DNMT3b-mediated methylation of ZSWIM3 enhances inflammation in alcohol-induced liver injury via regulating TRAF2-mediated NF-κB pathway.

The regulation of macrophages during inflammatory responses is a crucial process in alcoholic liver disease (ALD) and aberrant macrophage DNA methylation is associated with inflammation. Our preliminary screening results of macrophage methylation in the present study demonstrated the zinc finger SWI2/SNF2 and MuDR (SWIM)-domain containing 3 (ZSWIM3) were hypermethylated in the 5' untranslated region (5'-UTR) region. ZSWIM3, a novel zinc finger-chelate domain of SWIM, is predicted to function in DNA-binding and protein-binding interactions. Its expression was found to be consistently decreased in macrophages isolated from livers of ethyl alcohol (EtOH)-fed mice and in EtOH+lipopolysaccharide (LPS)-induced RAW264.7 cells. Over-expression of ZSWIM3 was found to attenuate chronic+binge ethanol feeding-induced liver injury and inhibit inflammatory responses in vivo. Enforced expression of ZSWIM3 in vitro was also found to have anti-inflammatory effects. Aberrant expression of ZSWIM3 in alcohol-induced liver injury (ALI) was found to be associated with hypermethylation. Analysis of CpG prediction indicated the presence of two methylated sites in the ZSWIM3 promoter region and methylation inhibitor and DNA methyltransferases (DNMTs)-siRNA transfection were found to restore down-regulated ZSWIM3. Chromatin immunoprecipitation (ChIP) assay and molecular docking affirmed the role of DNMT 3b (DNMT3b) as a principal regulator of ZSWIM3 expression. Mechanistically, ZSWIM3 might affect inflammation by binding with tumor necrosis factor receptor-associated factor 2 (TRAF2), which further mediates the activation of the nuclear transcription factor κB (NF-κB) pathway. The present study, therefore, provides detailed insights into the possible structure and function of ZSWIM3 and thus, contributes new substantial research in the elucidation of the pathogenesis of ALI.

Noncoding RNAs in alcoholic liver disease.

Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA-122 is a marker of hepatocyte damage, and miRNA-155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome-derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.

Protective effect of high concentration of BN52021 on retinal contusion in cat eyes.

BACKGROUND: Blunt injuries/contusion on eyes might cause retina blunt trauma. This study is to evaluate the protective function of BN52021 against retinal trauma. METHODS: A total of 70 cats, 6 months old, were divided into six groups: Group A to E (n = 12) and normal control (N) group (n = 10). The right eyes in Group A to E were contused. All experiments were performed under general anesthetization. Retrobulbar injections of medication in right eyes were performed. Cats were administrated with 0.5 mL of normal saline (NS), dimethyl sulphoxide, 0.2 g/L BN52021, 1 g/L BN52021 and 5 g/L BN52021, respectively. Cats in Group N were administrated with 0.5 mL of NS. Intraocular pressure (IOP), flash electroretinogram (ERG), and retinal nerve fiber layer (RNFL) thickness were measured. Hematoxylin and eosin (HE) staining and transmission electron microscope (TEM) were detected. RESULTS: No significant difference was observed in IOP levels among groups. Comparing with cats in Group N, those in Group A to E showed significant lower amplitudes of rod a- and b-waves (P < 0.05). Amplitudes of rod a- and b-waves were increased by administration of high concentration of BN52021 (≥ 1 g/L). Moreover, high concentration of BN52021 decreased the RNFL thickness increased by contusion. Axons in RNFL in Group E arranged neatly at 7 days after modeling. CONCLUSIONS: The degenerated axons caused by contusion were repaired by BN52021. The administration of high concentration of (≥ 1 g/L) BN52021 could partially repair retinal function in contused cat eyes.

Allergy-related evidences in relation to serum IgE: data from the China state key laboratory of respiratory disease, 2008-2013.

OBJECTIVE: To investigate the serum total IgE (tIgE) and specific IgE (sIgE) to common allergens among allergic patients in Guangzhou, China. METHODS: 7 085 patients were examined for tIgE and sIgE to 15 allergens, based on the protocols of reversed enzyme allergosorbent test and the sandwich enzyme-linked immunosorbent assay. RESULTS: 3 758 (53.04%) patients tested positive for tIgE, and 4 640 (65.49%) for sIgE. Der pteronyssinus, Der farinae, eggs, and cow's milk were the most common allergens leading to higher positive rates of sIgE responses. Several peaks of sensitization were: Der pteronyssinus, Der farinae, and Blomia tropicalis at age 10-12; cow's milk at age below 3; eggs at age 4-6. The mean level and positive rate of tIgE tended to increase in subjects sensitized to more allergens. Sensitization to Der pteronyssinus (OR, 1.6; P<0.05), Der farinae (OR, 1.5; P<0.05), Blomia tropicalis (OR, 1.4; P<0.05), Blattella germanica (OR, 1.5; P<0.05), cow's milk (OR, 1.3; P<0.05), and soy beans (OR, 2.0; P<0.05) were independently correlated with allergy-related conditions in preliminary diagnosis. CONCLUSION: The major allergens in Guangzhou include Der pteronyssinus, Der farinae, cow's milk, and eggs. Sensitization to these allergens appears to be predictors of allergy-related disorder.

Stem cell-derived conditioned medium for alopecia: A systematic review and meta-analysis.

BACKGROUND: Alopecia is a common and distressing medical condition that has been related to psychiatric disorders. Stem cell-derived conditioned medium (CM), a novel therapy for hair regeneration, has shown effectiveness in several trials. METHODS: This meta-analysis aims to explore the effectiveness of stem cell-derived CM in improving hair growth for patients of alopecia. We prospectively registered this systematic review and meta-analysis in PROSPERO (CRD42023410249). Clinical trials that the enrolled participants suffering from alopecia applied stem cell-derived CM were included. We calculated the mean and standard deviation for the hair density and thickness. RESULTS: Ten clinical trials were included in our analysis. On the basis of eight clinical trials (n = 221), our pooled results indicate that stem cell-derived CM is effective in increasing hair density (mean difference [MD]: 14.93, confidence interval [95% CI]: 10.20-19.67, p < 0.0001) and thickness (MD: 18.67, 95% CI: 2.75-34.59, p < 0.0001) (µm) in patients with alopecia. Moreover, our findings suggest that longer treatment duration is associated with significantly greater improvement than shorter treatment duration (p = 0.02). Three of the included studies were randomized controlled trials (RCTs), and when we specifically analyzed these RCTs; statistical significance could also be observed in terms of hair density (MD: 9.23, 95% CI: 1.79-16.68, p < 0.00001). KEY MESSAGES: Stem cell-derived conditioned medium can effectively increase hair density and thickness for alopecia, and there is no difference between each method (topical application, microneedling, or injection).

Relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage: a prospective observational study.

BACKGROUND: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage. METHODS: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively. RESULTS: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (rs = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization. CONCLUSIONS: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression.

[Mechanism of miR-155 Promoting Drug Resistance in Childhood Acute Lymphoblastic Leukemia by Regulating Wnt/ß-Catenin Signaling Pathway].

OBJECTIVE: To investigate the mechanism of miR-155 promoting drug resistance of children B-ALL to Ara-C by regulating Wnt/ß-Catenin signaling pathway. METHODS: The expression of miR-155 in bone marrow tissue and cell line of B-ALL was detected by PCR. The chemotherapy resistant strain REH/ Ara-C was constructed by using REH cells. REH/ Ara-C cells were transfected with miR-155 inhibitor. The proliferation of REH/Ara-C cells was detected by EdU. The apoptosis of REH/ Ara-C cells was detected by flow cytometry. The drug resistance of REH/Ara-C cells were analyzed by CCK-8 method and colony formation assay. The expression of Wnt/ß-Catenin signaling pathway related proteins were determined by Western blot. MiR-155 inhibitor and Wnt activator agonist were used to transfect REH/Ara-C cells, and their effects on cell proliferation, apoptosis and drug resistance were determined. RESULTS: Compared with normal tissues and cells, the expression level of miR-155 in B-ALL bone marrow tissue/cell line was increased (P<0.05); Compared with drug sensitive B-ALL tissues/cell lines, the expression level of miR-155 in drug resistant B-ALL tissues and cell lines was increased (P<0.05); Inhibition of miR-155 expression decreased the proliferation of REH/Ara-C cells (P<0.05), promoted apoptosis (P<0.05), enhanced the cytotoxicity of Ara-C (P<0.05), and inhibited Wnt/ß-Catenin signaling pathway related protein and MDR1 gene expression (P<0.05), which could be reversed by activating Wnt expression (P<0.05). CONCLUSION: The expression of miR-155 is up-regulated in bone marrow of children with B-ALL, which may be related to the activation of Wnt/ß-Catenin signaling pathway promotes the proliferation of B-ALL cells and inhibits apoptosis, which leads to chemotherapy resistance.

[Establishment of primary liver cancer model in mice].

Objective: Three modeling methods were used to establish a mouse primary liver cancer model, and compared them to find a more optimal modeling method. Methods: Forty 15-day-old C3H/HeN male mice were randomly divided into groups I-IV, 10 mice in each group. Group Ⅰ were not treated; Group Ⅱ were intraperitoneally injected with 25 mg/kg diethylnitrosamine (DEN) once; Group Ⅲ were intraperitoneally injected with 100 mg/kg DEN once; Group Ⅳ were intraperitoneally injected with 25 mg/kg DEN once and followed by another intraperitoneal injection of 100 mg/kg DEN at 42 days of age. The mortality of mice in each group was analyzed. At the 18th week of modeling, blood was collected from eyeballs after anesthesia, and liver was taken from abdominal cavity after neck was broken. The appearance of liver, the number of cancer nodules and the incidence of liver tumor were observed. The histopathological changes of liver were observed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Results: At the 18th week of modeling, compared with the group I, serum levels of ALT and AST in groups II-IV were increased significantly (P＜0.05); The number of cancer nodules and the incidence of tumors in the surviving mice of groups III and IV were also increased significantly (P＜0.05). At the 18th week of modeling, no mice died in both groups I and II, and the incidence of liver cancer was 0%; The incidence of liver cancer in surviving mice in both groups III and IV was 100%, but the mortality rate of mice in group III was as high as 50%, and that in group IV was only 20%. Conclusion: C3H/HeN male mice can successfully establish a mouse liver cancer model by intraperitoneal injection of 25 mg/kg of DEN once at the age of 15 days and another intraperitoneal injection of 100 mg/kg of DEN once at the age of 42 days with short cycle and low mortality, which is an ideal method to establish a primary liver cancer model.

Predictive serum biomarkers of patients with cerebral infarction.

OBJECTIVES: Stroke is the third most common cause of death and also causes seizures and disability. Biomarkers are abnormal signal indicators at the biological level that are present before the organism is seriously affected and are more sensitive to early diagnosis than are traditional imaging methods. Early diagnosis of stroke can prevent the progression of the disease. However, there are currently no widely accepted biomarkers for stroke that have been applied clinically. METHODS: A serum metabonomics method based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used to identify potential biomarkers and metabolic pathways of cerebral infarction. The receiver-operating characteristic (ROC) curve was used to verify the diagnostic and classification abilities of the biomarkers, and a support vector machine (SVM) model was developed for the prediction of cerebral infarction. RESULTS: Principal component analysis revealed a clear separation between the normal and cerebral infarction groups. A total of 13 potential serum biomarkers were identified, which were mainly involved in linoleic acid metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; arachidonic acid metabolism; and fatty acid biosynthesis. The ROC curve analysis showed that the potential biomarkers had high specificity and sensitivity for the diagnosis of cerebral infarction. The SVM model had good diagnostic ability and could accurately distinguish the control group from the cerebral infarction group. DISCUSSION: The metabonomics approach may be a useful bioanalytical method for understanding the pathophysiology of cerebral infarction and may provide an experimental basis for the development of clinical biomarkers for stroke.

Urinary metabonomics study of anti-depressive mechanisms of Millettia speciosa Champ on rats with chronic unpredictable mild stress-induced depression.

As a traditional Chinese medicine (TCM), Millettia speciosa Champ (MSC), exerts a wide range of pharmacological activities. Our research group previously found that MSC has antidepressant effects, but the specific antidepressant mechanisms remain unclear. Therefore, in this study, urine metabolomics based on ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) combined with pharmacodynamics was used to explore the pathogenesis of depression and the antidepressant effects of MSC. The results showed that MSC treatment could significantly improve chronic unpredictable mild stress (CUMS)-induced depression. Urine metabolic showed that the profiles of the CUMS model group were significantly separated from the control group, while the drug-treated groups were closer to the control group, especially the MSC group treated with a 14 g/kg dose of MSC. Furthermore, 9 metabolites, including glutaric acid, L-isoleucine, L-Dopa, sebacic acid, 3-methylhistidine, allantoin, caprylic acid, tryptophol, and 2-phenylethanol glucuronide, were identified as potential biomarkers of depression. Metabolic pathway analysis showed that these potential biomarkers were mainly involved in valine, leucine, and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine degradation, tyrosine metabolism, histidine metabolism, fatty acid biosynthesis, and pentose and glucuronate interconversions. Through Receiver operating characteristic (ROC) analysis and Pearson correlation analysis, the combination of L-isoleucine, sebacic acid, and allantoin, were further screened out as potential pharmacodynamic biomarkers associated with the efficacy of MSC. This study suggests that the integration of metabolomics with pharmacodynamics helps to further understand the pathogenesis of depression and provides novel insight into the efficacy of TCM.

Increased survival in dogs with malignant mammary tumours overexpressing HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene.

The aims of this study were to explore the relationship between clinical outcome and HER-2 protein expression in dogs with malignant mammary tumours after surgery and to determine the sequence of the HER-2 gene. Tissues from 91 dogs diagnosed with malignant mammary tumours, six with benign lesions and two normal mammary glands were analysed for the expression of HER-2 by immunohistochemistry (IHC). Exons 14-18 of the HER-2 gene were amplified by reverse transcriptase polymerase chain reaction and sequenced in 19 tumours with IHC scores >2+; larger coding regions of HER-2 were analysed in five tumours. HER-2 protein overexpression was found in 27/91 (29.7%) of canine malignant mammary tumours. Dogs with HER-2-overexpressing malignant mammary tumours tended to have a higher survival rate than those that expressed a normal level of HER-2 within 2 years of surgery. In 3/19 cases, HER-2 sequences had a single nucleotide polymorphism, T(1725)C, with no change in the amino acid identity (Cys). No other sequence aberration of HER-2 was found.

[The sedative effect of dexmedetomidine in outpatient undergoing dental surgery compared to several sedative drugs:a meta analysis].

PURPOSE: To evaluate the efficacy of dexmedetomidine and midazolam, ketamine or placebo administrated in outpatient dental surgery. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched from inception to October 2017,to find all randomized controlled trials(RCTs) about the sedative effect of dexmedetomidine versus midazolam, ketamine or placebo during outpatient dental surgery. The quality of the studies was evaluated by the method recommended by Cochrane collaboration. Meta analysis was conducted using Review Manager 5.3 software. RESULTS: Twelve clinical trials with 678 patients were included. The results of meta analysis showed that the sedation score of children was lower in group of dexmedetomidine than that of group of normal saline (SMD=-1.73,95%CI:-2.70～-0.77,P=0.0004) and the sedation score of adults was also lower in group of dexmedetomidine than that of group of normal saline(SMD=-2.23,95%CI:-4.39～-0.08,P=0.04).There was no significant difference in sedation satisfaction of children between dexmedetomidine and ketamine(RR=1.14,95%CI:1.00-1.30,P=0.05).Dexmedetomidine provided more satisfactory sedation of children than midazolam(RR=1.38,95%CI:1.15-1.67,P=0.0006),and there was no significant difference in sedation satisfaction of adults between dexmedetomidine and midazolam (RR=1.42,95%CI:0.86-2.33,P=0.17). Moreover,dexmedetomidine provided more satisfactory behavior of children than ketamine (RR=1.19,95%CI:1.03-1.36,P=0.01) and midazolam (RR=1.28,95%CI:1.07-1.54,P=0.008). CONCLUSIONS: Compared with other sedative drugs, dexmedetomidine may be a better choice for moderate sedation during outpatient dental surgery.

[Effect of Sludge Retention Time and pH on the Denitrifying Phosphorus Removal Process].

In this work, the effects of the sludge retention time (SRT, 35, 25, or 15 d) and pH (7.5, 8.0, 8.5) on denitrifying phosphorus removal were investigated using denitrifying phosphorus bacteria (DPBs) enriched in a sequencing batch reactor (SBR). The results indicated that shortening the SRT from 35 d to 25 d resulted in a decrease in the mixed liquor volatile suspended solids (MLVSS) from 2821 to 2301 mg·L-1, while the sludge loading rate (F/M) increased from 0.256 kg·(kg·d)-1to 0.312 kg·(kg·d)-1. Although the quantity of net phosphorus release and net phosphorus uptake decreased at this stage, the rates of anaerobic phosphorus release, anoxic phosphorus absorption, and denitrification reached their highest levels with values of 25.07, 15.92, and 9.45 mg·(g·h)-1, respectively, due to the increased sludge activity. Consequently, the phosphorus content of the sludge increased from 4.78% to 5.33%, and the removal rate of PO43--P was stable at above 95% with an average effluent PO43--P concentration below 0.5 mg·L-1. When the SRT was further shortened to 15 d, the MLVSS decreased to values as low as 1448 mg·L-1, and the proportion of DPBs in the phosphorus accumulating organisms (PAOs) decreased from 82.4% to 65.7%, indicating that the DPBs were gradually washed out from the system due to the excessively short SRT. At this stage, the phosphorus content of sludge decreased to 3.43%, while the rates of phosphorus release, phosphorus absorption, and denitrification also decreased to some extent. When the pH was increased (7.5-8.0), the anaerobic phosphorus release rate and the anoxic phosphorus absorption rate also increased, and reached 25.86 mg·(g·h)-1 and 16.62 mg·(g·h)-1, respectively, at a pH of 8.0. When the pH exceeded 8.0, the phosphorus removal efficiency dropped rapidly, supposedly due to phosphorus chemical precipitation.

[Effect of C/N and Sludge Concentration on the pH-Regulated Nitrosation System].

pH is one of the most important means of control for the realization and stability of the nitrosation system. To study the change rule of pH values of the nitrosation system and the influence of pollution removal and transformation at different pH under the conditions of different C/N (0, 1, 2, 3,4) and sludge concentrations (sludge amount:water content was 1:6, 1:3, 1:1), batch tests were conducted with tapered bottles using sodium acetate as the carbon source and inoculated with mature nitrosation sludge. The results showed that the higher the C/N, the higher the pH increment and the denitrification efficiency at the same sludge concentration. At the same C/N, a higher sludge concentration corresponded to a smaller pH increment but a higher denitrification efficiency. The removal and transformation of carbon and nitrogen was highly correlated with pH changes in the reaction system, and the denitrification and nitrosation reactions were in sequence. Throughout the operational period of the system, as pH increased, the specific organic matter removal rate was 7-16 times as much as when pH decreased. However, as pH decreased, the specific ammonia oxidation rate (SAOR) was 1-20 times that of when pH increased. When pH was less than 6.1, the system lost its ability to oxidize ammonia-nitrogen. The highest removal efficiency of carbon and nitrogen in the system was achieved when C/N was 4. Ammonia transformation 80% COD removal at the three sludge concentrations took 480, 350, and 300 min, respectively. Under different conditions, the proportion of nitrosation in the system remained above 50% and the concentration of NO3--N remained below 5 mg·L-1, which indicated that the system was dominated by nitrosation.

SUN2: A potential therapeutic target in cancer.

The incidence of cancer is increasing at an alarming rate despite recent advances in prevention strategies, diagnostics and therapeutics for various types of cancer. The identification of novel biomarkers to aid in prognosis and treatment for cancer is urgently required. Uncontrolled proliferation and dysregulated apoptosis are characteristics exhibited by cancer cells in the initiation of various types of cancer. Notably, aberrant expression of crucial oncogenes or cancer suppressors is a defining event in cancer occurrence. Research has demonstrated that SAD1/UNC84 domain protein-2 (SUN2) serves a suppressive role in breast cancer, atypical teratoid/rhabdoid tumors and lung cancer progression. Furthermore, SUN2 inhibits cancer cell proliferation, migration and promotes apoptosis. Recent reports have also shown that SUN2 serves prominent roles in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are critical for evading initiation of cancer. Additionally, increasing evidence has demonstrated that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in cancer cells. The focus of the present review is to provide an overview on the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a promising therapeutic target and novel predictive marker in various types of cancer.

The study of neuroprotective effect of ferulic acid based on cell metabolomics.

Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA.

Comparative analysis of the compatibility effects of Danggui-Sini Decoction on a blood stasis syndrome rat model using untargeted metabolomics.

Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM).

MicroRNA-125b protects hyperglycemia-induced, human retinal pigment epithelial cells (RPE) from death by targeting hexokinase 2.

Diabetic retinal disease (DR) is the main cause of visual disability and blindness in adults with diabetes mellitus. Currently, efficient prevention and treatment are still under investigation. MicroRNAs (miRNAs) are groups of short, non-coding RNAs that post-transcriptionally control their target genes' expression through complementary binding to the 3'UTR region. MiRNAs have been reported to play important roles in a variety of physiological and pathophysiological processes. However, the roles of miR-125b in DR are still unclear. In this study, we exposed human retinal pigment epithelial (RPE) cells to high glucose levels to mimic DR progression. Hyperglycemia induced RPE cell death in 1, 3 and 5 days. Meanwhile, we observed that miR-125b expressions were significantly downregulated by the high glucose treatments. We demonstrated elevated cellular glycolysis rates of RPE cells under hyperglycemia. The glycolysis key enzymes, GLUT1, Hexokinase 2 (HK2) and LDHA were upregulated by high glucose. Moreover, treatments of RPE cells with low-toxic dosages of the glycolysis inhibitor, 2-DG or Oxamate, rescued the high glucose-induced cell from death. We identified hexokinase 2 as a direct target of miR-125b in RPE cells by showing the binding of the miR-125b seed region to HK2 mRNA 3'UTR. Notably, we demonstrated that the overexpression of miR-125b significantly attenuated hyperglycemia-induced RPE cell death. This study reveals a new mechanism for miRNA-mediated cellular protection against RPE cell death, representing an effective DR-treatment approach.

[Effects of temporal and spatial variation of canopy structures and light conditions on population characteristics of Fargesia decurvata.] / å† å±‚ç»“æž„å’Œå ‰çŽ¯å¢ƒçš„æ—¶ç©ºå˜åŒ–å¯¹ç´«è€³ç®­ç«¹ç§ç¾¤ç‰¹å¾çš„å½±å“.

The canopy structures and light conditions and the population characteristics of Fargesia decurvata, a dominant understory species, were investigated in three typical communities, i.e., deciduous broad-leaved forest, evergreen and deciduous broad-leaved mixed forest, evergreen broad-leaved forest. The results showed that with the succession from deciduous broad-leaved forest to evergreen and deciduous broad-leaved mixed forest and to evergreen broad-leaved forest, the Shannon index, Simpson index and Pielou index were increased, suggesting that the development of communities in Jinfo Mountains tended to be stable. Moreover, canopy structures were significantly changed, in that the canopy openness and mean leaf angle decreased, leaf area index increased, and canopy extinction ability enhanced, resulting in the decrease of light intensity under the canopy. The upper canopy was the main contributor for canopy closure, with the crown depth and crown area of canopy being the two main influencing factors. Moreover, canopy structures were significantly correlated with light conditions in the forest, with the greatest influence on the diffuse solar radiation. With the growth season coming, canopy openness and understory light conditions were decreased, while leaf area index increased, and their maximum values appeared in June or July in the three forest types. The maximum and minimum value of mean leaf angle appeared in spring and summer, respectively. Clonal growth of F. decurvata was closely related to canopy structures and light conditions. In evergreen and deciduous broad-leaved mixed forest with moderate light, F. decurvata grew best, with high and thick ramets, high ramet density (29.69±1.68 ind·m-2) and high ability to expand rhizomes. In deciduous broad-leaved forest, the strong light condition caused the reduction of soil water might have effects on the growth of F. decurvata. However, in the evergreen broad-leaved forest with low light condition, ramets of F. decurvata tended to be short and thin, with low ramet density (5.80±1.16 ind·m-2) and the clonal expansion ability. Those results suggested that forest succession would change canopy structures and understory light conditions. Low understory light conditions prohibited the regeneration and development of F. decurvata population.

[Effects of Nanoscale Zero-valent Iron (nZVI) on Denitrifying Performance of an Upflow Granular Sludge Bed Reactor].

In order to examine the effects of nanoscale zero-valent iron (nZVI) on the performance of denitrifying granular sludge (DGS) in a continuous flow model, the variations of nitrogen removal efficiency in the reactor, sludge morphology, and denitrifying characteristics at different influent nZVI concentrations were investigated in an upflow sludge bed (USB). The results showed that nZVI concentrations lower than 5 mg·L-1 did not influence the nitrogen removal performance of the reactor significantly, and the activity of DGS was improved slightly. When the influent nZVI concentration was in the range of 5 to 10 mg·L-1, the DGS could adapt to the biological inhibition of nZVI partially, with the increase of sludge concentration and grain size. However, the higher total iron contents in the sludge resulted in the lower denitrifying activity of the DGS. The removal efficiencies of COD and NO3--N in the reactor decreased to 23.3% and 20.3%, respectively, at the influent nZVI concentration of 30 mg·L-1. Moreover, the DGS was a dark color and of a smaller grain size because of the adsorption of a large amount of nZVI, while the microbe density, such as that of the bacillus species, on the granule surface decreased significantly. In the recovery phase, the nitrogen removal performance of the reactor could almost reach its initial level at nZVI=0 mg·L-1 during an operation of 20 days due to the fast growth of heterotrophic microbes on the surface of the DGS.