| 1. |
- Altay, Özlem, et al.
(författare)
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Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
- 2021
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:17
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
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| 2. |
- Altay, Özlem, et al.
(författare)
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Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases
- 2024
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.
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| 3. |
- Altay, Özlem, et al.
(författare)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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| 4. |
- Altay, Özlem, et al.
(författare)
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Revealing the Metabolic Alterations during Biofilm Development of Burkholderia cenocepacia Based on Genome-Scale Metabolic Modeling
- 2021
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Burkholderia cenocepacia is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of B. cenocepacia. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases.
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| 5. |
- Altay, Özlem, et al.
(författare)
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Systems biology perspective for studying the gut microbiota in human physiology and liver diseases
- 2019
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 49:November, s. 363-373
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Forskningsöversikt (refereegranskat)abstract
- The advancement in high-throughput sequencing technologies and systems biology approaches have revolutionized our understanding of biological systems and opened a new path to investigate unacknowledged biological phenomena. In parallel, the field of human microbiome research has greatly evolved and the relative contribution of the gut microbiome to health and disease have been systematically explored. This review provides an overview of the network-based and translational systems biology-based studies focusing on the function and composition of gut microbiota. We also discussed the association between the gut microbiome and the overall human physiology, as well as hepatic diseases and other metabolic disorders.
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| 6. |
- Bayraktar, Abdulahad, et al.
(författare)
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Revealing the Molecular Mechanisms of Alzheimer's Disease Based on Network Analysis
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:21
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Tidskriftsartikel (refereegranskat)abstract
- The complex pathology of Alzheimer's disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified AMIGO1 and GRPRASP2 as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., beta-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.
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| 7. |
- Ceyhan, Atakan Burak, et al.
(författare)
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Novel drug targets and molecular mechanisms for sarcopenia based on systems biology
- 2024
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier BV. - 0753-3322 .- 1950-6007. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.
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| 8. |
- Demir, E. S., et al.
(författare)
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In vitro activity of ceragenins against Burkholderia cepacia complex
- 2022
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Ingår i: Journal of Antibiotics. - : Springer Nature. - 0021-8820 .- 1881-1469. ; 75:7, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l−1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.
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| 9. |
- Karlsson, Max, et al.
(författare)
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A single-cell type transcriptomics map of human tissues
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:31
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Tidskriftsartikel (refereegranskat)abstract
- Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibody-based protein profiling to create a high-resolution single-cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.
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| 10. |
- Kaynar, Ali, et al.
(författare)
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Systems Biology Approaches to Decipher the Underlying Molecular Mechanisms of Glioblastoma Multiforme
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:24, s. 13213-
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is one of the most malignant central nervous system tumors, showing a poor prognosis and low survival rate. Therefore, deciphering the underlying molecular mechanisms involved in the progression of the GBM and identifying the key driver genes responsible for the disease progression is crucial for discovering potential diagnostic markers and therapeutic targets. In this context, access to various biological data, development of new methodologies, and generation of biological networks for the integration of multi-omics data are necessary for gaining insights into the appearance and progression of GBM. Systems biology approaches have become indispensable in analyzing heterogeneous high-throughput omics data, extracting essential information, and generating new hypotheses from biomedical data. This review provides current knowledge regarding GBM and discusses the multi-omics data and recent systems analysis in GBM to identify key biological functions and genes. This knowledge can be used to develop efficient diagnostic and treatment strategies and can also be used to achieve personalized medicine for GBM.
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| 11. |
- Lam, S., et al.
(författare)
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Addressing the heterogeneity in liver diseases using biological networks
- 2021
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 22:2, s. 1751-1766
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Tidskriftsartikel (refereegranskat)abstract
- The abnormalities in human metabolism have been implicated in the progression of several complex human diseases, including certain cancers. Hence, deciphering the underlying molecular mechanisms associated with metabolic reprogramming in a disease state can greatly assist in elucidating the disease aetiology. An invaluable tool for establishing connections between global metabolic reprogramming and disease development is the genome-scale metabolic model (GEM). Here, we review recent work on the reconstruction of cell/tissue-type and cancer-specific GEMs and their use in identifying metabolic changes occurring in response to liver disease development, stratification of the heterogeneous disease population and discovery of novel drug targets and biomarkers. We also discuss how GEMs can be integrated with other biological networks for generating more comprehensive cell/tissue models. In addition, we review the various biological network analyses that have been employed for the development of efficient treatment strategies. Finally, we present three case studies in which independent studies converged on conclusions underlying liver disease.
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| 12. |
- Mohammadi, Elyas, et al.
(författare)
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Improvement of the performance of anticancer peptides using a drug repositioning pipeline
- 2022
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 17:1, s. 2100417-
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Tidskriftsartikel (refereegranskat)abstract
- The use of anticancer peptides (ACPs) as an alternative/complementary strategy to conventional chemotherapy treatments has been shown to decrease drug resistance and/or severe side effects. However, the efficacy of the positively-charged ACP is inhibited by elevated levels of negatively-charged cell-surface components which trap the peptides and prevent their contact with the cell membrane. Consequently, this decreases ACP-mediated membrane pore formation and cell lysis. Negatively-charged heparan sulphate (HS) and chondroitin sulphate (CS) have been shown to inhibit the cytotoxic effect of ACPs. In this study, we propose a strategy to promote the broad utilization of ACPs. In this context, we developed a drug repositioning pipeline to analyse transcriptomics data generated for four different cancer cell lines (A549, HEPG2, HT29, and MCF7) treated with hundreds of drugs in the LINCS L1000 project. Based on previous studies identifying genes modulating levels of the glycosaminoglycans (GAGs) HS and CS at the cell surface, our analysis aimed at identifying drugs inhibiting genes correlated with high HS and CS levels. As a result, we identified six chemicals as likely repositionable drugs with the potential to enhance the performance of ACPs. The codes in R and Python programming languages are publicly available in https://github.com/ElyasMo/ACPs_HS_HSPGs_CS. As a conclusion, these six drugs are highlighted as excellent targets for synergistic studies with ACPs aimed at lowering the costs associated with ACP-treatment.
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| 13. |
- Ovey, Ishak Suat, et al.
(författare)
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EGb 761 reduces Ca2+ influx and apoptosis after pentylenetetrazole treatment in a neuroblastoma cell line
- 2023
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transient receptor potential (TRP) channels have been found to have significant implications in neuronal outgrowth, survival, inflammatory neurogenic pain, and various epileptogenic processes. Moreover, there is a growing body of evidence indicating that transient receptor potential (TRP) channels have a significant impact on epilepsy and its drug-resistant subtypes. Objective: We postulated that EGb 761 would modulate TRPA1 channels, thereby exhibiting anti-inflammatory and neuroprotective effects in a neuroblastoma cell line. Our rationale was to investigate the impact of EGb 761 in a controlled model of pentylenetetrazole-induced generalized epilepsy. Methodology: We evaluated the neuroprotective, antioxidant and anti-apoptotic effects of EGb 761 both before and after the pentylenetetrazole application in a neuroblastoma cell line. Specifically, we focused on the effects of EGB 761 on the activity of Transient receptor potential (TRP) channels. Results: EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of EGb 761 in the pentylenetetrazole-induced epileptogenesis process. Conclusion: Our basic mechanistic framework for elucidating the pathophysiological significance of fundamental ion mechanisms in a pentylenetetrazole treated neuroblastoma cell line provided compelling evidence for the favorable efficacy and safety profile of Egb 761 in human-relevant in vitro model of epilepsy. To the best of our knowledge, this is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels and measure their activation level in a relevant model of human epileptic diseases.
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| 14. |
- Ozcan, Mehmet, et al.
(författare)
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Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach
- 2020
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Ingår i: Advanced Biosystems. - : Wiley. - 2366-7478. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death primarily due to the lack of effective targeted therapies. Despite the distinct morphological and phenotypic patterns of HCC, treatment strategies are restricted to relatively homogeneous therapies, including multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors. Therefore, more effective therapy options are needed to target dysregulated metabolic and molecular pathways in HCC. Integrative genomic profiling of HCC patients provides insight into the most frequently mutated genes and molecular targets, including telomerase reverse transcriptase, the TP53 gene, and the Wnt/β-catenin signaling pathway oncogene (CTNNB1). Moreover, emerging techniques, such as genome-scale metabolic models may elucidate the underlying cancer-specific metabolism, which allows for the discovery of potential drug targets and identification of biomarkers. De novo lipogenesis has been revealed as consistently upregulated since it is required for cell proliferation in all HCC patients. The metabolic network-driven stratification of HCC patients in terms of redox responses, utilization of metabolites, and subtype-specific pathways may have clinical implications to drive the development of personalized medicine. In this review, the current and emerging therapeutic targets in light of molecular approaches and metabolic network-based strategies are summarized, prompting effective treatment of HCC patients. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 15. |
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| 16. |
- Turanli, Beste Calimlioglu, et al.
(författare)
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Systems biology based drug repositioning for development of cancer therapy
- 2021
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 68, s. 47-58
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Forskningsöversikt (refereegranskat)abstract
- Drug repositioning is a powerful method that can assists the conventional drug discovery process by using existing drugs for treatment of a disease rather than its original indication. The first examples of repurposed drugs were discovered serendipitously, however data accumulated by high-throughput screenings and advancements in computational biology methods have paved the way for rational drug repositioning methods. As chemotherapeutic agents have notorious side effects that significantly reduce quality of life, drug repositioning promises repurposed noncancer drugs with little or tolerable adverse effects for cancer patients. Here, we review current drug-related data types and databases including some examples of web-based drug repositioning tools. Next, we describe systems biology approaches to be used in drug repositioning for effective cancer therapy. Finally, we highlight examples of mostly repurposed drugs for cancer treatment and provide an overview of future expectations in the field for development of effective treatment strategies.
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| 17. |
- Yang, Hong, et al.
(författare)
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Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Various causes of chronic hepatic injury and inflammation can lead to fibrosis and cirrhosis, potentially predisposing individuals to hepatocellular carcinoma. Despite extensive research, the molecular mechanisms underlying liver fibrosis and its associated progression to cancer remain incompletely understood. In this study, we employed an integrated proteotranscriptomics approach to characterize the molecular pathophysiology of liver fibrosis in both liver and plasma samples from 330 individuals. This cohort included 40 healthy subjects and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic-dysfunction associated steatotic liver disease. We demonstrated that pathways related to extracellular matrix alterations, immune response, inflammation, and metabolism are dysregulated in advanced hepatic fibrosis, regardless of the underlying cause. Additionally, our analysis of peritumoral hepatic tissues revealed transcription signatures linked to cell proliferation, survival, and inflammation in hepatocellular carcinoma. Furthermore, we observed extensive remodeling of the plasma proteome linked with severe fibrosis and identified 132 circulating proteomic signatures associated with advanced fibrosis by integrative analysis of plasma proteomics with hepatic transcriptomics. We finally developed predictive models using machine learning to facilitate the non-invasive detection of advanced fibrosis and cirrhosis.
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| 18. |
- Yulug, B., et al.
(författare)
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Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
- 2023
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
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| 19. |
- Yulug, Burak, et al.
(författare)
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Infection with COVID-19 is no longer a public emergency : But what about degenerative dementia?
- 2023
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 95:9
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Tidskriftsartikel (refereegranskat)abstract
- Although no longer considered a public health threat, post-COVID cognitive syndrome continues to impact on a considerable proportion of individuals who were infected with COVID-19. Recent studies have also suggested that COVID may be represent a critical risk factor for the development of Alzheimer's disease (AD). We compared 17 COVID patients with 20 controls and evaluated the effects of COVID-19 on general cognitive performance, hippocampal volume, and connections using structural and seed-based connectivity analysis. We showed that COVID patients exhibited considerably worse cognitive functioning and increased hippocampal connectivity supported by the strong correlation between hippocampal connectivity and cognitive scores. Our findings of higher hippocampal connectivity with no observable hippocampal morphological changes even in mild COVID cases may be represent evidence of a prestructural compensatory mechanism for stimulating additional neuronal resources to combat cognitive dysfunction as recently shown for the prodromal stages of degenerative cognitive disorders. Our findings may be also important in light of recent data showing that other viral infections as well as COVID may constitute a critical risk factor for the development of AD. To our knowledge, this is the first study that investigated network differences in COVID patients, with a particular focus on compensatory hippocampal connectivity.
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| 20. |
- Zeybel, M., et al.
(författare)
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Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
- 2021
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.
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| 21. |
- Zeybel, Mujdat, et al.
(författare)
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Multi-omics analysis reveals the influence of the oral and gut microbiome on host metabolism in non-alcoholic fatty liver disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Non-alcoholic fatty liver disease (NAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants, obesity and diabetes, we characterized 56 heterogeneous NAFLD patients by generating multi-omics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. We explored the dysbiosis in the oral and gut microbiome and revealed host-microbiome interactions based on global metabolic and inflammatory processes. We integrated this multi-omics data using the biological network and identified HS's key features using multi-omics data. We finally predicted HS using these key features and validated our findings in a validation dataset, where we characterized 22 subjects with varying degree of HS
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| 22. |
- Zeybel, M., et al.
(författare)
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Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis
- 2022
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 9:11, s. 2104373-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host–microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.
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| 23. |
- Zhong, Wen, et al.
(författare)
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Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74, s. 103723-
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Tidskriftsartikel (refereegranskat)abstract
- Background: COVID-19 has caused millions of deaths globally, yet the cellular mechanisms underlying the various effects of the disease remain poorly understood. Recently, a new analytical platform for comprehensive analysis of plasma protein profiles using proximity extension assays combined with next generation sequencing has been developed, which allows for multiple proteins to be analyzed simultaneously without sacrifice on accuracy or sensitivity. Methods: We analyzed the plasma protein profiles of COVID-19 patients (n = 50) with mild and moderate symptoms by comparing the protein levels in newly diagnosed patients with the protein levels in the same individuals after 14 days. Findings: The study has identified more than 200 proteins that are significantly elevated during infection and many of these are related to cytokine response and other immune-related functions. In addition, several other proteins are shown to be elevated, including SCARB2, a host cell receptor protein involved in virus entry. A comparison with the plasma protein response in patients with severe symptoms shows a highly similar pattern, but with some interesting differences. Interpretation: The study presented here demonstrates the usefulness of "next generation plasma protein profiling" to identify molecular signatures of importance for disease progression and to allow monitoring of disease during recovery from the infection. The results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus. (C) 2021 The Author(s). Published by Elsevier B.V.
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