-
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.
-
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.
-
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
-
-
Free full text
-
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.
-
4.
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.
-
5.
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.
-
6.
Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation.
Campione, E, Cosio, T, Rosa, L, Lanna, C, Di Girolamo, S, Gaziano, R, Valenti, P, Bianchi, L
International journal of molecular sciences. 2020;(14)
Abstract
Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.
-
7.
Culture and well-being in late adulthood: Theory and evidence.
Kitayama, S, Berg, MK, Chopik, WJ
The American psychologist. 2020;(4):567-576
-
-
Free full text
-
Abstract
Aging happens to everyone everywhere. At present, however, little is known about whether life-span adult development-and particularly development in late adulthood-is pancultural or culture-bound. Here, we propose that in Western cultural contexts, individuals are encouraged to maintain the active, positive, and independent self. This cultural expectation continues even in late adulthood, thus leading to a mismatch between aspirations to live up to the cultural expectation and the reality of aging. This mismatch is potentially alienating. In contrast, in Asian cultural contexts, a critical task throughout life is to achieve attunement with age-graded social roles. This ideal may be more attainable even in late adulthood. Our review of existent evidence lends support to this analysis. Specifically, in late adulthood, Americans showed a robust psychological bias toward high-arousal positive (vs. negative) emotions. This positivity, however, concealed a somber aspect of aging that manifested itself in more demanding realms of life. Thus, Americans in late adulthood also showed marked declines in certain desirable personality traits (e.g., extraversion and conscientiousness) and some aspects of the meaning in life (e.g., personal growth and purpose in life). None of these effects were apparent among East Asians. The current work underscores a need to extend research on life-span development beyond Western populations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
-
8.
Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial.
Ni, J, Chen, H, Chen, G, Ji, Y, Yi, F, Zhang, Z, Yang, Y, Wu, J, Cai, X, Shao, B, et al
BMC neurology. 2020;(1):282
Abstract
BACKGROUND Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke. METHODS Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram. RESULTS In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups. CONCLUSIONS The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported. TRIAL REGISTRATION Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827 . Retrospectively registered June 13, 2019.
-
9.
Reach Out Emergency Department: Partnering With an Economically Disadvantaged Community in the Development of a Text-Messaging Intervention to Address High Blood Pressure.
Champoux, E, Price, R, Cowdery, JE, Dinh, M, Meurer, WJ, Rehman, N, Schille, C, Oliver, A, Brown, DL, Killingsworth, J, et al
Health promotion practice. 2020;(5):791-801
-
-
Free full text
-
Abstract
Background. Hypertension affects nearly 30% of the U.S. adult population. Due to the ubiquitous nature of mobile phone usage, text messaging offers a promising platform for interventions to assist in the management of chronic diseases including hypertension, including among populations that are historically underserved. We present the intervention development of Reach Out, a health behavior theory-based, mobile health intervention to reduce blood pressure among hypertensive patients evaluated in a safety net emergency department primarily caring for African Americans. Aims. To describe the process of designing and refining text messages currently being implemented in the Reach Out randomized controlled trial. Method. We used a five-step framework to develop the text messages used in Reach Out. These steps included literature review and community formative research, conception of a community-centered behavioral theoretical framework, draft of evidence-based text messages, community review, and revision based on community feedback and finalization. Results. The Reach Out development process drew from pertinent evidence that, combined with community feedback, guided the development of a community-centered health behavior theory framework that led to development of text messages. A total of 333 generic and segmented messages were created. Messages address dietary choices, physical activity, hypertension medication adherence, and blood pressure monitoring. Discussion. Our five-step framework is intended to inform future text-messaging-based health promotion efforts to address health issues in vulnerable populations. Conclusion. Text message-based health promotion programs should be developed in partnership with the local community to ensure acceptability and relevance.
-
10.
Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence.
Bonora, BM, Avogaro, A, Fadini, GP
Diabetes, metabolic syndrome and obesity : targets and therapy. 2020;:161-174
Abstract
Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.