Alzheimer's disease (AD) is a degenerative cognitive condition that affects individuals with an increasing prevalence in older age groups. There are currently five drugs on the market for AD but no ...new effective ones have been discovered for decades. There has been increasing interest in the use of natural remedies such as special diets and plant extracts but these require further study. Based on the known effects on white matter and neuronal conductance in Alzheimer's disease, we present a protocol for proteomic analysis of myelin-enriched brain fractions as a way of identifying potential biomarkers of efficacy. This fingerprint could be used in screening assays for novel compounds for treatment of AD.
Neuroimmune biomarkers in schizophrenia Tomasik, Jakub; Rahmoune, Hassan; Guest, Paul C ...
Schizophrenia research,
09/2016, Letnik:
176, Številka:
1
Journal Article
Recenzirano
Abstract Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of clinical and biological manifestations. Due to the lack of objective tests, the accurate diagnosis and ...selection of effective treatments for schizophrenia remains challenging. Numerous technologies have been employed in search of schizophrenia biomarkers. These studies have suggested that neuroinflammatory processes may play a role in schizophrenia pathogenesis, at least in a subgroup of patients. The evidence indicates alterations in both pro- and anti-inflammatory molecules in the central nervous system, which have also been found in peripheral tissues and may correlate with schizophrenia symptoms. In line with these findings, certain immunomodulatory interventions have shown beneficial effects on psychotic symptoms in schizophrenia patients, in particular those with distinct immune signatures. In this review, we evaluate these findings and their potential for more targeted drug interventions and the development of companion diagnostics. Although currently no validated markers exist for schizophrenia patient stratification or the prediction of treatment efficacy, we propose that utilisation of inflammatory markers for diagnostic and theranostic purposes may lead to novel therapeutic approaches and deliver more effective care for schizophrenia patients.
Abstract The past decade has witnessed an explosion of knowledge on the impact of glia for the neurobiological foundation of schizophrenia. A plethora of studies have shown structural and functional ...abnormalities in all three types of glial cells. There is convincing evidence of reduced numbers of oligodendrocytes, impaired cell maturation and altered gene expression of myelin/oligodendrocyte-related genes that may in part explain white matter abnormalities and disturbed inter- and intra-hemispheric connectivity, which are characteristic signs of schizophrenia. Earlier reports of astrogliosis could not be confirmed by later studies, although the expression of a variety of astrocyte-related genes is abnormal in psychosis. Since astrocytes play a key role in the synaptic metabolism of glutamate, GABA, monoamines and purines, astrocyte dysfunction may contribute to certain aspects of disturbed neurotransmission in schizophrenia. Finally, increased densities of microglial cells and aberrant expression of microglia-related surface markers in schizophrenia suggest that immunological/inflammatory factors are of considerable relevance for the pathophysiology of psychosis. This review describes current evidence for the multifaceted role of glial cells in schizophrenia and discusses efforts to develop glia-directed therapies for the treatment of the disease.
Despite the ongoing vaccination efforts, there is still an urgent need for safe and effective treatments to help curb the debilitating effects of COVID-19 disease. This systematic review aimed to ...investigate the efficacy of supplemental curcumin treatment on clinical outcomes and inflammation-related biomarker profiles in COVID-19 patients. We searched PubMed, Scopus, Web of Science, EMBASE, ProQuest, and Ovid databases up to 30 June 2021 to find studies that assessed the effects of curcumin-related compounds in mild to severe COVID-19 patients. Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths. In addition, all of these studies showed that the intervention led to amelioration of cytokine storm effects thought to be a driving force in severe COVID-19 cases. This was seen as a significant (
< 0.05) decrease in proinflammatory cytokines such as IL1β and IL6, with a concomitant significant (
< 0.05) increase in anti-inflammatory cytokines, including IL-10, IL-35 and TGF-α. Taken together, these findings suggested that curcumin exerts its beneficial effects through at least partial restoration of pro-inflammatory/anti-inflammatory balance. In conclusion, curcumin supplementation may offer an efficacious and safe option for improving COVID-19 disease outcomes. We highlight the point that future clinical studies of COVID-19 disease should employ larger cohorts of patients in different clinical settings with standardized preparations of curcumin-related compounds.
Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported ...after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.
Cancer is one of the most frequent causes of worldwide death and morbidity and is a major public health problem. Although, there are several widely used treatment methods including chemo-, immune- ...and radiotherapies, these mostly lack sufficient efficiency and induce toxicities in normal surrounding tissues. Thus, finding new approaches to mitigate side effects and potentially accelerate treatment is paramount. In line with this, increasing preclinical evidence indicates that caloric restriction (CR) and fasting might have anticancer effects by reducing tumor progression, enhancing death of cancer cells, and elevating the effectiveness and tolerability of chemo- and radiotherapies. Nonetheless, clinical studies assessing the potential of CR and fasting in cancer are scarce and inconsistent, and more investigations are still required to clarify their effect in different aspects of cancer treatment. In this review, we have summarized the findings of preclinical and clinical studies of CR and fasting with respect to efficacy and on the adverse effects of standard cancer treatments.
The Goto-Kakizaki (GK) rat is a model of type 2 diabetes mellitus, produced originally by selective inbreeding for a hyperglycemic trait. These rats are characterized as having insulin resistance and ...an insulin secretory defect. Pancreatic islets from these mice show abnormal morphology in the distribution of glucagon-secreting α cells and insulin-secreting β cells, which may affect paracrine functions involved in the secretory response. This chapter describes the characterization of GK rat islets using immunofluorescence microscopy and Western blot analyses to demonstrate the effects on islet architecture and how this translates to changes in expression of predominant islet proteins.
This chapter describes the application of two-dimensional gel electrophoresis (2DGE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the ...analysis of rat eye lens proteins. The main purpose was to identify proteins that may serve as potential biomarkers in age-related cataract formation. This includes the family of proteins known as the crystallins. Structural proteins and enzymes involved antioxidant activities. In addition, we also analyzed lenses from other species to illustrate the potential of using this technique in clinical and preclinical biomarker studies.
Cardiovascular-related accidents such as stroke are currently ranked as the second leading cause of death worldwide, and the risk of stroke increases dramatically with age. Aging results in ...structural and functional alterations of the oligodendrocytes which lead to loss of neuronal connectivity, cognitive deficits, and increased susceptibility to ischemic damage. Here, we have carried out proteomic profiling of MO3.13 oligodendrocyte cells following treatment with NMDA channel blocker MK-801 to increase our understanding of the mechanisms involved in brain aging, as well as those which render it more susceptible to ischemic damage. The main objective was to identify potential biomarkers which could be used to track disease or therapeutic effects.
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