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| 1 | IDO1 in cancer: a Gemini of immune checkpoints显示文摘Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。 | Lijie Zhai Erik Ladomersky Alicia Lenzen Brenda Nguyen Ricky Patel Kristen L Lauing Meijing Wu Derek A Wainwright | 2018 | Cellular & Molecular Immunology2018，15，5： | 17 |
| 2 | Elevated serum uric acid level as a predictor for cardiovascu-lar and all-cause mortality in Chinese patients with high cardiovascular risk显示文摘Objective To assess the predictive value of serum uric acid levels for cardiovascular and all-cause mortality in a large prospective population based study.Methods The study was based on 3648 participants in Shanghai and Beijing,who were inpatients with high cardiovascular(CV) risk at baseLine (2004.7 to 2005.1),and blood was taken.Follow-up for death from cardiovascular disease and any cause was complete until January 1,2006.Results The mean follow-up was 1 years.There were 303 deaths during follow-up,of which 121 were cardiovascular.Crude mortality rates were 8.3 % for all patients,6.8% for female patients (116/1715),and 9.7% (187/1933) for male patients.Among men,patients in the lower and higher uric acid groups had increased cardiac and overall mortality risks compared with patients in the normal uric acid groups.Similar relation was found in women but not statistically significant.After adjusting for other conventional risk factors (age,diabetes,hypertension,diuretic use and smoking),baseline uric acid level was still associated with increased risk for death from cardiovascular disease (P=0.005),or death from all causes (P=0.014) Conclusion Our data suggest that abnormal serum uric acid levels are independently and significantly associated with risk of cardiovascular and all-cause mortality.(J Geriatr Cardiol 2008;5:15-20) | Yongquan Wu Meijing Li Jue Li Yingyi Luo Yan Xing Dayi Hu | 2008 | Journal of Geriatric Cardiology2008，5，1： | 0 |
| 3 | Generation of functional oligopeptides that promote osteogenesis based on unsupervised deep learning of protein IDRs显示文摘Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification. | Mingxiang Cai Baichuan Xiao Fujun Jin Xiaopeng Xu Yuwei Hua Junhui Li Pingping Niu Meijing Liu Jiaqi Wu Rui Yue Yong Zhang Zuolin Wang Yongbiao Zhang Xiaogang Wang Yao Sun | 2022 | Bone Research2022，10，2： | 0 |
| 4 | Pancreatic cancer-related pain:mechanism and management显示文摘Pancreatic cancer-related pain(PCRP)gains widespread attention for its high prevalence,extreme complexity,poor prognosis,and decreased survival rate.Current treatment of PCRP remains unsatisfactory since the underlying mechanism is not clear.The occurrence of PCRP is mainly related to the neurotropic nature of pancreatic cancer,and perineural invasion,neural remodeling and plasticity play important roles.Upon the understanding of PCRP mechanism,the management of PCRP is a multidisciplinary and multifaceted strategy.Traditional pain medications,invasive or intervention treatment,psychological support,integrative therapy,and palliative care are all the potential aspects for the management of PCRP. | Meijing Wu Afang Zhu Le Shen | 2023 | Journal of Pancreatology2023，6，4： | 0 |
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