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Tumor necrosis factor-alpha expression in ischemic neurons
... Cell death is a fundamental process in cell biology [1][2][3] and holds significant importance. Besides traditional types like apoptosis [4] and necrosis [5], several other types of cell death have been reported. The classification of cell death now includes non-programmed necrosis [6], programmed apoptosis, and programmed non-apoptotic cell death, which encompasses autophagy [7], mitoptosis [8], pyroptosis [9], and ferroptosis [10]. ...
This study presents a novel label-free approach for characterizing cell death states, eliminating the need for complex molecular labeling that may yield artificial or ambiguous results due to technical limitations in microscope resolution. The proposed holographic tomography technique offers a label-free avenue for capturing precise three-dimensional (3D) refractive index morphologies of cells and directly analyzing cellular parameters like area, height, volume, and nucleus/cytoplasm ratio within the 3D cellular model. We showcase holographic tomography results illustrating various cell death types and elucidate distinctive refractive index correlations with specific cell morphologies complemented by biochemical assays to verify cell death states. These findings hold promise for advancing in situ single cell state identification and diagnosis applications.
... В экспериментальных исследованиях выявлено повы-шение концентрации провоспалительных цитокинов (интерлейкинов 1, 6, 8, фактора некроза опухоли aльфа) в условиях фокальной ишемии мозга, что сопровождается развитием локального воспаления в очаге ишемического повреждения. Уровни провоспалительных цитокинов остаются достоверно повышенными в течение нескольких дней после развития инсульта, что свидетельствует об интенсивности воспалительных реакций и их роли в процессах повреждения ткани мозга [7]. ...
The study was based on data study of immunological parameters in 28 children with stroke in different periods of the disease. Thus, it was found that in children with acute disease there is a violation of the cytokine balance in favor of pro-inflammatory cytokine overproduction and excessive symptoms accompanied by inflammation, which is central to the pathogenesis of this disease. The level of autoantibodies to the vascular endothelium (ANCA) was 3 times higher than the control values, indicating that a pronounced inflammation of the intima of blood vessels. The children in the late recovery period are observed normalization of cytokine status due to lower inflammation of the intimae of blood vessels.
... TNF-α concentrations in plasma, cerebrospinal fluid, and brain tissue are elevated in certain CNS disorders, including Alzheimer's disease, multiple sclerosis, Parkinson's disease, and ischemic brain disorders 25 . Previous studies have demonstrated an association between some ocular diseases and increased levels of TNF-α [26][27][28][29] . ...
Background/Aim. Changes in the concentration of various mediators of inflammation and immune response in blood, aqueous humor, or eye tissues support the theory of inflammation and immune system activity in the pathogenesis of openangle glaucoma. Inflammatory biomarkers have a great potential for application in clinical practice. We investigated the plasma concentrations of tumor necrosis factor alpha (TNF-?) in patients with open-angle glaucoma and controls without glaucoma, and examined a correlation between plasma TNF-? levels in glaucoma patients and their clinical parameters. Methods. The present study included 87 participants (87 eyes) divided into three groups: 35 subjects (35 eyes) with primary open-angle glaucoma with elevated intraocular pressure - hypertension glaucoma (POAG-HTG), 23 subjects (23 eyes) with pseudoexfoliative open-angle glaucoma (XFG), and 29 subjects in the control group matched with the patient groups in terms of age and sex. We performed a complete clinical examination including standard automated perimetry and determination of changes in the participant's repeated visual field, and optical coherence tomography and determination of retinal peripapillary nerve fiber thickness (RNFL). The concentration of circulating TNF-? in participants? plasma was measured using commercial immunoadsorption enzyme tests (ELISA). Results. The concentrations of TNF-? in the plasma of glaucoma patients (POAG-HTG 2.04?1.98 pg/mL and XFG 2.05?1.48 pg/mL) were significantly higher than in healthy subjects (1.43?2.00 pg/mL, p<0.05). No statistically significant correlations of TNF-? concentration with any of the clinical parameters including IOP, C/D, MD, RNFL Avg, RNFL Sup and RNFL Inf were found in any of the groups of patients with glaucoma. Conclusion. The concentration of the pro-inflammatory cytokine, TNF-?, in the plasma is significantly higher in glaucoma patients compared to nonglaucomatous subjects, and confirms the role of the inflammation in the pathogenesis of glaucoma, as one of noninflammatory ocular diseases. The plasma concentration of TNF-? does not correlate with any of the examined clinical parameters; hence, it cannot be considered a measure of progression and damage in glaucoma.
... Inflammation is a complex process that plays a protective role against invading pathogens but can also lead to chronic diseases when dysregulated (20)(21)(22). LPSinduced activation of macrophages triggers the upregulation of nitric oxide and iNOS, which can be used as markers of inflammation, and inhibition of iNOS overproduction is a potential target for anti-inflammatory therapy (23)(24)(25). In this study, we found that treatment with yeast-derived vacuoles at various concentrations significantly inhibited the LPS-induced expression of iNOS protein and mRNA in macrophages ( Fig. 2 and 4A). ...
Saccharomyces cerevisiae is a single-celled fungal microorganism. S. cerevisiae -derived vacuoles are closely related to mammalian lysosomes, which play a role in the degradation of macromolecules by various hydrolytic enzymes. This study evaluated the anti-inflammatory efficacy of S. cerevisiae -vacuoles by inhibiting inflammatory mediators induced by lipopolysaccharide (LPS). The results showed that treatment with 5, 10, and 20 µg/mL of S. cerevisiae -derived vacuoles almost completely inhibited the LPS-induced expression of iNOS protein and mRNA. Moreover, vacuoles significantly reduced the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in LPS-stimulated macrophages compared to the control cells. The immunofluorescence analysis confirmed that S. cerevisiae -derived vacuoles inhibited the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated cells. Taken together, the treatment with S. cerevisiae -derived vacuoles alone activated macrophages, but LPS-activated macrophages modulated pro-inflammatory mediators by downregulating the NF-κB pathway. These results suggest that S. cerevisiae -derived vacuoles may have therapeutic potential in the treatment of inflammatory diseases. In conclusion, our study provides new insights into the immunomodulatory effects of S. cerevisiae -derived vacuoles and their potential as a novel anti-inflammatory agent.
IMPORTANCE
This study investigates the potential of using vacuoles derived from the yeast Saccharomyces cerevisiae as a new anti-inflammatory therapy. Inflammation is a natural response of the immune system to invading pathogens, but when it is dysregulated, it can lead to chronic diseases. The researchers found that treating macrophages with vacuoles significantly reduced the production of pro-inflammatory cytokines and iNOS, markers of inflammation when they were stimulated with lipopolysaccharide. The study also showed that vacuoles inhibited the NF-κB signaling pathway, which is involved in the induction of pro-inflammatory cytokines in macrophages. These findings suggest that S. cerevisiae -derived vacuoles may have potential as a new therapeutic agent for regulating the inflammatory response in various diseases. Further studies are needed to evaluate the efficacy and safety of vacuoles in vivo and to elucidate the underlying mechanisms of their anti-inflammatory effects.
... Cytokines, including IS, are released in the brain after insults and are expressed in cells of the immune system. In addition, production by resident brain cells, including neurons and glia, has been observed (Liu et al., 1994;Sairanen et al., 2001). The most studied cytokines related to pro-inflammation in stroke are IL-1 (Haqqani et al., 2005), and TNF-α (Han and Yenari, 2003). ...
... A complex of IL-1β with transmembrane recep-tors triggers intracellular signaling pathways including the NF-kB, the c-Jun N-terminal kinases (JNKs), and the p38 mitogen-activated protein kinase (P32 MAPKs). The final effects of these signaling pathways are displayed in the form of more inflammatory damage in the brain [18][19][20]. IL-1β antagonist limited excitotoxicity in damaged brain tissues of rats [21]. Wang et al found a negative association between serum levels of vitamin D and IL-6 in IS patients [22]. ...
Background:Previous studies have demonstrated the strong association of inflammatory cyto-kines and vitamin D (VitD) deficiency and ischemic stroke (IS) pathogenesis. Due to the negative correlation between long non-coding RNA (lncRNA) Malat1 and pro-inflammatory factors we decided to investigate the associations between Malat1 expression with serum interleukin-1β (IL-1β), and VitD levels in IS patients. Materials and Methods:In this cross-sectional study, 63 IS patients were included. We used enzyme-linked immunosorbent assays to evaluate the serum levels of VitD and IL-1β. Malat1 expression was evaluated by the real-time polymerase chain reaction test. The associations between Malat1expression with VitD and IL-1β were analysed with linear regression (Stepwise model) and Pearson's correlation analysis. Results: The Malat1 expression was inversely correlated with stroke severity (r=-0.25, P=0.043). Stepwise regression analysis showed a significant positive relationship between VitD level and Malat1 expression (Beta=0.28, P=0.02), and also showed a non-significant negative relationship between IL-1β and stroke severity. VitD level showed a positive Pearson correlation with Malat1 (r=0.28, P=0.023) and a negative correlation with IL-1β (r=-0.29, P=0.018) while it could not detect a significantly negative correlation with stroke severity. Conclusion: For the first time the associations between Malat1 expression with IL-1β and VitD in IS patients was analyzed. We found a significant positive relationship between VitD and Malat1. This correlation needs to be investigated with a larger sample size to achieve a strong and reliable association between VitD and Malat1.[GMJ.2023;12:e2457]
... A complex of IL-1β with transmembrane recep-tors triggers intracellular signaling pathways including the NF-kB, the c-Jun N-terminal kinases (JNKs), and the p38 mitogen-activated protein kinase (P32 MAPKs). The final effects of these signaling pathways are displayed in the form of more inflammatory damage in the brain [18][19][20]. IL-1β antagonist limited excitotoxicity in damaged brain tissues of rats [21]. Wang et al found a negative association between serum levels of vitamin D and IL-6 in IS patients [22]. ...
Background:Previous studies have demonstrated the strong association of inflammatory cytokines and vitamin D (VitD) deficiency and ischemic stroke (IS) pathogenesis. Due to the negative correlation between long non-coding RNA (lncRNA) Malat1 and pro-inflammatory factors we decided to investigate the associations between Malat1 expression with serum interleukin-1β (IL-1β), and VitD levels in IS patients. Materials and Methods:In this cross-sectional study, 63 IS patients were included. We used enzyme-linked immunosorbent assays to evaluate the serum levels of VitD and IL-1β. Malat1 expression was evaluated by the real-time polymerase chain reaction test. The associations between Malat1expression with VitD and IL-1β were analysed with linear regression (Stepwise model) and Pearson’s correlation analysis. Results: The Malat1 expression was inversely correlated with stroke severity (r=-0.25, P=0.043). Stepwise regression analysis showed a significant positive relationship between VitD level and Malat1 expression (Beta=0.28, P=0.02), and also showed a non-significant negative relationship between IL-1β and stroke severity. VitD level showed a positive Pearson correlation with Malat1 (r=0.28, P=0.023) and a negative correlation with IL-1β (r=-0.29, P=0.018) while it could not detect a significantly negative correlation with stroke severity. Conclusion: For the first time the associations between Malat1 expression with IL-1β and VitD in IS patients was analyzed. We found a significant positive relationship between VitD and Malat1. This correlation needs to be investigated with a larger sample size to achieve a strong and reliable association between VitD and Malat1.[GMJ.2023;12:e2457]
... Pro-inflammatory cytokines promote the progression of harmful neuroinflammation after cerebral ischemia. As one of the first cytokines to be produced, TNFα increases in the cerebral parenchyma following MCAO (Liu et al., 1994) and triggers secondary inflammatory reactions (Murakami et al., 2005). Following cerebral ischemia, IL-1β binds to its receptor and activates the nuclear factor-κB pathway (Liao et al., 2015). ...
β2-Microglobulin (β2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of β2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of β2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that β2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit β2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased β2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by β2M silencing. These findings suggest that β2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.
The
most frequent type of stroke, known as ischemic stroke (IS), is a significant global public health issue. The pathological process of IS and post-IS episodes has not yet been fully explored, but neuroinflammation has been identified as one of the key processes. Biomarkers are objective indicators used to assess normal or pathological processes, evaluate responses to treatment, and predict outcomes, and some biomarkers can also be used as therapeutic targets. After IS, various molecules are produced by different cell types, such as microglia, astrocytes, infiltrating leukocytes, endothelial cells, and damaged neurons, that participate in the neuroinflammatory response within the ischemic brain region. These molecules may either promote or inhibit neuroinflammation and may be released into extracellular spaces, including cerebrospinal fluid (CSF) and blood, due to reasons such as BBB damage. These neuroinflammatory molecules should be valued as biomarkers to monitor whether their expression levels in the blood, CSF, and brain correlate with the diagnosis and prognosis of IS patients or whether they have potential as therapeutic targets. In addition, although some molecules do not directly participate in the process of neuroinflammation, they have been reported to have potential diagnostic or therapeutic value against post-IS neuroinflammation, and these molecules will also be listed. In this review, we summarize the neuroinflammatory biomarkers in the brain, CSF, and blood after an IS episode and the potential value of these biomarkers for the diagnosis, treatment, and prognosis of IS patients.
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