Hydroxy Ceramides in Epidermis: Biosynthesis, Barrier Integrity and Analyzing Method.

Attached to the outer surface of the corneocyte lipid envelope (CLE), omega-hydroxy ceramides (ω-OH-Cer) link to involucrin and function as lipid components of the stratum corneum (SC). The integrity of the skin barrier is highly dependent on the lipid components of SC, especially on ω-OH-Cer. Synthetic ω-OH-Cer supplementation has been utilized in clinical practice for epidermal barrier injury and related surgeries. However, the mechanism discussion and analyzing methods are not keeping pace with its clinical application. Though mass spectrometry (MS) is the primary choice for biomolecular analysis, method modifications for ω-OH-Cer identification are lacking in progress. Therefore, finding conclusions on ω-OH-Cer biological function, as well as on its identification, means it is vital to remind further researchers of how the following work should be done. This review summarizes the important role of ω-OH-Cer in epidermal barrier functions and the forming mechanism of ω-OH-Cer. Recent identification methods for ω-OH-Cer are also discussed, which could provide new inspirations for study on both ω-OH-Cer and skin care development.

Accuracy improvement of single-sample calibration laser-induced breakdown spectroscopy with self-absorption correction.

The single sample calibration laser-induced breakdown spectroscopy (SSC-LIBS) is quite suitable for the fields where the standard sample is hard to obtain, including space exploration, geology, archaeology, and jewelry identification. But in practice, the self-absorption effect of plasma destroys the linear relationship of spectral intensity and element concentration based on the Lomakin-Scherbe formula which is the guarantee of the high accuracy of the SSC-LIBS. Thus, the self-absorption effect limits the quantitative accuracy of SSC-LIBS greatly. In this work, an improved SSC-LIBS with self-absorption correction (SSC-LIBS with SAC) is proposed for the promotion of quantitative accuracy of SSC-LIBS. The SSC-LIBS with SAC can correct the intensity ratio of spectral lines in the calculation of SSC-LIBS through relative self-absorption coefficient K without complicated preparatory information. The alloy samples and pressed ore samples were used to verify the effect of the SSC-LIBS with SAC. Compared with SSC-LIBS, for alloy samples, the average RMSEP and average ARE of SSC-LIBS with SAC decreased from 0.83 wt.% and 13.75% to 0.40 wt.% and 4.06%, respectively. For the pressed ore samples, the average RMSEP and average ARE of SSC-LIBS with SAC decreased from 4.77 wt.% and 90.48% to 2.34 wt.% and 14.60%. The experimental result indicates that SSC-LIBS with SAC has a great improvement of quantitative accuracy and better universality compared with traditional SSC-LIBS, which is a mighty promotion of the wide application of SSC-LIBS.

Indirect quantitative analysis of soluble solid content in citrus by the leaves using hyperspectral imaging combined with machine learning.

Due to the effect of bagging on fruit growth, non-destructive and in situ soluble solid content (SSC) in citrus detection remains a challenge. In this work, a new method for accurately quantifying SSC in citrus using hyperspectral imaging of citrus leaves was proposed. Sixty-five Ehime Kashi No. 28 citruses with surrounding leaves picked at two different times were picked for the experiment. Using the principal components analysis combined with Gaussian process regression model, the correlation coefficients of prediction-real value by citrus and its leaves in cross-validation were 0.972 and 0.986, respectively. In addition, the relationship between citrus leaves and SSC content was further explored, and the possible relationship between chlorophyll in leaves and SSC of citrus was analyzed. Comparing the quantitative analysis results by citrus and its leaves, the results show that the proposed method is a non-destructive and reliable method for determining the SSC by citrus leaves and has broad application prospects in indirect detection of citrus.

Laser ultrasonic improvement and its application in defect detection based on the composite coating method.

Herein, we studied the increasing tendency of photoacoustic (PA) conversion efficiency of the Au/polydimethylsiloxane (PDMS) composite. The thickness of the Au layer was optimized by modeling the PA process based on the Drude-Lorentz model and finite element analysis method, and corresponding results were verified. The results showed that the optimal Au thickness of the Au/PDMS composite was 35 nm. Finally, the Au/PDMS composites were coated onto the surface of aluminum alloys, which improved the thermoelastic laser ultrasonic (LU) signals to near 100 times. Besides, the defect mapping was performed by thermoelastic LU signals with Au/PDMS coating and ablation LU signals without coating; the Pearson correlation coefficient was higher than 0.95. The application in the defect detection in metal could provide guides for nondestructive detection on metals by laser ultrasound.

Meat species identification accuracy improvement using sample set portioning based on joint x-y distance and laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy (LIBS) was suitable for the identification of meat species due to fast and less sample preparation. However, the problem of low accuracy rate of the recognition model caused by improper selection of training set samples by random split has severely restricted the development of LIBS in meat detection. Sample set portioning based on the joint x-y distance (SPXY) method was applied for dividing the meat spectra into a training set and a test set. Then, the five kinds of meat samples (shrimp, chicken, beef, scallop, and pig liver) were classified by the support vector machine (SVM). With the random split method, Kennard-Stone method, and SPXY method, the recognition accuracies of the SVM model were 90.44%, 91.95%, and 94.35%, respectively. The multidimensional scaling method was used to visualize the results of the sample split for the interpretation of the classification. The results showed that the identification performance of the SPXY method combined with the SVM model was best, and the accuracy rates of shrimp, chicken, beef, scallop, and pig liver were 100.00%, 100.00%, 100.00%, 78.57%, and 92.00%, respectively. Moreover, to verify the broad adaptability of the SPXY method, the linear discriminant analysis model, the K-nearest neighbor model, and the ensemble learning model were applied as the meat species identification model. The results demonstrated that the accuracy rate of the classification model can be improved with the SPXY method. In light of the findings, the proposed sample portioning method can improve the accuracy rate of the recognition model using LIBS.

Cytoprotective Effects Evaluation of a Novel Danshensu Derivative DEX-018 against Oxidative Stress Injury in HUVECs.

Ischemic heart disease (IHD) is one of the most common cardiovascular diseases with high morbidity and mortality. Danshensu (DSS) is widely used in the treatment of coronary heart disease. In this study, the carboxy group of DSS was esterified with edaravone to synthesize the novel DSS derivative DEX-018 to achieve a synergistic protective effect and overcome the structural deficiency of DSS. The pharmacological effect of DEX-018 against tert-butyl hydrogen peroxide (t-BHP) induced oxidative damage in human umbilical vein endothelial cells (HUVECs) was evaluated. The results demonstrated that pretreatment with DEX-018 significantly increased cell viability and superoxide dismutase (SOD) activity and decreased the lactate dehydrogenase (LDH) leakage rate, malondialdehyde (MDA) level and intracellular reactive oxygen species (ROS) level. In addition, DEX-018 inhibited cell apoptosis and reversed the expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) in HUVECs stimulated by t-BHP. Further study on the mechanism of DEX-018 revealed that the expression of p-Akt and p-extracellular signal-regulated kinase 1/2 (ERK1/2) was increased, which suggested that DEX-018 may protect HUVECs against t-BHP induced oxidative injury via the Akt and ERK1/2 signaling pathways. To further validate the correlation, CCK8 was used to detect cell viability after treatment with DEX-018 plus Akt inhibitor (MK2206) and phosphadylinositol 3-kinase (PI3K) inhibitor (LY294002). Compared with DEX-018 alone, MK2206 or LY294002 significantly decreased cell viability of HUVECs, indicating that the protective effect of DEX-018 against t-BHP induced oxidative injury was significantly weakened. It was further verified that the antioxidant and anti-apoptotic effects of DEX-018 were partly related to the PI3K-Akt signaling pathway.

Investigation of the mechanism and influence of laser wavelength and energy on laser opto-ultrasonic dual detection.

Laser opto-ultrasonic dual (LOUD) detection, which uses laser irradiation of samples to generate spectral and ultrasonic signals simultaneously, can perform multimodal detection of element composition and structural property. As such, it has been applied to the detection of additive manufacturing (AM) components. Further, optimized parameters lead to better detection results. To the best of our knowledge, however, there is no study on the effect of laser properties on LOUD detection. Therefore, we studied the mechanism and influence of laser wavelength and energy on LOUD detection. In this work, the intensity, signal-to-noise ratio (SNR), and stability evolution of the laser excitation spectrum and ultrasonic signals at different wavelengths and energies were analyzed. It was found in the plasma evolution that high electron number density means a large amount of ablated mass generated, which was favorable for laser ultrasonic excitation and can produce higher SNR and a more stable signal. However, it also led to more atoms of the ground-state, which resulted in the self-absorption effect and reduced spectrum intensity in the spectrum analysis. Therefore, with self-absorption correction, better stability, and higher signal intensity, an SNR of spectral and ultrasonic signals can be obtained using 355 nm laser excitation at optimal energy. As a result, in the quantitative analysis of Cu and Si elements by LOUD detection, the determination coefficients (R2) were higher than 0.995, and the average relative errors were less than 2.5%, the limit of detection could reach the order of 100 ppm. Further, the defect size of 0.55 mm in the wire +arc additive manufacturing sample was detected by LOUD detection, and the average relative error was 5.59% compared with the digital radiography results, which indicate that laser wavelength and laser energy affect the intensity and stability of spectral and ultrasonic signals in LOUD detection, which means selecting appropriate laser parameters is important to obtain a high precision detection.

Stability improvement for dried droplet pretreatment by suppression of coffee ring effect using electrochemical anodized nanoporous tin dioxide substrate.

A novel nanoporous analytical platform is reported to improve the stability of the dried droplet method (DDM). This nanoporous platform was made of tin dioxide (Np SnO2) substrate by electrochemical anodization from tin (Sn) slide. The DDM is a widely used sample pretreatment in analytical chemistry that involves placing a droplet of solution onto the substrate and drying for analytical testing. However, during the droplet drying process, the solutes would converge at the droplet edge and cause inhomogeneous solutes distribution. This is the coffee ring effect (CRE). The Np SnO2 has irregular nanopores, which allows droplet solutions to penetrate into the substrate rather than spreading out, effectively suppressing CRE. Theoretical models were built to explain the formation of CRE on blank tin (Sn) substrate and suppression of CRE on Np SnO2. Better results were obtained in detecting lithium (Li) using the Np SnO2 by laser-induced breakdown spectroscopy (LIBS). The line scanning results indicated that the Li emission line (670.8 nm) intensities on Np SnO2 substrate had lower relative standard deviation (RSD = 3.3%) than those on Sn substrate (RSD = 31.5%), which illustrate suppression of CRE and stability improvement on Np SnO2 substrate. Furthermore, Li calibration curves were built for LIBS with DDM. The curve using Np SnO2 substrate had better linearity (R2 = 0.997), higher precision (RSD = 4.2%), and higher sensitivity (LOD = 0.13 mg/L) than that by Sn substrate (R2 = 0.954, RSD = 17%, and LOD = 1.21 mg/L). All in all, the anodic Np SnO2 substrate can suppress CRE in DDM and hence improve the stability and precision of subsequent analysis. Graphical abstract.

Determination of trace heavy metal elements in aqueous solution using surface-enhanced laser-induced breakdown spectroscopy.

Heavy metal pollution is one of the main problems in water pollution, which is harmful to humans. Surface-enhanced laser-induced breakdown spectroscopy (SENLIBS) has been applied to detect trace amounts of heavy metal elements in aqueous solution; however, it is still a big challenge to explore the relationship between the LIBS detection sensitivity and the substrate's physical properties. In this work, four typical substrates, zinc (Zn), magnesium alloy (Mg), nickel (Ni), and silicon (Si), were compared; and the mechanism of spectral enhancement by different substrates in SENLIBS was investigated. The results indicated that the limit of detection (LoD) of heavy metal elements on different substrates is positively proportional to the boiling of the substrate. That is mainly because a higher plasma excitation temperature and electron density are obtained, leading to more intense collision between particles. The signal enhancement is associated with the lower boiling point of the substrate (corresponding to a lower ablation threshold and higher ablation quantity from the substrate). As a result, the best LoD was 0.0011 mg/L for chromium (Cr) and 0.004 mg/L for lead (Pb) on an optimal Zn substrate, respectively. The LoDs were sufficiently low to meet the drinking water sanitation standard. These results showed that the detection sensitivity of heavy metal elements in aqueous solution can be improved by choosing a substrate with a lower boiling point in SENLIBS.

Investigation of the self-absorption effect using time-resolved laser-induced breakdown spectroscopy.

Self-absorption seriously affects the accuracy and stability of quantitative analysis in laser-induced breakdown spectroscopy (LIBS). To reduce the effect of self-absorption, we investigated the temporal evolution of the self-absorption effect by establishing exponential calibration curves. Meanwhile, the temporal evolution mechanism of the self-absorption effect was also investigated. The results indicated that self-absorption was weak at the early stage of plasma expansion. For determination of manganese (Mn) in steel, as an example, the concentration of upper bound of linearity (Cint) was 2.000 wt. % at the early stage of plasma expansion (in a time window of 0.2-0.4 µs)-much higher than 0.363 wt. % at a traditional optimization time window (2-3 µs). The accuracy and stability of quantitative analysis at the time window of 0.2-0.4 µs was also much better than at the time window of 2-3 µs. This work provides a simple method for improving quantitative analysis performance and avoiding the self-absorption effect in LIBS.

Nitidine chloride exerts anti-inflammatory action by targeting Topoisomerase I and enhancing IL-10 production.

In the effort to identify natural products that regulate immunity and inflammation, we found that nitidine chloride (NC), an alkaloid from herb Zanthoxylum nitidum, enhanced IL-10 production in lipopolysaccharide (LPS)-stimulated myeloid cells. While NC was shown to be capable of inhibiting topoisomerase I (TOP1), NC analogs that could not inhibit TOP1 failed to increase IL-10 production. Moreover, medicinal TOP1 inhibitors TPT and SN-38 also augmented IL-10 production significantly, whereas knockdown of TOP1 prevented NC, TPT, and SN-38 from enhancing IL-10 expression. Thus, NC promoted IL-10 production by inhibiting TOP1. In LPS-induced endotoxemic mice, NC and TOP1 inhibitors increased IL-10 production, suppressed inflammatory responses, and reduced mortality remarkably. The anti-inflammatory activities of TOP1 inhibition were markedly reduced by IL-10-neutralizing antibody and largely absent in IL-10-deficient mice. In LPS-stimulated RAW264.7 cells and in peritoneal macrophages from endotoxemic mice, NC and TOP1 inhibitors significantly enhanced the activation of Akt, a critical signal transducer for IL-10 production, and inhibition of Akt prevented these compounds from enhancing IL-10 production and ameliorating endotoxemia. These data indicated that NC and TOP1 inhibitors are able to exert anti-inflammatory action through enhancing Akt-mediated IL-10 production and may assist with the treatment of inflammatory diseases.

The Matrine Derivate MASM Inhibits Recruitment of Gr1hi Monocyte and Alleviates Liver Injury.

BACKGROUNDS: (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits better anti-inflammatory activity. This study was designed to evaluate the protective effect of MASM on acute and chronic liver injuries and explore the possible mechanisms. METHODS: Acute and chronic liver injury models were established by the CCl4 intraperitoneal injection and the protective effect of MASM was assessed by biochemical and histological examination. The infiltration of different monocyte subsets into the liver was characterized and analyzed by flow cytometry. The in vitro effect of MASM on liver nonparenchymal cells was evaluated by real-time PCR and transwell chemotaxis assays. RESULTS: Administration of MASM markedly attenuated acute liver injury and liver fibrosis induced by CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in injured livers and induced hepatic expression of monocyte chemoattractant protein-1 (MCP-1) were greatly inhibited. Cellular experiments demonstrated that MASM not only decreased the expression of MCP-1 but also inhibited its chemotactic activity. CONCLUSIONS: This study demonstrates that the protective effect of MASM on liver injury could be contributed to the suppression of Gr1hi monocyte infiltration to the liver and the inhibition of MCP-1 production and activity. These findings provide new insights into the protective role of MASM in liver injury.

Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation.

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair.

Alpha- and gamma-mangostins exhibit anti-acne activities via multiple mechanisms.

Objective: Acne is a chronic skin disease that involves four key pathogenic factors: excess sebum production, ductal epidermal hyperproliferation, Propionibacterium acnes (P. acnes) colonization, and skin inflammation. Mangostins are well-known for their anti-bacterial and anti-inflammatory effects, suggesting that mangostins may have therapeutic potential for acne. The present study aimed to explore the anti-acne effects of mangostins from the perspective of multiple pathogenic mechanisms of acne. Methods: The effects of α- and γ-mangostins on the growth of P. acnes and lipase activity were analyzed. Their effects on P. acnes-induced keratinocyte proliferation were examined by CCK-8. The expression of inflammatory genes and activation of NF-κB and MAPK signaling pathways were detected by quantitative real-time PCR and western blotting, respectively. Results: Alpha- and γ-mangostins not only inhibited the growth of P. acnes, but also reduced the proliferation of keratinocytes induced by heat-killed P. acnes. Furthermore, α- and γ-mangostins were able to suppress P. acnes-induced expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in keratinocytes by inhibiting the activation of NF-κB and MAPK signaling pathways. Discussion and conclusions: Mangostins appeared to possess multiple anti-acne activities, including the inhibition of P. acnes growth, regulation of keratinocytes proliferation, and attenuation of skin inflammatory reaction. Hence, mangostins might be developed into a potential therapeutic agent for the treatment of acne.

Norisoboldine, an alkaloid from Radix linderae, inhibits NFAT activation and attenuates 2,4-dinitrofluorobenzene-induced dermatitis in mice.

CONTEXT: The nuclear factor of activated T-cells (NFAT) is a family of transcription factors, essential for T-cell activation. Norisoboldine (NOR), an isoquinoline alkaloid from Radix linderae, has been demonstrated to possess anti-inflammatory activity. OBJECTIVE: This study examines NOR's effect on NFAT activation and its therapeutic potential for atopic dermatitis (AD). MATERIALS AND METHODS: The transcriptional activity of NFAT was examined with luciferase reporter assay, using K562-luc cells, stimulated with 20 ng/mL PMA plus 1 µM ionomycin. NFAT dephosphorylation was examined by immuno-blotting in K562-luc cells and Jurkat cells. Interleukin-2 (IL-2) expression in Jurkat cells was examined by real-time PCR. A mouse model of dermatitis, induced by 2,4-dinitrochlorobenzene (DNCB), was used to test NOR's therapeutic potential for AD. RESULTS: NOR, dose-dependently, inhibited PMA and ionomycin-induced NFAT reporter gene expression in K562-luc cells in the range of 2-50 µM. NOR also inhibited PMA and ionomycin-induced NFAT dephosphorylation in K562-luc cells and Jurkat cells. Consequently, NOR suppressed PMA plus ionomycin-induced IL-2 expression in Jurkat cells. The administration of NOR (10 mg/kg, i.p.), alleviated DNCB-induced dermatitis in mice, by the reduction of ear swelling and attenuation of inflammatory infiltration into ear tissue. Moreover, mRNA levels of INF-γ, TNF-α, IL-4 and IL-6 in ears of NOR-treated mice were reduced by 78.4, 77.8, 72.3 and 73.9%, respectively, compared with untreated controls. DISCUSSION AND CONCLUSION: This study demonstrates that NOR inhibits NFAT activation in T-cells and alleviates AD-like inflammatory reaction in a DNCB-induced dermatitis model, highlighting NOR as a potential therapeutic agent for AD.

MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.

Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

1ß-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in the mouse.

CONTEXT: 1ß-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions. OBJECTIVE: The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 µL of 5% DNCB on their shaved back skin and then challenging with 20 µL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge. RESULTS: IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFα, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFα, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 µM, respectively, and inhibited the activation of NF-κB pathway in TNFα-stimulated HaCat cells. DISCUSSION AND CONCLUSION: The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.

Bioactive compound reveals a novel function for ribosomal protein S5 in hepatic stellate cell activation and hepatic fibrosis.

UNLABELLED: Liver fibrosis and its endstage, cirrhosis, represent a major public health problem worldwide. Activation of hepatic stellate cells (HSCs) is a central event in hepatic fibrosis. However, the proteins that control HSC activation are incompletely understood. Here we show that (6aS, 10S, 11aR, 11bR, 11cS)-10-methylamino-dodecahydro-3a, 7a-diaza-benzo [de]anthracene-8-thione (MASM) exhibits potent inhibitory activity against liver fibrosis in vitro and in vivo associated with the reduction of Akt phosphorylation. Furthermore, ribosomal protein S5 (RPS5) was identified as a direct target of MASM, which stabilized RPS5 in cultured HSCs and in the liver of experimental animals after dimethylnitrosamine (DMN) or bile duct ligation (BDL). Functional studies revealed that RPS5 could prevent HSC activation. RPS5 overexpression in HSCs resulted in Akt dephosphorylation at both Ser473 and Thr308, and led to subsequent dephosphorylation of GSK3ß or P70S6K. Progression of DMN- and BDL-induced hepatic fibrosis was aggravated by Rps5 knockdown and alleviated by RPS5 overexpression, which correlated with the modulation of Akt phosphorylation and HSC number in the fibrotic livers. Moreover, RPS5 was substantially reduced in the transdifferentiated HSCs, experimental fibrotic livers, and human cirrhosis samples. CONCLUSION: These results demonstrate that RPS5 is implicated in hepatic fibrogenesis and may represent a promising target for potential therapeutic intervention in liver fibrotic diseases.