In Lhasa, Tibet, we found that Tibetan newborns had higher arterial oxygen saturation at birth and during the first four months of life than Han newborns. Genetic adaptations may permit adequate oxygenation and confer resistance to the syndrome of pulmonary hypertension and right-heart failure (subacute infantile mountain sickness).

The moss Physcomitrella patens has been shown to tolerate abiotic stresses, including salinity, cold, and desiccation. To better understand this plant's mechanism of desiccation tolerance, we have applied cellular and proteomic analyses. Gametophores were desiccated over 1 month to 10% of their original fresh weight. We report that during the course of dehydration, several related processes are set in motion: plasmolysis, chloroplast remodeling, and microtubule depolymerization. Despite the severe desiccation, the membrane system maintains integrity. Through two-dimensional gel electrophoresis and image analysis, we identified 71 proteins as desiccation responsive. Following identification and functional categorization, we found that a majority of the desiccation-responsive proteins were involved in metabolism, cytoskeleton, defense, and signaling. Degradation of cytoskeletal proteins might result in cytoskeletal disassembly and consequent changes in the cell structure. Late embryogenesis abundant proteins and reactive oxygen species-scavenging enzymes are both prominently induced, and they might help to diminish the damage brought by desiccation.

The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early dry age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that AhR activity and protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable in AMD, decrease with age. This finding is significant given that age is the most established risk factor for development of AMD. Moreover, AhR −/− mice exhibit decreased visual function and develop dry AMD-like pathology, including disrupted RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and linear-like deposit material, Bruch's membrane thickening, and progressive RPE and choroidal atrophy. High-serum low-density lipoprotein levels were also observed in AhR −/− mice. In its oxidized form, this lipoprotein can stimulate increased secretion of extracellular matrix molecules commonly found in deposits from RPE cells, in an AhR-dependent manner. This study demonstrates the importance of cellular clearance via the AhR signaling pathway in dry AMD pathogenesis, implicating AhR as a potential target, and the mouse model as a useful platform for validating future therapies.retinal pigment epithelium | retinal disease | toxin metabolism | oxidized low density lipoprotein A ge-related macular degeneration (AMD) is the leading cause of vision loss in individuals over the age of 55 y in the Western world (1). It is a complex and heterogeneous disease, multifactorial with genetic, systemic health, and environmental factors regulating its initiation and progression (2, 3). Phenotypically, eyes with the dry clinical subtype are characterized by accumulation of focal and diffuse extracellular lipid protein-rich deposits below the retinal pigment epithelial cells (sub-RPE in 85-87% of cases) and/or within Bruch's membrane. These deposits include drusen, basal laminar, and basal linear deposits (4, 5) and are associated with RPE dysfunction, apoptosis, and ultimately degeneration. The latter of which, RPE atrophy and degeneration, is seen in an advanced form of dry AMD called geographic atrophy. Currently, there are no treatment options available for these patients. Despite advances in our understanding of the composition of sub-RPE deposits (6-8), the critical molecular events and signaling pathways leading to progressive RPE dysfunction and extracellular deposit biogenesis are still unknown.

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The occurrence and development of cardiovascular complications are predominantly responsible for the increased morbidity and mortality observed in patients with diabetes. Oxidative stress under hyperglycemia is currently considered the initial link to diabetic cardiovascular complications and a key node for the prevention and treatment of diabetes-related fatal cardiovascular events. Numerous studies have indicated that the common upstream pathway in the context of oxidative stress in the cardiovascular system under diabetic conditions is the interaction of advanced glycation end products (AGEs) with their receptors (RAGEs). Therefore, a further understanding of the relationship between oxidative stress and AGEs is of great significance for the prevention and treatment of cardiovascular complications in patients with diabetes. In this review, we will briefly summarize the recent research advances in diabetes with an emphasis on oxidative stress and its association with AGEs in diabetic cardiovascular complications.

A model oxidant, H2O2, induces PI3K and thereby activates Akt. Akt activation enhances RPE cell survival and thus may protect RPE cells from oxidant-induced cell death under normal circumstances and in disease states such as age-related macular degeneration (AMD).

Long noncoding RNAs (lncRNAs) are implicated in human cancer, but their mechanisms of action are largely unknown. In this study, we investigated lncRNA alterations that contribute to colorectal cancer (CRC) through microarray expression profiling in CRC patient samples. Here, we report that the CRC-associated lncRNA PVT1-214 is a key regulator of CRC development and progression; patients with high PVT1-214 expression had a shorter survival and poorer prognosis. In vitro and in vivo investigation of the role of PVT1-214 revealed a complex integrated phenotype affecting cell growth, stem-like properties, migration, and invasion. Furthermore, using RNA pull-down and mass spectrometry, we found that Lin28 (also known as Lin28A), a highly conserved RNA-binding protein, is associated with PVT1-214. Strikingly, we found that PVT1-214 not only upregulated Lin28 protein expression in CRC cells by stabilizing Lin28, but also participated in crosstalk with Lin28 mRNA through competition for miR-128 binding, imposing an additional level of post-transcriptional regulation. In addition, we further show that PVT1-214 repressed expression of let-7 family miRNAs, which was abrogated by Lin28 knockdown. Taken together, our findings support a model in which the PVT1-214/Lin28/let-7 axis serves as a critical regulator of CRC pathogenesis, which may simulate a new direction for CRC therapeutic development.

Human and mouse RPE cell mCRPs are upregulated by inflammatory cytokines and repetitive nonlethal oxidant exposure in a species-specific manner. Increased cell mCRPs may help to protect RPE cells from complement- and oxidant-mediated injury in diseases such as AMD.