Metabolomic analysis of biochemical changes in the tissue and urine of proteoglycan-induced spondylitis in mice after treatment with moxibustion

Xiao Xu,Ya-Nan Shi,Rong-Yun Wang,Cai-Yan Ding,Xiao Zhou,Yu-Fei Zhang,Zhi-Ling Sun,Zhi-Qin Sun,Qiu-Hua Sun 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.1

Background: Moxibustion is widely used in East Asian countries to manage the symptom of rheumatic diseases. The aim of this study was to identify potential metabolic profiles of moxibustion on relieving ankylosing spondylitis (AS) mice through UHPLC-Q-TOF/MS metabolomic study. Methods: Thirty-two female Balb/c mice were randomized into healthy control (HC), AS model, moxibustion at acupuncture points (MA) in AS model, and moxibustion at non-acupuncture points (MNA) AS model groups. Moxibustion was administered daily at GV4, bilateral BL23 and bilateral ST36 acupuncture points for four weeks in the MA group. The overall health status, the thickness of hind paws and the tissue concentrations of IL-1β, PGE2, IL-6 and TNF-α were assessed. The UHPLC-Q-TOF/MS was used to explore the perturbations of endogenous metabolites in tissue and urine of AS model mice intervened by moxibustion. Results: Compared with the AS group, the overall health status was significantly improved after 4-week moxibustion intervention (p < 0.05). The results also showed that MA significantly reduced the levels of paw thickness and decreased the levels of four cytokines in the tissue (p < 0.01). Thirty-seven endogenous metabolites identified by the OPLS-DA were considered to be contributing to therapeutic effects of moxibustion. Moreover, metabolic pathway analysis further revealed that the identified metabolites were mainly involved in TCA cycle, Lipid metabolism, Amino Acid metabolism, Intestinal flora metabolism and Purine metabolism. Conclusions: UHPLC-Q-TOF/MS based metabolomics approach, as a novel and powerful tool, can help us to gain the insights into potential mechanisms of action of moxibustion for AS.

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

Lingjiang Sun,Dandan Ji,Feng Zhi,Yu Fang,Zigang Zhu,Tong Ni,Qin Zhu,Jie Bao 연세대학교의과대학 2022 Yonsei medical journal Vol.63 No.4

Purpose: Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species(ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40)in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion(I/R) injury. Materials and Methods: A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemiain vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation(OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. Therelationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays. Results: Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p wasverified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reversethe effects of miR-494-3p overexpression on ROS production and cell apoptosis. Conclusion: MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.

Robust Experimental Study of Data-driven Optimal Control for an Underactuated Rotary Flexible Joint

Ying Xin,Zhi-Chang Qin,Jian-Qiao Sun 제어·로봇·시스템학회 2020 International Journal of Control, Automation, and Vol.18 No.5

As an important component of industrial robot, the motion control of rotary flexible joint (RFJ) system is of great significance, especially when the system has unmodeled dynamics or is seriously disturbed. This paper presents an experimental robustness study on a kind data-driven optimal control approach based on an underactuated rotary flexible joint system. The data-driven approach combines the off-policy optimal control algorithm and the popular integral reinforcement learning technique. Through literature review, we find that the key step of the control design lies in that it learns the optimal value function and control policy simultaneously from the input and output (I/O) data. However, the I/O data are often disturbed by the system uncertainty or environmental noise, and then it will indirectly affect the optimal control performance. To investigate the robustness of the data-driven optimal control approach, we artificially set different experimental scenarios and take numerous control experiments on a RFJ experimental setup. The experimental results show that the data-driven optimal control method is quite robust against the system uncertainties in terms of maintaining the stability and delivering satisfactory tracking performance, even when the uncertainty is not a small quantity. In addition, the disturbance originating from environmental noise has certain impact on the controlling of RFJ system, but as long as the noise power is not too large, the control algorithm can converge to a satisfactory result. Finally, we find that the probing signal up has strong influence to this control algorithm, which reminds us to be cautious when selecting the probing signal.

A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways

( Lin Ye ),( Yang Xin ),( Zhi-yuan Wu ),( Hai-jian Sun ),( De-jian Huang ),( Zhi-qin Sun ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.1

Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

Deformation Feature of Sheet Metals During Inclined Hole-Flanging by Two-Point Incremental Forming

Xia Chen,Tong Wen,Jian Qin,Jin Hu,Meng Zhang,Zhi-sun Zhang 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.2

Incremental hole-flanging is an applicable extension of incremental sheet forming (ISF), but the knowledge on the deformation of metallic sheets during the course is lack, especially when the axes of the flanged necks are not perpendicular to the sheet plane. The current study used Al 6061 and SUS 304 stainless steel sheets with the thickness of 1 mm and 0.3 mm to examine the inclined hole-flanging processes on the flat plates by two-point ISF processes. It was found that, although as a whole the thickness variation is thinning, the decreasing degrees within upper and lower domain are not equal, and the difference increases with the inclination angle. Crack, buckling and local deformity are typical defects found in the experiments. The maximum springback increases with tool diameter, inclination angle and feeding pitch. Due to the material properties and a thinner thickness, local deformity is easier to take place on SUS 304 sheets during forming. Utilizing the tool feeding path along the oblique plane can obtain even force and consequently, more uniform deformation. Moreover, the equations for preliminarily determining the dimension of precut holes were derived according to the radial developed length of the flanged neck.

Disruption of the F-actin Cytoskeleton and Monolayer Barrier Integrity Induced by PAF and the Protective Effect of ITF on Intestinal Epithelium

Ling-fen Xu,Cheng Xu,Zhi-Qin Mao,Xu Teng,Li Ma,Mei Sun 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.2

To explore whether platelet-activating factor (PAF) can disrupt the intestinal epithelial barrier directly and is associated with structural alterations of the F-actin-based cytoskeleton, and to observe the protective effect of intestinal trefoil factor (ITF), we establish an intestinal epithelia barrier model using Caco-2 cells in vitro. Transepithelial electrical resistance and unidirectional flux of lucifer yellow were measured to evaluate barrier permeability; immunofluorescent staining and flow cytometry were applied to observe morphological alterations and to quantify proteins of the F-actin cytoskeleton: the tight junction marker ZO-1 and Claudin-1 were observed using immunofluorescent staining. PAF significantly increased paracellular permeability, at the same time, F-actin and tight junction proteins were disrupted. It was thought that ITF could reverse the high permeability by restoring normal F-actin, ZO-1 and Claudin-1 structures. These results collectively demonstrated that PAF plays an important role in the regulation of mucosal permeability and the effects of PAF are correlated with structural alterations of the F-actin-based cytoskeleton and of tight junctions. ITF can protect intestinal epithelium against PAF-induced disruption by restricting the rearrangement of the F-actin cytoskeleton and of tight junctions.

Tumor Markers for Diagnosis, Monitoring of Recurrence and Prognosis in Patients with Upper Gastrointestinal Tract Cancer

Jing, Jie-Xian,Wang, Yan,Xu, Xiao-Qin,Sun, Ting,Tian, Bao-Guo,Du, Li-Li,Zhao, Xian-Wen,Han, Cun-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

Triterpenoid Saponins from the Seeds of Caragana microphylla

Gui-Lin Jin,Cheng-Jian Zheng,Wen-Bo Xin,Zhu-Jun Mao,Pei-Xin Sun,Zhi-Xin Zeng,Lu-Ping Qin 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.6

Two new triterpenoid saponins, namely caraganoside C (1) and caraganoside D (2), were isolated from the seeds of Caragana microphylla. Their structures were elucidated on the basis of spectroscopic analyses, including homo- and hetero-nuclear correlation NMR experiments (COSY, HSQC and HMBC). Both 1 and 2 exhibited moderate inhibitory activity against NO production in LPS-stimulated RAW264.7 cells with IC_50 values of 26.4 μM and 32.2 μM, respectively. In addition, 1 showed weak cytotoxicity against MCF-7, HL-60, HCT116, and A549 cell lines.

Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

Shou-Xia Li,Ding-Li Chen,Su-Bin Zhao,Li-Li Guo,Hai-Qin Feng,Xiao-Fang Zhang,Li-Li Ping,Zhi-Ming Yang,Cai-Xia Sun,Gen-Dong Yao 대한이비인후과학회 2015 Clinical and Experimental Otorhinolaryngology Vol.8 No.3

Objectives. Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. Methods. Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. Results. Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. Conclusion. Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs.