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Sports Medicine - Open Jan 2024Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical...
BACKGROUND
Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure.
OBJECTIVE
This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research.
METHODS
PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality.
RESULTS
Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers-such as NfL-appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport.
CONCLUSION
Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers' utility.
PubMed: 38270708
DOI: 10.1186/s40798-023-00665-6 -
Journal of Personalized Medicine Dec 2023Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a... (Review)
Review
BACKGROUND
Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. In this study, we aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS.
METHODS
A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic.
RESULTS
The analyzed studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS as well as repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS.
CONCLUSION
Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.
PubMed: 38248736
DOI: 10.3390/jpm14010035 -
The Journal of Prevention of... 2024In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-β plaques... (Review)
Review
In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-β plaques and phosphorylation of tau-tangles. A rather recently considered risk factor for the onset of Alzheimer's disease is poor oral health. The aim of this systematic review of the literature was to assess the potential association(s) of oral health as a risk factor for the onset of Alzheimer's disease. After a systematic search of Pubmed, Embase and Web of Science. A total of 1962 studies were assessed, of which 17 studies demonstrated possible associations between oral health diseases and Alzheimer's disease. 4 theories could be distinguished that describe the possible links between oral health and the development or onset of Alzheimer's disease; 1) role of pathogens, 2) role of inflammatory mediators, 3) role of APOE alleles and 4) role of Aβ peptide. The main common denominator of all the theories is the neuroinflammation due to poor oral health. Yet, there is insufficient evidence to prove a link due to the diversity of the designs used and the quality of the study design of the included studies. Therefore, further research is needed to find causal links between oral health and neuroinflammation that possibly can lead to the onset of Alzheimer's disease with the future intention to prevent cognitive decline by better dental care.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Neuroinflammatory Diseases; Oral Health; Risk Factors
PubMed: 38230738
DOI: 10.14283/jpad.2023.82 -
International Journal of Molecular... Dec 2023Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria... (Review)
Review
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from HS and NH. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestinal Mucosa; Mitochondria
PubMed: 38069446
DOI: 10.3390/ijms242317124 -
Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.American Journal of Physiology.... Apr 2024Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS), older adults, Parkinson's disease, overweight, postmenopausal prediabetes, and Alzheimer's disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity, and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NADs use are muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters (e.g., a decrease in anxiety, maximum heart rate, inflammatory cytokines in serum, and cerebrospinal fluid). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.
Topics: Humans; Aged; Quality of Life; Fatigue Syndrome, Chronic; NAD; Dietary Supplements
PubMed: 37971292
DOI: 10.1152/ajpendo.00242.2023 -
Frontiers in Pharmacology 2023Intravenous thrombolysis is commonly used in the treatment of acute ischemic stroke damage. The existing thrombolytic drugs still suffer significant shortcomings,...
Intravenous thrombolysis is commonly used in the treatment of acute ischemic stroke damage. The existing thrombolytic drugs still suffer significant shortcomings, including a limited fibrin specificity and bleeding complications. Ferulic acid can directly bind the key thrombus enzymes and target to blood clots, suggesting its thrombolytic potency that may be beneficial with thrombolytic potency for the treatment of acute ischemic stroke damage. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ferulic acid in the treatment of acute ischemic stroke injury in rats and its potential mechanism of action. We conducted a literature search in six databases, including CNKI, up to July 2023. Sixteen trials were included in the meta-analysis, which demonstrated that ferulic acid significantly reduced infarct size, neurological deficit score, apoptosis index, cleaved caspase-3, and cytochrome C levels (all < 0.05). In addition, ferulic acid significantly increased the levels of phosphorylated Akt, mitochondrial Bcl-xL/Bax, phosphorylated astrocyte PEA15, hippocampal calcium binding protein, and mitochondrial Bcl-2/Bax ratio (all < 0.05). This study demonstrates that ferulic acid protects against acute ischemic stroke injury in rats by inhibiting ischemia-induced excitotoxicity, inflammatory response, and apoptosis.
PubMed: 37927604
DOI: 10.3389/fphar.2023.1278036 -
Journal of Alzheimer's Disease : JAD 2023The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described.
BACKGROUND
The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described.
OBJECTIVE
This systematic review aimed to gather the current understanding of the pathophysiological mechanisms linking periodontitis to AD.
METHODS
An electronic systematic search of the PubMed/MEDLINE, Scopus, and Embase databases was performed using the following PECO question: How can periodontitis or periodontal bacteria influence Alzheimer's disease features?". Only preclinical studies exploring the biological links between periodontitis and AD pathology were included. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and the Syrcle and Camarades protocols were used to assess the risk of bias.
RESULTS
After a systematic screening of titles and abstracts (n = 3,307), thirty-six titles were selected for abstract reading, of which 13 were excluded (k = 1), resulting in the inclusion of 23 articles. Oral or systemic exposure to periodontopathogens or their byproducts is responsible for both in situ brain manifestations and systemic effects. Significant elevated rates of cytokines and amyloid peptides (Aβ) and derivate products were found in both serum and brain. Additionally, in infected animals, hyperphosphorylation of tau protein, hippocampal microgliosis, and neuronal death were observed. Exposure to periodontal infection negatively impairs cognitive behavior, leading to memory decline.
CONCLUSIONS
Systemic inflammation and brain metastatic infections induced by periodontal pathogens contribute to neuroinflammation, amyloidosis, and tau phosphorylation, leading to brain damage and subsequent cognitive impairment.
Topics: Animals; Alzheimer Disease; Systematic Reviews as Topic; Periodontitis; Inflammation; Cognitive Dysfunction
PubMed: 37927257
DOI: 10.3233/JAD-230478 -
The role of CEACAMs versus integrins in Helicobacter pylori CagA translocation: a systematic review.Microbes and Infection 2024The delivery of Helicobacter pylori CagA into host cells was long believed to occur through the integrin cell surface receptors. However, the role of CEACAM receptors...
The delivery of Helicobacter pylori CagA into host cells was long believed to occur through the integrin cell surface receptors. However, the role of CEACAM receptors has recently been highlighted, instead. Here, we have categorized the existing experimental evidence according to whether deletion, upregulation, downregulation, or inhibition of the target ligands (T4SS or HopQ) or receptors (integrins or CEACAMs), result in alterations in CagA phosphorylation, cell elongation, or IL-8 production. According to our analysis, the statistics favor the essence of most of the T4SS constituents and the involvement of HopQ adhesin in all three functions. Concerning the integrin family, the collected data is controversial, but yielding towards it being dispensable or involved in CagA translocation. Yet, regarding cell elongation, more events are showing β1 integrin being involved, than αvβ4 being inhibitory. Concerning IL-8 secretion, again there are more events showing α5, β1 and β6 integrins to be involved, than those showing inhibitory roles for β1, β4 and β6 integrins. Finally, CEACAM 1, 3, and 5 are identified as mostly essential or involved in CagA phosphorylation, whereasCEACAM 4, 7, and 8 are found dispensable and CEACAM6 is under debate. Conversely, CEACAM1, 5 and 6 appear mostly dispensable for cell elongation. Noteworthy is the choice of cell type, bacterial strain, multiplicity and duration of infection, as well as the sensitivity of the detection methods, all of which can affect the variably obtained results.
Topics: Humans; Bacterial Proteins; Integrins; Antigens, Bacterial; Helicobacter pylori; Interleukin-8; Helicobacter Infections
PubMed: 37926369
DOI: 10.1016/j.micinf.2023.105246 -
Naunyn-Schmiedeberg's Archives of... Apr 2024The potential benefits of adiponectin replacement therapy extend to numerous human diseases, with current research showing particular interest in its effectiveness... (Review)
Review
The potential benefits of adiponectin replacement therapy extend to numerous human diseases, with current research showing particular interest in its effectiveness against specific cancer forms, especially hormone-related. However, limitations in the pharmacological use of the intact protein have led to a focus on alternative options. AdipoRon is an extensively studied non-peptidic drug candidate for adiponectin replacement therapy. While researchers have explored the efficacy and therapeutic applications of AdipoRon in various disease conditions, their effects against cancer models advanced more, with no review regarding AdipoRon's efficacy against hormone-related cancers being published. The present systematic review aims to fill this gap. Preclinical evidence was compiled from PubMed, EMBASE, COCHRANE, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the manuscript's quality assessment was conducted using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews' Quality. The included nine studies incorporated various cell and animal models of the pancreas, gynaecological system, and osteosarcoma cancers. AdipoRon demonstrated effectiveness against pancreatic cancer by activating p44/42 MAPK, mitochondrial dysfunction, and AMPK-mediated inhibition of ACC1. In gynaecological cancers, it exhibited promising anticancer effects through the activation of AMPK, potential inhibition of mTOR, and modulation of the SET1B/BOD1/AdipoR1 signaling cascade. Against osteosarcoma, AdipoRon worked by perturbing ERK1/2 signaling and reducing p70S6K phosphorylation. AdipoRon shows promise in preclinical studies, but human trials are crucial for clinical safety and effectiveness. Caution is needed due to potential off-target effects, especially in cancer therapy with multi-target approaches. Structural biology and computational methods can help predict these effects.
Topics: Animals; Humans; Adiponectin; AMP-Activated Protein Kinases; Logic; Osteosarcoma; Piperidines
PubMed: 37864589
DOI: 10.1007/s00210-023-02792-z -
Advances in Clinical Chemistry 2023There is a need for blood biomarkers to detect individuals at different Alzheimer's disease (AD) stages because obtaining cerebrospinal fluid-based biomarkers is...
There is a need for blood biomarkers to detect individuals at different Alzheimer's disease (AD) stages because obtaining cerebrospinal fluid-based biomarkers is invasive and costly. Plasma phosphorylated tau proteins (p-tau) have shown potential as such biomarkers. This systematic review was conducted according to the PRISMA guidelines and aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181), threonine 217 (p-tau217) and threonine 231 (p-tau231) is informative in the diagnosis of AD. All p-tau isoforms increase as a function of Aβ-accumulation and discriminate healthy individuals from those at preclinical AD stages with high accuracy. P-tau231 increases earliest, followed by p-tau181 and p-tau217. In advanced stages, all p-tau isoforms are associated with the clinical classification of AD and increase with disease severity, with the greatest increase seen for p-tau217. This is also reflected by a better correlation of p-tau217 with Aβ scans, whereas both, p-tau217 and p-tau181 correlated equally with tau scans. However, at the very advanced stages, p-tau181 begins to plateau, which may mirror the trajectory of the Aβ pathology and indicate an association with a more intermediate risk of AD. Across the AD continuum, the incremental increase in all biomarkers is associated with structural changes in widespread brain regions and underlying cognitive decline. Furthermore, all isoforms differentiate AD from non-AD neurodegenerative disorders, making them specific for AD. Incorporating p-tau181, p-tau217 and p-tau231 in clinical use requires further studies to examine ideal cut-points and harmonize assays.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Protein Isoforms; tau Proteins; Threonine
PubMed: 37852722
DOI: 10.1016/bs.acc.2023.05.001