Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Summary
Dexmedetomidine might reduce delirium after cardiac surgery. We allocated 326 participants to an infusion of dexmedetomidine at a rate of 0.6 μg kg−1 for 10 min and then at 0.4 μg.kg−1.h−1 ...until the end of surgery; 326 control participants received comparable volumes of saline. We detected delirium in 98/652 (15%) participants during the first seven postoperative days: 47/326 after dexmedetomidine vs. 51/326 after placebo, p = 0.62, adjusted relative risk (95%CI) 0.86 (0.56–1.33), p = 0.51. Postoperative renal impairment (Kidney Disease Improving Global Outcomes stages 1, 2 and 3) was detected in 46, 9 and 2 participants after dexmedetomidine and 25, 7 and 4 control participants, p = 0.040. Intra‐operative dexmedetomidine infusion did not reduce the incidence of delirium after cardiac valve surgery but might impair renal function.
AbstractAtherosclerosis is characterized by lipid accumulation, inflammatory response, cell death and fibrosis in the arterial wall, and is a major pathological basis for ischemic coronary heart ...disease (CHD), which is the leading cause of morbidity and mortality in the USA and Europe. Intervention studies with statins have shown to reduce plasma LDL cholesterol concentrations and subsequently the risk of developing CHD. However, not all the aggressive statin therapy could decrease the risk of developing CHD. Many clinical and epidemiological studies have clearly demonstrated that the HDL cholesterol is inversely associated with risk of CHD and is a critical and independent component of predicting this risk. Elucidations of HDL metabolism give rise to therapeutic targets with potential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. The concept of reverse cholesterol transport is based on the hypothesis that HDL displays an cardioprotective function, which is a process involved in the removal of excess cholesterol that is accumulated in the peripheral tissues (e.g., macrophages in the aortae) by HDL, transporting it to the liver for excretion into the feces via the bile. In this review, we summarize the latest advances in the role of the lymphatic route in reverse cholesterol transport, as well as the biliary and the non-biliary pathways for removal of cholesterol from the body. These studies will greatly increase the likelihood of discovering new lipid-lowering drugs, which are more effective in the prevention and therapeutic intervention of CHD that is the major cause of human death and disability worldwide.
Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
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Pharmacotherapy using natural substances can be currently regarded as a very promising future alternative to conventional therapy. With the rapid development of biotechnologies and analytical ...techniques, a great number of methods have been developed for the identification and quantification of the material, extracts, and products of natural ingredients. The advances available today. The need for safer drugs without side effects has led to the use of natural ingredients with proven safety. In recent years, some bioactive polysaccharides isolated from natural sources have attracted much attention in the field of biochemistry and pharmacology. As an example, polysaccharides or their glycoconjugates were shown to exhibit multiple biological activities including anticarcinogenic, anticoagulant, immunostimulating, antioxidant, etc. During the last several years, we have witnessed a steady expansion in the number of publications that focus in antioxidant polysaccharides. This review presents current findings on the latest advancements and trends in antioxidant polysaccharides isolated from the following: plants, fungi, bacteria, animal sources, and algae. Some interesting studies focus on investigation of the relationship between their structure and antioxidant activity, elucidation of their antioxidant mechanism at the molecular level, and improvement of their various biological activities by chemical modifications. Although the mechanism of their antioxidant action is still not completely clear, these polysaccharides are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers.
Abstract Radio observations of pulsars offer a potential method to probe the intricate microstructure in the turbulent interstellar medium. Here we report on a high-resolution dynamic spectral ...analysis of the “swooshing pulsar” B0919+06 observed with the Five-hundred-meter Aperture Spherical radio Telescope over multiple epochs and with the ultrawideband receiver on the Parkes radio telescope. For all observations, the dynamic scintillation spectra, two-dimensional autocovariance functions, and secondary spectra are presented. At 1250 MHz, the decorrelation bandwidth, diffraction timescale, and the drift rate are determined to be Δ ν d = 25.89 ± 7.55 MHz, Δ τ d = 14.42 ± 3.98 minutes, and dt / d ν = 0.07 ± 0.14 minutes MHz −1 , respectively. The frequency dependencies of the scintillation parameters exhibit single power-law spectral behaviors, indicating that the electron density fluctuations in the interstellar medium approximately follow the Kolmogorov spectrum. The secondary spectra exhibit two distinct parabolic arcs with well-determined curvatures of 0.002 and 0.02 s 3 for the outer and inner arcs, respectively. The locations of the scattering screens are approximately determined to be 157.3 and 726.0 pc, respectively, from the pulsar for isotropic scattering. The inner scintillation arc is present contemporaneously over a wide frequency range, indicating that the scintillation arc is a broadband phenomenon. The arc curvature scales with observing frequency as a power law with an index of −2.05 ± 0.05, which implies that the scattering screen spans a physical distance from 689.7 to 883.3 pc from the pulsar.
Abstract
In this work, 1272 superflares on 311 stars are collected from 22,539 solar-type stars from the second-year observation of the Transiting Exoplanet Survey Satellite (TESS), which almost ...covered the northern hemisphere of the sky. Three superflare stars contain hot Jupiter candidates or ultrashort-period planet candidates. We obtain
γ
= −1.76 ± 0.11 of the correlation between flare frequency and flare energy (
) for all superflares and get
β
= 0.42 ± 0.01 of the correlation between superflare duration and energy (
T
duration
∝
E
β
), which supports that a similar mechanism is shared by stellar superflares and solar flares. Stellar photometric variability (
R
var
) is estimated for all solar-type stars, and the relation of
is included. An indicator of chromospheric activity (
S
-index) is obtained by using data from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) for 7454 solar-type stars. Distributions of these two properties indicate that the Sun is generally less active than superflare stars. We find that saturation-like feature of
R
var
∼ 0.1 may be the reason for superflare energy saturating around 10
36
erg. Object TIC 93277807 was captured by the TESS first-year mission and generated the most energetic superflare. This superflare is valuable and unique in that it can be treated as an extreme event, which may be generated by different mechanisms than other superflares.
The stacking fault energy (SFE) values of several typical face-centered-cubic (fcc) high-entropy alloys (HEAs) were experimentally measured by weak-beam dark-field transmission electron microscopy. ...It was found that the SFE of the Fe-Co-Ni-Cr-Mn HEA system strongly depends on the SFE of the individual constituents. Specifically, the SFE of this HEA system is closely associated with the Ni concentration in the alloys. Additionally, the lower SFE tends to promote formation of more deformation twins with a smaller thickness under loading, leading to better mechanical properties, especially at low temperatures.
•SFE of six Fe-Co-Ni-Cr-Mn HEAs was measured experimentally.•Constituents play an important role in the SFE, particularly the Ni content.•Lower SFE promotes formation of thinner twins during loading and better properties.
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