[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis.

BACKGROUND: Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis. METHODS: A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described. RESULTS: Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = -2.08, 95% CI (-2.96, -1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups. CONCLUSION: The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.

Lycium barbarum Polysaccharides Regulating miR-181/Bcl-2 Decreased Autophagy of Retinal Pigment Epithelium with Oxidative Stress.

Disturbed structure and dysfunction of the retinal pigment epithelium (RPE) lead to degenerative diseases of the retina. Excessive accumulation of reactive oxygen species (ROS) in the RPE is thought to play an important role in RPE dysfunction and degeneration. Autophagy is a generally low-activity degradation process of cellular components that increases significantly when high levels of oxidative stress are present. Agents with antioxidant properties may decrease autophagy and provide protection against RPE dysfunction and damage caused by ROS. Lycium barbarum polysaccharide (LBP) has been widely studied as an antioxidant and cell-protective agent. Therefore, we designed this study to investigate the effects of LBP, which inhibits miR-181, on autophagy in retinal pigment epithelium (RPE) with oxidative stress in vitro and in vivo. In the current study, we found that the highly expressed miR-181 downregulated the expression of Bcl-2 in hydrogen peroxide- (H2O2-) induced ARPE-19 cells, resulting in an increase in ROS, apoptosis, and autophagy flux. LBP inhibited the expression of miR-181, decreased the levels of ROS, apoptosis, and autophagy flux, and increased cell viability in H2O2-induced ARPE-19 cells, suggesting that LBP provides protection against oxidative damage in ARPE-19 cells. We also found that LBP decreased RPE atrophy and autophagy flux in rd10 mice. Taken together, the results showed that LBP has a protective effect for RPE under oxidative stress by inhibiting miR-181 and affecting the Bcl-2/Beclin1 autophagy signaling pathway.

Gynostemma Glycosides Protect Retinal Ganglion Cells in Rats with Chronic High Intraocular Pressure by Regulating the STAT3/JAK2 Signaling Pathway and Inhibiting Astrocyte and Microglia Activation.

Objective: To observe the protective effect of gynostemma glycosides on retinal ganglion cells in rats with chronically high intraocular pressure. Materials and Methods: A total of 60 rats were randomly divided into group A (the blank group, 10 rats) and chronic high IOP model group (50 rats). The IOP model group (IOP above 22 mmHg) was then randomly divided into an additional 5 groups (10 rats per group): group B (negative control group) treated with normal saline; group C treated with gynostemma glycosides 25 mg/(kg-d); group D treated with gynostemma glycosides 50 mg/(kg-d); group E treated with gynostemma glycosides 100 mg/(kg-d); and group F (positive control group) treated with VitB1 and VitB12. The eyes of each rat were monitored from day 1 to 14 (D1-D14). On day 14, rats were euthanized, after which retinal tissue and optic nerve were examined using real-time PCR, western blot, HE staining, LFB staining, and TUNEL assay. Results: Groups A, C, D, E, and F had significantly lower expression of CD11b, GFAP, Brn3α, and more TUNEL cells than in group B (all P < 0.05). Moreover, the relative expression of STAT3 mRNA and JAK2 (mRNA and protein) in groups A, C, D, E, and F was significantly lower than in group B (P < 0.05), while in group E, the expression was lower than in group D (P < 0.05). Conclusion: Gynostemma glycosides protect retinal ganglion cells in rats with chronically high intraocular pressure possibly associated with the STAT3/JAK2 signaling pathway.

Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis.

Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 µM, respectively, compared to positive control indomethacin (IC50 16.40 µM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 µM: 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 µM).

Sijunzi Decoction Inhibits Stemness by Suppressing ß-Catenin Transcriptional Activity in Gastric Cancer Cells.

OBJECTIVE: To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs). METHODS: MKN74 and MKN45, two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1-5 mg/mL) for indicated time (48 h-14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs stemness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of ß-catenin after SJZD treatment, respectively. RESULTS: SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (P<0.05). Moreover, SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (P<0.05). Mechanistically, SJZD reduced nuclear accumulation and DNA binding activity of ß-catenin (P<0.05), the key regulator for maintaining CSC stemness. CONCLUSION: SJZD inhibits GCSCs by attenuating the transcriptional activity of ß-catenin.

Visualizing the intellectual structure and recent research trends of diabetic retinopathy.

AIM: To analyze the intellectual structure and recent research trends in diabetic retinopathy (DR) and unearth potential knowledge. METHODS: English DR publication included in this study was exported from the Web of Science Core Collection, and Chinese DR publication was exported from China National Knowledge Infrastructure from the establishment time of the database to 2019. CiteSpace and Microsoft Excel were used to visually analyze DR research, including analysis of the number of publications, highly cited publication analysis, spatial distribution analysis, and keyword co-occurrence analysis. RESULTS: A total of 23 795 English studies and 11 577 Chinese studies, including 2089 studies related to traditional Chinese medicine (TCM), were obtained. The data suggested the following: 1) The number of English and Chinese DR publications increased over time, and the growth rate of English publications was relatively fast. 2) The distribution of international scholars and institutions was close, while the distribution was scattered in China. Shanghai Jiao Tong University has the largest number of publications. Tien-Yin Wong was the core author with the largest number of publications. England and the United States are the core of international DR research cooperation. 3) Optical coherence tomography and risk factors are recent international research hot spots and trends. The difference is that TCM is a recent research trend under DR in China. CONCLUSION: DR has drawn an increasing amount of attention worldwide. The focus of research in this field has shifted from tertiary type DR treatment to secondary prevention strategies which focus on the screening and monitoring of disease progression. The advantages of TCM in the prevention of DR have attracted attention, and it is worth incorporating this with Western medicine to address this challenge.

Tripterygium Glycosides Combined with Leflunomide for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To undertake an overview on the overall effects of Tripterygium glycosides (TG) combined with Leflunomide (LEF) for rheumatoid arthritis (RA). METHODS: We searched electronic databases from database establishment time to December 1, 2019. The clinical trial data of TG combined with LEF (trial group) and control group in the treatment of RA were collected. The Cochrane system was used to evaluate the quality of the literature. RevMan 5.3 software was used to conduct a meta-analysis of the eligible studies. RESULTS: A total of 12 randomized controlled trials (RCTs) involving 834 patients with RA were included in this study. The meta-analysis results showed that morning stiffness (mean difference (MD) = -0.29, 95% confidential interval (CI) (-0.45, -0.12), P=0.0005), tender joint count (MD = -1.51, 95% CI (-2.20, -0.83), P=0.0001), swollen joint count (MD = -1.24, 95% CI (-1.59, -0.88), P=0.0001), erythrocyte sedimentation rate (MD = -7.26, 95% CI (-9.92, -4.61), P=0.0001), C-reactive protein (MD = -4.04, 95% CI (-4.93, -3.14), P=0.0001), and rheumatoid factor (MD = -50.88, 95% CI (-72.30, -29.45), P = 0.0001) in the trial groups were lower than those in the control groups. The total effective rate in the trial group was better than that in the control group (risk ratio (RR) = 1.20, 95% CI (1.13, 1.28), P=0.00001). However, there was no significant difference of adverse events (RR = 0.83, 95% CI (0.61, 1.13), P=0.23) while comparing the trial groups with the control groups. CONCLUSION: Our results were found to be superior but limited evidence on the effectiveness of TG combined with LEF in the treatment of RA is available.

miR-223 induces retinal ganglion cells apoptosis and inflammation via decreasing HSP-70 in vitro and in vivo.

PURPOSE: Glaucoma is an eye disease characterized by the loss of peripheral vision, high pressure in the eye, optic nerve damage, and the loss of peripheral vision due to loss of retinal ganglion cells (RGCs). A number of miRNA have been detected in the pathogenesis of glaucoma. The paper was to focus on the miR-223 in RGCs apoptosis and inflammation, and investigated the possible mechanisms in vitro and in vivo. MATERIALS AND METHODS: After miR-223 inhibitor and mimics transfected into RGCs, the expression of miR-223 was detected by QRT-PCR, cell proliferation were performed by CCK-8 and EdU assays, cell apoptosis were measured by flow cytometer and TUNEL assays, apoptosis and inflammation -related proteins were detected by western blot, and whether miR-223 target to HSP-70 was detected by Luciferease reporter assay. Moreover, the effects si-HSP-70 on RGCs or RGCs transfected with miR-223 inhibitor were detected. In vivo study. New Zealand White rabbits (20 females) were used to detect the effect of miR-223 on the rabbit glaucoma model induced by injection of carbomer. RESULTS: CCK-8 and EdU assays demonstrated that miR-223 mimics decreased RGCs proliferation. FITC-Annexin V/PI Apoptosis and TUNEL assays showed that miR-223 mimics induced RGCs apoptosis. Western blot revealed that miR-223 mimics enhanced the expression of relative apoptosis and inflammation factors. Further, we demonstrated that miR-223 could inhibit cell proliferation, induce cell apoptosis as well as inflammation by targeting HSP-70 in RGCs. Moreover, the results were confirmed in rabbit glaucoma model. CONCLUSIONS: In summary, miR-223 plays a vital role in RGCs by regulating HSP-70 expression, and the new therapeutic strategy might potentially contribute to benefit glaucoma treatment.

Astragalus polysaccharide attenuates metabolic memory-triggered ER stress and apoptosis via regulation of miR-204/SIRT1 axis in retinal pigment epithelial cells.

BACKGROUND: 'Metabolic memory' of early hyperglycaemic environment has been frequently suggested in the progression of diabetic retinopathy (DR). Retinal pigment epithelial (RPE) cells are crucial targets for DR initiation following hyperglycaemia. Astragalus polysaccharides (APS) has been long used as a traditional Chinese medicine in treating diabetes. In the present study, the preventive effects and mechanisms of APS on metabolic memory-induced RPE cell death were investigated. METHODS: The expressions of miR-204 and SIRT1 were determined by reverse transcription quantitative PCR (RT-qPCR). Dual luciferase assay was applied to detect the potential targeting effects of miR-204 on SIRT1. SIRT1, ER stress and apoptosis related proteins were monitored using Western blotting. Apoptosis was assessed by TUNEL assay and Annexin V/PI staining followed by flow cytometry analysis. MiR-204 mimics and shSIRT1 were applied for miR-204 overexpression and SIRT1 knockdown, respectively. RESULTS: High glucose exposure induced metabolic memory, which was accompanied with sustained dysregulation of miR-204/SIRT1 axis, high level of ER stress and activation of apoptotic pathway even after replacement with normal glucose. Pre-treatment with APS concentration-dependently reversed miR-204 expression, leading to disinhibition of SIRT1 and alleviation of ER stress-induced apoptosis indicated by decreased levels of p-PERK, p-IRE-1, cleaved-ATF6, Bax, cleaved caspase-12, -9, -3, and increased levels of Bcl-2 and unleaved PARP. The effects of APS on RPE cells were reversed by either miR-204 overexpression or SIRT1 knockdown. CONCLUSIONS: We concluded that APS inhibited ER stress and subsequent apoptosis via regulating miR-204/SIRT1 axis in metabolic memory model of RPE cells.

Yiqi Yangyin Huoxue Method in Treating Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of Yiqi Yangyin Huoxue method in the treatment of diabetic retinopathy (DR) with meta-analysis. METHOD: A randomized controlled trial of Yiqi Yangyin Huoxue method in the treatment of diabetic retinopathy in PubMed, Medline, Cochrane Library, Weipu Journal, China Knowledge Network, and Wanfang database was conducted. Two reviewers independently extracted data and methodological quality assessment. Data analysis was performed using Rev Man 5.3 software for statistical analysis. RESULTS: A total of 10 randomized controlled trials, including 661 patients, were included. The results showed that Yiqi Yangyin Huoxue method could significantly improve the vision [risk ratio (RR)=1.32, 95% confidence interval (CI) (1.18, 1.47), P<0.00001] and change the eye fundus [RR=1.23, 95% CI (1.10, 1.37), P=0.0002], fundus fluorescence angiography (FFA) [RR=1.33, 95% CI (1.11, 1.60), P=0.002], traditional Chinese medicine syndromes [RR=1.31, 95% CI (1.15, 1.49), P<0.0001], and hemorheological parameters [mean difference (MD) =-0.37, 95% CI (-0.41, -0.32), P<0.00001]. CONCLUSION: Yiqi Yangyin Huoxue method showed beneficial effects for DR on improving vision, eye fundus, FFA, TCM syndromes, and hemorheological parameters.

Astragalus polysaccharides suppresses high glucose-induced metabolic memory in retinal pigment epithelial cells through inhibiting mitochondrial dysfunction-induced apoptosis by regulating miR-195.

BACKGROUND: Metabolic memory contributes to the development of diabetic retinopathy (DR), which is the complication of diabetes. But it's still unknown how to prevent the metabolic memory to treat the DR. In our study, we want to examine the function of Astragalus polysaccharides (APS) in the metabolic memory of retinal pigment epithelium (RPE) pretreated with high glucose (HG). METHODS: ARPE-19 and PRPE cells were exposed to HG followed by normal glucose (NG) treatment with or without APS. QPCR was used to examine the levels of miR-195 and Bcl-2. MDA and SOD detection assays were used to examine the oxidative stress level. Western blotting and immunostaining were applied to detect the protein level of mitochondrial damage and apoptotic signaling pathway. Flow cytometry and TUNEL staining were used to analyze cell apoptosis. Luciferase assay was used to examine the direct target of miR-195. RESULTS: APS treatment significantly decreased the expression of miR-195, while increased the expression of Bcl-2 with optimized dosages which were induced by HG treatment, even after replacing the HG with NG. And we found Bcl-2 was the direct target of miR-195. APS alleviated the oxidative stress, mitochondrial damage and cell apoptosis induced by HG and HG + NG treatments in RPE cells via regulating miR-195. Furthermore, we found overexpression of miR-195 abolished the alleviated effects of APS on the HG-treated RPE cells. CONCLUSIONS: APS suppressed high glucose-induced metabolic memory in retinal pigment epithelial cells through inhibiting mitochondrial dysfunction-induced apoptosis by regulating miR-195.

Acidic Preconditioning Protects Against Ischemia-Reperfusion Lung Injury Via Inhibiting the Expression of Matrix Metalloproteinase 9.

BACKGROUND: Acidic preconditioning (APC) has been demonstrated to protect against ischemia-reperfusion (IR)-induced lung injury, which could occur during lung transplantation or cardiopulmonary bypass. However, the pathophysiological mechanisms underlying IR lung injury and APC protection are not completely understood. The key factors responsible for the protective effects of APC are not clear. In this study, bioinformatics was used to predict the potential key factor in IR lung injury and explore the important mediator of the APC protective effect in IR lung injury. METHODS: First, we screened GSE6730, which is related to both lung injury and IR in Gene Expression Omnibus, and STRING was used later to select the genes in GSE6730 needed in the future. Animal models were established and classified to validate the effect of matrix metalloproteinase 9 (MMP-9) on lung injury after IR by adding a selective inhibitor (4-phenoxyphenylsulfonyl) methylthiirane, MMP-9 inhibitor. Next, for better understanding of APC inhibition of the expression of MMP-9 in lung injury, assessment of lung tissues, Western blot analysis, and RNA extraction and reverse transcription quantitative polymerase chain reaction were conducted. RESULTS: MMP-9 was identified to be overexpressed after IR according to the analysis on GSE67370. MMP-9 was an unknown gene in relation to acute lung injury and found to be associated with interleukin (IL)-1B, IL-6, and IL-8. The expressions of these inflammatory factors, including MMP-9, were all elevated in IR. Furthermore, lung injury was ameliorated, and the level of MMP-9 was lower when an MMP-9 inhibitor, (4-phenoxyphenylsulfonyl) methylthiirane, was added. Compared with group IR, APC reversed the ischemia-induced lung injury, and the level of MMP-9 was lower, and the concentrations of IL-1ß, IL-6, and IL-8 were decreased. CONCLUSIONS: Our findings reveal a novel mechanism indicating that IR induces higher expression of MMP-9 in lung injury by increasing the expression of inflammation-related factors. APC might protect against IR lung injury by inhibiting the expression of MMP-9.

LncRNA-MEG3 alleviates high glucose induced inflammation and apoptosis of retina epithelial cells via regulating miR-34a/SIRT1 axis.

BACKGROUND: Diabetic retinopathy (DR) is the serious complication of diabetes, which could lead to blindness. Inflammation and apoptosis are hallmark of DR, but mechanism of their regulation is little known. LncRNA-MEG3 is associated with multiple biological processes including proliferation, apoptosis and inflammation response, and is dramatically decreased in DR. However, the role and underlying mechanism of MEG3 in DR is unclear. This study is aimed to reveal the signaling mechanisms of MEG3 in inflammation and apoptosis of DR. METHODS: ARPE-19 cells were applied for this research. MEG3 was cloned into pcDNA3.1. miR-34a was overexpressed and inhibited by transfecting with mimics and inhibitor, respectively. The expression level was detected by qRT-PCR and western blotting. The targeted regulatory relationship was analyzed by dual luciferase assay. Cytokine secretion, cell viability and apoptosis were detected by ELISA assay, MTT assay and flow cytometry analysis, respectively. RESULTS: High glucose (HG) inhibited MEG3 and SIRT1 expression and enhanced miR-34a expression. MEG3 could promote SIRT1 expression by targeting miR-34a. MEG3 overexpression and miR-34a knockdown could inhibit HG-induced apoptosis and secretion of inflammation cytokines including IL-1ß, IL-6 and TNF-α, but miR-34a overexpression alleviated such effects of MEG3. Furthermore, MEG3 overexpression also inhibited NF-κB signaling pathway and increased Bcl-2/Bax ratio via down-regulating miR-34a. CONCLUSION: MEG3 could alleviate HG-inducing apoptosis and inflammation via inhibiting NF-κB signaling pathway by targeting miR-34a/SIRT1 axis. This finding illustrated the function and mechanism of MEG3 in DR, and MEG3 might serve as potential therapeutic target for DR.

A Brief Review on the Pathological Role of Decreased Blood Flow Affected in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) represents a clinically and genetically heterogeneous disease characterized by progressive photoreceptor loss. In recent years, research has been rarely made in blood flow affected in RP. The specific mechanism of blood flow affected in RP is not completely clear. A number of studies indicated that the decreased blood flow was related to RP. According to clinical observation and treatment experience, Chinese medicine considered that blood stasis runs throughout the RP disease progression, and the blood stasis corresponding to Chinese herbal medicine has a positive effect on the clinical treatment of RP. Therefore, we proposed that the decreased blood flow may participate in the lesion. In this article, we will review the findings on the decreased blood flow affected in RP from the perspective of modern medicine and Chinese medicine.

Effect of Qingguang'an II on expressions of OX42 protein and IL-1ß mRNA of retinal microglia cells of rats with chronic high intraocular pressure.

The study investigated the effects of Qingguang'an II (a Chinese medicinal preparation) on expressions of OX42 protein and interleukin-1ß (IL-1ß) mRNA of retinal microglia cells of rats with chronic high intraocular pressure (IOP). SD rats were randomly divided into 6 groups, that were: A: blank group; B: model group; C: Qingguang'an II low dose group; D: Qingguang'an II medium dose group; E: Qingguang'an II high dose group; F: Yimaikang disket (a Chinese medicinal preparation) group. Experimental rats in B, C, D, E, F groups were established the model of chronic high IOP by cauterizing of superficial scleral vein. Tissues of eyes were obtained after intragastric administration for 2 and 4wk. At the time-point of 2wk, OX42 protein and IL-1ß mRNA in group B were statistically expressed in higher level comparing with other groups (P<0.05). Moreover, at the time-point of 4wk, OX42 protein and IL-1ß mRNA in groups C, D and E were statistically expressed in lower level comparing with group F (P<0.05). Besides, OX42 protein and IL-1ß mRNA in groups C and D were statistically expressed in higher level comparing with group E (P<0.05). OX42 protein and IL-1ß mRNA in groups C and D were expressed in similar level (P>0.05). The study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang'an II at the time-point of 4wk was the better choice.

Identification of potential diagnostic biomarkers of cerebral infarction using gas chromatography-mass spectrometry and chemometrics.

Cerebral infarction (CI) is one of the most common cerebrovascular diseases and remains a major health problem worldwide. In this study, we evaluated the potential diagnostic biomarkers and important relevant metabolic pathways associated with CI. Metabolomics based on gas chromatography-mass spectrometry coupled with the multivariate pattern recognition technique were used to characterize the potential serum metabolic profiles of CI. Forty healthy controls and thirty-three cerebral infarction patients were recruited for the nontargeted global metabolites' study and subsequent targeted fatty acid analysis. Overall, thirty-four endogenous metabolites were found in serum from the untargeted global study, four of which were detected to be significantly different between the CI group and healthy controls, including l-lysine, octadecanoic acid (fatty acid), l-tyrosine and lactic acid. Additionally, fourteen free fatty acids were identified by the subsequent targeted fatty acid analysis, and seven of them were detected to be significantly different between the CI group and healthy controls, which were mainly associated with arachidonic acid metabolism and fatty acid metabolism. Our results suggest several potential diagnostic biomarkers, and serum metabolism research is demonstrated as a powerful tool to explore the pathogenesis of CI.

[Chemical constituents from hypoglycemic active part of Plantaginis Semen].

The chemical constituents of Plantaginis Semen with hypoglycemic effect was investigated in this paper. The previous results of the in vivo hypoglycemic effect showed that 60% ethanol extract of Plantaginis Semen decreased the levels of FBG and improved the glucose tolerance in high fat diet(HFD)-induced diabetic C57BL/6 mice. Then, in the present study, the above potential bioactive extract was separated and purified by silica gel, ODS, Sephadex LH-20 column chromatography, medium pressure liquid chromatography(MPLC)and preparative HPLC. The structures of isolated compounds were identified by physicochemical properties and spectral analyses. Eight compounds were obtained and identified as 4, 4a, 5, 7a-tetrahydro-7-(hydroxymethyl)cyclopenta[c]pyran-3(1H)-one(1), iridolactone(2), pedicularislacton(3), rehmaglutin C(4), geniposidic acid(5), p-hydroxylphenylglycerol(6), 1, 2-benzenediol-4-(2-hydroxyethyl)(7), and 3-buten-2-one-4-[3-(ß-D-glucopyranosyloxy)-4-hydroxyphenyl](8). Among them, compounds 1-5 were iridoids, and 6-8 were phenolic acids. Compound 1 was a new natural product, and compounds 2-4, 6 and 8 were isolated from the Plantaginaceae family for the first time.

Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles.

Acute pancreatitis (AP) is defined as an acute inflammation of pancreas that may cause damage to other tissues and organs depending upon the severity of symptoms. The diagnosis of AP is usually made by detection of raised circulating pancreatic enzyme levels, but there are occasional false positive and false negative diagnoses and such tests are often normal in delayed presentations. More accurate biomarkers would help in such situations. In this study, the global metabolites' changes of AP patients (APP) were profiled by using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition techniques were used to establish the classification models to distinguish APP from healthy participants (HP). Some significant metabolites including 3-hydroxybutyric acid, phosphoric acid, glycerol, citric acid, d-galactose, d-mannose, d-glucose, hexadecanoic acid and serotonin were selected as potential biomarkers for helping clinical diagnosis of AP. Furthermore, the metabolite changes in APP with severe and mild symptoms were also analyzed. Based on the selected biomarkers, some relevant pathways were also identified. Our results suggested that GC-MS based serum metabolomics method can be used in the clinical diagnosis of AP by profiling potential biomarkers.

Research progress of stem cells on glaucomatous optic nerve injury.

Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.