An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

first_pagesettingsOrder Article Reprints Open AccessReview An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times by Cielo García-Montero 1ORCID,Oscar Fraile-Martínez 1,Coral Bravo 2,3,4,Diego Torres-Carranza 5,Lara Sanchez-Trujillo 1,6ORCID,Ana M. Gómez-Lahoz 1,Luis G. Guijarro 7,Natalio García-Honduvilla 1,8,Angel Asúnsolo 8,9ORCID,Julia Bujan 1,8ORCID,Jorge Monserrat 1,8ORCID,Encarnación Serrano 10,Melchor Álvarez-Mon 1,8,11,Juan A De León-Luis 3,4,5,*ORCID,Miguel A. Álvarez-Mon 1,8,12ORCID andMiguel A. Ortega 1,8,13ORCID 1 Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain 2 Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain 3 Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain 4 Health Research Institute Gregorio Marañón, 28009 Madrid, Spain 5 First of May Health Centre, Health Area I, Rivas Vaciamadrid, 28521 Madrid, Spain 6 Service of Pediatric, Hospital Universitario Principe de Asturias, 28801 Alcalá de Henares, Spain 7 Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcalá, 28801 Alcalá de Henares, Spain 8 Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain 9 Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain 10 Los fresnos of Health Centre, Health Area III, Torrejon de Ardoz, 28850 Madrid, Spain add Show full affiliation list * Author to whom correspondence should be addressed. Vaccines 2021, 9(5), 433; https://doi.org/10.3390/vaccines9050433 Received: 9 April 2021 / Revised: 21 April 2021 / Accepted: 22 April 2021 / Published: 27 April 2021 (This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19) Download Browse Figures Versions Notes Abstract Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac)

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn''s disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology. © 2021 The Author

Bioeconomy based on Scientific Research and Entrepreneurship

The bioeconomy can be defined as an activity that provides solutions to problems arising from the imbalance between increasing world population and the availability of resources and difficulties in supplying those needs. Bioeconomy is based on best and new uses of natural resources among which are important and essential plant species in areas such as agriculture, food industry, cosmetics and pharmaceutical industry, textile industry, landscaping and architecture, design of interior and exterior gardens, bioenergy, and the conservation and restoration of soils and natural ecosystems. Once checked problems, how to propose solutions in the context of the Bioeconomy? The universities base their activity in teaching and learning and scientific research. Furthermore, human societies and the habitats they occupy are social structures in which problems occur. If scientific research provides results that may constitute solutions to problems, it is necessary to build bridges between the academic activity and problems of society, bridges to convert research results in an entrepreneurial activity that allows its application as a solution to a given problem. That bridge is entrepreneurship to develop spin-offs and start-up. Something else to consider? The entrepreneurship is a process, it is learned, tested and developed, but solves nothing if not based on an entrepreneur, so the bridge is the entrepreneur instead of entrepreneurship. Consequently we must devote the effort to form new mindsets and attitudes to modern societies. If we have the necessary tools, learn to use them to be resolute and ask governments environments and mechanisms necessary to carry out the task

Five-coordinate complex [RuHCl(CO)(PPri 3)2] as a precursor for the preparation of new cyclopentadienylruthenium compounds containing unsaturated η1-carbon ligands

The five-coordinate complex [RuHCl(CO)(PPri 3)2] (1) reacts with cyclopentadiene in methanol under reflux to give [RuH(η5-C5H5)(CO)(PPri 3)] (2) and [HPPri 3]Cl. The protonation of 2 in dichloromethane-d2 leads to the dihydrogen complex [Ru(η5-C5H5)(η5-H 2)(CO)(PPri 3)]-BF4 (3) in equilibrium with traces of the dihydrido tautomer [RuH2(η5-C5H5)(CO)(PPr i 3)]-BF4 (4). The reaction of 2 with HBF4·Et2O in acetone affords the solvated complex [Ru(η5-C5H5)(CO){η 1-OC(CH3)2}(PPri 3)]BF4 (5), which reacts with CO, dimethyl acetylenedicarboxylate, and NaCl to give [Ru(η5-C5H5)(CO)2(PPr i 3)]BF4 (6), [Ru(η5-C5H5){η2-C 2(CO2CH3)2}(CO)(PPri 3)]-BF4 (7), and [Ru(η5-C5H5)Cl(CO)(PPri 3)] (8), respectively. Complex 5 also reacts with alkyn-1-ols. The reaction with 1,1-diphenyl-2-propyn-1-ol leads to the allenylidene complex [Ru(η5-C5H5)(C=C=CPh 2)(CO)(PPri 3)]BF4 (9), which affords [Ru(η5-C5H5){C(OH)CH=CPh 2}-(CO)(PPri 3)]BF4 (10) by reaction with water. 10 is converted into the acyl derivative [Ru-(η5-C5H5){C(O)CH=CPh 2}(CO)(PPri 3)] (11), when a CH2Cl2 solution of 10 is passed through an Al2O3 column. The structure of 11 was determined by an X-ray investigation. The reaction of 5 with 2-propyn-1-ol leads to the α,β-unsaturated hydroxycarbene complex [Ru-(η5-C5H5){C(OH)CH=CH 2}(CO)(PPri 3)]BF4 (12). Similarly to 10, 12 is converted into [Ru-(η5-C5H5){C(O)CH=CH 2}(CO)(PPri 3)] (13), when the solutions of 12 are passed through an Al2O3 column. Treatment of 5 with 1-ethynyl-1-cyclohexanol leads to a mixture of organometallic compounds including [Ru(η5-C5H5){C(OH)CH=C(CH2) 4CH2}(CO)(PPri 3)]BF4 (14). Chromatography of the mixture affords [Ru(η5-C5H5){C(O)CH=C(CH2) 4CH2}(CO)-(PPri 3)] (15) and [Ru(η5-C5H5){C≡CC=CH(CH 2)3CH2}(CO)(PPri 3)] (16). 9 reacts with alcohols and thiols to give [Ru(η5-C5H5){C(ER)CH=CPh 2}(CO)(PPri 3)]BF4 (ER = OMe (17), OEt (18), SPrn (21)), which by treatment with NaOMe afford [Ru(η5-C5H5){C(ER)=C=CPh 2}(CO)-(PPri 3)] (ER = OMe (19), OEt (20), SPrn (22)). Similarly, the reaction of 9 with benzophenone imine leads to [Ru(η5-C5H5){C(CH=CPh 2)=N=CPh2}(CO)(PPri 3)]BF4 (23), which by reaction with NaOMe gives [Ru(η5-C5H5){C(N=CPh 2)=C=CPh2}(CO)(PPri 3)] (24). The structure of 23 was also determined by an X-ray investigation. The C=N bond lengths are 1.283(9) and 1.252(9) Å, while the C-N-C angle is 149.9(6)°.We thank the DGICYT (Project PB-95-0806, Programa de Promoción General del Conocimiento) and the EU (European Union) (Project: Selective Processes and Catalysis Involving Small Molecules) for financial support.Peer Reviewe

Los corderos se pesan solos. Báscula de autopesaje para la selección ovina por capacidad maternal

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Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients

Abnormal Characterization and Distribution of Circulating Regulatory T Cells in Patients with Chronic Spinal Cord Injury According to the Period of Evolution

Spinal cord injury (SCI) is a progressive and complex neurological disorder accompanied by multiple systemic challenges. Peripheral immune dysfunction is a major event occurring after SCI, especially in its chronic phase. Previous works have demonstrated significant changes in different circulating immune compartments, including in T cells. However, the precise characterization of these cells remains to be fully unraveled, particularly when considering important variants such as the time since the initial injury. In the present work, we aimed to study the level of circulating regulatory T cells (Tregs) in SCI patients depending on the duration of evolution. For this purpose, we studied and characterized peripheral Tregs from 105 patients with chronic SCI using flow cytometry, with patients classified into three major groups depending on the time since initial injury: short period chronic (SCI-SP, <5 years since initial injury); early chronic (SCI-ECP, from 5–15 years post-injury) and late chronic SCI (SCI-LCP, more than 15 years post-injury. Our results show that both the SCI-ECP and SCI-LCP groups appeared to present increased proportions of CD4+ CD25+/low Foxp3+ Tregs in comparison to healthy subjects, whereas a decreased number of these cells expressing CCR5 was observed in SCI-SP, SCI-ECP, and SCI-LCP patients. Furthermore, an increased number of CD4+ CD25+/high/low Foxp3 with negative expression of CD45RA and CCR7 was observed in SCI-LCP patients when compared to the SCI-ECP group. Taken together, these results deepen our understanding of the immune dysfunction reported in chronic SCI patients and how the time since initial injury may drive this dysregulation

Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers

Chronic venous disease (CVD) is a common vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs. Pregnancy is a high-risk situation for developing CVD. Approximately a third of the women will develop this condition during pregnancy, and similarly to arterial hypertensive disorders, previous evidence has described a plethora of alterations in placental structure and function in women with pregnancy-induced CVD. It is widely known that arterial-induced placenta dysfunction is accompanied by an important immune system alteration along with increased inflammatory markers, which may provide detrimental consequences for the women and their offspring. However, to our knowledge, there are still no data collected regarding cytokine profiling in women with pregnancy-induced CVD. Thus, the aim of the present work was to examine cytokine signatures in the serum of pregnant women (PW) with CVD and their newborns (NB). This study was conducted through a multiplex technique in 62 PW with pregnancy-induced CVD in comparison to 52 PW without CVD (HC) as well as their NB. Our results show significant alterations in a broad spectrum of inflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α, and MIP-1β). Overall, we demonstrate that pregnancy-induced CVD is associated with a proinflammatory environment, therefore highlighting the potentially alarming consequences of this condition for maternal and fetal wellbeing

Glycemic variability and all-cause mortality in a large prospective southern European cohort of patients with differences in glycemic status

Background Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). Methods Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. Results A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26–1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15–1.73); T2DM, HR = 1.36 (1.10–1.67). Conclusion We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia