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Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation.

BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutan

[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital].

INTRODUCTION: Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients. PATIENTS AND METHODS: Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015. RESULTS: We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1

Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes.

Bone is the primarily preferred site for breast and prostate cancer to metastasize. Bone metastases are responsible for most deaths related to breast and prostate cancer. The bone's particular microenvironment makes it conducive for the growth of cancer cells. Studies on bone metastasis have focused on the interaction between cancer cells and the bone microenvironment. Osteocytes, the most common cell type of bone tissue, have received little attention in bone metastasis, although they are master signal sensors, integrators, and skeleton transducers. They play an important role in regulating b

Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.

BACKGROUND: Celiac disease (CD) is an autoimmune disorder of the small intestine which is triggered by dietary gluten in genetically predisposed (HLA-DQ2/DQ8 positive) individuals. Only a fraction of HLA-DQ2/DQ8 positive individuals develop CD indicating that other factors have a role in the disorder. Several studies have addressed intestinal microbiota aberrancies in pediatric CD, but the results are inconsistent. Previously, we demonstrated that pediatric CD patients have lower duodenal expression of TLR2 and higher expression of TLR9 as compared to healthy controls (HC) indicating that micr

Connexin43 knockdown accelerates wound healing but inhibits mesenchymal transition after corneal endothelial injury in vivo.

PURPOSE: To explore connexin43 (Cx43) knockdown as an efficient treatment for corneal endothelial injury in an in vivo rat corneal scrape injury model. METHODS: Scrape injury was induced in the corneal endothelium, and immunolabeling (ZO-1, alpha-SMA, Cx43) was performed to analyze changes in Cx43 expression during wound healing. Single injection of Cx43 antisense oligodeoxynucleotide (AS-ODN), small interfering RNA (siRNA), or adenovirus (CMV-Cx43-mRFP1) was applied into the anterior chamber simultaneously with the injury, and wound closure was examined by immunolabeling (ZO-1, Cx43) and pro

Sumoylation of the SOX10 transcription factor regulates its transcriptional activity.

SRY-related HMG box-containing factor 10 (SOX10) is a transcription factor essential for neural crest development and differentiation, and involved in Waardenburg syndrome type IV and PCWH syndrome. Here we show that the SOX10 protein is modified by sumoylation, a highly dynamic post-translational modification that affects stability, activity and localisation of some specific transcription factors. Three sumoylation consensus sites were found in the SOX10 protein, all of them are functional and modulate SOX10 activity. Sumoylation does not affect SOX10 sub-cellular localisation, but represses

Optical imaging of large-scale correlated wave activity in the developing rat CNS.

A simulation of the rat distal convoluted tubule (DCT) is completed with a model of the late portion, or connecting tubule (CNT). This CNT model is developed by relying on a prior cortical collecting duct (CCD) model (Weinstein AM. Am J Physiol Renal Physiol 280: F1072-F1092, 2001), and scaling up transport activity of the three cell types to a level appropriate for DCT. The major difference between the two tubule segments is the lower CNT water permeability. In early CNT the luminal solution is hypotonic, with a K(+) concentration less than that of plasma, and it is predicted that osmotic equ

Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy in comparison with human umbilical cord blood cell-mediated therapy of spinal cord injury in rat.

STUDY DESIGN: Experimental study. OBJECTIVE: To evaluate the treatment of spinal cord injury with glial cell-derived neurotrophic factor (GDNF) delivered using an adenoviral vector (AdV-GDNF group) in comparison with treatment performed using human umbilical cord blood mononuclear cells (UCB-MCs)-transduced with an adenoviral vector carrying the GDNF gene (UCB-MCs+AdV-GDNF group) in rat. SETTING: Kazan, Russian Federation. METHODS: We examined the efficacy of AdV-GDNF and UCB-MCs+AdV-GDNF therapy by conducting behavioral tests on the animals and morphometric studies on the spinal cord, perf

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be

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… Connexins are the key proteins in cell–cell communication and may affect CIBP at multiple levels, including nociceptive signaling and bone degradation. Carbenoxolone is a broad-acting connexin blocker. … These results suggest that connexins are involved in CIBP and that carbenoxolone could be a novel analgesic treatment for the pain state [ 85 ]. It has been demonstrated that several breast tumor cell lines release glutamate in vitro through the cystine/glutamate antiporter system xc− (xCT). …

Genetic Screening in a Large Cohort of Italian Patients Affected by Primary Lymphedema Using a Next Generation Sequencing (NGS) Approach.

Primary lymphedema is a rare inherited condition characterized by swelling of body tissues caused by accumulation of fluid, especially in the lower limbs. In many patients, primary lymphedema has been associated with variations in a number of genes involved in the development and maintenance of the lymphatic system. In this study, we performed a genetic screening in patients affected by primary lymphedema using a next generation sequencing (NGS) approach. With this technology, based on a custom-made oligonucleotide probe library, we were able to analyze simultaneously in each patient all the c

Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone.

OBJECTIVE: Myogenic tone (MT) of resistance arteries ensures autoregulation of blood flow in organs and relies on the intrinsic property of smooth muscle to contract in response to stretch. Nucleotides released by mechanical strain on cells are responsible for pleiotropic vascular effects, including vasoconstriction. Here, we evaluated the contribution of extracellular nucleotides to MT. APPROACH AND RESULTS: We measured MT and the associated pathway in mouse mesenteric resistance arteries using arteriography for small arteries and molecular biology. Of the P2 receptors in mouse mesenteric re

Circulating Zonulin Correlates with Density of Enteroviruses and Tolerogenic Dendritic Cells in the Small Bowel Mucosa of Celiac Disease Patients.

BACKGROUND: Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. AIM: To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D. MATERIALS AND METHODS: Altogether 80 patients

Etiology of Childhood Bilateral Sensorineural Hearing Loss in Shandong Province, China.

Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for

Benefit of combined therapy with nicorandil and colchicine in preventing monocrotaline-induced rat pulmonary arterial hypertension.

This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weigh

Essential and neural transcripts from the Drosophila shaking-B locus are differentially expressed in the embryonic mesoderm and pupal nervous system.

The shaking-B gene of Drosophila encodes two functions: one specifically neural and the other required for viability. Flies carrying neural mutations show a range of defects, the best characterized of which is a disruption of some synapses in the giant fibre system, while mutations in the essential function cause animals to die as first instar larvae. We have characterised an essential transcript from this locus and show that mutant lesions underlying two lethal shaking-B alleles map to its coding sequence. We also propose a new model for the topologies of Shaking-B proteins and their relative

The osteoblast in regulation of tumor cell dormancy and bone metastasis.

Breast and prostate cancer are among the most common malignancies worldwide. After treatment of the primary tumor, distant metastases often occur after a long disease-free interval. Bone is a major site for breast and prostate cancer metastasis and approximately 70% of patients with advanced disese suffer from osteolytic or osteoblastic bone metastases, a stage at which the disease is incurable. In bone, the disseminated tumor cells (DTCs) can become quiescent or "dormant", a state where they are alive but not actively dividing. Alternatively, the cancer cells can proliferate, disturb the bone

Fluid Shear Stress Increases Osteocyte and Inhibits Osteoclasts via Downregulating Receptor-Activator of Nuclear Factor κB (RANK)/Osteoprotegerin Expression in Myeloma Microenvironment.

BACKGROUND The aim of this study was to determine the effects of myeloma cells exposed to fluid shear stress on osteocytes and osteoclasts, and clarify the potential underlying mechanisms. MATERIAL AND METHODS A flow and a non-flow model were established using a flow fluid chamber. The myeloma cell line U266 and murine osteocytic MLO-Y4 cells were cultured in vitro. The osteocytes and osteoclasts were examined under a microscope. Osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) activity. RANKL and osteoprotegerin (OPG) gene expression were detected using reverse transcri

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… These small molecules may transfer mechanical loading-induced signals via connexins, resulting in connexin upregulation, increased osteogenesis, and increased osteocyte differentiation [ 20 ]. …

Keyword Index for Volume 111

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Spectrum of sublytic astrocytopathy in neuromyelitis optica.

Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcript

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… As components of tripartite CNS synapses, and the anatomical basis of the connexin-sustained astroglial syncytium that regulates the flow of water and small molecules throughout the CNS, astrocytes are crucial for synaptic plasticity and cognitive function. … Neurochem Int . 2013 ; 63 ( 7 ): 702 – 711 . 23684954 10.1016/j.neuint.2013.05.003 PMC3783552 71 Richard C , Ruiz A , Cavagna S , et al Connexins in neuromyelitis optica: A link between astrocytopathy and demyelination . …

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) ne

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… In support to these data, it has been recently reported that the incubation of SGCs primary cultures with OHP induced SGCs activation (increase of GFAP-positive cells), SGCs morphological changes, the increased expression of one of the main components of gap junctions (connexin Cx43) and pro-inflammatory … A more recent research from Robinson and colleagues described significant alterations in astrocytic connexins and glutamate transporters mediated neuropathic pain in the BIPN model. …