ResearchPad - short-report https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Towards individualised and optimalised positioning of non-ventilated COVID-19 patients: Putting the affected parts of the lung(s) on top?]]> https://www.researchpad.co/article/elastic_article_13508 The outbreak of COVID-19 led to an unprecedented inflow of hospitalised patients with severe acute respiratory syndrome (SARS), requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalised positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalised positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalised in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.

]]>
<![CDATA[Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy]]> https://www.researchpad.co/article/elastic_article_13328 Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of disorders characterized by epilepsy with comorbid intellectual disability. Recently, two de novo heterozygous mutations in the gene encoding TRPM3, a calcium permeable ion channel, were identified as the cause of DEE in eight probands, but the functional consequences of the mutations remained elusive. Here we demonstrate that both mutations (V990M and P1090Q) have distinct effects on TRPM3 gating, including increased basal activity, higher sensitivity to stimulation by the endogenous neurosteroid pregnenolone sulfate (PS) and heat, and altered response to ligand modulation. Most strikingly, the V990M mutation affected the gating of the non-canonical pore of TRPM3, resulting in large inward cation currents via the voltage sensor domain in response to PS stimulation. Taken together, these data indicate that the two DEE mutations in TRPM3 result in a profound gain of channel function, which may lie at the basis of epileptic activity and neurodevelopmental symptoms in the patients.

]]>
<![CDATA[Bacterial contribution to genesis of the novel germ line determinant <i>oskar</i>]]> https://www.researchpad.co/article/elastic_article_12752 New cellular functions and developmental processes can evolve by modifying existing genes or creating novel genes. Novel genes can arise not only via duplication or mutation but also by acquiring foreign DNA, also called horizontal gene transfer (HGT). Here we show that HGT likely contributed to the creation of a novel gene indispensable for reproduction in some insects. Long considered a novel gene with unknown origin, oskar has evolved to fulfil a crucial role in insect germ cell formation. Our analysis of over 100 insect Oskar sequences suggests that oskar arose de novo via fusion of eukaryotic and prokaryotic sequences. This work shows that highly unusual gene origin processes can give rise to novel genes that may facilitate evolution of novel developmental mechanisms.

]]>
<![CDATA[What is the significance of the traditional pinching mode of holding chopsticks?]]> https://www.researchpad.co/article/elastic_article_12642 The purpose of this study was to clarify the influence of manipulation mode of chopsticks on the learning process, using assessment of task performance and electromyography, and to understand the significance of the traditional manipulation mode from the viewpoint of physiological anthropology. Previous studies have described two modes of manipulating chopsticks, the traditional pincers-pinching mode and the scissors-pinching mode.MethodsWe conducted experiments with two conditions of holding chopsticks: scissors mode and pincers mode. Eight subjects participated and were assigned to these modes, and they learned handling tasks in their assigned mode for 5 days with the non-dominant hand. We measured task execution times and conducted electromyography of the following muscles: first dorsalis interosseus, flexor pollicis brevis, flexor digiti minimi brevis, flexor digitorum superficialis, and extensor digitorum.ResultsThe training effects were found in each mode. The pincers mode showed significantly shorter task performance times than did scissors mode. On electromyography, significant increases in activity of flexor digiti minimi brevis and tended an increase in flexor digitorum superficialis and a decrease in extensor digitorum occurred in pincers mode but not in scissors mode.ConclusionsThe traditional mode of holding chopsticks was associated with not only high task performance but also an advantage in terms of learning motor control. ]]> <![CDATA[Implementation of a prealert to improve in-hospital treatment of anticoagulant-associated strokes: analysis of a prehospital pathway change in a large UK centralised acute stroke system]]> https://www.researchpad.co/article/elastic_article_12545 <![CDATA[Recognizing One's Own Care Pattern in Cancer Nursing and Transforming toward A Unitary Nursing Practice Based on Margaret Newman's Theory]]> https://www.researchpad.co/article/elastic_article_11715 <![CDATA[Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia]]> https://www.researchpad.co/article/elastic_article_11217 The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton’s jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People’s Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3+, CD4+, and CD8+ T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.

]]>
<![CDATA[Use of a modified World Café process to discuss and set priorities for a Community of Practice supporting implementation of ReQoL a new mental health and quality of life Patient Reported Outcome Measure (PROM)]]> https://www.researchpad.co/article/elastic_article_9803 <![CDATA[The use of milk Fourier transform mid-infrared spectra and milk yield to estimate heat production as a measure of efficiency of dairy cows]]> https://www.researchpad.co/article/elastic_article_9624 Transformation of feed energy ingested by ruminants into milk is accompanied by energy losses via fecal and urine excretions, fermentation gases and heat. Heat production may differ among dairy cows despite comparable milk yield and body weight. Therefore, heat production can be considered an indicator of metabolic efficiency and directly measured in respiration chambers. The latter is an accurate but time-consuming technique. In contrast, milk Fourier transform mid-infrared (FTIR) spectroscopy is an inexpensive high-throughput method and used to estimate different physiological traits in cows. Thus, this study aimed to develop a heat production prediction model using heat production measurements in respiration chambers, milk FTIR spectra and milk yield measurements from dairy cows.MethodsHeat production was computed based on the animal’s consumed oxygen, and produced carbon dioxide and methane in respiration chambers. Heat production data included 168 24-h-observations from 64 German Holstein and 20 dual-purpose Simmental cows. Animals were milked twice daily at 07:00 and 16:30 h in the respiration chambers. Milk yield was determined to predict heat production using a linear regression. Milk samples were collected from each milking and FTIR spectra were obtained with MilkoScan FT 6000. The average or milk yield-weighted average of the absorption spectra from the morning and afternoon milking were calculated to obtain a computed spectrum. A total of 288 wavenumbers per spectrum and the corresponding milk yield were used to develop the heat production model using partial least squares (PLS) regression.ResultsMeasured heat production of studied animals ranged between 712 and 1470 kJ/kg BW0.75. The coefficient of determination for the linear regression between milk yield and heat production was 0.46, whereas it was 0.23 for the FTIR spectra-based PLS model. The PLS prediction model using weighted average spectra and milk yield resulted in a cross-validation variance of 57% and a root mean square error of prediction of 86.5 kJ/kg BW0.75. The ratio of performance to deviation (RPD) was 1.56.ConclusionThe PLS model using weighted average FTIR spectra and milk yield has higher potential to predict heat production of dairy cows than models applying FTIR spectra or milk yield only. ]]> <![CDATA[Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma]]> https://www.researchpad.co/article/elastic_article_9592 For valid and reliable assessment of patients’ Health-Related Quality of Life (HRQoL), it is crucial to use psychometrically robust instruments. In the context of rare diseases such as Merkel cell carcinoma (MCC), validated disease-specific instruments are often not available. The Functional Assessment of Cancer Therapy – Melanoma (FACT-M) was originally developed for use in melanoma. Its psychometric performance for use in MCC and minimal important difference (MID) thresholds have been previously reported based on a cohort of metastatic MCC patients who had disease progression following one or more prior line of chemotherapy (NCT02155647 Part A; n = 70). Since then, new data from the phase II JAVELIN Merkel 200 trial among treatment-naïve patients are available (NCT02155647 Part B; n = 102). This study aims to increase accuracy and precision of previously established psychometric properties and MID thresholds of FACT-M in metastatic MCC patients.MethodsPublished qualitative research suggests that patients with metastatic MCC had similar experiences and described similar concepts associated with their disease independent of whether they were treatment naïve or had prior treatment. Therefore, it was deemed appropriate to pool FACT-M data from Part A (previously treated) and Part B (treatment-naïve) cohorts for this study. Construct validity was assessed by evaluating item-factor correlations (convergent validity) and known-groups validity using ECOG performance status 0 versus 1. Concurrent validity was assessed using EQ-5D items. Internal consistency reliability was assessed using Cronbach’s α. Anchor- and distribution-based approaches were used to derive MID thresholds.ResultsOverall, psychometric tests based on various validity (convergent, known-groups, concurrent) and reliability (Cronbach α) analyses confirmed previous findings in that FACT-M performs well in MCC patients. MID thresholds derived from this study are largely in line with previously established thresholds with some minor adjustments.ConclusionsIn the context of rare diseases, which often have limited data available for psychometric testing, a reasonably large MCC patient sample was available for this study, enhancing accuracy and precision of previously established FACT-M psychometric properties and MID thresholds with only small deviations for use in metastatic MCC patients. Results suggest that the FACT-M is suitable for Merkel cell carcinoma regardless of patients’ treatment status.Trial registrationThis study is a pre-planned post-hoc analysis conducted on data collected in Part A and Part B of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647. ]]> <![CDATA[Effects of undigested protein-rich ingredients on polarised small intestinal organoid monolayers]]> https://www.researchpad.co/article/elastic_article_9352 Here, we describe the use of monolayers of intestinal epithelial cells derived from intestinal organoids and transcriptomics to investigate the direct effects of dietary protein sources on epithelial function. Mechanically dissociated 3D organoids of mouse duodenum were used to generate a polarized epithelium containing all cell types found in the tissue of origin. The organoid-derived cell monolayers were exposed to 4% (w/v) of ‘undigested (non-hydrolysed)-soluble’ fraction of protein sources used as feed ingredients [soybean meal (SBM) and casein], or alternative protein sources (spray dried plasma protein, and yellow meal worm), or controls for 6 h prior to RNA isolation and transcriptomics. All protein sources altered expression of unique biological processes in the epithelial cells. Exposure of intestinal organoids to SBM downregulated expression of retinol and retinoid metabolic processes as well as cholesterol and lipid biosynthetic pathways, consistent with the reported hypotriglyceridaemic effect of soy protein in vivo. These findings support the use of intestinal organoids as models to evaluate complex interactions between dietary ingredients and the intestinal epithelium and highlights some unique host effects of alternative protein sources in animal feed and potentially human food.Graphical abstractSchematic representation of the study. 3-dimensional organoids were generated from mouse duodenum (1). The organoids were subsequently dissociated into single cells (2) and grown as 2-dimensional polarised monolayers (3). Polarized monolayers of organoid cells were exposed to different protein sources [CAS, SBM, SDPP, YMW, or medium control (MC)] for 6 h (4) and further processed for imaging (5) gene expression (6), and biochemical assays (7), to investigate the effects of undigested protein sources on the duodenal epithelium. ]]> <![CDATA[Phosphorus supplementation raised the heart rate of male water polo players during a randomised graded dryland exercise test]]> https://www.researchpad.co/article/elastic_article_9103 The impact of phosphorus supplementation on athletic performance is unclear. Ingestion of phosphorus for several days has been reported to increase cardiac capacity, improve oxygen muscle kinetics and enhance lactate buffering capacity. Recent studies have shown that phosphorus ingestion with a meal increases postprandial glucose uptake and thermogenesis. The present study aimed to assess the effect of acute phosphorus ingestion with a meal on specific workload parameters.MethodsA double-blind, crossover trial of 12 male water polo players between 18 and 22 years old was conducted. Overnight fasted subjects were asked to cycle for 20 min before ingesting 100 g of glucose with phosphorus or placebo (400 mg). Three hours later, they were asked to perform a graded cycling exercise for 25 min.ResultsExpenditure, respiratory quotient, perception of fatigue and exercise efficiency were similar between treatments. However, heart rate was significantly higher in the phosphorus group (142±10 beats/min) compared with placebo (135±10 beats/min).ConclusionExercise performance 3 hours after the coingestion of glucose with phosphorus did not affect substrate use, while heart rate was increased. The heart rate increase could be attributed to a rise in core body temperature.Trial registration numberNCT03101215. ]]> <![CDATA[Intelligent classification of platelet aggregates by agonist type]]> https://www.researchpad.co/article/elastic_article_8130 Platelets are small cells in the blood that primarily help stop bleeding after an injury by sticking together with other blood cells to form a clot that seals the broken blood vessel. Blood clots, however, can sometimes cause harm. For example, if a clot blocks the blood flow to the heart or the brain, it can result in a heart attack or stroke, respectively. Blood clots have also been linked to harmful inflammation and the spread of cancer, and there are now preliminary reports of remarkably high rates of clotting in COVID-19 patients in intensive care units.

A variety of chemicals can cause platelets to stick together. It has long been assumed that it would be impossible to tell apart the clots formed by different chemicals (which are also known as agonists). This is largely because these aggregates all look very similar under a microscope, making it incredibly time consuming for someone to look at enough microscopy images to reliably identify the subtle differences between them. However, finding a way to distinguish the different types of platelet aggregates could lead to better ways to diagnose or treat blood vessel-clogging diseases.

To make this possible, Zhou, Yasumoto et al. have developed a method called the “intelligent platelet aggregate classifier” or iPAC for short. First, numerous clot-causing chemicals were added to separate samples of platelets taken from healthy human blood. The method then involved using high-throughput techniques to take thousands of images of these samples. Then, a sophisticated computer algorithm called a deep learning model analyzed the resulting image dataset and “learned” to distinguish the chemical causes of the platelet aggregates based on subtle differences in their shapes. Finally, Zhou, Yasumoto et al. verified iPAC method’s accuracy using a new set of human platelet samples.

The iPAC method may help scientists studying the steps that lead to clot formation. It may also help clinicians distinguish which clot-causing chemical led to a patient’s heart attack or stroke. This could help them choose whether aspirin or another anti-platelet drug would be the best treatment. But first more studies are needed to confirm whether this method is a useful tool for drug selection or diagnosis.

]]>
<![CDATA[Sonographic measurements of normal C5‐C8 nerve roots in children]]> https://www.researchpad.co/article/elastic_article_6788 The aim of this study was to use ultrasound to measure the cervical nerve roots in normal children to determine normal reference values.MethodsA total of 441 children of different ages at the Children's Hospital of Chongqing Medical University were examined by ultrasound. The diameter, circumference, and cross‐sectional area of the nerve roots were measured.ResultsUltrasonographic measurements were consistent with the ranking C5 < C6 < C7. The C8 nerve root was thicker than C7 in 60% of the participants. The nerve root measurements increased with increasing age, height, weight, and body surface area.DiscussionNormal reference ranges of the cervical nerve roots in children of different ages were established, and can serve as the basis for measurement in future studies. ]]> <![CDATA[Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior]]> https://www.researchpad.co/article/elastic_article_6337 Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MECP2. Mutations of Mecp2 that are restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potential key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneurons in Rett Syndrome. Here we find that loss of MeCP2 specifically from VIP interneurons replicates key neural and behavioral phenotypes observed following global Mecp2 loss of function.

]]>
<![CDATA[Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome]]> https://www.researchpad.co/article/elastic_article_6336 The COVID-19 pandemic represents an unprecedented threat to global health. Millions of cases have been confirmed around the world, and hundreds of thousands of people have lost their lives. Common symptoms include a fever and persistent cough and COVID-19 patients also often experience an excess of fluid in the lungs, which makes it difficult to breathe. In some cases, this develops into a life-threatening condition whereby the lungs cannot provide the body's vital organs with enough oxygen.

The SARS-CoV-2 virus, which causes COVID-19, enters the lining of the lungs via an enzyme called the ACE2 receptor, which is present on the outer surface of the lungs’ cells. The related coronavirus that was responsible for the SARS outbreak in the early 2000s also needs the ACE2 receptor to enter the cells of the lungs. In SARS, the levels of ACE2 in the lung decline during the infection.

Studies with mice have previously revealed that a shortage of ACE2 leads to increased levels of a hormone called angiotensin II, which regulates blood pressure. As a result, much attention has turned to the potential link between this hormone system in relation to COVID-19. However, other mouse studies have shown that ACE2 protects against a build-up of fluid in the lungs caused by a different molecule made by the body. This molecule, which is actually a small fragment of a protein, lowers blood pressure and causes fluid to leak out of blood vessels. It belongs to a family of molecules known as kinins, and ACE2 is known to inactivate certain kinins.

This led van de Veerdonk et al. to propose that the excess of fluid in the lungs seen in COVID-19 patients may be because kinins are not being neutralized due to the shortage of the ACE2 receptor. This had not been hypothesized before, even though the mechanism could be the same in SARS which has been researched for the past 17 years. If this hypothesis is correct, it would mean that directly inhibiting the receptor for the kinins (or the proteins that they come from) may be the only way to stop fluid leaking into the lungs of COVID-19 patients in the early stage of disease.

This hypothesis is unproven, and more work is needed to see if it is clinically relevant. If that work provides a proof of concept, it means that existing treatments and registered drugs could potentially help patients with COVID-19, by preventing the need for mechanical ventilation and saving many lives.

]]>
<![CDATA[Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial]]> https://www.researchpad.co/article/N4c92fa6c-d2bd-4fb2-bbb2-a2a7a7e7a9f7 Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.MethodsWe prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.ResultsChemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.ConclusionAfter profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.Trial registration numberNCT01857934. ]]> <![CDATA[Knowledge, attitude, practice and perceived barriers among healthcare workers regarding COVID-19: a cross-sectional survey from Pakistan]]> https://www.researchpad.co/article/N1c928444-e22c-4a55-8619-fc3a820dade6 A self-administered validated (Cronbach's alpha=0.077) questionnaire was used to assess knowledge, attitude and practice among healthcare workers (HCWs) in Pakistan regarding coronavirus disease 2019 (COVID-19). Findings showed that HCWs have good knowledge (93.2%, N=386), a positive attitude [mean 8.43 (standard deviation 1.78)] and good practice (88.7%, N=367) regarding COVID-19. HCWs perceived that limited infection control material (50.7%, N=210) and poor knowledge regarding transmission (40.6%, N=168) were the major barriers to infection control. Regression analysis indicated that pharmacists were more likely to demonstrate good practice than other HCWs (odds ratio 2.247, 95% confidence interval 1.11–4.55, P=0.025). This study found that HCWs in Pakistan have good knowledge, but there are gaps in specific aspects of knowledge and practice that warrant attention.

]]>
<![CDATA[Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients]]> https://www.researchpad.co/article/Nb5df6024-f0ef-4660-b81e-c12ec6cc8206 The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.

]]>
<![CDATA[The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer]]> https://www.researchpad.co/article/N6b271a00-7d6e-4c09-8828-f4012782b77c Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer.MethodsCisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells.ResultsSKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo.ConclusionOur results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer. ]]>