Genistein is a naturally occurring compound widely found in leguminous plants and is the primary active ingredient in traditional Chinese medicinal herbs such as Astragalus,Puer-aria lobata(Kudzu),Fagopyrum esculentum(Buckwheat),and Rhodiola.Modern pharmacological research indicates that genistein possesses a variety of biological activities,including anti-inflammatory,antioxidant,antitumor,lipid-lowering,an-tidiabetic,anti-ultraviolet,and neuroprotective effects.There-fore,by summarizing and generalizing the pharmacological ac-tions and mechanisms of genistein,it is hoped to provide a basis for its clinical application and drug development.

Genistein is a naturally occurring compound widely found in leguminous plants and is the primary active ingredient in traditional Chinese medicinal herbs such as Astragalus,Puer-aria lobata(Kudzu),Fagopyrum esculentum(Buckwheat),and Rhodiola.Modern pharmacological research indicates that genistein possesses a variety of biological activities,including anti-inflammatory,antioxidant,antitumor,lipid-lowering,an-tidiabetic,anti-ultraviolet,and neuroprotective effects.There-fore,by summarizing and generalizing the pharmacological ac-tions and mechanisms of genistein,it is hoped to provide a basis for its clinical application and drug development.

Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein δ (CEBPδ) mRNA, miR-3553 and rno-Acad8_0002 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT enhancer binding proteina (CEBPα) mRNA, miR-144-3p, rno-LOC100365958_0001, rno-Usp3_0010 and rno-AC241873_0010 regulate the hepatocytes in G

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein ζ (CEBPO mRNA, miR-136-3p, rno-Crebrf_0009, rno-Slc38a9_0001, rno-LOCl00362999_0001 and rno- Got1_0001 regulate the hepatocytes in G

Objective This study aims to investigate the expression profile and regulatory effect on cell proliferation of circular RNA(circRNA) in rat liver regeneration (LR). Methods CircRNA expression profile during rat LR of 114 rats ' regenerating liver which induced by 2/3 partial hepatectomy was detected by high-throughput sequencing. MiRanda and TargetScan were performed to predict their target microRNA (miRNAs) and mRNAs. Gene Ontology (GO) and IP A were used to analyze the physiological activities and signaling pathways they involved. Cytoscape v3. 0. 2 was used to construct the interaction network. Finally, the candidate key circRNAs were selected by the expression pattern combining with the number and function of target miRNAs. Results 20 878 circRNAs were detected during rat LR, among which 560 of them were differentially expressed, and 126 of them could bind to 117 target miRNAs, which were in turn to regulate 6510 downstream target mRNAs. They were involved in cell proliferation, stress response, substance metabolism and transforming growth factor-β (TGF-β), protein kinase A (PKA), Wnt/beta-catenin signaling pathways. 6 differential expressed circRNAs, including circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_l 1274 and circRNA_ 13559 might play a pivotal role in cell proliferation involved in rat LR by regulating 12 miRNAs and 15 mRNAs. Resultsing they were regarded as the candidate key circRNAs of rat LR. Conclusion 560 circRNAs were differentially expressed in rat LR, among which circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_l 1274 and circRNA_13559 might play a crucial role on cell proliferation involved in rat LR via 12 miRNAs-15 mRNAs axis.

BACKGROUNDBacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism.

METHODSForty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1'10(6), 2'10(6), 3'10(6), and 5'10(6) of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS (3 mg/kg) was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCl. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored: platelets (PLT), fibrinogen (Fib), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), interleukin-1b (IL-1b), creatinine (Cr), alanine aminotransferase (ALT), creatinine kinase-MB (CK-MB), and endothelin (ET).

RESULTSCompared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator (TNF-a, IFN-g, IL-1b), organ indicator (Cr, ALT, and CK-MB), and ET in the experimental groups were much lower (P < 0.05) than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P < 0.05), except the ALT and CK-MB levels (P > 0.05).

CONCLUSIONPre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.

Alanine Transaminase ; metabolism ; Animals ; Blood Coagulation ; drug effects ; Bone Marrow Cells ; cytology ; Creatinine ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Lipopolysaccharides ; pharmacology ; Male ; Mesenchymal Stromal Cells ; cytology ; physiology ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism

Background Bacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection.In recent years,it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines.Here,we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism.Methods Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group.In the treatment groups,0,1×106,2×106,3×106,and 5×106 of BMSCs were injected intravenously for 3 days before LPS injection,while the control group was treated with pure cell culture medium injection.Then,the LPS (3 mg/kg) was injected via the tail vein in the treatment groups,while the control group received 0.9％ NaCl.Blood was withdrawn before and 4 and 8 hours after LPS administration.The following parameters were monitored:platelets (PLT),fibrinogen (Fib),D-dimer (D-D),activated partial thromboplastin time (APTT),prothrombin time (PT),tumor necrosis factor-o (TNF-α),interferon-γ (IFN-γ),interleukin-1β (IL-1β),creatinine (Cr),alanine aminotransferase (ALT),creatinine kinase-MB (CK-MB),and endothelin (ET).Results Compared with the control group,a significant change of coagulation parameters were found in the experimental groups.The plasma level of the inflammatory mediator (TNF-α,IFN-γ,IL-1β),organ indicator (Cr,ALT,and CK-MB),and ET in the experimental groups were much lower (P ＜0.05) than that in the control group.Furthermore,some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P＜0.05),except the ALT and CK-MB levels (P＞0.05).Conclusion Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune ceils and proinflammatory cytokines in LPS-induced DIG rat model.