| 1. |
- Lafta, Muataz S, et al.
(författare)
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Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non-neurological controls
- 2023
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Ingår i: European Journal of Pain. - : WILEY. - 1090-3801 .- 1532-2149.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTrigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS).MethodsWe analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison.ResultsIn both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.ConclusionsWe conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.SignificanceThis study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.
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| 2. |
- Mälarstig, Anders, et al.
(författare)
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Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
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| 3. |
- Namiot, Eugenia D., et al.
(författare)
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Nanoparticles in Clinical Trials : Analysis of Clinical Trials, FDA Approvals and Use for COVID-19 Vaccines
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1
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Forskningsöversikt (refereegranskat)abstract
- Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines-Pfizer and Moderna-that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.
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| 4. |
- Namiot, Eugenia D., et al.
(författare)
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The international clinical trials registry platform (ICTRP) : data integrity and the trends in clinical trials, diseases, and drugs
- 2023
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Clinical trials are the gold standard for testing new therapies. Databases like ClinicalTrials.gov provide access to trial information, mainly covering the US and Europe. In 2006, WHO introduced the global ICTRP, aggregating data from ClinicalTrials.gov and 17 other national registers, making it the largest clinical trial platform by June 2019. This study conducts a comprehensive global analysis of the ICTRP database and provides framework for large-scale data analysis, data preparation, curation, and filtering.Materials and methods: The trends in 689,793 records from the ICTRP database (covering trials registered from 1990 to 2020) were analyzed. Records were adjusted for duplicates and mapping of agents to drug classes was performed. Several databases, including DrugBank, MESH, and the NIH Drug Information Portal were used to investigate trends in agent classes.Results: Our novel approach unveiled that 0.5% of the trials we identified were hidden duplicates, primarily originating from the EUCTR database, which accounted for 82.9% of these duplicates. However, the overall number of hidden duplicates within the ICTRP seems to be decreasing. In total, 689 793 trials (478 345 interventional) were registered in the ICTRP between 1990 and 2020, surpassing the count of trials in ClinicalTrials.gov (362 500 trials by the end of 2020). We identified 4 865 unique agents in trials with DrugBank, whereas 2 633 agents were identified with NIH Drug Information Portal data. After the ClinicalTrials.gov, EUCTR had the most trials in the ICTRP, followed by CTRI, IRCT, CHiCTR, and ISRCTN. CHiCTR displayed a significant surge in trial registration around 2015, while CTRI experienced rapid growth starting in 2016.Conclusion: This study highlights both the strengths and weaknesses of using the ICTRP as a data source for analyzing trends in clinical trials, and emphasizes the value of utilizing multiple registries for a comprehensive analysis.
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| 5. |
- Sokolov, Aleksandr V., et al.
(författare)
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Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
- 2023
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.
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