Abstract Background Exosomes are nanometer-sized vesicles that are released by normal and neoplastic cells. Previous studies have focused on the interaction between tumour-derived exosomes and the ...immune system, as a consequence of immune suppression or enhancement. However, the effects of tumour-derived exosomes on tumour cells themselves have not been well studied. Aims To investigate the effects of gastric cancer exosomes on tumour cell proliferation and the possible mechanisms. Methods By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, then viewed them by electron microscopy. Cell proliferation was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. Protein expression was assayed by Western blotting. Results SGC7901-cell-derived exosomes promoted the proliferation of SGC7901 and BGC823 cells. The increase in proliferation induced by exosomes was accompanied by activation of Akt and extracellular-regulated protein kinase, and phosphoinositide 3-kinase or extracellular-regulated protein kinase inhibitor partially reversed the proliferative effect of exosomes. Moreover, the exosome-induced increase in activity of Akt and extracellular-regulated protein kinase coincided with decreased expression of the Casitas B-lineage lymphoma family of ubiquitin ligases. Conclusion Gastric cancer exosomes promoted tumour cell proliferation, at least in part, by activation of PI3K/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinase pathways. The decreased expression of Casitas B-lineage lymphoma proteins might have contributed to the activation of Akt and extracellular-regulated protein kinase.
Summary Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease, which has a high prevalence and morbidity in the Eastern Siberia of Russia, and in the broad diagonal, northern-east to ...southern-west belt in China and North Korea. In 1990's, it was estimated that in China 1–3 million people had some degree of symptoms of the disease, although even higher estimates have been presented. In China, the extensive prevalence peaked in the late 1950's, but since then, in contrast to the global trend of the osteoarthritis (OA), the number of cases has been dramatically falling. Up to 2013, there are 0.64 millions patients with the KBD and 1.16 millions at risk in 377 counties of 13 provinces or autonomous regions. This is obviously thanks to the preventive efforts carried out, which include providing millions of people with dietary supplements and clean water, as well as relocation of whole villages in China. However, relatively little is known about the molecular mechanisms behind the cartilage damage, the genetic and the environmental risk factors, and the rationale of the preventive effects. During the last decade, new data on a cellular and molecular level has begun to accumulate, which hopefully will uncover the grounds of the disease.
Pneumocystis jirovecii pneumonia (PCP) can affect various types of immunocompromised patients. We sought to evaluate the diagnostic accuracy of (1 → 3)-β-D-glucan (BDG) for the diagnosis of PCP. We ...carried out a meta-analysis of relevant studies, identified through PubMed and Scopus. Eligible studies were those that reported BDG diagnostic data in cases with documented PCP and controls with other conditions. Cases of invasive fungal infections and healthy controls were excluded. We performed a bivariate meta-analysis of sensitivity and specificity and constructed a hierarchical summary receiver operating characteristics (HSROC) curve. Fourteen studies were included in the meta-analysis. BDG data were analysed for 357 PCP cases and 1723 controls. The average (95% confidence interval) sensitivity and specificity of BDG were 94.8% (90.8–97.1%) and 86.3% (81.7–89.9%), respectively. The positive and negative likelihood ratios were 6.9 (5.1–9.3) and 0.06 (0.03–0.11), respectively. The area under the HSROC curve was 0.965 (0.945–0.978). Serum BDG shows excellent sensitivity and very good specificity in the diagnosis of PCP. Still, in clinical practice the test results should be interpreted in the context of the underlying clinical characteristics of the individual patient.
The impact of compositional complexity on the ion-irradiation induced swelling and hardening is studied in Ni and six Ni-containing equiatomic alloys with face-centered cubic structure. The ...irradiation resistance at the temperature of 500°C is improved by controlling the number and, especially, the type of alloying elements. Alloying with Fe and Mn has a stronger influence on swelling reduction than does alloying with Co and Cr. The quinary alloy NiCoFeCrMn, with known excellent mechanical properties, has shown 40 times higher swelling tolerance than nickel.
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Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. Here, we report the discovery of a ...non-metabolic function of PGAM1 in promoting cancer metastasis. A proteomic study identified α-smooth muscle actin (ACTA2) as a PGAM1-associated protein. PGAM1 modulated actin filaments assembly, cell motility and cancer cell migration via directly interacting with ACTA2, which was independent of its metabolic activity. The enzymatically inactive H186R mutant retained its association with ACTA2, whereas 201-210 amino acids deleted PGAM1 mutant lost the interaction with ACTA2 regardless of intact metabolic activity. Importantly, PGAM1 knockdown decreased metastatic potential of breast cancer cells in vivo and PGAM1 and ACTA2 were jointly associated with the prognosis of breast cancer patients. Together, this study provided the first evidence revealing a non-metabolic function of PGAM1 in promoting cell migration, and gained new insights into the role of PGAM1 in cancer progression.
The Horn of Africa ((HOA), including Djibouti, Eritrea, Ethiopia, and Somalia) has been slammed by extreme drought within the past years, and has become one of the most food-insecure regions in the ...world. Millions of people in the HOA are undernourished and are at risk of famine. Meanwhile, global climate change continues to cause more extreme weather and climate events, such as drought and heat waves, which have significant impacts on crop production and food security. This study aimed to investigate extreme drought in the Horn of Africa region, using satellite remote sensing data products from the Moderate Resolution Imaging Spectroradiometer (MODIS), a key instrument onboard the National Aeronautics and Space Administration (NASA) satellites Terra and Aqua, as well as Tropical Rainfall Measuring Mission (TRMM) precipitation data products. Normalized Difference Vegetation Index (NDVI), Vegetation Condition Index (VCI), Temperature Condition Index (TCI), and Vegetation Health Index (VHI) data from 2000 to 2017 were derived from the MODIS measurements and analyzed for assessments of the temporal trend of vegetation health and the impacts of extreme drought events. The results demonstrated the severity of vegetation stress and extreme drought during the past decades. From 1998 to 2017, monthly precipitation over major crop growth seasons decreased significantly. From 2001 to 2017, the mean VHI anomaly of HOA cropland decreased significantly, at a trend of −0.2364 ± 0.1446/year, and the mean TCI anomaly decreased at a trend of −0.2315 ± 0.2009/year. This indicated a deterioration of cropland due to drought conditions in the HOA. During most of the crop growth seasons in 2015 and 2016, the VHI values were below the 10-year (2001–2010) average: This was caused by extreme drought during the 2015–2016 El Niño event, one of the strongest El Niño events in recorded history. In addition, monthly VHI anomalies demonstrated a high correlation with monthly rainfall anomalies in July and August (the growth season of major crops in the HOA), and the trough points of the monthly rainfall and VHI anomaly time series of July and August were consistent with the timing of drought events and El Niño events.
Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To ...test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors.
A new index, the Normalized Multi‐band Drought Index (NMDI), is proposed for monitoring soil and vegetation moisture from space. NMDI is defined as , where R represents the apparent reflectance ...observed by a satellite sensor. Similar to the Normalized Difference Water Index, NMDI uses the 860 nm channel as the reference; instead of using a single liquid water absorption channel, however, it uses the difference between two liquid water absorption channels centered at 1640 nm and 2130 nm as the soil and vegetation moisture sensitive band. Analysis revealed that by combining information from multiple near infrared, and short wave infrared channels, NMDI has enhanced the sensitivity to drought severity, and is well suited to estimate both soil and vegetation moisture. Typical soil reflectance spectra and satellite‐acquired reflectances, are used to validate the usefulness of NMDI. Its application to areas with moderate vegetation coverage, however, needs further investigation.
To investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted imaging to predict perineural invasion (PNI) preoperatively in resectable gastric cancer (GC).
This study ...prospectively recruited 85 surgically resected GC patients (58 men, 27 women) aged 60.87 ± 10.17 (39-81) years, who underwent IVIM sequence within 1 week before surgery. According to histopathological PNI diagnoses, patients were divided into PNI positive and negative groups. Conventional apparent diffusion coefficient (ADC) and the IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D∗), and pseudodiffusion fraction (f), were compared between the two groups. Morphological MRI features were also analysed. Multivariate logistic regression was used to screen independent predictors of PNI. Receiver-operating characteristic curve analyses were preformed to evaluate the efficacy. Spearman's correlation test was performed to analyse the relationship between MRI parameters and PNI.
Tumour thickness and f in PNI-positive group were higher, whereas the ADC, D were lower than those in PNI-negative group (p<0.05). These four parameters correlated with PNI (p<0.05). The D, f, and tumour thickness were independent predictors of PNI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D + f + thickness) were 0.648, 0.745, 0.698, 0.725, and 0.869, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p<0.05).
The ADC, D, and f can effectively distinguish PNI status in GC. The D, f, and thickness were independent predictors of PNI.
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