Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation

2018 ◽  
Vol 30 (4) ◽  
pp. 192-202
Author(s):  
Mikkel Vestergaard Olesen ◽  
Casper René Gøtzsche ◽  
Søren Hofman Christiansen ◽  
David Paul Drucker Woldbye
Keyword(s):  
Mrna Expression ◽  
Neuronal Excitability ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Receptor System ◽  
Beneficial Effects ◽  
Hippocampal Ca3 ◽  
Plastic Changes ◽  
Electroconvulsive Stimulation ◽  
Anticonvulsant Effects

ObjectiveElectroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects. However, little is known about how ECS might affect the SST receptor system. The present study examined effects of single and repeated ECS on the synthesis of SST receptors (SSTR1–4) and SST, and SST receptor binding ([125I]LTT-SST28) in mouse hippocampal regions and piriform/parietal cortices.ResultsA complex pattern of plastic changes was observed. In the dentate gyrus, SST and SSTR1 expression and the number of hilar SST immunoreactive cells were significantly increased at 1 week after repeated ECS while SSTR2 expression was downregulated by single ECS, and SSTR3 mRNA and SST binding were elevated 24 h after repeated ECS. In hippocampal CA1 and parietal/piriform cortices, we found elevated SST mRNA levels 1 week after repeated ECS and elevated SST binding after single ECS and 24 h after repeated ECS. In hippocampal CA3, repeated ECS increased SST expression 1 week after and SST binding 24 h after. In the parietal cortex, SSTR2 mRNA expression was downregulated after single ECS while SSTR4 mRNA expression was upregulated 24 h after repeated ECS.ConclusionConsidering the known anticonvulsant effects of SST, it is likely that these ECS-induced neuroplastic changes in the SST system could participate in modulating neuronal excitability and potentially contribute to therapeutic effects of ECT.

220 THE ESTROGEN-LIKE EFFECT OF 2-METHOXYESTRADIOL (2-ME) IN IN VITRO AND IN VIVO MODELS

2015 ◽  
Vol 27 (1) ◽  
pp. 200
Author(s):  
J.-S. Lee ◽  
E.-B. Jeung
Keyword(s):  
Mrna Expression ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Oestrogen Receptors ◽  
In Vivo Models ◽  
Ru 486 ◽  
Final Injection ◽  
M 10

2-Methoxyestradiol (2-ME), an endogenous metabolite of 17β-oestradiol, interacts with oestrogen receptors and microtubules and has a low affinity for oestrogen receptors (ER). It has attracted considerable interest due to its potential anti-cancer therapeutic effects. 2-ME is also recognised for its unique and profound actions on various tumour cell lines and cancer independent of the hormone receptor status. Regardless of differences in function, 2-ME has an affinity for ER, however, the exact mechanisms of 2-ME action via the ER are not fully understood. In the current study, we examined the estrogenic effect of 2-ME on mRNA levels of CaBP-9k, ER, and progesterone receptor (PR) in the absence or presence of the 17β-oestradiol (E2) and progesterone (P4) in both in vivo and in vitro models by real-time RT–PCR. In vitro, cells (n = 3 per group) were exposed to a single dose of E2 (10–9 M), P4 (10–6 M), 2-ME (10–8 M, 10–7 M, 10–6 M). The mechanism of CaBP-9k induction by these chemicals pre-treated with 10–7 M ICI 182, 780 and 10–6 M RU 486 for 30 min before exposure to E2 and 2-ME were analysed. In vivo, 35 female ICR mice (PND 14 days) were divided into 7 groups (n = 5 per group), and each group was administered subcutaneously with 24% DMSO, 38% ethanol, and 38% sterile saline as a vehicle, E2 [40 μg kg–1 of body weight (BW)] a physiological dose level), 2-ME (4, 40, and 80 mg kg–1 of BW) for 3 days. The mice were killed 24 h after the final injection. To investigate the effect of antagonism, 10 mice were injected SC with ICI 182 780 (10 mg kg–1 of BW) and RU 486 (10 mg kg–1 of BW) at 30 min before injection with 2-ME (40 mg kg–1 of BW) for 3 days and killed 24 h after the final injection. Results are presented as mean ± s.e.m.; P-values were calculated using one-way ANOVA. In GH3 cells, the mRNA level of CaBP-9k was induced in the E2 (10–9 M) treatment group, and expression of CaBP-9k was also up-regulated in the 2-ME (10–7 M)-treated group. Uterine lactoferrin (Ltf) mRNA expression was also increased in the 2-ME (40 mg kg–1 of BW) group, similar to the response with E2 (40 μg kg–1 of BW) in mice. As a blocker for ER and PR activity, ICI 182 780 and RU 486 reversed the E2 or 2-ME mediated increase of CaBP-9k and Ltf mRNA expression. We found that 2-ME significantly increased the levels of ERa and PR transcripts. In parallel with in vitro results, the mRNA levels of ERa and PR were induced by treatment with E2 and 2-ME. Taken together, our findings demonstrated that expression of estrogenic markers, CaBP-9k and Ltf, was regulated by 2-ME in both in vitro and in vivo, which may increase their estrogenic activities in female during the cycle through ER and/or PR-mediated pathway.

Sika deer (Cervus nippon) velvet antler ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like clinical signs in a rodent model

2020 ◽  
Vol 60 (10) ◽  
pp. 1357
Author(s):  
Young-Jin Choi ◽  
Meiqi Fan ◽  
Yonghai Yu ◽  
Xiaoli Wang ◽  
Yujiao Tang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cell ◽  
Lymph Node ◽  
Mechanisms Of Action ◽  
Cell Infiltration ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Beneficial Effects ◽  
Node Weight

Context Deer velvet is a rarely used component in traditional Chinese medicine and has beneficial effects against several diseases. As a substance that covers the bone and cartilage of immature antlers, deer velvet is a natural cytokine ‘storeroom’ that is rich in protein and proteoglycans. Recently, proteoglycans have been shown to have beneficial effects against inflammation. Aims To determine whether antler extract possesses therapeutic effects in a mouse model of atopic dermatitis (AD) and to explore the underlying mechanisms of action. Methods BALB/c mice were randomly divided into the following groups: control, AD, and AD + antler groups. We established an in vivo AD model by repeatedly exposing the ears of mice to Dermatophagoides farinae extract (house dust-mite extract) and 2,4-dinitrochlorobenzene once per week for 4 weeks. On the day after induction, ear thickness was measured. Antler extract (100 mg/kg) was administered orally once a day for 26 days. After 4 weeks of treatment with antler extract, the epidermal and dermal ear thickness, mast-cell infiltration, spleen weight, and lymph-node weight were measured. In addition, the mRNA levels of several pathogenic cytokines in the ears were measured. The concentrations of IL-4, IL-5, IL-10, IL-31 and IL-17 mRNA in the skin lesions of each group were measured by quantitative polymerase chain reaction. Key results Epidermal and dermal ear thickness, mast-cell infiltration, lymph-node weight, and gene expression levels of pathogenic cytokines in ear tissue were diminished following oral administration of antler extract, unlike in the control group. Conclusions The results of the present study strongly suggest that antler extract exhibits therapeutic activity against atopic dermatitis via regulation of inflammatory response. Implications Further exploration of the mechanisms of action of antler extract will be important for clinical application.

HBOT Application at Cases of Gingival Inflammation

2019 ◽  
Author(s):  
Ilma Robo
Keyword(s):  
Root Resorption ◽  
Periodontal Diseases ◽  
Therapeutic Effects ◽  
Clinical Effects ◽  
Gingival Inflammation ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Short Period ◽  
Mechanical Therapy ◽  
The Impact

The treatment of periodontal diseases, mainly of their origin, with the most common clinical manifestation in form of gingival inflammation, is manifold and powerful, including: mechanical therapy, antibiotic, antiseptic and various approaches to treatment, which are recommended to be used within a short period of time. New therapeutic approaches have been proven as alternative treatment to conventional therapy, or in combination with conventional therapies, to reduce the number of periodontopathic pathogens in gingival sulcus. HBOT has a detrimental effect on periodontal microorganisms, as well as beneficial effects on the healing of periodontal tissue, increasing oxygen pressure in gingival pockets. Our study is aimed at reviewing the current published literature on hyperbaric oxygen therapy and focuses on role of HBOT as a therapeutic measure for the individual with periodontal disease in general and for the impact on the recovery of gingival inflammation. HBOT and periodontal treatment together, reduce up to 99% of the gram-negative anaerobic load of subgingival flora. HBOT, significantly reduces subgingival anaerobic flora. Clinical effects in 2-year follow-up of treated patients are sensitive. Reduction of gingival hemorrhage indexes, depth of peritoneum, plaque index, occurs in cases of combination of HBOT and detraction. Reduced load persists up to 2 months after therapy. The significant increase in connective tissue removal starts at the end of 2nd week, to achieve the maximum in week 3-6 of application. HBOT used for re-implantation, stimulates the healing of periodontal membrane, pulp, prevents root resorption, healing of periodontal lining tissues. HBOT, significantly reduces the hemorrhage index with 1.2 value difference, 0.7mm probe depth, reduces gingival fluid by 2. HGH exposure is increased by gingival blood flow, with a difference of 2 in measured value. The therapeutic effects of HBOT in the value of the evaluation index can be saved up to 1-year post treatment.

ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

Yogic Intervention in Sexual Dysfunction - A Review

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Rakshith K. R. ◽  
Shivakumar . ◽  
Kaushal Sinha ◽  
Vijeth Kumar L. A.
Keyword(s):  
Psychological Functioning ◽  
Empirical Studies ◽  
Empirical Literature ◽  
Future Research ◽  
Therapeutic Effects ◽  
Yoga Therapy ◽  
Cognitive Component ◽  
Beneficial Effects ◽  
Breathing Exercises ◽  
The Mind

Yoga is an ancient practice with Eastern roots that involves both physical postures (Asanas) and breathing techniques (Pranayamas). Yoga therapy for male sexual problems can effectively be treated through Yoga therapy, particularly with the help of Yoga poses and breathing exercises, Yoga has proven itself highly very effective in the treatment of a number of incurable and sometimes terminable diseases. Then again, Yoga's therapeutic effects are just a spin-off and supplementary. Yoga which has proved to be very effective in the treatment of many impossible and incurable diseases, the therapeutic effect of Yoga is only a by product and incidental. Problems related to sex can very well be handled with Yoga as most often these problems are more related to the mind than body. Either they are caused by lack of confidence or stress or fatigue or fear and very few times some physical cause is there. There is also a cognitive component focusing on meditation and concentration, which aids in achieving the goal of union between the self and the spiritual. Although numerous empirical studies have found a beneficial effect of Yoga on different aspects of physical and psychological functioning, claims of Yoga's beneficial effects on sexuality derive from a rich but no empirical literature. The goal of this article is to review the philosophy and forms of Yoga, to review the no empirical and (limited) empirical literatures linking Yoga with enhanced sexuality, and to propose some future research avenues focusing on Yoga as a treatment for sexual disorder.

scholarly journals Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

2020 ◽  
Vol 22 (1) ◽  
pp. 164
Author(s):  
Khosbayar Lkhagvadorj ◽  
Zhijun Zeng ◽  
Karolin F. Meyer ◽  
Laura P. Verweij ◽  
Wierd Kooistra ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Nicotine Dependence ◽  
Susceptibility Gene ◽  
Smoke Exposure ◽  
Adverse Outcomes ◽  
Male Offspring ◽  
Adult Offspring ◽  
Mrna Levels ◽  
Nicotine Metabolism

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.

scholarly journals Reprogramming mRNA Expression in Response to Defect in RNA Polymerase III Assembly in the Yeast Saccharomyces cerevisiae

2021 ◽  
Vol 22 (14) ◽  
pp. 7298
Author(s):  
Izabela Rudzińska ◽  
Małgorzata Cieśla ◽  
Tomasz W. Turowski ◽  
Alicja Armatowska ◽  
Ewa Leśniewska ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Ribosome Biogenesis ◽  
Rna Polymerase Iii ◽  
Mrna Levels ◽  
Rna Seq ◽  
Yeast Saccharomyces Cerevisiae ◽  
Protein Coding ◽  
General Transcription Factor ◽  
Pol I ◽  
Pol Iii

The coordinated transcription of the genome is the fundamental mechanism in molecular biology. Transcription in eukaryotes is carried out by three main RNA polymerases: Pol I, II, and III. One basic problem is how a decrease in tRNA levels, by downregulating Pol III efficiency, influences the expression pattern of protein-coding genes. The purpose of this study was to determine the mRNA levels in the yeast mutant rpc128-1007 and its overdose suppressors, RBS1 and PRT1. The rpc128-1007 mutant prevents assembly of the Pol III complex and functionally mimics similar mutations in human Pol III, which cause hypomyelinating leukodystrophies. We applied RNAseq followed by the hierarchical clustering of our complete RNA-seq transcriptome and functional analysis of genes from the clusters. mRNA upregulation in rpc128-1007 cells was generally stronger than downregulation. The observed induction of mRNA expression was mostly indirect and resulted from the derepression of general transcription factor Gcn4, differently modulated by suppressor genes. rpc128-1007 mutation, regardless of the presence of suppressors, also resulted in a weak increase in the expression of ribosome biogenesis genes. mRNA genes that were downregulated by the reduction of Pol III assembly comprise the proteasome complex. In summary, our results provide the regulatory links affected by Pol III assembly that contribute differently to cellular fitness.

scholarly journals Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Birhan Alemnew ◽  
Soren T. Hoff ◽  
Tamrat Abebe ◽  
Markos Abebe ◽  
Abraham Aseffa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Patterns ◽  
Fold Change ◽  
Mrna Levels ◽  
Healthy Children ◽  
Toll Like Receptors ◽  
Relative Expression ◽  
Latently Infected ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

scholarly journals Bee Pollen Diet Alters the Bacterial Flora and Antimicrobial Peptides in the Oral Cavities of Mice

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1282
Author(s):  
Ariuntsetseg Khurelchuluun ◽  
Osamu Uehara ◽  
Durga Paudel ◽  
Tetsuro Morikawa ◽  
Yutaka Kawano ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Buccal Mucosa ◽  
Bacterial Flora ◽  
Control Group ◽  
Mrna Levels ◽  
Bee Pollen ◽  
Alpha And Beta Diversity ◽  
Beneficial Effects ◽  
Metagenomic Study ◽  
Systemic Health

Background: Bee pollen (BP) has a broad range of beneficial effects on health. The aim of this study was to examine the effect of BP on the oral environment, including the microbiome and antimicrobial peptides. Methods: C57BL/6J mice were randomly divided into two groups: control and BP. The BP group was fed with a 5% BP diet for 1 month. Swabs from the oral and buccal mucosa and samples of the intestinal stool were collected. Genomic DNA was extracted and the microbiome was analyzed via 16S rRNA sequencing. Results: BP inhibited the growth of P. gingivalis at a concentration of >2.5%. The metagenomic study showed that the abundance of genus Lactococcus was significantly elevated in the oral and intestinal microbiomes of the BP group when compared to those of the control group. Significant alterations in alpha and beta diversity were observed between the oral microbiomes of the two groups. The mRNA levels of beta-defensin-2 and -3 were significantly upregulated in the buccal mucosa of the BP group. Conclusion: A BP diet may have a beneficial effect on oral and systemic health by modulating the bacterial flora and antimicrobial peptides of the oral cavity. Further investigations are needed to clarify how a BP diet affects overall human health.

scholarly journals Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 393
Author(s):  
Oliver Neuhaus ◽  
Wolfgang Köhler ◽  
Florian Then Bergh ◽  
Wolfgang Kristoferitsch ◽  
Jürgen Faiss ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Neurotrophic Factors ◽  
Common Symptom ◽  
Mrna Levels ◽  
Open Label ◽  
Immunological Parameters ◽  
Beneficial Effects

Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue.

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