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Copyright of China Brewing is the property of China Brewing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the mechanism by cryptotanshinone regulates the signaling pathway of stromal cell derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) and inhibits hydrogen peroxide induced cell apoptosis of human bone marrow mesenchymal stem cells (BMSCs). Methods: Cultivated human bone marrow mesenchymal stem cells (HBMSCs) in vitro and established an oxidative stress model by H2O2. Divided HBMSC cells into control group (without oxidative stress induction) and model group (500 μmol/L H2O2 induction for 24 hours), low-dose group of cryptotanshinone(10 μmol/L), medium dose group of cryptotanshinone (20 μmol/L), high-dose group of cryptotanshinone(40 μmol/L). Cell activity was detected by Cell Count Kit (CCK-8). Cell apoptosis was detected by flow cytometry detection. Cellular glucose uptake and lactate levels was detected by enzyme linked immunosorbent assay(Elisa) testing. The content of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells were detected by micro method. Cysteine aspartate protease 3(caspase-3), B-lymphoblastoma-2 associated X protein (Bax), B-lymphoblastoma-2 (Bcl-2), expression of SDF-1 and CXCR4 proteins was detected by western blot detection (Western blot). Results: Compared with the control group, the glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression of HBMSC cells in the model group decreased, while the cell apoptosis rate, expression of apoptotic protein caspase-3, Bax, and MDA content increased(P<0.05). Compared with the model group, the low, medium, and high dose groups of cryptotanshinone showed an increase in glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression in HBMSC cells, while the cell apoptosis rate, expression of apoptotic proteins caspase-3, Bax, and MDA content decreased (P<0.05). The differences in various indicators among the low, medium, and high dose groups of cryptotanshinone were statistically significant(P<0.05). Conclusion: Cryptotanshinone may inhibit oxidative stress damage and apoptosis of BMSC induced by hydrogen peroxide by promoting SDF-1/CXCR4 signaling pathway transduction, with high-dose cryptotanshinone having the best effect. [ABSTRACT FROM AUTHOR]

Objective: To analyze and explore the expression of TRIM29 in osteosarcoma and its potential molecular mechanism. E3 ubiquitination ligase TRIM29 is closely related to the malignant growth of tumors. Methods: The expression of TRIM29 gene in osteosarcoma was analyzed by Western blot, IHC and qRT-PCR, CCK8 and EDU were used to detect the value-added level of osteosarcoma cells after downregulation of TRIM29. Further, glucose uptake, lactate production and G6P were used to detect the changes of glycolysis level and analyze the underlying mechanism. A subcutaneous tumor model of BACB/C nude mice was established to observe the effect of downregulation of TRIM29 on the growth of transplanted tumors. Results: qRT-PCR results confirmed that the mRNA expression level of TRIM29 in osteosarcoma tissues was significantly higher than that in normal tissues. Similarly, Western blot and IHC results also confirmed that the protein level of TRIM29 in osteosarcoma tissues was significantly higher. After downregulating the expression of TRIM29 in osteosarcoma cells, CCK-8 and EDU experiments both showed that its value-added ability was weakened, on the contrary, its apoptosis rate was increased. In the G1 phase of cells, its lactate production, glucose consumption, G6P were also correspondingly weakened, and the glycolytic joint rate limiting enzymes HKII, PFKFB3, PKM, LDHAA, GLUT1 and other proteins were also correspondingly reduced. Similarly, in vivo experiments also showed that after downregulating the expression of TRIM29, the weight and growth rate were reduced accordingly. Conclusion: TRIM29 is highly expressed in osteosarcoma cells. After inhibiting the expression of TRIM29 in osteosarcoma cells, its cell proliferation ability and glycolysis level are decreased. TRIM29 inhibits the growth of osteosarcoma cells by restraining the glycolysis level of cells [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of UCP2 inhibitor genipin (GEN) on the proliferation and mitochondrial function of human hypopharyngeal carcinoma FaDu cells. Methods: FaDu cells were treated with different concentrations of GEN for 24 hours and divided into the GEN 0 μmol/L (control) group, the 50 μmol/L group, the 100 μmol/L group, the 200 μmol/L group and the 400 μmol/L group. The CCK-8 method was employed to assess cell proliferation, and the DCFH-DA probe and JC-1 flow cytometry were utilized to measure the impact of GEN on reactive oxygen species (ROS) levels and mitochondrial membrane potential in FaDu cells. Laser confocal microscopy was utilized to observe the effect of GEN on the mitochondrial membrane permeability transition pore (MPTP) in FaDu cells. Spectrophotometry was employed to measure lactate levels in cells, and Western blot analysis was conducted to monitor changes in UCP2 protein expression. Results: In comparison with the control group, GEN significantly inhibited the proliferation activity of FaDu cells (P<0.05, P<0.01), reduced the expression of UCP2 protein in cells (P<0.05), decreased the mitochondrial membrane potential (P<0.05, P<0.01) and lactate content (P<0.001), altered mitochondrial membrane permeability, and increased the levels of ROS in cells (P<0.05, P<0.01). Conclusion: GEN modulates the expression of UCP2 in cells, consequently altering their redox potential and mitochondrial function, thus inhibiting the viability and inducing apoptosis in human nasopharyngeal carcinoma FaDu cells. [ABSTRACT FROM AUTHOR]

Post translational modifications (PTMs) can change the properties of a protein by covalent addition of functional groups to one or more amino acids, and influence almost all aspects of normal cell biology and pathogenesis. Lactylation is a novel identified PTM, and has been found in both histone and non-histone proteins. Since associated with the end product of glycolysis--lactate, lactylation modification could provide a new perspective for understanding the relationship between metabolic reprogramming and epigenetic modifications. Accumulated evidences suggest that lactylation play important roles in tumor progression and links to poor prognosis in clinical studies. Histone lactylation can affect gene expression in tumor cells and immunological cells, further promoting tumor progression and immune suppression. Lactylation on non-histone proteins can also regulate tumor progression and drug resistance. In this review, we aimed to summarize the roles of lactylation in cancer progression, microenvironment interactions and immune suppression, try to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resveratrol is a natural antioxidant extracted from plants. Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation. In this study, the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis. OBJECTIVE: To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats. METHODS: After 1 week of adaptive training, male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group: blank control group, resveratrol group, exercise group, resveratrol + exercise group. Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise. After swimming with a weight of 5% for 1 hour every day, 50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally, 6 days a week, for a total of 6 weeks. Samples were collected 24 hours after the last exercise, and the levels of urea nitrogen, creatine kinase, blood glucose, liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit. The activity of phosphoenolpyruvate carboxykinase was detected by microassay, and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1, cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α. RESULTS AND CONCLUSION: In the exercise group, plasma urea nitrogen and creatine kinase levels of rats were significantly increased (both P < 0.05), liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased (all P < 0.01), and blood glucose and liver glycogen contents were significantly decreased (both P < 0.01). Resveratrol supplementation could effectively improve the above conditions. Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (P < 0.01, P < 0.05), and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue (P < 0.01). The mRNA expression levels of silent information regulator 1, cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased (all P < 0.01), while resveratrol supplementation could significantly increase the gene expression levels of this pathway. To conclude, resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise, and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway, improving rate-limiting enzyme activity, promoting liver gluconeogenesis, and increasing blood glucose and liver glycogen levels. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the predictive value of D-dimer （D-D）, lactic acid, and soluble platelet endothelial adhesion molecule-1（ sPECAM-1） in patients with sepsis-associated disseminated intravascular coagulation （DIC）. Methods According to the prognosis of patients at 28 days, 300 patients with sepsis-related DIC in the ICU of the Affiliated Hospital of Xuzhou Medical University were gathered and split into death and survival groups. The two groups' general statistics, APACHEⅡ score, serum D-D, lactate, and sPECAM-1 levels were compared. The operating characteristic curve （ROC） was used to evaluate the predictive value of serum D-D, lactate, and sPECAM-1 on the poor prognosis of patients with sepsis-related DIC. Results The 28-day mortality rate of patients with sepsis-related DIC was 22%, and the death group had higher APACHEⅡ scores, serum D-D, lactate, and sPECAM-1 levels than the survival group （P < 0.05）. Multivariate logistic regression results showed that serum D-D, lactic acid and sPECAM-1 were risk factors for 28-day death in patients with sepsis-related DIC. The AUC of serum D-D, lactic acid, and sPECAM-1 was 0.863 （95%CI: 0.768 ~ 0.958）, 0.831 （95%CI: 0.734 ~ 0.928）, 0.774 （95%CI: 0.653 ~ 0.896）, respectively. The AUC of the combination of serum D-D, lactic acid and sPECAM-1 was 0.965（ 95%CI: 0.928 ~ 1.000）, with the sensitivity 0.864 and the specificity 0.974, each of which were greater than the individual predictions. Conclusion In patients with sepsis-related DIC, higher serum D-D, lactate, and sPECAM-1 levels were highly correlated with 28-day death. In patients with sepsis-related DIC, higher serum D-D, lactate, and sPECAM-1 levels were highly correlated with 28-day death. The combination of serum D-D, lactate, and sPECAM-1 levels provided a high predictive value for the prognosis of sepsis-related DIC and might be employed in therapeutic treatment. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and purpose: Methyltransferase Wilms’ tumor 1-associating protein (WTAP) has been proven to play an important role in the development of tumors. This study aimed to explore the influence of WTAP on the occurrence and development of glioma from the perspective of N6-methyladenosine (m6A) modification. Methods: The differentially expressed m6A regulators in glioma were screened from GEO database. The expression of WTAP/B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) in glioma tissue and cell lines was evaluated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Methyl thiazoyl terazolium (MTT) was used to explore the effects of WTAP/BMI1 on glioma cell proliferation. Extracellular acidification rate (ECAR) kits and glucose consumption and lactate production detection kits were utilized to detect aerobic glycolysis of glioma cells. Results: Compared with normal tissues, WTQP and BMI1 expressions were upregulated in glioma tissues. Otherwise, compared with WTAP (1.01±0.13) and BMI1 (1.02±0.11) expressions in HEB cells, WTAP (2.38±0.17) and BMI1 (2.25±0.14) expressions in U251 cells were increased (P＜0.05). Downregulation of WTAP inhibited cell proliferation and glycolytic potential in vitro, while overexpression of WTAP showed opposite effects. The effects of WTAP overexpression on glioma cell proliferation and glycolysis were partially rescued by BMI1 inhibition (P＜0.05). WTAP promoted m6A methylation modification of BMI1 and enhanced the stability of BMI1 mRNA (P＜0.05). Conclusion: WTAP upregulates the level of BMI1 in a m6A methylation modification dependent manner, subsequently promotes glioma cell proliferation and aerobic glycolysis. Molecular therapy targeting WTAP may provide a new method for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of China Pulp & Paper is the property of China Pulp & Paper Magazines Publisher and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Supersulfate cement is a kind of resource saving and environmentally friendly cementitious material, but its application is limited because of its low strength in early stage. In order to improve its early strength, the effect of sodium lactate content on the strength of supersulfate cement was studied, the ion concentration, hydration products and microstructure were analyzed by ICP-OES, MIP, XRD and SEM, and the related mechanism was discussed. The results show that the strength of supersulfate cement, especially the early strength, is improved by adding a small amount of sodium lactate, but it is detrimental to the strength when adding too much. Considering the increasing effect of early strength and late strength, the suitable content of sodium lactate is about 0. 25% (mass fraction). The main reason why sodium lactate improves the strength of supersulfate cement is that sodium lactate can promote the dissolution of slag, accelerate the formation of ettringite and C-S-H, and thus improve the microstructure of cement. [ABSTRACT FROM AUTHOR]

Background and purpose: Gastric cancer is one of the most common malignant tumors of digestive system. Previous study demonstrated that circSMARCA5 was downregulated and could function as a tumor suppressor in gastric cancer. However, the molecular mechanism has not yet been documented. This study aimed to investigate the effects of circSMARCA5 on the proliferation and invasion of gastric cancer cells and their molecular mechanisms. Methods: Cell counting kit-8 (CCK-8) assays and transwell assays were performed to examine the cell proliferative and invasive abilities, respectively. The effect of circSMARCA5 on gastric cancer cell glycolysis was assessed by detecting the extracellular acidification rate, glucose uptake level and lactate production. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay was performed to detect the expression levels of circSMARCA5, miR-4295 and PTEN. The levels of GLUT1 and LDHA were measured by Western blot assay. The transplanted xenograft model in nude mice was established, and the effects of circSMARCA5 on the tumor growth were observed. Immunohistochemistry assays were performed to examine the expression levels of GLUT1, LDHA and Ki-67 proliferation index in xenograft tumors. Dual luciferase reporter gene assays, Pearson's correlation analysis and RNA immunoprecipitation (RIP) assays were used to confirm the targeting relationship of circSMARCA5 and miR-4295 as well as miR-4295 and PTEN. Results: CircSMARCA5 overexpression inhibited the proliferation and invasion of gastric cancer cells. Compared to the control group, the glycolysis rate, glycolysis capacity, glucose uptake and lactate production in the circSMARCA5-overexpresing group were significantly decreased. In addition, nude mouse transplanted xenograft assays showed that the volume and the weight of the tumors in the circSMARCA5-overexpressing group were lower compared with the control group. Further studies indicated that circSMARCA5 acted as a molecular sponge to inhibit the expression of miR-4295. Besides, miR-4295 could inhibit the expression of PTEN by binding with the 3'-UTR of PTEN mRNA. Rescue experiments by upregulating miR-4295 or downregulating PTEN expression in the circSMARCA5-overexpressing gastric cancer cells were performed, and the results showed that upregulation of miR-4295 or PTEN knockdown could abolish the inhibitory effects of circSMARCA5 overexpression on cell proliferation, invasion and glycolysis. Conclusion: CircSMARCA5 suppresses the proliferation and invasion of gastric cancer cells by targeting miR-4295, increasing the expression level of PTEN and subsequently regulating glycolysis. [ABSTRACT FROM AUTHOR]

Objective: To investigate which TLR receptors in the TLR family ligand-dependent activation of TLR receptors can cause metabolic reprogramming in gastric cancer cells. Methods: Expression of TLR family members was measured in a panel of human GC cells by real-time quantitative PCR (RT-qPCR) and western blotting (WB). Metabolic changes induced by agonists in human GC cells induced by different TLRs (TLR2, 4, 9) were determined by performing a Seahorse bioenergetic assay and measuring L-lactate and reactive oxygen species (ROS) production; by RT-qPCR in stimulated Expression of genes involved in oxidative phosphorylation and glycolysis was analyzed in GC cells; SOD2 expression was characterized by Western blotting. RESULTS: TLR2 signaling activated by synthetic molecules or holopathogen antigen enhanced glycolytic activity and mitochondrial respiration in gastric cancer cell lines with high TLR2 expression, whereas ligand-induced activation of TLR4 and TLR9 inhibited mitochondrial respiration or extracellular acidification Rate. Meanwhile, genes involved in the regulation of glucose metabolism and redox system, such as HIF1A, PFKFB3 and SOD2, were up-regulated downstream of TLRs. Conclusions: Ligand-induced activation of specific TLRs mediates distinct metabolic phenotypes in human GC cells. TLR2 is the only family member that promotes both OXPHOS and glycolysis, which may contribute to tumor progression. [ABSTRACT FROM AUTHOR]

[Objectives]The purpose of this study was to investigate the effects of chitosan-chelated zinc on cecal microbiota composition, microbial metabolites and inflammatory response in weaned piglets challenged with Escherichia coli K88. [Methods]48 crossbred piglets(average body weight 6.21 kg)weaned at 21 days of age were randomly assigned(4 pens per diet; 3 pigs per pen)to 4 groups:control group(CON, basal diet), high dose zinc oxide group(ZnO, basal diet supplemented with 1 600 mg·kg-1 Zn from ZnO), chitosan-chelated zinc group(CS-Zn, basal diet supplemented with 100 mg·kg-1 Zn and 766 mg·kg-1 chitosan from CS-Zn)and chitosan group(CS, basal diet supplemented with 766 mg·kg-1 chitosan). Piglets were orally challenged with E.coli K88 on 15 days and six piglets from each group were slaughtered 48 hours after infection. The morphology of cecum, the microbiota composition, the concentration of short-chain fatty acids(SCFA)in cecum disgesta, and concentration of cytokines in cecum mucosa were determined. [Results]Compared with the CON group, the cecal crypt depth of piglets in ZnO group and CS-Zn group significantly reduced(P<0.05). The cecal pathological scores of the piglets in the CS-Zn group and the CS group were significantly lower than those of the CON group(P<0.05). Compared with the CON treatment, the relative abundance of Proteobacteria significantly decreased in CS-Zn group. Meanwhile, CS-Zn upregulated the relative abundance of Lactobacillus and Prevotella-9, and down-regulated the relative abundance of Streptococcus and Blautia. In addition, the contents of acetate, butyrate, total short chain fatty acids(SCFA)and lactate in cecal digesta of CS-Zn piglets significantly increased. There were no significant differences in the concentration of butyrate, total SCFA and lactate between CS-Zn and CS group piglets. Furthermore, the level of interleukin-1β(IL-1β), Tumor necrosis factor-α(TNF-α), myeloperoxidase(MPO)and interferon-γ(INF-γ)in the cecal mucosa of CS-Zn group were significantly lower than those of CON group. [Conclusions]Dietary supplementation with CS-Zn could modulate the composition of cecal microbiota, increase the concentration of lactate and SCFA in cecal contents, and reduce the concentration of inflammatory factors in cecal mucosa, which is helpful to alleviating the intestinal inflammatory response in weaned piglets challenged with E.coli K88. [ABSTRACT FROM AUTHOR]

Copyright of China Brewing is the property of China Brewing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of China Brewing is the property of China Brewing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the impact of Pseudomonas aeruginosa (PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P <0.05),down-regulated mRNA level of CDH5( P =0.023),disrupted continuity and down-regulated protein level of VE-cadherin( P <0.001),and elevated lactate level( P =0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5( P =0.043),lowered lactate level( P =0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3( P =0.013 and P =0.003),elevated lactate level( P =0.015),and down-regulated mRNA level of CDH5( P =0.020) and protein level of VE-cadherin( P =0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

Copyright of Clean Coal Technology is the property of Clean Coal Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To analyze the clinical and genetic features of patients with mitochondrial pyruvate carrier deficiency (MPYCD). Methods: This was a case series research. The clinical data, genetic characteristics, and glutamine treatment efficacy of 3 patients diagnosed with MPYCD at the Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, Guizhou Provincial People's Hospital, from August 2019 to June 2023 were retrospectively collected. A literature search with "MPC1 gene" "MPC2 gene and" "mitochondrial pyruvate carrier deficiency" as keywords was conducted at the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CNKI) and PubMed (up to June 2023). Clinical and genetic characteristics of patients with MPYCD were summarized. Results: Case 1 was a 3 years and 11 months old boy, while case 2 was a 4 years and 10 months old boy and case 3 was an 8 years and 9 months old girl. Case 2 and case 3 were siblings from one consanguineous family. All 3 patients presented with general developmental delay, growth failure and elevated serum lactate. Cranial magnetic resonance imaging (MRI) showed subtle bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus in case 1, but normal in case 2 and 3. Trio-WES revealed case 1 harboring compound heterozygous missense variants c.208G>A (p.Ala70Thr) and c.290G>A (p.Arg97Gln) in MPC1 gene, while case 2 and 3 revealed a homozygous variant c.290G>A (p.Arg97Gln) in the same gene. All 3 cases were diagnosecl as MPYCD. Clinical symptoms including motor ability, cognition and activity endurance were improved in these 3 patients after taking glutamine for 2 years. A total of 5 articles published in English were reviewed, and no Chinese literature was found. Including these 3 cases, 15 cases were enrolled for analysis. Eleven patients carried MPC1 gene variants and 4 cases carried MPC2 gene variants. Except for 3 cases died during prenatal period, 9 of 12 enrolled born cases were onset before 6 months old. The most common clinical symptoms were mental and motor general developmental delay, microcephaly, growth failure and hypotonia. All patients had elevated blood lactate and pyruvate, but the ratio of lactate/pyruvate was normal. Seven patients performed cranial MRI, 3 exhibited non-specific changes, 2 showed bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus, and 3 were normal. A total of 5 MPC1 gene missense variants and 2 MPC2 gene variants were identified in 15 cases. Conclusions: Onset age of patients with MPYCD is usually within 6 months. The main clinical characteristics are developmental delay, microcephaly and growth failure, accompanied by increased serum lactate and pyruvate. Glutamine supplement could lead to clinical improvements.

Objective: To study the effect of SIRT3 on the proliferation and oxidation resistance of clear cell renal cell carcinoma (ccRCC) 769-P cells, and to explore its mechanism. Methods: We established SIRT3 overexpressing stable cell line in 769-P cells. The CCK-8 assay was used to measure the proliferation rate of 769-P SIRT3 OE, while flow cytometry was used to determine the level of cellular reactive oxygen species in 769-P SIRT3 OE cells. To explore the mechanism of SIRT3 on 769-P cells by quantitative proteomics and metabonomics. Results: CCK-8 assay showed that SIRT3 overexpression decreased cell proliferation rate. Quantitative proteomics found that SIRT3 overexpression decreased the expression of ALDOA, ALDOA, ENO2, PKM, LDHA, LDHB, which increased the expression of SDHB and CS. Metabolomics found that SIRT3 overexpression decreased the level of PEP, pyruvic acid, lactate, carnitine, which increased the level of isocitric acid and acetyl-CoA. Furthermore, SIRT3 overexpression also increased the expression of SOD2, TXN, GPX4 and GLRX5, which decreased the level of cellular reactive oxygen species and enhanced resistance to oxidative stress. Conclusion: SIRT3 Overexpression inhibits growth of kidney tumor cells via regulating cellular metabolic transformation, while SIRT3 overexpression decreased the level of ROS and enhanced resistance to oxidative stress. [ABSTRACT FROM AUTHOR]

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Objective: To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells., Methods: We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting., Results: Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients ( P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t =36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ 2 =29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC ( P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects ( P < 0.05)., Conclusion: A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.

Objective: To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2, 6-diphosphatase 3 (PFKFB3)., Methods: Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α (TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na + -K + -ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting., Results: Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na + -K + -ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na + -K + -ATPase activity was further decreased (mmol×L -1 ×h -1 : 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na + -K + -ATPase activity was increased (mmol×L -1 ×h -1 : 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved., Conclusions: Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

Objectives: To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF)., Methods: A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group ( n =199), a mild/moderate MAS group ( n =77), and a severe MAS group ( n =19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF., Results: Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score ( P <0.05) and a significantly higher blood lactate level in the umbilical artery ( P <0.05). Compared with the non-MAS group, the severe MAS group had a significantly higher level of interleukin-6 (IL-6) in peripheral blood at 1 hour after birth ( P <0.017). In the severe MAS group, 79% (15/19) of the neonates were born inactive, among whom 13 underwent meconium suctioning, and 100% of the neonates started to receive mechanical ventilation within 24 hours. Peripheral blood IL-6 >39.02 pg/mL and white blood cell count (WBC) >30.345×10 9 /L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF ( P <0.05)., Conclusions: Meconium suctioning cannot completely prevent the onset of severe MAS in neonates with MSAF. The neonates with severe MAS may develop severe respiratory distress and require mechanical ventilation early after birth. Close monitoring of blood lactate in the umbilical artery and peripheral blood IL-6 and WBC at 1 hour after birth may help with early prediction of the development and severity of MAS.

Objective: To investigate the clinical characteristics and risk factors of postoperative atrial fibrillation (POAF) in patients with critical burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, two hundred and twenty-seven critically burned aldult patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University, including 173 males and 54 females, aged 19-83 (43±14) years. The admission years of patients were collected, and the percentage of patients complicated with POAF in each year was calculated. According to whether the patients were complicated with POAF or not, they were divided into POAF group ( n =17) and non-POAF group ( n =210). Following data were collected in patients in POAF group, including operation methods, duration of operation, intraoperative blood loss before occurrence of POAF each time, occurrence time and times of POAF, postoperative body temperature, blood pressure, hemoglobin, blood glucose, blood lactate, sepsis, and electrolyte, and type, duration, and treatment of POAF. General data of patients in the two groups including age, gender, burn reason, total burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sepsis-related organ failure evaluation (SOFA) scores on admission, combined with underlying diseases (hypertension, diabetes, and other types of arrhythmias), and sepsis were collected and analyzed. The mortality and factors influencing the prognosis of patients in the two groups such as mechanical ventilation time, operations times, and burn intensive care unit (BICU) length of stay were also collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test or Kruskal-Wallis H test. The multivariate logistic regression analysis was performed on the general data with statistically significant differences between the two groups, and the independent risk factors influencing the onset of POAF in 227 patients with critical burns were screened. Results: From 2017 to 2021, the percentage of critically burned patients complicated with POAF increased year by year. In POAF group, eschar debridement in limbs was the main surgical procedure prior to POAF complication, with the operation time of (3.5±1.2) h and the intraoperative blood loss volume of (365±148) mL.The POAF occurred 25 times in total in patients of POAF group, mostly within one week after the injury and within 6 hours after the operation with most of these patients having POAF only once. When POAF happened, the patients were often complicated with hypothermia, anemia, hyperglycemia, high blood lactate, sepsis, and electrolyte disturbance, and few patients had complications of hypotension. The POAF lasted (5±3) h, with all being paroxysmal atrial fibrillation, and most of POAF patients were reverted to sinus rhythm after amiodarone intervention. Most patients in the two groups suffered from flame burn, and the gender, age, and SOFA score on admission of patients in the two groups were similar ( P >0.05); the APACHEⅡ score on admission, total burn area, full-thickness burn area, incidence proportion of sepsis, combined with diabetes and hypertension and other types of arrhythmias of patients in POAF group were significantly higher or larger than those in non-POAF group ( t =3.47, with χ 2 values of 7.44, 10.86, 12.63, 14.65, 6.49, and 7.52, respectively, P <0.05 or P <0.01). The full-thickness burn area, combined with other types of arrhythmias, and sepsis were the independent risk factors for POAF in 227 critically burned patients (with odds ratios of 4.45, 0.04, and 3.06, respectively, with 95% confidence intervals of 2.23-8.87, 0.01-0.22, and 1.77-5.30, respectively, P <0.01). Compared with those in non-POAF group, the mechanical ventilation time, BICU length of stay, number of operations, and mortality rate of patients in POAF group were significantly increased ( Z =3.89, Z =2.57, t =3.41, χ 2 =3.72, P <0.05 or P <0.01). Conclusions: POAF is a common postoperative complication in critically burned patients, and the incidence is increasing year by year, which seriously affects the prognosis of patients. The full-thickness burn area together with other types of arrhythmias and sepsis are the high-risk factors for POAF complication in patients with critical burns.

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old( HR =2.14, 95% CI : 1.09 to 4.21, P =0.03), high lactate values 12 hours after CRRT( HR =1.13, 95% CI : 1.06 to 1.20, P =0.01) and postoperative EF<45%( HR =2.21, 95% CI : 1.09 to 4.51, P =0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.

We have investigated theoretical conformational feature of an isolated poly(lactic acid) (PLA) chain involving a racemic unit at the central position. Two polymers were employed, one with the sequence of 25 units of L-lactic acid (1) and one in which the 13th position is substituted by the D-isomer (1-D). In both PLAs, several initial conformers were geometry-optimized with the semi-empirical molecular orbital method. The energy value of each converged structure was re-evaluated with DFT single-point computation. In the optimization of 1 from eight periodic conformers, a "g-t"-helical conformer was found to be the most stable. In the case of 1-D, most of the corresponding eight structures were energetically destabilized or deformed at around the central position. The D-isomer incorporated into the most stable "g-t'-helical conformer of 1 led the whole chain to a triangle-like shape that reduced the edge-to-edge distance by ca. 25%. The present simulation reveals that the introduction of a single heterochiral unit into a long homochiral PLA chain generates large con formational flexibility to vary its physicochemical properties. [ABSTRACT FROM AUTHOR]

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C&#95;(18) column(2.1 mm×100 mm, 1.7 μm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

Escherichia coli was metabolically engineered to produce poly(glycolate-co-lactate-co-3-hydroxybutyrate) using glucose and xylose as carbon sources. The combinatorial biosynthetic route was constructed by the overexpression of a series of enzymes including D-tagatose 3-epimerase, L-fuculokinase, L-fuculose-phosphate aldolase, aldehyde dehydrogenase, propionyl-CoA transferase, β-ketothiolase, acetoacetyl-CoA reductase, and polyhydroxyalkanoate synthase. Overexpression of polyhydroxyalkanoate granule associated protein significantly improved biopolymer synthesis, and the recombinant strain reached 3.73 g/L cell dry weight with 38.72% (W/W) biopolymer content. A co-culture engineering strategy was developed to produce biopolymer from a mixture of glucose and xylose, achieving 4.01 g/L cell dry weight containing 21.54% (W/W) biopolymer. The results of this work offer an approach for simultaneously utilizing glucose and xylose and indicate the potential for future biopolymer production from lignocellulosic biomass.

Objective: To investigate the protective effect and potential mechanism of tanshinol borneol ester (TBE) on homocysteine(Hcy) induced rat bone marrow mesenchymal stem cells (BMSCs) damage. Methods: BMSCs were isolated and cultured in vitro by density gradient centrifugation and adherent culture method. BMSCs were divided into the control (normal isolation and culture), TBE-1(10 μmol/L TBE-1 solution with 100 μl), TBE-2 (10 μmol/L TBE-2 solution with 100 μl), Hcy (0.5 mmol/L Hcy solution with 100 μl), Hcy + TBE-1(0.5 mmol/L Hcy solution with 100 μl, and 10 μmol/L TBE-1 solution with 100 μl), Hcy + TBE-2 (0.5 mmol/L Hcy solution with 100 μl, and 10 μmol/L TBE-2 solution with 100 μl), Hcy+ TBE-1+ inhibitor group(0.5 mmol/L Hcy solution with 100 μl, 10 μmol/L TBE-1 solution with 100 μl, and 25 μmol/L LY294002(specific blocker of phosphatidylinositol 3 kinase) solution with 100 μl), Hcy+ TBE-2+ inhibitor group(0.5 mmol/L Hcy solution with 100 μl, 10 μmol/L TBE-2 solution with 100 μl, and 25 μmol/L LY294002 solution with 100 μl). Cell proliferation activity was detected by MTT assay. The T-SOD activity and malonaldehyde level of cells were measured by anthineoxidase method and TBA method, respectively, to evaluate cell oxidative and antioxidative activities. The ultrastructure of cells was observed under transmission electron microscope. The expression level of PKB and NF-κB of cells in various groups were detected with the immunocytochemical method. Results: (1)Cell proliferation activity in TBE-1 group and TBE-2 group was significantly increased compared with the control group (both P <0.01), and was similar between TBE-1 group and TBE-2 groups after 1, 12, 24 and 48 hours treatment.(2)The T-SOD activity in TBE-1 group and TBE-2 group was significantly higher than in control group (both P <0.01), while it was significantly lower in Hcy group, Hcy+ TBE-1 group, and Hcy+ TBE-2 group than in control group(all P <0.01), and was similar between control group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group(all P >0.05). The T-SOD activity was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P <0.01), and was higher in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group( P <0.05) and was higher in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group( P <0.05). The malonaldehyde level was lower in TBE-1 group and TBE-2 group than in control group(both P <0.01), was higher in Hcy group, Hcy+ TBE-1 group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group(all P <0.01), was lower in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P <0.01), was higher in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group( P <0.05), was higher in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group( P <0.05). (3)Under electron microscope, BMSCs showed profound swelling, senescence and apoptosis of cells increased significantly in Hcy group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group when compared with control group. BMSCs in the TBE-1 and TBE-2 groups presented with abundant rough endoplasmic reticulum, and very active cell metabolism signs. Compared with Hcy group, BMSCs edema, the number of aging and apoptotic cells, and cell injury severity were significantly less in TBE-1+ Hcy group and TBE-2+ Hcy. (4)The PKB level was higher in TBE-1 group and TBE-2 group than in control group(both P <0.01), was lower in Hcy group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group(all P <0.01), was similar between control group and Hcy+ TBE-1 group( P >0.05), was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P <0.05), was lower in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group( P <0.05), and was lower in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group( P <0.05). The NF-κB level was higher in TBE-1 group and TBE-2 group than in control group(both P <0.01), was lower in Hcy group, Hcy+ TBE-1 group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group( P <0.01 or 0.05), was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P <0.05), was lower in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group( P <0.05) and was lower in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group( P <0.05). Conclusion: Tanshinol borneol ester can promote the proliferation of BMSC, and attenuate the homocysteine induced rat BMSCs damage possibly through activation of phosphatidylinositol 3 kinase/PKB signal transduction and its downstream signal pathway protein NF-κB.

Objective: To investigate the organ protective effects and the timing of continuous blood purification (CBP) in the treatment of severe sepsis., Methods: A double-blind randomized controlled trial was conducted. Seventy-four patients with severe sepsis aged between 35 years and 80 years with acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores over 20 admitted to Department of Critical Care Medicine of the First Hospital of Wuhan from January 2013 to January 2015 were enrolled. They were divided into control group (n = 37) and treatment group (n = 37) by random number table method. All patients in these two groups received conventional therapy following the guidelines for management of severe sepsis in 2012. In addition the patients in treatment group received continuous veno-venous hemofiltration (CVVH). The critical score, liver and kidney function indexes, etc., levels of pro-inflammatory cytokines in plasma and ultra filtrate before and 24, 48, and 72 hours after treatment, and the clinical picture 2 weeks after treatment in two groups were observed., Results: APACHE Ⅱ scores, multiple organ dysfunction syndrome (MODS) scores, Murray scores of acute lung injury, and systemic inflammatory response syndrome (SIRS) scores of the patients of the above two groups were gradually declined after the treatment. The levels of white blood cell count (WBC), procalcitonin (PCT), lactate (Lac), tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-8), and endotoxin gradually lowered. Levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine transaminase (ALT) and the oxygenation index (PaO2/FiO2) showed a tendency of lowering. There were statistically significant differences in scores of critical illness, WBC, PCT, Lac, pro-inflammatory cytokine, liver and kidney function indexes, etc. between treatment group and control group 48 hours after treatment (APACHE Ⅱ score: 15.5±4.7 vs. 20.3±5.3, MODS score: 4.6±1.4 vs. 7.3±2.2, Murray score: 1.4±0.5 vs. 1.7±0.6, SIRS score: 2.9±0.8 vs. 3.7±1.0, WBC (×109/L): 1.1±0.5 vs. 1.6±0.5, PCT (μg/L): 26.7±12.0 vs. 32.4±14.1, Lac (mmol/L): 7.6±2.2 vs. 9.3±2.8, TNF-α (μg/L): 96.3±17.4 vs. 153.4±24.2, IL-6 (μg/L): 146.8±20.6 vs. 213.8±29.2, IL-8 (μg/L): 287.1±43.6 vs. 354.5±56.2, endotoxin (kEU/L): 1.4±0.5 vs. 2.6±0.8, BUN (mmol/L): 8.7±3.6 vs. 18.5±6.4, SCr (μmol/L): 143±39 vs. 197±42, ALT (U/L): 141±27 vs. 183±34, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 150.3±45.4 vs. 124.7±32.1, all P < 0.05], and the difference was significant up to 72 hours. In the treatment group, TNF-α, IL-6, IL-8, and endotoxin could be decreased in the filtrate 24 hours and 48 hours after treatment and they correlated with the lowering tendency of their plasma levels. Compared with the control group, CVVH based on conventional treatment of severe sepsis could significantly reduce the incidence of MODS (10.8% vs. 29.7%, χ2 = 4.423, P = 0.038) and mortality (5.4% vs. 13.5%, χ2 = 4.674, P = 0.032), and remarkably shortened the duration of mechanical ventilation (days: 3.1±0.6 vs. 5.3±1.7, t = 2.103, P = 0.045), and the length of intensive care unit (ICU) stay (days: 8.5±1.7 vs. 13.2±2.4, t = 2.245, P = 0.042)., Conclusion: Early CBP can decrease the level of pro-inflammatory cytokines, prevent MODS, and remarkably improve the prognosis of patients with severe sepsis.

Objective: To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides(Aβ) in cerebrospinal fluid in rats., Methods: A total of 80 male Sprague-Dawley rats were randomly divided into solvent control(distilled water) group and low-, medium-, and high-dose aluminum poisoning groups(10, 30, and 90 mg/kg aluminum lactate), with 20 rats in each group, and the poisoning procedure was performed by gavage for 2 months. The Morris water maze test was used to test the rats' learning and memory, Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1(LRP-1) in rats' choroid plexus, and enzyme-linked immunosorbent assay(ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma., Results: The Morris water maze test showed that in the place navigation test, with the increasing training time, the escape latency was significantly shortened in each group and showed significant differences between any two groups(P<0.05). In the spatial probe test, the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43±5.27 s, respectively, which was significantly shorter than that in the control group and the low-dose group(15.81±3.01 s and 13.91±2.17 s)(P<0.05). The numbers of platform crossings in the medium-and high-dose groups were 2.64±1.39 and 1.50±0.76, respectively, which were significantly lower than those in the control group and the low-dose group(4.29±0.914 and 3.56±1.38)(P<0.05). The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid(320.35±84.82 pg/ml and 327.68±67.51 pg/ml), which was significantly higher than that in the control group(203.46±74.36 pg/ml) (P<0.05). The content of Aβ1-42 in plasma showed no significant difference between any two groups(P>0.05), and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups(P>0.05). The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24, P<0.05)., Conclusion: Subchronic aluminum exposure may reduce learning and memory in rats, and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus, suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1, influencing the transportation of Aβ, and leading to the accumulation of Aβ.

Objective: To explore potency material bases of Xuebijing (XBJ) formula, and to analyze its effects at the molecular network level., Methods: Totally 16 sepsis-related targets were selected and classified into three categories such as inflammation, immune, and coagulation referring to biological roles. Then molecular database of chemical compositions in XBJ formula were constructed to explore mutual actions with inflammation, immune, and coagulation targets., Results: Danshen root and safflower, with more effector molecules with immune and coagulation targets, have extensive anticoagulation and anti-inflammation effects. The former 10 molecules with better mutual actions with sepsis targets were sequenced as tryptophane, danshensu, gallic acid, salvianolic acid D, protocatechuic acid, salvianolic acid A, danshensu C, vanillic acid, rosmarinic acid, phenylalanine. There existed two phenomena in XBJ formula as follows. One component had stronger actions with multi-targets, for example, danshensu had actions with 13 targets. Meanwhile, different components acted on the same target protein, for example, 8 molecules acted with MD-2., Conclusion: XBJ formula had certain potential synergistic effects with sepsis targets, which could provide certain referential roles for findina new type anti-septic drugs.

Objective: To establish the HPLC fingerprint of water-soluble components of Salvia miltiorrhiza in Songtao, Guizhou, and to perform simultaneous determination of six components in it, so as to provide analytical method for its quality control., Methods: The analyses were performed on a Phenomenex Luna C18 (2) (250 mm x 4. 6 mm, 5µm) column eluted with 0. 4% formic acid(A) - acetonitrile(B) in a gradient mode. The flow rate was 1. 0 mL/min, column temperature was set at 30 °C., Results: Eleven common peaks were identified form the HPLC fingerprint of Salvia miltiorrhiza from 10 batches, the HPLC fingerprint similarities of 10 batches were not less than 0. 999. The linear ranges of danshensu, protocatechuic aldehyde, caffeic acid, rosmarinic acid, lithospermic acid and salvianolic acid B were 0. 0680 ~ 1. 3583 mg/mL, 0. 0008 ~ 0. 3967 mg/mL, 0. 0005 ~ 0. 2660 mg/mL, 0. 0020 ~ 0. 3992 mg/mL, 0. 0063 ~ 0. 6311 mg/mL and 0. 0097 ~ 1. 9306 mg/mL with r ≥ 0. 9999, respectively. The recovery rates were 100. 84%,102. 44%, 100. 53% ,100. 63%, 100. 83% and 100. 35% with RSD <2. 3%, respectively., Conclusion: The established method is simple, accurate and can provide reference for quality control of Salvia miltiorrhiza.

Objective: To estimate the efficacies of fluid resuscitations as guided by lactate clearance rate (LC) and central venous oxygen saturation (ScvO₂) in patients with septic shock., Methods: 100 patients diagnosed with septic shock from June 2012 to June 2014 in department of critical care medicine of sixteen hospitals were enrolled. They were randomly divided into two groups of study and control (each n = 50). After a diagnosis of sepsis shock, they were treated symptomatically timely and fluid resuscitation was started as early as possible according to the 2008 Guideline for Managing Sepsis & Septic Shock. Central venous pressure (CVP) ≥ 8 mmHg (1 mmHg = 0.133 kPa), mean arterial pressure (MAP) ≥ 65 mmHg, urine output ≥ 0.5 ml × kg⁻¹ × h⁻¹, ScvO₂≥ 70% and LC ≥ 10% (or lactate ≤ 2.0 mmol) served as target values for fluid resuscitation therapy in study group versus CVP ≥ 8 mmHg, MAP ≥ 65 mmHg, urine output ≥ 0.5 ml × kg⁻¹ × h⁻¹ and ScvO₂≥ 70% in control group. The general conditions and clinical characteristics, changes in CVP, MAP, urine output, ScvO₂, lactate level and/or LC before (0 hour) and every hour (1-6 h) after the start of fluid resuscitation and other related outcome indicators were recorded., Results: No significant difference existed in general data. The 28-day mortality was 40% for study group versus 56% for control group. There was no significant inter-group difference (P > 0.05). The time of mechanical ventilation and length of intensive care unit (ICU) stay were lower in study group than those in control group [mechanical ventilation time (11.200 ± 17.069) vs (15.760 ± 14.215), P = 0.150; length of ICU stay (13.240 ± 17.127) vs (23.980 ± 18.298), P = 0.003]. The 28-day mortality was independently associated with LC and ScvO₂reaching target values for fluid resuscitation in study group (χ² = 10.930, P = 0.001) while the 28-day mortality was independently associated with ScvO₂reaching target value for fluid resuscitation in control group (χ² = 6.395, P = 0.011). Among all patients, the 28-day mortality was independently associated with ScvO₂reaching target value for fluid resuscitation (χ² = 14.530, P = 0.000), but not LC (χ² = 1.175, P = 0.278)., Conclusion: A combination of LC and ScvO₂may serve an index in confirming the endpoint of fluid resuscitation for patients with septic shock. Fluid resuscitation therapy under the guidance of LC and ScvO₂is more accurate and reliable than the guidance of ScvO₂alone.

Objective: To explore the mechanism that continuous blood purification (CBP) improve the lung mechanical ventilation parameters, cytokine levels and blood gas analysis results in severe asthma patients, and compare the differences in those parameters between bicarbonate and lactate displacement liquid., Methods: According to the random number table, 26 severe asthma patients were allocated into control group (n=10), bicarbonate group (n=8) and lactate group (n=8). Twenty-four hours treatment with mechanical ventilation (control group), mechanical ventilation + CBP (bicarbonate group) or mechanical ventilation + CBP (lactate group) were conducted respectively. Lung mechanical ventilation parameters, serum cytokine level and blood gas analysis results, arterial blood lactate, and electrolytes level were compared among groups., Results: After 24-hour CBP, the lung mechanical ventilation parameters were improved, cytokine levels were decreased, and pH value and partial pressure of oxygen were improved in bicarbonate group and lactate group. The two kinds of displacement liquid had no influence in arterial partial pressure of oxygen (PaO(2)), arterial blood lactate, and serum electrolytes level. The pH value in lactate group was higher than that in bicarbonate group (7.39±0.05 vs. 7.30±0.01, P<0.01). The arterial partial pressure of carbon dioxide (PaCO(2)) was lower in lactate group than that in bicarbonate group (57.14±5.04 mm Hg vs. 89.00±3.66 mm Hg, P<0.01)., Conclusions: Combine CBP might improve the lung mechanical ventilation parameter, cytokine level and blood gas analysis more quickly in severe asthma treatment. The lactate displacement liquid improves the retention of carbon dioxide more.

Objective: To investigate the biocompatibility of new bone tissue engineering scaffolds, A:D, L-polylactic acid (PDLLA)/polylactic acid-polyethylene glycol-polylactic acid-polylactic acid (PLA-PEG-PLA)/Tricalcium phosphate and B: PDLLA/PLA-PEG-PLA in vivo, compared with PDLLA in repair of a rabbit mandibular body defect., Methods: 24 New Zealand adult rabbits were divided into 4 groups randomly. 15 mm x 6 mm defects were made surgically in the bilateral mandibular bodies and each hemi-mandible was assigned as an experimental unit. The defects were randomly repaired with scaffold materials in each group. Specimens obtained were evaluated with general observation, X-ray, histomorphology and computerized graphical analysis at 2, 4 , 8, 12 weeks after surgery., Results: Compared with PDLLA, the new scaffold materials B showed biocompatibility. At the same time the quantity of new bone produced was much more than that in control group (P<0.05). The new scaffold materials A showed the clear chronic granulomatous inflammation., Conclusion: New scaffold material B had sound biocompatibility. It was much better than PDLLA. So it may be an ideal bone tissue engineering scaffold material. A is not adapted to be used as scaffold material.

To study the rheological properties of sucrose acetate isobutyrate (SAIB) in situ gel and the influencing factors. Measurements of shear stress and viscosity were carried out at different shear rate. The rheological properties of SAIB solution were similar to those of Newtonian fluid. The factors such as the type of solvent, concentration, additive, drug and temperature had effect on the rheological properties. Ethanol was a suitable solvent compared with ethyl lactate and N-methylpyrrolidone (NMP). The solution viscosity of SAIB was reduced from 1.29 to 0.11 Pa x s with only increasing the content of ethanol from 10% to 20%. Polylactic acid (PLA) and risperidone could increase the intermolecular force and viscosity. However, adding 10% (w/w) PLA, the initial release of risperidone was reduced from 20.2% to 3.5%. The solution viscosity reduced significantly by stepping up the temperature. The results obtained support the using of SAIB is satisfactorily injectable in situ gel formulation.

Background & Objective: Biodegradable colloidal nano-micelles is a novel targeting drug delivery and controlled release system, which could prolong the biological half-life and lighten the toxicity of chemotherapeutant, meanwhile, present fine biocompatibility. This study was to prepare the biodegradable 5-fluorouracil (5-FU)/DEX-g-PLA nano-micelles, and investigate their killing effect on hepatocarcinoma cell line HepG2 in vitro and in vivo., Methods: 5-FU/DEX-g-PLA nano-micelles were prepared by 'self-assembly'. Its morphology was observed by transmission electron microscopy. The encapsulating efficiency of 5-FU was determined by ultraviolet spectrophotometry. The in vivo releasing of 5-FU from nano-micelles was investigated by high-performance liquid chromatography (HPLC). The inhibitory effect of 5-FU/DEX-g-PLA on HepG2 cells in vitro was measured by MTT assay., Results: 5-FU/DEX-g-PLA nano-micelles were round or elliptical; the diameter was about 50 nm. The encapsulating efficiency was about 9.3%. The concentration of 5-FU released from 5-FU/DEX-g-PLA nano-micelles was sustained for longer time than that of the naked drug. The in vitro inhibition rate of cell growth was similar in 5-FU/DEX-g-PLA group and naked 5-FU group (58.8% vs. 58.0%, P>0.05); the in vivo inhibition rate of tumor growth was significantly higher in 5-FU/DEX-g-PLA group than in naked 5-FU group (73.1% vs. 57.5%, P<0.05)., Conclusion: 5-FU/DEX-g-PLA nano-micelles can effectively inhibit the growth of HepG2 cells.

Aim: To establish culture procedures of neural stem cells from embryonic rat brain, determine their stem-cell characteristics and observe the effects of several compounds on their proliferation ability., Methods: Firstly, a stem cell culture system was set up from embryonic rat cortex. The cells were identified as neural stem cells through immunocytochemistry, in which antibodies to neural stem cell specific protein and markers of mature neural cells were used. Then, by using MTT assay, the survival rate of neurospheres incubated with various concentrations of ginsenoside Rg1, (-)-clausenamide and salvianolic acid A were observed. Furthermore, the effect of these drugs was measured with 3[H] thymidine incorporation assay., Results: In this study, a culture model of neural stem cell was successfully set up. In this model, primary cells from E16-18 rat cortex were dissected out, and cultured as floating neurospheres. The results of immunocytochemistry showed that nestin was expressed by the majority of cells within the sphere. After growing for 8 days in differentiation medium, cells from a single neurosphere were shown to differentiate into 3 main kinds of neural cells: neurons, astrocytes and oligodendrocytes. MTT assay revealed that the three drugs all enhanced the survival rate of neural stem cells, but 3[H] thymidine incorporation assay suggested that only Rg1 significantly accelerated the proliferation rate., Conclusion: One culture model of neural stem cell was set up successfully. Meanwhile, several drugs were found to increase the proliferation and/or survival rate of neural stem cells. It has been demonstrated that neural stem cells exist in adult mammalian brains. So, these drugs may become promising candidates for the therapy of neurodegenerative diseases; such as Alzheimer's disease and Parkinson's disease.

Pharmacokinetics of levonorgestrel (LNG) in the form of injectable microspheres made of biodegradable co-polymer of polylactic acid and polyglycolic acid(9: 1 PLGA) that contained 17.76% LNG, were tested in rats. Rats were given a single intramuscular injection (im) of LNG microspheres at doses of 20.4, 41.1 and 83.3 mg.kg-1. Six rats were treated with a single im of LNG microcrystals at dose of 35.0 mg.kg-1. Plasma samples obtained before injection and at various time after injection were analyzed for LNG by RIA method. Peak plasma LNG level of 67.66 nmol.L-1 was obtained 4.88 h after im of LNG microcrystals, T1/2 = 5.78 d, MRT = 10.16 d and T < 0.32 nmol.L-1 = 41.50 d. Plasma LNG levels among rats after im of three different doses of LNG microspheres showed similar biphasic changes. Cmax1 (the first phase) were 15.19, 33.61 and 38.55 nmol.L-1; Tp1 were 6, 4.67 and 4.33h; Ctrough were 1.21, 4.36 and 9.06 nmol.L-1; Ttrough were 55, 53.67 and 54.83 d; Cmax2 (the second phase) were 3.80, 9.48 and 19.68 nmol.L-1; Tp2 were 100.49, 102.21 and 89.27 d; AUC were 440.27, 1082.82 and 1931.47 nmol.d.L-1; MRT were 69.23, 65.12 and 63.25 d; T < 0.32 nmol.L-1 were 167.81, 169.73 and 167.23 d after im of LNG microspheres in doses of 20.4, 41.1 and 83.3 mg (LNG).kg-1, respectively. Cmax1, Ctrough, Cmax2 and AUC showed significantly positive correlation with LNG dose, while Tp1, Tp2, Ttrough, MRT and T < 0.32 nmol.L-1 did not.(ABSTRACT TRUNCATED AT 250 WORDS)