Notes

Paediatric rhombencephalitis presenting with bradycardia: a good recovery even with heart failure involvement.
Neurogenic inflammation and central sensitization play a role in chronic prostatitis/chronic pelvic pain syndrome. We explore the molecular effects of low-intensity shock wave therapy (Li-ESWT) on central sensitization in a capsaicin-induced prostatitis rat model. Male Sprague-Dawley rats underwent intraprostatic capsaicin (10 mM, 0.1 cm3) injections. After injection, the prostate received Li-ESWT twice, one day apart. The L6 dorsal root ganglion (DRG)/spinal cord was harvested for histology and Western blotting on days 3 and 7. The brain blood oxygenation level-dependent (BOLD) functional images were evaluated using 9.4 T fMRI before the Li-ESWT and one day after. Intraprostatic capsaicin injection induced increased NGF-, BDNF-, and COX-2-positive neurons in the L6 DRG and increased COX-2, NGF, BDNF, receptor Trk-A, and TRPV1 protein expression in the L6 DRG and the dorsal horn of the L6 spinal cord, whose effects were significantly downregulated after Li-ESWT on the prostate. Intraprostatic capsaicin injection increased activity of BOLD fMRI responses in brain regions associated with pain-related responses, such as the caudate putamen, periaqueductal gray, and thalamus, whose BOLD signals were reduced after Li-ESWT. These findings suggest a potential mechanism of Li-ESWT on modulation of peripheral and central sensitization for treating CP/CPPS.MicroRNAs (miRNAs) are essential post-transcriptional gene regulators involved in various neuronal and non-neuronal cell functions and play a key role in pathological conditions. Numerous studies have demonstrated that miRNAs are dysregulated in major neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, or Huntington's disease. Hence, in the present work, we constructed a comprehensive overview of individual microRNA alterations in various models of the above neurodegenerative diseases. We also provided evidence of miRNAs as promising biomarkers for prognostic and diagnostic approaches. In addition, we summarized data from the literature about miRNA-based therapeutic applications via inhibiting or promoting miRNA expression. We finally identified the overlapping miRNA signature across the diseases, including miR-128, miR-140-5p, miR-206, miR-326, and miR-155, associated with multiple etiological cellular mechanisms. However, it remains to be established whether and to what extent miRNA-based therapies could be safely exploited in the future as effective symptomatic or disease-modifying approaches in the different human neurodegenerative disorders.The link between substance abuse and the development of schizophrenia remains elusive. In this study, we assessed the molecular and behavioural alterations associated with schizophrenia, opioid addiction, and opioid withdrawal using zebrafish as a biological model. Larvae of 2 days post fertilization (dpf) were exposed to domperidone (DMP), a dopamine-D2 dopamine D2 receptor antagonist, and morphine for 3 days and 10 days, respectively. MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, served as a positive control to mimic schizophrenia-like behaviour. The withdrawal syndrome was assessed 5 days after the termination of morphine treatment. The expressions of schizophrenia susceptibility genes, i.e., pi3k, akt1, slc6a4, creb1 and adamts2, in brains were quantified, and the levels of whole-body cyclic adenosine monophosphate (cAMP), serotonin and cortisol were measured. The aggressiveness of larvae was observed using the mirror biting test. After the short-term treatment with DMP and morphine, all studied genes were not differentially expressed. As for the long-term exposure, akt1 was downregulated by DMP and morphine. Downregulation of pi3k and slc6a4 was observed in the morphine-treated larvae, whereas creb1 and adamts2 were upregulated by DMP. The levels of cAMP and cortisol were elevated after 3 days, whereas significant increases were observed in all of the biochemical tests after 10 days. Compared to controls, increased aggression was observed in the DMP-, but not morphine-, treated group. These two groups showed reduction in aggressiveness when drug exposure was prolonged. VH298 Both the short- and long-term morphine withdrawal groups showed downregulation in all genes examined except creb1, suggesting dysregulated reward circuitry function. These results suggest that biochemical and behavioural alterations in schizophrenia-like symptoms and opioid dependence could be controlled by common mechanisms.The β1-integrin receptor is broadly expressed on tumor and other cells in the tumor microenvironment (TME), and is an unfavorable prognostic factor for cancers. Nature-derived resveratrol has preventive and apoptotic effects on tumors, but whether resveratrol can exert its suppressive actions on TME-induced tumorigenesis through β1-integrin on the surface of CRC cells is still unknown. HCT116 or SW480 cells were exposed to inhibitory antibodies against β1-integrin, bacitracin (selective β1-integrin inhibitor), integrin-binding RGD (Arg-Gly-Asp) peptide, and/or resveratrol. We evaluated the anti-tumor actions and signaling impacts of resveratrol in colorectal cancer (CRC)-TME. We found that resveratrol completely altered the β1-integrin distribution pattern and expression on the surface of CRC cells in TME. Moreover, resveratrol down-regulated CRC cell proliferation, colony formation, viability, and up-regulated apoptosis in a concentration-dependent way. These actions of resveratrol were antagonized mainly by inhibitory antibodies against β1-integrin but not β5-integrin, and by an integrin-binding RGD peptide but not by RGE peptide, and by bacitracin in TME. Similarly, resveratrol-blocked TME-induced p65-NF-kB and its promoted gene markers linked to proliferation (cyclin D1), invasion (focal adhesion kinase, FAK), or apoptosis (caspase-3), were largely abrogated by anti-β1-integrin or RGD peptide, suggesting that β1-integrin is a potential transmission pathway for resveratrol/integrin down-stream signaling in CRC cells. The current results highlight, for the first time, the important gateway role of β1-integrins as signal carriers for resveratrol on the surfaces of HCT116 and SW480 cells, and their functional cooperation for the modulatory effects of resveratrol on TME-promoted tumorigenesis.Serotonin (5-HT) is an attractive neurotransmitter system, in terms of physiology, physiopathology, and medicines [...].Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin's relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.Modification of an ion-exchange membrane with a thin layer, the charge of which is opposite to the charge of the substrate membrane, has proven to be an effective approach to obtaining a composite membrane with permselectivity towards monovalent ions. However, the mechanism of permselectivity is not clear enough. We report a 1D model based on the Nernst-Planck-Poisson equation system. Unlike other similar models, we introduce activity coefficients, which change when passing from one layer of the membrane to another. This makes it possible to accurately take into account the fact that the substrate membranes usually selectively sorb multiply charged counterions. We show that the main cause for the change in the permselectivity coefficient, P1/2, with increasing current density, j, is the change in the membrane/solution layer, which controls the fluxes of the competing mono- and divalent ions. At low current densities, counterion fluxes are controlled by transfer through the substrate membrane, which causes selective divalent ion transfer. When the current increases, the kinetic control goes first to the modification layer (which leads to the predominant transfer of monovalent ions) and then, at currents close to the limiting current, to the depleted diffusion layer (which results in a complete loss of the permselectivity). Thus, the dependence P1/2 - j passes through a maximum. An analytical solution is obtained for approximate assessment of the maximum value of P1/2 and the corresponding fluxes of the competing ions. The maximum P1/2 values, plotted as a function of the Na+ ion current density at which this maximum is reached, gives the theoretical trade-off curve between the membrane permselectivity and permeability of the bilayer monovalent selective ion-exchange membrane under consideration.The cytoarchitecture and tensile characteristics of ocular lenses play a crucial role in maintaining their transparency and deformability, respectively, which are properties required for the light focusing function of ocular lens. Calcium-dependent myosin-II-regulated contractile characteristics and mechanosensitive ion channel activities are presumed to influence lens shape change and clarity. Here, we investigated the effects of load-induced force and the activity of Piezo channels on mouse lens myosin II activity. Expression of the Piezo1 channel was evident in the mouse lens based on immunoblot and immufluorescence analyses and with the use of a Piezo1-tdT transgenic mouse model. Under ex vivo conditions, change in lens shape induced by the load decreased myosin light chain (MLC) phosphorylation. While the activation of Piezo1 by Yoda1 for one hour led to an increase in the levels of phosphorylated MLC, Yoda1 treatment for an extended period led to opacification in association with increased calpain activity and degradation of membrane proteins in ex vivo mouse lenses. In contrast, inhibition of Piezo1 by GsMTx4 decreased MLC phosphorylation but did not affect the lens tensile properties. This exploratory study reveals a role for the mechanical load and Piezo1 channel activity in the regulation of myosin II activity in lens, which could be relevant to lens shape change during accommodation.
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