Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signaling by controlling acetylcholine receptor clustering. High MMP-3 levels in a proportion of myasthenia gravis (MG) patients have been reported. A pathogenic role of MMP-3 in other neurological disorders has been suggested but not proven. We have therefore examined the levels of MMP-3 in 124 MG patients and compared them to 59 multiple sclerosis (MS) patients, 74 epilepsy patients, 33 acute stroke patients, and 90 healthy controls. 15.3% of the patients in the MG group were MMP-3-positive (defined as higher than cutoff value 48 ng/mL) with very high mean MMP-3 concentration (79.9 ng/mL), whereas the proportion of MMP-3 positive patients in the MS (3.4%), epilepsy (6.7%), stroke (0%), and the control group (4.4%) was significantly lower. Mean MMP-3 concentration in the total MG group (25.5 ng/mL) was significantly higher than in the MS (16.6 ng/mL) and stroke (11.7 ng/mL) groups, but did not differ significantly from the epilepsy (19.4 ng/mL) and the control group (23.4 ng/mL). MMP-3 may have a specific pathogenic effect in MG in addition to being associated with autoimmune diseases in general.

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Autophagy Modulators and Neuroinflammation

Current Medicinal Chemistry ◽

10.2174/0929867325666181031144605 ◽

2020 ◽

Vol 27 (6) ◽

pp. 955-982 ◽

Cited By ~ 4

Author(s):

Kyoung Sang Cho ◽

Jang Ho Lee ◽

Jeiwon Cho ◽

Guang-Ho Cha ◽

Gyun Jee Song

Keyword(s):

Neurodegenerative Disorders ◽

Neurological Disorders ◽

Mammalian Cells ◽

Critical Role ◽

Therapeutic Agents ◽

Mechanisms Of Action ◽

Scientific Interest ◽

Therapeutic Tools ◽

Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

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Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

BioMed Research International ◽

10.1155/2020/7828392 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 6

Author(s):

Wanxin Liu ◽

Ren Zhang ◽

Rong Shu ◽

Jinjing Yu ◽

Huan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Susceptibility ◽

Precancerous Lesions ◽

Bacterial Community Composition ◽

Intestinal Flora ◽

Control Group ◽

Healthy Controls ◽

Healthy Individuals

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

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High prevalence of campylobacter excretors among Liberian children related to environmental conditions

Epidemiology and Infection ◽

10.1017/s0950268800067364 ◽

1988 ◽

Vol 100 (2) ◽

pp. 227-237 ◽

Cited By ~ 16

Author(s):

Kåre Mølbak ◽

Niels Højlyng ◽

Knud Gaarslev

Keyword(s):

Environmental Contamination ◽

Environmental Conditions ◽

High Intensity ◽

Bacterial Pathogen ◽

Urban Slum ◽

Pathogenic Role ◽

High Prevalence ◽

Very High

SUMMARYCampylobacter was the bacterial pathogen most prevalent in 850 children, aged 6–59 months, examined in a house-to-house diarrhoea survey in two Liberian communities. 44·9% of the children from an urban slum and 28·4% from a rural area were excretors. Since the prevalence of diarrhoea was very high and consequently many convalescent carriers were found, it was not possible to evaluate the pathogenic role of campylobacter.The excretor rate increased with ago and was significantly correlated to the uso of supplementary feeding, inversely correlated to the quality of the water supply, and also associated with helminthic infestation. Results from re-examination of 172 children suggested a high intensity of transmission.The findings all indicate the existence of a heavy environmental contamination with campylobacter, probably of both human and animal faecal origin.

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Association of NOS3 gene with metabolic syndrome in hypertensive patients

Thrombosis and Haemostasis ◽

10.1160/th04-02-0103 ◽

2004 ◽

Vol 92 (08) ◽

pp. 413-418 ◽

Cited By ~ 35

Author(s):

Maria Fernandez ◽

Rocio Ruiz ◽

Maria Gonzalez ◽

Reposo Ramirez-Lorca ◽

Carmen Couto ◽

...

Keyword(s):

Metabolic Syndrome ◽

Geographical Area ◽

Allelic Frequency ◽

Control Group ◽

Risk Haplotype ◽

Healthy Controls ◽

Hypertensive Patients ◽

Genotypic Distribution ◽

Nos3 Gene

SummaryRecent data from animal models indicate that the eNOS null mice present a phenotype that resemble the human metabolic syndrome (hypertension, insulin resistance and hypertriglyceridemia). In this work, we have studied whether NOS3 gene, previously related to endothelial dysfunction, might have a role in metabolic syndrome susceptibility in hypertensive patients. To carry out the study, we genotyped 105 hypertensive patients ≤ 60 years old with two polymorphisms of NOS3 gene: 1132 T>C and 7164 G>T (GeneBank:AF519768.1).To check the allelic frequency of these polymorphisms in our geographical area, we also genotyped 94 unselected healthy controls (control group). To perform sample genotyping, we designed a novel FRET system coupled to real time PCR. There were no differences in genotypic distribution or allelic frequency between hypertensive patients and the control group. However, we observed that 786CC genotype was significantly more frequent in hypertensive patients with metabolic syndrome than in those without the syndrome (p=0.0022). When both polymorphisms were analyzed, we identified the 786C894G as the risk haplotype for metabolic syndrome susceptibility (p=0.011). These data suggest a role of the NOS3 gene in the pathogenesis of metabolic syndrome in hypertensive patients.

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Increased Zinc Serum Level: New Clues in Babol Stroke Patients, Northern Iran

Stroke Research and Treatment ◽

10.1155/2018/7681682 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Alijan Ahmadi Ahangar ◽

Payam Saadat ◽

Sona Niroomand ◽

Shayan Alijanpour ◽

Reza Sohrabnezhad ◽

...

Keyword(s):

Heart Disease ◽

Serum Level ◽

Ischemic Heart Disease ◽

Serum Levels ◽

Ischemic Heart ◽

Control Group ◽

Stroke Patients ◽

Northern Iran ◽

The Difference

Background. Stroke is the second leading cause of death worldwide. The role of zinc as a new predictor of stroke was considered. Methods. This prospective study was conducted in Ayatollah Rouhani Hospital within a year on 100 stroke and 100 control patients. Findings. The difference in zinc serum level in two groups was significant (deficiency: 3 (3%) in patients versus 20 (20%) in control group, normal: 25 (25%) versus 54 (54%), and increased level: 72 (72%) versus 26 (26%); p<0.001). Difference in zinc serum levels was statistically significant with ischemic heart disease (deficiency: 0 cases (0%), normal: 8 cases (24%), increased level: 24 cases (75%), p=0.003). Increases in zinc serum level were significantly correlated with the frequency of hemorrhagic and ischemic patients (deficiency: 3 (3.3%) hemorrhagic versus 0 (0%) ischemic; normal: 19 (21%) versus 6 (60%), increased level: 68 (75.6%) versus 4 (40%); p=0.025). Regression logistics showed that ischemic heart disease (p<0.001; OR = 28.29, %95 CI: 5.53; 144.87), hyperlipidemia (p<0.001; OR = 0.26, %95 CI: 0.12; 0.56), and zinc serum level (p<0.001, OR = 15.53, %95 CI: 4.03; 59.83) each had a significant role. Conclusions. Babol stroke patients are prone to increased zinc serum level as a new parameter. Ischemic heart disease, increased levels of zinc, and hyperlipidemia were found to be probable predictor factors for stroke in Babol.

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Fractional Exhaled Nitric Oxide Measurement in Pulmonary Hypertension: A Follow-Up Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617702243 ◽

2017 ◽

Vol 24 (3) ◽

pp. 483-488 ◽

Cited By ~ 3

Author(s):

Nilay Orak Akbay ◽

Zuleyha Bingol ◽

Esen Kiyan ◽

Ekrem Bilal Karaayvaz ◽

Ahmet Kaya Bilge ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Function Tests ◽

Exhaled Nitric Oxide ◽

World Health ◽

Control Group ◽

Healthy Controls ◽

Fractional Exhaled Nitric Oxide

Pulmonary hypertension (PH) is a fatal disease although significant improvements in treatment are achieved. Easily implemented and noninvasive prognostic techniques are needed while following-up these patients. The aim was to investigate the role of fractional exhaled nitric oxide (FeNO) in follow-up for patients with PH. In this longitudinal study, patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) who were seen in PH Outpatient Clinic, Istanbul Faculty of Medicine, Istanbul University, were enrolled in the study. Echocardiography, 6-minute walking test, brain natriuretic peptide, and FeNO measurements were performed, and World Health Organization functional class was evaluated to all patients at baseline, and third, and sixth months. Right-heart catheterization and pulmonary function tests at the time of diagnosis were recorded. The study comprised 31 patients (23 women, 8 men; mean age: 53.4 ± 17.1 years) with PAH (n = 19) and CTEPH (n = 12) and 80 healthy controls. Patients with PH had lower FeNO values than the control group (16.5 ppb vs 19.8 ppb; P < .05). Fractional exhaled nitric oxide values did not change during follow-up and did not correlate with other follow-up measures except tricuspid annular plane systolic excursion values. Fractional exhaled nitric oxide was higher in the idiopathic PAH subgroup at baseline and at third month than patients with PAH associated with other diseases. Fractional exhaled nitric oxide did not change in patients who had clinical deterioration. As a conclusion; Patients with PH had lower FeNO values than healthy controls, but FeNO did not change significantly during follow-up. Large-scale studies with prolonged follow-up periods are needed to understand the role of FeNO in the follow-up of the patients with PH.

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Sleep and Prospective Memory: A Retrospective Study in Different Clinical Populations

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17176113 ◽

2020 ◽

Vol 17 (17) ◽

pp. 6113 ◽

Cited By ~ 1

Author(s):

Lorenzo Tonetti ◽

Miranda Occhionero ◽

Michele Boreggiani ◽

Andreas Conca ◽

Paola Dondi ◽

...

Keyword(s):

Sleep Quality ◽

Prospective Memory ◽

Control Group ◽

Poor Sleep ◽

Clinical Group ◽

Healthy Controls ◽

Time Activity ◽

Clinical Populations

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. This ability could be influenced by poor sleep quality, the role of which, however, is still being debated. To examine the role of sleep quality in PM in depth, we decided to perform a retrospective naturalistic study examining different clinical populations with a primary sleep disorder or comorbid low sleep quality. If sleep is important for PM function, we could expect poor sleep to affect PM performance tasks both directly and indirectly. We examined a total of 3600 nights, recorded using actigraphy in participants belonging to the following groups: primary insomnia (731 nights); narcolepsy type 1 (1069 nights); attention deficit hyperactivity disorder (152 nights in children and 239 in adults); severe obesity (232 nights); essential hypertension (226 nights); menopause (143 nights); healthy controls (808 nights). In a naturalistic activity-based PM task, each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker button at two specific times of day: bedtime (activity 1) and get-up time (activity 2). Each clinical group showed significantly lower sleep quality in comparison to the control group. However, only narcolepsy type 1 patients presented a significantly impaired PM performance at get-up time, remembering to push the event-marker button around half the time compared not only to healthy controls but also to the other clinical groups. Overall, the present results seem to point to sleep quality having no effect on the efficiency of a naturalistic activity-based PM task. Moreover, the data indicated that narcolepsy type 1 patients may show a disease-specific cognitive deficit of PM.

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Plasma nitric oxide and oxidized LDL levels in systemic lupus erythematosus (SLE)

LaboratoriumsMedizin ◽

10.1515/labmed-2014-0037 ◽

2014 ◽

Vol 38 (6) ◽

Author(s):

Mohammad Najafi ◽

Freshteh Parto ◽

Parisa Mohammadi ◽

Mohammad Shabani

Keyword(s):

Nitric Oxide ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Critical Role ◽

Clinical Manifestations ◽

Oxidative Modification ◽

Healthy Controls ◽

Systemic Lupus ◽

Ldl Particles

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease with different clinical manifestations. The inflammatory and oxidative modification reactions are the most important events associated with cardiovascular complications of SLE patients. The aim of this study was to investigate the nitric oxide (NO) and the oxidized low-density lipoprotein (Ox-LDL) levels in order to explain the role of oxidized particles in development of clinical manifestations.A total of 80 subjects, SLE patients (n=40) and healthy controls (n=40), were recruited and matched regarding to age, gender, and body mass index (BMI). The biochemical parameters were measured using routine laboratory methods. The plasma Ox-LDL and NO levels were assayed with ELISA and colorimetric techniques, respectively.The plasma NO level was significantly high in SLE patients (33.03±18.09 μmol/mL) in comparison to healthy controls (15.25±11.54 μmol/mL). In contrast, the total and normalized (Ox-LDL/LDL) plasma Ox-LDL values were low in SLE patients (p=0.2 and p<0.05, respectively). A linear negative correlation was also observed between the plasma Ox-LDL and NO levels (r=0.25, p<0.05). Multiple logistic regression analysis showed the critical role of NO on Ox-LDL level. Moreover, the disease activity and medications did not relate to the plasma Ox-LDL level (p>0.5).The results showed that the excess NO prevents the oxidation of LDL particles so that the inflammatory events in comparison to oxidative modifications may be most involved in clinical complications of SLE patients.

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A review of the pathogenesis of ankylosing spondylitis

Neurosurgical FOCUS ◽

10.3171/foc/2008/24/1/e2 ◽

2008 ◽

Vol 24 (1) ◽

pp. E2 ◽

Cited By ~ 39

Author(s):

Elias Dakwar ◽

Jaypal Reddy ◽

Fernando L. Vale ◽

Juan S. Uribe

Keyword(s):

Ankylosing Spondylitis ◽

Strong Association ◽

Critical Role ◽

Axial Skeleton ◽

Causative Role ◽

Hla B27 ◽

Pathogenic Role ◽

The Past ◽

New Findings

✓ Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited. Despite the strong association between human leukocyte antigen B27 (HLA-B27) and susceptibility to AS reported over the past 30 years, the exact pathogenic role of HLA-B27 in AS and other spondyloarthropathies has yet to be determined. The authors present a review of the literature pertaining to the pathogenesis of AS over the past several decades. Ankylosing spondylitis is a polygenic disorder, with HLA-B27 playing a critical causative role in its pathogenesis. Animal studies of the immunobiology of HLA-B27 have provided significant insight into the pathogenic role of HLA-B27. The search for the antigenic peptide to support the “arthritogenic peptide” hypothesis has been disappointing. Over the past decade there has been increasing interest in the critical role of the misfolding and unfolded protein response of the heavy chain HLA-B27 in the modulation of the inflammatory response. Although there have been significant new findings in the understanding of the pathogenesis of AS, the exact mechanisms have yet to be identified. There is considerable optimism that additional susceptibility genes, predisposing factors, and regulators of the inflammatory process will be identified that will provide avenues for future treatment.

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