Insights into Endothelin-3 and Multiple Sclerosis

AbstractEndothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.

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Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

Journal of Neuroinflammation ◽

10.1186/s12974-021-02145-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Sarinnapha M. Vasunilashorn ◽

◽

Long H. Ngo ◽

Simon T. Dillon ◽

Tamara G. Fong ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Blood Brain Barrier ◽

Plasma Levels ◽

Inflammatory Markers ◽

Brain Barrier ◽

Markers Of Inflammation ◽

Blood Brain ◽

Csf Levels ◽

The Relationship

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

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Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Cancers ◽

10.3390/cancers13030533 ◽

2021 ◽

Vol 13 (3) ◽

pp. 533

Author(s):

Rania F. Zaarour ◽

Bilal Azakir ◽

Edries Y. Hajam ◽

Husam Nawafleh ◽

Nagwa A. Zeinelabdin ◽

...

Keyword(s):

Cell Death ◽

Type I ◽

Dependent Manner ◽

Destruction Process ◽

Tumor Cell Death ◽

Complex Regulation ◽

Cancer Immunotherapies ◽

The Relationship ◽

Shed Light

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

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The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

Cells ◽

10.3390/cells9071711 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1711 ◽

Cited By ~ 1

Author(s):

Conor P. Duffy ◽

Claire E. McCoy

Keyword(s):

Multiple Sclerosis ◽

Autoimmune Disorder ◽

Cell Types ◽

Repair Process ◽

Rna Molecules ◽

Current State ◽

Non Coding Rna ◽

Repair Mechanisms ◽

Different Cell Types

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.

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Relationship between Social Support, Time Perspective and Suicide Ideations in Patients with Multiple Sclerosis

Asian Social Science ◽

10.5539/ass.v12n8p192 ◽

2016 ◽

Vol 12 (8) ◽

pp. 192 ◽

Cited By ~ 3

Author(s):

Saeed Ariapooran ◽

Masuod Rajabi ◽

Amirhosein Goodarzi

Keyword(s):

Multiple Sclerosis ◽

Social Support ◽

At Risk ◽

Time Perspective ◽

Suicide Ideation ◽

Significant Other ◽

Cross Sectional ◽

The Relationship ◽

Support Time

Introduction: Patients with Multiple Sclerosis (MS) are at risk for Suicide Ideation (SI). The relationship between Social Support (SS) and Time Perspective (TP) with SI is important among patients with MS. This study was performed to determine the prevalence of SI and the correlation between SS and TP with SI in Iranian patients with MS in Nahavand and Malayer.Methods: Using a cross-sectional analytic research design, we selected 79 participants among patients with MS in Nahavand and Malayer, Iran. Beck Scale for Suicidal Ideation, Multidimensional Scale of Perceived Social Support and Zimbardo’s Time Perspective Inventory were used for collecting the data.Results: The obtained results indicated that 30.3% of the patients with MS suffered from SI. There was a negative correlation between SS (from family, friends and significant other), Past Positive (PP) and Future (F) orientations and a positive correlation between Past Negative (PN) orientation and SI; SS from significant other and PP negatively predicted the SI in patients with MS.Conclusion: Based on the obtained results, the relationship between SS, PN, PP, F and SI and the role of SS from significant other and PP in predicting the SI in Nahavand and Malayer patients with MS were confirmed. Thus, it is necessary to develop support systems and apply the TP-based treatments for patients with MS who are at risk for SI.

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Increased Levels of Hepatocyte Growth Factor in Patients with DIC.

Blood ◽

10.1182/blood.v104.11.1041.1041 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1041-1041

Author(s):

Kazuo Kawasugi ◽

Maho Noguchi ◽

Haruko Tashiro ◽

Moritaka Gotoh ◽

Naoki Shirafuji ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Plasma Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Growth Factor ◽

One Step ◽

Sandwich Enzyme Immunoassay ◽

The Relationship ◽

Hepatocyte Growth

Abstract Injury of endothelial cells has been postulated as an initial trigger of the progression of DIC. Although hepatocyte growth factor (HGF) is a member of endothelium-specific growth factor, the relationship between HGF and DIC has not been described. To investigate the role of HGF, we measured plasma levels of HGF in patients with sepsis-associated (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=6). Plasma samples from those patients groups were assayed for HGF levels by enzyme-linked immunosorbent assay (ELIZA, TECHNE Corporation, USA). The VEGF levels were determined by one-step sandwich enzyme immunoassay (EIA, Chemicon International, USA). The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. In the septic patients with DIC, we found significant elevations in HGF levels compared to normal controls. Also, the HGF levels were elevated in the APL patients with DIC. However, we did not find any difference in plasma levels of VEGF in the APL and septic patients with DIC. There was a slight correlation between the TAT and HGF levels in both (septic and APL) patients groups with DIC. These results suggest that plasma levels of HGF may be candidates for a marker of DIC. It appears that HGF may contribute to the severity of DIC. Sepsis associated DIC APL with DIC Controls (n=10) *(P<0.005) significantly different controls HGF 7949±71230* 11902±10726 846±216pg/ml VEGF 172±7.0 209±35 188±8pg/ml TAT 28.4±17.5* 22.5±15.3* <3 μg/ml

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The relationship between disability and depression in multiple sclerosis: the role of uncertainty, coping, and hope

Multiple Sclerosis Journal ◽

10.1177/135245850100700611 ◽

2001 ◽

Vol 7 (6) ◽

pp. 411-416 ◽

Cited By ~ 101

Author(s):

Sharon G Lynch ◽

Dawn C Kroencke ◽

Douglas R Denney

Keyword(s):

Multiple Sclerosis ◽

Depression Scale ◽

Psychological Variables ◽

Disability Status ◽

Definite Multiple Sclerosis ◽

Clinically Definite Multiple Sclerosis ◽

Attending Physician ◽

The Relationship ◽

Predictors Of Depression

The relationship between disability and depression was studied in 188 patients with clinically definite multiple sclerosis (MS). Patients were administered the Zung Self-Rating Depression Scale, Ways of Coping, Uncertainty of Illness Scale, and Hope Scale during their regular clinic appointments. Their current level of disability was rated by the attending physician using the Expanded Disability Status Scale. Even when the depression measure was corrected for items overlapping with other symptoms or consequences of MS, depression was correlated with disability. Depression was also correlated with an array of psychological variables, including uncertainty concerning ones illness, hope, and the use of various emotion-centered, though not problem-centered coping strategies. Multiple regression analyses revealed that none of these psychological correlates mediated or moderated the relationship between disability and depression. Instead, disability, uncertainty, hope, and emotion-centered coping were significant independent predictors of depression, together accounting for approximately 40% of the variance in patients' self-reported depression. The relationship between disability and depression in MS is usually interpreted as evidence that depression is psychogenic and reactive to the demands and limitations of this disease. The demonstration that this relationship is not diminished when an array of potentially intervening psychological variables are included in the analysis raises questions concerning the validity of this interpretation.

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Mediating Role of Sense of Coherence in the Relationship of Perceived Stress with Fatigue and Pain in Multiple Sclerosis Patients

Qom Univ Med Sci J ◽

10.52547/qums.14.11.38 ◽

2021 ◽

Vol 14 (11) ◽

pp. 38-47

Author(s):

Samira Zarrabi-Ajami ◽

Hadi Zamanian ◽

Adis Kraskian Mujembari ◽

Sara Pashang ◽

◽

...

Keyword(s):

Multiple Sclerosis ◽

Perceived Stress ◽

Sense Of Coherence ◽

Mediating Role ◽

Multiple Sclerosis Patients ◽

Relationship Of ◽

The Relationship

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The relationship between disability and depression in multiple sclerosis: the role of uncertainty, coping, and hope

Multiple Sclerosis Journal ◽

10.1191/135245801701566998 ◽

2001 ◽

Vol 7 (6) ◽

pp. 411-416 ◽

Cited By ~ 12

Author(s):

S.G. Lynch ◽

D.C. Kroencke ◽

D.R. Denney

Keyword(s):

Multiple Sclerosis ◽

The Relationship

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CDPK6 phosphorylates and stabilizes MYB30 to promote hyperoside biosynthesis that prolongs the duration of full-blooming in okra

Journal of Experimental Botany ◽

10.1093/jxb/eraa174 ◽

2020 ◽

Vol 71 (14) ◽

pp. 4042-4056

Author(s):

Qing Yang ◽

Biying Dong ◽

Litao Wang ◽

Zhihua Song ◽

Lili Niu ◽

...

Keyword(s):

Ectopic Expression ◽

Fold Increase ◽

Bimolecular Fluorescence Complementation ◽

Dependent Manner ◽

Flavonoid Pathway ◽

Calcium Dependent ◽

Key Enzyme ◽

Dependent Protein ◽

The Relationship

Abstract The flowers of okra (Abelmoschus esculentus) open and wilt within only a few hours, and this is accompanied by accumulation of hyperoside, a secondary metabolite in the flavonoid pathway. However, little is known about the relationship between flavonoids and flowering. Here, we found that exogenous application of hyperoside extended the duration of the full-blooming period by more than 3-fold, and this was accompanied by a 14.7-fold increase in the expression of CALCIUM-DEPENDENT PROTEIN KINASE6 (AeCDPK6). Gene expression profiling indicated that the transcription factor AeMYB30 was co-expressed with AeCDPK6, and detailed protein interaction and phosphorylation experiments together with yeast two-hybrid and bimolecular fluorescence complementation assays demonstrated an interaction between AeMYB30 and AeCDPK6. AeCDPK6 specifically phosphorylated AeMYB30S191, leading to increased protein stability and prevention of degradation. Furthermore, AeMYB30 directly bound to the promoter of AeUF3GaT1, a key enzyme in the hyperoside biosynthesis pathway. Analysis of transgenic plants showed that AeCDPK6 was required for the hyperoside-induced phosphorylation of AeMYB30 to enhance its stability and transcriptional activity. Ectopic expression of AeCDPK6 promoted hyperoside accumulation and prolonged the full-blooming period in an AeMYB30-dependent manner. Our results indicate the role of AeCDPK6–AeMYB30 in the molecular mechanism by which hyperoside regulates the period of full blooming in okra, a plant with a short duration of flowering.

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