Background: A 28-kDa HO-1 isoform is induced by oxidative stress and cancer and accumulates in the nucleus. Results: Nuclear HO-1 interacts with Nrf2 and alters expression of its target genes. Conclusion: HO-1 modulates Nrf2 function. Significance: Exploiting the synergistic benefits of the HO-1⅐Nrf2 protein complex is important for developing therapeutic strategies against oxidative stress or cancer.

Early-term births are associated with high neonatal morbidity and with NICU or neonatology service admission. Evaluation of local prevalence data will assist in implementation of specific preventive measures and plans, as well as prioritize limited health care resources.

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses-ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation-are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation. Circadian rhythms are daily variations in behavior and biological activity that stem from an intrinsic ability of organisms to align themselves with the environmental 24-hour light/dark cycle. These rhythms originate from an internal biological clock that drives many aspects of human physiology, including the sleepwake cycle and daily variations in blood pressure, body temperature, and cortisol (1). A growing body of epidemiological evidence demonstrates an association between altering circadian timing through shift work or frequent time zone travel and increased rates of cardiovascular disorders, metabolic syndrome, and cancer (2-4). Clinical aspects of disease such as pain perception, asthma exacerbations, and myocardial infarctions are more common at certain times of day or night (5, 6). The discovery of the genetic basis for the circadian clock in the 1980s and 1990s has ushered in a new era in which long-appreciated circadian rhythms in physiology and clinical medicine are being reframed in terms of gene expression, metabolism, signal transduction, and cellular physiology (7). The translation of circadian discovery into strategies to improve the prevention and management of disease promises to be transformative, but at present, fundamental research is outpacing clinical application (Figure 1A). Much will depend on research identifying the critical mechanisms and targets to which circadian rhythm-based therapeutic strategies can be applied. An emerging example of exciting circadian discovery with potential clinical relevance is the intersection between circadian function and immune regulation (Figure 1B). The NIH recently sponsored a workshop entitled "Sleep Insufficiency, Circadian Misalignment, and the Immune Response" (May 16-17, 2019, Rockville, Maryland, USA). Its aim was to highlight basic and clinical advances linking sleep and circadian biology to immune dysfunction, thereby stimulating the application of circadian biology to translational medicine. The Workshop was cosponsored by four NIH institutes-the National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA), National Institute of Allergy and Infectious Diseases (NIAID), and National Institute on Alcohol Abuse and Alcoholism (NIAAA)-reflecting a...

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.