scholarly journals Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery

2021 ◽  
Vol 12 ◽  
Author(s):  
Wensi Wu ◽  
Xiaojun Zhang ◽  
Jiaxin Zhou ◽  
Hongmei Yang ◽  
Junjun Chen ◽  
...  

Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.

2020 ◽  
Vol 15 (1) ◽  
pp. 598-605
Author(s):  
Shiyi Tan ◽  
Shang Yang ◽  
Mingke Chen ◽  
Yurun Wang ◽  
Li Zhu ◽  
...  

AbstractAlveolar macrophages (AMs) play an important defensive role by removing dust and bacteria from alveoli. Apoptosis of AMs is associated with lung fibrosis; however, the relationship between this apoptotic event and environmental factors, such as the presence of lipopolysaccharides (LPSs) in the workplace, has not yet been addressed. To investigate whether exposure to LPS can exacerbate fibrosis, we collected AMs from 12 male workers exposed to silica and incubated them in the presence and absence of LPS for 24 h. We show that the levels of cleaved caspase-3 and pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha were increased in these AMs following LPS treatment. Moreover, we demonstrate that LPS exposure aggravated apoptosis and the release of inflammatory factors in AMs in a mouse model of silicosis, which eventually promoted pulmonary fibrosis. These results suggest that exposure to LPS may accelerate the progression of pulmonary fibrosis in silicosis by increasing apoptosis and inflammation in AMs.


Author(s):  
Ali-Reza Ahmadi ◽  
Roya Ayazi-Nasrabadi

Inflammation acts like a double-edged sword and can be harmful if not appropriately controlled. COVID-19 is created through a novel species of coronavirus SARS-CoV-2 (2019-nCoV). Elevated levels of inflammatory factors such as inter- leukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), etc. lead to Acute Respiratory Distress Syndrome (ARDS) and severe complications of infection in the lungs of coronavirus-infected patients. Astaxanthin is a natural and potent carotenoid with powerful antioxidant activity as well as an anti-inflammatory agent that supports good health. The effects of astaxanthin on the regulation of cyclooxygenase-2 (COX-2) pathways and the reduction and suppression of cytokines and other inflam- matory agents such as IL-6 and TNF-α have already been identified. Therefore, these unique features can make this natural compound an excellent option to minimize inflammation and its consequences.


2019 ◽  
Vol 65 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Hong Xiao Cui ◽  
Xiu Rong Xu

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.


2001 ◽  
Vol 69 (11) ◽  
pp. 6912-6922 ◽  
Author(s):  
Annette Kolb-Mäurer ◽  
Alexandra Unkmeir ◽  
Ulrike Kämmerer ◽  
Claudia Hübner ◽  
Thomas Leimbach ◽  
...  

ABSTRACT Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-α, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1β, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.


2007 ◽  
Vol 86 (9) ◽  
pp. 878-882 ◽  
Author(s):  
C. Bodet ◽  
F. Chandad ◽  
D. Grenier

Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with 3H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1β, IL-6, IL-8, and TNF-α by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.


Author(s):  
Masoomeh Yosefifard ◽  
Gholamhassan Vaezi ◽  
Ali Akbar Malekirad ◽  
Fardin Faraji ◽  
Vida Hojati

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS


2017 ◽  
Vol 11 (1) ◽  
pp. 573-580 ◽  
Author(s):  
Masoome Eivazi ◽  
Negar Falahi ◽  
Nastaran Eivazi ◽  
Mohammad Ali Eivazi ◽  
Asad Vaisi Raygani ◽  
...  

Objective:Periodontitis is one of the main diseases in the oral cavity that causes tooth loss. The host immune response and inflammatory factors have important role in periodontal tissue. The current study was done with the objective to determine the effect of scaling and root planning on the salivary concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-alpha (IL-1α).Methods:In this quasi-experimental clinical trial, 29 patients with chronic periodontitis and 29 healthy subjects without periodontitis were studied. Clinical examination findings and salivary TNF-α and IL-1α (using ELISA method) were compared before and after scaling, root planning.Results:Before starting treatment, salivary TNF-α and IL-1α concentrations were higher in healthy control group than in periodontitis group (P< 0.05). Non-surgical treatment increased the concentration of these two biomarkers in the saliva. However, increase in IL-1α concentration was not statistically significant (P= 0.056). There was a negative relationship between TNF-α and IL-1α levels with pocket depth and attachment loss (P< 0.05).Conclusion:Scaling and root planning improved periodontal disease indices and salivary TNF-α and IL-1α levels.


2022 ◽  
pp. 153537022110669
Author(s):  
Hassan Ahmed ◽  
Urooj Amin ◽  
Xiaolun Sun ◽  
Demetrius R Pitts ◽  
Yunbo Li ◽  
...  

Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.


Sign in / Sign up

Export Citation Format

Share Document