The role of MMP genes in recurrent depressive disorders and cognitive functions

2016 ◽  
Vol 28 (4) ◽  
pp. 221-231 ◽  
Author(s):  
Kinga Bobińska ◽  
Janusz Szemraj ◽  
Piotr Gałecki ◽  
Monika Talarowska
Keyword(s):  
Gene Expression ◽  
Cognitive Functions ◽  
Protein Level ◽  
Verbal Fluency ◽  
Verbal Learning ◽  
Rna Extraction ◽  
Human Organism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Separate Analysis

ObjectiveAmong the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance.MethodsThe study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay.ResultsBoth mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed.ConclusionsThe results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory–verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions.

scholarly journals Functional roles of COMP and TSP-4 in articular cartilage and their relevance in osteoarthritis

2021 ◽  
Author(s):  
◽  
Kathrin Maly
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Protein Level ◽  
Functional Role ◽  
Human Articular Cartilage ◽  
Serum Samples ◽  
Superficial Zone ◽  
Ecm Proteins ◽  
Healthy Cartilage

Osteoarthritis (OA) is a slowly progressing disease, resulting in the degradation of cartilage and the loss of joint functionality. The cartilage extracellular matrix (ECM) is degraded and undergoes remodelling in OA progression. Chondrocytes start to express degrading proteases but are also reactivated and synthesise ECM proteins. The spectrum of these newly synthesised proteins and their involvement in OA specific processes and cartilage repair is hardly investigated. Human articular cartilage obtained from OA patients undergoing knee replacement surgery was evaluated according to the OARSI histopathology grading system. Healthy, non-OA cartilage samples were used as controls. The expression and distribution of thrombospondin-4 (TSP-4) and the closely related COMP were analysed on the gene level by PCR and on the protein level by immunohistology and immunoblot assays. The potential of TSP-4 as a diagnostic marker was evaluated by immunoblot assays, using serum samples from OA patients and healthy individuals. The functional role of both proteins was further investigated in in vitro studies using chondrocytes isolated from femoral condyles of healthy pigs. The effect of COMP and TSP-4 on chondrocyte migration and attachment was investigated via transwell and attachment assays, respectively. Moreover, the potential of COMP and TSP-4 to modulate the chondrocyte phenotype by inducing gene expression, ECM protein synthesis and matrix formation was investigated by immunofluorescence staining and qPCR. The activation of cartilage relevant signalling pathways was investigated by immunoblot assays. These results showed for the first time the presence of TSP-4 in articular cartilage. Its amount dramatically increased in OA compared to healthy cartilage and correlated positively with OA severity. In healthy cartilage TSP-4 was primarily found in the superficial zone while it was wider distributed in the middle and deeper zones of OA cartilage. The amount of specific TSP-4 fragments was increased in sera of OA patients compared to healthy controls, indicating a potential to serve as an OA biomarker. COMP was ubiquitously expressed in healthy cartilage but degraded in early as well as re-expressed in late-stage OA. The overall protein levels between OA severity grades were comparable. Contrary to TSP-4, COMP was localised primarily in the upper zone of OA cartilage, in particular in areas with severe damage. COMP could attract chondrocytes and facilitated their attachment, while TSP-4 did not affect these processes. COMP and TSP 4 were generally weak inducers of gene expression, although both could induce COL2A1 and TSP-4 additionally COL12A1 and ACAN after 6 h. Correlating data were obtained on the protein level: COMP and TSP-4 promoted the synthesis and matrix formation of collagen II, collagen IX, collagen XII and proteoglycans. In parallel, both proteins suppressed chondrocyte hypertrophy and dedifferentiation by reducing collagen X and collagen I. By analysing the effect of COMP and TSP-4 on intracellular signalling, both proteins induced Erk1/2 phosphorylation and TSP-4 could further promote Smad2/3 signalling induced by TGF-β1. None of the two proteins had a direct or modulatory effect on Smad1/5/9 dependent signalling. In summary, COMP and TSP-4 contribute to ECM maintenance and repair by inducing the expression of essential ECM proteins and suppressing chondrocyte dedifferentiation. These effects might be mediated by Erk1/2 phosphorylation. The presented data demonstrate an important functional role of COMP and TSP-4 in both healthy and OA cartilage and provide a basis for further studies on their potential in clinical applications for OA diagnosis and treatment.

scholarly journals EXPRESSION OF ANTIVIRAL GENE ON TIGER SHRIMP Penaeus monodon AT DIFFERENT TISSUE AND BODY SIZE

2012 ◽  
Vol 7 (2) ◽  
pp. 95
Author(s):  
Andi Parenrengi ◽  
Andi Tenriulo ◽  
Samuel Lante
Keyword(s):  
Gene Expression ◽  
Defense Mechanism ◽  
Rna Extraction ◽  
Penaeus Monodon ◽  
Specific Response ◽  
Tiger Shrimp ◽  
Phenotype Distribution ◽  
Organ Tissue ◽  
Antiviral Gene

The role of tiger shrimp defense against invading pathogen on molecular level such antiviral gene expression is limited to be reported. Gene expression is a process which codes information of genes that is converted to the protein as a phenotype. Distribution of PmAV antivirus gene, that has been reported as an important gene on non-specific response immune, is needed to be observed to several organs/tissues and size of tiger shrimp. The aim of this study is to determine the distribution of gene antiviral expression at several organ/tissue and size of shrimp. The organs/tissues observed in this study were: gill, hepatopancres, muscle tissue, eyes, heart, stomach, gonad, and intestine. While the size of shrimp consisted of three groups, those are: (A) 10-20 g/ind., (B) 30-40 g/ind., and (C) 60-70 g/ind. Analysis of antiviral gene expression was performed by RNA extraction, followed by the cDNA syntesis, and amplification of gene expression by semi-quantitative PCR. The result of PCR optimation showed the optimal concentration of cDNA and primer was 1 μL and 50 mol, respectively for PCR final volume of 25 μL. Antiviral gene was expressed on the hepatopancreas and stomach in percentage of 50.0% and 16.7%, respectively. While the highest percentage of individual expressing the antiviral gene was observed in the shrimp size of C (66.7%), followed by B (50.0%) and A (16.7%). The result of study implied that the hepatopancreas has importantly involed in tiger shrimp defense mechanism on viral infection.

scholarly journals Is there a link between TNF gene expression and cognitive deficits in depression?

1970 ◽  
Vol 64 (1) ◽  
Author(s):  
Kinga Bobińska ◽  
Elżbieta Gałecka ◽  
Janusz Szemraj ◽  
Piotr Gałecki ◽  
Monika Talarowska
Keyword(s):  
Gene Expression ◽  
Verbal Memory ◽  
Verbal Fluency ◽  
Depressive Disorders ◽  
Verbal Learning ◽  
Test Group ◽  
Entire Group ◽  
Expression Levels ◽  
Protein Levels ◽  
Tnf Α

Neuroinflammation is a known factor in the pathogenesis of recurrent depressive disorders. Depression is accompanied by activated immune-inflammatory pathways including increased levels of TNFα, sTNFR1and sTNFR2.The purpose of this study was to analyse the TNF-α, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in patients with rDD, and to investigate the relationship between TNF-α,TNFRSF1A and TNFRSF1B gene expression and cognitive performance. The study comprised 158 subjects: patients with recurrent depressive disorder (n=89) and healthy subjects (n=69). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Both mRNA and protein expression levels of all genes were significantly higher in rDD subjects when compared to healthy controls. No statistically significant correlations were observed between the analysed variables in both the rDD group and the HS test group. The only exception was noticed in the HS test group, where increased expression of TNFRSF1A and TNFRSF1B gene negatively affected the performance of the AVLT test. However, statistically significant correlations between TNF, TNFRSF1A, TNFRSF1B mRNA gene expression levels and all the neuropsychological tests used in the survey for the entire group were observed. 1.The results of our study show increased expression of the TNF, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in depression. 2. Elevated expression of TNF-α, TNFRSF1A and TNFRSF1B negatively correlates with cognitive efficiency: working memory, executive functions, attention, auditory-verbal memory, effectiveness of learning processes and verbal fluency.

scholarly journals Relationship between antipsychotic medication, obesity and cognitive functions

2017 ◽  
Vol 18 (4) ◽  
pp. 272-278
Author(s):  
Urszula Łopuszańska ◽  
Marta Makara-Studzińska
Keyword(s):  
Cognitive Function ◽  
Waist Circumference ◽  
Abdominal Obesity ◽  
Cognitive Functions ◽  
Verbal Fluency ◽  
Verbal Learning ◽  
The Body ◽  
Typical Antipsychotic ◽  
Antipsychotic Medications ◽  
Learning Test

AbstractIntroduction: The purpose of this study was to examine whether the combination of atypical and typical antipsychotic medications is related with metabolism and cognitive functions in the same manner and degree as taking medications of one kind only, i.e. atypical or typical.Material and methods: The participants of the study comprised of 91 adults with diagnosed mental illness (F-20-F69). The participants were divided into groups on the basis of the kind of administered medications: T+A (typical and atypical medications), A (atypical medications), T (typical medications), P (antidepressants, sedatives, normothymic/antiepileptic drugs). In the study, Short Test of Mental Status (STMS), Verbal Fluency Test (VFT), Rey Auditory Verbal Learning Test (RAVLT) were used for the purpose of examining cognitive functions.Results: The kind of antipsychotic medications taken by the patients did not differentiate the group in relation to BMI (p<0.13), nor in relation to the level of general cognitive function (p<0.72) or verbal fluency (p<0.34). Both atypical antipsychotic medications and the combination of atypical and typical medications were related to the occurrence of abdominal obesity (p<0.01). An increase in waist circumference decreased an ability of abstract reasoning (p<0.005). When it comes to the body mass index, waist circumference negatively correlated with the delayed memory (p< 0.03, p<0.004).Discussion: Both the combination of atypical and typical antipsychotic medications and atypical medications are associated with the occurrence of abdominal obesity. The deposition of fat tissue in the abdomen negatively correlated with an ability to learn.Conclusions: The future studies might explain the interactions between antipsychotic medications, obesity and cognitive function.

The Possibilities of the Improvement Language Competencies in Children with Dyslexia. The Evaluation of the Tomatis Therapy in Children Aged 6–10 years of Age

2017 ◽  
Vol 41 (S1) ◽  
pp. s790-s790
Author(s):  
E. Mojs ◽  
A. Sudol ◽  
W. Samborski
Keyword(s):  
Reaction Time ◽  
Cognitive Functions ◽  
Verbal Memory ◽  
Verbal Fluency ◽  
Verbal Learning ◽  
Special Device ◽  
Learning Abilities ◽  
Competing Interest ◽  
Age Range ◽  
Language Competencies

Audio psycho–phonological stimulation training is a method based on listening to various musical sounds by way of a special device called electronic ear. The goal of this therapy is to enhance damaged hearing and consequently facilitate greater stimulation of central nervous system and improve cognitive functions i.e. attention and learning abilities. The second goal was to evaluate the effectiveness of the Tomatis method in the treatment of cognitive functions in children with developmental dyslexia. Data were collected from forty children (age range 6–10 all of whom had various lexical impairments and diagnosed as dyslexia. All children IQ ranged 78–110. All subjects underwent therapy based on the Tomatis method. The relevance group constituted, by healthy ones. Further assessment included reaction time, over sensitivity of hearing sense, verbal fluency, attention, abilities of verbal learning and learning memory–immediate and long term. The effects of the therapy were measured after 9 months of stimulation. Statistically relevant improvement of most evaluated functioning parameters, including shorter time of adequate reaction to presented stimuli was observed. Not only did the patients have lower threshold of sensitivity of hearing sense, ability to localize sources of sound significantly improved (P 0.05) also. Subjects’ verbal fluency, attention and immediate verbal memory were enhanced. The phonological abilities improved. Tomatis training significantly improved subjects’ cognitive functioning. We could demonstrate its efficiency in relation to such parameters as reaction time, localization of sources of sound and over sensitivity to audio stimuli. The Tomatis method is a useful way of the speech treatment impediments.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals RNA Polymrase II gene expression in clinical Leishmania major isolates with no-response-to-drug pattern

2019 ◽  
Vol 9 (4) ◽  
pp. 4126-4130
Keyword(s):  
Gene Expression ◽  
Leishmania Major ◽  
Rna Extraction ◽  
Effective Vaccine ◽  
North Of Iran ◽  
Rnap Ii ◽  
The One ◽  
Day By Day ◽  
Written Informed Consent

Cutaneous leishmaniasis (CL) is one of the most important infectious diseases in the world and is increasing day by day. No effective vaccine has been made against this disease, so far. An important issue with this disease is the development of drug resistance or no response to drug, which is going to spreading that its mechanism has not yet been completely identified. The main aim of this study was to assessment the expression of RNAPII gene in no response to drug and susceptible isolates of Leishmania major. The patients with CL from the central and North of Iran were considered for this study. The samples were transferred in RNAlater solution and stored in -20 °C. RNA extraction and cDNA synthesis were performed. The gene expression analysis was done with SYBR Green Real Time PCR. Written informed consent was filled up by patients and then information forms were written based on Helsinki declaration. Statistical analysis was done with SPSS (16.0; SPSS Inc, Chicago) using independent t-test. P ≤ 0.05 was considered significant. It was observed that the gene expression of RNAPII in the no response to drug isolates was lower than that the one in drug sensitive isolates. A change in the expression of RNAP II in no response to drug isolates of L. major can indicate the potential role of this gene in the related mechanism.

scholarly journals Role of the Distal sarA Promoters in SarA Expression in Staphylococcus aureus

2005 ◽  
Vol 73 (7) ◽  
pp. 4391-4394 ◽  
Author(s):  
Ambrose L. Cheung ◽  
Adhar C. Manna
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Protein Level ◽  
Target Gene ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Regulatory Locus ◽  
Target Gene Expression

ABSTRACT The global regulatory locus sarA comprises a 375-bp open reading frame that is driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We mutated the weaker P3 and P2 promoters to ascertain the effect of the change on SarA protein and target gene expression. Our results indicated that the solely active P1 promoter led to a lower SarA protein level, which has an effect on agr transcription and subsequently had corresponding effects on hla, sspA, and spa transcription, probably in both agr-independent and agr-dependent manners.

Early Role of NFKB2 on the Myeloid Differentiation of CD34+ Hematopoietic Cells

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1276-1276
Author(s):  
Greice A. Molfetta ◽  
Dalila L. Zanette ◽  
Rodrigo A. Panepucci ◽  
Wilson A. Silva ◽  
Marco A. Zago
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Rna Extraction ◽  
Myeloid Differentiation ◽  
Signaling Proteins ◽  
Myeloid Lineage ◽  
Before And After ◽  
A Subunit ◽  
And Control

Abstract Efforts to understand the molecular mechanisms underlying the differentiation of hematopoietic progenitor cells into mature blood cells have focused mainly on late events that largely reflect the differentiated state of the cells. In order to evaluate early changes of the gene expression profile of HSPC subjected to differentiation stimuli, transcriptional profiles of immuno-magnetically sorted bone marrow CD34+ HSPC were generated before and after 12 and 40 hours of culture with supplemented media favoring myeloid or erythroid commitment. Four independent samples were pooled and submitted to each treatment, and cells aliquots were subjected to RNA extraction and to methylcellulose cultures. CD34+ HSPC without previous stimulation generated about equal percentages (50% each) of erythroid (BFU-E) and myeloid (CFU-GM) colonies, whereas upon erythroid stimulation the median percentages of BFU-E, CFU-GM and mixed colonies (CFU-Mix) were, respectively, 61%, 38% and 1% for the12 hour treatment and 83%, 17% and 0% for 40 hours treatment. Conversely, upon myeloid stimulation, respectively, 37%, 61% and 2% colonies were observed after 12 hours and 23%, 61% and 14% for 40 hours treatment. These results indicate that after 12 and 40 hours of treatment, the genetic program of those cells were shifted towards the desired phenotype. Serial analysis of gene expression (SAGE) was employed to generate four independent libraries, each with more than 60,000 tags sequenced, representing more than 12,000 annotated transcripts. By analyzing the differentially regulated transcripts between the control CD34+ HSPC and the stimulated cells, we observed a set of genes that were initially up-regulated at 12 hours but were then down-regulated at 40 hours, exclusively after myeloid stimuli. Among those we found transcripts for IL1B, LTB, TNFRSF4 and NFKB2. Additionally, the receptor for LTB and the inhibitor of NF-κB signaling NFKBIA (IKBA) were respectively, up and down modulated at both time points. All those transcripts code for signaling proteins of the nuclear factor kappa B (NF-κB) pathway. More specifically, NFKB2 is a subunit of the NF-κB transcription factor (TF) that together with RELB mediates the non-canonical NF-κB pathway. The up-regulation followed by a down regulation was confirmed for NFKB2 and also demonstrated for RELB and NFKB1, indicating that the NF-κB pathway could be involved in the early commitment of CD34+ HSPC towards the myeloid lineage. To test this hypothesis, interference RNA (RNAi) against NFKB2 and control RNAi were transfected into BM CD34+ HSPC. Cells submitted to transfection with RNAi were stimulated towards the myeloid lineage and subjected to evaluation on methylcellulose cultures. Transcript levels of NFKB2 and RELB (a transcription target of NFKB2) were shown to be down-modulated, confirming the successful inhibition of NFKB2. After inhibition of NFKB2, the percentage of CFU-GM and BFU-E colonies shifted from 53% and 47% on control cells, respectively, to 22% and 78%. Altogether, our results indicate that NFKB2 has a role in the early commitment of CD34+ HSPC towards the myeloid lineage, directly inducing the differentiation program or, alternatively, protecting early myeloid progenitors from apoptosis.

scholarly journals Expression and Secretion of CXCL-8 and CXCL-10 FromMycobacterium BovisBCG-Infected Human Epithelial Cells: Role of IL-4

2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Patricia Méndez-Samperio ◽  
Elena Miranda ◽  
Abraham Vázquez
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Mrna Level ◽  
Neutralizing Antibody ◽  
Active Role ◽  
Polymerase Chain Reaction Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chemokine Production ◽  
Human Epithelial Cells

CXC chemokine release can be modulated by Th2-derived cytokines. Interleukin(IL)-4 is one of the cytokines that are the hallmark of the Th-2 response, and plays an important role in human tuberculosis. In the current study, we investigated the effect of IL-4 on chemokine production by human epithelial cells infected withMycobacterium bovisbacillus calmette-guérin (BCG). Gene expression of CXCL-8 and CXCL-10 was determined by the reverse transcription (RT)-polymerase chain reaction method. The levels of immunoreactive CXCL-8 and CXCL-10 were determined by enzyme-linked immunosorbent assay. We found that, althoughM. bovisBCG induced gene expression of CXCL-8 and CXCL-10 inM. bovisBCG-infected human epithelial cells, CXCL-8 mRNA level was significantly reduced by IL-4, whereas no significant effect of IL-4 was observed on CXCL10 mRNA level. In addition, IL-4 decreased CXCL-8 (in a graded and significant manner) but not CXCL-10 secretion. These results were further confirmed, since a significant reversion was obtained with a neutralizing antibody to human IL-4, whereas an isotype-matched control antibody had no significant effect on CXCL-8 secretion. Furthermore, we found a similar effect of IL-4 onM. bovisBCG-induced CXCL-8 and CXCL-10 secretion by using other human epithelial A549 cell line. Collectively, these data demonstrate thatM. bovisBCG-infected human epithelial cells can have an active role in a local inflammatory immune response via the secretion of CXC chemokines which can be selectively regulated by Th2-derived cytokines.

scholarly journals Novel HDGF/HIF-1α/VEGF axis in oral cancer impacts disease prognosis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Wei Lin ◽  
Shih-Tsung Huang ◽  
Jian-Ching Wu ◽  
Tian-Huei Chu ◽  
Shih-Chung Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Oral Cancer ◽  
Protein Expression ◽  
Protein Level ◽  
Neutralizing Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Vegf Gene ◽  
Vegf Expression

Abstract Background Hepatoma-derived growth factor (HDGF) participates in angiogenesis and represents a negative prognostic factor in oral cancer. The current study was designed to elucidate the regulatory mechanism between HDGF and vascular endothelial growth factor (VEGF) and the clinical impact of oral cancer. Methods TCGA data and surgical samples from oral cancer patients were used for the clinicopathological parameter and survival analysis. Human oral cancer SCC4 and SAS cells were treated with recombinant HDGF protein. VEGF gene expression and protein level were analyzed by RT-PCR, Western blotting, and enzyme-linked immunosorbent assay. The signaling pathways for regulating VEGF expression were investigated. The nucleolin neutralizing antibody and HIF-1α inhibitor were applied to SCC4 cells to investigate their effects on the HDGF-stimulated VEGF pathways. Results TCGA and immunohistochemical analysis revealed a positive correlation between HDGF and VEGF expression in oral cancer tissues. Recombinant HDGF significantly increased VEGF gene and protein expression in oral cancer SCC4 cells in a dose-dependent manner. HDGF enhanced the phosphorylation levels of AKT and IkB and the protein level of HIF-1α and NF-κB. The nucleolin-neutralizing antibody abolished HDGF-stimulated HIF-1α, NF-κB and VEGF protein expression in SCC4 cells. The HIF-1α inhibitor antagonized the HDGF-induced VEGF gene expression. High VEGF expression was strongly correlated with HDGF expression, advanced disease, and poor survival. Conclusion This study postulated a new pathway in which HDGF activated HIF-1α and then induced VEGF expression through binding to membrane nucleolin under normoxic conditions, leading to poor disease control. The HDGF/HIF-1α/VEGF axis is important for developing future therapeutic strategies.

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