SciCombinator

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PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro. PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17±3.59% in 24h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79μm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0h to infinity (AUC0(-∞)) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12h after single dose administration.

Concepts: Animal testing, In vivo, In vitro

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Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials.

Concepts: Pharmacology, Spinal cord, Clinical trial, ClinicalTrials.gov, The Trial, Spinal cord injury, Food and Drug Administration, Investigational New Drug

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Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma (MM) has been less explored.

Concepts: Cell nucleus, Blood, Red blood cell, Bone marrow, Types of cancer, Anemia, Hematology, Erythrocyte sedimentation rate

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Previous studies indicated that microRNA-338-5p (miR-338-5p) functions as tumor suppressor in some cancer types including glioma. However, the clinical significance and biological function of miR-338-5p in glioma still need to be explored.

Concepts: DNA, Epidemiology, Cancer, Oncology, Function, Cell division, Brain tumor

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Oral submucous fibrosis (OSF) is a chronic insidious disease which predisposes to oral cancer. Understanding the molecular markers for OSF is critical for diagnosis and treatment of oral cancer. In this study, the proteins expression profile of OSF tissues was compared to normal mucous tissues by 2 dimensional electrophoresis (2-DE). The 2-DE images were analyzed through cut, spot detection and match analysis using mass spectrometry (MS). Differentially expressed genes were identified as candidates. RT-PCR, Western Blot and immunohistochemistry were performed to validate the difference in expression of the candidates between OSF and normal mucous tissues. The shRNA targeted to the candidates were then transfected by Lipofectamine2000 to the 3T3 cells to study gene function. Cell proliferation and apoptosis were measured by MTT, clonogenic formation, PI and TUNEL staining. From the proteomic analysis, 94 of the 182 selected spots with differential expression were identified by MS analysis and Cyclophilin A (CYPA) was determined to be the OSF-associated protein candidate. The significant differences in expression between OSF and normal tissues were verified and confirmed by RT-PCR, Western blot and Immunohistochemical analysis. Inhibition of CYPA expression by RNA interference suggested its potential activities involved in cell proliferation and apoptosis process. In conclusion, these results indicated a novel molecular mechanism of OSF pathogenesis and demonstrated CYPA as a potential biomarker and gene intervention targets of OSF. These data may help the development for therapeutics of oral cancer.

Concepts: DNA, Protein, Gene, Gene expression, Bacteria, Molecular biology, RNA, Laboratory techniques

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This study aims to discuss clinical characteristics, image manifestation and treatment methods of temporal bone lesions with facial paralysis as the main manifestation for deepening the understanding of such type of lesions and reducing erroneous and missed diagnosis.

Concepts: Skull, Logic

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Patients with Alzheimer’s disease (AD) are more prone to seizures and myoclonus, but relative risk of these symptoms among other dementia types is unknown.

Concepts: Alzheimer's disease, Epidemiology, Neurology, Parkinson's disease, Dementia, Lewy body, Dementia with Lewy bodies, Frontotemporal lobar degeneration

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Increasing evidence suggests that neuroinflammation comprises a major characteristic of Alzheimer’s disease (AD). Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine implicated in neurodegenerative diseases including AD, and has been proposed as a potent therapeutic target for AD. Although a number of studies focusing on pharmacological or genetic manipulation of TNF-α and its receptors in AD mice have provided significant knowledge regarding the role of TNF-α signaling pathway in the pathogenesis of AD, the consequences of TNF-α genetic deletion have not been thoroughly examined. Here, we focused on the effect of TNF-α deficiency on the amyloid phenotype of 5XFAD mice. Our analysis revealed that amyloid deposition, amyloid-β (Aβ) levels, and AβPP-carboxyterminal fragments are significantly reduced in the brains of 5XFAD/TNF-α-/- mice compared to the 5XFAD/TNF-α+/+. We found decreased protein levels of β- and α-secretases in the 5XFAD/TNF-α-/- brains, suggesting for an effect of TNF-α on AβPP processing and Aβ generation. We also show for the first time that TNF-α affects PS1in vivo, as 5XFAD mice lacking TNF-α expression display reduced PS1-carboxyterminal fragments implying for diminished PS1 activity. Moreover, TNF-α deficiency decreases microglial and astrocytic activation and significantly restricts the phagocytic activity of macrophages against Aβ, supporting for reduced responsiveness of phagocytes toward Aβ. Overall, our results reveal that TNF-α genetic deletion in 5XFAD mice attenuates amyloid plaque formation by lowering Aβ generation through the reduction of functionally active PS1 and β-secretase rather than promoting Aβ clearance by phagocytic cells. Our data further suggest TNF-α inhibition as a therapeutic approach for AD.

Concepts: Immune system, DNA, Gene, Genetics, Phagocytosis, Amyloid, Beta amyloid, Phagocyte

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The clinical and structural trajectories of suspected non-Alzheimer' pathology (SNAP) remain elusive due to its heterogeneous etiology. Baseline and longitudinal clinical (global cognition, daily functioning, symptoms of dementia, and learning memory) and hippocampal volume trajectories over two years were compared between patients with amnestic mild cognitive impairment (aMCI) with SNAP with reduced hippocampal volumes (SNAP+HIPPO) and aMCI patients with SNAP without reduced hippocampal volumes. SNAP+HIPPO showed overall worse baseline cognitive functions. Longitudinally, SNAP+HIPPO showed faster deterioration of clinical symptoms of dementia. Having both hippocampal atrophy and cortical hypometabolism without amyloid pathology may exacerbate symptoms of dementia in aMCI.

Concepts: Alzheimer's disease, Psychology, Brain, Cognition, Memory, Hippocampus, Psychiatry, Amnesia

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Impaired cardiac function has been related to accelerated cognitive decline in late-life.

Concepts: Cognition, Educational psychology, Troponin, Troponin T