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Journal of Trace Elements in Medicine... Jan 2024Cardiac surgeries are known to induce an inflammatory response. Besides, dietary factors such as trace elements contribute to promoting cardiovascular health by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac surgeries are known to induce an inflammatory response. Besides, dietary factors such as trace elements contribute to promoting cardiovascular health by maintaining oxidative balance. Here we systematically review the literature about alterations in serum concentrations of zinc (Zn), copper (Cu), and selenium (Se) in response to cardiac surgeries.
METHODS
A systematic search was performed on databases until the end of December 2022. Studies assessing the changes of mentioned elements in adult patients undergoing cardiac surgery were included. Changes in the means and standard deviations of the elements before and after the cardiac surgery were utilized as desired effect sizes.
RESULTS
Among 1252 records found in the primary search, 23 and 21 articles were included in the systematic review and meta-analysis respectively. Seventeen studies evaluated the changes in serum Zn and Cu levels, and fifteen studies assessed Se levels. According to the results of quantitative analysis, Zn, Cu, and Se concentrations, one day after the surgery were significantly lower than preoperative values (WMD for Zn: 4.64 µmol/L [3.57-5.72], WMD for Cu: 1.62 µmol/L [0.52-2.72], and WMD for Se: 0.1 µmol/L [0.03-0.16]). The concentration of trace elements recovered gradually during the first-week post-operation and reached preoperative levels or even higher.
CONCLUSION
Serum trace elements dropped significantly soon after the cardiac surgery, but they reached their baseline levels mostly during the first week after the surgery. Future studies are warranted to elucidate the impact of alterations in serum concentration of trace elements on the outcomes and complications of open-heart surgeries.
Topics: Adult; Humans; Trace Elements; Zinc; Copper; Selenium; Cardiac Surgical Procedures
PubMed: 37897922
DOI: 10.1016/j.jtemb.2023.127331 -
European Journal of Medicinal Chemistry Dec 2023Alzheimer's disease (AD) is a global health problem in the medical sector that will increase over time. The limited treatment of AD leads to the search for a new...
Discovery of novel multifunctional ligands targeting GABA transporters, butyrylcholinesterase, β-secretase, and amyloid β aggregation as potential treatment of Alzheimer's disease.
Alzheimer's disease (AD) is a global health problem in the medical sector that will increase over time. The limited treatment of AD leads to the search for a new clinical candidate. Considering the multifactorial nature of AD, a strategy targeting number of regulatory proteins involved in the development of the disease is an effective approach. Here, we present a discovery of new multi-target-directed ligands (MTDLs), purposely designed as GABA transporter (GAT) inhibitors, that successfully provide the inhibitory activity against butyrylcholinesterase (BuChE), β-secretase (BACE1), amyloid β aggregation and calcium channel blockade activity. The selected GAT inhibitors, 19c and 22a - N-benzylamide derivatives of 4-aminobutyric acid, displayed the most prominent multifunctional profile. Compound 19c (mGAT1 IC = 10 μM, mGAT4 IC = 12 μM and BuChE IC = 559 nM) possessed the highest hBACE1 and Aβ aggregation inhibitory activity (IC = 1.57 μM and 99 % at 10 μM, respectively). Additionally, it showed a decrease in both the elongation and nucleation constants of the amyloid aggregation process. In contrast compound 22a represented the highest activity and a mixed-type of eqBuChE inhibition (IC = 173 nM) with hBACE1 (IC = 9.42 μM), Aβ aggregation (79 % at 10 μM) and mGATs (mGAT1 IC = 30 μM, mGAT4 IC = 25 μM) inhibitory activity. Performed molecular docking studies described the mode of interactions with GATs and enzymatic targets. In ADMET in vitro studies both compounds showed acceptable metabolic stability and low neurotoxicity. Successfully, compounds 19c and 22a at the dose of 30 mg/kg possessed statistically significant antiamnesic properties in a mouse model of amnesia caused by scopolamine and assessed in the novel object recognition (NOR) task or the passive avoidance (PA) task.
Topics: Mice; Animals; Butyrylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; GABA Plasma Membrane Transport Proteins; Cholinesterase Inhibitors; Molecular Docking Simulation; Structure-Activity Relationship; Drug Design; Aspartic Acid Endopeptidases; Acetylcholinesterase
PubMed: 37837674
DOI: 10.1016/j.ejmech.2023.115832 -
International Journal of Molecular... Sep 2023Pseudorabies virus (PRV), an alpha herpesvirus, induces significant economic losses to the swine industry and infects multiple kinds of animals. Therefore, it is of...
Pseudorabies virus (PRV), an alpha herpesvirus, induces significant economic losses to the swine industry and infects multiple kinds of animals. Therefore, it is of great importance to explore anti-PRV compounds. In this study, to explore the anti-PRV compounds, a library of natural compounds was screened through a cell-based ELISA assay, and it was discovered that bufalin, a Na/K-ATPase inhibitor, had a robust inhibitory effect on PRV replication. A time-of-addition experiment and temperature-shift assay showed that bufalin significantly inhibited the entry stage of PRV. NaCl- or KCl-treatment showed that NaCl could enhance the inhibitory effect of bufalin on PRV replication, whereas there was no significant effect under the treatment of KCl. Meanwhile, it was also found that bufalin possessed antiviral activity against other alpha herpesviruses, including human herpes simplex virus type 1 (HSV-1) and chicken Marek's disease virus (MDV). Finally, it was found that bufalin could decrease the viral load in multiple tissues, and reduce the morbidity and mortality in PRV-challenged BALB/c mice. Overall, our findings demonstrated that bufalin has the potential to be developed as an anti-PRV compound.
Topics: Mice; Animals; Swine; Humans; Herpesvirus 1, Suid; Sodium Chloride; Adenosine Triphosphatases; Herpesviridae
PubMed: 37833925
DOI: 10.3390/ijms241914479 -
Poultry Science Dec 2023Marek's disease virus (MDV), a naturally oncogenic, highly contagious alpha herpesvirus, induces a T cell lymphoma in chickens that causes severe economic loss. Marek's...
Marek's disease virus (MDV), a naturally oncogenic, highly contagious alpha herpesvirus, induces a T cell lymphoma in chickens that causes severe economic loss. Marek's disease (MD) outcome in an individual is attributed to genetic and environmental factors. Further investigation of the host-virus interaction mechanisms that impact MD resistance is needed to achieve greater MD control. This study analyzed genome-wide DNA methylation patterns in 2 highly inbred parental lines 6 and 7 and 5 recombinant congenic strains (RCS) C, L, M, N, and X strains from those parents. Lines 6 and 7, are MD resistant and susceptible, respectively, whereas the RCS have different combinations of 87.5% Line 6 and 12.5% Line 7. Our DNA methylation cluster showed a strong association with MD incidence. Differentially methylated regions (DMRs) between the parental lines and the 5 RCS were captured. MD-resistant and MD-susceptible markers of DNA methylation were identified as transgenerational epigenetic inheritable. In addition, the growth of v-src DNA tumors and antibody response against sheep red blood cells differed among the 2 parental lines and the RCS. Overall, our results provide very solid evidence that DNA methylation patterns are transgenerational epigenetic inheritance (TEI) in chickens and also play a vital role in MD tumorigenesis and other immune responses; the specific methylated regions may be important modulators of general immunity.
Topics: Animals; Sheep; Chickens; Disease Resistance; Marek Disease; Herpesvirus 2, Gallid; Disease Susceptibility; Epigenesis, Genetic; Sheep Diseases
PubMed: 37832188
DOI: 10.1016/j.psj.2023.103036 -
Frontiers in Aging Neuroscience 2023To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing...
INTRODUCTION
To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems).
OBJECTIVE
We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls.
METHODS
We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6.
RESULTS
Constipation had an adjusted odds ratio, 6.14 [95% CI: 2.94-12.80] showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 [95% CI: 7.88-48.81] showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively.
DISCUSSION
Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.
PubMed: 37810617
DOI: 10.3389/fnagi.2023.1232387 -
BMC Veterinary Research Oct 2023Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head...
BACKGROUND
Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head shaking. Approximately 2.1% of chickens died or were culled due to severe symptoms. Five carcasses were submitted to the Avian Disease Division of the Animal and Plant Quarantine Agency (APQA) for disease diagnosis.
RESULTS
Broilers displayed severe pericarditis and perihepatitis associated with gross lesions. Broilers also displayed microscopic lesions in the cerebrum and in the granular layer of the cerebellum, which were associated with multifocal perivascular cuffing and purulent necrosis in the cerebrum, and severe meningitis with heterophil and lymphocyte infiltration. Staphylococcus spp. were identified in the liver and heart using bacteriological culture. PCR/RT-PCR assays revealed that broilers were negative for avian Clostridium botulinum, Newcastle disease virus, and avian encephalomyelitis virus. Bacterial and viral metagenomic analysis of brain sample further revealed the presence of Pseudomonas spp. and Marek's disease virus, which are known etiological agents of chicken meningoencephalitis.
CONCLUSIONS
This study reports a diagnostic analysis of gross and histopathological lesions from 32-day-old broilers displaying unique neurological symptoms that revealed the presence of the several neurological diseases including meningoencephalitis. The causative agents associated with meningoencephalitis of broilers that had not been identified by routine diagnostic methods could be diagnosed by metagenomics, which proves the usefulness of metagenomics as a diagnostic tool for unknown neurological diseases in broilers.
Topics: Animals; Chickens; Newcastle disease virus; Newcastle Disease; Brain; Meningoencephalitis; Poultry Diseases
PubMed: 37798783
DOI: 10.1186/s12917-023-03732-y -
Alzheimer's Research & Therapy Oct 2023Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly...
BACKGROUND
Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer's disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected.
METHODS
We examined 237 men ages 45-74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates.
RESULTS
There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [- 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [- 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning.
CONCLUSIONS
Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications.
TRIAL REGISTRATION
NCT02798185.
Topics: Male; Humans; Chronic Traumatic Encephalopathy; Football; Neurodegenerative Diseases; Alzheimer Disease; Cognitive Dysfunction; Amyloid beta-Peptides; Amyloid; Cognition; Positron-Emission Tomography
PubMed: 37798671
DOI: 10.1186/s13195-023-01315-5 -
Journal of Clinical Oncology : Official... Dec 2023There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across...
Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group.
PURPOSE
There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel.
METHODS
Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually).
RESULTS
The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text.
CONCLUSION
These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.
Topics: Humans; Clinical Trials as Topic; Urinary Bladder Neoplasms; Adjuvants, Immunologic; Carcinoma, Transitional Cell; Immunotherapy
PubMed: 37793077
DOI: 10.1200/JCO.23.00307 -
Annals of Agricultural and... Sep 2023Intensive poultry farming is usually associated with massive exposure to organic dust, which is largely composed of microbiological origin particulates. The aim of the...
INTRODUCTION AND OBJECTIVE
Intensive poultry farming is usually associated with massive exposure to organic dust, which is largely composed of microbiological origin particulates. The aim of the study is to assess occupational and environmental exposures to airborne bacteria, fungi, and Marek's disease virus emitted by a poultry house.
MATERIAL AND METHODS
The concentrations of airborne microorganisms in a poultry house and its vicinity (250-500 m) at 3 different stages of the production cycle (i.e. empty poultry house, with 7-day-old and 42-day-old chickens) were stationary measured using Andersen and MAS impactors, as well as Coriolis and BioSampler impingers. The collected microbiota was taxonomically identified using molecular and biochemical techniques to characterize occupational exposure and its spatial dissemination.
RESULTS
Although Marek's disease virus was not present in the tested air samples, the appearance of reared chickens in the poultry house resulted in an increase in airborne bacterial and fungal concentrations up to levels of 1.26 × 10 CFU/m and 3.77 × 10 CFU/m, respectively. These pollutants spread around through the ventilation system, but their concentrations significantly decreased at a distance of 500 m from the chicken coop. A part of the identified microbiota was pathogens that were successfully isolated from the air by all 4 tested samplers.
CONCLUSIONS
The poultry house employees were exposed to high concentrations of airborne microorganisms, including pathogens that may lead to adverse health outcomes. To protect them, highly efficient hygienic and technical measures regarding the poultry house interior and its ventilation, respectively, should be introduced to prevent both unwanted pollution and subsequent emission of microbial contaminants during intensive chicken breeding.
PubMed: 37772519
DOI: 10.26444/aaem/172770 -
Molecules (Basel, Switzerland) Sep 2023Marek's disease virus (MDV) is a highly contagious and persistent virus that causes T-lymphoma in chickens, posing a significant threat to the poultry industry despite...
Identification of Disalicyloyl Curcumin as a Potential DNA Polymerase Inhibitor for Marek's Disease Herpesvirus: A Computational Study Using Virtual Screening and Molecular Dynamics Simulations.
Marek's disease virus (MDV) is a highly contagious and persistent virus that causes T-lymphoma in chickens, posing a significant threat to the poultry industry despite the availability of vaccines. The emergence of new virulent strains has further intensified the challenge of designing effective antiviral drugs for MDV. In this study, our main objective was to identify novel antiviral phytochemicals through in silico analysis. We employed Alphafold to construct a three-dimensional (3D) structure of the MDV DNA polymerase, a crucial enzyme involved in viral replication. To ensure the accuracy of the structural model, we validated it using tools available at the SAVES server. Subsequently, a diverse dataset containing thousands of compounds, primarily derived from plant sources, was subjected to molecular docking with the MDV DNA polymerase model, utilizing AutoDock software V 4.2. Through comprehensive analysis of the docking results, we identified Disalicyloyl curcumin as a promising drug candidate that exhibited remarkable binding affinity, with a minimum energy of -12.66 Kcal/mol, specifically targeting the DNA polymerase enzyme. To further assess its potential, we performed molecular dynamics simulations, which confirmed the stability of Disalicyloyl curcumin within the MDV system. Experimental validation of its inhibitory activity in vitro can provide substantial support for its effectiveness. The outcomes of our study hold significant implications for the poultry industry, as the discovery of efficient antiviral phytochemicals against MDV could substantially mitigate the economic losses associated with this devastating disease.
PubMed: 37764352
DOI: 10.3390/molecules28186576