Phosphorylation of DYNLT1 at Serine 82 Regulates Microtubule Stability and Mitochondrial Permeabilization in Hypoxia

Xue Xu,Yue-sheng Huang,Qiong Zhang,Jiong-yu Hu,Dong-xia Zhang2,Xu-pin Jiang,jie-zhi Jia,Jing-ci Zhu 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.4

Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection. But the underlying regulatory mechanism of DYNLT1 remains illusive. Here we aimed to investigate the phosphorylation alteration of DYNLT1 at serine 82 (S82) in hypoxia (1% O2). We therefore constructed recombinant adenoviruses to generate S82E and S82A mutants, used to transfect H9c2 and HeLa cell lines. Development of hypoxia-induced mPT (MMP examining, Cyt c release and mPT pore opening assay), hypoxic energy metabolism (cellular viability and ATP quantification), and stability of MTs were examined. Our results showed that phosph-S82 (S82-P) expression was increased in early hypoxia; S82E mutation (phosphomimic) aggravated mitochondrial damage, ele-vated the free tubulin in cytoplasm and decreased the cellular viability; S82A mutation (dephosphomimic) seemed to diminish the hypoxia-induced injury. These data suggest that DYNLT1 phosphorylation at S82 is involved in MTs and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. Thus, we provide new insights into a DYNLT1 mechanism in stabilizing MTs and mitochondria, and propose a potential therapeutic target for hypoxia cytoprotective studies.

A New ent-Kaurane type Diterpenoid Glycoside from Inula japonica Thunb

Jiang Jiang Qin,Jia Xian Zhu,Wei Dong Zhang1,2,Yan Zhu,Jian Jun Fu,Xiao Hua Liu,Hui Zi Jin 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.10

A new ent-kaurane type diterpenoid glycoside, 17-O-β-D-glucopyranosyl-16α-ent-kauran-19-oic acid (1), together with 17-hydroxy-16α-ent-kauran-19-oic acid (2), 16α,17-dihydroxyl-ent-kauran-19-oic acid (3), and 16α-hydroxy-17-acetoxy-ent- kauran-19-oic acid (4) were isolated from the aerial parts of Inula japonica Thunb. The structure of 1 was determined mainly by use of 1D and 2D NMR spectroscopic techniques including HSQC, 1H-1H COSY, HMBC, and NOESY. In addition, 4 exhibited significant inhibitory activity on NO production in LPS-stimulated RAW264.7 cells with IC50 value of 14.3 μg/mL.

A national survey on how to improve traditional Chinese medicine learning internationally: Perceptions from both teachers and students

Zhu Yu-Hang,Yan Wu,Hao Zhang,Yanfei Zhao,Yule Ren,Wei Hu,Pan Li,Huiyi Wang,Ying Wang,Boda Zhang,Yujie Wang,Hongwen Yuan,Jiping Zhang,Wenqiang Li,Yufang Zhao,Jie Zhao,Yedong Shi,Yanye Shu,Xiao Zhang,Ya 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.4

Background With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. Methods A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Results Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). Conclusion To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.

Risk Factors for Cervical Cancer in Rural Areas of Wuhan China: a Matched Case-control Study

Zhang, Bin,Zhou, Ai-Fen,Zhu, Chang-Cai,Zhang, Ling,Xiang, Bing,Chen, Zhong,Hu, Rong-Hua,Zhang, Ya-Qi,Qiu, Lin,Zhang, Yi-Ming,Xiong, Chao-Du,Du, Yu-Kai,Shi, Yu-Qin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Cervical cancer is a serious public health problem in developing countries. We investigated possible risk factors for cervical cancer in rural areas of Wuhan China using a matched case-control study with 33 women diagnosed with cervical cancer and 132 healthy women selected from the same area as matched controls. A questionnaire, which included questions about general demography conditions, environmental and genetic factors, the first sexual intercourse, first marriage age, age at first pregnancy, pregnancy first child's age, female personal health history, social psychological factors, dietary habits, smoking and alcohol status and other living habits was presented to all participants. At the same time, HPV infection of every participant was examined in laboratory testing. Results showed HPV infection (P<0.000, OR=23.4) and pregnancy first child's age (P<0.000, OR=13.1) to be risk factors for cervical cancer. Menopause (P=0.003, OR=0.073) was a protective factor against cervical cancer. However, there was no indication of associations of environmental (drinking water, insecticide, disinfectant) genetic (cancer family history), or life-style factors (smoking status, alcohol status, physical training, sleep quality), including dietary habits (intake of fruit and vegetable, meat, fried food, bean products and pickled food) or social psychological factors with cervical cancer. The results suggest that the risk of cervical cancer in Chinese rural women may be associated with HPV infection, menopause and the pregnancy first child's age.

White-light crosslinkable milk protein bioadhesive with ultrafast gelation for first-aid wound treatment

Zhu Qinchao,Zhou Xuhao,Zhang Yanan,Ye Di,Yu Kang,Cao Wangbei,Zhang Liwen,Zheng Houwei,Sun Ziyang,Guo Chengchen,Hong Xiaoqian,Zhu Yang,Zhang Yajun,Xiao Ying,Valencak Teresa G.,Ren Tanchen,Ren Daxi 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background : Post-traumatic massive hemorrhage demands immediately available first-aid supplies with reduced operation time and good surgical compliance. In-situ crosslinking gels that are flexibly adapting to the wound shape have a promising potential, but it is still hard to achieve fast gelation, on-demand adhesion, and wide feasibility at the same time. Methods : A white-light crosslinkable natural milk-derived casein hydrogel bioadhesive is presented for the first time. Benefiting from abundant tyrosine residues, casein hydrogel bioadhesive was synthesized by forming di-tyrosine bonds under white light with a ruthenium-based catalyst. We firstly optimized the concentration of proteins and initiators to achieve faster gelation and higher mechanical strength. Then, we examined the degradation, cytotoxicity, tissue adhesion, hemostasis, and wound healing ability of the casein hydrogels to study their potential to be used as bioadhesives. Result : Rapid gelation of casein hydrogel is initiated with an outdoor flashlight, a cellphone flashlight, or an endoscopy lamp, which facilitates its usage during first-aid and minimally invasive operations. The rapid gelation enables 3D printing of the casein hydrogel and excellent hemostasis even during liver hemorrhage due to section injury. The covalent binding between casein and tissue enables robust adhesion which can withstand more than 180 mmHg blood pressure. Moreover, the casein-based hydrogel can facilitate post-traumatic wound healing caused by trauma due to its biocompatibility. Conclusion : Casein-based bioadhesives developed in this study pave a way for broad and practical application in emergency wound management.

Study of upfront surgery versus neoadjuvant chemotherapy followed by interval debulking surgery for patients with stage IIIC and IV ovarian cancer, SGOG SUNNY (SOC-2) trial concept

Rong Jiang,Jianqing Zhu,김재원,Jihong Liu,Kazuyoshi Kato,김희승,Yuqin Zhang,Ping Zhang,Tao Zhu,Daisuke Aoki,Aijun Yu,Xiaojun Chen,Xipeng Wang,Ding Zhu,Wei Zhang,Huixun Jia,Ting-Yan Shi,Wen Gao,Sheng Yin,Yan 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.5

Background: Two randomized phase III trials (EORTC55971 and CHORUS) showed similarprogression-free and overall survival in primary or interval debulking surgery in ovariancancer, however both studies had limitations with lower rate of complete resection and lack ofsurgical qualifications for participating centers. There is no consensus on whether neoadjuvantchemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approachin the management of advanced epithelial ovarian cancer (EOC) in the clinical practice. Methods: The Asian SUNNY study is an open-label, multicenter, randomized controlled,phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS instages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS inadvanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS inthe treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of nogross residual (NGR) in PDS group in all centers and participating centers should be nationalcancer centers or designed ovarian cancer section or those with the experience participatingsurgical trials of ovarian cancer. Any participating center should be monitored evaluatingthe proportions of NGR by a training set. The aim of the surgery in both arms is maximalcytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy orpositron emission tomography/computed tomography scan. Patients assigned to PDS groupwill undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal timeinterval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusioncriteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performancestatus of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as wellas borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456subjects. Primary endpoint is overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT02859038

Addendum: A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum- sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study

Ting-Yan Shi,Libing Xiang,Jianqing Zhu,Ji-hong Liu,Ping Zhang,Hua-ying Wang,Yanling Feng,Tao Zhu,Yingli Zhang,Aijun Yu,Wei Jiang,Xipeng Wang,Yaping Zhu,Sufang Wu,Yincheng Teng,Jiejie Zhang,Rong Jiang 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4

Expression of the Arabidopsis vacuolar $H^+$-pyrophosphatase gene AVP1 in peanut to improve drought and salt tolerance

Qin, Hua,Gu, Qiang,Kuppu, Sundaram,Sun, Li,Zhu, Xunlu,Mishra, Neelam,Hu, Rongbin,Shen, Guoxin,Zhang, Junling,Zhang, Yizheng,Zhu, Longfu,Zhang, Xianlong,Burow, Mark,Payton, Paxton,Zhang, Hong 한국식물생명공학회 2013 Plant biotechnology reports Vol.7 No.3

The Arabidopsis gene AVP1 encodes an $H^+$-pyrophosphatase that functions as a proton pump at the vacuolar membranes, generating a proton gradient across vacuolar membranes, which serves as the driving force for many secondary transporters on vacuolar membranes such as $Na^+/H^+$-antiporters. Overexpression of AVP1 could improve drought tolerance and salt tolerance in transgenic plants, suggesting a possible way in improving drought and salt tolerance in crops. The AVP1 was therefore introduced into peanut by Agrobacterium-mediated transformation. Analysis of AVP1-expressing peanut indicated that AVP1-overexpression in peanut could improve both drought and salt tolerance in greenhouse and growth chamber conditions, as AVP1-overexpressing peanuts produced more biomass and maintained higher photosynthetic rates under both drought and salt conditions. In the field, AVP1-overexpressing peanuts also outperformed wild-type plants by having higher photosynthetic rates and producing higher yields under low irrigation conditions.

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

Kaili Lin,Stephen Cho-Wing Sze,Bin Liu,Zhang Zhang,Zhu Zhang,Peili Zhu,Ying Wang,Qiudi Deng,Ken Kin-Lam Yung,Shiqing Zhang 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2

Background: Alzheimer"s disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

Identifying natural genotypes of grain number per panicle in rice (Oryza sativa L.) by association mapping

Jianyin Xie,Fengmei Li,Najeeb Ullah Khan,Xiaoyang Zhu,Xueqiang Wang,Zhifang Zhang,Xiaoqian Ma,Yan Zhao,Quan Zhang,Shuyang Zhang,Zhanying Zhang,Jinjie Li,Zichao Li,Hongliang Zhang 한국유전학회 2019 Genes & Genomics Vol.41 No.3

Introduction As one of the main yield components, grain number per panicle (GNP) played critical role in the rice yield improvement. The identification of natural advantageous variations under different situations will promote the sustainable genetic improvement in rice yield. Objectives This study was designed to identify natural genotypes in a rice mini-core collection, to examine the genotypic effects across the indica and japonica genetic background in different environments, and excavating the superior genotypes that had drove the modern genetic improvement. Methods The association mapping of GNP was carried out using a mini-core collection including 154 indica and 119 japonica accessions in seven different environments. Genotypic effects of each genotype for each QTL were calculated and genotype frequency distortion between the commercial rice cultivars and landraces was screened by χ2-test. Results In total, 74 QTLs containing stable and sensitive QTLs in various environments were detected. Within them, 20 positive and 24 negative genotypes in indica, and 24 positive and 16 negative genotypes in japonica were identified. When checking the accumulation of positive genotypes identified in indica across cultivars in each of the two subspecies, it indicated that increased number of positive genotypes identified in indica results in the substantially increased GNP in both indica and japonica across all of the environments, while this trend was not obvious for the positive genotypes identified in japonica especially in short day environments. Moreover, the positive and negative genotype frequency distortion between the landraces and commercial rice cultivars indicated that both positive selection of positive genotypes and negative selection of negative genotypes had driven the genetic improvement on GNP. Conclusion Our findings suggested that the accumulation of positive genotypes and purifying negative genotypes played equivalently important roles in the improvement of rice yield, but the efficient use for some QTLs or genotypes depends on the comprehensive evaluation of their effect under diverse genetic backgrounds and environments.