2,618 research outputs found
Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis
PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Extra-hepatic fascioliasis with peritoneal malignancy tumor feature
Fascioliasis is a zoonose parasitic disease
caused by Fasciola hepatica and Fasciola gigantica and is
widespread in most regions of the world. Ectopic fascioliasis
usually caused by juvenile Fasciola spp., but in
recent years a few cases of tissue-embedded ova have been
reported from different endemic areas. A 79-year-old Iranian
man resident in Eird-e-Mousa village from Ardabil
Province, north-west of Iran, complained with abdominal
pain, nausea, and intestinal obstruction symptoms referred
to Ardabil Fatemi hospital. In laparotomy multiple intestinal
masses with peritoneal seeding resembling of a
malignant lesion were seen. After appendectomy and peritoneal
mass biopsy with numerous intraperitoneal adenopathy,
paraffin embedded blocks were prepared from
each tissues. A blood sample was taken from the patient
5 months later for serological diagnosis. Histopathological
examination of sections showed fibrofatty stroma with
dense mixed inflammatory cells infiltration and fibrosis in
peritoneal masses. Large numbers of ova of Fasciola spp.
were noted with typical circumscribed granulomas. Despite
of anti-fasciola treatment, IHA test for detecting anti F.
hepatica antibodies was positive 5 months after surgery
with a titer of 1/128. Due to multiple clinical manifestation
of extra-hepatic fascioliasis, its differential diagnosis from
intraperitoneal tumors or other similar diseases should be
considered
Sign-reversal of the in-plane resistivity anisotropy in hole-doped iron pnictides
The in-plane anisotropy of the electrical resistivity across the coupled
orthorhombic and magnetic transitions of the iron pnictides has been
extensively studied in the parent and electron-doped compounds. All these
studies universally show that the resistivity across the long
orthorhombic axis - along which the spins couple antiferromagnetically
below the magnetic transition temperature - is smaller than the resistivity
of the short orthorhombic axis , i. e. .
Here we report that in the hole-doped compounds
BaKFeAs, as the doping level increases, the
resistivity anisotropy initially becomes vanishingly small, and eventually
changes sign for sufficiently large doping, i. e. . This
observation is in agreement with a recent theoretical prediction that considers
the anisotropic scattering of electrons by spin-fluctuations in the
orthorhombic/nematic state.Comment: This paper has been replaced by the new version offering new
explanation of the experimental results first reported her
TNF-alpha differentially modulates subunit levels of respiratory electron transport complexes of ER/PR plus ve/-ve breast cancer cells to regulate mitochondrial complex activity and tumorigenic potential
Background: Tumor necrosis factor-α (TNF-α) is an immunostimulatory cytokine that is consistently high in the
breast tumor microenvironment (TME); however, its differential role in mitochondrial functions and cell survival in
ER/PR +ve and ER/PR −ve breast cancer cells is not well understood.
Methods: In the current study, we investigated TNF-α modulated mitochondrial proteome using high-resolution
mass spectrometry and identified the differentially expressed proteins in two different breast cancer cell lines, ER/PR
positive cell line; luminal, MCF-7 and ER/PR negative cell line; basal-like, MDA-MB-231 and explored its implication in
regulating the tumorigenic potential of breast cancer cells. We also compared the activity of mitochondrial
complexes, ATP, and ROS levels between MCF-7 and MDA-MB-231 in the presence of TNF-α. We used Tumor
Immune Estimation Resource (TIMER) webserver to analyze the correlation between TNF-α and mitochondrial
proteins in basal and luminal breast cancer patients. Kaplan-Meier method was used to analyze the correlation
between mitochondrial protein expression and survival of breast cancer patients.
Results: The proteome analysis revealed that TNF-α differentially altered the level of critical proteins of
mitochondrial respiratory chain complexes both in MCF-7 and MDA-MB-231, which correlated with differential
assembly and activity of mitochondrial ETC complexes. The inhibition of the glycolytic pathway in the presence of
TNF-α showed that glycolysis is indispensable for the proliferation and clonogenic ability of MDA-MB-231 cells (ER/
PR −ve) as compared to MCF-7 cells (ER/PR +ve). The TIMER database showed a negative correlation between the
expressions of TNF-α and key regulators of mitochondrial OXPHOS complexes in basal breast vs lobular carcinoma.
Conversely, patient survival analysis showed an improved relapse-free survival with increased expression of
identified proteins of ETC complexes and survival of the breast cancer patients.
Conclusion: The evidence presented in our study convincingly demonstrates that TNF-α regulates the survival and
proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in
mitochondrial respiratory chain supercomplexes organization and function. This favors the rewiring of
mitochondrial metabolism towards anaplerosis to support the survival and proliferation of breast cancer cells.
Collectively, the results strongly suggest that TNF-α differentially regulates metabolic adaptation in ER/PR +ve (MCF-
7) and ER/PR −ve (MDA-MB-231) cells by modulating the mitochondrial supercomplex assembly and activity
Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles
<p>Abstract</p> <p>Background</p> <p>It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound.</p> <p>Methods</p> <p>5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres.</p> <p>Results</p> <p>5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t<sub>1/2</sub>, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (V<sub>D</sub>, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05).</p> <p>Conclusion</p> <p>In our model system, 5-FU/PEG-PBLG nanoparticles changed the pharmacokinetic behavior of 5-FU, thus increasing its anticancer activity. 5-Fluorouracil loaded nanoparticles have potential as a novel anticancer drug that may have useful clinical applications.</p
Anisotropic Impurity-States, Quasiparticle Scattering and Nematic Transport in Underdoped Ca(Fe1-xCox)2As2
Iron-based high temperature superconductivity develops when the `parent'
antiferromagnetic/orthorhombic phase is suppressed, typically by introduction
of dopant atoms. But their impact on atomic-scale electronic structure, while
in theory quite complex, is unknown experimentally. What is known is that a
strong transport anisotropy with its resistivity maximum along the crystal
b-axis, develops with increasing concentration of dopant atoms; this
`nematicity' vanishes when the `parent' phase disappears near the maximum
superconducting Tc. The interplay between the electronic structure surrounding
each dopant atom, quasiparticle scattering therefrom, and the transport
nematicity has therefore become a pivotal focus of research into these
materials. Here, by directly visualizing the atomic-scale electronic structure,
we show that substituting Co for Fe atoms in underdoped Ca(Fe1-xCox)2As2
generates a dense population of identical anisotropic impurity states. Each is
~8 Fe-Fe unit cells in length, and all are distributed randomly but aligned
with the antiferromagnetic a-axis. By imaging their surrounding interference
patterns, we further demonstrate that these impurity states scatter
quasiparticles in a highly anisotropic manner, with the maximum scattering rate
concentrated along the b-axis. These data provide direct support for the recent
proposals that it is primarily anisotropic scattering by dopant-induced
impurity states that generates the transport nematicity; they also yield simple
explanations for the enhancement of the nematicity proportional to the dopant
density and for the occurrence of the highest resistivity along the b-axis
Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.
Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate.
Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation.
Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined.
Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks.
Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics
Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum
Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology
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