Earlier age at menarche is a major risk factor for breast cancer. Our previous study identified Nrip1 (also known as Rip140) as a candidate gene for delaying female sexual maturation (FSM) and found that knocking out Nrip1 could significantly delay FSM in mice. To investigate the effects of NRIP1 in breast cancer we used human cell lines and tissue arrays along with an in vivo study of DMBA-induced carcinogenesis in Nrip1 knockout mice. Analysis of tissue arrays found that NRIP1 is elevated in tumors compared to cancer adjacent normal tissue. Interestingly, in benign tumors NRIP1 levels are higher in the cytosol of stromal cells, but NRIP1 levels are higher in the nuclei of epithelial cells in malignancies. We also found overexpression of NRIP1 in breast cancer cell lines, and that suppression of NRIP1 by siRNA in these cells significantly induced apoptosis and inhibited cell growth. Furthermore, in vivo data suggests that NRIP1 is upregulated in DMBA-induced breast cancer. Importantly, we found that DMBA-induced carcinogenesis is suppressed in Nrip1 knockdown mice. These findings suggest that NRIP1 plays a critical role in promoting the progression and development of breast cancer and that it may be a potential therapeutic target for the new breast cancer treatments.

Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of lowdensity lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, therefore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also used cultured human keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by imiquimod treatment and inhibit hyperproliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a therapeutic target.

It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of mechanistic target of rapamycin (mTOR), extends life span, but less is known about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here, rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling, to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on life span. We found that rapamycin extended life span in control normal (N) mice, whereas it had the opposite effect in GHR-KO mice. In the rapamycin-treated GHR-KO mice, mTORC2 signaling was reduced without further inhibition of mTORC1 in the liver, muscle, and s.c. fat. Glucose and lipid homeostasis were impaired, and old GHR-KO mice treated with rapamycin lost functional immune cells and had increased inflammation. In GHR-KO MEF cells, knockdown of Rictor, but not Raptor, decreased mTORC2 signaling. We conclude that drastic reduction of mTORC2 plays important roles in impaired longevity in GHR-KO mice via disruption of whole-body homeostasis.

Using age of female sexual maturation as a biomarker, we previously identified nuclear receptor interacting protein 1 (Nrip1) as a candidate gene that may regulate aging and longevity. In the current report, we found that the deletion of Nrip1 can significantly extend longevity of female mice (log-rank test, p = .0004). We also found that Nrip1 expression is altered differently in various tissues during aging and under diet restriction. Remarkably, Nrip1 expression is elevated with aging in visceral white adipose tissue (WAT), but significantly reduced after 4 months of diet restriction. However, in gastrocnemius muscle, Nrip1 expression is significantly upregulated after the diet restriction. In mouse embryonic fibroblasts, we found that the deletion of Nrip1 can suppress fibroblast proliferation, enhance autophagy under normal culture or amino acid starvation conditions, as well as delay oxidative and replicative senescence. Importantly, in WAT of old animals, the deletion of the Nrip could significantly upregulate autophagy and reduce the number of senescent cells. These results suggest that deleting Nrip1 can extend female longevity, but tissue-specific deletion may have varying effects on health span. The deletion of Nrip1 in WAT may delay senescence in WAT and extend health span.

Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response.The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could significantly inhibit cell growth and induce apoptosis, and the suppression of NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1 knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65 expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is overexpressed both in skin and PBMCs of psoriasis patients and may be involved in the abnormal proliferation and apoptosis of keratinocytes, as well as the immune reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential therapeutic target for psoriasis.

Our previous studies found that deletion of nuclear receptor interacting protein 1 (Nrip1) extended longevity in female mice and delayed cell senescence. The current study investigates the role of NRIP1 in regulating functions of adipose-derived mesenchymal stem cells (ADMSCs) and explores the mechanisms of NRIP1 in skin aging. We first verified the skin aging phenotypes in young (6 months) and old (20 months) C57BL/6J (B6) mice and found deletion of Nrip1 can delay skin aging phenotypes, including reduced thickness of dermis and subcutaneous white adipose tissue (sWAT), as well as the accumulation of senescent cells in sWAT. In ADMSCs isolated from sWAT, we found that deletion of Nrip1 could decrease cell proliferation, prevent cell apoptosis, and suppress adipogenesis. Interestingly, deletion of Nrip1 also reduced cell senescence and maintain cell quiescence of ADMSCs. Moreover, the expressions of genes associated with senescence (p21, and p53), inflammation (p65, IL6, and IL1a), and growth factor (mTOR, Igf1) were reduced in Nrip1 knockout ADMSCs, as well as in siNrip1-treated ADMSCs. Suppression of Nrip1 by siNrip1 also decreased the expressions of mTOR, p-mTOR, p65, and p-p65 in ADMSCs. Reduced expressions of p65 and p-p65 were also confirmed in the skin of Nrip1 knockout mice. These findings suggest that NRIP1 plays an important role in delaying skin aging by reducing ADMSCs senescence and maintaining ADMSCs quiescence.

Phyllotis Waterhouse 1837 is one of the most studied genera of South American cricetid rodents. As currently understood, it includes 20 small to medium‐sized species of predominantly rocky habitats. Among them, populations of the yellow‐rumped leaf‐eared mouse, traditionally referred to P. xanthopygus (Waterhouse 1837), are the most widely distributed, extending from central Peru to southern Chile and Argentina. Based mostly on molecular evidence, previous studies suggested that P. xanthopygus constitutes a species complex, being characterized by geographically structured and genetically divergent clades. In this work, we compare the molecular phylogenetic hypothesis for populations distributed on the eastern slopes of the central Andes with morphometric evidence using univariate and multivariate analyses. Quantitative morphological and molecular evidence suggests that at least four nearly cryptic species of the P. xanthopygus complex occur from southern Bolivia to west‐central Argentina. Three of these taxa have available names; one of them, P. caprinus, is currently recognized to the species level; the other two, the clades of P. x. posticalis‐P. x. rupestris and P. vaccarum, are both recognized as subspecies of P. xanthopygus. The remaining taxon represents a new species distributed in the west‐central Andes of Argentina. We discuss our morphological results in the light of other sources of evidence (e.g. qualitative and quantitative state characters, genetic and phylogenetic studies, and cytogenetic data) and name the new species as P. pehuenche, honouring the original native people that historically inhabited west‐central Andes of Argentina.

En 2021, Jayat et al. propusimos una nueva especie de roedor sigmodontino, nombrada Phyllotis pehuenche, para las poblaciones del complejo de especies de Phyllotis xanthopygus del sudoeste de la provincia de Mendoza y el oeste de la provincia de Neuquén, Argentina.  La descripción formal de la especie, publicada en un material suplementario electrónico modificable, no cumple con los requerimientos establecidos en la enmienda sobre publicaciones electrónicas (ICZN 2012) de la Cuarta Edición del Código Internacional de Nomenclatura Zoológica (ICZN 1999), haciendo que el nombre no esté disponible.  El objetivo de esta nota es cumplir con los requerimientos del código y hacer el nombre disponible.  Aquí ofrecemos una versión resumida de la descripción original de esta especie.  En esta nota, ofrecemos un tratamiento taxonómico para P. pehuenche, incluyendo su sinonimia, localidad tipo, holotipo y paratipos, proveyendo la etimología del epíteto específico, y ofreciendo una diagnosis para la especie y comentarios acerca de su distribución geográfica.  Con toda la información provista, cumplimos con los lineamientos del Código Internacional de Nomenclatura Zoológica (ICZN 1999, 2012) haciendo el nombre disponible.