Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered as potential therapies. This review focuses on the impact of both external and internal stressors on the ER in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) and discusses the role of the UPR signaling pathway activation in the control of cellular damage and specifically highlights the potential involvement of non-coding RNAs in COPD. Summaries of pathogenic mechanisms associated with the ER stress/UPR axis contributing to IPF and COPD, and promising pharmacological intervention strategies, are also presented.
Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER) resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs.Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Further, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Further, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage.We also present an overview of the pathogenic mechanisms with a brief focus on potential strategies for pharmacological interventions.
Recent astronomical observations show that the universe may be anisotropic on large scales. The Union2 SnIa data hint that the universe has a preferred direction. If such a cosmological privileged axis indeed exists, one has to consider an anisotropic expanding Universe instead of the isotropic cosmological model. In this paper, we present a detailed analysis of the dark energy dipole in f (R, T ) = f 1 (R) + f 2 (T ) Cosmological Model using three types of dipole fit (DF) method which are (I) dipole + monopole fitting for distance modulus (DMFDM), (II) dipole + monopole fitting for luminosity distance (DMFLD) and (III) general dipole fitting for luminosity distance (GDFLD). We have found the maximum anisotropic deviation direction for (DMFDM) method as (l, b) = (315
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