Continuous DC-CIK Infusions Restore CD8⁺ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

Zhao, Yan-Jie,Jiang, Ni,Song, Qing-Kun,Wu, Jiang-Ping,Song, Yu-Guang,Zhang, Hong-Mei,Chen, Feng,Zhou, Lei,Wang, Xiao-Li,Zhou, Xin-Na,Yang, Hua-Bing,Ren, Jun,Lyerly, Herbert Kim Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Partial-state Feedback Stabilization for a Class of Generalized Nonholonomic Systems with ISS Dynamic Uncertainties

Yan Zhao,Chunxiao Wang,Jiang-Bo Yu 제어·로봇·시스템학회 2018 International Journal of Control, Automation, and Vol.16 No.1

In this paper, the problem of global stabilization control via partial-state feedback is addressed for a class of uncertain nonholonomic systems with the disturbed virtual control directions. The investigated nonholonomic system has the input-to-state stable (ISS) dynamic uncertainties. The small gain theorem and the changing supply function technique are employed to derive a global stabilization controller. Additionally, we develop a switching control strategy in order to get around the smooth stabilization burden associated with nonholonomic systems. The simulation results illustrate the efficacy of the presented algorithm.

Establishment of a novel myocarditis mouse model based on cyclosporine A

Zhao Tian Hao,Jiang Yi Xuan,Chen Kai Qin,Qiu Dan,Xu Yan Zhe,Ye Chun,Ren Ting,Zhang Bo,Dai Bin,Hu Jue,Lu Jun,Zhou Fang Liang,Xiao Rong,Lu Fang Guo,Wei Ke 한국유전학회 2022 Genes & Genomics Vol.44 No.12

Background: Myocarditis is a myocardial injury that can easily cause adolescent death. Traditional research models of animal invasion with viral components, lipopolysaccharide (LPS) or porcine myocardial myosin, among others, have the shortcomings of potential biological safety hazards and high animal mortality. Objective: To explore the construction of a novel myocarditis model with cyclosporine A and the potential genes and pathways associated with it. Methods: BALB/c mice were used in this study, and cyclosporin A and LPS were injected into the peritoneal cavity of mice. The successful establishment of the model was assessed by detecting serum myocardial injury markers and inflammatory factors levels, HE, IHC staining, and RT-qPCR methods. Key genes were obtained using the GSE35182 dataset from the GEO database and validated with the RT-qPCR method. Results: We found that a large number of inflammatory cells infiltrated the myocardium of mice in each group of Cyclosporin A constructed model, while the expression of inflammatory factor indicators was increased, and this model has the characteristics of high degree of local inflammation in myocardial tissue, low mortality, and safe and non-toxic treatment. Using GSE35182 data, we selected 18 Hub genes and validated Hub genes in myocardial tissue with RT-qPCR and found that multiple signaling pathways such as Toll-likereceptor signaling pathway(TLRs), Rap1 signal pathway(Rap1), and Chemokine signaling pathway may be involved in the development of myocarditis. Conclusion: Cyclosporin A can construct a new myocarditis model, and TLRs, Chemokines and Rap1 signaling pathways may be the core pathways of myocarditis.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke

Zhao-jian Ying,Yuan-Yuan Huang,Meng-Meng Shao,Chu-Huai Chi,Ming-Xia Jiang,Yi-Hui Chen,Yu-Chen,Miao-Xuan Sun,Yan-Yan Zhu,Xianmei Li 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.3

Background and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). Methods We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow- up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. Results IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. Conclusions Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Yan Lan,Yan-Zhao Yang,Xian Jiang,Guang-Shi Jin,김민선,박병림,Yuan-Zhe Jin,Li-Wei Li 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

3D Printed Flexible Cathode Based on Cu-EDTA that Prepared by Molecular Precursor Method and Microwave Processing for Electrochemical Machining

Yan, Binggong,Song, Xuan,Tian, Zhao,Huang, Xiaodi,Jiang, Kaiyong The Korean Electrochemical Society 2020 Journal of electrochemical science and technology Vol.11 No.2

In this work, a metal-ligand solution (Cu-EDTA) was prepared based on the molecular precursor method and the solution was spin-coated onto 3D printed flexible photosensitive resin sheets. After being processed by microwave, a laser with a wavelength of 355 nm was utilized to scan the spin-coated sheets and then the sheets were immersed in an electroless copper plating solution to deposit copper wires. With the help of microwave processing, the adhesion between copper wires and substrate was improved which should result from the increase of roughness, decrease of contact angle and the consistent orientation of coated film according to the results of 3D profilometer and SEM. XPS results showed that copper seeds formed after laser scanning. Using the 3D printed flexible sheets as cathode and galvanized iron as anode, electrochemical machining was conducted.

Transient Stability Simulation Analysis of Multi Node Power Network with Variable Speed Pumped Storage Units

Zhao Chong,Wang Longze,Ma Yiyi,Xiang Pengfei,Jiang Siyu,Chen Weidong,Zhang Yan,Li Meicheng 대한전기학회 2023 Journal of Electrical Engineering & Technology Vol.18 No.4

The output characteristics of variable speed pumped storage are different from conventional hydropower and constant speed pumped storage units. The continuous increase of installed capacity of variable speed pumped storage, poses a severe challenge to the safe and stable operation of the local power grid. Proposed in this paper is a kind suitable for multi-node containing variable speed pump machine storage unit electric power network transient stability method, considering the variable speed pumped storage units by the end of the instantaneous failure prone to sudden drop transient power, the power network with more nodes each busbar voltage stable operation as the goal, according to the regional power grid data under typical operation modes, Based on the power system analysis software package, an electromechanical simulation model of the 7-node power grid with variable speed pumped storage unit was established. The influence on the transient stability of a 7-node power grid is analyzed by removing variable speed pumped-storage units and three-phase short-circuit faults. The transient stability of the power grid can be maintained under the conditions of removing variable speed pumped-storage units and three-phase short-circuit faults, but some bus voltages are higher than the specified voltage upper limit. The reactive power compensation device is installed to improve the voltage stability of the power grid system, which can prevent the overvoltage accident caused by the fault of the communication system, achieve the purpose of multi-node power network stability, and improve the safety and stability of the regional power system when the fault occurs.

Cytotoxic triterpene glycosides from the roots of Sanguisorba officinalis

Jiang Hu,Yan Song,Hui Li,Benshou Yang,Xia Mao,Yongmao Zhao,Xiaodong Shi 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.6

Phytochemical investigation of the ethanolextract of the roots of Sanguisorba officinalis resulted inthe isolation of three new triterpene glycosides, 3b-[(a-Larabinopyranosyl)oxy]-19a,23-dihydroxyolean-12-en-28-oicacid 28-[6-O-acetyl-b-D-glucopyranosyl] ester (1),2a,3b,19a,23-tetrahydroxyurs-12-en-28-oic acid 28-[6-Oacetyl-b-D-glucopyranosyl] ester (2), and 3b-[(a-L-arabinopyranosyl)oxy]-19a-hydroxyurs-12,20(30)-dien-28-oicacid 28-[6-O-acetyl-b-D-glucopyranosyl] ester (3). All thetriterpene glycosides exhibited the significant cytotoxicpotential with low IC50 values (IC50\5.0 lM) against sixtumor cell lines (MCF-7, HeLa, HepG2, SGC-7901, NCIH460,and BGC-823).

Inotodiol Inhabits Proliferation and Induces Apoptosis through Modulating Expression of cyclinE, p27, bcl-2, and bax in Human Cervical Cancer HeLa Cells

Zhao, Li-Wei,Zhong, Xiu-Hong,Yang, Shu-Yan,Zhang, Yi-Zhong,Yang, Ning-Jiang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, p<0.01). A sub-$G_1$ peak (apoptotic cells) of HeLa cells was detected after treatment and the apoptosis rate with the concentration and longer incubation time (r=1.0, p<0.01), while the percentage of cells in S phase and $G_2$/M phase decreased significantly. Immunocytochemistry assay showed that the expression of cyclin E and bcl-2 in the treated cells significantly decreased, while the expression of p27 and bax obviously increased, compared with the control group (p<0.05). The results of our research indicate that inotodiol isolated from Inonotus obliquus inhibited the proliferation of HeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer.