scholarly journals Correlation between Hyperalgesia and Upregulation of TNF-α and IL-1β in Aqueous Humor and Blood in Second Eye Phacoemulsification: Clinical and Experimental Investigation

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ruibo Yang ◽  
Chang Liu ◽  
Di Yu ◽  
Lechong Ma ◽  
Yan Zhang ◽  
...  

The aim of this study was to explore the correlation between intraoperative hyperalgesia of the second eye and the dynamic changes of tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in aqueous humor (AH) of the second eye and whole blood after the first eye cataract surgery. A rabbit model of monocular phacoemulsification was established by administration of 0.3% levofloxacin. Whole blood and AH samples from non-surgical eyes in the experimental group (n =25) and second eye in the blank control group (n =15) were obtained and corneal sensitivity was examined after surgery (1, 3, 7, 14, and 21 days postoperatively). TNF-α and IL-1β levels in AH and TNF-α mRNA and IL-1β mRNA levels in whole blood were measured. In a clinical study, 30 patients who underwent bilateral phacoemulsification within 1 month were divided into six groups in accordance with the operation intervals (1, 3, 7, 10, 14, and 21days). TNF-α and IL-1β levels in AH were measured at the beginning of surgery and intraoperative pain was assessed immediately after surgery. Corneal sensitivity (F =244.910, P <0.05), TNF-α and IL-1β levels in AH (F =184.200, 82.900, P <0.05) of non-surgical eyes and in whole blood (F =272.800, 193.530, P <0.05) in the experimental group were significantly higher than the baseline levels after phacoemulsification. In the clinical study, NRS scores of second eye surgery were higher than those of the first eye(P =0.0025) and 19 (63.3%) patients reported more pain during the second eye surgery. TNF-α and IL-1β concentrations in AH of the second eye were significantly higher than those of the first eye (F =123.60, P <0.05; F =59.60, P <0.05). In conclusion, within 1 month after the first eye phacoemulsification, higher pain sensitivity (hyperalgesia) exists in the second eye, which may be related to dynamic changes in TNF-α, IL-1β levels in AH or whole blood.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng Zheng ◽  
Yan Chen ◽  
Yinzhou Wang ◽  
Yongkun Li ◽  
Qiong Cheng

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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2483-2483
Author(s):  
Carla Fernanda Franco-Penteado ◽  
Carolina Lanaro ◽  
Dulcinéia M Albuquerque ◽  
Ana Paula Gimenes ◽  
Luiz Augusto C Passos ◽  
...  

Abstract Studies in vitro, and in vivo using animal models show that leukocytes play a key role in vasoocclusion and clinical research suggests that high leukocyte counts correlate with mortality, stroke and acute chest syndrome in sickle cell disease (SCD). Lungs are particularly vulnerable to vaso-occlusive events because of their anatomic features in SCD. Transgenic mice expressing exclusively human sickle hemoglobin (SS) are well-established models for the study of vascular inflammation. Previous studies have shown that systemic LPS challenge causes exaggerated inflammation, including increased serum and broncoalveolar lavage (BAL) TNF-α and IL-1 cytokines and sVCAM-1 in sickle mice. The aim of this study was to examine the contribution of acute airway inflammation in SCD using SS mice and the role of chemokines and matrix metalloproteinases (MMPs) in this process. Acute lung inflammation and injury were induced by intranasal administration of lipopolysaccharide (LPS, 50 μl of 250 μg/ml) in control (C57BL/6) and SS mice. The vehicle mice group received a similar volume of sterile PBS. BAL was performed 4 h after LPS challenge. qRT-PCR analysis was used to examine gene expression and ELISA protein production. The intranasal administration of LPS to mice triggered a huge influx of leukocytes (neutrophils, NS) in BAL of control and SS mice compared with the respective vehicle groups, but this influx was greater in SS mice, when compared with control mice (1.4 ± 0.06 vs 0.66 ± 0.12 WBCx106/BAL); p=0.0006, 1.06 ± 0.1 vs 0.40 ±0.12 NSx106/BAL; p=0.004, respectively). At baseline levels, KC and MIP-2 chemokines (functional homologues of human IL-8 in mice) are higher in BAL fluid of SS mice compared to control mice (186.6 ± 14.1 pg/ml vs 14.1 ± 5.8 pg/ml; 41.2 ± 7.9 pg/ml vs 11.4 ± 7.3 pg/ml, p=, respectively). Corresponding with influx of NS, lung lavage levels of KC and MIP-2 were significantly higher in SS BALF compared to control mice (2491 ± 454 pg/ml vs 798.1 vs 98.2 pg/ml; 1726 ± 307 pg/ml vs 887.3 ± 149.5 pg/ml, respectively). Enhanced levels of TNF-α were also observed at baseline and after LPS instillation compared to those of the control mice (20.8 ± 8.8 pg/ml vs 2.5 ± 1.6 pg/ml; 4250 ± 636 pg/ml vs 1585 ± 263 pg/ml, respectively). Instillation of LPS markedly increased KC, TNF-α, MMP-8, MMP-9 and TIMP-1 mRNA levels in the lungs of control and SS mice compared to animals that received PBS instead of LPS (Control, KC: 0.19 ± 0.047 vs 0.01 ± 0.005; TNF-α: 0.30 ± 0.07 vs 0.01 ± 0.002; MMP-8: 0.2 ± 0.06 vs 0.016 ± 0.004; MMP-9: 0.22 ± 0.03 vs 0.08 ± 0.01; TIMP-1: 0.32 ± 0.06 vs 0.09 ± 0.03); (SS, KC: 0.42 ± 0.1 vs 0.039 ± 0.02; TNF-α: 0.23 ± 0.025 vs 0.02 ± 0.007; MMP-8: 0.42 ± 0.06 vs 0.06 ± 0.03; MMP-9: 0.49 ± 0.11 vs 0.11 ± 0.05; TIMP-1: 0.49 ± 0.11 vs 0.09 ± 0.03). However, the LPS-induced KC, MMP-8 and MMP-9 expression was significantly higher in SS mice lung compared than that of the control group (p&lt;0.05). Lung MMP-2, MMP-12 and TIMP-2 gene expressions were similar in the PBS and LPS groups and were not significantly different between SS and control mice. Our results indicate that chemokines and MMPs are critically involved in the recruitment of neutrophils to the lung following LPS challenge, and suggest that these inflammatory mediators may play a role in the development of pulmonary diseases in SCD. The findings from this study provide further support to the claim that a proinflammatory state is present in SCD and have important implications for the pathophysiology of lung injury in SCD.


2009 ◽  
Vol 87 (11) ◽  
pp. 963-972 ◽  
Author(s):  
Diethart Schmid ◽  
Florian Woehs ◽  
Martin Svoboda ◽  
Theresia Thalhammer ◽  
Peter Chiba ◽  
...  

Cimicifuga racemosa (black cohosh) is commonly used in traditional medicines as treatment for menopausal symptoms and as an antiinflammatory remedy. To clarify the mechanism of action and active principle for the antiinflammatory action, the effects of aqueous C. racemosa root extracts (CRE) and its major constituents on the release of the proinflammatory cytokines IL-6, TNF-α, IFN-γ, and the chemokine IL-8 were investigated in lipopolysaccharide (LPS)-stimulated whole blood of healthy volunteers. CRE (3 µg/µL and 6 µg/µL) reduced LPS-induced release of IL-6 and TNF-α in a concentration- and time-dependent manner and almost completely blocked release of IFN-γ into the plasma supernatant. Except for IFN-γ, these effects were attenuated at longer incubation periods. IL-8 secretion was stimulated by CRE. As shown by quantitative real-time RT-PCR, effects on cytokines were based on preceding changes in mRNA levels except for IL-8. According to their content in CRE, the phenolcarboxylic compounds caffeic acid, ferulic acid, and isoferulic acid, as well as the triterpene glycosides 23-epi-26-deoxyactein and cimigenol-3-O-xyloside, were tested at representative concentrations. Among these, isoferulic acid was the prominent active principle in CRE, responsible for the observed inhibition of IL-6, TNF-α, and IFN-γ, but not for IL-8 stimulation. The effect of this compound may explain the antiinflammatory activities of CRE and its beneficial actions in rheumatism and other inflammatory diseases.


2021 ◽  
Author(s):  
Chunnuan Zhang ◽  
Yuheng Wang ◽  
Hongtao Ren ◽  
Junhui Wang ◽  
Dongxue Jiang ◽  
...  

Abstract The objective of this study was to determine the effects of quercetin on oxidative stress and apoptosis induced by TPT in zebrafish. 240 fish were divided into 4 groups with three repeats. D1: fish fed with the basal diet as the control group. D2: fish fed with basal diet and exposed in 10 ng/L TPT. D3: fish fed diets containing 100 mg/Kg quercetin and exposed in 10ng/L TPT. D4: fish fed diets containing 100 mg/Kg quercetin. The results showed that quercetin could ameliorate oxidative stress, which decreased MDA, NO levels and improved antioxidant enzyme activities. The key apoptotic gene expressions, including caspase3, Bax and caspase9 mRNA expression were significantly induced by TPT exposure as compared with the control group, while notably decreased the Bcl-2 gene. However, dietary quercetin prevented a significant increase in Bax, caspase3 and caspase9 mRNA levels induced by TPT exposure, but increased Bcl-2 mRNA levels. The results of our study also demonstrated that 10 ng/L TPT significantly up-regulated TNF-α, IL-1β, IL-8, and NF-kB p65 gene expression and down-regulated IL-10 and IkB expression compared to the control group. However, TPT-induced inflammation was significantly mitigated in the quercetin treatment group. In conclusion, our findings suggested that quercetin might alleviate hepatic oxidative damage and apoptosis induced by TPT.


2020 ◽  
Author(s):  
Tiande Zou ◽  
Jin Yang ◽  
Xiaobo Guo ◽  
Qin He ◽  
Zirui Wang ◽  
...  

Abstract Background: Seaweed-derived polysaccharides (SDP) represent an attractive source of prebiotic nutraceuticals for the food and animal husbandry industry. However, the mechanism by which SDP from Enteromorpha mediates pig growth are not fully understood. This study aimed to investigate how SDP supplementation influences the growth performance and intestinal health in weaned pigs.Results: In Exp. 1, 240 weaned pigs were randomly assigned to four dietary treatments and fed with a basal diet or a basal diet containing 200, 400 or 800 mg/kg SDP, respectively, in a 21-d trial. Pigs on the 400 or 800 mg/kg SDP-supplemented group had greater ADG and lower F/G ratio than those on the control group (P<0.05). In Exp. 2, 20 male weaned pigs were randomly assigned to two treatments and fed with a basal diet (CON group) or a basal diet supplemented with 400 mg/kg SDP (the optimum does from Exp. 1), in a 21-d trial. Pigs fed the SDP diet had greater ADG, the concentrations of serum IL-6 and TNF-α and the activities of glutathione peroxidase, superoxide dismutase and catalase (P<0.05), and lower F/G, diarrhea rate, as well as serum D-lactate concentrations and diamine oxidase activity (P<0.05). Moreover, dietary SDP supplementation enhanced secretory immunoglobulin A content, villus height and villous height: crypt depth ratio in small intestine, as well as the lactase and maltase activities in jejunum mucosa (P<0.05). SDP supplementation elevated the mRNA levels of inflammatory response-related genes (IL-6, TNF-α, TLR4, TLR6 and MyD88), and the mRNA and protein levels of ZO-1, Claudin-1 and Occludin in jejunum mucosa (P<0.05). Importantly, SDP not only increased the Lactobacillus population but also reduced the Escherichia coli population in cecum (P<0.05). Furthermore, SDP increased acetic acid and butyric acid concentrations in cecum (P<0.05).Conclusions: These results not only suggest a beneficial effect of SDP on growth performance and intestinal barrier functions, but also offer potential mechanisms behind SDP-facilitated intestinal health in weaned pigs.


2021 ◽  
Author(s):  
Xiang Yan ◽  
Meng Fu ◽  
Ye Gao ◽  
Qin Han ◽  
Shuang Li ◽  
...  

Abstract Background Delayed neuropsychologic sequelae is common in patients after carbon monoxide poisoning without effective methods worldwide. Fasudil exerts neuroprotective effect and alleviates oxidative stress in some neurodegenerative disorders. However, the mechanism between DNS and FS remains unclear. The study aims to explore the efficacy and mechanism of Fasudil in DNS mice model. Objective The delayed neuropsychologic sequelae model was induced with a hyperbaric oxygen chamber. All rats were randomly assigned to three groups (n=10): air control group (AC), CO poisoning group (CO), and CO poisoning +Fasudil group (CO+FS). Rats in the CO+FS group were given Fasudil (10 mg/kg/day, ip). The morris water maze was documented to estimate spatial learning and memory of mice. The demyelination state in brain was observed through LFB staining. The protein of MBP was examined with immunofluorescence staining. The levels of IL-6, TNF-α, TGF-β, SOD, and MDA were examined by ELISA. The mRNA levels of Rho, ROCK2, MLC1 and MYPT1 were analyzed by rt-PCR. Result The cognitive impairment in the CO+FS group were significantly reduced than those of the CO group (P<0.05). LFB staining and immunofluorescence staining of MBP results showed that FS significantly treatment attenuated demyelination (P<0.05). Compared with the CO group, the levels of TNF-α, IL-6, MDA, ROCK2, MLC1, and MYPT1 significantly decreased (P<0.05), and the levels of SOD were significantly increased in the CO+FS group (P<0.05). Conclusion In a word, Fasudil attenuated delayed neuropsychologic sequelae by inhibiting inflammation, oxidative stress and downregulating Rho/ROCK pathway in DNS mice model. We conclude that Fasudil may be a novel treatment for delayed neuropsychologic sequelae.


2020 ◽  
Author(s):  
Heping Wang ◽  
Yuqi Li ◽  
Song Han ◽  
Tongtong Niu

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes. Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified. Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group , while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group. Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yonghuan Yu ◽  
Xinfeng Cui ◽  
Jingjing Zhao ◽  
Ting Jia ◽  
Baofeng Ren ◽  
...  

Objective. The purpose of the study was to investigate the effect of entecavir combined with adefovir dipivoxil on clinical efficacy and TNF-α and IL-6 levels in patients with hepatitis B cirrhosis. Methods. A total of 100 patients with hepatitis B cirrhosis admitted to our hospital between January 2018 and June 2019 were randomly selected and divided into the control group (n = 50) and experimental group (n = 50) according to the order of admission. Among them, the control group patients were treated with entecavir, while the patients in the experimental group received entecavir combined with adefovir dipivoxil. After that, the effective rate of treatment, the incidence of adverse reactions, liver function indexes, liver fibrosis condition, and TNF-α and IL-6 expression levels were all compared between the two groups. Results. The effective rate of treatment in the experimental group was significantly higher than that in the control group, with statistical significance ( p < 0.001 ); the incidence of adverse reactions of the patients in the experimental group was significantly lower than that in the control group, with statistical significance ( p < 0.001 ); the liver function indexes in the experimental group were significantly better than those in the control group, with statistical significance ( p < 0.001 ); the number of patients with liver fibrosis in the experimental group was significantly less than that in the control group, with statistical significance ( p < 0.001 ); the TNF-α and IL-6 expression levels in the experimental group were significantly lower than those in the control group, with statistical significance ( p < 0.001 ). Conclusion. Entecavir combined with adefovir dipivoxil in the treatment of hepatitis B cirrhosis can effectively improve the therapeutic effect and reduce the serum inflammatory factor levels, with high safety, which is worthy of application and popularization.


2014 ◽  
Vol 18 (6) ◽  
pp. 13-16
Author(s):  
V.P. Zhula

Purpose: The effect of the experimental procedure on the development of motor abilities of students in the course of employment volleyball. Material : The experiment involved 80 students of the Faculty of Physical Education. Results : Studies have shown that when passing the ball with two hands at the bottom of the students there is a certain dynamic changes in the structure of support interactions, which is expressed by the increase of biodynamic and time indicators on 8.19% of the students in the control group and 16.17% of the students in the experimental group. The technique allowed tenzodynamometry qualitatively assess the level of development of motor abilities of students in performing the ball with two hands at the bottom. Determine the validity of the growth of average indicators support reactions of the body of students in the experimental group when the transfer of the ball with two hands at the bottom. Conclusions : Recommended every lesson during warmup volleyball include special exercises, tasks are executed sequentially, with a gradual increase in load as the assimilation of motor actions, use the methods of biomechanical control.


2014 ◽  
Vol 34 (7) ◽  
pp. 707-717 ◽  
Author(s):  
S-J Hong ◽  
D Zhang ◽  
L-H Zhang ◽  
P Yang ◽  
J Wan ◽  
...  

Objectives: To observe the expression of the dopamine transporter (DAT) in six cerebral regions of a methamphetamine (MA)-dependent rat, which were frontal cortex, nucleus accumbens septi, striatum, hippocampus, substantia nigra and ventral tegmental area. Methods: The rats were administrated intraperitoneally with 10 mg/kg/day of MA for 10 days consecutively; the behaviour changes were measured via the conditioned place preference (CPP), and the scores of stereotyped behaviour (SB) were used to confirm animal addiction. Then, the animals were further injected with MA respectively for 1, 2, 4 and 8 weeks to establish different periods of MA-dependent models. The expressions of DAT and DAT messenger RNA in six cerebral regions were detected. Results: The results of CPP and SB scores were significant different when comparing all four experimental groups with the control group ( p < 0.05). Comparing between different experimental groups, the expression of DAT mainly decreased and had dynamic changes in the same regions ( p < 0.05). Comparing the different regions with each other in the same experimental group, the expression of DAT also had significant difference in several regions p < 0.05). Conclusions: The expression of DAT mainly decreased and had different in the six cerebral regions at the same MA-dependent time period as well as at different time periods in the same cerebral region. It was speculated that DAT might play a crucial role in the mechanism of MA dependence.


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