Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Endovascular Treatment for Iliac Vein Compression Syndrome: a Comparison between the Presence and Absence of Secondary Thrombosis

Wen-Sheng Lou,Jian-Ping Gu,Xu He,Liang Chen,Hao-Bo Su,Guo-Ping Chen,Jing-Hua Song,Tao Wang 대한영상의학회 2009 Korean Journal of Radiology Vol.10 No.2

Objective: To evaluate the value of early identification and endovascular treatment of iliac vein compression syndrome (IVCS), with or without deep vein thrombosis (DVT). Materials and Methods: Three groups of patients, IVCS without DVT (group 1, n = 39), IVCS with fresh thrombosis (group 2, n = 52) and IVCS with non-fresh thrombosis (group 3, n = 34) were detected by Doppler ultrasonography, magnetic resonance venography, computed tomography or venography. The fresh venous thrombosis were treated by aspiration and thrombectomy, whereas the iliac vein compression per se were treated with a self-expandable stent. In cases with fresh thrombus, the inferior vena cava filter was inserted before the thrombosis suction, mechanical thrombus ablation, percutaneous transluminal angioplasty, stenting or transcatheter thrombolysis. Results: Stenting was performed in 111 patients (38 of 39 group 1 patients and 73 of 86 group 2 or 3 patients). The stenting was tried in one of group 1 and in three of group 2 or 3 patients only to fail. The initial patency rates were 95% (group 1), 89% (group 2) and 65% (group 3), respectively and were significantly different (p = 0.001). Further, the six month patency rates were 93% (group 1), 83% (group 2) and 50% (group 3), respectively, and were similarly significantly different (p = 0.001). Both the initial and six month patency rates in the IVCS patients (without thrombosis or with fresh thrombosis), were significantly greater than the patency rates of IVCS patients with non-fresh thrombosis. Conclusion: From the cases examined, the study suggests that endovascular treatment of IVCS, with or without thrombosis, is effective. Objective: To evaluate the value of early identification and endovascular treatment of iliac vein compression syndrome (IVCS), with or without deep vein thrombosis (DVT). Materials and Methods: Three groups of patients, IVCS without DVT (group 1, n = 39), IVCS with fresh thrombosis (group 2, n = 52) and IVCS with non-fresh thrombosis (group 3, n = 34) were detected by Doppler ultrasonography, magnetic resonance venography, computed tomography or venography. The fresh venous thrombosis were treated by aspiration and thrombectomy, whereas the iliac vein compression per se were treated with a self-expandable stent. In cases with fresh thrombus, the inferior vena cava filter was inserted before the thrombosis suction, mechanical thrombus ablation, percutaneous transluminal angioplasty, stenting or transcatheter thrombolysis. Results: Stenting was performed in 111 patients (38 of 39 group 1 patients and 73 of 86 group 2 or 3 patients). The stenting was tried in one of group 1 and in three of group 2 or 3 patients only to fail. The initial patency rates were 95% (group 1), 89% (group 2) and 65% (group 3), respectively and were significantly different (p = 0.001). Further, the six month patency rates were 93% (group 1), 83% (group 2) and 50% (group 3), respectively, and were similarly significantly different (p = 0.001). Both the initial and six month patency rates in the IVCS patients (without thrombosis or with fresh thrombosis), were significantly greater than the patency rates of IVCS patients with non-fresh thrombosis. Conclusion: From the cases examined, the study suggests that endovascular treatment of IVCS, with or without thrombosis, is effective.

Forensic biogeographical ancestry inference: recent insights and current trends

Wen Yufeng,Liu Jing,Su Yonglin,Chen Xiacan,Hou Yiping,Liao Linchuan,Wang Zheng 한국유전학회 2023 Genes & Genomics Vol.45 No.10

Background As a powerful complement to the paradigmatic DNA profiling strategy, biogeographical ancestry inference (BGAI) plays a significant part in human forensic investigation especially when a database hit or eyewitness testimony are not available. It indicates one’s biogeographical profile based on known population-specific genetic variations, and thus is crucial for guiding authority investigations to find unknown individuals. Forensic biogeographical ancestry testing exploits much of the recent advances in the understanding of human genomic variation and improving of molecular biology. Objective In this review, recent development of prospective ancestry informative markers (AIMs) and the statistical approaches of inferring biogeographic ancestry from AIMs are elucidated and discussed. Methods We highlight the research progress of three potential AIMs (i.e., single nucleotide polymorphisms, microhaplotypes, and Y or mtDNA uniparental markers) and discuss the prospects and challenges of two methods that are commonly used in BGAI. Conclusion While BGAI for forensic purposes has been thriving in recent years, important challenges, such as ethics and responsibilities, data completeness, and ununified standards for evaluation, remain for the use of biogeographical ancestry information in human forensic investigations. To address these issues and fully realize the value of BGAI in forensic investigation, efforts should be made not only by labs/institutions around the world independently, but also by inter-lab/institution collaborations.

Preoperative Neutrophil to Lymphocyte Ratio as a Prognostic Factor in Patients with Non-metastatic Renal Cell Carcinoma

Wen, Ru-Min,Zhang, Yi-Jing,Ma, Sha,Xu, Ying-Li,Chen, Yan-Su,Li, Hai-Long,Bai, Jin,Zheng, Jun-Nian Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

Zhang, Jing-Wen,Yu, Wan-Jia,Sheng, Xiao-Min,Chang, Fu-Hou,Bai, Tu-Ya,Lv, Xiao-Li,Wang, Guang,Liu, Su-Zhen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Purpose: To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibility among Mongolian and Han populations in the Inner Mongolian region. Materials and Methods: CYP2E1 and NAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. Results: (1) Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1 RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178-1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared with rapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1 together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1 c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CC and NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lung cancer risk than others with rapid acetylation. Conclusions: Disequilibrium distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2 slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lung cancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasing lung cancer risk.

Study on the Application of Canola Oil and Cottonseed Oil in SolutionPolymerized Styrene-butadiene Rubber

Yuan Jing,Chunwei Zhang,Su Zhang,Guangyi Lin,Huidong Cao,Jiahui Wen,Zonglong Wang,Yuanyuan Niu,Zetao Lin 한국고분자학회 2023 폴리머 Vol.47 No.6

The application of vegetable oil-based softeners canola oil and cottonseed oil in Solution polymerized styrene-butadiene rubber (SSBR) system composites was investigated. The results showed that when the aromatic oil was replaced by 5 parts of vegetable oil-based softeners in equal amounts in the base formulation of SSBR system, the work-ing performance of the rubber was better, the tear strength and elongation at break were improved and the tensile strength was reduced; the vulcanization time of the rubber prepared with vegetable oil-based softeners was significantly reduced compared with that of aromatic oil; the glass transition temperature of the rubber was significantly reduced and the cold resistance and snow performance of the rubber were improved.

Pathologic Response During Chemo-radiotherapy and Variation of Serum VEGF Levels Could Predict Effects of Chemo-Radiotherapy in Patients with Esophageal Cancer

Yu, Jing-Ping,Lu, Wen-Bin,Wang, Jian-Lin,Ni, Xin-Chu,Wang, Jian,Sun, Zhi-Qiang,Sun, Su-Ping Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: To investigate the relationship between pathologic tumor response to concurrent chemoradiotherapy and variation of serum VEGF in patients with esophageal cancer. Materials and Methods: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. Results: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. Conclusions: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

Chinese Patients with Gastric Cancer Need Targeted Adjuvant Chemotherapy Schemes

Shi, Wen-Tao,Wei, Lei,Xiang, Jin,Su, Ke,Ding, Qiong,Tang, Meng-Jie,Li, Ji-Qiang,Guo, Yi,Wang, Pu,Zhang, Jing-Wei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Background: Gastric cancer (GC) is one of the most common cancers in China. Adjuvant chemotherapy (AC) is a routine auxiliary treatment for GC recommended by the guidelines issued in 2011 by the Ministry of Health of the People's Republic of China, but the relevant credible consequences in China have been insufficient because of China's late start and ethical concerns. Methods: A series of databases, including Cochrane Library, MEDLINE, EMBASE, the Chinese database of the National Knowledge Infrastructure and the VIP database, were searched by 2 reviewers independently for studies investigating AC for GC through March 2012. The retrieved literature was screened according to the eligibility criteria. Results: A total of 35 randomized control trials (RCTs) were subjected to the final analysis, including 4,043 patients in treatment group and 3,884 in the control group, as well as 4 clinical-control trials (CCTs), which accessed the final analysis with 238 and 252 patients, respectively. AC reduced the risk of death as a protective treatment with statistical significance (HR=0.91, 95%CI: [0.85, 0.97], P=0.002), and it seemed more effective for Asian than non-Asian patients. The effects of AC were not influenced by the starting time (P>0.05). D2 lymphadenectomy-based chemotherapy was effective (HR=0.89, 95%CI: [0.80, 0.99], P=0.04). Oral S-1 40 mg/m2 after D2 lymphadenectomy might be a better choice for Asians with advanced GC and might result in a greater reduction of adverse events than in non-Asian patients. GRADE quality assessment determined that the strength of the evidence from foreign studies from Europe, the United States and Asian countries other than China was high, while it was moderate for Chinese studies. Conclusion: AC was effective or even curative in Chinese patients in general, although it is still necessary to optimize a targeted AC scheme for Chinese patients with GC.

Physicochemical, Antibacterial Properties, and Compatibility of ZnO-NP/Chitosan/β-Glycerophosphate Composite Hydrogels

( Pingping Huang ),( Wen Su ),( Rui Han ),( Hao Lin ),( Jing Yang ),( Libin Xu ),( Lei Ma ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

In this study we aimed to develop novel ZnO-NP/chitosan/β-glycerophosphate (ZnO-NP/CS/β-GP) antibacterial hydrogels for biomedical applications. According to the mass fraction ratio of ZnO-NPs to chitosan, mixtures of 1, 3, and 5% ZnO-NPs/CS/β-GP were prepared. Using the test-tube inversion method, scanning electron microscopy and Fourier-transform infrared spectroscopy, the influence of ZnO-NPs on gelation time, chemical composition, and cross-sectional microstructures were evaluated. Adding ZnO-NPs significantly improved the hydrogel's antibacterial activity as determined by bacteriostatic zone and colony counting. The hydrogel's bacteriostatic mechanism was investigated using live/dead fluorescent staining and scanning electron microscopy. In addition, crystal violet staining and MTT assay demonstrated that ZnO-NPs/CS/β-GP exhibited good antibacterial activity in inhibiting the formation of biofilms and eradicating existing biofilms. CCK-8 and live/dead cell staining methods revealed that the cell viability of gingival fibroblasts (L929) cocultured with hydrogel in each group was above 90% after 24, 48, and 72 h. These results suggest that ZnO-NPs improve the temperature sensitivity and bacteriostatic performance of chitosan/β-glycerophosphate (CS/β-GP), which could be injected into the periodontal pocket in solution form and quickly transformed into hydrogel adhesion on the gingiva, allowing for a straightforward and convenient procedure. In conclusion, ZnO-NP/CS/β-GP thermosensitive hydrogels could be expected to be utilized as adjuvant drugs for clinical prevention and treatment of peri-implant inflammation.

Oceanobacillus manasiensis sp. nov., a Moderately Halophilic Bacterium Isolated from the Salt Lakes of Xinjiang, China

Lei Wang,Wen-Yan Liu,Zhi-Jing Gu,San-Feng Chen,Su-Sheng Yang 한국미생물학회 2010 The journal of microbiology Vol.48 No.3

Three Gram reaction positive, rod-shaped, moderately motile halophilic bacterial strains, designated YD3-56T, YD16, and YH29, were isolated from the sediments of Manasi and Aiding salt lakes in the Xinjiang region of China, respectively. The strains grew optimally at 30-37°C, pH 8-11, in the presence of 5-10% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains were closely related to members of the genus Oceanobacillus, exhibiting 99.1-99.2% similarity to O. kapialis KCTC 13177T, 99.2-99.3% to O. picturae KCTC 3821T, and 94.2-96% sequence similarity to other described Oceanobacillus species. SDS-PAGE of whole cell proteins preparations demonstrated that the strains exhibited high similarity to each other, but distinguished from O. kapialis KCTC 13177T and O. picturae KCTC 3821T (75%). DNA-DNA hybridization revealed that the similarity between the representative strain YD3-56T and O. kapialis KCTC 13177T was 35.3%, and the similarity between YD3-56T and O. picturae KCTC 3821T was 22.3%. Chemotaxonomic analysis of the strains showed menaquinone-7 was the predominant respiratory quinine. Major cellular fatty acids were anteiso-C15:0 and anteiso-C17:0. The polar lipid pattern for strain YD3-56T predominantly contained phosphatidylcholine, and trace to moderate amounts of phosphatidyl ethanolamine and hydroxy-phosphatidyl ethanolamine. The diamino acid in murein was meso-diaminopimelic acid. The DNA G+C content of the strains was 39.7-40.1 mol%. On the basis of these results, the three strains should be classified as a novel species of the genus Oceanobacillus, for which the name Oceanobacillus manasiensis sp. nov. has been proposed, with the type strain as YD3-56T (=CGMCC 1.9105T =NBRC 105903T).