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International Journal of Molecular... Feb 2024The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the... (Review)
Review
The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the manner of death and for the individuation of forensic markers for the timing of lesions and vitality of injury. In the literature, various tissues have been studied; the most investigated are the lungs, brain, kidneys, skin, and blood vessels. A systematic literature review on PubMed following PRISMA 2020 guidelines enabled the identification of 96 articles. In all, 34 of these were enrolled to identify Aquaporin-like (AQP-like) forensic markers. The analysis of the literature demonstrated that the most significant markers among the AQPs are as follows: for the brain, AQP4, which is very important in brain trauma and hypoxic damage; AQP3 in the skin lesions caused by various mechanisms; and AQP5 in the diagnosis of drowning. Other applications are in organ damage due to drug abuse and thrombus dating. The focus of this review is to collect all the data present in the literature about the forensic application of AQPs as forensic markers in the most important fields of application. In the current use, the individuation, validation, and application of markers in forensic investigation are very useful in real forensic applications in cases evaluated in court.
Topics: Humans; Aquaporins; Lung; Hypoxia; Brain; Skin
PubMed: 38473914
DOI: 10.3390/ijms25052664 -
ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.Movement Disorders : Official Journal... May 2024Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10).
BACKGROUND
Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10).
METHODS
Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients.
RESULTS
Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis.
CONCLUSIONS
The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Age of Onset; Anoctamins; Genetic Association Studies; Spinocerebellar Ataxias; Aged
PubMed: 38469933
DOI: 10.1002/mds.29729 -
Translational Psychiatry Mar 2024The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential... (Meta-Analysis)
Meta-Analysis
The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search. The significance of these reports was limited since it is not clear if a coincidental or causal relationship exists between SARS-CoV-2 infection or vaccination and manifestation of NMDA receptor encephalitis. The included studies were hampered by difficulties in establishing if these patients had pre-existing NMDA receptor antibodies which entered the brain by infection- or vaccination-associated transient blood-brain barrier leakage. In addition, four cases had comorbid ovarian teratoma, which is a known trigger for development of NMDA receptor encephalitis. Considering that billions of people have contracted COVID-19 or have been vaccinated against this virus, the publication of only 19 case reports with a possible link to NMDA receptor encephalitis, indicates that it is rare. In conclusion, these findings do not support the case that SARS-CoV-2 infection or vaccination led to an increase of existing or de novo encephalitis mediated by an autoimmune response targeting NMDA receptor function. Nevertheless, this work underscores the importance of ongoing vigilance in monitoring viral outbreaks and their potential impact on the central nervous system through basic, epidemiological and translational research.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antibodies; COVID-19; Receptors, N-Methyl-D-Aspartate; SARS-CoV-2
PubMed: 38459000
DOI: 10.1038/s41398-024-02831-0 -
World Neurosurgery May 2024Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation or even death. Current treatment strategies are limited to decompressive craniectomy and the intravascular administration of hypertonic drugs, which have significant side effects. Acetazolamide (ACZ) plays a therapeutic role in cerebral edema by inhibiting aquaporin-4 (AQP-4) and improving collateral circulation. This study aimed to perform a meta-analysis and systematic review of ACZ therapy for ischemic stroke and evaluate its efficacy in animal models.
METHODS
We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke.
RESULTS
After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, -2.00; 95% confidence interval, -3.57 to -0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference-1.46; 95% confidence interval, -2.01 to -0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals' neurological function is uncertain because of the limited research data.
CONCLUSIONS
ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function.
Topics: Acetazolamide; Ischemic Stroke; Animals; Brain Edema; Humans; Treatment Outcome; Aquaporin 4; Carbonic Anhydrase Inhibitors; Disease Models, Animal
PubMed: 38423457
DOI: 10.1016/j.wneu.2024.02.123 -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
Journal of Psychiatric Research Apr 2024This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs)... (Meta-Analysis)
Meta-Analysis Review
The effect of N-methyl-D-aspartate receptor antagonists on the mismatch negativity of event-related potentials and its regulatory factors: A systematic review and meta-analysis.
This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs) in healthy subjects and explores whether NMDAR antagonists have different effects on MMN components under different types of antagonists, drug dosages, and deviant stimuli. We conducted a comprehensive literature search of PubMed, EMBASE, and the Cochrane Library from inception to August 1, 2023 for studies comparing the MMN components between the NMDAR antagonist intervention group and the control group (or baseline). All statistical analyses were performed using Stata version 12.0 software. Sixteen articles were included in the systematic review: 13 articles were included in the meta-analysis of MMN amplitudes, and seven articles were included in the meta-analysis of MMN latencies. The pooled analysis showed that NMDAR antagonists reduced MMN amplitudes [SMD (95% CI) = 0.32 (0.16, 0.47), P < 0.01, I = 47.3%, p < 0.01] and prolonged MMN latencies [SMD (95% CI) = 0.31 (0.13, 0.49), P = 0.16, I = 28.3%, p < 0.01]. The type of antagonist drug regulates the effect of NMDAR antagonists on MMN amplitudes. Different antagonists, doses of antagonists, and types of deviant stimuli can also have different effects on MMN. These findings indicate a correlation between NMDAR and MMN, which may provide a foundation for the application of ERP-MMN in the early identification of NMDAR encephalitis.
Topics: Humans; Receptors, N-Methyl-D-Aspartate; Evoked Potentials, Auditory; Electroencephalography; Evoked Potentials; Acoustic Stimulation
PubMed: 38402843
DOI: 10.1016/j.jpsychires.2024.02.004 -
Cells Jan 2024Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine... (Review)
Review
Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial.
Topics: Humans; Alzheimer Disease; Receptors, Nicotinic; Brain; Nicotinic Agonists; Cognition
PubMed: 38334629
DOI: 10.3390/cells13030237 -
Biomedical and Environmental Sciences :... Jan 2024This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the...
OBJECTIVE
This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.
METHODS
We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( = 113,154) and MDD ( = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.
RESULTS
The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that , , , , and expression are associated with an increased risk of depression. In contrast, , , , , and genes are candidate protective factors against depression.
CONCLUSION
This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.
Topics: Humans; Depressive Disorder, Major; Depression; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Serotonin Plasma Membrane Transport Proteins
PubMed: 38326723
DOI: 10.3967/bes2024.007 -
International Immunopharmacology Mar 2024Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain relief in cancer patients. This study aims to clarify the prognostic impact of opioid use in advanced NSCLC patients receiving ICI therapy.
METHODS
A systematic literature review was carried out using online databases before July 2023. The meta-analysis was used to clarify the correlation of opioid use with the overall survival (OS) or progression-free survival (PFS) of ICI-treated NSCLC patients, both of which were determined using hazard ratios (HRs) coupled with 95 % confidence intervals (CIs). Then, an independent cohort enrolling 181 NSCLC patients was utilized for validation. Finally, a comprehensive bioinformatics analysis based on TCGA cohort was performed to investigate the prognostic significance of opioid target genes (OTGs) and their correlation with immune infiltration in NSCLC patients.
RESULTS
A total of 8 studies enrolling 1174 patients were included in the meta-analysis. Opioid use was negatively associated with worse PFS (HR = 2.16, 95 %CI: 1.26-3.71) and OS (HR = 2.02, 95 %CI: 1.54-2.63) in ICI-treated NSCLC patients. The retrospective validation confirmed the above result and identified opioid use as an independent unfavorable predictor for PFS and OS in both the entire cohort and ICI subgroup. The bioinformatic analysis identified 14 prognostic OTGs (CYP17A1, PDYN, PYCARD, FGA, NTSR1, FABP1, HPCA, PENK, PDGFB, LIN7A, FKBP5, TYMS, CACNA1H and LDHA), most of which were correlated with immune infiltration in NSCLC. A risk model was constructed based on 14 OTGs and found to effectively stratify the clinical outcome in both the training and validation set, independent of age, gender and TNM staging system. The model was also significantly correlated with infiltration of activated dendritic cells, neutrophils and tumor infiltrating lymphocytes. Finally, a nomogram was constructed based on the model, age, gender and TNM stage, which could predict well the 1-, 3- and 5-year survival of NSCLC patients.
CONCLUSION
Opioid use is correlated with the poor clinical outcome in ICI-treated NSCLC patients. Precise pain management is highly advocated and opioids are recommended to be cautiously used in these patients. OTGs have the potential to be prognostic biomarkers for NSCLC patients and their role in tumor immunity needs to be further investigated.
Topics: Humans; Analgesics, Opioid; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Membrane Proteins; Opioid-Related Disorders; Retrospective Studies; Vesicular Transport Proteins
PubMed: 38325047
DOI: 10.1016/j.intimp.2024.111611 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254