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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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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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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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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.
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5.
Culture and well-being in late adulthood: Theory and evidence.
Kitayama, S, Berg, MK, Chopik, WJ
The American psychologist. 2020;(4):567-576
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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).
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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.
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Is it time to reconcile HDL with cardiovascular diseases and beyond? An update on a paradigm shift.
Martinez, LO, Ingueneau, C, Genoux, A
Current opinion in lipidology. 2020;(5):302-304
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Insights into the Role of Renal Biopsy in Patients with T2DM: A Literature Review of Global Renal Biopsy Results.
Tong, X, Yu, Q, Ankawi, G, Pang, B, Yang, B, Yang, H
Diabetes therapy : research, treatment and education of diabetes and related disorders. 2020;(9):1983-1999
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Abstract
INTRODUCTION Renal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of "clinical indicators" to differentiate DKD from NDKD has been an area of active research. METHODS The PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD. RESULTS The literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified. CONCLUSION To date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.
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Artificial Intelligence and Orthopaedics: An Introduction for Clinicians.
Myers, TG, Ramkumar, PN, Ricciardi, BF, Urish, KL, Kipper, J, Ketonis, C
The Journal of bone and joint surgery. American volume. 2020;(9):830-840
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Abstract
➤. Artificial intelligence (AI) provides machines with the ability to perform tasks using algorithms governed by pattern recognition and self-correction on large amounts of data to narrow options in order to avoid errors. ➤. The 4 things necessary for AI in medicine include big data sets, powerful computers, cloud computing, and open source algorithmic development. ➤. The use of AI in health care continues to expand, and its impact on orthopaedic surgery can already be found in diverse areas such as image recognition, risk prediction, patient-specific payment models, and clinical decision-making. ➤. Just as the business of medicine was once considered outside the domain of the orthopaedic surgeon, emerging technologies such as AI warrant ownership, leverage, and application by the orthopaedic surgeon to improve the care that we provide to the patients we serve. ➤. AI could provide solutions to factors contributing to physician burnout and medical mistakes. However, challenges regarding the ethical deployment, regulation, and the clinical superiority of AI over traditional statistics and decision-making remain to be resolved.
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Understanding short bowel syndrome: Current status and future perspectives.
Massironi, S, Cavalcoli, F, Rausa, E, Invernizzi, P, Braga, M, Vecchi, M
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2020;(3):253-261
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Abstract
Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients' quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS. This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances. Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.