The aim of this study was to investigate the effect of NaCl salinity (0, 100 and 300 mM) on the individual response of the quinoa varieties Kcoito (Altiplano Ecotype) and UDEC-5 (Sea-level Ecotype) with physiological and proteomic approaches. UDEC-5 showed an enhanced capacity to withstand salinity stress compared to Kcoito. In response to salinity, we detected overall the following differences between both genotypes: Toxicity symptoms, plant growth performance, photosynthesis performance and intensity of ROS-defense. We found a mirroring of these differences in the proteome of each genotype. Among the 700 protein spots reproducibly detected, 24 exhibited significant abundance variations between samples. These 24 proteins were involved in energy and carbon metabolism, photosynthesis, ROS scavenging and detoxification, stress defense and chaperone functions, enzyme activation and ATPases. A specific set of proteins predominantly involved in photosynthesis and ROS scavenging showed significantly higher abundance under high salinity (300 mM NaCl). The adjustment was accompanied by a stimulation of various metabolic pathways to balance the supplementary demand for energy or intermediates. However, the more salt-resistant genotype UDEC-5 presented a beneficial and significantly higher expression of nearly all stress-related altered enzymes than Kcoito. Salinity, halophyte, quinoa, proteomic, photosynthesis, antioxidant, salt resistance, oxidative stress.
This study was conducted at the experimental area of the Cukurova University, Faculty of Agriculture in 2017, 2018 and 2019 in Adana (Mediterranean Region)-Turkey. The objective of this study was to compare of fatty acids composition and oil quality factors of different market type peanut (Arachis hypogaea L.) varieties grown as a main crop. Four different market type peanut varieties, including Virginia (Halisbey), Runner (G.Green), Spanish (Florispan) and Valencia (G.Red) were used as plant material in this research. The experimental design was a randomized complete block design with three replications. Oil content, fatty acids composition such as oleic acid, linoleic acid, stearic acid palmitic acid and oil quality factors such as Oleic/linoleic acid ratio (O/L) and iodine value (IV) of peanut seed oil were investigated. According to a three-year results; the oil content of the peanut varieties varied between 45.38% and 51.28%. The total saturated fatty acid was higher in Spanish and Valencia types than Virginia and Runner types. On the other hand, the total unsaturated fatty acid was higher in Virginia and Runner types than the others types.
Objective: Social determinants of health (SDH) have been shown to correlate with adverse cancer outcomes. It is unclear if their impact goes beyond behavioral risk or healthcare access. We aimed to evaluate the association of SDH with endometrial cancer outcomes in a public healthcare system. Design and Setting: A retrospective cohort study of endometrial cancer patients in Ontario, Canada. Population: Women diagnosed with endometrial cancer in Ontario between 2009-2017. Methods: Clinical and sociodemographic variables were extracted from administrative databases. Validated marginalization scores for material deprivation, residential instability and ethnic concentration were used. Associations between marginalization and survival were evaluated using log-rank testing and Cox proportional hazards regression. Results: 20228 women with endometrial cancer were identified. Fewer patients in marginalized communities presented with early disease (70% vs. 76%, p<0.001) and received surgery (89% vs. 93%, p<0.001). Overall survival was shorter among marginalized patients (p<0.001). On multivariable analysis adjusted for patient and disease factors, overall marginalization (HR=1.22, 95% CI 1.03-1.08), material deprivation (HR=1.22, 95% CI 1.10-1.35) and residential instability (HR=1.32, 95% CI 1.19-1.46) were associated with increased risk of death (p<0.001). Conclusions: Socioeconomic marginalization is associated with an increased risk of death in endometrial cancer patients. Targetable events in the cancer care pathway should be identified to improve health equity Funding: This study was supported by a grant (#RD-196) from the Hamilton Health Sciences Juravinski Hospital and Cancer Center Foundation Keywords: uterine cancer, endometrial cancer, social determinants of health
Background and Purpose: Obesity and depression are highly comorbid and far from effective treating. Celastrol was reported useful for obesity, but its role in the obesity-depression comorbidity remains unknown. This study aims to investigate the efficacy and associated mechanism of celastrol in this comorbidity. Experimental Approach: A comorbidity mice model of obesity and depression were constructed. Bodyweight, adipose tissue rate, blood glucose, and blood lipids were used to assess obesity. Forced swimming test and tail suspension test were investigated to evaluate depression. In microglial cells, direct targets of celastrol were screened and determined by chemical proteomics, pull-down experiment, and competitive binding assay. In the mice model, the target gene’s mediating effect was investigated by stereotactic injection of AAV9 virus. The expression level of target molecules was detected by immunofluorescence. Key Results: Celastrol relieved the comorbid symptoms, inhibited the mal-activated Neuropeptide Y, and activated the mal-inhibited 5-HT neurons in the amygdala. The efficacy was associated with the inhibition of the mal-activated microglia. Chemical proteomics, pull-down experiment, and competitive binding assay results indicated celastrol’s directly binding hnRNPA1. In the animal model, downregulation of hnRNPA1 in the amygdala relived symptoms and NPY and 5-HT neurons’ changes. Meanwhile, overexpression of hnRNPA1 aggravated the comorbidity and antagonized the effect of celastrol. Conclusion and Implications: Celastrol alleviated comorbid obesity and depression in a mouse model by directly binding hnRNPA1 in the amygdala. Celastrol may become a potential drug, and hnRNPA1 in the amygdala could be a useful target to combat the comorbidity.
Transient receptor potential ankyrin 1 (TRPA1) channel is a calcium permeable, non-selective cation channel, expressed in the sensory neurons and non-neuronal cells of different tissues. Initially studied for its role in pain and inflammation, TRPA1 has now functionally involved in multiple other physiological functions. TRPA1 channel has been extensively studied for modulation by pungent compounds present in the spices and herbs. In the last decade, the role of TRPA1 agonism in body weight reduction, secretion of hunger and satiety hormones, insulin secretion and thermogenesis, has unveiled the potential of the TRPA1 channel to be used as a preventive target to tackle obesity and associated comorbidities including insulin resistance in type 2 diabetes. In this review, we summarized the recent findings of TRPA1 based dietary/non-dietary modulation for its role in obesity prevention and therapeutics.
Objective: To investigate the connections among social support, stress, and depression. Design: Cross-sectional study. Setting: Guizhou Province in China. Population or Sample: An aggregate of 1,056 expectant ladies, had finished our questionnaire during pregnancy from March to April in 2020. Methods: The Edinburgh prenatal sadness scale, an independent pressure scale, and social support scale evaluated the downturn, stress, and social support of pregnant people during the pestilence. An auxiliary condition model was utilized to examine the immediate and aberrant connection between social support and prenatal misery. Main Outcome Measures: Incidence of depression. Results: During the pandemic time, 73.01% of pregnant ladies experienced prenatal misery. The model is suitable (chi-square = 11.96, CFI = 0.97, RMSEA = 0.07, RMR = 0.03). The auxiliary condition model indicated that the immediate pathway of social support to depression was critical (normalized pathway coefficient = - 0.34), and the aberrant pathway of stress to depression via social support was additionally huge (normalized pathway coefficient = 0.50). Stress partially intercedes the connection between social support and depression. Conclusion: Our discoveries posit that social support is related to an expanded danger of depression. Stress is decidedly corresponding to depression and assumes an interceding position between social support and stress. Thusly, directed mediation ought to be completed to lessen the depression of pregnant ladies and improve their psychological wellness status. Keywords: stress, depression, social support, structural equation model
The metabolism of cancer is remarkably different from that of normal cells and confers variety of benefits including the promotion of other cancer hallmarks. As the rewired metabolism is a near-universal property of cancer cells, efforts are underway to exploit metabolic vulnerabilities for therapeutic benefit. In the continued search for a safer and effective ways of cancer treatment, structurally diverse plant-based compounds have gained substantial attention. Here, we present an extensive assessment of the role of phytocompounds in modulating cancer metabolism and make a case for the use of plant-based compounds in targeting metabolic vulnerabilities of cancer. We discuss the interactions of phytocompounds with major metabolic pathways and evaluate the role of phytochemicals in the regulation of growth signaling and transcriptional programs involved in metabolic transformation of cancer. Lastly, we examine the potential of these compounds in clinical management of cancer along with limitations and challenges
With the advancement of epigenetic tools and technologies associated with intervention medicine, stroke research has entered into a new fertile, dynamic era of epigenetic studies, a wide plethora of intervention procedure, administration of tissue plasminogen activator, the introduction of mechanical thrombectomy, clinical studies, and drug developments over the last decennium. Against this vivid background of newly emerging pieces of knowledge, there is little to none advancement in the overall outcome of the disease. The stroke involves an overabundance of inflammatory responses arising in part due to the body's immune response to brain injury. Neuroinflammation contributes to significant neuronal cell death and the development of functional impairment and death in stroke patients. Recent studies demonstrated epigenetic plays a key role in the overall outcome of the disease. In this review, we summarize the progress of epigenetics which provides an overview of recent advancements on the emerging key role of epigenetics over the last decade contributing to the regulation of neuroinflammation in stroke, potential epigenetic targets that might be key factors in the development of stroke therapies and their relation in respect to clinical practice.
P2Y receptors (P2YRs), a δ group of rhodopsin-like G protein-coupled receptors (GPCRs), have many essential functions in physiology and pathology, such as platelet aggregation, immune responses, neuroprotective effects, inflammation, and cellular proliferation; thus, they are among the most researched therapeutic targets for use in the clinical treatment of diseases (e.g., clopidogrel, an antithrombotic drug, and Prolacria, a treatment for dry eye). Over the past two decades, GPCRs have been revealed to transmit signals as dimers to increase the diversity of signalling pathways or pharmacological activities. Many studies have frequently confirmed dimerization between P2YRs and other GPCRs due to their functions in cardiovascular and cerebrovascular processes in vivo and in vitro. Recently, some P2YR dimers that dynamically balance physiological functions in the body were shown to be involved in effective signal transduction and exert pathological pharmacological effects. In this review, we summarize the types, pharmacological changes, and active regulators of P2YR-related dimerization. In summary, our review delineates that P2YR-related dimers have new functions and pharmacological activities and maybe a novel direction to improve the effectiveness of medications such as thrombotic events associated with COVID-19.
Background and Purpose: Diabetic nephropathy (DN) is a common and severe chronic complication in diabetes mellitus. The purpose of this study was to explore the effect and mechanism of Astragaloside IV (AS-IV) on renal pyroptosis in DN. Experimental Approach: High-fat diet and a small dose of streptozotocin were used to establish the DN model. Rats were treated with vehicle or AS-IV (20-, 40- and 80-mg/kg/day) or valsartan (30mg/kg/day) by gavage. After 12 weeks, animals were euthanized; samples of urine and blood were collected to examine biochemical indicators, advanced glycation end products (AGEs), inflammatory cytokines; kidney tissues were collected for histological observation, TUNEL staining, AGEs, inflammatory cytokines, redox indicators, western blot, and immunohistochemistry. Key Results: Biochemical results showed that AS-IV could significantly alleviate the degree of clinical symptoms and the levels of blood glucose, HbA1C, TG, MDA, AGEs, Interleukin (IL)-1β, and IL-18 while improving the activity of SOD and the secretion and sensitivity of insulin. Histological examination and TUNEL staining indicated that AS-IV attenuated the damage of tissues and cells in the kidney from DN rats. Western blot results revealed that AS-IV relieved the activation of NOX4/TXNIP/NLRP3 pathway and the expression of collagen IV and fibronectin in DN rats. Immunohistochemistry results showed that AS-IV attenuated collagen IV and fibronectin in the kidney from DN rats. Conclusion and Implications: The NOX4/TXNIP/NLRP3 pathway mediated renal pyroptosis could play a crucial role in kidney damage and DN development in rats. Restoration of renal pyroptosis by AS-IV be a potential therapeutic strategy against DN.
Objective: Describe & validate flow index (FiO2×flow rate/weight) to report the degree of respiratory support to children on high flow nasal cannula (HFNC) Methods: Retrospective chart review. Children managed with HFNC from 01/01/15 to 12/31/19. Variables included in the flow index (weight, FiO2, flow rate) and outcomes (hospital and ICU length of stay [LOS], escalation to the ICU) extracted from medical records. Max flow index defined by the earliest timestamp when patients FiO2×Flow rate was maximum. Step-wise regression used to determine the relationship between outcome (length of stay and escalation to ICU) and flow index Results: 1537 patients met the study criteria. Median 1st and maximum flow index of the population 24.1 and 38.1, respectively. Both 1st and maximum flow indexes showed a significant correlation with the LOS (r 0.25 and 0.31). Correlation for the index was stronger than that of the variables used to calculate them and remained significant after controlling for age, race, sex, and diagnoses. Mild, moderate, and severe categories of 1st and max flow index derived using quartiles and showed significant age and diagnosis independent association with LOS. Patients with 1st flow index >20 and maximum flow index >59.5 had increased odds ratio of escalation to ICU (OR 2.39 and 8.08). The 1st flow index had a negative association with rapid response activation. Conclusions: Flow index is a valid measure for assessing the degree of respiratory support for children on HFNC. High flow index associated with longer hospital LOS and the risk of escalation to ICU.
Bird strike is a significant threat to the parts of the flying aircrafts. The wing is a central part, which provides stability to the aircraft. Mostly at wing, bird attack the leading edge. Worldwide aviation regulation FRA, EASA, required 4Ib bird strike on the wing of aircraft, and after this bird strike, aircraft is able to be safely landed. This study aims to investigate the resistance of the wing against the bird strike and damage analysis of the high-velocity bird collision on the model wing, inner structure, spar, and ribs. By using the Coupled Eulerian-Lagrangian (CEL) approach in ABAQUS/Explicit. Our contribution 1) bird strike on a wing with assembled inner structure by aluminium and outer skin composed of unidirectional fiber-reinforced composite material. 2) bird strike on-wing which is similar with the first test in which the difference is of spar designed layers of horizontal plates like a comb. 3) bird strike on-wing which is similar with second model wing difference in this wing put an aluminium leading edge on the skin leading-edge, final to analyze the damage of bird impact on the wing, the velocity of bird strike is 200m/s and analyze the behavior of the bird at this velocity. Resistance behavior of composite skin After penetration in the wing, analyze the impact on the spar and stress on the inner structure. Analysis of the kinetic and internal energy graph and Comparison all of these results and check the performance, which gives an excellent result at this velocity. based on these results suggest which inner part is sensitive.
Objective To assess the prevalence of endometriosis using pelvic ultrasound examination in women attending for early pregnancy care Design Prospective observational study. Setting A dedicated early pregnancy unit. Population We included 1341 consecutive women who attended for an early pregnancy assessment and had transvaginal ultrasound scans performed by a single clinician. Methods In addition to the presence of endometriosis on ultrasound scan, we collected data on patient demographics and concurrent gynaecological conditions. Data analysis was performed using logistic regression and multivariate analysis. Main outcome measures The prevalence of endometriosis in addition to possible associations with demographic and clinical variables. Results The prevalence of endometriosis in women attending the early pregnancy unit was 4.9% (95% CI 3.8 – 6.2); In 33/66 (50%, 95% CI 37.9 – 62.1) women with endometriosis, this was a new diagnosis made for the first time during their early pregnancy scan. The presence of endometriosis was strongly associated with congenital uterine anomalies (p < 0.001; OR 5.69, 95% CI 2.17 – 14.9) and uterine fibroids (p = 0.004; OR 2.37, 95% CI 1.31, 4.28). Conclusions Endometriosis is present in nearly 5% of women attending for early pregnancy assessment. In half of the women with endometriosis, the diagnosis was made for the first time during pregnancy. We propose that ultrasound may be a useful tool for the detection of endometriosis and to identify pregnant women who may benefit from specialist antenatal care. Funding No funding was obtained for this work. Keywords Endometriosis, Prevalence, Pregnancy, Ultrasonography
Objective: To investigate the relationship between cannabinoid receptor expression within the placenta after delivery and the problem of preterm delivery. Design, setting, and participants: The retrospective, observational study was conducted on a multicenter material of 150 women. The study group included 115 women after premature delivery. The control group consisted of 35 women after term delivery. Methods. To determine the expression of cannabinoid receptors after the end of the third stage of labour, several sections were taken from the placenta. RNA isolation, reverse transcription, and Real-Time PCR were performed to assess the expression of the cannabinoid receptors in the placenta. Results: Cannabinoid receptor type 2 expression was lower in the placentas of women after preterm delivery. Urinary tract infections and bleeding at any stage of pregnancy occurred statistically more frequently in the study group and correlated with cannabinoid receptor type 2 expression. In the study group, the history of preterm labor, history of intrauterine fetal deaths, pregnancies terminated by a Caesarean section, and uterine tenderness correlated with lower expression of cannabinoid receptor type 2 and 1a. Conclusions: Cannabinoid receptors mRNA were present in human placental tissue during pregnancy. Decreased cannabinoid receptor type 2 expression in preterm delivered placentas should be further investigated, as perinatal endocannabinoid receptor expression could serve as a predicting tool of preterm birth. For example, liquid-based cytology could be used as a noninvasive perinatal method of measuring the expression level of cannabinoid receptors in decidual cells during pregnancy. KEYWORDS: Cannabinoid receptor; CB2; endocannabinoid system; preterm delivery; PTB
Studying complex metazoan communities requires taxonomic expertise and laborious work if done using the traditional morphological approach. Nowadays, the popular use of molecular-based methods accompanied by massively parallel sequencing (MPS) provides rapid and higher resolution diversity analyses. However, diversity estimates derived from the molecular-based approach can be biased by the co-detection of environmental DNA (eDNA), pseudogene contamination, and PCR amplification biases. Here, we constructed microcrustacean zooplankton mock communities to compare species diversity and composition estimates from PCR-based methods using genomic (gDNA) and complementary DNA (cDNA), metatranscriptomic transcripts, and morphology data. Mock community analyses show that gDNA mitochondrial cytochrome c oxidase I (mtCOI) amplicons inflate species richness due to environmental and nontarget species sequence contamination. Significantly higher amplicon sequence variant (ASV) and nucleotide diversity in gDNA amplicons than cDNA indicated the presence of putative pseudogenes. Last, PCR-based methods failed to detect the most abundant species in mock communities due to priming site mismatch. Overall, metatranscriptomic transcripts provided estimates of species richness and composition that closely resembled morphological data. The use of metatranscriptomic transcripts was further tested in field samples. The results showed that it could provide consistent species diversity estimates among biological and technical replicates while allowing monitoring of the zooplankton temporal species composition changes using different mitochondrial markers. These findings show that community characterization based on metatranscriptomic transcripts reflects the actual community more than PCR-based approaches.
Background: Early-life exposures to geohelminths may protect against the development of wheeze/asthma and atopy. Objective: Study effect of maternal geohelminths and infections in children during the first 5 years of life on atopy, wheeze/asthma, and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2,404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO), and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1,933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and in 45.5% of children to 5 years. Frequencies of outcomes at 8 years were: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%), and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced prevalence of SPT (OR 0.72). Childhood T. trichiura infections were associated with reduced wheeze (OR 0.57) but greater parasite burdens with A. lumbricoides were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).
i. Rationale, Aims and Objectives: Despite guideline recommendations against their use, clinicians prescribe benzodiazepines for various symptoms to patients with posttraumatic stress disorder (PTSD). Clinicians’ reasons in making these decisions are not fully understood. This qualitative study sought to characterize factors identified by prescribing clinicians in clinical decision making in PTSD regarding the use of benzodiazepines. ii. Methods: The descriptive study involved semi-structured interviews with 26 prescribing clinicians across thirteen VA medical centers. Our overall aim in the study was to explore clinicians’ benzodiazepine practices in veterans with a PTSD diagnosis. We audio-recorded, transcribed, and analyzed the interviews using grounded theory methodology. iii. Results: Facilitators and barriers that contribute to benzodiazepine prescribing to veterans with PTSD included organizational, provider, and patient aspects. Most providers interviewed indicated that they inherited patients already on these medications initiated by other clinicians. These providers, as well as others interviewed, voiced concerns that tapering benzodiazepines may cause more harm than the risks of maintenance, particularly in older patients. Clinicians who noted consistent treatment practices among their hospital colleagues found it easier to decrease both new and maintenance benzodiazepine prescribing. iv. Conclusions: Patients with PTSD at increased risk of harms, such as older patients, are still receiving benzodiazepines suggesting that innovative solutions are now needed to decrease use. Specific protocols for inherited patient caseloads, increased dissemination of effective psychotherapies for symptoms such as insomnia and anxiety and the use of direct to consumer educational materials should help to foster needed culture change and increased evidence-based PTSD practice.
Background: Revascularization has been considered the gold standard treatment for critical limb ischemia (CLI). Due to the high morbidity and mortality associated with intervention, evidence has emerged recently supporting the suitability of conservative management as a primary option to achieve amputation-free survival (AFS) in CLI patients even when revascularization is technically feasible. Methods: A prospective database of CLI patients was developed during pre-screening of patients for a phase 1 stem cell therapy clinical trial. The overall survival (OS) and AFS rates for patients treated with revascularization were compared to those treated conservatively. Statistical significance was set as p value < 0.05. OS and AFS for the two groups were estimated by Kaplan-Meier survival curves. Results: Patients in the conservative group were more likely to have Rutherford Class 5 and be diabetic while they were less likely to be active smokers or have hyperlipidemia (Table 1). There were no significant differences between the two groups in mortality, amputation, overall AFS or one-year AFS rates. Kaplan-Meier cumulative OS and AFS over the 3 years follow-up period of the study demonstrated significant differences between the conservative and revascularization groups (Log Rank: 0.031 & 0.045; respectively). This statistical significance was not detected when one-year AFS was evaluated (Log Rank 0.096). Conclusion: Conservative management can be a suitable management option to achieve one-year AFS for some CLI patients. Further studies are needed to identify robust clinical criteria for identifying patients who will benefit from conservative management.