The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation. What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .

Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.

The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.

Gene regulation by steroid hormones.

Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fasebj.5.8.1850705

Matrix metalloproteinases and their inhibitors in connective tissue remodeling.

https://www.cell.com/cell/pdf/0092-8674(90)90396-V.pdf

Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interaction

Directly monitoring the oxygen reduction reaction (ORR) process in situ is very important to deeply understand the reaction mechanism and is a critical guideline for the design of high-efficiency catalysts, but there is still lack of definite in situ evidence to clarify the effect between adsorbed intermediates and the strain/electronic effect for enhanced ORR performance. Herein, in situ surface-enhanced Raman spectroscopy (SERS) was employed to detect the intermediates during the ORR process on the Au@Pd@Pt core/shell heterogeneous nanoparticles (NPs). Direct spectroscopic evidence of the *OOH intermediate was obtained, and an obvious red shift of the *OOH frequency was identified with the controllable shell thickness of Pd. Detailed experimental characterizations and density functional theory (DFT) calculations demonstrated that such improved ORR activity after inducing Pd into Au@Pt NPs can be attributed to the optimized adsorbate-substrate interaction due to the strain and electronic effect, leading to a higher Pt-O binding energy and a lower O-O binding energy, which was conducive to O-O dissociation and promoted the subsequent reaction. Notably, this work illustrates a relationship between the performance and strain/electronic effect via the intermediate detected by SERS and paves the way for the construction of ORR electrocatalysts with high performance.

Exploring the Effect of Pd on the Oxygen Reduction Performance of Pt by In Situ Raman Spectroscopy.

The challenging sluggish reaction kinetics of hydrogen energy‐related electrocatalysis can be overcome via exploring electrocatalysts with high‐efficient activity and long‐term durability. However, the deficiency of comprehensive and in‐depth understanding of the evolution of the electrocatalysts, nature of active centers, intermediate species absorbed in the electrocatalysts, and the reaction pathway during the electrocatalytic processes seriously limits the elucidation of the composition/structure–activity relationship of electrocatalysts. To this end, plenty of powerful in situ techniques that can provide atomic/molecular information are employed to bridge the understanding of fundamental mechanisms to the practical development of electrocatalysts. This review summarizes design strategies based on composition regulation and morphology design for tuning the electronic/geometric structures of electrocatalytic materials with improved activity and stability. Moreover, the recent application of in situ infrared, Raman, and X‐ray absorption spectroscopy is elaborated with emphases on tracking the dynamic evolution during electrocatalysis and building a link between the composition/structure and activity of electrocatalysts. Finally, the current challenges and future perspectives for in situ monitoring techniques to gain an understanding more deeply and comprehensively in the hydrogen energy‐related electrocatalysis are proposed. This review provides insights into the rational optimization of electrocatalysts and inspire the unraveling mechanism of the enhanced electrocatalytic performance in future research.

Design Strategies and in situ Infrared, Raman, and X‐ray Absorption Spectroscopy Techniques Insight into the Electrocatalysts of Hydrogen Energy System

Both tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine can be metabolized by cytochrome P450 2A13 (CYP2A13). Previous studies have shown that nicotine has a potential inhibitory effect on the toxicity of NNK. However, due to the lack of CYP2A13 activity in conventional lung cell lines, there had been no systematic in vitro investigation for the key target organ, the lung. Here, BEAS-2B cells stably expressing CYP2A13 (B-2A13 cells) were constructed to investigate the effects of nicotine on the cytotoxicity and genotoxicity of NNK. The results showed more sensitivity for NNK-induced cytotoxicity in B-2A13 cells than in BEAS-2B and B-vector cells. NNK significantly induced DNA damage, cell cycle arrest, and chromosomal damage in B-2A13 cells, but had no significant effect on BEAS-2B cells and the vector control cells. The combination of different concentration gradient of nicotine without cytotoxic effects and a single concentration of NNK reduced or even counteracted the cytotoxicity and multi-dimensional genotoxicity in a dose-dependent manner. In conclusion, CYP2A13 caused the cytotoxicity and genotoxicity of NNK in BEAS-2B cells, and the addition of nicotine could inhibit the toxicity of NNK.

/pdf/nicotine-inhibits-the-cytotoxicity-and-genotoxicity-of-nnk-rgiqj00k.pdf

Yu-Lin Sun

Papers

Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interaction

Exploring the Effect of Pd on the Oxygen Reduction Performance of Pt by In Situ Raman Spectroscopy.

Design Strategies and in situ Infrared, Raman, and X‐ray Absorption Spectroscopy Techniques Insight into the Electrocatalysts of Hydrogen Energy System

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells