Phosphorylation of S6 Protein as a Potential Biomarker in Surgically Treated Refractory Epilepsy

2020 ◽  
Vol 42 (5-6) ◽  
pp. 230-236
Author(s):  
Felipe I. Chodraui ◽  
Camila Araújo B. Garcia ◽  
Niele D. Mendes ◽  
Marcelo V. Santos ◽  
Pâmela S. Beggiora ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Clinical Aspects ◽  
Control Group ◽  
Type I ◽  
Phosphorylated Protein ◽  
Downstream Target ◽  
Molecular Features ◽  
Brain Anomalies ◽  
Potential Biomarker

The tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) exhibit similar molecular features that are dependent on the hyperactivation of the mTOR pathway. They are all associated with refractory epilepsy and the need for surgical resection with varying outcomes. The phosphorylated protein S6 (pS6) is a downstream target of mTOR, whose increased expression might indicate mTOR hyperactivation, but which is also present when there is no alteration in the pathway (such as in FCD type I). We have performed immunohistochemical marking and quantification of pS6 in resected brain specimens of 26 patients clinically and histologically diagnosed with TSC, FCD IIB, or HME and compared this data to a control group of 25 patients, to measure the extent of pS6 positivity and its correlation with clinical aspects. Our results suggest that pS6 may serve as a reliable biomarker in epilepsy and that a greater percentage of pS6 marking can relate to more severe forms of mTOR-dependent brain anomalies.

Serum MicroRNA-4521 is a Potential Biomarker for Focal Cortical Dysplasia with Refractory Epilepsy

2015 ◽  
Vol 41 (4) ◽  
pp. 905-912 ◽  
Author(s):  
Xiaofeng Wang ◽  
Yuqiang Sun ◽  
Zeshi Tan ◽  
Ningwei Che ◽  
Anlong Ji ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Serum Microrna ◽  
Potential Biomarker

scholarly journals Ultrasonographic features of focal cortical dysplasia and their relevance for epilepsy surgery

2018 ◽  
Vol 45 (3) ◽  
pp. E5 ◽  
Author(s):  
Kevin Akeret ◽  
David Bellut ◽  
Hans-Jürgen Huppertz ◽  
Georgia Ramantani ◽  
Kristina König ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Diagnostic Yield ◽  
Focal Cortical Dysplasia ◽  
Intraoperative Ultrasound ◽  
Cortical Dysplasia ◽  
Added Value ◽  
Seizure Outcome ◽  
Type I ◽  
Type Ii ◽  
Drug Refractory Epilepsy

OBJECTIVESurgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)–associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy.METHODSThe authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome.RESULTSThe neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis.CONCLUSIONSMorphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.

scholarly journals Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1867
Author(s):  
Shang-Der Chen ◽  
Hsiu-Yung Pan ◽  
Jyun-Bin Huang ◽  
Xuan-Ping Liu ◽  
Jie-Hau Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cortical Neurons ◽  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Expression Profiles ◽  
Cortical Dysplasia ◽  
Sequencing Analysis ◽  
Circulating Mirnas ◽  
Potential Biomarker ◽  
Serum Exosomes

Focal cortical dysplasia (FCD) is a congenital malformation of cortical development where the cortical neurons located in the brain area fail to migrate in the proper formation. Epilepsy, particularly medically refractory epilepsy, is the most common clinical presentation for all types of FCD. This study aimed to explore the expression change of circulating miRNAs in patients with FCD from serum exosomes. A total of nine patients with FCD and four healthy volunteers were enrolled in this study. The serum exosomes were isolated from the peripheral blood of the subjects. Transmission electron microscopy (TEM) was used to identify the exosomes. Both exosomal markers and neuronal markers were detected by Western blotting analysis to prove that we could obtain central nervous system-derived exosomes from the circulation. The expression profiles of circulating exosomal miRNAs were assessed using next-generation sequencing analysis (NGS). We obtained a total of 107 miRNAs with dominant fold change (>2-fold) from both the annotated 5p-arm and 3p-arm of 2780 mature miRNAs. Based on the integrated platform of HMDD v3.2, miRway DB and DIANA-miRPath v3.0 online tools, and confirmed by MiRBase analysis, four potentially predicted miRNAs from serum exosomes in patients with FCD were identified, including miR194-2-5p, miR15a-5p, miR-132-3p, and miR-145-5p. All four miRNAs presented upregulated expression in patients with FCD compared with controls. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category of four target miRNAs, we found eight possible signaling pathways that may be related to FCD. Among them, we suggest that the mTOR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, and cell cycle regulation and TGF-beta signaling pathway are high-risk pathways that play a crucial role in the pathogenesis of FCD and refractory epilepsy. Our results suggest that the circulating miRNAs from exosomes may provide a potential biomarker for diagnostic, prognostic, and therapeutic adjuncts in patients with FCD and refractory epilepsy.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

2020 ◽  
pp. 21-25
Author(s):  
Tupitsyn V.V. ◽  
Bataev Kh.M. ◽  
Men’shikova A.N. ◽  
Godina Z.N.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Digestive System ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Internal Organs ◽  
History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

PENGARUH PEMBERIAN KOMBINASI EKSTRAK BUAH MENGKUDU (Morinda citrifolia L.) DAN KUNYIT (Curcuma longa) TERHADAP HISTOPATOLOGI GINJAL TIKUS WISTAR YANG DIINDUKSI ALLOXAN

2020 ◽  
Vol 5 (2) ◽  
pp. 319-327
Author(s):  
Pelastri Rahayu ◽  
◽  
Retno Hestiningsih ◽  
Martini Martini ◽  
Dwi Sutiningsih ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Curcuma Longa ◽  
Morinda Citrifolia ◽  
Control Group ◽  
Type I ◽  
Turmeric Extract ◽  
Measurement Results ◽  
Diabetes Nephropathy

The prevalence of DM in Riskesdas in 2018 according to the Perkeni consensus in 2015 is higher than according to the Perkeni consensus in 2011, the prevalence was10.9%. The disease can develop into diabetes nephropathy, Increased prevalence of diabetic nephropathy directly proportional with an increase in diabetes prevalence. Diabetic nephropathy is a microvascular complication in diabetics that develops around 30% in patients with type I DM and about 40% in patients with type II DM. Turmeric extract has antioxidant and anti-inflammatory effects to prevent the bad development of diabetes nephropathy. This study looked at the effect of giving a combination of noni and turmeric extract on histopathology of alloxan-induced renal rats. A total of 25 mice were divided into 5 treatment groups, namely the PI group (250 mg / kgBB extract dose), PII group (500 mg / kgBB extract dose), PIII group (750 mg / kgBB extract dose), positive control group (glibenklamid) and negative control group (without extract and glibenklamid). The study used Post Test Only Group. The highest percentage decrease in blood glucose in the PI group was 56.11% and the lowest decrease in the PIII group was 24.12% with p = 0.012. The results of the study were not based on the number of extract doses. The measurement results of rat body weight and glomerular diameter were not affected by blood glucose level with p = 0.700 for body weight and p = 0.187 for glomerular measurement results.

Antidiabetic and Hypolipidemic Effects of Extracts of Gymnema Sylvestre in Streptozotocin Induced Type I Diabetes in Rats

2017 ◽  
Vol 12 (3) ◽  
Author(s):  
Nishtha R. Mahida ◽  
G. . Mandali ◽  
Vijaysinh V. Sindha ◽  
S. K. Raval
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Type I Diabetes ◽  
Histopathological Examination ◽  
Diabetic Control ◽  
Hypolipidemic Activity ◽  
Control Group ◽  
Type I ◽  
Gymnema Sylvestre ◽  
Altered Glucose

Gymnema sylvestre of the family Asclepiadaceae is one of the most important medicinal plants of the central eco-region. It is popularly known as Gurmar, which means “sugar killer”. Extract of leaves is reported to have tannins, gum, flavonoids, proteins and saponins. It has displayed a wide array of pharmacological activities. This study was aimed to investigate the antidiabetic and hypolipidemic effects of Gymnema sylvestre extract in experimentally induced diabetes in rats. Diabetes was produced in adult Wistar rats with single dose of streptozotocin (STZ) @ 60 mg/kg b.wt. intraperitoneally. After the confirmation of diabetes on 7th day (sugar >200 mg/dl), alcoholic and aqueous extracts of G. sylvestre (400 mg/kg) were administered orally to the experimental rats from 8th day and continued for 42 days thereafter. The antidiabetic and hypolipidemic activity was estimated by measuring blood glucose, lipid profile and histopathological examination of various tissues from all the groups. Administration of STZ resulted in a significant (p less than 0.01) increase in blood glucose and lipid profile and histopathological alterations in Diabetic control group as compared to healthy control group. Gymnema treatment demonstrated significant (p less than 0.01) antidiabetic effect indicated by restoration of blood glucose compared to STZ control group. The study concluded that extracts of Gymnema sylvestre improved the altered glucose and lipid profile in diabetic rats, suggesting that the Gymnema Sylvestre extracts exhibit the antidiabetic and hypolipidemic activity.

scholarly journals MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng Zheng ◽  
Yan Chen ◽  
Yinzhou Wang ◽  
Yongkun Li ◽  
Qiong Cheng
Keyword(s):  
Cell Death ◽  
Intracranial Aneurysm ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Control Group ◽  
Type I ◽  
Mrna Levels ◽  
Reporter Assay ◽  
Over Expression ◽  
Tnf Α

AbstractCollagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

scholarly journals POS0611 THE EFFECT OF RITUXIMAB BIOSIMILAR THERAPY ON THE EXPRESSION OF INTERFERON-STIMULATED GENES (“INTERFERON SIGNATURE”) IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Signature ◽  
Response To Therapy ◽  
Type I Interferons ◽  
Control Group ◽  
Type I ◽  
Acute Phase Reactants ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Healthy Donors

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared

scholarly journals Camelina Oil Supplementation Improves Bone Parameters in Ovariectomized Rats

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1343
Author(s):  
Iwona Puzio ◽  
Dorota Graboś ◽  
Marek Bieńko ◽  
Radosław P. Radzki ◽  
Aneta Nowakiewicz ◽  
...  
Keyword(s):  
Serum Level ◽  
Recovery Period ◽  
Physiological Saline ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Sham Operation ◽  
Type I ◽  
Camelina Oil ◽  
Bone Parameters ◽  
Ovx Rats

The aim of the present study was to determine the effect of administration of Camelina sativa oil (CO) as a source of polyunsaturated fatty acids (PUFA) on bone parameters in ovariectomized rats (OVX). Overall, 40 10-week-old healthy female Wistar rats were divided into 4 groups with 10 animals in each. Rats in the control group (SHO) were subjected to a sham operation, whereas experimental rats (OVX) were ovariectomized. After a 7-day recovery period, the SHO the rats received orally 1 mL of physiological saline for the next 6 weeks. The OVX rats received orally 1 mL of physiological saline (OVX-PhS), 5 g/kg BW (OVX-CO5), or 9 g/kg BW (OVX-CO9) of camelina oil. The use of camelina oil had a significant effect on body weight, lean mass, and fat mass. The camelina oil administration suppressed the decrease in the values of some densitometric, tomographic, and mechanical parameters of femur caused by estrogen deficiency. The CO treatment increased significantly the serum level of osteocalcin and decreased the serum level of C-terminal telopeptide of type I collagen in the OVX rats. In conclusion, camelina oil exerts a positive osteotropic effect by inhibiting ovariectomy-induced adverse changes in bones. Camelina oil supplementation can be used as an efficient method for improving bone health in a disturbed state. However, further research must be carried out on other animal species supplemented with the oil.

Cartilage Regeneration with Cell-free Type 1 Collagen Matrix – Past, Present and Future (Part 1 – Clinical Aspects)

2020 ◽  
Author(s):  
Philip Peter Roessler ◽  
Turgay Efe ◽  
Dieter Christian Wirtz ◽  
Frank Alexander Schildberg
Keyword(s):  
Type I Collagen ◽  
Case Series ◽  
Cartilage Regeneration ◽  
Collagen Matrix ◽  
Treatment Method ◽  
Collagen Type I ◽  
Legal Framework ◽  
Clinical Aspects ◽  
Type I ◽  
Collagen Hydrogel

AbstractCartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified as matrix-induced autologous cartilage regeneration (MACR), all rely on the chemotactic stimulus of a cross-linked matrix, which mostly consists of collagens. Given the example of a commercially available type I collagen hydrogel, the state of clinical experience with MACR shall be summarized and an outlook on the development of the method shall be provided. It has been demonstrated in the clinical case series summarized here over the past few years that the use of the matrix is not only safe but also yields good clinical-functional and MR-tomographic results for both small (~ 10 mm) and large (> 10 mm) focal cartilage lesions. Depending on the size of the defect, MACR with a collagen type I matrix plays an important role as an alternative treatment method, in direct competition with both: microfracture and MACT.

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