Extension of a biotic ligand model for predicting the toxicity of neodymium to wheat: The effects of pH, Ca2+ and Mg2.

The damage excessive neodymium (Nd) causes to animals and plants should not be underestimated. However, there is little research on the impact of pH and associated ions on the toxicity of Nd. Here, a biotic ligand model (BLM) was expanded to predict the effects of pH and chief anions on the toxic impact of Nd on wheat root elongation in a simulated soil solution. The results suggested that Nd3+ and NdOH2+ were the major ions causing phytotoxicity to wheat roots at pH values of 4.5-7.0. The Nd toxicity decreased as the activities of H+, Ca2+, and Mg2+ increased but not when the activities of K+ and Na+ increased. The results indicated that H+, Ca2+, and Mg2+ competed with Nd for binding sites. An extended BLM was developed to consider the effects of pH, H+, Ca2+, and Mg2+, and the following stability constants were obtained: logKNdBL = 2.51, logKNdOHBL = 3.90, logKHBL = 4.01, logKCaBL = 2.43, and logKMgBL = 2.70. The results demonstrated that the BLM could predict the Nd toxicity well while considering the competition of H+, Ca2+, Mg2+ and the toxic species Nd3+ and NdOH2+ for binding sites.

Value of electrophysiological indicators in differential diagnosis of parkinson's disease and multiple system atrophy.

BACKGROUND: We evaluated the value of electrophysiological indicators by external anal sphincter electromyography (EAS-EMG), sympathetic skin response (SSR), R-R interval variation (RRIV), and Bulbocavernosus Reflex (BCR) in differential diagnosis of multiple system atrophy (MSA) and Parkinson's disease (PD). METHODS: A total of 41 patients with MSA and 32 patients with PD were enrolled. The electrophysiological changes of autonomic dysfunction were assessed with BCR, EAS-EMG, SSR, and RRIV, and the abnormal rate of each indicator was calculated. The diagnostic value of each indicator was analyzed with ROC curve. RESULTS: The incidence rate of autonomic dysfunction in MSA group was significantly higher than that in PD group (p < 0.05). The abnormal rates of BCR and EAS-EMG indicators in MSA group were higher than those in PD group (p < 0.05). The abnormal rates of SSR and RRIV indicators in MSA group and PD group were high; however, there was no significant difference between MSA and PD groups (p > 0.05). The sensitivity of BCR combined with EAS-EMG indicators in differential diagnosis of MSA and PD were 92.3% in males and 86.7% in females, respectively, and the specificity was 72.7% in males and 90% in females, respectively. CONCLUSIONS: Combined analysis of BCR and EAS-EMG has high sensitivity and specificity for differential diagnosis of MSA and PD.

Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial.

BACKGROUND: The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. METHODS/DESIGN: A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. DISCUSSION: To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. TRIAL REGISTRATION NUMBER: ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

Biotic ligand modeling to predict the toxicity of HWO4- and WO42- on wheat root elongation in solution cultures: Effects of pH and accompanying anions.

Increasing evidence demonstrates that hexavalent tungsten (W(VI)) can affect the survival of various organisms. This study explored the influences of pH and common anions on W(VI) toxicity on wheat and established a biotic ligand model (BLM) for predicting W(VI) toxicity. It was found that as the pH value increased from 6.0 to 8.5, the EC50[W(VI)]T values increased greatly from 24.7 to 46.6 µM, indicating that increasing pH values can alleviate W(VI) toxicity. A linear relationship between the ratio of HWO4- to WO42- and EC50{WO42-} indicated that WO42- and HWO4- were two toxic species of W(VI). The toxicity of W(VI) decreased as the H2PO4- and SO42- activities increased but not when the activities of Cl- and NO3- increased, demonstrating that the competition from H2PO4- and SO42- significantly influenced W(VI) toxicity. By applying BLM theory, the stability constants for HWO4-, WO42-, H2PO4-, and SO42- were obtained: logKWO4BL = 4.08, logKHWO4BL = 6.44, logKH2PO4BL = 2.09, and logKSO4BL = 1.87, fWBL50% = 0.300, ß = 1.99. Results demonstrated that BLM outperformed the free metal activity model(FIAM) in predicting W(VI) toxicity when considering the influences of pH, W(VI) species, and H2PO4- and SO42- competition for active ligand sites.

[Correlation of gut microbiota and ischemic stroke: a review].

With the widespread application of next-generation sequencing(NGS), especially 16 S rRNA and shotgun sequencing, researchers are no longer troubled with massive data on the gut microbiota, and the correlation between the gut microbiota and the brain(central nervous system) has been gradually revealed. Research on the microbiota-gut-brain axis(MGBA) based on the gut microbiota have provided insights into the exploration of the pathogenesis and risk factors of ischemic stroke(IS), a cerebrovascular disease with high disability and mortality rates, and also facilitate the selection of therapeutic targets of this class of drugs. This study reviewed the application of NGS in the study of gut microbiota and the research progress of MGBA in recent years and systematically collated the research papers on the correlation between IS and gut microbiota. Furthermore, from the bi-directional regulation of MGBA, this study also discussed the high-risk factors of IS under the dysregulation of gut microbiota and the pathophysiological changes of gut microbiota after the occurrence of IS and summarized the related targets to provide a reliable reference for the therapeutic research of IS from the gut microbiota.

Pharmacological activities of dihydrotanshinone I, a natural product from Salvia miltiorrhiza Bunge.

Salvia miltiorrhiza Bunge (Danshen), a famous traditional Chinese herb, has been used clinically for the treatment of various diseases for centuries. Document data showed that tanshinones, a class of lipophilic abietane diterpenes rich in this herb, possess multiple biological effects in vitro and in vivo models. Among which, 15,16-dihydrotanshinone I (DHT) has received much attention in recent years. In this systematical review, we carefully selected, analyzed, and summarized high-quality publications related to pharmacological effects and the underlying mechanisms of DHT. DHT has anti-cancer, cardiovascular protective, anti-inflammation, anti-Alzheimer's disease, and other effects. Furthermore, several molecules such as hypoxia-inducible factor (HIF-1α), human antigen R (HuR), acetylcholinesterase (AchE), etc. have been identified as the potential targets for DHT. The diverse pharmacological activities of DHT provide scientific evidence for the local and traditional uses of Salvia miltiorrhiza Bunge. We concluded that DHT might serve as a lead compound for drug discovery in related diseases while further in-depth investigations are still needed.

ITRAQ-based quantitative proteomic analysis of processed Euphorbia lathyris L. for reducing the intestinal toxicity.

BACKGROUND: Euphorbia lathyris L., a Traditional Chinese medicine (TCM), is commonly used for the treatment of hydropsy, ascites, constipation, amenorrhea, and scabies. Semen Euphorbiae Pulveratum, which is another type of Euphorbia lathyris that is commonly used in TCM practice and is obtained by removing the oil from the seed that is called paozhi, has been known to ease diarrhea. Whereas, the mechanisms of reducing intestinal toxicity have not been clearly investigated yet. METHODS: In this study, the isobaric tags for relative and absolute quantitation (iTRAQ) in combination with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic method was applied to investigate the effects of Euphorbia lathyris L. on the protein expression involved in intestinal metabolism, in order to illustrate the potential attenuated mechanism of Euphorbia lathyris L. processing. Differentially expressed proteins (DEPs) in the intestine after treated with Semen Euphorbiae (SE), Semen Euphorbiae Pulveratum (SEP) and Euphorbiae Factor 1 (EFL1) were identified. The bioinformatics analysis including GO analysis, pathway analysis, and network analysis were done to analyze the key metabolic pathways underlying the attenuation mechanism through protein network in diarrhea. Western blot were performed to validate selected protein and the related pathways. RESULTS: A number of differentially expressed proteins that may be associated with intestinal inflammation were identified. They mainly constituted by part of the cell. The expression sites of them located within cells and organelles. G protein and Eph/Ephrin signal pathway were controlled jointly by SEP and SE. After processing, the extraction of SEP were mainly reflected in the process of cytoskeleton, glycolysis and gluconeogenesis. CONCLUSIONS: These findings suggest that SE induced an inflammatory response, and activated the Interleukin signaling pathway, such as the Ang/Tie 2 and JAK2/ STAT signaling pathways, which may eventually contribute to injury result from intestinal inflammatory, while SEP could alleviate this injury by down-regulating STAT1 and activating Ang-4 that might reduce the inflammatory response. Our results demonstrated the importance of Ang-4 and STAT1 expression, which are the target proteins in the attenuated of SE after processing based on proteomic investigation. Thus iTRAQ might be a novel candidate method to study scientific connotation of hypothesis that the attenuated of SE after processing expressed lower toxicity from cellular levels.

Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology.

Qijian mixture, a new traditional Chinese medicine (TCM) formula comprising of Astragalus membranaceus, Ramulus euonymi, Coptis chinensis and Pueraria lobata, was designed to ameliorate the type 2 diabetes (T2D), and its safety and efficacy were evaluated in the research by metabonomics, gut microbiota and system pharmacology. To study the hypoglycemic effect of Qijian mixture, male KKay mice (28-30 g, 8-9 week) and C57/BL6 mice (18-19 g, 8-9 week) were used. Thirty KKay diabetic mice were randomly distributed into 5 groups, abbreviated as Model group (Model), Low Qijian Mixture group (QJM(L)), High Qijian Mixture group (QJM(H)), Chinese Medicine (Gegen Qinlian Decoction) Positive group (GGQL), and Western Medicine (Metformin hydrochloride) Positive group (Metformin). C57/BL6 was considered as the healthy control group (Control). Moreover, a system pharmacology approach was utilized to assess the physiological targets involved in the action of Qijian mixture. There was no adverse drug reaction of Qijian mixture in the acute toxicity study and HE result, and, compared with Model group, Qijian mixture could modulate blood glycemic level safely and effectively. Qijian Mixture was lesser effective than metformin hydrochloride; however, both showed similar hypoglycemic trend. Based on 1H NMR based metabonomics study, the profoundly altered metabolites in Qijian mixture treatment group were identified. Qijian mixture-related 55 proteins and 4 signaling pathways, including galactose metabolism, valine, leucine and isoleucine degradation metabolism, aminoacyl-tRNA biosynthesis metabolism and alanine, aspartate and glutamate metabolism pathways, were explored. The PCoA analysis of gut microbiota revealed that Qijian mixture treatment profoundly enriched bacteroidetes. In addition, the system pharmacology paradigm revealed that Qijian mixture acted through TP53, AKT1 and PPARA proteins. It was concluded that Qijian mixture effectively alleviated T2D, and this effect was linked with the altered features of the metabolite profiles and the gut microbiota.

[Research and application of quercetin-loaded nano drug delivery system].

Quercetin has a variety of biological activities and pharmacological effects, but its clinical application is limited due to its low water solubility, low bioavailability and poor chemical stability. In order to overcome the above shortcomings of quercetin and achieve better clinical efficacy, many new drug delivery systems have been studied and developed in recent years, of which nano drug delivery system has become a research hotspot. Nano drug delivery system includes nanoparticles, nanocapsules, nanoliposomes, nanomicelles, nanosuspensions and nanoemulsions, with the advantages of reducing particle size, enlarging surface area, increasing drug permeability, improving intracorporeal circulation and distribution of the drug, enhancing drug targeting and so on. This article reviewed the latest progress at home and abroad about the studies and application of quercetin in nano drug delivery system, such as increasing solubility and dissolution, elevating bioavailability, raising drug stability, delaying drug release, enhancing skin permeability, promoting antioxidant capacity and improving therapeutic effect, in the hope of providing references for further research of quercetin preparations.

Expression of AQP2, AQP4 and AQP 8 in mouse intestine induced by unprocessed and processed Euphorbia lathyris.

The present research was designed to study expression of AQP2, AQP4 and AQP8 in mouse intestines induced by unprocessed and processed Euphorbia lathyris. KM mice were given by different dose lavage of unprocessed and processed Euphorbia lathyris, Euphorbia factor L1, Euphorbia factor L2, Euphorbia factor L3. Samples of mouse intestine were collected for protein levels of AQP2, AQP 4 and AQP 8 which were assessed by immunohistochemical staining and mRNA expression of AQP2, AQP 4 and AQP 8 which were quantified by Real Time-PCR. Comparing to the normal control group, the protein levels of AQP2, AQP 4 and AQP 8 were significantly decreased (P<0.05)by Semen Euphorbiae group and Semen Euphorbiae Pulveratum group (unprocessed and processed Euphorbia lathyris) induced. Protein expression of AQP2, AQP 4 and AQP 8 in the Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 group were not significantly lower than normal control group. There had no differences on the levels of AQP2 and AQP 8 mRNA expressions between the high-dose group of semen Euphorbiae group, semen Euphorbiae Pulveratum group and positive control group, while significantly lower than normal control group (P<0.05). Expression of AQP4 mRNA in the Semen Euphorbiae group and Semen Euphorbiae Pulveratum group has not significantly decreased. But levels of AQP2, AQP 4 and AQP 8 mRNA in the Euphorbia factor L1 group had no significant differences in normal control group and positive control group. These findings suggest that semen Euphorbiae could regulate expression of AQP2, AQP 4 and AQP 8 protein and mRNA, which may be the possible one reason of semen Euphorbiae induces diarrhea. The semen Euphorbiae group has more significant effects on the levels of AQP2, AQP 4 and AQP 8 protein and mRNA than semen Euphorbiae Pulveratum group, which may be one of the mechanisms of processing attenuation.

Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKß pathways.

Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKß, p-IκBα, p-p65 expression, and p-IκBα-IKKß interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKß pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect.

Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia.

Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs' metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network.

Immune responses of prophenoloxidase in the mud crab Scylla paramamosain against Vibrio alginolyticus infection: in vivo and in vitro gene silencing evidence.

Phenoloxidase (PO) plays an important role in arthropod melanization. In the present study, a proPO gene was obtained from the mud crab Scylla paramamosain, then we localized the proPO mRNA in hemocytes and detected the expression of proPO after bacterial challenge. In vivo and in vitro gene silencing mediated by dsRNA was also used to investigate the function of proPO in innate immune. The full-length of the proPO cDNA was 2600 bp and the predicted ORF encoded a protein of 673 amino acids with a predicted molecular mass of 77.3 kDa. The deduced amino acid and the main functional domain of proPO shared a high similarity to the mud crab Scylla serrata. In situ hybridization assay showed that the proPO mRNA was localized in the granular and semi-granular cells. The expression level of proPO in hemocytes showed a clear time-dependent pattern during the 96 h course after stimulated by Vibrio alginolyticus. In this study, high expression levels were observed at 3, 12, 24 and 48 h, respectively and the highest expression level was observed at 12 h, and this suggested that proPO was induced by bacteria and involved in immune response. In vivo proPO and GFP dsRNA treatment experiments showed that, proPO mRNA transcript was reduced to 39%, but the PO activity showed no significant difference (P > 0.05). Results indicated that the expression of proPO could be inhibited by dsRNA, and the enzyme activity may be influenced by incomplete knockdown of proPO, or hemocyanin, and other proPO isoforms as well. In vitro proPO-silenced experiments showed that the levels of proPO were decreased by 36%, 64% and 77% at 8, 16 and 32 h, respectively. Meanwhile, the quantity of bacteria was significantly larger in proPO dsRNA treatment than that in control at 3 h, calculated by 4,6-diamino-2-phenylindole staining (P < 0.01). These data demonstrated that the proPO gene plays an important role in the control of systemic bacterial infections and could help us to elucidate the defense role of the proPO-activating system in crabs. In addition, in vitro gene silencing operation mediated by dsRNA was expected to be a new tool for investigating the function of genes in crustaceans in the case of lacking cell line.

MAP7 drives EMT and cisplatin resistance in ovarian cancer via wnt/ß-catenin signaling.

Methods: Our approach encompasses analyzing MAP7's expression levels across various datasets and clinical specimens, evaluating its association with patient outcomes, and probing its influence on ovarian cancer cell dynamics such as proliferation, migration, invasion, and apoptosis. Results: We have identified significant upregulation of MAP7 in ovarian cancer tissues, which correlates with advanced disease stages, higher pathological grades, and unfavorable prognoses. Functionally, the inhibition of MAP7 suppresses cancer cell proliferation, migration, and invasion while promoting apoptosis. Notably, the silencing of MAP7 attenuates the epithelial-mesenchymal transition (EMT) and disrupts Wnt/ß-catenin pathway signaling-two critical processes implicated in metastasis and chemoresistance. In cisplatin-resistant A2780-DDP cells, the downregulation of MAP7 effectively reverses their resistance to cisplatin. Furthermore, the nuclear localization of MAP7 in these cells underscores its pivotal role in driving cisplatin resistance by modulating the transcriptional regulation and interaction dynamics of ß-catenin. Conclusion: Our findings position MAP7 as a pivotal element in ovarian cancer advancement and cisplatin resistance, primarily through its modulation of EMT and the Wnt/ß-catenin pathway. Its association with poor clinical outcomes underscores its potential as both a prognostic marker and a therapeutic target. Strategies aimed at MAP7 could represent a new frontier in combating chemotherapy resistance in ovarian cancer, emphasizing its significance in crafting complementary treatments for this disease.

HIF-1α regulates DcR3 to promote the development of endometriosis.

OBJECTIVE: The aim of this study was to investigate the expression and clinical significance of HIF-1α and DcR3 in endometriosis by analysing clinical case data. Tissue samples were collected for tissue chip analysis and staining, and human endometrial stromal cells were isolated and cultured for cell experiments. Additionally, experiments were conducted on collected peritoneal fluid to explore the association and role of HIF-1α and DcR3 in endometriosis. STUDY DESIGN: Patients who visited the Department of Obstetrics and Gynaecology at Central Hospital in Fengxian District, Shanghai, from January 2018 to December 2021 were recruited for this controlled study. Clinical data and tissue chip staining results were collected for multiple regression analysis on the clinical significance of HIF-1α and DcR3. Endometrial tissue, ovarian cysts, and pelvic fluid were collected, and human endometrial stromal cells were cultured. The impact of HIF-1α on DcR3 in different oxygen environments and its role in endometriosis were investigated through PCR, Western blotting, enzyme-linked immunosorbent assay, as well as adhesion and migration assays. RESULTS: In patients with endometriosis, the expression of DcR3 and HIF-1α was found to be upregulated and correlated in ectopic endometrium. The expression of DcR3 served as an indicator of the severity of endometriosis. Hypoxia induced the expression of DcR3, which was regulated by HIF-1α and promoted migration and adhesion. CONCLUSION: DcR3 can be used as a clinical indicator to assess the severity of endometriosis. The hypoxic environment in endometriosis enhances disease progression by regulating DcR3 through HIF-1α.

Dual-modality probe nanodrug delivery systems with ROS-sensitivity for atherosclerosis diagnosis and therapy.

Most acute cardiovascular and cerebrovascular diseases are caused by atherosclerotic plaque rupture leading to blocked arteries. Targeted nanodelivery systems deliver imaging agents or drugs to target sites for diagnostic imaging or the treatment of various diseases, providing new insights for the detection and treatment of atherosclerosis. Based on the pathological characteristics of atherosclerosis, a hydrogen peroxide-sensitive bimodal probe PPIS@FC with integrated diagnosis and treatment function was designed. Bimodal probes Fe3O4@SiO2-CDs (FC) were prepared by coupling superparamagnetic iron oxide and carbon quantum dots synthesized with citric acid, and self-assembled with hydrogen peroxide stimulus-responsive amphiphilic block polymer PGMA-PEG modified with simvastatin (Sim) and target molecule ISO-1 to obtain drug-loaded micelles PGMA-PEG-ISO-1-Sim@FC (PPIS@FC). PPIS@FC could release Sim and FC in an H2O2-triggered manner, achieving the goal of releasing drugs using the special microenvironment at the plaque. At the same time, in vivo magnetic resonance and fluorescence imaging results proved that PPIS@FC possessed targeting ability, magnetic resonance imaging and fluorescence imaging effects. The results of the FeCl3 and ApoE-/- model showed that PPIS@FC had an excellent therapeutic effect and in vivo safety. Therefore, dual-modality imaging drug delivery systems with ROS response will become a promising strategy for the diagnosis and treatment of atherosclerosis.

Characterization and expression of SpHsp60 in hemocytes after challenge to bacterial, osmotic and thermal stress from the mud crab Scylla paramamosain.

Hsp60 play a crucial role in the process of pathogenic and protective immune responses and is implicated in autoimmune disease. In order to understand the environmental response and immune response of this gene, we cloned a Hsp60 (SpHsp60) gene from the mud crab Scylla paramamosain, localized SpHsp60 in hemocytes by in situ hybridization, and detected the expression of SpHsp60 after stresses in relation to three housekeeping genes (ß-actin, 18S rRNA and GAPDH). The full-length of the SpHsp60 cDNA was found to be 2424 bp. The predicted ORF encoded a protein of 576 amino acids with a predicted molecular mass of 61.19 kDa and a theoretical isoelectric point (pI) of 5.46. It shared high scoring identity 95% with the swimming crab Portunus trituberculatus. In situ hybridization assay showed that a higher expression occurred in the granular and semigranular cells when compared to the hyaline hemocytes. It suggested that SpHsp60 was mainly contributed from the granular and semigranular cells in hemolymph. The expression level of SpHsp60 in hemocytes showed a clear time-dependent pattern during the 96 h after stimulated by Vibrio alginolyticus. During this experiment the gene was induced and the highest expression level was observed at 3 h. The significantly up-regulated expression and rapid response of SpHsp60 indicated that the crabs were sensitive to bacterial challenge. After osmotic stress, the expression of SpHsp60 in hemocytes showed that this gene was induced by the high salinity (30‰) and the crabs had its adaptive responses to high salinity, when compared to the normal salinity (15‰). SpHsp60 mRNA expression in hemocytes was analyzed after thermal stress at 6 h, the highest and the lowest expression levels of SpHsp60 were observed at 36 and 32 °C, respectively. This study demonstrated that SpHsp60 was easily induced at the higher temperatures. Based on our research, SpHsp60 participate in innate immune and environmental response of S. paramamosain. It could be used as a biomarker to test the stress caused by the local aquaculture environment.

[Determination of endogenous amino acids in brain tissues after cerebral ischemia by RRLC-QQQ].

OBJECTIVE: To establish a method to determine underivatized endogenous amino acids in brain tissues after cerebral ischemia based on RRLC-QQQ. METHOD: Diamonsil chromatographic column C18 (4.6 mm x 250 mm, 5 microm) was adopted to determine 12 amino acids in 15 min, with acetonitrile-0.1% formic acid for gradient elution. The flow rate was set at 0.5 mL x min(-1). With ESI as the ion source, positive ion scanning mode was adopted for multi-reaction monitoring. RESULT: Each amino acid standard curve (AAs) showed good linear relationship within the detection range (r > 0.996), with the limit of detection of less than 11%, the limit of quantitation of less than 3.09 microg x L(-1). The RSD of intra- and inter-day precisions at high, middle and low concentrations were less than 11%. CONCLUSION: The determination results of actual samples showed that compared with the levels of AAs of the sham operation group, all of the remaining amino acids apart from N-acetyl-aspartate increased in brain tissues. Some amino acids showed significant changes in a time-dependent manner after the operation. The method is so simple, rapid and sensitive that it can be used for finding biological metabolite markers of cerebral ischemia, and exploring cerebral ischemia molecular mechanisms and synergistic mechanism of combined administration of multi-component traditional Chinese medicines.

Increased FOXM1 Expression was Associated with the Prognosis and the Recruitment of Neutrophils in Endometrial Cancer.

Background: Although the biological functions of Forkhead box protein M1 (FOXM1) were explored in a variety of cancer, to date, however, little attention has been paid to the situation of FOXM1 in EC endometrial cancer (EC). Method: Bioinformatics analysis, including GEPIA, TIMER, cBioPortal, LinkedOmics, and STRING were used to analyze the FOXM1 gene expression, genetic alteration, and immune cell infiltration in EC. IHC staining, qPCR, cell viability, and migration assay were applied to identify the functions of FOXM1 in EC. Results: FOXM1 was highly expressed in EC tissues and closely correlated with the prognosis of EC patients. FOXM1 knockdown inhibited EC cell proliferation and invasion as well as migration. FOXM1 genetic alteration was verified in EC patients. Coexpression network of FOXM1 indicated that it had roles in the EC cell cycle and the infiltration of immune cells in EC. Furthermore, bioinformatic and immunohistochemical analysis indicated that FOXM1 induced the increased CD276 expression and also enhanced the neutrophil recruitment in EC. Conclusion: Our present study discovered a novel role of FOXM1 in EC, suggesting FOXM1 could be treated as a potential prognostic biomarker and immunotherapeutic target in EC diagnosis and treatment.

Urine metabolites and viral pneumonia among children: a case-control study in China.

Background: Viral pneumonia in children is common and has grave consequences. The study aims to better understand the pathophysiological processes involved in the onset and progression of viral pneumonia and identify common effects or biomarkers across different viruses. Methods: This study collected urine samples from 96 patients with viral pneumonia including respiratory syncytial virus (RSV) (n=30), influenza virus (IV) (n=23), parainfluenza virus (PIV) (n=24), and adenovirus (ADV) (n=19), and 31 age- and sex-matched normal control (NC) subjects. The samples were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS) to identify endogenous substances. The XCMS Online platform was utilized for data processing and analysis , including feature detection, retention time correction, alignment, annotation, and statistical analysis for difference between groups and biomarker identification. Results: A total of 948 typical metabolites were identified using the XCMS Online platform with the Mummichog technique. After analyzing the data, 24 metabolites were selected as potential biomarkers for viral pneumonia, of which 16 were aspartate and asparagine metabolites, byproducts of alanine, leucine, and isoleucine degradation, and butanoate metabolites. Conclusions: This study specific metabolites and altered pathways in children with viral pneumonia and propose that these findings could contribute to the discovery of new treatments and the development of antiviral drugs.