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Bone marrow mesenchymal stem cells (BMSC) or BMSC-derived exosome transplantation improves rat ovarian function after chemotherapy-induced ovarian failure. Furthermore, transfer of miR-144-5p using BMSC-derived exosomes decreases granulosa cell (GCs) apoptosis via the PTEN pathway. Thus, a cell-free therapeutic strategy may be possible for ovarian failure.
This study reveals that adhesion molecule ICAM-1 is markedly upregulated in the aorta after angiotensin II infusion. Blockage of soluble ICAM-1 prevents Ang II-induced arterial hypertension and vascular remodeling by reducing macrophage adhesion, suggesting that targeting ICAM-1 may represent a new therapeutic target for hypertension.
The role of the prostaglandin E1 receptor EP1 in hypertensive kidney disease remains controversial. EP1 mediates thick ascending limb chloride transport response to prostaglandin E2 and inhibits vasopressin-mediated water transport in the inner medullary collecting duct (IMCD). Though the IMCD transport is unaltered by hypertension, its responsiveness to vasopressin is reduced in diabetes. Moreover, EP1 is protective against glomerular and endothelial injury in hypertensive kidney disease, unlike its harmful role in diabetic kidney disease. This highlights the importance of carefully examining disease state (diabetes vs hypertension) when characterizing underlying disease processes.
The authors investigated global analysis coupled shotgun proteomics and in silico metabolic pathway analyses in malignant lymphoma and normal lymphocytes. Trifunctional protein subunit alfa (HADHA) was detected as a lymphoma-specific protein and a prognostic predictor. In vitro, downregulation of HADHA inhibited cell growth and increase susceptibility of cell death stimuli. Therefore, HADHA may be a potential therapeutic target in refractory malignant lymphoma cases.
In this study, the authors show that RIP1/RIP3/MLKL-mediated necroptosis is activated in a mouse model of Parkinson’s disease. Blockade of necroptosis through pharmacological intervention by Nec-1 or deletion of RIP3/MLKL gene increased dopamine levels and the number of dopaminergic neurons in mice. Moreover, necroptosis enhanced the expression of pro-inflammatory genes, which may have initiated neuroinflammation and in turn aggravated dopaminergic neuron necroptosis.
The paper describes a fully automated numerical analysis for an unbiased quantification of non-alcoholic fatty liver disease (NAFLD) histological features in rodent models. The technique offers a quantitative high-throughput method to rapidly detect NAFLD in large preclinical studies and for accurately monitoring disease evolution.
This study shows a negative regulation of autophagy-related RNA transcripts and the upregulation and downregulation of p62 and LC3-B proteins, respectively, in the central nervous system of scrapie-infected transgenic mice at clinical stage. These findings likely reflect an impairment of the autophagic pathway at the late symptomatic stage of prion infection.
This study shows that scavenger receptor type I knockout mice (Scarb1-/-) have high adrenocorticotropic hormone (ACTH) levels but are osteopenic. Bone differentiation of Scarb1-/- mesenchymal stem cells at normal ACTH concentrations is reduced. However, 0–10 nM ACTH increases, but 100–1000 nM ACTH reduces wild-type osteoblast differentiation. Therefore, ACTH and the high-density lipoprotein receptor Scarb1 play independent roles in osteoblast differentiation.
The NanoSuit method permits the study of paraffin sections using correlative light and electron microscopy at low and high magnification, with the following features: (i) the integrity of the glass slide is maintained, (ii) 3D microstructures of tissue and pathogens can be visualized, (iii) nuclei and 3,3′-diaminobenzidine-stained areas are distinct because of gold chloride usage, (iv) immunohistochemical staining is quantitative, and (v) contained elements can be analyzed.
Vitamin D and its analogues demonstrated in this study antifibrotic effects in a murine fibrosis model compared to calcitriol. In this study, the hypocalcemic vitamin D analog paricalcitol was superior in respect to side effects and efficacy, indication that such analogs could be considered for the treatment of liver fibrosis.
Acute kidney injury and endothelial hyperpermeability are main features observed during severe sepsis with low survival rate. Transient receptor potential melastatin 7 (TRPM7) calcium channel inhibition protects against endotoxemia-induced kidney injury potentially by means of endothelial hyperpermeability decreasing. Remarkably, TRPM7 inhibition improves survival in endotoxemic animals.
CRISPR/dCas9 blocks TGF-β2-induced mouse double minute 2 (MDM2) expression by targeting its second promoter, without affecting the basal expression. Epithelial to mesenchymal transition is blocked by MDM2 suppression in retinal pigment epithelial cells. In this way, CRIPSR/dCas9 is a promising novel therapy for proliferative vitreoretinopathy without interfering basal gene function.
Allergic asthma is one of the most common immune-mediated disorders. The authors investigated the possibility that TPRV4 cation channels facilitate the development of allergic asthma and subsequent pulmonary fibrosis in the lung. Their data suggest that TPRV4 is dispensable in the initiation and development of airway asthma and subsequent fibrosis.
The Niemann–Pick C1-like intracellular cholesterol transporter gene and a number of genes in the cholesterol synthesis pathway are transcriptionally regulated by SREBP-2. The liganded Ah receptor increases proteolytic turnover of transcriptionally active SREBP2. Thus, Ah receptor ligands are capable of attenuating cholesterol uptake into Caco-2 cells.
In chondrocytes, TGF-β1 increases the expression of hypertrophic genes, suggesting that this treatment could mimic osteoarthritis in vitro. EZH2 and Sik3 inhibition, as well as HIF induction repress the expression of hypertrophy markers in TGF-β stimulated chondrocytes, validating the reliability of this model to predict anti-hypertrophic effects of drugs.