SYMPOSIUM 2 : Chronic Hepatitis B Antiviral Therapy vs. Immune Modulation

( Qin Ning ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Hepatitis B virus (HBV) infection is a worldwide health problem. About a quarter of the world population, more than 2 billion people have been infected with HBV. Chronic HBV hepatitis (CHB) is an important risk factor for the development of liver cirrhosis and hepatocellular carcinoma. Nature course of CHB closely related with immune status. The persistent infection of HBV is now regarded as the result of inefficacy of both innate and adaptive immune response. Most information has been derived from data on the adaptive immune response, in which the roles of T cells and its regulation by T regulatory (Treg) cells have been elucidated. An increasing number of studies have suggested the importance of the components of innate immunity, such as macrophage, natural killer (NK) cell, natural killer T (NKT) cell and immune modulation molecules, in the pathogenesis of HBV infection. Sustained immune control was found associated with sustained off-antiviral therapy response, and the critical step towards HBsAg seroclearance. The immune control models among different nucleotide analogues, and interferon could be different. Better understanding the immune system before and post antiviral treatment shed light on improvement of treatment strategy. How to combine or sequential these agents to achieve an optimal treatment response need further investigation. The OSST study is one of the examples of these efforts.

T-SPOT.TB for Detection of Tuberculosis Infection among Hematological Malignancy Patients and Hematopoietic Stem Cell Transplant Recipients

Qin, Li-Li,Wang, Qin-Rong,Wang, Qian,Yao, Hong,Wen, Li-Jun,Wu, Li-Li,Ping, Na-Na,Xie, Jun-Dan,Chen, Mei-Yu,Chen, Su-Ning Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is recommended in hematological malignancy patients and before hematopoietic stem cell transplantation (Guidelines for the prevention and management of infectious complications of solid organ transplantation, 2004). Compared to traditional methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was performed, among which 295 patients also received the TST test. The agreement (79%) between T-SPOT.TB and TST was poor (x=0.274, P<0.001). The patients with positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the 41 receiving the TST test had positive results. A majority of the patients with T-SPOT.TB positive results had some other evidence ofTB, such as TB history, clinical symptoms and an abnormal chest CT scan. Active TB was found in 9 patients, in which 2 had negative TST results. We followed up the patients and no one developed active TB. Our study suggested that the T-SPOT.TB may be more useful for screening LTBI and active TB in hematological malignancy patients and hematopoietic stem cell transplant recipients than the TST test.

Towards Hepatitis B Virus Cure and Immunology

( Qin Ning ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Currently, there are two main types of antiviral drugs approved in the treatment of chronic hepatitis B (CHB): nucleos(t)ide analogue with high barrier to resistance (i.e., entecavir and tenofovir), or pegylated interferon alpha.1 Currently majority of CHB patients require long-term or lifelong treatment dur to limited treatment options, thus there is a need for strategies toward an hepatitis B virus (HBV) cure. The definition of chronic hepatitis B cure includes 1) absolute or complete cure, which is defined by elimination of cccDNA, undetectable HBV DNA in serum and liver and off-therapy HBsAg loss 2) functional (immunological) cure, which is defined by HBsAg loss or seroconversion 3) disease cure, which is defined by no risk of disease progression to cirrhosis, liver failure or hepatocellular carcinoma (HCC).2 However, there are some obstacles for HBV cure. On the one hand, NAs do no directly affect the viral cccDNA or have significant effect on HBsAg level. On the other hand, HBV-specific T cells are exhausted in chronic infection and HBV has evolved mechanisms to evade both innate and adaptive immune responses.3 Combinations of potent NA with immunotherapeutic approaches are highly promising and should help to circumvent these obstacles in the future. In patients on long-term NA therapy, PegIFNα can be used as a ‘switch to’ or ‘add-on’ strategy. Several cohort studies, including OSST study, Endeavor study, Anchor study, New Switch Study, SWAP study in Asia and PEGAN Study, PEGON study, HERMES study in the West, have been carried on in either treatment naïve or NA suppressed CHB patients. In most of these studes with OSST as the first report, HBeAg seroconversion and/or HBsAg reductions or loss rates increase significantly in the combination/switch group.4 Based on these studies, a roadmap to clinical cure of CHB has been proposed5 and recently we launched the COST study to validate the roadmap and OCEAN study to follow up a long term outcome of these approaches. The novel antiviral therapies aim to cure HBV can be categorized into direct-acting antivirals and immunotherapeutic agents. The direct-acting antivirals include HBV entry inhibitors, drugs targeting cccDNA, siRNA or anti-sense oligonucleotides targeting viral transcripts, nucleocapsid assembly modulators, and approaches to inhibit HBsAg release in serum.6 Several potential mechanisms for restoration of immune responses have been suggested. Among them, Toll-like receptor agonists or specific antiviral cytokine delivery are supposed to work for restoration of innate immunity; inhibitors of negative checkpoint regulators, therapeutic vaccines, or autologous transfer of engineered HBV-specific T cells are supposed to work for restoration of adaptive immunity.5,7

Ni-NTA-COATED NANOWIRE MATERIALS FOR PROTEIN ENRICHMENT AND THE APPLICATION IN A MEDICAL DEVICE USED FOR BLOOD GLUCOSE DEGRADATION

QIN HU,YING QI LIU,NING LI,CHUN CHENG,SHUIGANG XU,NING WANG,WEI QIN,BEN ZHONG TANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2013 NANO Vol.8 No.3

A general and reliable method has been developed to functionalize either the iron oxide or the silicon nanowires (NWs) with nickel–nitriloacetic acid (Ni–NTA) complex, which was manufactured to manipulate His-tagged proteins and enzymes. The Ni–NTA-functionalized sea-urchin-shaped α-Fe2O3 NWs exhibit the superior protein purification efficiency and excellent stability in the form of dry powder. Application of this new nanotechnology in biomedical research field has been explored. A glucose degradation bio-matrix was made via the Ni–NTA-modified silicon NW-chips, which were conjugated with an enzyme essential to glycolysis. The glucose level in a simulated blood solution was found to be reduced from 14.4 mM to 9 mM after incubating the hexokinase I-functionalized silicon NW-chips for 12 h. These results suggest a possible way to build up a medical device using enzymes functionalized NW-chips for the removal of excess blood glucose.

HCV, Acute, LT : Hepatic Stellate Cells Modulate Functions of Tregs in IFNγ-mediated Hepatitis of Mice

( Qin Ning ),( Young Sun Lee ),( Hyon Seung Yi ),( Hyuk Soo Eun ),( Won Il Jeong ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Hepatic stellate cells (HSCs) perform important roles not only in liver fibrosis but also in inflammation by regulating activation or induction of immune cells and producing various chemokines and cytokines. Moreover, it has been reported that HSCs are also involved in the induction of regulatory T cells (Tregs). Therefore, we investigated the immune regulatory role of HSCs to Tregs in interferon γ (IFNγ)- mediated hepatitis of mice. Methods: To induce IFNγ-mediated hepatitis in mice, we injected concanavalin A (ConA) to mice through tail vein at dose of 12 μg/g. Mice were sacrificed at 0, 3, 12 and 24 hours after ConA treatment. In vitro experiment, isolated natural Tregs from lymph nodes and spleen were co-cultured with HSCs and then analyzed the FoxP3 expression and gene expressions. Results: After ConA treatment, liver injuries sharply increased a n d p e a k e d a t 2 4 h o u r s a n d t h e p o p u l a t i o n o CD4+CD25+FoxP3+ Tregs was also significantly increased. In addition, isolated HSCs after ConA treatment showed enhanced expressions of TGF-β and IL-10. In vitro co-culturing Tregs with HSCs, HSCs significantly up-regulated Foxp3 expression in Tregs compared to that of non-co-cultured Tregs. Moreover, levels of IL-10 and TGF-β at supernatant remarkably increased in the co-cultured group compared with those of Tregs or HSCs only cultured group. Conclusions: In ConA-induced hepatitis, HSCs might regulate the expression of FoxP3 in Tregs by producing cytokines such as IL-10 and TGF-β. Therefore, the regulation of function in HSCs could be a new therapeutic target for immune-mediated hepatitis.

Characteristics and Risk Factors of Functional Dyspepsia Fulfilling the Rome IV Criteria Overlapping With Gastroesophageal Reflux Disease, Irritable Bowel Syndrome, and Functional Constipation in South China

( Yan-qin Long ),( Wen-li Xu ),( Lu-xiu Li ),( Hui-qin He ),( Jing-jie Wang ),( Guo-dong Shan ),( Ning Dai ),( Hong-tan Chen ) 대한소화기기능성질환·운동학회 2024 Journal of Neurogastroenterology and Motility (JNM Vol.30 No.2

Background/Aims Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice. (J Neurogastroenterol Motil 2024;30:184-193)

Glucosamine induces cell death via proteasome inhibition in human ALVA41 prostate cancer cell

Bao-Qin Liu,Hua-Qin Wang,Xin Meng,Chao Li,Yan-Yan Gao,Ning Li,Xiao-Fang Niu,Yifu Guan 생화학분자생물학회 2011 Experimental and molecular medicine Vol.43 No.9

Glucosamine, a naturally occurring amino monosaccharide,has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDPGlcNAc substrates for O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28γ and overexpression of PA28γ rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28γ suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28γ and inhibition of proteasomal activity via O-GlcNAc modification.

Glucosamine induces cell death $via$ proteasome inhibition in human ALVA41 prostate cancer cell

Liu, Bao-Qin,Meng, Xin,Li, Chao,Gao, Yan-Yan,Li, Ning,Niu, Xiao-Fang,Guan, Yifu,Wang, Hua-Qin Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.9

Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose- 6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked ${\beta}$-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition $via$ affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator $PA28{\gamma}$ and overexpression of $PA28{\gamma}$ rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated $PA28{\gamma}$ suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of $PA28{\gamma}$ and inhibition of proteasomal activity via O-GlcNAc modification.

Experimental and Numerical Researches on the Seismic Behavior of Tubular Reinforced Concrete Columns of Air-Cooling Structures

Ning-jun Du,Guo-liang Bai,Ya-zhou Xu,Chao-gang Qin 한국콘크리트학회 2017 International Journal of Concrete Structures and M Vol.11 No.3

Tubular reinforced concrete columns of air-cooling condenser structures, which undertake the most weight of air cooling equipment, are the major components to resist lateral forces under earthquake. Once collapsed, huge casualties and economic loss would be caused. Thus, four 1/8 scaled specimens were fabricated and tested through the pseudo-static testing method. Failure modes and crack patterns of the specimens under cyclic loading were observed. Then, finite element models of tubular reinforced concrete columns were established using OpenSees and were verified with the experimental results. Finally, the influence of axial compression ratio and longitudinal reinforcement on energy dissipation capacity and stiffness degradation were studied based on the validated finite element modes. It is confirmed that tubular reinforced concrete columns of air-cooling condenser structure exhibit a moderate ability of energy dissipation, and the nonlinear finite element model could reasonably simulate its seismic behavior. Furthermore, axial compression ratio and longitudinal reinforcement are main factors which affect the seismic behavior of the tubular reinforced concrete columns. The experimental results and simulation method provide an available way to design this kind of large tubular reinforced concrete columns with thin-wall.

Chromatic Characteristics and Anthocyanin Compositions of Cabernet Sauvignon Wines: Influence of Indigenous Saccharomyces cerevisiae Strains in Ningxia, China

Ning Liu,Yu-Yang Song,Yi Qin,Xue Gong,Yan-Lin Liu 한국식품과학회 2015 Food Science and Biotechnology Vol.24 No.6

Eight Saccharomyces cerevisiae strains were used for preparation of Cabernet Sauvignon musts from Yuma vineyard in China, where the strains were isolated, to study the importance of yeast strain for optimization of Cabernet Sauvignon wine color and anthocyanin composition. Differences in chromatic characteristics between indigenous yeast strains and a commercial F15 control were not found. Twenty-one anthocyanins were detected and quantified using HPLC-MS. Concentrations of anthocyanins were significantly (p<0.05) influenced by the yeast strain used. Use of the commercial F15 yeast resulted in the highest anthocyanin concentration. Among 9 pyranoanthocyanins detected, amounts of must were influenced by the yeast strain used. The color of wine produced using the N11424 yeast was more stable because of a higher pyranoanthocyanin concentration. Use of Principal Component Analysis indicated that indigenous yeast treatments were separated from the F15 control yeast treatment based on anthocyanin components.