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  • 1
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    Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 9 ( 2023-04-22), p. 7692-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 9 ( 2023-04-22), p. 7692-
    Kurzfassung: Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24097692
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    High-Tech Methods of Cytokine Imbalance Correction in Intervertebral Disc Degeneration
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 17 ( 2023-08-28), p. 13333-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 17 ( 2023-08-28), p. 13333-
    Kurzfassung: An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241713333
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 5 ( 2023-05-15), p. 1085-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 5 ( 2023-05-15), p. 1085-
    Kurzfassung: Antipsychotic (AP)—induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel “Transporter protein (PT)—Antipsychotic (AP) Pharmacogenetic test (PGx)” (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.
    Materialart: Online-Ressource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14051085
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2527218-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 8 ( 2022-08-05), p. 726-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 8 ( 2022-08-05), p. 726-
    Kurzfassung: Metabolic syndrome (MetS) is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Antipsychotic (AP)-induced MetS (AIMetS) is the most common adverse drug reaction (ADR) of psychiatric pharmacotherapy. Herein, we review the results of studies of blood (serum and plasma) and urinary biomarkers as predictors of AIMetS in patients with schizophrenia (Sch). We reviewed 1440 studies examining 38 blood and 19 urinary metabolic biomarkers, including urinary indicators involved in the development of AIMetS. Among the results, only positive associations were revealed. However, at present, it should be recognized that there is no consensus on the role of any particular urinary biomarker of AIMetS. Evaluation of urinary biomarkers of the development of MetS and AIMetS, as one of the most common concomitant pathological conditions in the treatment of patients with psychiatric disorders, may provide a key to the development of strategies for personalized prevention and treatment of the condition, which is considered a complication of AP therapy for Sch in clinical practice.
    Materialart: Online-Ressource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12080726
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2662251-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Genetic Biomarkers of Antipsychotic-Induced Prolongation of the QT Interval in Patients with Schizophrenia
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-13), p. 15786-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-13), p. 15786-
    Kurzfassung: Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs’ dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415786
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 2 ( 2022-01-18), p. 222-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 2 ( 2022-01-18), p. 222-
    Kurzfassung: Background: The usage of antipsychotics (APs) is the most robust and scientifically based approach in the treatment of schizophrenia spectrum disorders (SSDs). The efficiency of APs is based on a range of target receptors of the central nervous system (CNS): serotoninergic, dopaminergic, adrenergic, histaminergic and cholinergic. Metabolic disorders are the most severe adverse drug reactions (ADRs) and lead to cardiovascular diseases with a high rate of mortality in patients with SSDs. Neuropeptide Y receptor Y5 (NPY5R) is known in the chain of interaction to target receptors for APs, agouti-related peptide receptors and proopiomelanocortin receptors. We studied the association of the single-nucleotide variants (SNVs) rs11100494 and rs6837793 of the NPY5R gene, and rs16147, rs5573, rs5574 of the NPY gene, with metabolic disorders in Russian patients with SSDs. Methods: We examined 99 patients with SSDs (mean age—24.56 years old). The mean duration of APs monotherapy was 8 weeks. The biochemical blood test included levels of glucose, cholesterol, lipoproteins, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin. Anthropometry included weight, height, waist circumference and hip circumference. We used real-time PCR to study the carriage of major and minor alleles of the SNV rs11100494 (1164C 〉 A) of the NPY5R gene (chromosome localization—4q32.2). Group 1 comprised 25 patients with SSDs taking APs with a change in body weight of more than 6% since the start of APs therapy. Group 2 comprised 74 patients with SSDs taking APs with a change in body weight of less than 6% since the start of APs therapy. Results: We show the significance of genetic risk factors (carriage of major allele C of SNV rs11100494 of the NPY5R gene) for the development of AP-induced weight gain in Russian patients with SSDs. The allele C predisposes to AP-induced weight gain (OR = 33.48 [95% CI: 12.62; 88.82], p-value 〈 0.001). Additionally, the results of our study demonstrate that first-generation APs (FGAs) are more likely to cause an increase in serum transaminase levels but are less likely to increase body weight. Second-generation APs (SGAs) are more likely to cause weight gain and changes in serum glucose levels. Conclusion: Our study shows the predictive role of the allele C of SNV rs11100494 of the NPY5R gene in the development of AP-induced weight gain. However, we did not find a significant association between biochemical markers and this SNV in Russian patients with SSDs.
    Materialart: Online-Ressource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14020222
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2527217-2
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    New Genetic Biomarkers of the Overlap Syndrome Tension-Type Headache and Arterial Hypertension
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 10 ( 2022-10-09), p. 1823-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 10 ( 2022-10-09), p. 1823-
    Kurzfassung: Background: Nitric oxide (NO) is an important autocrine and paracrine signaling molecule that plays a crucial role in cardiovascular physiology and pathology regulation. NO is an important molecule involved in regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. Reduced bioavailability of NO in the endothelium is an important precursor for impaired vasodilation and arterial hypertension (AH). Furthermore, NO is involved in nociceptive processing. A NO-induced biphasic response with immediate and a delayed headache is typical for chronic tension-type headaches (TTH) in humans. The aim was to study the association of allelic variants and genotypes of the single nucleotide variant (SNV) rs3782218 of the NOS1 gene with the TTH and AH overlap syndrome development in middle age adults. Materials and Methods: We observed 91 Caucasian participants who resided in Krasnoyarsk city: group 1 (TTH and AH overlap syndrome)—30 patients; group 2 (AH without headache)—30 patients; group 3 (control)—31 healthy volunteers. The diagnosis of AH was based on criteria of the European Society of Cardiology and the European Society of Hypertension (2018) и criteria of the Russian Society of Cardiology (2020). Diagnosis of TTH was based on criteria of the International Classification of Headache Disorders (2018). Real-time polymerase chain reaction was used for the determination of allelic variants and genotypes of the SNV rs3782218 of the NOS1 gene in all groups of participants. Results: The frequency of the minor allele T of rs3782218 was statistically significantly higher by 16.7 times in group 1 (TTH and AH) compared to group 3 (control): 26.7% versus 1.6%, respectively (p-value = 0.000065) and 3.2 times higher in group 1 (TTH and AH) compared to group 2 (AH without headache): 26.7% versus 8.3%, respectively (p-value = 0.008). The frequency of the heterozygous (CT) genotype was statistically significantly higher in group 1 (TTH and AH) compared to group 3 (control): 40.0% versus 3.2% (p-value = 0.000454) and in group 1 (TTH and AH) compared to group 2 (AH without headache): 40.0% versus 16.7% (p-value = 0.045). The minor allele T was statistically significantly associated with a high risk of developing the TTH and AH overlap syndrome compared with the controls (odds ratio (OR) = 22.2 (95% confidential interval (CI): 2.8–173.5)) and compared with AH without headache (OR = 4.0 (95% CI: 1.4–11.8)). Although the frequency of the minor allele T was 5.2 times higher in group 2 (AH without headache) compared with group 3 (control), there were not statistically significantly differences (p-value = 0.086). Conclusion: Thus, the minor allele T of rs3782218 of the NOS1 gene is an important genetic biomarker for a high risk of developing the TTH and AH overlap syndrome in hypertensive patients.
    Materialart: Online-Ressource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13101823
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2527218-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Association of Single-Nucleotide Polymorphisms Rs2779249 (chr17:26128581 C〉A) and Rs rs2297518 (chr17: chr17:27769571 G〉A) of the NOS2 Gene with Tension-Type Headache and Arterial Hypertension Overlap Syndrome in Eastern Siberia
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 2 ( 2023-02-17), p. 513-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 2 ( 2023-02-17), p. 513-
    Kurzfassung: Inducible nitric oxide (NO) synthase (iNOS), encoded by the NOS2 gene, promotes the generation of high levels of NO to combat harmful environmental influences in a wide range of cells. iNOS can cause adverse effects, such as falling blood pressure, if overexpressed. Thus, according to some data, this enzyme is an important precursor of arterial hypertension (AH) and tension-type headache (TTH), which are the most common multifactorial diseases in adults. The purpose of this study was to investigate the association of rs2779249 (chr17:26128581 C 〉 A) and rs2297518 (chr17: chr17:27769571 G 〉 A) of the NOS2 gene with TTH and AH overlap syndrome (OS) in Caucasians in Eastern Siberia. The sample size was 91 participants: the first group—30 patients with OS; the second group—30 patients AH; and the third group—31 healthy volunteers. RT-PCR was used for the determination of alleles and genotypes of the SNPs rs2779249 and rs2297518 of the NOS2 gene in all groups of participants. We showed that the frequency of allele A was significantly higher among patients with AH compared with healthy volunteers (p-value 〈 0.05). The frequency of the heterozygous genotype CA of rs2779249 was higher in the first group vs. the control (p-value = 0.03), and in the second group vs. the control (p-value = 0.045). The frequency of the heterozygous genotype GA of rs2297518 was higher in the first group vs. the control (p-value = 0.035), and in the second group vs. the control (p-value = 0.001). The allele A of rs2779249 was associated with OS (OR = 3.17 [95% CI: 1.31–7.67], p-value = 0.009) and AH (OR = 2.94 [95% CI: 1.21–7.15] , p-value = 0.015) risks compared with the control. The minor allele A of rs2297518 was associated with OS (OR = 4.0 [95% CI: 0.96–16.61], p-value = 0.035) and AH (OR = 8.17 [95% CI: 2.03–32.79] , p-value = 0.001) risks compared with the control. Therefore, our pilot study demonstrated that the SNPs rs2779249 and rs229718 of the NOS2 gene could be promising genetic biomarkers for this OS risk in Caucasians from Eastern Siberia.
    Materialart: Online-Ressource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14020513
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2527218-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Candidate Genes and Proteomic Biomarkers of Serum and Urine in Medication-Overuse Headache
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 16 ( 2021-08-21), p. 9024-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 16 ( 2021-08-21), p. 9024-
    Kurzfassung: Chronic headache is a topical problem of neurology, psychiatry and general practice. The medication-overuse headache (MOH) is one of the leading pathologies in the structure of chronic headache. However, early diagnosis of the MOH is challenging. We analyzed potential proteomic biomarkers of serum and urine in patients with MOH. Methods: We searched PubMed, Springer, Scopus, Web of Science, ClinicalKey, and Google Scholar databases for English publications over the past 10 years using keywords and their combinations. Results: We found and analyzed seven studies that met the search criteria for the purpose of the review, including 24 serum proteomic biomarkers and 25 urine proteomic biomarkers of MOH. Moreover, the candidate genes and locus of the studied serum (vitamin D-binding protein, lipocalin-type prostaglandin D2 synthase, apolipoprotein E, etc.) and urine proteomic biomarkers (uromodulin, alpha-1-microglobulin, zinc-alpha-2-glycoprotein, etc.) of MOH are presented in this review. Conclusions: The serum and urine proteomic biomarkers of MOH can potentially help with the identification of patients with MOH development. Due to the relevance of the problem, the authors believe that further investigation of the MOH proteomic biomarkers in different ethnic and racial groups of patients with primary headache is necessary. In addition, it is important to investigate whether medications of different drug classes influence the levels of serum and urine proteomic biomarkers.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22169024
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Cytokine Imbalance as a Biomarker of Treatment-Resistant Schizophrenia
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 19 ( 2022-09-26), p. 11324-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 19 ( 2022-09-26), p. 11324-
    Kurzfassung: Treatment-resistant schizophrenia (TRS) is an important and unresolved problem in biological and clinical psychiatry. Approximately 30% of cases of schizophrenia (Sch) are TRS, which may be due to the fact that some patients with TRS may suffer from pathogenetically “non-dopamine” Sch, in the development of which neuroinflammation is supposed to play an important role. The purpose of this narrative review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines during the development of therapeutic resistance to APs and their pathogenetic and prognostic significance of cytokine imbalance as TRS biomarkers. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to maintaining or changing the cytokine balance can become a new key in unlocking the mystery of “non-dopamine” Sch and developing new therapeutic strategies for the treatment of TRS and psychosis in the setting of acute and chronic neuroinflammation. In addition, the inconsistency of the results of previous studies on the role of pro-inflammatory and anti-inflammatory cytokines indicates that the TRS biomarker, most likely, is not the serum level of one or more cytokines, but the cytokine balance. We have confirmed the hypothesis that cytokine imbalance is one of the most important TRS biomarkers. This hypothesis is partially supported by the variable response to immunomodulators in patients with TRS, which were prescribed without taking into account the cytokine balance of the relation between serum levels of the most important pro-inflammatory and anti-inflammatory cytokines for TRS.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231911324
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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