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International Immunopharmacology Jul 2023Progressive multiple sclerosis (PMS) is a debilitating condition characterized by progressively worsening symptoms. Monoclonal antibodies are novel therapies for MS, but... (Review)
Review
BACKGROUND
Progressive multiple sclerosis (PMS) is a debilitating condition characterized by progressively worsening symptoms. Monoclonal antibodies are novel therapies for MS, but their safety and efficacy in the progressive form have not been comprehensively studied. In this systematic review, we aimed to evaluate the available evidence regarding monoclonal antibody treatment for PMS.
METHODS
After registration of the study protocol in PROSPERO, we systematically searched three major databases for clinical trials involving monoclonal antibodies administration for PMS treatment. All the retrieved results were imported into the EndNote reference manager. After removing the duplicates, two independent researchers did the study selection and data extraction. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist.
RESULTS
Of the 1846 studies in the preliminary search, 13 clinical trials investigating monoclonal antibodies (Ocrelizumab, Natalizumab, Rituximab, and Alemtuzumab) in PMS patients were included. Ocrelizumab was significantly effective in reducing clinical disease progression measures in primary PMS patients. The results for Rituximab were not completely reassuring and only showed significant changes for some endpoints on MRI and clinical measures. Natalizumab decreased the relapse rate and improved MRI features for secondary PMS patients, but not clinical endpoints. The studies on Alemtuzumab treatment revealed conflicting outcomes, with improvements observed in MRI endpoints but clinical worsening in patients. Additionally, among the studied adverse events, upper respiratory infections, urinary tract infections, and nasopharyngitis were frequently reported.
CONCLUSION
Based on our findings, Ocrelizumab is the most efficient monoclonal antibody for primary PMS, although it is associated with a higher risk of infection. While other monoclonal antibodies did not show significant promise in treating PMS, more research is necessary.
Topics: Humans; Antibodies, Monoclonal; Rituximab; Natalizumab; Alemtuzumab; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 37209514
DOI: 10.1016/j.intimp.2023.110266 -
Pharmacological Research Jan 2024Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and...
Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.
Topics: Humans; Cation Transport Proteins; Disease Progression; Homeostasis; Neurodegenerative Diseases; Zinc
PubMed: 38123108
DOI: 10.1016/j.phrs.2023.107039 -
Journal of Biomolecular Structure &... Sep 2023Protein subcellular localization is a promising research question in Proteomics and associated fields, including Biological Sciences, Biomedical Engineering,... (Review)
Review
Protein subcellular localization is a promising research question in Proteomics and associated fields, including Biological Sciences, Biomedical Engineering, Computational Biology, Bioinformatics, Proteomics, Artificial Intelligence, and Biophysics. However, computational techniques are preferred to explore this attribute for a massive number of proteins. The byproduct of this conjunction yields diversified location identifiers of proteins. These protein subcellular localization identifiers are unique regarding the database used, organisms, Machine Learning Technique, and accuracy. Despite the availability of these identifiers, the majority of the work has been done on the subcellular localization of proteins and, less work has been done specifically on locations of transmembrane proteins. This systematic review accounts for computational techniques implemented on transmembrane protein localization. Moreover, a literature search on PubMed, Science Direct, and IEEE Databases disclosed no systematic review or meta-analysis on the cell's transmembrane protein locale. A Systematic review was formed under the guidelines of PRISMA by using Science Direct, PubMed, and IEEE Databases. Journal publications from 2000 to 2023 were taken into consideration and screened. This review has focused only on computational studies rather than experimental techniques. 1004 studies were reviewed and were categorized as relevant and non-relevant according to inclusion and exclusion criteria. All the screening was done through Endnote after importing citations. This systematic review characterizes the gap in targeting the locale of the transmembrane protein and will aid researchers in exploring its new horizons.Communicated by Ramaswamy H. Sarma.
PubMed: 37768108
DOI: 10.1080/07391102.2023.2260490 -
International Journal of Health Policy... 2023This review was conducted to identify the impact of economic sanctions on household food and nutrition security and policies to cope with them in countries exposed to...
BACKGROUND
This review was conducted to identify the impact of economic sanctions on household food and nutrition security and policies to cope with them in countries exposed to sanctions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020 were used to identify, select, appraise, and synthesize studies. Electronic databases in addition to Persian ones have been systematically searched for all related documents published until March 2022. Exclusion criteria were: lack of data related to food insecurity in countries subject to sanction and very low quality of the article. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal checklists. The results were presented as qualitative and quantitative syntheses.
RESULTS
Of 1428 identified studies, 36 publications remained in the review, which belong to Iran (n=8), Cuba (n=8), Russia (n=7), Iraq (n=7), and Haiti (n=6), respectively. Declining gross domestic product (GDP), devaluation of the national currency, and the quality of food, increase in inflation, unemployment, and consumer prices, infant and under 5 years mortality, energy, and protein deficiency, and the poverty rate were reported as sanction consequences. The most important strategies to improve food security were the humanitarian assistance provided by the international community (Haiti), equity and priority for vulnerable groups mainly by expanding the healthcare system (Cuba), adopting a food ration system in the oil-for-food program, and fixing the price of food baskets (Iraq), import substitution and self-sufficiency (Russia), support domestic production, direct and indirect support and compensation packages for vulnerable households (the approach of resistance economy in Iran).
CONCLUSION
Due to the heterogeneity of studies, meta-analysis was not possible. Since inadequate physical and economic food access caused by sanctions affects especially disadvantaged and vulnerable groups, planning to improve food security and providing support packages for these groups seems necessary.
Topics: Infant; Humans; Gross Domestic Product; Policy; Academies and Institutes; Checklist; Cuba
PubMed: 38618825
DOI: 10.34172/ijhpm.2023.7362 -
BMC Geriatrics Aug 2022Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in...
INTRODUCTION
Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging.
METHODS
Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging.
RESULTS
Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity.
DISCUSSIONS
Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.
Topics: Aging; Healthy Aging; Humans; Longevity; Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Polymorphism, Single Nucleotide
PubMed: 35964003
DOI: 10.1186/s12877-022-03337-4 -
International Journal of Molecular... Mar 2023Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to... (Review)
Review
Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords "cancer", "Monocarboxylate transporter 1", "SLC16A1" and "prognosis". Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter's overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lactic Acid; Lung Neoplasms; Monocarboxylic Acid Transporters; Pancreatic Neoplasms; Prognosis; Symporters
PubMed: 36982217
DOI: 10.3390/ijms24065141 -
Neurochemical Research Dec 2023Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD).... (Review)
Review
Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
Topics: Animals; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Neuroprotective Agents; Xanthones
PubMed: 37578655
DOI: 10.1007/s11064-023-04005-8 -
PeerJ 2022Bovine mastitis is the commonest episode of infection in the dairy industry, which often occurs after damage of epithelial cells lining the teat duct. It is ranked as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bovine mastitis is the commonest episode of infection in the dairy industry, which often occurs after damage of epithelial cells lining the teat duct. It is ranked as the second most important cause of milk production loss directly and a devastating disease with a higher incidence leading to the culling of dairy cows. Thus, this systematic review and meta-analysis is aimed to quantitatively estimate the current status of mastitis in general and bacterial mastitis particular in Ethiopia.
METHODS
A literature search was carried from major databases and indexing services including PubMed, Google Scholar, Science Direct. Also, local institution repositories were searched to retrieve unpublished MSc and PhD theses. All studies were included addressing the prevalence of mastitis and bacterial isolates conducted in Ethiopia. Microsoft Excel was used to extract data and was imported to R Studio for the analyses. The random-effects model at a 95% confidence level was used for pooled estimates of outcomes. The degree of heterogeneity was computed by Higgins's I statistics. Publication bias was checked by using the funnel plots of standard error augmented by Begg's and Egger's tests.
RESULTS
A total of 46 studies with 15,780 cows were included in this study. All studies have collected 18,478 suspected samples for bacterial isolation. While pooled prevalence estimate of mastitis was 47.6%, the bacterial isolates pooled prevalence was 33.1%. The bacterial mastitis was 6.5% in cows infected by clinical patients and was 28.3% subclinical patients. The common isolates were , species, , , , Coagulase Negative and species. A univariate meta-regression analysis evidenced that the type of mastitis and management system was a possible source of heterogeneity (-value = 0.001).
CONCLUSION
The pooled prevalence of bacterial mastitis in Ethiopian dairy cattle was high. The analysis showed bacterial pathogens like , , species and Coagulase Negative are majorly accounted for bovine mastitis in Ethiopia. Therefore, the highly prevalent and commonly isolated pathogens cause contagious mastitis which require immediate attention by dairy producers to put under control by devising robust mastitis prevention and control interventions.
Topics: Female; Animals; Cattle; Humans; Mastitis, Bovine; Ethiopia; Coagulase; Milk; Staphylococcal Infections; Bacteria; Staphylococcus; Staphylococcus aureus; Streptococcal Infections
PubMed: 35547189
DOI: 10.7717/peerj.13253 -
American Journal of Medical Genetics.... Jul 2019Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to...
Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.
Topics: Gene Ontology; Genome-Wide Association Study; Humans; Self-Injurious Behavior; Signal Transduction; Suicidal Ideation; Suicide
PubMed: 31045331
DOI: 10.1002/ajmg.b.32731 -
Medicine Jul 2023To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network pharmacology and molecular docking.
METHODS
The active ingredients and potential targets of SJTLG were obtained through databases such as traditional Chinese medicine system (TCMSP) and BATMAN-traditional Chinese medicine (TCM), and the relevant human targets of CS were identified through databases such as OMIM, GeneCards, and DisGeNET. The intersection targets were imported into STRING for protein-protein interaction (PPI) analysis. The obtained data were imported into Cytoscape 3.9.0 software for visualization, and module analysis was performed using the MCODE plug-in. The representative targets were screened through the Metascape website for pathway enrichment analysis in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Cytoscape software was used to build networks such as "drug-compound-target" and "drug-compound-target-pathway." Finally, the key targets were selected for molecular docking with the corresponding compounds by Autodock Tools 1.5.7 and visualized by PyMol.
RESULTS
A total of 132 active compounds and 996 targets from SJTLG and 678 targets from CS were screened with 116 intersection targets. The key targets were AKT1, GAPDH, ALB, IL-6, TP53, TNF, VEGFA, IL-1β, EGFR, HSP90AA1, ESR1, and JUN. The results of GO and KEGG enrichment analysis showed that the treatment of CS was mainly related to biological processes such as cellular response to nitrogen compound, cellular response to organonitrogen compound, and positive regulation of locomotion, and the targets were mainly focused on pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid, and atherosclerosis. Molecular docking results showed that the minimum binding energy between the core targets and the corresponding compound was <-5.0 kcal·mol-1.
CONCLUSION
This study preliminarily elucidates the potential active ingredients and mechanism of anti-inflammatory, analgesic, microcirculation improvement, vasodilation, osteoporosis inhibition and nerve nutrition effects of SJTLG in the treatment of CS and provides a reference for its clinical application.
Topics: Humans; Drugs, Chinese Herbal; Molecular Docking Simulation; Network Pharmacology; Spondylosis
PubMed: 37478234
DOI: 10.1097/MD.0000000000034030