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| 1 | Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction显示文摘Zika 病毒(ZIKV ) 的最近的爆发为治疗学加亮迫切需要。朊酶建筑群 NS2B-NS3 在 flaviviral polyprotein 处理期间起必要作用,并且因此代表一个吸引人的药目标。这里,我们开发了裂口酶识别直接指向 flavivirus NS2B-NS3 相互作用的 orthosteric 禁止者的基于互补的高产量的屏蔽试金。由屏蔽一个总数 2 816 同意了并且 investigational 药,我们识别了三个有势力候选人, temoporfin, niclosamide,和 nitazoxanide,,有 nanomolar 力量的 flavivirus NS2B-NS3 相互作用禁止者。显著地,在老鼠的在人的胎盘、神经的祖先房间的大多数有势力化合物, temoporfin,不是仅仅禁止的 ZIKV 复制,而且阻止的导致 ZIKV 的 viremia 和死亡当模特儿。结构的停靠建议 temoporfin 潜在地绑保持批评 NS2B 残余的 NS3 衣袋,因此禁止以一种非竞争的方式处理的 flaviviral polyprotein。当这些药已经在 USA 或另外的国家在另外的指示任何一个为临床的使用被同意了,他们由 ZIKV 和另外的 flaviviruses 为感染的管理代表有希望、容易开发的治疗。 | Zhong Li Matthew Brecher Yong-Qiang Deng Jing Zhang Srilatha Sakamuru Binbin Liu Ruili Huang Cheri A Koetzner Christina A Allen Susan A Jones Haiying Chen Na-Na Zhang Min Tian Fengshan Gao Qishan Lin Nilesh Banavali Jia Zhou Nathan Boles Menghang Xia Laura D Kramer Cheng-Feng Qin Hongmin Li | 2017 | Cell Research2017，27，8： | 11 |
| 2 | Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation显示文摘Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes. | Qiubing Chen Qian Li Yuqi Liang Menghang Zu Nanxi Chen Brandon S.B.Canup Liyong Luo Chenhui Wang Liang Zeng Bo Xiao | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 4 |
| 3 | Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy显示文摘Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin(DOX)-loaded silk fibroinbased nanoparticles(NPs) with surface functionalization by photosensitizer(N770). The obtained nanotheranostics(N770-DOX@NPs) had desirable particle size(157 nm) and negative surface charge(-25 m V). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli(acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared(NIR) fluorescence imaging, photothermal imaging,and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumorretardation effect among all treatment groups based on tumor-bearing mouse models and a patientderived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imagingguided mitochondrial phototherapy(photothermal therapy and photodynamic therapy) and chemotherapy.Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors. | Shuangquan Gou Nanxi Chen Xiaoai Wu Menghang Zu Shixiong Yi Binwu Ying Fangyin Dai Bowen Ke Bo Xiao | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 2 |
| 4 | Efficacy of ICIs on patients with oncogene-driven non-small cell lung cancer:a retrospective study显示文摘Aim:The objective of our study was to assess the efficacy of immune checkpoint inhibitors(ICIs)on patients with non-small-cell lung cancer(NSCLC)harboring oncogenic alterations.Methods:We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy.Major characteristics including PD-L1 expression,treatment,and survival were analyzed.Results:In total,309 non-squamous NSCLC patients with a median age of 61 years(range 20-88 years)including 70.9%male were retrospectively enrolled.The molecular alterations involved epidermal growth factor receptor(EGFR)(n=81),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)(n=31),anaplastic lymphoma kinase(ALK)(n=1),human epidermal growth factor receptor 2(HER2)(n=12),V-raf murine sarcoma viral oncogene homolog(BRAF)(n=2),rearranged during transfection(n=4),and c-ros oncogene 1(ROS1)(n=3).In the EGFR subset,the ORR was 30.9%(n=81)and PFS was significantly shorter than WT group(median PFS:5.7 months vs.7.1 months;P=0.0061).In subgroup analyses,ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy(median PFS:7.7 months vs.4.7 months;P=0.0112).In KRAS patients,ORR was 51.6%(n=31).No significant difference was found in subgroup analyses.The ORR and PFS were 16.7%(n=12)and 28.6%(n=7),7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients,respectively.Three ROS1 patients were enrolled with a PFS of 16.0,34.2,and 45.0 months individually,and one ALK patient with PFS of 4.4 months was identified.No response was found in two BRAF patients.Conclusion:ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC.ICI-based combination therapy could be considered for patients with ROS1 rearrangement,HER2 mutation and EGFR Exon20 insertion NSCLC. | Xiaojin Guo He Du Jiayu Li Menghang Yang Anweng Xiong Haiping Zhang Fengying Wu | 2022 | Cancer Drug Resistance2022，5，1： | 2 |
| 5 | Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity显示文摘Haloacetamides(HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs(iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM > BAM > CAM for Rad51, and BAM ≈ IAM > CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM. | Justin A.Pals Elizabeth D.Wagner Michael J.Plewa Menghang Xia Matias S.Attene-Ramos | 2017 | Journal of Environmental Sciences2017，29，8： | 1 |
| 6 | Identification of known drugs that act as inhibitors of NF-κB signaling and their mechanism of action显示文摘 | Susanne C. Miller Ruili Huang Srilatha Sakamuru Sunita J. Shukla Matias S. Attene-Ramos Paul Shinn Danielle Van Leer William Leister Christopher P. Austin Menghang Xia | 2010 | Biochemical Pharmacology2010，，： | 1 |
| 7 | Mechanism of HERG potas- sium channel inhibition by tetra - n - octylammonium bromide and benzethonium chloride显示文摘 | Yah L Zuoxian L Menghang X | 2013 | Toxico and Appl Pharmaco2013，267，2： | 1 |
| 8 | High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice显示文摘Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles.Previous studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein adducts.The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes.In the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers.Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,respectively.Mechanistically,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against AILI.We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists.Among these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in mice.In conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI. | Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
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