Primary effusion lymphoma (PEL) is an incurable non-Hodgkin's lymphoma and novel biology-based treatments are urgently needed in clinical settings. Shikonin (SHK), a napthoquinone derivative, has been used for the treatment of solid tumors. Here, we report that SHK is an effective agent for the treatment of PEL. Treatment with SHK results in significant reduction of proliferation in PEL cells and their rapid apoptosis in vitro. SHK-induced apoptosis of PEL cells is accompanied by the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (Δψm), an activation of c-Jun-N-terminal kinase (JNK), p38, as well as caspase-3, -8, and -9. Scavenging of ROS in the presence of N-acetylcysteine (NAC) almost blocks the loss of mitochondrial membrane Δψm, activation of JNK, cleavage of caspase-3, -9, and an induction of apoptosis in SHK treated PEL cells. SP600125, a specific inhibitor of JNK, also rescues a proportion of cells from the apoptotic effect of SHK. In addition, inhibition of caspase activation in the presence of pan-caspase inhibitor, Q-VD-OPh, blocks the SHK-inducing apoptosis, but doesn't completely inhibit SHK-mediated JNK activation. Therefore, ROS is an upstream trigger of SHK-induced caspase dependent apoptosis of PEL cells through disruption of mitochondrial membrane Δψm in an intrinsic pathway and an activation of JNK in an extrinsic pathway. In a PEL xenografted mouse model, SHK treatment suppresses PEL-mediated ascites formation without showing any significant adverse toxicity. These results suggested that SHK could be a potent anti-tumor agent for the treatment of PEL.Endocrine-disrupting chemicals have the ability to interfere with and alter functions of the hormone system, leading to adverse effects on reproduction, growth and development. Despite growing concerns over their now ubiquitous presence in the environment, endocrine-related human health effects remain largely outside of comparative human toxicity characterization frameworks as applied for example in life cycle impact assessments. In this paper, we propose a new methodological framework to consistently integrate endocrine-related health effects into comparative human toxicity characterization. We present two quantitative and operational approaches for extrapolating towards a common point of departure from both in vivo and dosimetry-adjusted in vitro endocrine-related effect data and deriving effect factors as well as corresponding characterization factors for endocrine-active/endocrine-disrupting chemicals. Following the proposed approaches, we calculated effect factors for 323 chemicals, reflecting their endocrine potency, and related characterization factors for 157 chemicals, expressing their relative endocrine-related human toxicity potential. Developed effect and characterization factors are ready for use in the context of chemical prioritization and substitution as well as life cycle impact assessment and other comparative assessment frameworks. Endocrine-related effect factors were found comparable to existing effect factors for cancer and non-cancer effects, indicating that (1) the chemicals' endocrine potency is not necessarily higher or lower than other effect potencies and (2) using dosimetry-adjusted effect data to derive effect factors does not consistently overestimate the effect of potential endocrine disruptors. Calculated characterization factors span over 8-11 orders of magnitude for different substances and emission compartments and are dominated by the range in endocrine potencies.
Of the complications that can occur during endovascular surgery in aneurysmal subarachnoid hemorrhage (aSAH) patients, thromboembolism remains a particular challenge for many surgeons. Heparin has been widely used for its prevention, but it has not been able to eliminate concerns about bleeding. Eribulin price Therefore, in this study, we tried to determine the risk of rebleeding associated with heparin use.
We retrospectively analyzed the medical and surgical records of 109 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2010 to 2014. These patients were divided into two groups according to whether heparin was loaded or not, to determine the effect of heparin on rebleeding and to identify other risk factors of rebleeding.
This series included 40 men (36.7 %) and 69 women (63.3 %) of mean age 57.9 ± 14.8 years. In 80 patients (73.4 %), endovascular embolization was conducted using an intraoperative bolus of 5000 units of heparin, whereas in the other 29 (26.6 %) endovascular embolization was performed without an intraoperative heparin bolus. After procedures, 16 patients (14.7 %) experienced rebleeding and 2 (1.8 %) a thromboembolic event. Intraoperative heparin loading (OR 0.683 [95 % CI 0.199-2.338]) was not found to be related to postoperative rebleeding. link2 Rather, logistic regression analysis showed preoperative modified Fisher grade (OR 2.037 [95 % CI 1.077-3.853]) and external ventricular drainage (OR 5.389 [95 % CI 1.171-24.801]) independently predicted rebleeding.
Heparin loading during endovascular treatment of ruptured cerebral aneurysms did not affect rebleeding. We conclude heparin loading to prevent thromboembolism during endovascular treatment may be considered a good option in aSAH patients.
Heparin loading during endovascular treatment of ruptured cerebral aneurysms did not affect rebleeding. We conclude heparin loading to prevent thromboembolism during endovascular treatment may be considered a good option in aSAH patients.
Early life stress exposures may cause dysregulation of the Hypothalamic Pituitary Adrenal (HPA)-axis and cortisol production, with timing and sex-specific effects. Studies examining the impact of early life stress on cortisol responses to stress have focused on severe trauma and have produced inconsistent results. The aim of this study was to investigate whether common early life stressors, experienced prenatally or throughout childhood and adolescence, play a role in the dysregulation of the HPA-axis in early adulthood.
Exposures to common life stress events were examined prenatally and as longitudinal trajectories of stress exposure from birth to age 17 in males and females from Gen2 of the Raine Study. At age 18 years, 986 participants were assessed for their salivary cortisol response to a psychosocial stressor - the Trier Social Stress Test (TSST).
In males there was an association between high prenatal stress exposure at 18 weeks gestation and a heightened TSST response. We found evidence for sex-specific associations with increasing stress exposure during adolescence (the ascending trajectory) whereby males were more likely to be non-responders to the TSST and females were more likely to be responders.
Our results point to sex differences in how stress exposure in-utero and exposure increasing during adolescence may affect regulation of the HPA-axis later in life. However, overall common life stress events experienced in-utero, during childhood and adolescence show limited impact on the HPA-axis stress response in early adulthood.
Our results point to sex differences in how stress exposure in-utero and exposure increasing during adolescence may affect regulation of the HPA-axis later in life. However, overall common life stress events experienced in-utero, during childhood and adolescence show limited impact on the HPA-axis stress response in early adulthood.
Nanocellulose and nanochitin are both biobased materials with complementary structures and properties. Both exhibit pH-dependent surface charges which are opposite in sign. Hence, it should be possible to manipulate them to form complexed structures via ionic bond formation at prescribed pH conditions.
Nanocellulose and nanochitin were mixed after exposure to acidic or neutral conditions to influence their ionization state. The heat of interaction during the introduction of nanochitin to nanocellulose was monitored via isothermal titration calorimetry. The strength and gel properties of the resulting structures were characterized via rheological measurement.
The resultant gel properties in the designed hybrid systems were found to depend directly on the charge state of the starting materials, which was dictated by pH adjustment. Different interparticle interactions including ionic attraction, hydrophobic associations, and physical entanglement were identified in the systems and the influence of each wass. Ionic complex formation was found to provide enhanced stability under broader pH conditions, while physical entanglement of cellulose nanofibers was a substantial thickening mechanism in all systems.Nucleic acid amplification tests (NAATs) are a crucial diagnostic and monitoring tool for infectious diseases. A key procedural step for NAATs is sample preparation separating and purifying target nucleic acids from crude biological samples prior to nucleic acid amplification and detection. Traditionally, sample preparation has been performed with liquid- or solid-phase extraction, both of which require multiple trained user steps and significant laboratory equipment. The challenges associated with sample preparation have limited the dissemination of NAAT point-of-care diagnostics in low resource environments, including low- and middle-income countries. We report on a paper-based device for purification of nucleic acids from whole blood using isotachophoresis (ITP) for point-of-care NAATs. We show successful extraction and purification of target nucleic acids from large volumes (33 µL) of whole human blood samples with no moving parts and few user steps. Our device utilizes paper-based buffer reservoirs to fu simple, fully integrated sample preparation system for nucleic acid amplification tests at the point-of-care.This work aims to compare the performance of the continuous operation (CO) and intermittent operation (IO) of upflow anaerobic sludge blanket (UASB) reactors for the removal of estrone (E1) and 17α-ethinylestradiol (EE2) from wastewaters. link3 Results suggest that the IO contribute to the improvement of the overall removal of estrogens (above 95% for E1 and EE2) when compared to CO (49% for E1 and 39% for EE2). For both CO and IO, biodegradation was the main removal mechanism for E1, while for EE2, adsorption to sludge was the major removal pathway. Moreover, a higher biodegradation of estrogens was obtained with the IO compared to CO (69.4% vs. 43.3% for E1 and 21.8% vs. 8.0% for EE2). The favourable effect of IO can be justified by effluent recirculation during the feedless period which promotes the adaptation of microbial biomass to estrogens' biodegradation.Soil acidity is one of the vital factors that influence organic matter transformation and accumulation. Long-term studies on the mechanisms of biochar's effects on soil organic matter (SOM) accumulation dependent on pH values are lacking. A four-year column experiment was conducted without and with biochar application (11.3 Mg ha-1 crop-1) in acid (pH = 5.24) and alkaline (pH = 8.22) soils under paddy rice/wheat annual rotation. To explore organic matter accumulation mechanisms, SOM pools were extracted (physical-chemical fractionation) and their chemical structures were analyzed using advanced solid-state 13C nuclear magnetic resonance (13C NMR) techniques. Biochar increased the proportion of aromatic carbon (C) in all SOM pools, which led to an increased C content in two soils. The elevated pH after biochar application (∆pH = 1.03) increased Fe (III) oxidation and precipitation, and therefore, stimulated amorphous Fe content in 53-μm pool in the acid soil. This change increased the interaction between organic compounds and Fe (hydr)oxide, which impeded bacteria access to substrates, and in turn, promoted SOM accumulation in the acid soil.Eribulin price
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