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  • Kragelund Whitaker posted an update 5 days, 9 hours ago

    To preliminary assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models.

    NOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptor’s status was carried out after the MR images acquisition by immunohistochemistry on excised tumours.

    Manganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (p<0.01), whereas TRPV6 expression levels appeared not relevant to the Mn uptake.

    Our preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors.

    Our preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors.Olfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adult mice, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that centrioles are amplified in immediate neuronal precursors (INPs) concomitant with elevation of mRNA for polo-like kinase 4 (Plk4) and SCL/Tal1-interrupting locus gene (Stil), key regulators of centriole duplication. These results support a model in which centriole amplification occurs during a transient state characterized by elevated Plk4 and Stil in early INP cells. These cells then go on to divide at least once to become OSNs, demonstrating that cell division with amplified centrioles, known to be tolerated in disease states, can occur as part of a normal developmental program.BACKGROUND Diabetic nephropathy (DN), the formation of albuminuria, is one of the most important complications seen in diabetic patients. IL-37, an inhibitor of congenital inflammation and immune response, plays an important role in the occurrence and development of diabetes, but its study in DN has not been previously reported. MATERIAL AND METHODS Podocyte transfection techniques were used to overexpress STAT3 and cyclophilin A (CypA). The expression of IL-37, STAT3, and CypA was detected by RT-qPCR and western blot. Cell survival was detected by CCK-8. The expression of inflammatory factors and molecules related to oxidative stress was detected by ELISA and western blot, and cell apoptosis was detected by flow cytometry and western blot. RESULTS The expression of IL-37 was significantly decreased in high glucose-treated podocytes. IL-37 improved the survival rate of podocytes suffering from high glucose-induced apoptosis. It inhibited the expression of the inflammation-related factors tumor necrosis factorpregulation of the STAT3-CypA signaling pathway can inhibit the protective effect of IL-37 against podocyte injury induced by high glucose.BACKGROUND Spontaneous intracranial hypotension (SIH) is a rare cause of postural headache. In most patients, the site of cerebrospinal fluid (CSF) leak is at the cervical or thoracic spinal level. The imaging modalities to establish the diagnosis of SIH include computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, CT, and MRI myelography, and radionuclide cisternography. Treatment usually consists of conservative measures, but patients unresponsive to these treatments can be treated by epidural blood patch (EBP) administration at the site of CSF leak. CASE REPORT A 25-year-old-man presented with headache aggravated upon sitting or standing and relieved by lying supine or consuming coffee. There was no history of recent trauma, lumbar puncture, or spinal anesthesia. His neurological examination was unremarkable. MRI of his head and entire spine showed features of intracranial hypotension with no obvious CSF leak. He was treated conservatively but his symptoms persisted. CT spinal myelography showed significant leakage of contrast medium at the retrospinal region between C1 and C2 spinous processes. The patient underwent cervical EBP administration under fluoroscopic guidance. His symptoms resolved completely and he remains asymptomatic more than 6 months later. CONCLUSIONS SIH is an important cause of postural headache. selleck compound In patients with non-resolving symptoms, further investigations are warranted to identify potential CSF leak. Patients found to have a CSF leak at the level of the cervical spine can be safely and effectively treated by cervical EBP administration.Dilated cardiomyopathy (DCM) is often associated with sarcomere protein mutations that confer reduced myofilament tension-generating capacity. We demonstrated that cardiac twitch tension-time integrals can be targeted and tuned to prevent DCM remodeling in hearts with contractile dysfunction. We employed a transgenic murine model of DCM caused by the D230N-tropomyosin (Tm) mutation and designed a sarcomere-based intervention specifically targeting the twitch tension-time integral of D230N-Tm hearts using multiscale computational models of intramolecular and intermolecular interactions in the thin filament and cell-level contractile simulations. Our models predicted that increasing the calcium sensitivity of thin filament activation using the cardiac troponin C (cTnC) variant L48Q can sufficiently augment twitch tension-time integrals of D230N-Tm hearts. Indeed, cardiac muscle isolated from double-transgenic hearts expressing D230N-Tm and L48Q cTnC had increased calcium sensitivity of tension development and increased twitch tension-time integrals compared with preparations from hearts with D230N-Tm alone.

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