A study of acupoint specificity and mechanism of electroacupuncture intervention on chronic colitis in rats based on PI3K/AKT/mTOR signaling pathway

Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic experimental colitis in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty pathogen-free SD rats were randomly assigned to six groups:the normal,model,Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)groups,each with 10 rats.Chronic colitis was induced in rats by combining immunization and local stimulation.After model establishment,electrical needle intervention combined with dispersing wave of 2 Hz/50 Hz with a current intensity of 2 mA once daily for 20 min was applied on acupoints of each group.Subsequently,the inflammation of colonic mucosa and serum levels of inflammatory factors(IL-23,IL-17,IL-10)were observed;ELISA was used to detect mRNA expressions of PI3K,Akt and mTOR in colitic tissues by RT-PCR as well as protein content of p-PI3k/PI3K,p-Akt/Akt,and p-mTOR/mTOR in colitic tissues by Western blotting.Result:Compared with the normal group,the model rats showed a poor general condition,serious damage to the colonic mucosa with a large number of inflammatory cells infiltration.The serum IL-23 and IL-17 expressions were significantly increased(P<0.01),while the serum IL-10 expression was significantly decreased(P<0.01);the mRNA and protein expressions of PI3K,Akt,mTOR and p-PI3K,p-Akt and p-mTOR were significantly increased(P<0.05,P<0.01).Compared with the model group,the pathological slices of rats in each acupoints intervention group showed obvious improvement of colitis inflammatory reaction and tissue damage;the serological levels of IL-23 and IL-17 were significantly reduced(P<0.01),while the serology level of IL-10 was significantly increased(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Compared with Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)groups,the recovery degree of mucosa layers in Shang Ju Xu(ST37)group was closer to that of normal group,and the curative effect was relatively the best;in terms of serological levels of IL-23 and IL-17,the Shang Ju Xu(ST37)group was significantly lower(P<0.05),while the level of IL-10 was significantly higher(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Conclusion:Results indicate that electrical acupuncture at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)show similar effects in relieving the colitis-induced damage in the mucosa of chronic colitis rats,as well as inflammatory response.Among them,Shang Ju Xu(ST25)has a superior overall effect in treating chronic colitis compared to Tian Shu(ST25),Da Chang Shu(BL25)and Zu San Li(ST36).The mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway.

Total flavonoids of Scutellaria barbata improving podocyte injury induced by high glucose through Smad4/PKM2/HIF‑1α pathway

Objective: To observe the effect of total flavonoids of Scutellaria barbata (TF‑SB) on the injury of high glucose induced podocytes (MPC‑5) and the influence of Smad4/PKM2/HIF‑1α pathway. Methods: Firstly, CCK8 was used to analyze the safety and efficacy concentration of TF‑SB on MPC‑5 cells. Then, MPC‑5 was then divided into the control group, model group and TF‑SB group. In addition to the control group, model group and TF‑SB group were induced by high glucose to establish MPC‑5 cell injury model. The effects of TF‑SB on ATP, apoptosis and ROS levels of MPC‑5 cells were detected respectively. The contents of IL‑1β, TNF‑α, and MCP‑1 were determined by ELISA, the expression abundance of glycolytic genes (GLU1, PFK1 and HK1) were detected by RT‑PCR. Western blot method was used to detect the expression level of related proteins in Smad4/PKM2/HIF‑1α pathway. Results: Compared with the blank group, ATP content, GLU1, PKF1 and HK1 expression abundance of MPC‑5 cells in the model group decreased significantly, apoptosis, ROS level and IL‑1 β、 TNF‑ α And MCP‑1 significantly increased (P<0.01);Compared with model group, ATP content, GLU1, PKF1 and HK1 expression abundance, apoptosis, ROS level and IL‑1β in TF‑SB group were significantly increased , TNF‑ α The contents of MCP‑1 and MCP‑1 decreased significantly (P<0.01). In addition, compared with the blank group, the model group Smad4 and HIF‑1 α The protein expression and PKM2 expression in nucleus were significantly increased, while PKM2 expression in cytoplasm was significantly decreased (P<0.01);Compared with model group, TF‑SB group Smad4, HIF‑1 α The expression of PKM2 in the nucleus and expression of PKM2 were significantly decreased, while the expression of PKM2 in the cytoplasm was significantly increased (P<0.01). Conclusion: TF‑SB promotes the mitochondrial activity of MPC‑5 cells to induce glycolysis, and then inhibits the secretion of inflammation, which may play a role in treating diabetes nephropathy by inhibiting Smad4/PKM2/HIF‑1α signaling pathway.

Molecular Mechanism of Induction on Apoptosis of Human Esophageal Cancer HCE-4 Cells by Active Components from Astragalus membranaceus

[Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measured by MTT assay. The induction of active components from A. membranaceus on apoptosis of HCE-4 cells was detected by Annexin V-FITC/PI double staining. The apoptotic-related protein expression levels were determined by Western blotting. [Results] Formononetin and astragaloside IV suppressed the proliferation of HCE-4 cells in a dose-dependent manner. The Annexin V-FITC/PI double staining results showed that formononetin and astragaloside IV could induce HCE-4 cells apoptosis in a time-dependent manner. The Western blotting results showed that formononetin and astragaloside IV could significantly down-regulate p-AKT,pro-caspase-3,and increase cle-caspase-3 protein expression in HCE-4 cells. [Conclusions]Active components from A. membranaceus such as formononetin and astragaloside IV significantly inhibited the proliferation of human esophageal cancer HCE-4 cells by inducing mitochondrial dependent apoptosis via AKT signaling pathway.

Proactive Connection Recovery Strategy with Recovery Time Constraint for Survivable Elastic Optical Networks

This paper presents a halfway signaling exchange shared path protection(HSE-SPP)on the backup route for a fast connection recovery strategy.In the proposed HSE-SPP,a pre-assigned intermediate node on the backup route is chosen for signaling exchange.When connection fails,source and destination nodes simultaneously generate backup connection setup messages to the pre-assigned intermediate node on the reserved backup route.At the intermediate node,signaling process occurs,and acknowledgment is generated for data transmission to the respective end nodes.Consequently,connection recovery time by applying HSE-SPP becomes very low.Simulations are performed for network parameters and results are verified with existing strategies.The average recovery time(RT),bandwidth blocking probability(BBP),bandwidth provisioning ratio(BPR),and resource overbuild(RO)ratio of HSE-SPP for ARPANET is 13.54 ms,0.18,3.02,0.55,and for dedicated path protection(DPP)are 13.20 ms,0.56,6.30,3.75 and for shared path protection(SPP)22.19 ms,0.22,3.23,0.70 respectively.Similarly,average RT,BBP,BPR and RO of HSE-SPP for COST239 are8.33 ms,0.04,1.64,0.26,and for DPP 4.23,0.47,3.50,2.04,and for SPP 11.81,0.08,1.66,0.27 respectively.Hence,results of the proposed strategy are better in terms of RT,BBP,BPR,and RO ratio.

Molecular mechanism of Duhuojisheng Decoction in the treatment of knee osteoarthritis based on the network pharmacology

Objective:To explore the molecular mechanism of Duhuojisheng Decoction in the treatment of knee osteoarthritis(KOA).Methods:through tcmsp database and Batman TCM database,the compounds in Duhuo Jisheng decoction,such as Duhuo,sangparasitic,eucommia,Achyranthes bidentata,asarum,Gentiana macrophylla,Poria cocos,cinnamon,Fangfeng,chuanxiong,ginseng,liquorice,angelica,white peony and raw rehmannia,were searched,and their active components and targets were screened The target of KOA was acquired by database;the drug compound target network was constructed by using the software of cycloscape 3.7.2,and PPI network was constructed and analyzed by using string database;go analysis and KEGG enrichment analysis were conducted by using David database(P<0.05).Results:after screening,217 components and 155 targets were obtained for the treatment of KOA;5653 targets were related to koa;79 proteins were related to PPI core network,including INS,IL6,TNF and VEGFA;301 go biological processes and 114 related signal pathways were obtained,including rheumatoid arthritis,osteoclast differentiation,MAPK signal pathway,HIF-1 signal pathway and PI3K Akt signal pathway,TNF signal pathway,etc.Conclusion:Duhuo parasitic decoction may regulate cell proliferation,apoptosis and inflammatory response to treat koa,which is the result of multi-component,multi-target and multi-channel interaction,providing theoretical support for Duhuo parasitic Decoction to treat KOA.

Single-shot incoherent optical processing of microwave signals： opening the path to low cost high performance analog photonics

Incoherent optical processing of microwave signals,where low-coherence broadband light sources are employed instead of costly mode locked lasers,has attracted great interest thanks to its wide applications in microwave photonics filtering[1–3],arbitrary generation[4–6]and analog to digital conversion[7]。

Design for an IO block array in a tile-based FPGA

A design for an IO block array in a tile-based FPGA is presented. Corresponding with the characteristics of the FPGA, each IO cell is composed of a signal path, local routing pool and configurable input/output buffers. Shared programmable registers in the signal path can be configured for the function of JTAG, without specific boundary scan registers/latches, saving layout area. The local routing pool increases the flexibility of routing and the routability of the whole FPGA. An auxiliary power supply is adopted to increase the performance of the IO buffers at different configured IO standards. The organization of the IO block array is described in an architecture description file, from which the array layout can be accomplished through use of an automated layout assembly tool. This design strategy facilitates the design of FPGAs with different capacities or architectures in an FPGA family series. The bond-out schemes of the same FPGA chip in different packages are also considered. The layout is based on SMIC 0.13 μm logic 1P8M salicide 1.2/2.5 V CMOS technology. Our performance is comparable with commercial SRAM-based FPGAs which use a similar process.