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1.
Beyond thrombosis: the impact of tissue factor signaling in cancer.
Unruh, D, Horbinski, C
Journal of hematology & oncology. 2020;(1):93
Abstract
Tissue factor (TF) is the primary initiator of the coagulation cascade, though its effects extend well beyond hemostasis. When TF binds to Factor VII, the resulting TF:FVIIa complex can proteolytically cleave transmembrane G protein-coupled protease-activated receptors (PARs). In addition to activating PARs, TF:FVIIa complex can also activate receptor tyrosine kinases (RTKs) and integrins. These signaling pathways are utilized by tumors to increase cell proliferation, angiogenesis, metastasis, and cancer stem-like cell maintenance. Herein, we review in detail the regulation of TF expression, mechanisms of TF signaling, their pathological consequences, and how it is being targeted in experimental cancer therapeutics.
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2.
Coelenterazine-Dependent Luciferases as a Powerful Analytical Tool for Research and Biomedical Applications.
Krasitskaya, VV, Bashmakova, EE, Frank, LA
International journal of molecular sciences. 2020;(20)
Abstract
: The functioning of bioluminescent systems in most of the known marine organisms is based on the oxidation reaction of the same substrate-coelenterazine (CTZ), catalyzed by luciferase. Despite the diversity in structures and the functioning mechanisms, these enzymes can be united into a common group called CTZ-dependent luciferases. Among these, there are two sharply different types of the system organization-Ca2+-regulated photoproteins and luciferases themselves that function in accordance with the classical enzyme-substrate kinetics. Along with deep and comprehensive fundamental research on these systems, approaches and methods of their practical use as highly sensitive reporters in analytics have been developed. The research aiming at the creation of artificial luciferases and synthetic CTZ analogues with new unique properties has led to the development of new experimental analytical methods based on them. The commercial availability of many ready-to-use assay systems based on CTZ-dependent luciferases is also important when choosing them by first-time-users. The development of analytical methods based on these bioluminescent systems is currently booming. The bioluminescent systems under consideration were successfully applied in various biological research areas, which confirms them to be a powerful analytical tool. In this review, we consider the main directions, results, and achievements in research involving these luciferases.
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3.
Derivation and Application of a Tool to Estimate Benefits From Multiple Therapies That Reduce Recurrent Stroke Risk.
Richards, A, Jackson, NJ, Cheng, EM, Bryg, RJ, Brown, A, Towfighi, A, Sanossian, N, Barry, F, Li, N, Vickrey, BG
Stroke. 2020;(5):1563-1569
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Abstract
Background and Purpose- Lowering blood pressure and cholesterol, antiplatelet/antithrombotic use, and smoking cessation reduce risk of recurrent stroke. However, gaps in risk factor control among stroke survivors warrant development and evaluation of alternative care delivery models that aim to simultaneously improve multiple risk factors. Randomized trials of care delivery models are rarely of sufficient duration or size to be powered for low-frequency outcomes such as observed recurrent stroke. This creates a need for tools to estimate how changes across multiple stroke risk factors reduce risk of recurrent stroke. Methods- We reviewed existing evidence of the efficacy of interventions addressing blood pressure reduction, cholesterol lowering, antiplatelet/antithrombotic use, and smoking cessation and extracted relative risks for each intervention. From this, we developed a tool to estimate reductions in recurrent stroke risk, using bootstrapping and simulation methods. We also calculated a modified Global Outcome Score representing the proportion of potential benefit (relative risk reduction) achieved if all 4 individual risk factors were optimally controlled. We applied the tool to estimate stroke risk reduction among 275 participants with complete 12-month follow-up data from a recently published randomized trial of a healthcare delivery model that targeted multiple stroke risk factors. Results- The recurrent stroke risk tool was feasible to apply, yielding an estimated reduction in the relative risk of ischemic stroke of 0.36 in both the experimental and usual care trial arms. Global Outcome Score results suggest that participants in both arms likely averted, on average, 45% of recurrent stroke events that could possibly have been prevented through maximal implementation of interventions for all 4 individual risk factors. Conclusions- A stroke risk reduction tool facilitates estimation of the combined impact on vascular risk of improvements in multiple stroke risk factors and provides a summary outcome for studies testing alternative care models to prevent recurrent stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00861081.
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4.
Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies.
Odutola, MK, Nnakelu, E, Giles, GG, van Leeuwen, MT, Vajdic, CM
Cancer causes & control : CCC. 2020;(11):979-1000
Abstract
PURPOSE To investigate the relationship between follicular lymphoma (FL) risk and common modifiable lifestyle factors, specifically smoking, alcohol, body mass index (BMI), and hair dye use. METHODS We performed a systematic review and meta-analysis of observational studies published prior to 01 January 2020. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science and the reference lists of original studies and review articles. We used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95% CI). RESULTS Twenty-four cohort and ten case-control studies were eligible. Ten articles examined smoking, 11 alcohol, 13 BMI, and four hair dye use and risk of FL. The meta-estimate for current smoking was 1.11 (95% CI 0.92-1.35; I2 = 51%) and there was no significant dose-response per 5-year increase in duration (p-trend = 0.087). Current alcohol intake was inversely associated with FL risk (meta-RR 0.87, 95% CI 0.81-0.94; I2 = 0%) and there was a significant dose-response per 5 drinks/week increase in intake (p-trend = 0.008). There was no association with 5 kg/m2 increase in early adulthood BMI (meta-RR 1.05, 95% CI 0.91-1.20; I2 = 7%) or being overweight (meta-RR 0.99, 95% CI 0.92-1.07; I2 = 0%) or obese (meta-RR 1.08, 95% CI 0.99-1.17; I2 = 0%) as an adult. Hair dye use before 1980 was positively associated with FL risk (meta-RR 1.66, 95% CI 1.22-2.25; I2 = 55%) and no evidence of effect after 1980. CONCLUSION We found consistent evidence of an inverse association between current alcohol intake and FL risk, and a significant increased risk with hair dye use before 1980. The evidence for smoking is heterogeneous, but most studies did not support an association. Further research is required to understand the mechanisms underlying these associations and the potential for prevention strategies.
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5.
The Impact of Individualizing Sodium Bicarbonate Supplementation Strategies on World-Class Rowing Performance.
Boegman, S, Stellingwerff, T, Shaw, G, Clarke, N, Graham, K, Cross, R, Siegler, JC
Frontiers in nutrition. 2020;:138
Abstract
Contemporary meta-analyses have generally demonstrated a positive effect of sodium bicarbonate (NaHCO3) supplementation on exercise performance. However, despite these claims, there is limited data on contrasting individualized and standardized timing of NaHCO3 ingestion prior to exercise to further enhance performance outcomes. Purpose: To determine whether NaHCO3 ingestion timing impacts 2,000-m rowing time-trial (TT) performance in elite-level rowers (Senior National team including Olympic/World Championships level) adhering to their own individualized pre-race strategies (e.g. nutrition, warm-up, etc.). Methods: Twenty three (n = 23) rowers across two research centers (using the exact same methods/protocols) completed three trials: NaHCO3 loading profile at rest to determine the individual's time-to-peak bicarbonate concentration [ HCO3- ], followed by two randomized 0.3 g·kgBM-1 NaHCO3 supplementation experimental trials conducted at different time points [consensus timing (CON): TT performed 60 min post-NaHCO3 ingestion; and individualized peak (IP): TT performed at the rower's individual peak [ HCO3- ] determined from the profiling trial post-NaHCO3 ingestion]. Results: There was a significant mean difference of +2.9 [± 0.4 mmol·L-1 HCO3- for IP vs. CON (95% CI 2.0 to 3.8 mmol·L-1); p = 0.02; d = 1.08] at pre warm-up, but not immediately prior to the TT (post warm-up). Performance times were significantly different between IP (367.0 ± 10.5 s) vs. CON (369.0 ± 10.3 s); p = 0.007; d = 0.15). Conclusions: The present study demonstrated a small but significant performance effect of an individualized NaHCO3 ingestion strategy. Similarities after warm-up between pre-TT sHCO3- values (CON ~ + 5.5 mmol·L-1; IP ~ + 6 mmol·L-1), however, would suggest this effect was not a result of any meaningful differences in blood alkalinity.
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6.
Protective Effects of Pomegranate in Endothelial Dysfunction.
Delgado, NTB, Rouver, WN, Dos Santos, RL
Current pharmaceutical design. 2020;(30):3684-3699
Abstract
BACKGROUND Punica granatum L. is an infructescence native of occidental Asia and Mediterranean Europe, popularly referred to as pomegranate. It has been used in ethnomedicine for several applications, including the treatment of obesity, inflammation, diabetes, and the regulation of blood lipid parameters. Thus, pomegranate has been linked to the treatment of cardiovascular diseases that have endothelial dysfunction as a common factor acting mainly against oxidative stress due to its high polyphenol content. Its biocomponents have antihypertensive, antiatherogenic, antihyperglycemic, and anti-inflammatory properties, which promote cardiovascular protection through the improvement of endothelial function. METHODS Different electronic databases were searched in a non-systematic way to uncover the literature of interest. CONCLUSION This review article presents updated information on the role of pomegranate in the context of endothelial dysfunction and cardiovascular diseases. We have shown that pomegranate, or rather its components (e.g., tannins, flavonoids, phytoestrogens, anthocyanins, alkaloids, etc.), have beneficial effects on the cardiovascular system, improving parameters such as oxidative stress and the enzymatic antioxidant system, reducing reactive oxygen species formation and acting in an anti-inflammatory way. Thus, this review may contribute to a better understanding of pomegranate's beneficial actions on endothelial function and possibly to the development of strategies associated with conventional treatments of cardiovascular diseases.
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7.
Melatonin in business with abiotic stresses in plants.
Khan, TA, Fariduddin, Q, Nazir, F, Saleem, M
Physiology and molecular biology of plants : an international journal of functional plant biology. 2020;(10):1931-1944
Abstract
Melatonin (MEL) is the potential biostimulator molecule, governing multiple range of growth and developmental processes in plants, particularly under different environmental constrains. Mainly, its role is considered as an antioxidant molecule that copes with oxidative stress through scavenging of reactive oxygen species and modulation of stress related genes. It also enhances the antioxidant enzyme activities and thus helps in regulating the redox hemostasis in plants. Apart from its broad range of antioxidant functions, it is involved in the regulation of various physiological processes such as germination, lateral root growth and senescence in plants. Moreover this multifunctional molecule takes much interest due to its recent identification and characterization of receptorCandidate G-protein-Coupled Receptor 2/Phytomelatonin receptor(CAND2/PMTR1) in Arabidopsis thaliana. In this compiled work, different aspects of melatonin in plants such as melatonin biosynthesis and detection in plants, signaling pathway, modulation of stress related genes and physiological role of melatonin under different environmental stresses have been dissected in detail.
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8.
Low dose of isotretinoin: A comprehensive review.
Abdelmaksoud, A, Lotti, T, Anadolu, R, Goldust, M, Ayhan, E, Dave, DD, Vestita, M, Ebik, B, Gupta, M
Dermatologic therapy. 2020;(2):e13251
Abstract
Isotretinoin is a first-generation retinoid initially approved for the treatment of severe cases of acne vulgaris (nodulocystic acne). Because of its broad anti-inflammatory and immunomodulatory properties, it has been used beyond its initial approval in a myriad of other indications. Adverse effects of isotretinoin vary from xerosis to teratogenicity. Herein, we reviewed the literature, through date-unlimited PubMed search, from inception till December 2019, using the following search terms: "low-dose isotretinoin" and "dermatology," "isotretinoin and safety," "isotretinoin, off-label uses," "isotretinoin and male fertility," "isotretinoin, iPLEDGE system," aiming to deliver a therapeutic update relevant to clinical practice. All English-language articles were considered with no limitation based on the articles' type. Low-dose isotretinoin is not limited to old and novel dermatological conditions, but also showed promising results in the field of infertility and safety in the field of gastroenterology. We also highlight on the safety profile of the drug and experts' recommendations to enhance safety measures to decrease fetal risk while on isotretinoin.
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Oxylipin regulation by phenolic compounds from coffee beverage: Positive outcomes from a randomized controlled trial in healthy adults and macrophage derived foam cells.
Lara-Guzmán, OJ, Medina, S, Álvarez, R, Oger, C, Durand, T, Galano, JM, Zuluaga, N, Gil-Izquierdo, Á, Muñoz-Durango, K
Free radical biology & medicine. 2020;:604-617
Abstract
Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).
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10.
Pharmacological Methods of Postoperative Pain Management After Laparoscopic Cholecystectomy: A Review of Meta-analyses.
Eftekhariyazdi, M, Ansari, M, Darvishi-Khezri, H, Zardosht, R
Surgical laparoscopy, endoscopy & percutaneous techniques. 2020;(6):534-541
Abstract
BACKGROUND Laparoscopic cholecystectomy (LC) is the optimal approach for patients with symptomatic cholecystolithiasis. Although LC has some advantages, many patients experience postoperative pain. METHODS In this review, we aimed to study the available information and meta-analyses of pharmacological methods of postoperative pain management in patients undergoing LC. Two researchers conducted a literature search in multiple databases (PubMed, Web of Science, Science Direct, Scopus, EMBASE, and Cochrane Library). Papers on pharmacological management of postoperative pain for patients undergoing LC were considered eligible. All meta-analyses, with or without a systematic search, were included in our review. The researchers read the study titles and abstracts to identify relevant articles and appraise the full-text manuscripts. Of 145 papers, the full-text of 11 articles, which met the inclusion criteria, was studied. Information, including the authors' names, publication data, type of review, patients' characteristics, interventions, outcomes, sample size, pooled effect size, publication bias, and statistical and methodological heterogeneity, was extracted. The collected data were presented descriptively, without further statistical analysis. RESULTS AND CONCLUSIONS Very low to low-quality evidence indicated that pharmacological agents, such as nonsteroidal anti-inflammatory drugs, lidocaine, parecoxib, nefopam, dexamethasone, and magnesium sulfate, could decrease pain intensity in patients undergoing LC. Moreover, moderate to high-quality evidence showed that intravenous infusion of ketamine and opioids, as well as pregabalin, was effective in pain control. Further, robust clinical trials are needed with several arms (eg, pharmacological agents) to compare the efficacy and safety of analgesics under similar clinical conditions and to find optimal regimens for pain management in patients undergoing LC.