A Systematic Review and Meta-Analysis of the Inflammatory Biomarkers in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite its high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI has been previously provided. Thus, this systematic review and meta-analysis aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. In this regard, eight studies comprising 1184 individuals were selected. Thus, it was shown that the increase in IL-6, TNF-α, and IL-1ß plasma levels could be implicated in the development of early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

Vitamin B12 Ameliorates Pesticide-Induced Sociability Impairment in Zebrafish (Danio rerio): A Prospective Controlled Intervention Study.

Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component plays an important part in determining the overall picture. Moreover, the lack of therapies to relieve existing symptoms complicates the fight against this condition. As a result, animal models have been used to make biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, followed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function nerve tissue, and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes is recognized for its help against free radicals. To investigate the effect of vit. B12, fish were divided into four different groups and exposed to a pesticide mixture (600 µg L-1 fipronil + 600 µg L-1 pyriproxyfen) and 0.24 µg L-1 vit. B12 for 14 days. The impact of the compounds was assessed daily with EthoVision XT 11.5 software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. The results showed significant improvements in locomotor activity parameters and a positive influence of the vitamin on sociability. Regarding the state of oxidative stress, high activity was found for SOD and GPx in the case of vit. B12, while fish exposed to the mixture of pesticides and vit. B12 had a lower level of MDA. In conclusion, the study provides new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and support the function of the organism.

Cashew (Anacardium occidentale) Extract: Possible Effects on Hypothalamic-Pituitary-Adrenal (HPA) Axis in Modulating Chronic Stress.

Depression presents a significant global health burden, necessitating the search for effective and safe treatments. This investigation aims to assess the antidepressant effect of the hydroethanolic extract of Anacardium occidentale (AO) on depression-related behaviors in rats. The depression model involved 42 days of unpredictable chronic mild stress (UCMS) exposure and was assessed using the sucrose preference and the forced swimming (FST) test. Additionally, memory-related aspects were examined using the tests Y-maze and Morris water maze (MWM), following 21 days of treatment with varying doses of the AO extract (150, 300, and 450 mg/kg) and Imipramine (20 mg/kg), commencing on day 21. The monoamines (norepinephrine, serotonin, and dopamine), oxidative stress markers (MDA and SOD), and cytokines levels (IL-1ß, IL-6, and TNF-α) within the brain were evaluated. Additionally, the concentration of blood corticosterone was measured. Treatment with AO significantly alleviated UCMS-induced and depressive-like behaviors in rats. This was evidenced by the ability of the extract to prevent further decreases in body mass, increase sucrose consumption, reduce immobility time in the test Forced Swimming, improve cognitive performance in both tests Y-maze and the Morris water maze by increasing the target quadrant dwelling time and spontaneous alternation percentage, and promote faster feeding behavior in the novelty-suppressed feeding test. It also decreased pro-inflammatory cytokines, corticosterone, and MDA levels, and increased monoamine levels and SOD activity. HPLC-MS analysis revealed the presence of triterpenoid compounds (ursolic acid, oleanolic acid, and lupane) and polyphenols (catechin quercetin and kaempferol). These results evidenced the antidepressant effects of the AO, which might involve corticosterone and monoaminergic regulation as antioxidant and anti-inflammatory activities.

Exploring the Potential of Exosomal Biomarkers in Mild Traumatic Brain Injury and Post-Concussion Syndrome: A Systematic 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 (Aß), 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.

Mild Traumatic Brain Injury as a Risk Factor for Parkinsonism, Tics, and Akathisia: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was conducted using PubMed, Embase, and Cochrane Library databases. Studies were eligible if they reported on the association between MTBI and Parkinsonism. Pooled odds ratios (ORs) were calculated using a random-effects model. Publication bias was assessed using Egger's and Begg's tests. A total of 18 studies were included in this meta-analysis, with 1,484,752 participants. The overall OR for Parkinsonism in individuals with a history of mTBI was 1.637 (95% CI, 1.203-2.230; p = 0.01), indicating a significant association. The OR for Parkinson's disease (PD) specifically was 1.717 (95% CI, 1.206-2.447; p = 0.01). However, insufficient data on tics and akathisia limited a meta-analysis. There was no evidence of publication bias according to Egger's (p = 0.8107) and Begg's (p = 0.4717) tests. This meta-analysis provides evidence that mTBI is a significant risk factor for Parkinsonism, particularly PD. However, the findings should be interpreted with caution due to the heterogeneity among the studies included and the study's limitations. Further research is needed to confirm these findings and to investigate the underlying mechanisms of the mTBI-Parkinsonism association.

Correlation between Carbonic Anhydrase Isozymes and the Evolution of Myocardial Infarction in Diabetic Patients.

(1) Background: Myocardial infarction was, until recently, recognized as a major coronary event, often fatal, with major implications for survivors. According to some authors, diabetes mellitus is an important atherogenic risk factor with cardiac determinations underlying the definition of the so-called "diabetic heart". The present study aims to establish a correlation between the evolution of myocardial infarction in diabetic patients, by determining whether lactic acid levels, the activity of carbonic anhydrase isoenzymes, and the magnitude of ST-segment elevation are correlated with the subsequent evolution of myocardial infarction. (2) Methods: The study analyzed 2 groups of 30 patients each: group 1 consisted of diabetic patients with acute myocardial infarction, and group 2 consisted of non-diabetic patients with acute myocardial infarction. Patients were examined clinically and paraclinical, their heart markers, lactic acid, and the activity of carbonic anhydrase I and II isozymes were determined. All patients underwent electrocardiogram and echocardiography analyses. (3) Results: The results showed that diabetics develop acute myocardial infarction more frequently, regardless of how much time has passed since the diagnosis. The value of myocardial necrosis enzymes was higher in diabetics than in non-diabetics, and acute coronary syndrome occurs mainly in diabetics with poor metabolic balance. Lethality rates in non-diabetic patients with lactic acid values above normal are lower than in diabetics. (4) Conclusions: Lactic acid correlated with the activity of isozyme I of carbonic dioxide which could be early markers of the prognosis and evolution of diabetic patients with acute myocardial infarction.

Comparative Study of Cytokine Storm Treatment in Patients with COVID-19 Pneumonia Using Immunomodulators.

(1) Background: In patients hospitalized with COVID-19 pneumonia, especially moderate and severe forms, a cytokine storm may occur, characterized by the worsening of symptoms and the alteration of biological parameters on days 8-12 of the disease. The therapeutic options for cytokine storms are still controversial, requiring further clarification; (2) Methods: Our study included 344 patients with moderate and severe pneumonia admitted to the internal medicine department who developed a cytokine storm (diagnosed by clinical and biochemical criteria). In group A, 149 patients were treated with Remdesivir and Tocilizumab (together with other drugs, including corticosteroids, antibiotics and anticoagulants), and in group B, 195 patients received Remdesivir and Anakinra. Patients were monitored clinically and by laboratory tests, with the main biochemical parameters being CRP (C-reactive protein), LDH (lactic dehydrogenase) and ferritin; (3) Results: Patients were followed up from a clinical point of view and also by the measurement of CRP, LDH and ferritin at the beginning of therapy, on days three to four and on the tenth day. In both groups, we registered a clinical improvement and a decrease in the parameters of the cytokine storm. In group A, with the IL-6 antagonist Tocilizumab, the beneficial effect occurred faster; in group B, with the IL-1 antagonist Anakinra, the beneficial effect was slower. (4) Conclusions: The use of the immunomodulators, Tocilizumab and Anakinra, in the cytokine storm showed favorable effects, both clinical and biochemical.

Biocomposite Hydrogels for the Treatment of Bacterial Infections: Physicochemical Characterization and In Vitro Assessment.

Hydrogels based on natural and synthetic polymers and inorganic nanoparticles proved to be a viable strategy in the fight against some Gram-positive and Gram-negative bacteria. Additionally, numerous studies have demonstrated the advantages of using ZnO nanoparticles in medicine due to their high antibacterial efficacy and relatively low cost. Consequently, the purpose of our study was to incorporate ZnO nanoparticles into chitosan/poly (vinyl alcohol)-based hydrogels in order to obtain a biocomposite with antimicrobial properties. These biocomposite hydrogels, prepared by a double crosslinking (covalent and ionic) were characterized from a structural, morphological, swelling degree, and mechanical point of view. FTIR spectroscopy demonstrated both the apparition of new imine and acetal bonds due to covalent crosslinking and the presence of the sulfate group following ionic crosslinking. The morphology, swelling degree, and mechanical properties of the obtained hydrogels were influenced by both the degree of covalent crosslinking and the amount of ZnO nanoparticles incorporated. In vitro cytotoxicity assessment showed that hydrogels without ZnONPs are non-cytotoxic while the biocomposite hydrogels are weak (with 3% ZnONPs) or moderately (with 4 and 5% ZnONPs) cytotoxic. Compared to nanoparticle-free hydrogels, the biocomposite hydrogels show significant antimicrobial activity against S. aureus, E. coli, and K. pneumonia.

Evaluation of Hepatic Biochemical Parameters during Antiviral Treatment in COVID-19 Patients.

(1) Background: The antiviral treatment for COVID-19 disease started to be largely used in 2020 and has been found to be efficient, although it is not specific for SARS-CoV-2 virus. There were some concerns that it may produce liver damage or other side effects. (2) Methods: The aim of this study was to observe if antiviral therapy is affecting liver parameters or producing other side-effects in patients hospitalized for COVID-19 disease. The study included a group of patients hospitalized in the internal medicine department of Oradea Municipal Clinical Hospital, Romania, between August 2020-June 2021, diagnosed with SARS-CoV-2 viral infection by RT-PCR method or rapid antigen test. During hospitalization, patients were treated with a Lopinavir/Ritonavir (Kaletra) combination, or with Favipiravir or Remdesivir. In addition to monitoring the evolution of the disease (clinical and biochemical), also hepatic parameters were analyzed at admission, during hospitalization, and at discharge. (3) Results: In the group of studied patients, the mean value of aspartat aminotrensferase did not increase above normal at discharge, alanin aminotransferase increased, but below twice the normal values, and cholestasis registered a statistically insignificant slight increase. (4) Conclusions: In our study, we found that all three antivirals were generally well tolerated and their use did not alter liver function in a significant manner.