Inhibition of α-glucosidase by 2-thiobarbituric acid: Molecular dynamics simulation integrating parabolic noncompetitive inhibition kinetics

Qin, Xiu-Yuan,Lee, Jinhyuk,Zheng, Li,Yang, Jun-Mo,Gong, Yan,Park, Yong-Doo Elsevier 2018 Process biochemistry Vol.65 No.-

<P><B>Abstract</B></P> <P>The phenomenon of α-glucosidase inhibition has attracted the attention of researchers due to its association with type 2 diabetes treatment in humans. In this study, we found that 2-thiobarbituric acid (TBA) induces complex inhibition of α-glucosidase using kinetics tests and molecular dynamics (MD) simulations. Computational MD and docking simulations demonstrate that TBA interacts with three residues on active sites of α-glucosidase such as Met69, Arg212, and His348. These biochemical tests indicate that TBA reversibly inhibits α-glucosidase in a parabolic noncompetitive manner (<I>IC</I> <SUB>50</SUB> =17.13±1.14mM; <I>K</I> <SUB>i</SUB> =13.25±0.56mM) and that this inhibition is accompanied by a biphasic kinetic process. The tertiary conformational changes were not synchronized with TBA inhibition but we observed hydrophobic disruption after inactivation at higher concentrations of TBA. Our results provide insight into the functional roles of residues located at the active sites of α-glucosidase, and we suggest that compounds similar to TBA (heterocyclic compounds) targeting the key residues of active sites are potential α-glucosidase inhibitors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 2-Thiobarbituric acid (TBA) induces complex inhibition of α-glucosidase. </LI> <LI> Computational MD simulations demonstrate that TBA interacts with Met69, Arg212, and His348. </LI> <LI> TBA reversibly inhibits α-glucosidase in a parabolic noncompetitive manner (<I>IC</I> <SUB>50</SUB> =17.13±1.14mM; <I>K</I> <SUB>i</SUB> =13.25±0.56mM). </LI> <LI> The high dose of TBA induces hydrophobic disruption after inactivation. </LI> <LI> Heterocyclic compounds targeting the key residues of active sites are potential α-glucosidase inhibitors. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

High-fidelity bioelectronic muscular actuator based on porous carboxylate bacterial cellulose membrane

Wang, Fan,Jin, Zhen,Zheng, Shaohui,Li, Hao,Cho, Sunghoon,Kim, Hyeon Joe,Kim, Seong-Jun,Choi, Eunpyo,Park, Jong-Oh,Park, Sukho Elsevier 2017 Sensors and actuators. B Chemical Vol.250 No.-

<P><B>Abstract</B></P> <P>Human-friendly electronic products, such as smart mobile phones, soft haptic devices, wearable electronics, and implantable or disposal biomedical devices, will require the use of high-performance durable soft electroactive actuators with eco-friendly, biocompatible, and biodegradable functionalities. Here, we report a high-fidelity bioelectronic muscular actuator based on porous carboxylate bacterial cellulose (CBC) membranes fabricated using the facile zinc oxide (ZnO) particulate leaching (PL) method. The proposed CZ-PL muscular actuator exhibits large deformation, low actuation voltage, fast response, and high-durability in open air environment. In particular, the CZ-PL membrane shows a dramatic increase in the ionic liquid uptake ratio, ionic exchange capacity, and ionic conductivity of up to 70.63%, 22.50%, and 18.2%, respectively, for CBC, resulting in a 5.8 times larger bending deformation than that of the pure CBC actuator. The developed high-performance CZ-PL muscular actuator can be a promising candidate for meeting the tight requirements of human-friendly electronic devices such as wearable devices, biomimetic robots, and biomedical active devices.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a novel dry-type muscular actuator based on porous carboxylate bacterial cellulose (CBC) membrane. </LI> <LI> The porous CBC membrane was prepared by ZnO particulate leaching method. </LI> <LI> The proposed actuator showed better actuation performance than that of the pure CBC actuator. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

Jun-Cheng Guo,Yi-Jun Yang,Jin-Fang Zheng,Jian-Quan Zhang,Min Guo,Xiang Yang,Xiang-Ling Jiang,Li Xiang,You Li,Huang Ping,Liu Zhuo 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

Differences in the mandibular premolar positions in Angle Class I subjects with different vertical facial types

Jun Duan,Feng Deng,Wan-Shan Li,Xue-Lei Li,Lei-Lei Zheng,Gui-Yuan Li,Yan-Jie Bai 대한치과교정학회 2015 대한치과교정학회지 Vol.45 No.4

Objective: To compare the positions of the mandibular premolars in Angle Class I subjects according to vertical facial type. The results will provide a theoretical basis for predicting effective tooth movement in orthodontic treatment. Methods: Cephalometric parameters were determined using cone-beam computed tomography in 120 Angle Class I subjects. Subjects were categorized as short, normal, and long face types according to the Frankfort mandibular angle. Parameters indicating the position of the mandibular right premolars and the mandible were also measured. Results: The angle between the mandibular first premolar axis and buccal cortex, the distance between the root apex and buccal cortex, angle of vestibularization, arc of vestibularization, and root apex maximum movable distance were significantly greater in the short face type than in the long and norm face types. The angle between the mandibular second premolar axis and buccal cortex, the distance from root apex to buccal cortex, and the arc of vestibularization were significantly greater in the short face type than in the normal face type. Conclusions: There are significant differences in the mandibular premolar positions in Class I subjects according to vertical facial type.

Tribological study of three-dimensionally braided carbon fiber-nylon 6 composites against 316L stainless steel

Li-yun Zheng,Li-xin Zhao,Jing-jun Zhang 한국물리학회 2007 Current Applied Physics Vol.7 No.s1

A new type of material for orthopaedic devices, a three-dimensional braided carbon ber-reinforced nylon 6 (C3D/MCN) composite,was prepared by anionic polymerization. It was characterized by using a block-on-ring wear tester equipped with real-time friction mea-surement capabilities. Scanning electron microscope and an optical microscope were used to study the wear surfaces of the compositesand metallic ring counterpart. The eects of carbon-ber volume fraction, braiding angle, and friction condition on the tribological prop-erties and wear mechanism of C3D/MCN composites were observed. Experiments showed an optimum wear resistance when the carbon-conditions. The wear mechanism under dry sliding conditions is adhesive wear and abrasive wear. The C3D/MCN composites exhibitedmainly abrasive wear under Hank’s-solution-lubricated conditions.

Induction of Interleukin-22 (IL-22) production in CD4+ T Cells by IL-17A Secreted from CpG-Stimulated Keratinocytes

( Zheng Jun Li ),( Dae Kyoung Choi ),( Kyung Cheol Sohn ),( Seul Ki Lim ),( Myung Im ),( Young Lee ),( Young Joon Seo ),( Chang Deok Kim ),( Jeung Hoon Lee ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.5

Background: Interleukin-17A (IL-17A) is mainly secreted from Th17 cells that are activated by various stimuli including CpG oligodeoxynucleotide, a Toll-like receptor 9 (TLR9) ligand. Recently, it has been demonstrated that keratinocytes play an important role in the pathogenesis of psoriasis. Objective: To investigate the potential role of keratinocytes, we examined whether TLR9 ligand CpG induces IL-17A expression in keratinocytes. Methods: We used HaCaT keratinocytes as a model system, and determined CpG-induced IL-17A using enzyme-linked immunosorbent assay and Western blot. Results: When HaCaT keratinocytes were treated with CpG, the expression of several cytokines including IL-17A, tumor necrosis factor-α and CCL20 was markedly increased. Treatment with nuclear factor (NF)-κB inhibitor significantly blocked the CpG-induced IL-17A production, indicating that CpG induced IL-17A expression through the NF-κB signaling pathway. In addition, IL-17A secreted from keratinocytes stimulated the CD4+ T cells, resulting in strong induction of IL-22 production. Conclusion: Since IL-22 is an important mediator for psoriatic inflammation, our data suggest that keratinocytes can participate in the pathogenesis of psoriasis via the TLR9-dependent IL-17A production. (Ann Dermatol 28(5) 579∼585, 2016)

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Li, Qiong,Yin, Jun,Wang, Xu,Wang, Li-Ming,Shi, Yi-Jun,Zheng, Liang,Tang, Wei-Feng,Ding, Guo-Wen,Liu, Chao,Liu, Rui-Ping,Gu, Hai-Yong,Sun, Jia-Ming,Chen, Suo-Cheng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.

Experimental Study of Two-step Phase-shifting Digital Holography based on the Calculated Intensity of a Reference Wave

Jun Li,Yang yang Pan,Jiaosheng Li,Rong Li,Tao Zheng 한국광학회 2014 Current Optics and Photonics Vol.18 No.3

Two-step quadrature phase-shifting digital holography based on the calculated intensity of a reference wave is proposed. In the Mach-Zehnder interferometer (MZI) architecture, the method only records two quadrature-phase holograms, without reference-wave intensity or object-wave intensity measurement, to perform object recoding and reconstruction. When the reference-wave intensity is calculated from the 2D correlation coefficient (CC) method that we presented, the clear reconstruction image can be obtained by some specific algorithm. Its feasibility and validity were verified by a series of experiments with 2D objects and 3D objects. The presented method will be widely used in real-time or dynamic digital holography applications.