Association of miR-155, miR-187 and Inflammatory Cytokines Il-10 and TNF-α in Chronic Opiate Abusers

Author(s):  
PURVI PUROHIT ◽  
Dipayan Roy ◽  
Shailender Dwivedi ◽  
Naresh Nebhinani ◽  
Praveen Sharma

Abstract The current study determined levels of inflammatory cytokines TNF-α, IL-6, IL-10 and immune-regulatory miR-155 and miR-187 expressions in chronic opiate abuse. Adults (n = 48), meeting the 5th Edition of the DSM criteria regarding opioid use disorder, and healthy controls (n = 46) were included in the study. Serum samples were analysed for inflammatory cytokines IL-10, IL-6, TNF-α using ELISA and PBMCs processed for miRNA expression using SybrGreen chemistry. Cases showed significantly raised IL-10 and TNF-α and reduced IL-6. Using RNU6 for normalization, dose-dependent corresponding upregulation of miR-155-5p and downregulation of miR-187-5p were evident at opiate dose > 1500 gm/day, with a corresponding increase of TNF-α and IL-10. MiR-155 showed a significant negative correlation with IL-6 and TNF-α; miR-187 showed a significant positive association with TNF-α at > 1000 g/day consumption. Therefore, increasing consumption of opium probably enhances inflammation leading to immunomodulation and aberrant expression of has-miR-155-5p and has-miR-187-5p in opiate abusers.

2020 ◽  
Vol 5 (02) ◽  
pp. 203-207
Author(s):  
Mohan Vamsi D. ◽  
Sandhyasree G. ◽  
Meena H. P. ◽  
Payasi S. K.

The present investigation was carried out at the Research Fields, ICAR-Indian Institute of Oilseeds Research, Rajendranagar, Hyderabad, Telangana, India. The material for present study consisted of twenty newly developed mono and multi headed restorer lines including CMS lines. The data for agronomic and yield traits i.e. days to 50% flowering, days to physiological maturity, plant height, head diameter, volume weight, 100 seed weight, seed yield per plant oil content and oil yield was recorded. The analysis of variance revealed significant differences among the genotypes for almost all characters which favour the selection. Associations among characters especially indicated that among the seven traits studied, seed yield per plant had a highly significant positive association with head diameter and significant negative correlation with days to 50% flowering and days to maturity. The genotypes, COSF-6B, COSF-7B, RGP-11-P1-S2, RGP-58-P4-S1-1 and RGP-46-P3 were identified as the most important genotypes for different traits and should be utilized in heterosis breeding programme to realize high heterosis for yield and yield contributing traits.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sicong Tu ◽  
Mengjie Huang ◽  
Jashelle Caga ◽  
Colin J. Mahoney ◽  
Matthew C. Kiernan

Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS (p = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A (R2 = 0.14, p = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem (R2 = 0.46, p &lt; 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: R2 = 0.44, p &lt; 0.01; right: R2 = 0.44, p &lt; 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS. The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter.


2021 ◽  
Vol 27 ◽  
Author(s):  
Peng Lu ◽  
Ye Zhang ◽  
Huanjiang Niu ◽  
Yirong Wang

Background: ALMS1-IT1, a recently identified lncRNA, has been proven to play a crucial role in regulating tumor progression and predicting the survival time of tumor patients. Data analysis from the Human Body Map (HBM) revealed that ALMS1-IT1 is expressed mainly in brain tissues. Methods: In this study, the role of ALMS1-IT in regulating neuro-inflammation and functional recovery was investigated after ischemic cerebral damage. To this end, the rat model of transient middle cerebral artery occlusion (tMCAO) was constructed, the cell model of oxygen-glucose deprivation (OGD) was established using BV2 microglial cells, and the aberrant expression of ALMS1-IT1 was assessed in brain tissues. After ALMS1-IT1 knockdown through intrathecal injection of Lv-shALMS1-IT1, neuro-inflammatory response and functional tests including a modified neurological severity score (mNSS) and a foot-fault test were assessed. Results: The level of ALMS1-IT1 was promptly enhanced at 12 hours (h) following MCAO, peaking at 48 h, and remaining high at day 14 compared to the sham group. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after MCAO, whereas ALMS1-IT1 inhibition suppressed the expression of IL-1β, IL-6 and TNF-α in MCAO rats. The results from mNSS and foot-fault test showed that ALMS1-IT1 knockdown significantly improved spatial learning and sensorimotor function of MCAO rats. Mechanistically, ALMS1-IT1 knockdown suppressed the activation of NF-κB signaling in vitro and in vivo, as evidenced by decreased p65 expression and p65 nuclear translocation. ALMS1-IT1 overexpression facilitated pro-inflammatory cytokines expression in microglia, whereas the effect was blocked by treatment with JSH-23 (a specific NF-κB inhibitor). Conclusions: These data demonstrated that ALMS1-IT1 inhibition improved neurological function of MCAO rats, at least in part by repressing NF-κB-dependent neuro-inflammation.


1939 ◽  
Vol 17c (11) ◽  
pp. 388-409 ◽  
Author(s):  
A. G. McCalla ◽  
J. R. Weir ◽  
K. W. Neatby

Measurements of the height of the main stems of maize and gladiolus plants were made at four-hour intervals starting at 4 a.m. The increases in elongation were analyzed statistically, together with mean temperature, hours of sunlight, and mean relative humidity.Partial correlation coefficients showed that there was a highly significant positive association between the rate of stem elongation (growth) and temperature, regardless of the time of day, the variations in temperature accounting for from 40 to 70% of the variability in growth rates. There was likewise a significant negative correlation between growth and sunlight, but sunlight was apparently effective only during the midday periods (8 a.m. to 4 p.m.). The depressing effect of sunlight on the growth of gladiolus was approximately four times as great as on maize. This depressing effect on maize was entirely removed by shading the plants with light white cotton.Variations in relative humidity were only slightly associated with growth rates. No significant effect was observed for any of the periods. It seems possible that these factors might be more important under conditions of deficiency in soil moisture.The approximate minimum temperature at which growth look place was 40° F.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
L. A. Ramos-Chávez ◽  
G. Roldán-Roldán ◽  
B. García-Juárez ◽  
D. González-Esquivel ◽  
G. Pérez de la Cruz ◽  
...  

Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.


Author(s):  
Ameneh Zare-Chahoki ◽  
Meysam Ahmadi-Zeidabadi ◽  
Saeid Azadarmaki ◽  
Samira Ghorbani ◽  
Farshid Noorbakhsh

Perturbed expression of microRNAs (miRs) has been reported in different diseases includingautoimmune and chronic inflammatory disorders. In this study, we investigated the expression of miR25-3p and its targets in the central nervous system (CNS) tissue from mice with experimentalautoimmune encephalomyelitis (EAE). We also analyzed the expression of miR-25 and its targets inactivated macrophages and splenocytes.EAE was induced in 12-week old female C57BL/6 mice; using myelin oligodendrocyteglycoprotein 35-55/complete Freund's adjuvant (MOG35-55/CFA) protocol. The expression of miR25-3p and its targets, as well as the expression of inflammatory cytokines, were analyzed. We nextestablished primary macrophage cultures as well as splenocyte cultures and evaluated the levels of miR25-3p and its target genes in these cells following activation with lipopolysaccharide (LPS) and antiCD3/anti-CD28 antibodies, respectively.MiR-25-3p expression showed a strong positive correlation with the expression of tumor necrosisfactor-alpha (TNF-α), interleukin (IL)-1α, and IL-6 pro-inflammatory cytokines. The expression ofphosphatase and tensin homolog (Pten) and Krüppel-like factor 4 (Klf4) was significantly reduced at the peak ofthe disease. Interestingly, Pten and Klf4 expression showed a significant negative correlation with miR25-3p. Analysis of miR-25-3p expression in LPS-treated primary macrophages revealed significantupregulation in cells treated with 100ng/ml of LPS. This was associated with suppressed levels of miR25-3p targets in these cells. However, anti-CD3/anti-CD28-stimulated splenocytes failed to show anyalterations in miR-25-3p expression compared with vehicle-treated cells.Our results indicate that miR-25-3p expression is likely induced by inflammatory mediators duringautoimmune neuroinflammation. This upregulation is associated with decreased levels of Pten and Klf4, genes with known roles in cell cycle regulation and inflammation. 


Author(s):  
Sumaira Kayani ◽  
Tayyaba Kiyani ◽  
Saima Kayani ◽  
Tony Morris ◽  
Michele Biasutti ◽  
...  

The present study examined the role of self-enhancement and self-criticism in the relationship between physical activity and anxiety. A total of 305 students from Chinese universities, ranging in age from 18 to 36, completed a questionnaire package comprising a physical activity questionnaire, a self-enhancement strategies scale, a level of self-criticism scale, and a short form of state and trait anxiety scale. Findings highlighted that physical activity had a significant negative correlation with anxiety (r = −0.31, p < 0.01), a significant positive association with self-enhancement (r = 0.43, p < 0.01), and a significant negative relationship with self-criticism (r = −0.14, p < 0.05). It was also found that anxiety was significantly predicted by self-enhancement (−0.21, p < 0.01) and self-criticism (0.44, p < 0.01). Moreover, the mediation model supports the mediation of self-enhancement and self-criticism between physical activity and anxiety in university students. The findings suggest that interventions aimed at promoting physical activity and enhancing the self-system should be worthy strategies for reducing students’ anxiety.


2013 ◽  
Vol 169 (6) ◽  
pp. 767-772 ◽  
Author(s):  
Pietro Ameri ◽  
Andrea Giusti ◽  
Mara Boschetti ◽  
Marta Bovio ◽  
Claudia Teti ◽  
...  

ObjectivesPrevious studies suggested that vitamin D modulates circulating IGF1. We investigated this effect in adults and its clinical relevance in the management of GH deficiency (GHD).Design and methodsIGF1 levels were prospectively measured before and after 12 weeks of treatment with oral vitamin D3(5000 or 7000 IU/week) vs no intervention in 39 subjects 61.9±7.9 years old. The frequency of IGF1 values ≥50th age- and sex-specific percentile in relation to vitamin D status, as determined by the concentration of 25-hydroxyvitamin D (25(OH)D), was retrospectively assessed in 69 GHD patients (57.4±16.6 years) on stable hormone replacement and with 25(OH)D and IGF1 concurrently measured.ResultsTreatment with 5000 and 7000 IU vitamin D3/week significantly raised 25(OH)D by 12.7±8.4 and 13.1±6.5 ng/ml respectively (bothP<0.001 vs baseline). In the 7000 IU group, IGF1 levels also significantly increased by 31.3±36.7 ng/ml (P=0.01). Neither 25(OH)D nor IGF1 significantly varied in controls. IGF1 was ≥50th percentile more frequently in GHD patients with 25(OH)D levels ≥15 than <15 ng/ml (65.9 vs 40.0%,P<0.05). Logistic regression with adjustment for recombinant human GH (rhGH) dose, vitamin D supplements, gender, use of thyroid hormones, corticosteroids or estrogen/testosterone, and season revealed a significant positive association between ≥15 ng/ml 25(OH)D and IGF1 ≥50th percentile (OR 4.4, 95% CI 1.0–18.8,P<0.05). A significant negative correlation between 25(OH)D concentrations and rhGH dose was found after correcting for age and IGF1 (β−0.042,P<0.01), but not after further adjusting for sex, thyroid, adrenal or gonadal replacement, and season (β−0.037,P=0.06).ConclusionsVitamin D increases circulating IGF1 in adults. As a result, a better vitamin D status may ease the achievement of normal IGF1 values in GHD.


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