Efficacy of bioactive compounds of Chaihu () on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway.

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.

The autophagy in ischemic stroke: A regulatory role of non-coding-RNAs.

Ischemic stroke (IS) is a central nervous system neurological disorder ascribed to an acute focal trauma, with high mortality and disability, leading to a heavy burden on family and society. Autophagy is a self-digesting process by which damaged organelles and useless proteins are recycled to maintain cellular homeostasis, and plays a pivotal role in the process of IS. Non-coding RNAs (ncRNAs), mainly contains microRNA, long non-coding RNA and circular RNA, have been extensively investigated on regulation of autophagy in human diseases. Recent studies have implied that ncRNAs-regulating autophagy participates in pathophysiological process of IS, including cell apoptosis, inflammation, oxidative stress, blood-brain barrier damage and glial activation, which indicates that regulating autophagy by ncRNAs may be beneficial for IS treatment. This review summarizes the role of autophagy in IS, as well as focuses on the role of ncRNAs-mediated autophagy in IS, for the development of potential therapeutic strategies in this disease.

The antifibrotic role of natural killer cells in liver fibrosis.

Liver fibrosis is the common pathological change of chronic liver diseases characterized by increased deposition of extracellular matrix and reduced matrix degradation. In response to liver injury caused by a variety of pathogenic agents, such as virus and alcohol, hepatic stellate cells (HSCs) are differentiated into myofibroblast-like cells and produce excessive collagens, thus resulting in fibrogenesis. Natural killer (NK) cells are the essential innate immune cells in the liver and generally control fibrosis by killing activated HSCs. This review briefly describes the fibrogenesis process and the phenotypic features of hepatic NK cells. Besides, it focuses on the antifibrotic mechanisms of NK cells and explores the potential of activating NK cells as a therapeutic strategy for the disease.

Effects of Qishen Erlian Decoction on Serum MMP-1 and TIMP-1 in Liver Fibrosis Model Rats / 中国中医药信息杂志

Objective To investigate the effects of Qishen Erlian Decoction on serum MMP-1 and TIMP-1 levels in thioacetamide (TAA) induced liver fibrosis rats; To discuss its mechanism of action. Methods Liver fibrosis model was created by the TAA gavage method. 120 SD male rats were randomly assigned to control group, model group, colchicine group, Qishen Erlian Decoction low-, medium- and high-dose group (20 in each group). Each medication group was given relevant medicine for gavage. Control group and model group were given the same amount of normal saline for gavage, once a day for 5 weeks. HE staining and Masson trichrome staining were used to observe the pathological changes in liver tissue and liver tissue damage. Biochemistry, radioimmunoassay, and ELISA were used to detect the serum liver function, hepatic fibrosis index, MMP-1 and TIMP-1 levels. Results Compared with the model group, serum ALT, AST, TBIL, γ-GGT, HA, LN, Ⅳ-C and PCⅢ levels, MMP-1 and the ratio of MMP-1/TIMP-1 increased significantly and level of TIMP-1 decreased significantly in Qishen Erlian Decoction groups, with statistical significance (P<0.05, P<0.01). And there is a certain dose-effect relationship, with Qishen Erlian Decoction high-dose group the best effect. Conclusion Qishen Erlian Decoction can improve the liver function and liver fibrosis indexes, regulate the level of MMP-1 and TIMP-1, and prevent the progression of liver fibrosis.

Clinical Study onQishen Erlian Decoction Combined with Entecavir for Patients with Liver Fibrosis of Hepatitis B / 中国中医药信息杂志

Objective To observe the clinical efficacy ofQishen Erlian Decoction combined with entecavir for patients with liver fibrosis of hepatitis B.MethodsTotally 74 patients were divided into treatment group (38 cases) and control group (36 cases). The control group was given entecavir, while treatment group was given Qishen Erlian Decoction combined with entecavir, 48 weeks for 1 course. Entecavir was given to both groups after treatment, and two groups were followed up for 24 weeks. The liver function, DNA-HBV, serum TGF-β1, BMP-7, liver fibrosis indexes and clinical symptom changes of the two groups were observed.Results 3 cases were excluded and 3 cases were lost during follow-up in treatment group; 6 cases were lost during follow-up in the control group. Liver function and HBV-DNA in 12, 24, 36, 48 weeks and 24 weeks in follow-up were significantly lower than those pre-treatment (P<0.01) in the treatment group, and were significantly better than those in the control group (P<0.01). TGF-β1 decreased (P<0.05), BMP-7 increased (P<0.01), and the ratio of TGF-β1/BMP-7 decreased (P<0.01) in both groups after treatment. There was significant difference between the two groups (P<0.05). HA, LN, PCⅢ,Ⅳ-C, and FS decreased significantly in treatment group after treatment and in the follow-up (P<0.01), fatigue, discomfort in liver region, disgust oil and anorexia were improved (P<0.05), the difference was significant compared with control group (P<0.05).Conclusion Qishen Erlian Decoction combined with entecavir can not only protect liver and reduce aminotransferase, but also be antiviral and reverse liver fibrosis.

Diagnostic value of serum ferritin, alpha-fetoprotein and alpha-fetoprotein-L3 alone or in combination for diagnosis of primary hepatic carcinoma / 中华检验医学杂志

Objective To investigate the diagnostic value of serum FER, AFP and AFP-L3 alone or in combination for diagnosis of primary hepatic carcinoma( PHC).Methods This was a case-control study. Serum FER, AFP and AFP-L3 were determined in 212 patients with PHC ( StageⅠ45 cases, StageⅡ78 cases, StageⅢ81 cases, StageⅣ8 cases) , 127 patients with cirrhosis, 101 patients with chronic hepatitis and 98 controls in the Beijing Youan Hospital affiliated to Capital Medical University from January 2014 to December 2014.Levels of FER, AFP and AFP-L3 were measured by chemiluminescence, while serum samples were pre-treatment with affinity adsorption before AFP-L3 detection.FER, AFP and AFP-L3 levels were analyzed using the nonparametric Wilcoxon test among all groups.Diagnostic performance were analyzed among the groups with the three biomarkers independently and combined.Logistic regression, plotted ROC curve and calculated the area under ROC curve ( AUC) were applied to assess the diagnostic value of each index.Results Serum concentration of FER in PHC, cirrhosis, chronic hepatitis groups and healthy controls were 308.45 ( 148.98 -662.80 ) , 151.70 ( 51.44 -507.40 ) , 298.20 ( 157.30 -701.80 ) , 113.50( 54.98-221.38) μg/L, respectively.The concentration of AFP were 48.50(5.25 -748.40), 3.91(1.80-17.53), 4.76 (2.29-30.56), 2.57 (0.93-3.68) μg/L in each group.The serum levels of AFP-L3 in each group were 4.75(0.61-127.95), 0.61 (0.61-2.50), 0.61 (0.61-2.85), 0.61 (0.61-0.61) μg/L.The concentration of FER, AFP and AFP-L3 differs statistically in PHC, cirrhosis, chronic hepatitis group and healthy controls (χ2 =67.66,146.31,119.02,P<0.001).The content of serum FER, AFP and AFP-L3 increased gradually as the stage level aggravating ( StageⅠ-Ⅳ) , there was significant differences among groups (χ2 =21.63,22.68,21.98, P<0.001) .When using one serum marker, FER had the highest sensitivity (75.00%) , while AFP-L3 had the highest specificity (82.52%). While using two serum markers, FER/AFP had the highest sensitivity (89.15%) , FER+AFP-L3 and AFP+AFP-L3 had a higher specificity (86.20%).The combined detection of FER/AFP/AFP-L3 improved the sensitivity of the test to 89.15%, while FER+AFP+AFP-L3 had a specificity of 86.50%.The AUC of combination of FER, AFP and AFP-L3 was 0.803 ±0.019 (95% CI:0.765-0.841), which was higher than the AUC of either FER(0.748 ±0.022,95% CI:0.705-0.790, Z=4.67,P<0.001) and AFP-L3 (0.726 ±0.024,95% CI: 0.679 -0.772, Z=3.64,P<0.001).However, there was no significant difference in AUC between AFP alone ( 0.776 ±0.021, 95% CI: 0.735 -0.818 ) and the combined detection ( Z=1.34, P=0.18 ) .Conclusions FER was a potential marker for PHC diagnosis.The combination of FER, AFP and AFP-L3 has higher value of clinical applications than one of them independently.

The effects of combined general-epidural anaesthesia on perioperative myocardial enzymogram and troponin T of the myocardium in old patients undergoing thoracic surgery / 中国医师进修杂志

Objective To observe the effects of combined generalepidural anesthesia on perioperative myocardial enzymogram and troponin T of the myocardium(cTnT)in old patients undergoing thoracic surgery.Methods Thirty-eight ASAⅠ-Ⅱ patients aged 60～80 years old were randomly divided into two groups.General anesthesia group(group G): anesthesia was induced with fentanly,propofol and vecuronium and maintained with isoflurane,propofol and vecuronium.Combined anesthesia group(group C):general anesthesia was performed as in group G and continuous epidural block with(1.6%) lidocaine was added during operation.Peripheral blood CK,CK-MB,AST,LDH and cTnT were measured before anesthesia,at the end of operation and at 6,24,48 hours after operation.Results Two groups could provide same postoperative analgesia.There was no change for HR,RR and MAP in two groups.Serum CK,AST,LDH and cTnT concentration in group G after operation were significantly higher than those before anesthesia(P