Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke

2021 ◽  
pp. 0271678X2110008
Author(s):  
Cellas A Hayes ◽  
M Noa Valcarcel-Ares ◽  
Nicole M Ashpole
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
The Elderly ◽  
Clinical Settings ◽  
Mortality And Morbidity ◽  
Routes Of Administration ◽  
Insulin Growth Factor ◽  
Cellular Processes ◽  
Preclinical Animal Models

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.

scholarly journals Approaching 3R teaching in biomedical engineering

2020 ◽  
Author(s):  
Valeria Chiono
Keyword(s):  
Animal Models ◽  
Biomedical Engineering ◽  
Experimental Models ◽  
Preclinical Testing ◽  
Preclinical Trials ◽  
European Standards ◽  
Preclinical Animal Models ◽  
In Silico Models

Since its adhesion to Centro3R, Politecnico di Torino has approached 3R teaching through a new Master course, entitled “New advances in alternative preclinical trials”. This is a multidisciplinary optional course for Master students in Biomedical Engineering, with the contribution of different teachers, who are experts on different aspects of preclinical testing of biomedical devices: European Standards for preclinical experimentation; preclinical animal models; protection of animal welfare in the European legislation; the role of statistics on the application of the 3R principle; preclinical experimental models in vitro; in silico models. This contribution describes the subjects faced by the course and their importance in the context of the 3R Principle.

Role of DAMPs and of Leukocytes Infiltration in Ischemic Stroke: Insights from Animal Models and Translation to the Human Disease

2020 ◽  
Author(s):  
Rosita Stanzione ◽  
Maurizio Forte ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
Human Disease

scholarly journals Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 682 ◽  
Author(s):  
Francesca Citron ◽  
Linda Fabris
Keyword(s):  
Patient Outcomes ◽  
Chromatin Remodeling ◽  
Cancer Biology ◽  
Poor Prognosis ◽  
Molecular Medicine ◽  
Genomic Alteration ◽  
Clinical Settings ◽  
Cellular Processes ◽  
Improve Patient

Extensive efforts recently witnessed the complexity of cancer biology; however, molecular medicine still lacks the ability to elucidate hidden mechanisms for the maintenance of specific subclasses of rare tumors characterized by the silent onset and a poor prognosis (e.g., ovarian cancer, pancreatic cancer, and glioblastoma). Recent mutational fingerprints of human cancers highlighted genomic alteration occurring on epigenetic modulators. In this scenario, the epigenome dependency of cancer orchestrates a broad range of cellular processes critical for tumorigenesis and tumor progression, possibly mediating escaping mechanisms leading to drug resistance. Indeed, in this review, we discuss the pivotal role of chromatin remodeling in shaping the tumor architecture and modulating tumor fitness in a microenvironment-dependent context. We will also present recent advances in the epigenome targeting, posing a particular emphasis on how this knowledge could be translated into a feasible therapeutic approach to individualize clinical settings and improve patient outcomes.

scholarly journals Predictors of Medication Adherence in the Elderly: The Role of Mental Health

2017 ◽  
Vol 75 (6) ◽  
pp. 746-761 ◽  
Author(s):  
Jo E. Rodgers ◽  
Emily M. Thudium ◽  
Hadi Beyhaghi ◽  
Carla A. Sueta ◽  
Khalid A. Alburikan ◽  
...  
Keyword(s):  
Mental Health ◽  
Medication Adherence ◽  
Reading Ability ◽  
The Elderly ◽  
Clinical Settings ◽  
Atherosclerosis Risk In Communities ◽  
Optimal Outcomes ◽  
Poor Memory ◽  
Lower Adherence

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky–Green–Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence.

Protein degradation: a validated therapeutic strategy with exciting prospects

2017 ◽  
Vol 61 (5) ◽  
pp. 517-527 ◽  
Author(s):  
Honorine Lebraud ◽  
Tom D. Heightman
Keyword(s):  
Animal Models ◽  
Protein Degradation ◽  
Small Molecules ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Therapeutic Strategy ◽  
Substrate Recognition ◽  
Pharmacological Targets ◽  
Preclinical Animal Models

In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified through genetic knockdown. Targeted protein degradation holds the potential to expand the range of proteins that can be effectively modulated. Drugs inducing protein degradation through misfolding or by modulating cereblon (CRBN) substrate recognition are already approved for treatment of cancer patients. The last decade has seen the development of proteolysis targeting chimeras (PROTACs), small molecules that elicit proteasomal degradation by causing protein polyubiquitination. These have been used to degrade a range of disease-relevant proteins in cells, and some show promising efficacy in preclinical animal models, although their clinical efficacy and tolerability is yet to be proven. This review introduces current strategies for protein degradation with an emphasis on PROTACs and the role of click chemistry in PROTAC research through the formation of libraries of preclicked PROTACs or in-cell click-formed PROTACs (CLIPTACs).

scholarly journals The central role of T-cell memory in Alzheimer’s disease vaccination

2010 ◽  
Vol 1 (1) ◽  
pp. 5
Author(s):  
Brian Giunta ◽  
Amanda Ruscin ◽  
Jon Salemi ◽  
Alan Wolfson ◽  
Francisco Fernandez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cell ◽  
Animal Models ◽  
The Elderly ◽  
Active Immunization ◽  
T Cell Subsets ◽  
Neurocognitive Deficits ◽  
Cell Reactivity

Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disease as well as the most common dementia among the elderly. In the future as the average lifespan continues to extend, the number of AD patients will continue to grow. Amyloid-beta (Aβ) peptides, in both soluble oligomeric, and insoluble forms, are key in the neuropathogenesis of AD and have thus been a therapeutic target for vaccines. Multiple Aβ vaccination strategies in animal models of AD have demonstrated a marked reduction in both amyloid burden and neurocognitive deficits. Due to the success of these studies, initial human clinical trials of an active Aβ vaccine were conducted. These were discontinued due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Studies examining the brains of Aβ-vaccinated patients developing meningoencephalitis implicate Aβ-reactive T-cell subsets as major components of this deleterious response to active Aβ vaccination. To subvert possible meningoencephalitis resulting from Aβ vaccination second generation of vaccines has been more recently developed. These however have met with little success in humans. To build on these findings, an understanding of the role of T-cells in vaccination against Aβ is presented in this review. Various methods of Aβ immunotherapy are reviewed including studies in both animal models and humans. Recent works suggest that Aβ-derived peptides delivered intranasally or transcutaneously results in effective clearance of Aβ plaques and improvement of cognitive function in animal models of AD. Moreover, undesired T-cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In spite of the past clinical studies, these findings imply that Aβ vaccination may be both efficacious and safe depending route of delivery, adjuvant choice, and Aβ epitope administered.

scholarly journals Prevention of Preterm Birth with Progesterone

2021 ◽  
Vol 10 (19) ◽  
pp. 4511
Author(s):  
Gian Carlo Di Renzo ◽  
Valentina Tosto ◽  
Valentina Tsibizova ◽  
Eduardo Fonseca
Keyword(s):  
Preterm Birth ◽  
Critical Factor ◽  
Public Health Issue ◽  
Clinical Settings ◽  
Main Determinant ◽  
Mortality And Morbidity ◽  
Routes Of Administration ◽  
Positive Effects ◽  
Junction Formation ◽  
Gestational Age At Birth

Gestational age at birth is a critical factor for perinatal and adulthood outcomes, and even for transgenerational conditions’ effects. Preterm birth (PTB) (prematurity) is still the main determinant for infant mortality and morbidity leading cause of infant morbidity and mortality. Unfortunately, preterm birth (PTB) is a relevant public health issue worldwide and the global PTB rate is around 11%. The premature activation of labor is underlined by complex mechanisms, with a multifactorial origin influenced by numerous known and probably unknown triggers. The possible mechanisms involved in a too early labor activation have been partially explained, and involve chemokines, receptors, and imbalanced inflammatory paths. Strategies for the early detection and prevention of this obstetric condition were proposed in clinical settings with interesting results. Progesterone has been demonstrated to have a key role in PTB prevention, showing several positive effects, such as lower prostaglandin synthesis, the inhibition of cervical stromal degradation, modulating the inflammatory response, reducing gap junction formation, and decreasing myometrial activation. The available scientific knowledge, data and recommendations address multiple current areas of debate regarding the use of progesterone in multifetal gestation, including different formulations, doses and routes of administration and its safety profile in pregnancy.

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