The Biocompatibility of Multi-Source Stem Cells and Gelatin-Carboxymethyl Chitosan-Sodium Alginate Hybrid Biomaterials

Wang Xinzhe,Li Siqi,Yu Honglian,Lv Jianzhi,Fan Minglun,Wang Ximing,Wang Xin,Liang Yanting,Mao Lingna,Zhao Zhankui 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3

BACKGROUND: Nowadays, biological tissue engineering is a growing field of research. Biocompatibility is a key indicator for measuring tissue engineering biomaterials, which is of great significance for the replacement and repair of damaged tissues. METHODS: In this study, using gelatin, carboxymethyl chitosan, and sodium alginate, a tissue engineering material scaffold that can carry cells was successfully prepared. The material was characterized by Fourier transforms infrared spectroscopy. In addition, the prepared scaffolds have physicochemical properties, such as swelling ratio, biodegradability. we observed the biocompatibility of the hydrogel to different adult stem cells (BMSCs and ADSCs) in vivo and in vitro. Adult stem cells were planted on gelatin-carboxymethyl chitosan-sodium alginate (Gel/SA/CMCS) hydrogels for 7 days in vitro, and the survival of stem cells in vitro was observed by live/died staining. Gel/SA/CMCS hydrogels loaded with stem cells were subcutaneously transplanted into nude mice for 14 days of in vivo culture observation. The survival of adult stem cells was observed by staining for stem cell surface markers (CD29, CD90) and Ki67. RESULTS: The scaffolds had a microporous structure with an appropriate pore size (about 80 lm). Live/died staining showed that adult stem cells could stably survive in Gel/SA/CMCS hydrogels for at least 7 days. After 14 days of culture in nude mice, Ki67 staining showed that the stem cells supported by Gel/SA/CMCS hydrogel still had high proliferation activity. CONCLUSION: Gel/SA/CMCSs hydrogel has a stable interpenetrating porous structure, suitable swelling performance and degradation rate, can promote and support the survival of adult stem cells in vivo and in vitro, and has good biocompatibility. Therefore, Gel/SA/CMCS hydrogel is a strong candidate for biological tissue engineering materials.

Anti-proliferation Effects of Interferon-gamma on Gastric Cancer Cells

Zhao, Ying-Hui,Wang, Tao,Yu, Guang-Fu,Zhuang, Dong-Ming,Zhang, Zhong,Zhang, Hong-Xin,Zhao, Da-Peng,Yu, Ai-Lian Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma

Wang, J.,Wang, S.,Zhang, W.,Wang, X.,Liu, X.,Liu, L.,Li, L.,Liang, Y.,Yu, J.,Jeong, L.S.,Jia, L.,Zhao, H.,Zhang, Y. Academic Press 2017 Biochemical and biophysical research communication Vol. No.

Inhibition of protein neddylation pathway has emerged an attractive anticancer strategy in preclinical studies by using Nedd8-activating enzyme (NAE) inhibitor MLN4924 (Pevonedistat). Previous studies have reported the antitumor activity of MLN4924 mediated by its efficacy on apoptosis, autophagy and senescence. However, whether MLN4924 has any effect on renal carcinoma cells (RCC) remains unexplored. Here we reported that MLN4924 specifically inhibited protein neddylation pathway, leading to statistically significantly suppress the proliferation, survival and migration of RCC cells by inducing G<SUB>2</SUB> cell-cycle arrest, followed by apoptosis in a MLN4924 dose-dependent manner. Further mechanistic study revealed that MLN4924-induced apoptosis was mediated by substantial up-regulation of pro-apoptotic NOXA. These findings highlighted the anticancer effects of the neddylation inhibitors (e.g. MLN4924) for the treatment of RCC.

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao, Cheng-Xiao,Liu, Ming,Xu, Yong,Yang, Kuo,Wei, Dong,Shi, Xiao-Hong,Yang, Fan,Zhang, Yao-Guang,Wang, Xin,Liang, Si-Ying,Zhao, Fan,Zhang, Yu-Rong,Wang, Na-Na,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Yuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, $P=7.3{\times}10^{-5}$), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, $Padj=1.1{\times}10^{-4}$). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, $P=1.0{\times}10^{-5}$) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

Taxol Produced from Endophytic Fungi Induces Apoptosis in Human Breast, Cervical and Ovarian Cancer Cells

Wang, Xin,Wang, Chao,Sun, Yu-Ting,Sun, Chuan-Zhen,Zhang, Yue,Wang, Xiao-Hua,Zhao, Kai Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first-level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were $0.1-1.0{\mu}g/ml$, $0.001-0.01{\mu}g/ml$ and $0.01-0.1{\mu}g/ml$, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the $0.01-1.0{\mu}g/ml$ had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

PERELMAN TYPE ENTROPY FORMULAE AND DIFFERENTIAL HARNACK ESTIMATES FOR WEIGHTED DOUBLY NONLINEAR DIFFUSION EQUATIONS UNDER CURVATURE DIMENSION CONDITION

Wang, Yu-Zhao Korean Mathematical Society 2021 대한수학회보 Vol.58 No.6

We prove Perelman type 𝒲-entropy formulae and differential Harnack estimates for positive solutions to weighed doubly nonlinear diffusion equation on weighted Riemannian manifolds with CD(-K, m) condition for some K ≥ 0 and m ≥ n, which are also new for the non-weighted case. As applications, we derive some Harnack inequalities.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

Wang Lu,Dai Ying-Jie,Cui Yu,Zhang Hong,Jiang Chang-Hao,Duan Ying-Jie,Zhao Yong,Feng Ye-Fang,Geng Shi-Mei,Zhang Zai-Hui,Lu Jiang,Zhang Ping,Zhao Li-Wei,Zhao Hang,Ma Yu-Tong,Song Cheng-Guang,Zhang Yi,Ch 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; <i>P</i>=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, <i>P</i>=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study

Wang Qi,Dai Huajie,Hou Tianzhichao,Hou Yanan,Wang Tiange,Lin Hong,Zhao Zhiyun,Li Mian,Zheng Ruizhi,Wang Shuangyuan,Lu Jieli,Xu Yu,Liu Ruixin,Ning Guang,Wang Weiqing,Bi Yufang,Zheng Jie,Xu Min 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family, <i>Desulfovibrio</i> genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all <i>P</i><0.044). The causal associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas <i>Desulfovibrio</i> genus was negatively associated with ApoB/ApoA1 (all <i>P</i><0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (<i>P</i>=0.028) and 4.6% (<i>P</i>=0.033); the association between <i>Desulfovibrio</i> genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (<i>P</i>=0.019), 4.2% (<i>P</i>=0.035), and 9.1% (<i>P</i>=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Differences Between Breast Cancer Patients Younger and Older than 40 Years: Mammographic Findings

Zhao, Yu-Mei,Wang, Jian-Tao,Liu, Jing,Wang, Ju,Wang, Hong-Li,Liu, Pei-Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Objective: To compare the mammogarphic appearance between breast cancer patients aged <40 and ${\geq}40$ years. Methods: Needle localization and biopsy of suspicious mammographic lesions identified 1,959 breast carcinomas in a single institution from Jun 2012 to Apr 2013. According to the age, we divided patients into two groups: <40 and ${\geq}40$ years old, and analyzed mammographic appearance separately. Results: Young patients had 44.2% foci with calcification, but old patients only had 39.4% (P<0.001). In younger group, the ratios of cases according to mass density were 41.8% or higher, 58.2% equivalent and lower. In older group, the ratios were 55.5 % and 44.5%, respectively. There were statistical differences between high density and others (P<0.05). The ratios of cases according to mass margin were 13.9% circumscribed and microlobulated, 86.1% indistinct and spiculated in the younger group, as compared to 6.5% and 93.5%, respectively, in the older group (P<0.05). Conclusions: Mammographic findings differ between young and old patients with breast cancer, for example regarding mass density, mass margin and microcalcification ratios.

Regioselective Enzymatic Procedure for Preparing 3'-O-stearoyl-6- azauridine by Using Burkholderia cepacia Lipase

Zhao-Yu Wang,Yan-Hong Bi,Min-Hua Zong 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.2

Previous studies on the lipase-mediated acylation of 6-azauridine with vinyl stearate in organic solvents revealed that while preparing a potential prodrug, 3'-Ostearoyl-6-azauridine, a lipase from Burkholderia cepacia showed high regioselectivity toward the second hydroxyl group. The most suitable reaction solvent, molar ratio of vinyl stearate to 6-azauridine, and reaction temperature were anhydrous acetone, 15:1, and 45°C, respectively. Under these conditions, the initial reaction rate, 3'-regioselectivity,and maximum substrate conversion were as high as 10.4mM/h, 86.0, and 99.0%, respectively.