Crystal structures of WrbA, a spurious target of the salicylidene acylhydrazide inhibitors of type III secretion in Gram-negative pathogens, and verification of improved specificity of next-generation compounds.

The enterohemorrhagic Escherichia coli pathotype is responsible for severe and dangerous infections in humans. Establishment of the infection requires colonization of the gastro-intestinal tract, which is dependent on the Type III Secretion System. The Type III Secretion System (T3SS) allows attachment of the pathogen to the mammalian host cell and cytoskeletal rearrangements within the host cell. Blocking the functionality of the T3SS is likely to reduce colonization and therefore limit the disease. This route offers an alternative to antibiotics, and problems with the development of antibiotics resistance. Salicylidene acylhydrazides have been shown to have an inhibitory effect on the T3SS in several pathogens. However, the main target of these compounds is still unclear. Past work has identified a number of putative protein targets of these compounds, one of which being WrbA. Whilst WrbA is considered an off-target interaction, this study presents the effect of the salicylidne acylhydrazide compounds on the activity of WrbA, along with crystal structures of WrbA from Yersinia pseudotuberculosis and Salmonella serovar Typhimurium; the latter also containing parts of the compound in the structure. We also present data showing that the original compounds were unstable in acidic conditions, and that later compounds showed improved stability.

The effects of Antimicrobial Peptides and Hyaluronic Acid compound mask on wound healing after ablative fractional Carbon Dioxide laser resurfacing.

Background: Fractional carbon dioxide laser resurfacing (FxCR) is a routine treatment of Dermatology while many patients suffered the damage of skin barrier function after FxCR. Objective: To evaluate the benefits of antimicrobial peptides (AMPs) and hyaluronic acid (HA) compound mask on wound healing after FxCR on human and mouse skin. Methods: Twenty-four subjects were treated with FxCR on the bilateral cheeks. AMPs and HA compound mask was applied on the FxCR-treated area of left cheek. The erythema index (EI), melanin index (MI), transepidermal water loss (TEWL) of FxCR-treated areas on both cheeks were measured. By HE staining, immunohistostaing and western blotting, we analyzed epidermal thickness, FLG, IVL expression and protein levels of cramp in FxCR treated dorsal mice skin. Results: The EI, MI, and TEWL in the AMPs and HA compound mask-treated area of left cheek were significantly lower than those in the untreated area of right cheek. Topically application of AMPs and HA compound mask reduced thickening of mouse skin and also result in an increase in the production of FLG, IVL and cramp. Conclusion: Application of AMPs and HA compound mask is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

Beta-Ecdysone Protects Mouse Osteoblasts from Glucocorticoid-Induced Apoptosis In Vitro.

Glucocorticoid-induced osteoporosis is a common form of secondary osteoporosis. Glucocorticoids affect both bone formation and resorption, and prolonged glucocorticoid exposure can suppress osteoblast activities. beta-Ecdysone, found in many plants, is involved in protein synthesis, carbohydrate and lipid metabolism, and immunologic modulation. Here, we evaluated the effects of beta-ecdysone on osteoblast viability by assessing apoptosis following treatment with excess glucocorticoids. Mouse bone marrow stromal cells were induced to differentiate and grow into osteoblasts, and then treated with 10 µM glucocorticoid and 10, 1, or 0.1 µM beta-ecdysone. The expression levels of osteoblast growth and differentiation factors (runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase), apoptosis-related genes (transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8), and Akt1 and phospho-Akt (Thr308) were then assessed via alkaline phosphatase staining, acridine orange-propidium iodide staining, annexin V/PI apoptosis assay, real-time RT-PCR, and Western blot analyses. Notably, treatment with 10 µM glucocorticoid resulted in reduced osteoblast viability and the specific activity of alkaline phosphatase as well as reduced runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase mRNA expression in vitro, indicating that glucocorticoid inhibited osteogenic differentiation. Moreover, glucocorticoid treatment yielded increased transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8 expression and decreased Akt1 and phospho-Akt levels, indicating glucocorticoid-induced apoptosis. Meanwhile, beta-ecdysone inhibited glucocorticoid function, preserving the expression of Akt1 and phospho-Akt and reducing the expression of transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8. Thus, beta-ecdysone prevented glucocorticoid-induced osteoblast apoptosis in vitro. These data highlight the potential for beta-ecdysone as a treatment for preventing the effects of glucocorticoid on bone growth.

Comprehensive analysis of degradation and accumulation of ametryn in soils and in wheat, maize, ryegrass and alfalfa plants.

Ametryn is a selective herbicide belonging to the triazine family and widely used for killing annual grasses or weeds in China and other parts of the world. However, reports on its environmental risk assessment with regard to soil and crop contamination are limited. In this study, accumulation of ametryn in wheat, maize, ryegrass and alfalfa crops along with ametryn residues in the soil planted with the plants were comparatively investigated. Soil enzyme activities and low molecular weight organic acids (LMWOAs), as well as antioxidant and degradation enzyme activities in plant tissues were measured. The maximum accumulation of ametryn was found in shoots and roots of wheat and alfalfa. Ryegrass had the maximum ametryn translocation factor (TF) from roots to shoots, with more than three times over the other crops. The ametryn residue in ryegrass-planted soil was much lower than that in soil planted with others. The residual content of ametryn in crop-planted soils was ordered as rhizosphere soil

Microarray Expression Profile of Circular RNAs in Heart Tissue of Mice with Myocardial Infarction-Induced Heart Failure.

BACKGROUND/AIMS: Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. This study is aimed to assess the global changes in and characteristics of the transcriptome of circular RNAs (circRNAs) in heart tissue during MI induced heart failure (HF). METHODS: Using a post-myocardial infarction (MI) model of HF in mice, we applied microarray assay to examine the transcriptome of circRNAs deregulated in the heart during HF. We confirmed the changes in circRNAs by quantitative PCR. RESULTS: We revealed and confirmed a number of circRNAs that were deregulated during HF, which suggests a potential role of circRNAs in HF. CONCLUSIONS: The distinct expression patterns of circulatory circRNAs during HF indicate that circRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.

Glycyrrhetinic Acid protects the heart from ischemia/reperfusion injury by attenuating the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat hearts.

BACKGROUND/AIMS: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid (GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. MATERIALS AND METHODS: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). RESULTS: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. CONCLUSION: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.

[Ozone Pollution Characteristics and Formation Mechanism in a Typical Tropical Seaside City].

To investigate the pollution characteristics and formation mechanism of ambient air ozone(O3) in a typical tropical seaside city, we conducted an observational experiment on O3 and its precursors at an urban site in Haikou, Hainan Province, from June to October 2019. The O3 pollution characteristics were analyzed comprehensively; the O3-NOx-VOCs sensitivities and key precursors were determined, and the control strategies for O3 pollution were carried out. The results were as follows:1 O3 pollution in Haikou mainly occurred in September and October, with daily maximum 8-h O3 concentrations in the range of 39-190 µg·m-3, and the daily variation in O3 was unimodal, peaking at approximately 14:00. 2 The concentrations of NO2 and VOCs were higher during O3 pollution episodes than their respective mean values in Haikou City. The increased O3 precursor concentrations were an important factor leading to O3 pollution, whereas O3 pollution was also influenced by regional transport, with pollutants mainly transported from the northeastern part of Haikou City. 3 O3-NOx-VOCs sensitivity in Haikou City was in the VOCs and NOx transitional regime, and the most sensitive precursors in various months were different. O3 formation in September was sensitive to anthropogenic VOCs the most; however, in October it was sensitive to NOx. 4 In the future, the reduction ratio of VOCs to NOx should be 1:1-4:1 to control O3 pollution effectively in Haikou.

[Effects of glycyrrhetinic acid on sodium ion channel currents of rats' ventricular myocardial cells].

OBJECTIVE: To study the effects of glycyrrhetinic acid (GA) on the sodium ion channel currents (I(Na)) of rats' ventricular myocardial cells, and to explore its anti-arrhythmic mechanisms at the ion channel level. METHODS: Single ventricular myocardial cells was isolated from SD rats. The whole cell patch clamp was used to record the effects of GA on I(Na) of rats' ventricular myocardial cells. RESULTS: GA could inhibit I(Na) of rats' ventricular myocardial cells dose-dependently. GA at 1, 5, and 10 micromol/L decreased I(Na) of rats' ventricular myocardial cells from (-4.26 +/- 0.15) nA to (-3.54 +/- 0.10) nA, (-2.19 +/- 0.09) nA, and (-1.25 +/- 0.08) nA, respectively. GA at 1, 5, and 10 micromol/L inhibited I(Na) by 16.08% +/- 2.3%, 50.82% +/- 3.56%, and 75.98% +/- 5.12%, showing statistical difference when compared with the control group (P < 0.05). GA at 10 micromol/L shifted I(Na) current-voltage curve more positively, but the activation potential and the peak potential were not changed. CONCLUSION: GA inhibited the I(Na) of rats' ventricular myocardial cells dose-dependently, which was possibly associated with its antiarrhythmia effects.

[Analysis on pulse diagram characteristics of subjects with subhealth state].

OBJECTIVE: To study the pulse diagram parameters of subjects with subhealth state and to find the pulse parameters for subhealth state evaluation. METHODS: A total of 1 275 subjects without diagnosed diseases were recruited and their health conditions were assessed with Health Evaluating Questionnaire H20 V2009. The subjects were assigned to health group or subhealth group according to the scale score. Subjects' syndrome in the subhealth group was differentiated using score of "subhealth state of syndrome differentiation V2010". Another 121 patients with cardiovascular diseases were enrolled as a control. The pulse information was collected with YJJ-101 subhealth pulse monitoring system and the parameters include amplitude of main wave (h1), amplitude of repeat wave (h5) and its front wave (h3), 1/3 or 1/5 width of main wave (w1) or (w2), time of rapid ejection phase (t2), period of pulse (t), pulse pressure (Pp), square (S), area in systole (As) and area in diastole (Ad) of pulse diagram and ratios of h3/h1, h5/h1, w1/t, w2/t and h1/t1. RESULTS: Pulse diagram analysis showed significant differences among health, subhealth and disease group in Pp, h1, S and As and ratios of h5/h1 and w2/t. Compared with the health group, the values of w1/t and w2/t of the subhealth group increased (P<0.05), and Pp, h1, h5, h5/h1, S, As and Ad decreased (P<0.05). Compared with health group, the parameters of pulse of the subhealth group were increased in Pp and h5/h1 (P<0.05) and decreased in h1, w2/t, S and As (P<0.05). Compared with health group, pulse parameters h3/h1, w1, w1/t, w2/t of excess and deficiency syndrome group increased, and h1, h5, h1/t 1and h5/h1 decreased. Among different syndromes of subhealth state, pulse diagram parameters h1, h5, h3/h1, h5/h1 and w1/t of yin deficiency, qi deficiency, liver stagnation and excess heat group were significantly different (P<0.05) from the health group, for example, pulse parameters h1 and h5 of stagnation, yin deficiency, qi deficiency and excess heat group declined in order, and pulse parameters h3/h1 and w1/t of liver stagnation, excess heat, yin deficiency and qi deficiency group increased in order. Pulse index h1 in the kidney deficiency group was higher than that in the health group and the other syndrome groups. CONCLUSION: Results of analyzing sphygmogram parameters showed different characteristics among different health status and the subhealth state due to different syndromes. Sphygmogram parameters may be used for objective evaluation of health status or subhealth syndrome differentiation.

[Facial spectrum and color characteristics of five viscera reflecting on the face in sub-health status].

OBJECTIVE: To observe the facial spectrum and color of different points, the positions of heart, liver, spleen, lung and kidney of traditional Chinese medicine reflecting on the face, in healthy participants and those with a sub-health status, so as to provide an objective basis for health evaluation. METHODS: The health condition of 470 subjects without acute and chronic conditions was assessed using the Health Evaluating Questionnaire H20 V2009. The subjects were diagnosed with health (more than 80 score) or sub-health (score between 60 and 80) status according to the questionnaire score. The subjects with a subhealth status were also analyzed using the five-viscera syndrome differentiation of traditional Chinese medicine using the form for collecting information according to the four examinations. Then for gathering the facial color information, CIE L*a*b and C values and reflections of wavelengths ranged from 400 to 700 nm were measured using a CM-2600D spectrophotometer on 8 points of the face, including the frontal part, glabella, nose, mandible, two cheeks and eyelids. RESULTS: L value of the sub-health group was higher than that of the health group (P<0.05), and a, b and C values were lower than those of the health group (P<0.05), suggesting that the facial complexion of the sub-health group was pale/whiter than the health group. The reflectance rates of wavelengths (from 400 to 550 nm) of the sub-health group were higher than those of the health group (P<0.05), which suggested that the facial complexion of the sub-health group was partially green. The a, b and C values of the forehead, glabella and nose of subjects in the sub-health group were apparently different from the health subjects. L values of five-viscera types were significantly different from people of a health status (P<0.05). There were some differences in color values among the five-viscera groups: lung group's color values were significantly different from the others in terms of a, b and C values. The spectral reflectance of different viscera groups of the sub-health group also showed certain differences: reflectance of wavelengths at 400 to 490 nm in the lung group and at 520 to 580 nm in the spleen group showed significant difference from the other groups, and the lung group was lower and the spleen group was higher than the others. CONCLUSION: There are some differences in facial spectrum and color in different sites of the face in sub-health status of different viscera syndrome types, which can provide an objective basis for health evaluation.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model.

OBJECTIVE: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish. METHODS: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 µmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio. RESULTS: According to the Chinese Pharmacopoeia (2015), ß-ecdysone (ß-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of ß-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 µmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 µmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and ß-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1. CONCLUSION: RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

[Identification of differentially expressed genes in myocardium of patients with heart failure by human whole genomic oligonucleotide microarray-assisted pathways analysis].

OBJECTIVE: To identify the differentially expressed gene profiles in myocardium of patients with heart failure using human whole genomic oligonucleotide microarray-assisted pathway analysis. METHODS: Phalanx whole genomic oligonucleotide microarrays were used to detect the gene expression profiles of myocardium in four patients died of heart failure and 4 brain died patients without heart diseases. The microarray findings were confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. The genes with a threshold of 1.2 times fold-change were selected and BioCarta Pathway and KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway databases were used to identify functionally related gene pathways. RESULTS: A total of 2806 genes with differentially expression were detected between the failing and non-failing heart samples, expression changes of 399 genes were more than 2-folds. Eleven pathways were identified by BioCarta pathway database and sixteen pathways were identified by KEGG PATHWAY Database. CONCLUSION: Genomic microarray-assisted pathway analysis could help to identify gene expression profiles in failing heart.

[Effects of nitrogen addition on tree root traits.] / æ°®æ·»åŠ å¯¹æ ‘æœ¨æ ¹ç³»ç‰¹æ€§çš„å½±å“.

Atmospheric nitrogen deposition has complex effects on individual plants and terrestrial ecosystems. We synthesized results from 39 published papers (16 papers in English and 23 papers in Chinese) and conducted a meta-analysis to evaluate the general responses of tree root traits to nitrogen addition, and further analyzed the difference of N-induced results between English papers and Chinese papers. Our results showed that N addition significantly increased fine root diameter (+6.7%), fine root N content (+8.9%), and root respiration rate (+17.5%), but did not affect fine root biomass, fine root length, specific root length, fine root C content, and fine root C:N ratio. Different climatic zone and fertilizer types had different effects on the experimental results. In addition, experimental results published in English papers were generally more significant than those in Chinese papers. We summarized the general effects of N addition on tree root systems, and further analyzed the mechanisms underlying the effects of N enrichment on forest ecosystem carbon cycle.

[Effects of fufangdenshen tablets on human atherosclerotic plasma protein using proteomic technique].

OBJECTIVE: To research the effects of fufangdenshen tablets on atherosclerotic plasma protein using proteomic technique and further explore its potential molecular mechanism to cure atherosclerosis. METHOD: The plasma of normal, atherosclerosis and cured group were collected, and the albumin in plasma was removed. Proteomic protocol involved of 2-DE, image analysis and spectrometry detection was used to detect regulated plasma protein by fufangdenshen tablets. RESULT: 3 decreased expressed and 6 higher protein in atherosclerotic plasma could be recovered by fufangdenshen tablets. The levels of fibrinogen, Granzyme C and immunoglobulin were decreased by fufangdenshen tablets. CONCLUSION: The levels of fibrinogen, Granzyme C in atherosclerotic plasma could be decreased by fufangdenshen tablets. The effects of fufangdenshen tablets on atherosclerosis included that: inhibition of adhesion of monocyte, inhibition of proliferation and migration of VSMC, and weakening of inflammation.

Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs.

OBJECTIVE: MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis. DATA SOURCES: Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms "microRNA", "miR", "transforming growth factor ß", "tgf ß", "mitogen-activated protein kinase", "mapk", "integrin", "p38", "c-Jun NH2-terminal kinase", "jnk", "extracellular signal-regulated kinase", "erk", and "fibrosis". STUDY SELECTION: Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis. RESULTS: Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis, such as immune cell sensitization, effector cell activation, and extracellular matrix remodeling. Moreover, several important molecular signaling pathways involve in fibrosis, such as the transforming growth factor-beta (TGF-ß) pathway, mitogen-activated protein kinase (MAPK) pathways, and the integrin pathway are regulated by miRNAs. Third, regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart, lung, liver, and kidney. Interestingly, the actions of many drugs on the human body are also induced by miRNAs. It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways, thereby protecting the structures and functions of different organs. CONCLUSIONS: miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases.

Pyogenic granuloma in a patient with psoriasis successfully treated by 5-aminolevulinic acid photodynamic therapy: A case report.

Pyogenic granuloma (PG) is an acquired benign vascular tumor of unknown etiology. In the present case report, PG was detected in a 49-year-old Chinese male patient with chronic plaque psoriasis. The psoriasis lesions on the finger where the granuloma had developed had been scratched excessively, as declared by the patient. No retinoid therapeutic agents were used during treatment. The patient responded poorly to cryotherapy and surgical curettage. However, following one session of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), signs of improvement were demonstrated 1 week after the treatment, and 1 month following treatment, there were no signs of reoccurrence. Although a report demonstrating treatment success in one patient may be inadequate to estimate the true efficiency of ALA-PDT, dermatologists may consider ALA-PDT as an alternative therapy for stubborn PG.

Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway.

5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in-vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1α in the cell supernatant, and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1α expression, and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses.

Shenfu Injection suppresses inflammation by targeting haptoglobin and pentraxin 3 in rats with chronic ischemic heart failure.

OBJECTIVE: To investigate the regulatory effects of Shenfu Injection (SFI, ) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure (CHF). METHODS: Forty-five healthy Wistar rats were randomized into three groups: sham, heart failure (model) and SFI group. The CHF was induced by left coronary artery ligation. Seven days after the surgical operation, animals in the sham group and the model group received saline (6.2 mL/kg/d), while animals in the SFI group received SFI (6.2 mL/kg d) intraperitoneally. Four weeks later, cardiac hemodynamic parameters were measured via the carotid route. The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). RESULTS: Recording of hemodynamic parameters showed that left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure (+dp/dtmax) rise, and maximum rate of left ventricular pressure (-dp/dtmax) decrease, while the left ventricular end diastolic pressure (LVEDP) rose in the model group compared to those in the sham group (P <0.05). The results of the MALDI-TOF MS indicated that haptoglobin (HP), pentraxin 3 (PTX3) and alpha-1-antitrypsin were up-regulated, while serum albumin and 40S ribosomal protein were down-regulated in the model group (P <0.05). Compared with the model group, LVSP, +dp/dtmax and -dp/dtmax were higher, while LVEDP was lower in the SFI group (P<0.05). Expression levels of HP and PTX3 were lower than in the model group (P<0.05). CONCLUSION: SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF. The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure, and they could also be the serum protein targets of SFI.

Akt suppresses DLK for maintaining self-renewal of mouse embryonic stem cells.

Mouse embryonic stem cells (ES cells) can proliferate indefinitely. To identify potential signals involved in suppression of self-renewal, we previously screened a kinase/phosphatase expression library in ES cells, and observed that inhibition of Dual Leucine zipper-bearing Kinase (DLK) increased relative cell numbers. DLK protein was detected in both the pluripotent and differentiated states of mouse ES cells while DLK kinase activity increased upon differentiation. Overexpression of DLK in mouse ES cells displayed reductions in relative cell/colony numbers and Nanog expression, suggesting a suppressive role of DLK in self-renewal. By examining protein sequences of DLK, we identified 2 putative Akt phosphorylation sites at S584 and T659. Blocking PI3K/Akt signaling with LY-294002 enhanced DLK kinase activity dramatically. We found that Akt interacts with and phosphorylates DLK. Mutations of DLK amino acid residues at putative Akt phosphorylation sites (S584A, T659A, or S584A and T659A) diminished the level of DLK phosphorylation. While the mutated DLKs (S584A, T659A, or S584A and T659A) were expressed, a further reduction in cell/colony numbers and Nanog expression appeared in mouse ES cells. In addition, these mutant DLKs (S584A, T659A, or S584A and T659A) exhibited more robust kinase activity and cell death compared to wild type DLK or green fluorescence (GFP) controls. In summary, our results show that DLK functions to suppress self-renewal of mouse ES cells and is restrained by Akt phosphorylation.