Also published as: B. Tian, Bei Tian, Erkang Tian, H Tian, H. Tian, Hongling Tian, Hua Tian, J Tian, K Tian, K. Tian, L. Tian, Liya Tian, M Tian, M. Tian, Meng Tian, R Tian, S Tian, Shuang Tian, Shubo Tian, T Tian, W Tian, Wang Tian, X Tian, XY Tian, Xiaofang Tian, Xiaohong Tian, Y Tian, Y. Tian, Yi Tian, Yun-Feng Tian, Z Tian, Zhenzhen Tian, Zichao Tian
The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or are under oxidative stress. Therapeutic activation of NRF2 can also be used prior to insult as a means of d Show more
The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or are under oxidative stress. Therapeutic activation of NRF2 can also be used prior to insult as a means of disease prevention. However, prolonged expression of NRF2 has been shown to protect cancer cells by inducing the metabolism and efflux of chemotherapeutics, leading to both intrinsic and acquired chemoresistance to cancer drugs. This effect has been termed the "dark side" of NRF2. In an effort to combat this chemoresistance, our group discovered the first NRF2 inhibitor, the natural product brusatol, however the mechanism of inhibition was previously unknown. In this report, we show that brusatol's mode of action is not through direct inhibition of the NRF2 pathway, but through the inhibition of both cap-dependent and cap-independent protein translation, which has an impact on many short-lived proteins, including NRF2. Therefore, there is still a need to develop a new generation of specific NRF2 inhibitors with limited toxicity and off-target effects that could be used as adjuvant therapies to sensitize cancers with high expression of NRF2. Show less
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence Show more
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence of many pathologies, particularly chronic non-communicable diseases such as obesity and diabetes. Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective. Furthermore, we describe recent advances such as the discovery that a broad complement of immune cells play a role in immunometabolism and the emerging evidence that nutrients and metabolites modulate inflammatory pathways. Lastly, we discuss how this work may eventually lead to tangible therapeutic advancements to promote health. Show less
Z-DNA, an active element in genome, has drawn intense interest in chemical and biological field. Its dynamic and transient state makes it challenging to target and regulate. Thus, stabilizing and indu Show more
Z-DNA, an active element in genome, has drawn intense interest in chemical and biological field. Its dynamic and transient state makes it challenging to target and regulate. Thus, stabilizing and inducing Z-DNA both in vitro and in vivo is essential, so far, much many efforts have been made in these aspects. However, Z-DNA's induction and stabilization are always performed in high salt condition and sequence-dependent, limited inducers or stabilizers have been achieved with breakthrough in the aspects of real physiological condition and sequence-independence. Herein, we give a review of some typical kinds of Z-DNA inducers and stabilizers, discussing their inducing or stabilizing condition, mechanism, structural relationship and their limitation as well, attempted to get some implication and guidance for Z-DNA inducer or stabilizer design. Show less
The condensation of DNA is essential for biological processes such as DNA transcription and replication, and its study receives additional impetus from an interest in gene therapy. Although many effic Show more
The condensation of DNA is essential for biological processes such as DNA transcription and replication, and its study receives additional impetus from an interest in gene therapy. Although many efficacious condensing agents have been discovered and investigated, little is known about the conversation of condensation-release under suitable conditions. A novel class of DNA condensing agents based on small azaheterocyclic metal-binding molecules has been discovered and described. Both linear and plasmid DNA can be condensed to nanoparticles by the title compounds with 50 °C incubation, especially in the presence of divalent metal ions. Importantly, this condensation may be released to original forms with little or no damage to the DNA under incubation at physiological temperatures. These changes in DNA morphology over time have been analyzed by gel electrophoresis, circular dichroism (CD), and atomic force microscopy (AFM). The present work might help to develop strategies for the design and synthesis of controllable condensing agents, which may also be applied to control gene expression and delivery. Show less