Lindedalgaard3445

Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.

The aim of this study was to develop a nasal powder formulation of the antifibrinolytic drug, tranexamic acid (TXA), in combination with the wound-healing agent hyaluronic acid (HA) for the local treatment of epistaxis (nose bleeding).

Formulations of TXA alone and with different concentrations of HA were freeze-dried and characterised according to their physicochemical properties. Aerosol performance was assessed to ensure nasal deposition with minimal lung deposition. Nasal epithelial cells were used to assess cytotoxicity, transport across the nasal epithelium, antioxidant, wound-healing and anti-inflammatory properties of all formulations.

Formulations containing TXA and HA were produced and found to be mostly deposited in the nasal cavity (more than 90%). Formulation of TXA + 0.3%HA showed wound reduction of 29.3% when assessed in ALI culture. At this concentration, formulations also reduced ROS production in RPMI 2650, and IL-8 production in primary nasal epithelial cells. Furthermore, for formulations containing HA, the higher viscosity may lead to larger residence time in the nasal cavity.

Combination of TXA with HA shows promising results for the treatment of nasal epistaxis.

Combination of TXA with HA shows promising results for the treatment of nasal epistaxis.The main challenge of pain management with opioids is development of acute and chronic analgesic tolerance. Several studies on neuronal cells have focused on the molecular mechanisms involved in tolerance such as cyclic AMP (cAMP) activation, and nitric oxide (NO) pathway. However, the effects of opioids on non-neuronal cells and tolerance development have been poorly investigated. Lithium chloride is a glycogen synthase kinase 3β (GSK-3β) inhibitor and exert its effects through modulation of nitric oxide pathway. In this study we examined the effect of lithium on acute/chronic morphine and methadone administration in endothelial cells which express mu opioid receptors. Human umbilical vein endothelial cells (HUVECs) were treated with different doses of morphine, methadone, and lithium for six and 48 h. Then we evaluated cell viability, nitrite and cyclic AMP levels, as well as the expression of endothelial nitric oxide synthase (eNOS) protein using Immunocytochemistry (ICC) assay and phosphorylated GSK-3β enzyme by western blot analysis in cells. Both chronic morphine and methadone treatment increased NO level and eNOS expression in HUVECs. Morphine induced cAMP overproduction after 48 h exposure with cells. Lithium pretreatment (10 mM) in both morphine and methadone received groups significantly reduced nitrite and cAMP levels as well as eNOS expression as compared to the control. The decreased amount of phospho GSK-3β due to the opioid exposure was increased following lithium treatment. Tolerance like pattern may occur in non-neuronal cells with opioid receptors and this study clearly revealed the attenuation of morphine and methadone tolerance like behavior by lithium treatment in HUVECs.In fish and other vertebrates, growth hormone (GH) is an essential polypeptide required for normal growth and development. In an attempt to understand growth regulation in yellowtail kingfish (YTK), the full-length cDNA sequences encoding gh and its receptors (ghr1 and ghr2) were cloned, characterized and the expression profiles of these three genes were investigated during embryonic development. The full-length cDNA sequences of GH and its receptors were obtained by RT-PCR combined with RACE methord. YTK gh cDNA sequence was 852 base pairs (bp) that comprised an open reading frame (ORF) of 615 bp encoding a 204-amino acids (aa) precursor. The preprohormone compassed a signal peptide (17 aa) and the mature peptide (187 aa). YTK GHR1 protein consisted of a signal peptide (28 aa), an extracellular domain (222 aa), a single transmembrane domain (23 aa) and an intracellular domain (361 aa). GHR2 protein included 18 aa, 223 aa, 23 aa, and 321 aa, respectively. Tissue distribution analysis showed that the maximal level of gh expression was observed in the pituitary, and ghr1 mRNA was mainly detected in the liver, while ghr2 transcripts were most abundant in the gonad. Moreover, both ghr1 and ghr2 mRNAs were expressed in all embryonic stages and displayed different gene expression profiles. Overall, these results provide initial evidences for the involvement of the GH/GHR system in the early ontogeny of yellowtail kingfish.Emergence of MDR 'superbugs' inflamed a severe sense of urgency amongst scientists aiming at the discovery of novel potential drug molecules. Bacteria of the genus Streptomyces are really worth investigating for their immense potential to produce natural compounds of pharmaceutical importance. In the present study, the genome of Streptomyces sp. strain 196 was sequenced, studied and secondary metabolite biosynthetic gene clusters (smBGCs) were detected. FAME analysis was used for taxonomic validation of strain 196. Genome of strain 196 was sequenced using the Illumina NextSeq system which has resulted in a draft genome of 7.4 Mb. Rapid annotation using subsystem technology (RAST) results revealed the presence of 6682 CDS, 64 tRNA genes and 7 rRNA genes. Comparative studies revealed that strain 196 have 93.5% nucleotide and 96% protein level similarities with Streptomyces rhizosphaericola 1AS2c. Genome mining using antiSMASH predicted the presence of BGCs responsible for diverse bioactive compound production. The detected gene clusters were two PKS-III, one PKS-I, five NRPS, two hybrid PKS-I/NRPS, one thiopeptide/LAP, and one bacteriocin types. Furthermore, many other types BGCs such as three ectoine, two siderophore, one arylpolyene, two butyrolactone, one lassopeptide, one lanthipeptide and one melanin were also found. The results of this study provides information about genome and BGCs of strain 196, this information is valuable for researchers who are interested in isolation of bioactive compounds and working on heterologous expression of cryptic BGCs for novel bioactive compounds production.Simple, multiplex qPCR methods are advantages for rapid molecular diagnosis of multiple antibiotics-resistant genes simultaneously. However, the number of genes can be detected in a single reaction tube is often limited by the fluorescence channels of a real-time PCR instrument. In this study, we developed a simple 2-D multiplex qPCR method by combining the probe colors and amplicon Tm values to overcome the mechanical limit of the machine. The principle of the novel assay was validated by detection of nine bacterial antibiotic-resistance genes (KPC, NDM, VIM, OXA-48, GES, CIT, EBC, ACC and DHA) in a single reaction tube. This assay is highly sensitive within a range of 30-3000 copies per reaction. The simplicity, rapidity, high sensitivity and specificity, and low cost of the novel method make it a promising tool for developing clinical diagnostic kits for monitoring resistance and other genetic determinants of infectious diseases.Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1β and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1β was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1β in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1β protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1β and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1β mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1β and increasing IL-11 production.Overexpression of semaphorin 4D (SEMA4D), an immune semaphorin, is found in various human malignancies, including colorectal cancer (CRC). In this study, we explored the relationship between silencing SEMA4D expression and 5-fluorouracil (5-FU) response in the colorectal cancer cell line. SW48 cells were transfected with a short interfering RNA (siRNA) in order to silence SEMA4D gene expression and then exposed to 5-FU for 48 h. The down-regulation of SEMA4D expression was confirmed by qRT-PCR and the particular concentration of 5-FU was acquired using MTT assay. Flow cytometry and western blot were used to evaluate apoptosis rate and pro- and anti-apoptotic expression levels of proteins involved in apoptosis including Bax, Bcl-2, P53, and caspase-3. Other oncogenic activities including epithelial-mesenchymal transition (EMT) process, cancer stem cell (CSC) markers, and β-catenin pathway were investigated using qRT-PCR, and western blot. The proliferation was analyzed via colony formation test and cell invasion was assessed by transwell assay. Our data demonstrate that SEMA4D silencing results in strikingly elevated apoptosis in response to 5-FU treatment and leads to down-regulation of Bcl-2 and overexpression of Bax, P53, and caspase-3 in protein levels. Furthermore, the mRNA and protein expression levels of β-catenin, as well as transcript expressions of CSCs and EMT markers, were remarkably diminished. However, mRNA expression of E-cadherin as an epithelial marker was significantly increased in 5-FU treatment combined with siRNA SEMA4D. Phospholipase (e.g. inhibitor This study implicates that the silencing of SEMA4D by siRNA promotes the chemosensitivity of SW48 cells to 5-FU and it may be a potential therapeutic agent for colon cancer therapy.