scholarly journals Adolescent Social Isolation Increases Vulnerability to Cocaine

2018 ◽  
Author(s):  
Anne Q. Fosnocht ◽  
Kelsey E. Lucerne ◽  
Alexandra S. Ellis ◽  
Nicholas A. Olimpo ◽  
Lisa A. Briand
Keyword(s):  
Social Isolation ◽  
Molecular Mechanisms ◽  
Lateral Septum ◽  
Ratio Schedule ◽  
Operant Response ◽  
Self Administration ◽  
Male And Female ◽  
Targeted Interventions ◽  
Increased Risk ◽  
Wide Range

AbstractChildhood and adolescent adversity is associated with a wide range of psychiatric disorders, including an increased risk for substance abuse. Despite this, the molecular mechanisms underlying how chronic stress during adolescence alters reward signaling remains largely unexplored. Understanding how adolescent stress increases addiction-like phenotypes could inform the development of targeted interventions both before and after drug use. The current study examined how adolescent-onset isolation stress affected behavioral, molecular, and physiological responses to cocaine in male and female mice. Adolescent-onset social isolation did not alter the ability of mice to learn an operant response for food, nor influence food self-administration or motivation for food on a progressive ratio schedule. However, male and female socially stressed mice exhibited an increase in motivation for cocaine and cocaine seeking during a cue-induced reinstatement session. Additionally, we demonstrated that adolescent-onset social isolation increased cocaine-induced neuronal activation, as assessed by Fos expression, within the nucleus accumbens core and shell, ventral pallidum, dorsal bed nucleus of the stria terminalis, lateral septum and basolateral amygdala. Taken together, the present studies demonstrate that social stress during adolescence augments the behavioral responses to cocaine during adulthood and alters the responsiveness of reward-related brain circuitry.

scholarly journals Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

2021 ◽  
Author(s):  
Agnieszka Wnuk ◽  
Małgorzata Kajta
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Cells ◽  
Industrial Applications ◽  
Mammalian Brain ◽  
Human Environment ◽  
Developmental Abnormalities ◽  
Increased Risk ◽  
Wide Range ◽  
And Function

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

scholarly journals Mechanisms of Bone Metastasis of Malignancies of the Genito-Mammary Area

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 42
Author(s):  
R. Bohîlțea ◽  
N. Turcan ◽  
T.A. Georgescu ◽  
M.M. Cîrstoiu
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Molecular Mechanisms ◽  
Bone Matrix ◽  
Cell Activity ◽  
Hematopoietic Stem ◽  
Wnt Proteins ◽  
Increased Risk ◽  
Wide Range

Abstract Bone metastasis is a frequent complication of advanced genito-mammary cancer patients. Skeletal involvement is particularly common in breast cancer. Bone metastases induce a wide range of symptoms, lowering the quality of life and shortening survival. The normal bone remodeling process is deeply affected in all types of metastases: osteolytic, osteoblastic, and mixed. The main mechanisms involved in bone metastatic dissemination are the expression of adhesion tumor molecules and corresponding receptors within bone marrow and bone matrix cells; local growth factors, molecular mechanisms of remodeling the hematopoietic stem cell activity, and alteration of the expression of the post-transcriptional regulatory microRNAs of the gene expression are the new theories developed from recent studies. Abnormalities in the number of copies of the 16q23 gene explain the increased risk of bone metastasis of breast cancer compared to its dissemination to the other organs; the mutual interaction between tumor cells and the bone microenvironment constitutes the element that stimulates both bone destruction and tumor development. Endothelin -1, bone morphogenic proteins, platelet-derived growth factor, Wnt proteins stimulate proliferation and osteoblastic activity. Genomic and proteomic studies underlie the development of new therapeutic agents for the treatment and prevention of bone metastases.

scholarly journals Effect of Resveratrol on Metabolic Syndrome

2021 ◽  
Vol 6 (5) ◽  
pp. 408-413
Author(s):  
N. A. Markhon ◽  
◽  
V. М. Baibakov ◽  
V. A. Kosse ◽  
I. V. Lyulko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Wide Range ◽  
Prevention And Treatment

The purpose of the study is to analyze the sources of modern literature of domestic and foreign researchers on the prospects of resveratrol in the prevention and treatment of metabolic syndrome. Metabolic syndrome is a clinical manifestation characterized by many comorbidities, including hyperglycemia, abdominal obesity, hypertension, and dyslipidemia. All components of metabolic syndrome are involved in the induction of low-quality inflammation and oxidative stress, characteristic of this symptom complex. Metabolic syndrome is associated with an increased risk of cardiovascular disease and early mortality, which has a significant impact on health care costs. Finding an effective and alternative therapeutic strategy, which is natural and has no side effects, can be a useful tool in the fight against metabolic syndrome. This review focuses on the potential beneficial effects of a polyphenolic natural compound – resveratrol – on various molecular targets with programming for the development of disorders associated with metabolic syndrome and its comorbidities. A number of data on the effects of resveratrol on body weight, insulin sensitivity, glucose tolerance, lipid profile, blood pressure, oxidative stress indicate that this compound has a wide range of beneficial effects on human health, and also has a beneficial effect on metabolic syndrome. A numerous data on the improvement of homeostasis, glucose, lipids, fat reduction, blood pressure, oxidative stress may demonstrate how resveratrol may be useful in the prevention and treatment of metabolic syndrome and related disorders due to its anti-inflammatory, antiplatelet and antioxidant properties. Resveratrol can be used either early as a reprogramming agent or later as a part of the treatment of metabolic syndrome. A few of the main molecular mechanisms underlying the beneficial effects of resveratrol on metabolic syndrome are given in the article. Conclusion. Presented review of literature outlined the potential of resveratrol as supplementary or alternative medicine. Thus, resveratrol could be a useful regimen for the prevention and treatment of metabolic syndrome and its related conditions. The article considers some molecular level targets for resveratrol in terms of its effect on the metabolic syndrome, such as adenosine monophosphate-activated protein kinase, SIRT1 protein, the main switch of the cellular defense system (Nrf2), nuclear factor-kappa B, estrogen receptor and the like

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Developing Equations for Converting Digestible Energy to Metabolizable Energy for Korean Hanwoo Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1696
Author(s):  
Ridha Ibidhi ◽  
Rajaraman Bharanidharan ◽  
Jong-Geun Kim ◽  
Woo-Hyeong Hong ◽  
In-Sik Nam ◽  
...  
Keyword(s):  
Linear Regression ◽  
Beef Cattle ◽  
Strong Relationship ◽  
Dietary Factors ◽  
Metabolizable Energy ◽  
Coefficient Of Determination ◽  
Simple Linear Regression ◽  
Male And Female ◽  
Digestible Energy ◽  
Wide Range

This study was performed to update and generate prediction equations for converting digestible energy (DE) to metabolizable energy (ME) for Korean Hanwoo beef cattle, taking into consideration the gender (male and female) and body weights (BW above and below 350 kg) of the animals. The data consisted of 141 measurements from respiratory chambers with a wide range of diets and energy intake levels. A simple linear regression of the overall unadjusted data suggested a strong relationship between the DE and ME (Mcal/kg DM): ME = 0.8722 × DE + 0.0016 (coefficient of determination (R2) = 0.946, root mean square error (RMSE) = 0.107, p < 0.001 for intercept and slope). Mixed-model regression analyses to adjust for the effects of the experiment from which the data were obtained similarly showed a strong linear relationship between the DE and ME (Mcal/kg of DM): ME = 0.9215 × DE − 0.1434 (R2 = 0.999, RMSE = 0.004, p < 0.001 for the intercept and slope). The DE was strongly related to the ME for both genders: ME = 0.8621 × DE + 0.0808 (R2 = 0.9600, RMSE = 0.083, p < 0.001 for the intercept and slope) and ME = 0.7785 × DE + 0.1546 (R2 = 0.971, RMSE = 0.070, p < 0.001 for the intercept and slope) for male and female Hanwoo cattle, respectively. By BW, the simple linear regression similarly showed a strong relationship between the DE and ME for Hanwoo above and below 350 kg BW: ME = 0.9833 × DE − 0.2760 (R2 = 0.991, RMSE = 0.055, p < 0.001 for the intercept and slope) and ME = 0.72975 × DE + 0.38744 (R2 = 0.913, RMSE = 0.100, p < 0.001 for the intercept and slope), respectively. A multiple regression using the DE and dietary factors as independent variables did not improve the accuracy of the ME prediction (ME = 1.149 × DE − 0.045 × crude protein + 0.011 × neutral detergent fibre − 0.027 × acid detergent fibre + 0.683).

scholarly journals COVID-19 and Its Symptoms’ Panoply: A Case-Control Study of 919 Suspected Cases in Locked-Down Ovar, Portugal

2021 ◽  
pp. 1-8
Author(s):  
Regina Sá ◽  
Tiago Pinho-Bandeira ◽  
Guilherme Queiroz ◽  
Joana Matos ◽  
João Duarte Ferreira ◽  
...  
Keyword(s):  
Large Scale ◽  
Case Control Study ◽  
Statistical Significance ◽  
Case Control ◽  
Case Definition ◽  
Suspected Case ◽  
Risk Characteristics ◽  
Increased Risk ◽  
Wide Range ◽  
Control Study

<b><i>Background:</i></b> Ovar was the first Portuguese municipality to declare active community transmission of SARS-CoV-2, with total lockdown decreed on March 17, 2020. This context provided conditions for a large-scale testing strategy, allowing a referral system considering other symptoms besides the ones that were part of the case definition (fever, cough, and dyspnea). This study aims to identify other symptoms associated with COVID-19 since it may clarify the pre-test probability of the occurrence of the disease. <b><i>Methods:</i></b> This case-control study uses primary care registers between March 29 and May 10, 2020 in Ovar municipality. Pre-test clinical and exposure-risk characteristics, reported by physicians, were collected through a form, and linked with their laboratory result. <b><i>Results:</i></b> The study population included a total of 919 patients, of whom 226 (24.6%) were COVID-19 cases and 693 were negative for SARS-CoV-2. Only 27.1% of the patients reporting contact with a confirmed or suspected case tested positive. In the multivariate analysis, statistical significance was obtained for headaches (OR 0.558), odynophagia (OR 0.273), anosmia (OR 2.360), and other symptoms (OR 2.157). The interaction of anosmia and odynophagia appeared as possibly relevant with a borderline statistically significant OR of 3.375. <b><i>Conclusion:</i></b> COVID-19 has a wide range of symptoms. Of the myriad described, the present study highlights anosmia itself and calls for additional studies on the interaction between anosmia and odynophagia. Headaches and odynophagia by themselves are not associated with an increased risk for the disease. These findings may help clinicians in deciding when to test, especially when other diseases with similar symptoms are more prevalent, namely in winter.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

scholarly journals Changes in Health Behaviors, Mental and Physical Health among Older Adults under Severe Lockdown Restrictions during the COVID-19 Pandemic in Spain

2021 ◽  
Vol 18 (13) ◽  
pp. 7067
Author(s):  
Esther García-Esquinas ◽  
Rosario Ortolá ◽  
Iago Gine-Vázquez ◽  
José A. Carnicero ◽  
Asier Mañas ◽  
...  
Keyword(s):  
Mental Health ◽  
Physical Activity ◽  
Older Adults ◽  
Social Isolation ◽  
Community Dwelling ◽  
Housing Conditions ◽  
Older Individuals ◽  
Lifestyle Risk Factors ◽  
Increased Risk ◽  
Lifestyle Risk

We used data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain collected through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning of the COVID-19 lockdown. On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet, or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Males, older adults with greater social isolation or greater feelings of loneliness, those with poorer housing conditions, as well as those with a higher prevalence of chronic morbidities were at increased risk of developing unhealthier lifestyles or mental health declines with confinement. On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement. If another lockdown were imposed during this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, sub-optimal housing conditions, and chronic morbidities because of their greater vulnerability to the enacted movement restrictions.

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