The effect of rebamipide on non-steroidal antiinflammatory drug-induced gastro-enteropathy: a multi-center, randomized pilot study

Dong Jun Oh,Hyuk Yoon,Hyun Soo Kim,Yoon Jin Choi,Cheol Min Shin,Young Soo Park,Nayoung Kim,Dong Ho Lee,You-Jung Ha,Eun Ha Kang,Yun Jong Lee,Nayoung Kim,Ki-Jeoung Kim,Fei Liu 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.6

Background/Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs, which can induce gastroenteropathy with bleeding and ulcers. This study investigated the associations between efficacy, safety, and gastrointestinal symptoms linked to rebamipide and proton pump inhibitor administration in patients requiring long-term NSAID use. Methods: This study was a multi-center, randomized, open-labeled, pilot design. Results: Thirty-three patients were included. Of these, 15 were included in the study group and 18 were in the control group. NSAID-induced gastric ulcers, which were the primary outcome of this study, did not occur in either the study or control group. Changes in the number of small bowel erosions and ulcers were –0.6 ± 3.06 in the study group and 1.33 ± 4.71 in the control group. The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) was three (20%) in the study group and six (40%) in the control group (p = 0.427). No serious adverse events occurred in either group. However, dyspepsia and skin rashes occurred in six patients (31.58%) in the study group and 13 (65%) in the control group (p = 0.036). Conclusions: Although statistically significant differences were not generated, possibly as a result of the small sample size, mucosal breaks observed via capsule endoscopy revealed that rebamipide was likely to be more effective than lansoprazole in preventing small intestine damage caused by NSAIDs. Furthermore, fewer side-effects emerged with rebamipide.

STING Negatively Regulates Double-Stranded DNA-Activated JAK1-STAT1 Signaling via SHP-1/2 in B Cells

Dong, Guanjun,You, Ming,Ding, Liang,Fan, Hongye,Liu, Fei,Ren, Deshan,Hou, Yayi Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5

Recognition of cytosolic DNA initiates a series of innate immune responses by inducing IFN-I production and subsequent triggering JAK1-STAT1 signaling which plays critical roles in the pathogenesis of infection, inflammation and autoimmune diseases through promoting B cell activation and antibody responses. The stimulator of interferon genes protein (STING) has been demonstrated to be a critical hub of type I IFN induction in cytosolic DNA-sensing pathways. However, it still remains unknown whether cytosolic DNA can directly activate the JAK1-STAT1 signaling or not. And the role of STING is also unclear in this response. In the present study, we found that dsDNA directly triggered the JAK1-STAT1 signaling by inducing phosphorylation of the Lyn kinase. Moreover, this response is not dependent on type I IFN receptors. Interestingly, STING could inhibit dsDNA-triggered activation of JAK1-STAT1 signaling by inducing SHP-1 and SHP-2 phosphorylation. In addition, compared with normal B cells, the expression of STING was significantly lower and the phosphorylation level of JAK1 was significantly higher in B cells from MRL/lpr lupus-prone mice, highlighting the close association between STING low-expression and JAK1-STAT1 signaling activation in B cells in autoimmune diseases. Our data provide a molecular insight into the novel role of STING in dsDNA-mediated inflammatory disorders.

Numerical investigation on Rayleigh-Bénard-Marangoni flow of water near the maximum density in cylindrical pools with large aspect ratios

Dong-Ming Mo,Liu-Zhu Cao,Li Zhang,Shuang Ye,You-Rong Li 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.10

We report a set of direct numerical simulation results on Rayleigh-BénardMarangoni (R-B-M) flow of cold water in the cylindrical pools. The heat transfer between the free surface and the environment is considered. The aspect ratio Г of the cylindrical pool varies from 2 to 8. Rayleigh (Ra) and Biot (Bi) numbers are respectively confined in Ra ≤ 10 4 and 0 < Bi ≤ 50. The flow onset critical Ra is determined and the influences of Bi and the density inversion parameter ( mΘ ) on the critical Ra are analyzed. The primary bifurcation flow structures of R-B-M flow are shown and the evolution of the flow structures with Ra and Bi at different mΘ is observed. Furthermore, the heat transfer ability is estimated by Nusselt number. The results indicate that the critical Ra of the flow onset increases with increasing Bi and Θ m . But it decreases with the increase of Г. The primary bifurcation pattern is multicellular flow. With increasing Г, the number of flow cells in multicellular flow increases fast. With increasing Ra, the up-triangular and up-quadrilateral flow structures appear at Г = 4, and finally transits to the up one-torus. With increasing Ra and Г, and decreasing Θ m , average Nusselt number increases monotonically. However, with increasing Bi, it first increases, and then decreases.

Role of a Novel Pyridostigmine Bromide-Phospholipid Nanocomplex in Improving Oral Bioavailability

Qun-you Tan,Jing-qing Zhang,Ni-ni Hu,Guo-dong Liu,Hua-feng Yin,Li Zhang,Hong Wang,Lu-yang Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.3

A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X1, X2, and X3 were 8, 40oC, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and −25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (Tmax) 2 h vs 2 h, the maximum concentration (Cmax) 22.79 μg/mL vs 6.00 μg/mL, and the value of the area under the concentration vs time curve (AUC0-∞) 7128.21 μg·min/mL vs 1772.36 μg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.

THEORETICAL AND EXPERIMENTAL STUDY ON FLOW CHARACTERISTICS OF A DIAPHRAGM PUMP FOR UREA-SCR SYSTEMS

Shu Dong Yang,You Cheng Shi,Xi Wei Pan,Yin Shui Liu 한국자동차공학회 2019 International journal of automotive technology Vol.20 No.4

Urea selective catalytic reduction (SCR) is the primary technology used to reduce the nitrogen oxides (NOx) of diesel engine exhaust. To meet the requirements of an SCR system, a novel type of miniature diaphragm pump was designed. Based on the theory of large deflection of annular plates, the equilibrium equations of a diaphragm with a rigid inclusion were established, and the equations were solved by the nondimensional method and the finite difference method. Theoretical and approximated flow model for this pump were proposed. A theoretical relationship between back pressure, rigid inclusion size and volumetric efficiencies were calculated. To verify the validity of theoretical model, a prototype pump was fabricated and tested. Experimental results demonstrated that the flow is proportional to the pump speed. The deviation between theoretical, approximated flow and experimental flow was less than 4 % and 9.4 %, respectively. The difference between theoretical and experimental volumetric efficiency was varied from 2.7 % to 6.1 % when back pressure changed from 0 to 0.9 MPa. The volumetric efficiency was growing with the increasing of the rigid inclusion size. The pressures in the working chamber showed almost the same overall trends between the theoretical results and experimental values. The experimental results show that the proposed theoretical model is effective.

Heat-Shock Protein 70 as a Tumor Antigen for in vitro Dendritic Cell Pulsing in Renal Cell Carcinoma Cases

Meng, Fan-Dong,Sui, Cheng-Guang,Tian, Xin,Li, Yan,Yang, Chun-Ming,Ma, Ping,Liu, Yun-Peng,Jiang, You-Hong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-${\alpha}$. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-${\alpha}$. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

Fangchinoline Inhibits Cell Proliferation Via Akt/GSK-3beta/cyclin D1 Signaling and Induces Apoptosis in MDA-MB-231 Breast Cancer Cells

Wang, Chang-Dong,Yuan, Cheng-Fu,Bu, You-Quan,Wu, Xiang-Mei,Wan, Jin-Yuan,Zhang, Li,Hu, Ning,Liu, Xian-Jun,Zu, Yong,Liu, Ge-Li,Song, Fang-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk-3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA-MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.

Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB

( Su Jian Liu ),( Cai Xia Yin ),( Ming Chao Ding ),( Shao You Xia ),( Qin Min Shen ),( Ji Dong Wu ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.7

Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dose- dependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-κB were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-κB mediated signaling pathways. [BMB Reports 2014; 47(7): 388-392]

Application of Intraoperative Ultrasonography for Guiding Microneurosurgical Resection of Small Subcortical Lesions

Jia Wang,Yun You Duan,Xi Liu,Yu Wang,Guo Dong Gao,Huai Zhou Qin,Liang Wang 대한영상의학회 2011 Korean Journal of Radiology Vol.12 No.5

Objective: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. Materials and Methods: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. Results: All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. Conclusion: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions. Objective: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. Materials and Methods: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. Results: All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. Conclusion: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions.

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Qian, Ying-Ying,Liu, Xin-You,Pei, Dong,Xu, Jia-Li,Shen, Hua,Chen, Xiao-Feng,Liu, Yi-Qian,Shen, Li-Zong,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.