High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial–mesenchymal transition in lung adenocarcinoma

Hai‑Bo Hu,Xiao‑Ping Yang,Pei‑Xia Zhou,Xin‑Ai Yang,Bin Yin 한국유전학회 2020 Genes & Genomics Vol.42 No.2

Background Lung adenocarcinoma (LUAD) is a more frequent subtype of lung cancer and most cases are discovered in the late stages. The proliferation and metastasis of LUAD are pivotal for disease progression. Despite unremitting deeper understanding of LUAD biology, the mechanisms involved in the proliferation and metastasis of LUAD remain unclear. The objective of our article was to inquiry the expression and the function of keratin 6C (KRT6C) in LUAD cells. Methods First, the expression level and prognostic value of KRT6C in LUAD tissues were analyzed on the basis of the data acquired from TCGA database. Through qRT-PCR, the expression level of KRT6C on LUAD cell lines (A549, H1299, PC-9) and human normal lung cell line MRC-5 was tested. After that, CCK8 and colony formation assays was utilized to detect cell proliferation. In addition, to explore the influence of KRT6C on LUAD migration and invasion ability, scratch wound healing and transwell assays were utilized. Through western blotting, the protein expression levels of KRT6C, PCNA, E-cadherin, N-cadherin, Snail and Vimentin were detected. Results The outcomes revealed that KRT6C was highly expressed in LUAD tissues and cell lines. Besides, elevated level of KRT6C was related to worse prognosis in LUAD patients. Ablation of KRT6C restrained proliferation, migration and invasion of A549 cells. KRT6C deficiency augmented the expression of E-cadherin as well as reduced the expression of N-cadherin, Snail and Vimentin. Conclusion Above all, these consequences indicated that depletion of KRT6C suppressed A549 cell proliferation, migration and invasion, which might be achieved by regulating EMT. In general, KRT6C is identified as a potential therapeutic target for LUAD.

Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARa partially through the ubiquitin–proteasome pathway

Yang Hai,Xin Wang,Peng Song,Jian-yin Li,Longhe Zhao,Fei Xie,Xiang-min Tan,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.8

PML/retinoic acid receptor alpha (RARa), as ahallmark of acute promyeloid leukemia (APL), is directlyrelated to the outcome of clinical APL remedy. It isreported that arsenicals can effectively degrade PML/RARa, such as arsenic trioxide and realgar. However, thehigh toxicity or insolubility have hampered their clinicalapplications. Realgar transforming solution (RTS) wasproduced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significantanti-cancer ability on chronic myeloid leukemia throughoncoprotein degradation. The capacity of RTS on treatingAPL is what is focused on in this study. The results showedthat RTS had a noticeable sensitivity in NB4 cell, and RTSremarkably down-regulated PML/RARa expression andinduced cell differentiation. Further, RTS could accumulatePML/RARa into the nuclear bodies and then executedegradation, which could be reversed by proteasomeinhibitor MG132. The results also exhibited that thereduction of RTS-induced PML/RARa expression accompaniedby the elevation of ubiquitin and SUMO-1 proteinexpression. Finally, PML and SUMO-1 had been demonstratedto be co-localized after RTS treatment byimmunofluorescence co-localization assay and immunoprecipitationassay. In conclusion, these results suggestedthat RTS-induced cell differentiation may attribute to thePML/RARa degradation partially through the ubiquitin–proteasome pathway.

The diversity, recombination and horizontal transmission of Wolbachia in spiders in China

Yang Xiao-Hui,Gong Yu-Hui,Xu Xiang,Yin Hai-Qiang,Zhu Dao-Hong 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.3

Wolbachia are maternally inherited endosymbiotic bacteria. These intracellular bacteria are common in ar thropods and could manipulate host reproduction in diverse ways, such as feminization, parthenogenesis, male killing and cytoplasmic incompatibility. In spiders, infection by Wolbachia has been found in a total of 99 species belonging to 62 genera and 17 families. Furthermore, recent studies analyzed the phylogeny of Wolbachia in Hylyphantes graminicola, 2 cave spiders and Agelenopsis species using multilocus sequence typing (MLST) approach. However, the diversity of Wolbachia strains determined by MLST in spiders from China is still largely unknown. In this study, we collected 1153 spider individuals from Mangshan in China and screened for Wolbachia in 975 individuals representing 68 spider species belonging to 45 genera of 16 families. We analyzed the phylogenetic relationship between Wolbachia and their host spiders by MLST approach. We found novel infections of Wol bachia in 1 family, 9 genera and 20 species of spiders. We found 13 new Wolbachia strains and suggest that group A is more common than group B in Wolbachia that infect spiders. Our results revealed three recombination events of the concatenated multilocus sequences in Wolbachia that infect spiders. Furthermore, our results demonstrated the phylogenetic incongruence between Wolbachia and spiders, suggesting the horizontal transmission of Wol bachia in spiders. We suggest that recombination and horizontal transmission may play an important role in the diversity and evolution of Wolbachia in spiders.

Triterpenoid saponins from Clinopodium chinense (Benth.) O. Kuntze and their biological activity

Yin-Di Zhu,Jing-Yi Hong,Feng-Da Bao,Na Xing,Ling-Tian Wang,Zhong-Hao Sun,Yun Luo,Hai Jiang,Xudong Xu,Nai-Liang Zhu,Hai-Feng Wu,Gui-Bo Sun,Jun-Shan Yang 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12

Four new ursane-type triterpenoid saponins, clinopoursaponins A–D (1–4), six new oleanane-type triterpenoid saponins, clinopodiside VII–XII (5–10), as well as eight known triterpene analogues (11–18), were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. The structures of the new compounds were determined based on extensive spectral analyses, including 1D (1H and 13C) and 2D NMR experiments (COSY, NOESY, HSQC, 2D TOCSY, HSQC-TOCSY and HMBC), HR-ESI-MS and chemical methods. Compounds 1–18 were evaluated for their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells and cytotoxicities against murine mammary carcinoma cell line 4T1. Compounds 8, 9 and 18 exhibited significant protective effects, while compound 1 exhibited cytotoxic activity with IC50 value of 7.4 μm compared to 7.6 μm for the positive control 10-hydroxycamptothecin.

Trifluoroethanol-induced changes in activity and conformation of manganese-containing superoxide dismutase.

Yin, Shang-Jun,L?, Zhi-Rong,Park, Daeui,Chung, Hae Young,Yang, Jun-Mo,Zhou, Hai-Meng,Qian, Guo-Ying,Park, Yong-Doo Humana Press 2012 Applied biochemistry and biotechnology Vol.166 No.2

<P>Superoxide dismutase (SOD, EC 1.15.1.1) plays an important role in antioxidant defense in organisms exposed to oxygen. However, there is a lack of research into the regulation of SOD activity and structural changes during folding, especially for SOD originating from extremophiles. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of manganese-containing SOD (Mn-SOD) from Thermus thermophilus. TFE decreased the degree of secondary structure of Mn-SOD, which directly resulted in enzyme inactivation and disrupted the tertiary structure of Mn-SOD. The kinetic studies showed that TFE-induced inactivation of Mn-SOD is a first-order reaction and that the regional Mn-contained active site is very stable compared to the overall structure. We further simulated the docking between Mn-SOD and TFE (binding energy for Dock 6.3, -9.68 kcal/mol) and predicted that the LEU9, TYR13, and HIS29 residues outside of the active site interact with TFE. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of TFE and allow us to describe ligand binding via inhibition kinetics combined with computational predictions.</P>

Whole-liver Radiotherapy Concurrent with Chemotherapy as a Palliative Treatment for Colorectal Patients with Massive and Multiple Liver Metastases: a Retrospective Study

Yin, Hang,Lu, Kai,Qiao, Wen-Bo,Zhang, Hai-Yang,Sun, Di,You, Qing-Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) and invasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy. The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenous dose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months. The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presented with abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice were confirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded. There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases.

Synthesis and Cytotoxicity of Novel 3-Amino-4-indolylmaleimide Derivatives

Sheng-Yin Zhao,Yan-Wu Yang,Hai-Quan Zhang,Yun Yue,Mei Fan 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4

In an attempt to develop potent and selective antitumor agents, a series of novel 3-amino-4-indolylmaleimides were designed and synthesized. The reaction showed high regioselectivity. The structure of compound 7a was determined by an X-ray single crystal diffraction method. The cytotoxicities of the title compounds were evaluated against HeLa, SMMC 7721 and HL 60 cancer cell lines by a standard MTT assay in vitro. The pharmacological results showed that some of the title compounds displayed moderate or high cytotoxic activity against the tested cell lines. Compound 7d was the most promising compound against the tested cancer cell lines. Structure-activity relationships are discussed based on the experimental data obtained. A hydroxyethylamino group at the 3-position in the side chain of indolylmaleimide is associated with an increase in cytotoxicity.

Associations of hypoxia inducible factor-1a gene polymorphisms with susceptibility to digestive tract cancers: a case–control study and meta-analysis

Zhi-Hai Ni,Xian-Jun Liang,Jing-Gang Mo,Yi Zhang,Jian-Hua Liang,Yu-Sha Yang,Yong Zhou,Zhao-Hua Li,Jian-Liang Zhang,Yin-Lu Ding,Peng Zhang,Jin-Qing Wang 한국유전학회 2015 Genes & Genomics Vol.37 No.11

We aim to investigate the correlations of hypoxia inducible factor-1a (HIF-1a) C1772T (rs11549465) and G1790A (rs11549467) gene polymorphisms with digestive tract cancers. A sum of 267 digestive tract cancers patients were hospitalized in Taizhou Central Hospital of Zhejiang Province as case group between December 2012 and December 2014. Additionally, 275 healthy people who had a physical examination in our hospital at the same time were selected as control group. Polymerase chain reaction-restriction fragment length polymorphism was utilized for detecting allele and genotype frequency of different locus in case and control group. Meta-analysis was performed using Comprehensive Metaanalysis 2.0 (Biostat Inc., Englewood, New Jersey, USA). Our result showed statistical significance only exists in family history of cancer between case and control group (P\0.05). Both C1772T (rs11549465) and G1790A (rs11549467) polymorphisms showed positive correlations with an increasing risk of digestive tract cancers. The frequencies of TT genotype of C1772T (rs11549465) and GA, AA genotypes of G1790A (rs11549467) polymorphisms in case group were evidently higher compared with the controls (all P\0.05). Besides, the comparison of allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) between two groups showed a significant difference (all P\0.05). Meta-analysis results further confirmed that the onset risk of digestive tract cancers may be improved under allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) (all P\0.05). Single nucleotide polymorphisms of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) may play a role in development of digestive tract cancers.

Biotransformation of natural polyacetylene in red ginseng by Chaetomium globosum

Wang, Bang-Yan,Yang, Xue-Qiong,Hu, Ming,Shi, Li-Jiao,Yin, Hai-Yue,Wu, Ya-Mei,Yang, Ya-Bin,Zhou, Hao,Ding, Zhong-Tao The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.6

Background: Fermentation has been shown to improve the biological properties of plants and herbs. Specifically, fermentation causes decomposition and/or biotransformation of active metabolites into high-value products. Polyacetylenes are a class of polyketides with a pleiotropic profile of bioactivity. Methods: Column chromatography was used to isolate compounds, and extensive NMR experiments were used to determine their structures. The transformation of polyacetylene in red ginseng (RG) and the production of cazaldehyde B induced by the extract of RG were identified by TLC and HPLC analyses. Results: A new metabolite was isolated from RG fermented by Chaetomium globosum, and this new metabolite can be obtained by the biotransformation of polyacetylene in RG. Panaxytriol was found to exhibit the highest antifungal activity against C. globosum compared with other major ingredients in RG. The fungus C. globosum cultured in RG extract can metabolize panaxytriol to Metabolite A to survive, with no antifungal activity against itself. Metabolites A and B showed obvious inhibition against NO production, with ratios of 42.75 ± 1.60 and 63.95 ± 1.45% at 50 µM, respectively. A higher inhibitory rate on NO production was observed for Metabolite B than for a positive drug. Conclusion: Metabolite A is a rare example of natural polyacetylene biotransformation by microbial fermentation. This biotransformation only occurred in fermented RG. The extract of RG also stimulated the production of a new natural product, cazaldehyde B, from C. globosum. The lactone in Metabolite A can decrease the cytotoxicity, which was deemed to be the intrinsic activity of polyacetylene in ginseng.

Effect of Abiotic Factors on Fumosorinone Production from Cordyceps fumosorosea via Solid-State Fermentation

Khan Tahir,Hou Dong-Hai,Zhou Jin-Na,Yang Yin-Long,Yu Hong 한국균학회 2023 Mycobiology Vol.51 No.3

Cordyceps fumosorosea is an important species in the genus of Cordyceps, containing a variety of bioactive compounds, including fumosorinone (FU). This study was a ground-breaking assessment of FU levels in liquid and solid cultures. The present study focused on the impacts of solid-state fermentation (SSF) using solid substrates (wheat, oat, and rice), as well as the effects of fermentation parameters (pH, temperature, and incubation period), on the generation of FU. All the fermentation parameters had significant effects on the synthesis of FU. In a study of 25 C, 5.5 pH, and 21 days of incubation period combinations calculated -to give maximal FU production, it was found that the optimal values were 25 C, 5.5 pH, and 21 days, respectively. In a solid substrate medium culture, FU could be produced from SSF. At 30 days, a medium composed of rice yielded the most FU (798.50mg/L), followed by a medium composed of wheat and oats (640.50 and 450.50mg/L), respectively. An efficient method for increasing FU production on a large scale could be found in this approach. The results of this study might have multiple applications in different industrial fermentation processes.