Panax notoginseng saponin Rl attenuates allergic rhinitis through AMPK/DRP1 mediated mitochondrial fission / 中国药理学通报

Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Polydatin alleviates allergic rhinitis by regulating PINK1-Parkin-mediated mitophagy / 中国药理学通报

Objective To investigate the protective effect and mechanism of polydatin ( PD) on allergic rhinitis (AH) by regulating mitophagy through PINK1- Parkin signaling pathway, and to provide a new target for clinical treatment of AH.Methods Thirty-two BALB/c murine were randomly divided into 4 groups: control group, OVA group, PD low-dose (30 mg • kg 1 ) and high-dose ( 45 mg • kg 1 ) treatment groups.At the end of modeling, the total number of sneezing and nasal nibbing of murine was recorded.HE staining was used to observe the morphology of na- sal mucosal epithelium and eosinophil infiltration.Western blot was used to detect the expression of P1NK1 , Parkin, TOM20 and mitochondrial apoptosis- related proteins Bax, Bcl-2, caspase-3, cleaved- caspase-3 and Cytochrome C.Hie expression of P1NK1 and cleaved-caspase-3 in nasal epithelial cells (HNEpC) was observed by immunofluorescence.Re¬sults The frequency of sneezing and nasal rubbing movements was significantly increased, the nasal mu¬cosa epithelium was thickened, and eosinophils were accumulated in AH murine , these results were reversed after PD treatment.Western blot results shower] that signaling proteins PINK1/Parkin anrl pro-apoptotie pro¬teins, including Bax, caspase-3, cleaved-caspase-3 and Cytochrome C were significantly overexpressed, the expression of TOM20 and Bcl-2 was decreased in OVA group, and PD up-regulated the levels of P1NK1 , Parkin, as well as Bcl-2 and inhibited the expression of TDM20 and pro-apoptotic proteins, while after pre- treatment with mitochondrial division inhibitor 1 ( Mdi- vi-1 ) , the expression of P1NK1 and Parkin was re¬duced , the expression of TOM20 was increased, while PD treatment did not significantly affect this effect.From the immunofluorescence results, it can be seen that the level of P1NK1 was increased after IL-13 stim¬ulation of HNEpCs compared with the control group, and PD further up-regulated the expression of P1NK1 , which was suppressed after pretreatment with Mdivi-1 , while PD did not change this phenomenon.Western blot results for P1NK1 and cleaved-caspase-3 were con¬firmed by immunofluorescence.Conclusion PD may activate mitophagy through the P1NK1 -Parkin signaling pathway, thereby protecting against AR.

Effects of the composite of buckwheat-oat-pea on blood glucose in diabetic rats / 北京大学学报(医学版)

OBJECTIVE@#To study the effects of buckwheat-oat-pea (BOP) composite flour [buckwheat ∶ oats ∶ peas=6 ∶ 1 ∶ 1 (quality ratio)] on blood glucose in diabetic rats.@*METHODS@#In this study, 64 male Sprague-Dawley rats were divided into 8 groups by fasting blood glucose (FBG) and body weight: normal control group, model control group, metformin group, buckwheat group, oats group, BOP low-dose group (BOP-L), medium-dose group (BOP-M), and high-dose group (BOP-H). The rats in the normal control group were fed with normal diet, the rats in the model control group and metformin group were fed with a high-fat diet (HFD), and the rats in the buckwheat group, oats group, and BOP-L, BOP-M, BOP-H groups were fed with HFD containing 10% buckwheat flour, 10% oat flour, 3.3% BOP, 10% BOP, 30% BOP, respectively. The HFD in all the groups had the same percentage of energy from fat (45%). After 30 days, the rats fed with HFD received intraperitoneal injection of streptozotocin (30 mg/kg, once a week for two weeks) to establish diabetes mellitus. After the model was successful established, the rats were fed for another 28 days. During the study, the body weight, food intake/body weight (FI/BW) and water intake/body weight (WI/BW), food utilization rate, 24 h urine volume, FBG, glucose area under curve (GAUC) of oral glucose tolerance test were measured regularly. At the end of the study, the fasting serum glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.@*RESULTS@#With the inducing of HFD and streptozotocin, compared with the normal control group, the rats in the model control group had higher FI/BW, WI/BW, 24 h urine volume, FBG, GAUC, HOMA-IR (P < 0.05), and lower body weight, food utilization rate (P < 0.05). Compared with the model control group, the rats in the three BOP groups all had higher body weight, food utilization rate (P < 0.05), and lower WI/BW, HOMA-IR (P < 0.05); the rats in the BOP-L and BOP-M groups had lower FI/BW, 24 h urine volume, FBG (P < 0.05), and the rats in the BOP-M group also had lower GAUC (P < 0.05). After the establishment of diabetes, there was no significant difference in blood glucose and the other indicators between the rats in the three BOP groups and the buckwheat group or the oats group (P>0.05).@*CONCLUSION@#The BOP had the effects of reducing blood glucose, insulin resistance and diabetic symptoms on diabetic rats, and had the value for further development and utilization.

Effect of Bmi-1 on Multidrug Resistance in K562/ADR Cells and Its Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Bmi-1 gene silencing on drug resistance of leukemia cell K562/ADR and to explore its possible mechanism.@*METHODS@#After two sequences of Bmi-1-siRNA were transfected into drug-resistant K562/ADR cells, the mRNA and protein expressions of Bmi-1 gene were detected. After Bmi-1 gene silencing the expression of P-gp and MDR1 were detected and the accumulation of doxorubicin in K562/ADR cells were detected by flow cytometry to determine the effect of Bmi-1 gene silencing on drug resistance of K562/ADR cells. The protein expression of NF-κB was analyzed after Bmi-1 gene silencing. Then after K562/ADR cells were treated with NF-κB inhibitor PDTC, the protein expression of P-gp and its functional changes were analyzed to determine the effect of NF-κB on drug resistance of leukemia cells. The protein expressions of PTEN, AKT and p-AKT after Bmi-1 gene silencing were detected and the effect of Bmi-1 gene silencing on PTEN/PI3K/AKT signaling pathway in drug-resistant cells was determined. After K562/ADR cells were treated with PI3K/AKT pathway inhibitor LY294002, the protein expressions of NF-κB and P-gp were analyzed to determine the regulation of AKT on the expression of NF-κB and P-gp. The protein expressions of AKT, p-AKT, NF-κB and P-gp were detected after the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV. Above-mentioned expression of mRNA was detected by RT-PCR, and the protein expression was detected by Western blot.@*RESULTS@#The expression of Bmi-1 gene in K562/ADR cells decreased at both mRNA and protein levels and the doxorubicin accumulation increased after Bmi-1 gene silencing. The expression of MDR1/P-gp in Bmi-1-siRNA transfected cells was lower than that in K562/ADR cells (P＜0.05). After Bmi-1 gene silencing, the activity of NF-κB decreased. The activity of NF-κB and P-gp expression was inhibited and the function of P-gp in K562/ADR cells was reduced by using NF-κB inhibitor (PDTC). The protein expression of PTEN increased while the protein expression of p-AKT decreased after Bmi-1 gene silencing (P＜0.05). The protein expressions of p-AKT, P-gp and the activity of NF-κB were inhibited significantly by using PI3K/AKT inhibitor LY294002 (P＜0.05). After the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV, the activity of NF-κB and the protein expressions of P-gp were restored.@*CONCLUSION@#Bmi-1 plays a key role in MDR-mediated multidrug resistance in K562/ADR cells, which may be mediated by activating PTEN/AKT pathway to regulate NF-κB.

Progress of mechanism and therapy on cerebral vasospasm after subarachnoid hemorrhage / 解剖学报

Subarachnoid hemorrhage (SAH) accounts for about 5% of all stroke patients, with high disability and mortality. Secondary cerebral vasospasm (CVS) after SAH interrupts cerebral blood flow to important parts of the brain, and then causes cerebral ischemia, which is one of the major complications of the disability and mortality. CVS usually occurring 3 to 12 days after SAH and lasted for an average of two weeks. The mechanism of CVS after SAH is very complex, and it is a process involving multiple factors and links, including hemolysis products, imbalance of vasodilator and vasoconstrictors, inflammation, activation of signal cascade reaction, apoptosis and expression of related genes. The treatment of CVS after SAH is divided into interventional therapy and drug therapy. Effective prediction, prevention, and treatment of CVS will significantly improve survival and quality of life after SAH. This article briefly reviews progress of the research on the mechanism and treatment of cerebral vasospasm after SAH.

Clinical Analysis and Echocardiographic Evaluation of Paravalvular Leaks After Surgical Aortic Valve Replacement / 中国循环杂志

Objectives: To explore the clinical features and the value of echocardiographic examination of paravalvular leaks after surgical aortic valve replacement. Methods: A total of 123 patients (aged from 12-74 [mean age 45 ± 13] years) hospitalized in our hospital from 2002-03 to 2017-03 because of paravalvular leaks after surgical aortic valve replacement were included in this study. The first operation was performed in our hospital or other hospitals. All patients had a confirmed diagnosis of paravalvular leaks by transthoracic or transesophageal echocardiography. Among them, 28 cases received non-surgical treatment and paravalvular leaks were corrected by reoperation in 95 cases. Results: Diastolic paravalvular regurgitation was detected by color doppler echocardiography in most patients, and dehiscence between the artificial valve and adjacent tissue was evidenced by two-dimensional echocardiography in some patients. The causes of paravalvular leaks, defined by imaging modalities including echocardiography, operative findings and pathological results included: infective endocarditis in 45 patients, Bechet's syndrome in 23 patients, Takayasu arteritis in 4 patients, suspected diagnosis of immune system diseases in 5 patients, aortic dissection in 2 patients, suspected operative technical reasons in 3 patients, and unknown in 41 patients. There were 13 deaths in this cohort, 5 patients gave up the further treatment and self-discharged due to the serious disease conditions. During follow-up, mild degree or above paravalvular leaks were found in 27 patients, 1 patient suffered from heart failure, improvement or recovery were seen in 55 patients.Conclusions: The paravalvular leaks with significant clinical consequence is an important complication after surgical aortic valve replacement, and most patients need to be treated with reoperation. Despite reoperation, the recurrence rate remains high and the prognosis is poor. Infective endocarditis is the most common cause of paravalvular leaks in prosthetic aortic valves, followed by non-specific vasculitis. Echocardiography plays an important role on diagnosis and monitoring in these patients.

Theory and research of dryness in traditional Chinese medicine / 中国中药杂志

Dryness is the inherent performance in traditional Chinese medicine. Dryness with a specific efficacy and side effect can be reduced suitably by processing and compatibility in the clinical application. Nowadays domestic scholars have developed research of dryness in traditional Chinese medicine. However, it remains problems such as evaluation index of dryness not clear. This paper takes medical literature mining technology to analyze the historical origin and features of dryness theory. Combing the modern literatures to explicate the dryness' research status and existing problems. Putting forward the traditional Chinese medicine and research should adopt multidisciplinary knowledge and study the system of comprehensive evaluation. Dryness is expected to further application in traditional Chinese medicine clinical research.

A accurate identification method for Chinese materia medica--systematic identification of Chinese materia medica / 中国中药杂志

This paper put forward a more accurate identification method for identification of Chinese materia medica (CMM), the systematic identification of Chinese materia medica (SICMM) , which might solve difficulties in CMM identification used the ordinary traditional ways. Concepts, mechanisms and methods of SICMM were systematically introduced and possibility was proved by experiments. The establishment of SICMM will solve problems in identification of Chinese materia medica not only in phenotypic characters like the mnorphous, microstructure, chemical constituents, but also further discovery evolution and classification of species, subspecies and population in medical plants. The establishment of SICMM will improve the development of identification of CMM and create a more extensive study space.