Browsing by Author "Zhang, Qian"

Now showing 1 - 4 of 4
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    A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells
    (American Association for the Advancement of Science, 2025) Eduardo, Mariana Bustamante; Cottone, Gannon; McCloskey, Curtis W.; Liu, Shiyu; Palma, Flavio R.; Zappia, Maria Paula; Islam, Abul B. M. M. K.; Gao, Peng; Setya, Joel; Dennis, Saya; Gao, Hongyu; Zhang, Qian; Xuei, Xiaoling; Luo, Yuan; Locasale, Jason; Bonini, Marcelo G.; Khokha, Rama; Frolov, Maxim V.; Benevolenskaya, Elizaveta V.; Chandel, Navdeep S.; Khan, Seema A.; Clare, Susan E.; Medical and Molecular Genetics, School of Medicine
    Lipid metabolism and the serine, one-carbon, glycine (SOG) and methionine pathways are independently and significantly correlated with estrogen receptor-negative breast cancer (ERneg BC). Here, we propose a link between lipid metabolism and ERneg BC through phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine pathway. We demonstrate that the metabolism of the paradigmatic medium-chain fatty acid octanoic acid leads to a metabolic shift toward the SOG and methionine pathways. PHGDH plays a role in both the forward direction, contributing to the production of S-adenosylmethionine, and the reverse direction, generating the oncometabolite 2-hydroxyglutarate, leading to epigenomic reprogramming and phenotypic plasticity. The methionine cycle is closely linked to the transsulfuration pathway. Consequently, we observe that the shift increases the antioxidant glutathione, which mitigates reactive oxygen species (ROS), enabling survival of a subset of cells that have undergone DNA damage. These metabolic changes contribute to several hallmarks of cancer.
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    Detecting and phenotyping of aneuploid circulating tumor cells in patients with various malignancies
    (Taylor & Francis, 2019) Ye, Zhenlong; Ding, Yongmei; Chen, Zhuo; Li, Zhong; Ma, Shuo; Xu, Zenghui; Cheng, Liang; Wang, Xinyue; Zhang, Xiaoxia; Ding, Na; Zhang, Qian; Qian, Qijun; Pathology and Laboratory Medicine, School of Medicine
    Circulating tumor cells (CTCs) have been exclusively studied and served to assess the clinical outcomes of treatments and progression of cancer. Most CTC data have mainly been derived from distinct cohorts or selected tumor types. In the present study, a total of 594 blood samples from 479 cases with 19 different carcinomas and 30 healthy samples were collected and analyzed by Subtraction enrichment method combined with immunostaining-fluorescence in situ hybridization (iFISH). Non-hematopoietic cells with aneuploid chromosome 8 (more than 2 copies) were regarded as positive CTCs. The results showed that none of CTCs was found in all 30 healthy samples. The overall positive rate of CTCs was 89.0% in diagnosed cancer patients (ranging from 75.0% to 100.0%). Average number of 11, 5, 8 and 4 CTCs per 7.5 mL was observed in lung cancer, liver cancer, renal cancer and colorectal cancer, respectively. Among 19 different carcinomas, the total number of CTCs, tetraploid chromosome 8, polyploid chromosome 8, CTM (Circulating tumor microemboli) and large CTCs in patients with stage Ⅲ and Ⅳ were statistically higher than patients with stage Ⅰ and Ⅱ (P < 0.05). Furthermore, EpCAM expression was more frequently found in most CTCs than vimentin expression, confirming that these CTCs were of epithelial origin. In addition, small and large CTCs were also classified, and the expression of vimentin was mostly observed in small CTCs and CTM. Our results revealed that there are higher numbers of CTCs, tetraploid, polyploid and large CTCs in patients with stage Ⅲ and Ⅳ, indicating that the quantification of chromosome ploidy performed by SE-iFISH for CTCs might be a useful tool to predict and evaluate therapeutic efficacy as well as to monitoring disease progression.
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    Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex
    (Oxford University Press, 2021-04-08) Jonsson, William O.; Margolies, Nicholas S.; Mirek, Emily T.; Zhang, Qian; Linden, Melissa A.; Hill, Cristal M.; Link, Christopher; Bithi, Nazmin; Zalma, Brian; Levy, Jordan L.; Pettit, Ashley P.; Miller, Joshua W.; Hine, Christopher; Morrison, Christopher D.; Gettys, Thomas W.; Miller, Benjamin F.; Hamilton, Karyn L.; Wek, Ronald C.; Anthony, Tracy G.; Biochemistry and Molecular Biology, School of Medicine
    Background: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). Objective: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. Methods: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. Results: We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. Conclusions: Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice.
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    Quantifying river water contributions to the transpiration of riparian trees along a losing river: lessons from stable isotopes and an iteration method
    (EGU, 2023) Li, Yue; Ma, Ying; Song, Xianfang; Zhang, Qian; Wang, Lixin; Earth and Environmental Sciences, School of Science
    River water plays a critical role in riparian plant water use and riparian ecosystem restoration along losing rivers (i.e., river water recharging underlying groundwater). How to quantify the contributions of river water to the transpiration of riparian plants under different groundwater levels and the related responses of plant water use efficiency is a great challenge. In this study, observations of stable isotopes of water (δ2H and δ18O), 222Rn, and leaf δ13C were conducted for the deep-rooted riparian weeping willow (Salix babylonica L.) in 2019 (dry year) and 2021 (wet year) along the Chaobai River in Beijing, China. We proposed an iteration method in combination with the MixSIAR model to quantify the river water contribution to the transpiration of riparian S. babylonica and its correlations with the water table depth and leaf δ13C. Our results demonstrated that riparian S. babylonica took up deep water (in the 80–170 cm soil layer and groundwater) by 56.5 % ± 10.8 %. River water recharging riparian deep water was an indirect water source and contributed 20.3 % of water to the transpiration of riparian trees near the losing river. Significantly increasing river water uptake (by 7.0 %) and decreasing leaf δ13C (by −2.0 ‰) of riparian trees were observed as the water table depth changed from 2.7 m in the dry year of 2019 to 1.7 m in the wet year of 2021 (p<0.05). The higher water availability probably promoted stomatal opening and thus increased transpiration water loss, leading to the decreasing leaf δ13C in the wet year compared to the dry year. The river water contribution to the transpiration of riparian S. babylonica was found to be negatively linearly correlated with the water table depth and leaf δ13C (p<0.01). The rising groundwater level may increase the water extraction from the groundwater and/or river and produce a consumptive river-water-use pattern of riparian trees, which can have an adverse impact on the conservation of both river flow and riparian vegetation. This study provides new insights into understanding the mechanisms of the water cycle in a groundwater–soil–plant–atmosphere continuum and managing water resources and riparian afforestation along losing rivers.