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Antioxidants (Basel, Switzerland) Mar 2024Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis,... (Review)
Review
Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis, necroptosis, and autophagy. It is characterized by the accumulation of intracellular iron, overproduction of reactive oxygen species, depletion of glutathione, and extensive lipid peroxidation of lipids in the cell membrane. It was discovered that ferroptosis is interconnected with many diseases, such as neurodegenerative diseases, ischemia/reperfusion injury, cancer, and chronic kidney disease. Polyphenols, plant secondary metabolites known for many bioactivities, are being extensively researched in the context of their influence on ferroptosis which resulted in a great number of publications showing the need for a systematic review. In this review, an extensive literature search was performed. Databases (Scopus, Web of Science, PubMed, ScienceDirect, Springer) were searched in the time span from 2017 to November 2023, using the keyword "ferroptosis" alone and in combination with "flavonoid", "phenolic acid", "stilbene", "coumarin", "anthraquinone", and "chalcone"; after the selection of studies, we had 311 papers and 143 phenolic compounds. In total, 53 compounds showed the ability to induce ferroptosis, and 110 compounds were able to inhibit ferroptosis, and out of those compounds, 20 showed both abilities depending on the model system. The most researched compounds are shikonin, curcumin, quercetin, resveratrol, and baicalin. The most common modes of action are in the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axis and the modulation of iron metabolism.
PubMed: 38539867
DOI: 10.3390/antiox13030334 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z -
Current Drug Research Reviews Feb 2024Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this...
BACKGROUND
Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this condition.
OBJECTIVE
This qualitative systematic review aimed to highlight the therapeutic potential of omega- 3 (n-3) in people with sickle cell disease.
METHODS
The search was performed by combining sickle cell disease and n-3 descriptors in DeCS/ MeSH databases, including Scopus, PubMed, ScienceDirect, Web of Science, and Virtual Health Library. The risk of bias assessment in the primary studies was performed using the Cochrane risk of bias tool for randomized controlled trials. The evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.
RESULTS
From the 187 records identified, seven were selected for data collection. Based on the evidence, n-3 supplementation contributes to lower activation of pro-inflammatory biomarkers, improves the concentration of docosahexaenoic and eicosapentaenoic acids in the erythrocyte membrane, provides better hemostatic response, and helps in vaso-occlusive crisis, pain episodes, and hospitalization reduction.
CONCLUSION
The findings suggest that n-3 adjuvant therapy favors the clinical and general aspects of people with sickle cell disease.
PubMed: 38409715
DOI: 10.2174/0125899775286425240129110903 -
Gels (Basel, Switzerland) Jan 2024Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This... (Review)
Review
Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue-organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue-material interface, and organ-organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives.
PubMed: 38391432
DOI: 10.3390/gels10020102 -
Current Pharmaceutical Design 2024Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively...
BACKGROUND
Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex.
OBJECTIVES
We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse.
METHODS
We searched EMBASE, MEDLINE, and other sources to identify clinical or preclinical reports on the effects of HEDMDs on co-signaling and adhesion molecules that participate in the formation of immune synapses in patients with MS or other autoimmune disorders. We included reports on cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors of Bruton's Tyrosine Kinase, and natalizumab.
RESULTS
In 56 eligible reports among 7340 total publications, limited relevant evidence was uncovered. Not all co-signaling and adhesion molecules have been studied in relation to every HEDMD, with more data being available on the anti-CD20 monoclonal antibodies (that affect CD80, CD86, GITR and TIGIT), cladribine tablets (affecting CD28, CD40, ICAM-1, LFA-1) and the S1P modulators (affecting CD86, ICAM-1 and LFA-1) and less on Natalizumab (affecting CD80, CD86, CD40, LFA-1, VLA-4) and Alemtuzumab (affecting GITR and CTLA-4).
CONCLUSION
The puzzle of HEDMD effects on the immune synapse is far from complete. The available evidence suggests that distinguishing differences exist between drugs and are worth pursuing further.
Topics: Animals; Humans; Cell Adhesion Molecules; Immunological Synapses; Multiple Sclerosis
PubMed: 38343058
DOI: 10.2174/0113816128288102240131053205 -
Annals of Nuclear Medicine Mar 2024Fluoro-deoxy glucose positron emission tomography/computed tomography (PET/CT), the workhorse of nuclear medicine, has limited utility for renal cell carcinoma (RCC),... (Meta-Analysis)
Meta-Analysis Review
Fluoro-deoxy glucose positron emission tomography/computed tomography (PET/CT), the workhorse of nuclear medicine, has limited utility for renal cell carcinoma (RCC), particularly clear cell variant. Thus, various other tracers have been tried for evaluation of RCC. One of the most promising targets for radiotracers is prostate-specific membrane antigen (PSMA) expressed in abundance in carcinoma-associated neo-vasculature. Thus, we tried to review and analyse the role of PSMA-targeted PET/CT in evaluation of RCC. Databases like PubMed, EMBASE and SCOPUS were searched for original studies published on PSMA-targeted PET/CT in RCC till 30 September 2023. Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist was used to assess the included studies. Pooled sensitivity and specificity were calculated and represented with 95% confidence intervals (95%CI). Heterogeneity in the studies was assessed by I-square index. Pooled sensitivity and specificity of PSMA-targeted PET/CT for detection of local disease estimates were 87.2% (95%CI: 77-94%) and 100% (95%CI: 92.9-100%), respectively. Pooled sensitivity and specificity for detection of local recurrent disease are 100% (95%CI: 71.5-100%) and 100% (95%CI: 89.4-100%), respectively. Pooled sensitivity and specificity for detection of metastatic disease are 92% (95%CI: 86.2-96%) and 96.9% (95%CI: 83.8-99.9%), respectively. Pooled sensitivity of PSMA-targeted PET/CT for detection of clear cell renal cell carcinoma (ccRCC) and non-ccRCC are 94.7% (95%CI: 88-98.3%) and 75% (95%CI: 35-96.8%), respectively. PSMA-targeted PET-CT demonstrated better diagnostic efficacy for the detection of recurrent RCC. Whilst for staging RCC, it had higher specificity but lower sensitivity. Thus, it can serve as a non-invasive adjuvant tool to conventional imaging in the evaluation of staging of RCC, particularly clear cell variant.
Topics: Male; Humans; Carcinoma, Renal Cell; Positron Emission Tomography Computed Tomography; Radionuclide Imaging; Sensitivity and Specificity; Kidney Neoplasms; Prostatic Neoplasms
PubMed: 38340144
DOI: 10.1007/s12149-024-01904-w -
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 -
Ophthalmic Research 2024Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize... (Review)
Review
INTRODUCTION
Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis.
METHODS
The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date.
RESULTS
Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes.
CONCLUSION
By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.
Topics: Humans; Optic Neuropathy, Ischemic; Diagnosis, Differential; Tomography, Optical Coherence; Nerve Fibers; Retinal Ganglion Cells; Optic Disk; Glaucoma; Visual Fields; Intraocular Pressure
PubMed: 38262372
DOI: 10.1159/000535568 -
PloS One 2024In some laboratories, mosquitoes' direct blood-feeding on live animals has been replaced with various membrane blood-feeding systems. The selection of blood meal sources...
A scoping review on the use of different blood sources and components in the artificial membrane feeding system and its effects on blood-feeding and fecundity rate of Aedes aegypti.
In some laboratories, mosquitoes' direct blood-feeding on live animals has been replaced with various membrane blood-feeding systems. The selection of blood meal sources used in membrane feeding is crucial in vector mass rearing as it influences the mosquitoes' development and reproductive fitness. Therefore, this scoping review aimed to evaluate the existing literature on the use of different blood sources and components in artificial membrane feeding systems and their effects on blood-feeding and the fecundity rate of Ae. aegypti. A literature review search was conducted by using PubMed, Scopus, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR). The EndNote version 20 software was used to import all searched articles. Relevant information was retrieved for analysis into a Microsoft Excel Spreadsheet. A total of 104 full-text articles were assessed for eligibility criteria, whereby the articles should include the comparison between different types of blood source by using the membrane feeding systems. Only 16 articles were finally included in the analysis. Several studies had reported that human blood was superior in blood-feeding Ae. aegypti as compared to sheep blood which resulted in lower fecundity due to accumulation of free fatty acids (FFA) in the cuticles. In contrast, cattle whole blood and pig whole blood showed no significant differences in the blood-feeding and fecundity rate as compared to human blood. This review also indicated that bovine whole blood and pig whole blood enhanced Ae. aegypti's vitellogenesis and egg production as compared to plasma and blood cells. In addition, human blood of up to 10 days after the expiration date could still be used to establish Ae. aegypti colonies with good blood-feeding rates and number of eggs produced. Thus, future studies must consider the importance of selecting suitable blood sources and components for membrane blood feeding especially in mosquito colonisation and control measure studies.
Topics: Animals; Cattle; Humans; Aedes; Fertility; Membranes, Artificial; Mosquito Vectors; Sheep; Swine
PubMed: 38252615
DOI: 10.1371/journal.pone.0295961