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1.
MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review.
Petrone, I, Bernardo, PS, Dos Santos, EC, Abdelhay, E
Genes. 2021;(4)
Abstract
Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.
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2.
Evaluation and management of the critically ill adult asthmatic in the emergency department setting.
Long, B, Lentz, S, Koyfman, A, Gottlieb, M
The American journal of emergency medicine. 2021;:441-451
Abstract
INTRODUCTION Asthma is a common reason for presentation to the Emergency Department and is associated with significant morbidity and mortality. While patients may have a relatively benign course, there is a subset of patients who present in a critical state and require emergent management. OBJECTIVE This narrative review provides evidence-based recommendations for the assessment and management of patients with severe asthma. DISCUSSION It is important to consider a broad differential diagnosis for the cause and potential mimics of asthma exacerbation. Once the diagnosis is determined, the majority of the assessment is based upon the clinical examination. First line therapies for severe exacerbations include inhaled short-acting beta agonists, inhaled anticholinergics, intravenous steroids, and magnesium. Additional therapies for refractory cases include parenteral epinephrine or terbutaline, helium‑oxygen mixture, and consideration of ketamine. Intravenous fluids should be administered, as many of these patients are dehydrated and at risk for hypotension if they receive positive pressure ventilatory support. Noninvasive positive pressure ventilation may prevent the need for endotracheal intubation. If mechanical ventilation is required, it is important to avoid breath stacking by setting a low respiratory rate and allowing permissive hypercapnia. Patients with severe asthma exacerbations will require intensive care unit admission. CONCLUSIONS This review provides evidence-based recommendations for the assessment and management of severe asthma with a focus on the emergency clinician.
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3.
Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.
Chisari, A, Golán, I, Campisano, S, Gélabert, C, Moustakas, A, Sancho, P, Caja, L
Frontiers in pharmacology. 2021;:723798
Abstract
Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination. For these reasons, eliminating CSCs is necessary in order to achieve long-term survival of cancer patients. New insights in cancer metabolism have revealed that cellular metabolism in tumors is highly heterogeneous and that CSCs show specific metabolic traits supporting their unique functionality. Indeed, CSCs adapt differently to the deprivation of specific nutrients that represent potentially targetable vulnerabilities. This review focuses on three of the most aggressive tumor types: pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC) and glioblastoma (GBM). The aim is to prove whether CSCs from different tumour types share common metabolic requirements and responses to nutrient starvation, by outlining the diverse roles of glucose and amino acids within tumour cells and in the tumour microenvironment, as well as the consequences of their deprivation. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, glucose and amino acid derivatives contribute to immune responses linked to tumourigenesis and metastasis. Furthermore, potential metabolic liabilities are identified and discussed as targets for therapeutic intervention.
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4.
Pulmonary Functional Imaging: Part 1-State-of-the-Art Technical and Physiologic Underpinnings.
Ohno, Y, Seo, JB, Parraga, G, Lee, KS, Gefter, WB, Fain, SB, Schiebler, ML, Hatabu, H
Radiology. 2021;(3):508-523
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Abstract
Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.
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Boosting nitric oxide in stress and respiratory infection: Potential relevance for asthma and COVID-19.
Ritz, T, Salsman, ML, Young, DA, Lippert, AR, Khan, DA, Ginty, AT
Brain, behavior, & immunity - health. 2021;:100255
Abstract
Nitric oxide (NO) is a ubiquitous signaling molecule that is critical for supporting a plethora of processes in biological organisms. Among these, its role in the innate immune system as a first line of defense against pathogens has received less attention. In asthma, levels of exhaled NO have been utilized as a window into airway inflammation caused by allergic processes. However, respiratory infections count among the most important triggers of disease exacerbations. Among the multitude of factors that affect NO levels are psychological processes. In particular, longer lasting states of psychological stress and depression have been shown to attenuate NO production. The novel SARS-CoV-2 virus, which has caused a pandemic, and with that, sustained levels of psychological stress globally, also adversely affects NO signaling. We review evidence on the role of NO in respiratory infection, including COVID-19, and stress, and argue that boosting NO bioavailability may be beneficial in protection from infections, thus benefitting individuals who suffer from stress in asthma or SARS-CoV-2 infection.
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Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver.
Zobeiri, M, Parvizi, F, Kalhori, MR, Majnooni, MB, Farzaei, MH, Abdollahi, M
Evidence-based complementary and alternative medicine : eCAM. 2021;:6641031
Abstract
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell's biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene's expression and noncoding RNAs, especially miRNAs.
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7.
Potassium and phosphorus transport and signaling in plants.
Wang, Y, Chen, YF, Wu, WH
Journal of integrative plant biology. 2021;(1):34-52
Abstract
Nitrogen (N), potassium (K), and phosphorus (P) are essential macronutrients for plant growth and development, and their availability affects crop yield. Compared with N, the relatively low availability of K and P in soils limits crop production and thus threatens food security and agricultural sustainability. Improvement of plant nutrient utilization efficiency provides a potential route to overcome the effects of K and P deficiencies. Investigation of the molecular mechanisms underlying how plants sense, absorb, transport, and use K and P is an important prerequisite to improve crop nutrient utilization efficiency. In this review, we summarize current understanding of K and P transport and signaling in plants, mainly taking Arabidopsis thaliana and rice (Oryza sativa) as examples. We also discuss the mechanisms coordinating transport of N and K, as well as P and N.
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8.
Methods for Chromosome Doubling.
Shariatpanahi, ME, Niazian, M, Ahmadi, B
Methods in molecular biology (Clifton, N.J.). 2021;:127-148
Abstract
The completely homozygous genetic background of doubled haploids (DHs) has many applications in breeding programs and research studies. Haploid induction and chromosome doubling of induced haploids are the two main steps of doubled haploid creation. Both steps have their own complexities. Chromosome doubling of induced haploids may happen spontaneously, although usually at a low rate. Therefore, artificial/induced chromosome doubling of haploid cells/plantlets is necessary to produce DHs at an acceptable level. The most common method is using some mitotic spindle poisons that target the organization of the microtubule system. Colchicine is a well-known and widely used antimitotic. However, there are substances alternative to colchicine in terms of efficiency, toxicity, safety, and genetic stability, which can be applied in in vitro and in vivo pathways. Both pathways have their own advantages and disadvantages. However, in vitro-induced chromosome doubling has been much preferred in recent years, maybe because of the dual effect of antimitotic agents (haploid induction and chromosome doubling) in just one step, and the reduced generation of chimeras. Plant genotype, the developmental stage of initial haploids, and type-concentration-duration of application of antimitotic agents, are top influential parameters on chromosome doubling efficiency. In this review, we highlight different aspects related to antimitotic agents and to plant parameters for successful chromosome doubling and high DH yield.
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9.
Neurogenic Bowel Dysfunction in Children and Adolescents.
Mosiello, G, Safder, S, Marshall, D, Rolle, U, Benninga, MA
Journal of clinical medicine. 2021;(8)
Abstract
Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common cause of pediatric NBD). Many methods of conservative and medical management of NBD are reported, including relatively recently Transanal Irrigation (TAI). Based on the literature and personal experience, an expert group (pediatric urologists/surgeons/gastroenterologists with specific experience in NBD) focused on NBD in children and adolescents. A statement document was created using a modified Delphi method. The range of causes of pediatric NBD are discussed in this paper. The various therapeutic approaches are presented to improve clinical management. The population of children and adolescents with NBD is increasing, due both to the higher survival rate and better diagnosis. While NBD is relatively predictable in producing either constipation or fecal incontinence, or both, its various effects on each patient will depend on a wide range of underlying causes and accompanying comorbidities. For this reason, management of NBD should be tailored individually with a combined multidisciplinary therapy appropriate for the status of the affected child and caregivers.
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10.
Determining the effect size of aerobic exercise training on the standard lipid profile in sedentary adults with three or more metabolic syndrome factors: a systematic review and meta-analysis of randomised controlled trials.
Wood, G, Taylor, E, Ng, V, Murrell, A, Patil, A, van der Touw, T, Sigal, R, Wolden, M, Smart, N
British journal of sports medicine. 2021
Abstract
OBJECTIVES To estimate the change in the standard lipid profile (SLP) of adults diagnosed with ≥3 metabolic syndrome (MetS) factors following aerobic exercise training (AET); and to investigate whether study/intervention covariates are associated with this change. DESIGN Systematic review with univariate meta-analysis and meta-regression. DATA SOURCES English language searches of online databases from inception until July 2020. ELIGIBILITY CRITERIA (1) Published randomised controlled human trials with study population ≥10 per group; (2) sedentary adults with ≥3 MetS factors but otherwise free of chronic disease, not pregnant/lactating; (3) AET-only intervention with duration ≥12 weeks; and (4) reporting pre-post intervention SLP outcomes. RESULTS Various univariate meta-analyses pooled 48 data sets of 2990 participants. Aerobic exercise training significantly (P<.001) improved all lipids (mmol/L mean difference ranges, 95% CIs): total cholesterol, -0.19 (-0.26 to -0.12) to -0.29 (-0.36 to -0.21); triglycerides, -0.17 (-0.19 to -0.14) to -0.18 (-0.24 to -0.13); high-density lipoprotein-cholesterol (HDL-C), 0.05 (0.03 to 0.07) to 0.10 (0.05 to 0.15); and low-density lipoprotein-cholesterol (LDL-C), -0.12 (-0.16 to -0.9) to -0.20 (-0.25 to -0.14). Meta-regression showed that intensity may explain change in triglycerides and volume may explain change in HDL-C and LDL-C. CONCLUSION Aerobic exercise training positively changes the SLP of sedentary and otherwise healthy adults with ≥3 MetS factors. Adjusting AET intervention training variables may increase the effects of AET on triglycerides and HDL-C. PROSPERO REGISTRATION NUMBER CRD42020151925.