Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not ...yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC.
To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues.
Secretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy.
Our data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Viral Load Kinetics of MERS Coronavirus Infection Oh, Myoung-don; Park, Wan Beom; Choe, Pyoeng Gyun ...
New England journal of medicine/The New England journal of medicine,
09/2016, Letnik:
375, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Middle East respiratory syndrome coronavirus continues to circulate in the Middle East. During a recent outbreak in Korea, changes in MERS coronavirus viral load were determined during the course of ...illness in 17 patients.
To the Editor:
The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in South Korea involved 186 patients and resulted in 38 deaths, with four large hospital outbreaks accounting for 82% of the total cases.
1
,
2
Here, we report changes in viral load over time in patients with MERS.
We included all patients who were admitted to three Seoul National University–affiliated hospitals; the institutional review boards of these hospitals approved this study and waived the need for written informed consent on public health grounds. The patients were categorized into a group with severe disease (severe group) or a group . . .
A feeding trial was designed to examine the potential of yellow mealworm, Tenebrio molitor, as a locally available renewable protein source in juvenile mandarin fish feed. Triplicate groups of fish ...(Initial mean body weight ± S E.; 20.8 ± 0.05 g) were assigned to each of four isonitrogenous (50%) and isocaloric (22 MJ kg−1) practical diets containing graded level of a full fat yellow mealworm meal (WM) (0, 10, 20, and 30%) at the expense of fish meal (FM) (designated as WM0, WM10, WM20, and WM30). Each group of 20 fish were housed in a 60-L aquarium connected to a closed freshwater recirculating system, with a delivery rate of about 2 L min−1, and fed twice daily to apparent satiation for a period of 8 weeks. The results revealed that fish growth rates and efficiency of nutrient utilization tended to increase with increasing dietary WM levels from 0 to 20%, and then declined as dietary WM level further increased from 20 to 30%, with the most pronounced effect observed in those of fish fed the WM20 diet. Plasma total cholesterol contents were significantly reduced in fish fed the diet with the highest WM level (WM30). Fish carcass composition did not show any definite pattern of change due to feed composition. Fillets of juvenile mandarin fish fed diets containing WM in place of FM had much higher levels of saturated and monounsaturated fatty acids and lower levels of n-3 polyunsaturated fatty acids (PUFA) than those fed WM-free control diet (WM0). Serum lysozyme and glutathione peroxidase (GPx) activities were found to be significantly higher for fish fed the WM30 diet compared with fish fed WM0 diet. Overall, the efficacy of WM as alternative dietary protein source for juvenile mandarin fish has been proved not only in relation to weight gain and efficiency of feed utilization, but also the view point of health-promoting effects in fish.
•This is the first report on the use of Tenebrio molitor meal (WM) as a substitute for fish meal in Siniperca scherzeri diet.•Formulated diets with up to 30% WM caused no adverse effects on fish performance and feed utilization.•Fatty acid composition of fish fillet was altered by dietary inclusion of WM.•30% WM inclusion significantly enhanced lysozyme and glutathione peroxidase activities of fish compared to the control group.•The present findings could help to promote the utilization of the WM in S. scherzeri production.
Use of the physiological mechanisms promoting midbrain DA (mDA) neuron survival seems an appropriate option for developing treatments for Parkinson's disease (PD). mDA neurons are specifically marked ...by expression of the transcription factors Nurr1 and Foxa2. We show herein that Nurr1 and Foxa2 interact to protect mDA neurons against various toxic insults, but their expression is lost during aging and degenerative processes. In addition to their proposed cell‐autonomous actions in mDA neurons, forced expression of these factors in neighboring glia synergistically protects degenerating mDA neurons in a paracrine mode. As a consequence of these bimodal actions, adeno‐associated virus (AAV)‐mediated gene delivery of Nurr1 and Foxa2 in a PD mouse model markedly protected mDA neurons and motor behaviors associated with nigrostriatal DA neurotransmission. The effects of the combined gene delivery were dramatic, highly reproducible, and sustained for at least 1 year, suggesting that expression of these factors is a promising approach in PD therapy.
Synopsis
Gene therapy of Nurr1 and Foxa2 protects midbrain dopamine (mDA) neurons from degeneration in a mouse model of Parkinson's disease (PD), suggesting that exploitation of the physiological mechanisms promoting mDA neuron survival might be an option for developing treatments for PD.
Nurr1 and Foxa2 are specifically expressed in mDA neurons of adult mouse midbrain and synergistically interact to promote neuronal survival.
Nurr1 and Foxa2 protein expression is lost in mDA neurons during aging and degenerative processes.
Forced expression of Nurr1 and Foxa2 protects mDA neurons from various toxic insults in vitro and in vivo, and relieved motor deficits associated with mDA neuronal loss in the PD mouse model.
In addition to cell‐autonomous actions in mDA neurons, combined Nurr1+Foxa2 transgene expression in glial cells creates a neuroprotective environment by suppressing the secretion of pro‐inflammatory cytokines as well as promoting the release of neurotrophic factors.
Gene therapy of Nurr1 and Foxa2 protects midbrain dopamine (mDA) neurons from degeneration in a mouse model of Parkinson's disease (PD), suggesting that exploitation of the physiological mechanisms promoting mDA neuron survival might be an option for developing treatments for PD.
All‐solid‐state batteries (ASSBs) have lately received enormous attention for electric vehicle applications because of their exceptional stability by engaging all‐solidified cell components. However, ...there are many formidable hurdles such as low ionic conductivity, interface instability, and difficulty in the manufacturing process, for its practical use. Recently, carbon, one of the representative conducting agents, turns out to largely participate in side reactions with the solid electrolyte, which finally leads to the formation of insulating side products at the interface. Although the battery community mentioned that parasitic reactions are presumably attributed to carbon itself or the generation of electronic conducting paths lowering the kinetic barrier for reactions, the underlying origin for such reactions as well as appropriate solutions have not been provided yet. In this study, for the first time, it is verified that the functional group on carbon is an origin for causing negative effects on interfacial stability and a graphitized hollow nanocarbon as a promising solution for improving‐electrochemical performance is introduced. This work offers an invaluable lesson that a relatively minor part, such as a conducting agent, in ASSBs sometimes gives more positive impact on improving electrochemical performance than huge efforts for resolving other parts.
Graphitic hollow nanocarbon (GHC), a promising conducting agent for all‐solid‐state batteries: As the functional group on conventional carbon additives is one of major origins of parasitic reactions with solid electrolytes (SE), GHC with few functional groups is introduced as a conducting agent to mitigate the side reactions with the SE, finally warranting ionic/electronic conductivities in all‐solid‐state batteries.
Bulk-type all-solid-state lithium-ion batteries (ASLBs) have the potential to be superior to conventional lithium-ion batteries (LIBs) in terms of safety and energy density. Sulfide SE materials are ...key to the development of bulk-type ASLBs because of their high ionic conductivity (max of ∼10–2 S cm–1) and deformability. However, the severe reactivity of sulfide materials toward common polar solvents and the particulate nature of these electrolytes pose serious complications for the wet-slurry process used to fabricate ASLB electrodes, such as the availability of solvent and polymeric binders and the formation of ionic contacts and networks. In this work, we report a new scalable fabrication protocol for ASLB electrodes using conventional composite LIB electrodes and homogeneous SE solutions (Li6PS5Cl (LPSCl) in ethanol or 0.4LiI–0.6Li4SnS4 in methanol). The liquefied LPSCl is infiltrated into the tortuous porous structures of LIB electrodes and solidified, providing intimate ionic contacts and favorable ionic percolation. The LPSCl-infiltrated LiCoO2 and graphite electrodes show high reversible capacities (141 and 364 mA h g–1) at 0.14 mA cm–2 (0.1 C) and 30 °C, which are not only superior to those for conventional dry-mixed and slurry-mixed ASLB electrodes but also comparable to those for liquid electrolyte cells. Good electrochemical performance of ASLBs employing the LPSCl-infiltrated LiCoO2 and graphite electrodes at 100 °C is also presented, highlighting the excellent thermal stability and safety of ASLBs.
A 1.2 V 20 nm 307 GB/s high-bandwidth memory (HBM) DRAM is presented to satisfy a high-bandwidth requirement of high-performance computing application. The HBM is composed of buffer die and multiple ...core dies, and each core die has 8 Gb DRAM cell array with additional 1 Gb ECC array. At-speed wafer level, a u-bump IO test scheme and an adaptive refresh scheme considering temperature distribution are proposed to guarantee test coverage and stable operation in a power-efficient manner.
The incidence of invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) has decreased with the introduction of antimold prophylaxis. Although acute lymphoblastic leukemia (ALL) ...has a lower risk of IFI than does AML, the incidences of IFI in both AML and ALL in the era of antimold prophylaxis should be re-evaluated. We analyzed adults with AML or ALL who had undergone induction, re-induction, or consolidation chemotherapy from January 2017 to December 2019 at Seoul National University Hospital. Their clinical characteristics during each chemotherapy episode were reviewed, and cases with proven or probable diagnoses were regarded as positive for IFI. Of 552 episodes (393 in AML and 159 in ALL), 40 (7.2%) were IFI events. Of the IFI episodes, 8.1% (12/148) and 5.9% (13/220) (P = 0.856) occurred in cases of ALL without antimold prophylaxis and AML with antimold prophylaxis, respectively. After adjusting for clinical factors, a lack of antimold prophylaxis (adjusted odds ratio aOR, 3.52; 95% confidence interval CI, 1.35-9.22; P = 0.010) and a longer duration of neutropenia (per one day, aOR, 1.02; 95% CI, 1.01-1.04; P = 0.001) were independently associated with IFI. In conclusion, the incidence of IFI in ALL without antimold prophylaxis was not lower than that in AML. A lack of antimold prophylaxis and prolonged neutropenia were independent risk factors for IFI. Clinicians should be on guard for detecting IFI in patients with ALL, especially those with risk factors.
Summary Rationale Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups ...that may have individual characteristics and distinct responses to treatment. Objectives We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. Methods We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV1 more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index ≤ 20% and FEV1 ≤ 45%, the mild-mixed subtype had an emphysema index ≤ 20% and FEV1 > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV1 ≤ 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. Results After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV1 increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV1 compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV1 or dyspnea after the 3-month treatment period. Conclusion The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.
Eccrine sweat is a rich and largely unexplored biofluid that contains a range of important biomarkers, from electrolytes, metabolites, micronutrients and hormones to exogenous agents, each of which ...can change in concentration with diet, stress level, hydration status and physiologic or metabolic state. Traditionally, clinicians and researchers have used absorbent pads and benchtop analyzers to collect and analyze the biochemical constituents of sweat in controlled, laboratory settings. Recently reported wearable microfluidic and electrochemical sensing devices represent significant advances in this context, with capabilities for rapid,
in situ
evaluations, in many cases with improved repeatability and accuracy. A limitation is that assays performed in these platforms offer limited control of reaction kinetics and mixing of different reagents and samples. Here, we present a multi-layered microfluidic device platform with designs that eliminate these constraints, to enable integrated enzymatic assays with demonstrations of
in situ
analysis of the concentrations of ammonia and ethanol in microliter volumes of sweat. Careful characterization of the reaction kinetics and their optimization using statistical techniques yield robust analysis protocols. Human subject studies with sweat initiated by warm-water bathing highlight the operational features of these systems.
Soft microfluidics with reference reactions enable quantitative sweat ammonia-ethanol assay.
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