Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that can affect nearly every organ system in the body. Besides genetic and environmental factors, unbalanced ...pro‐inflammatory and anti‐inflammatory cytokines contribute to immune dysregulation, trigger an inflammatory response, and induce tissue and organ damage. Inflammatory responses in SLE can be promoted and/or maintained by the availability of cytokines that are overproduced systemically and/or in local tissues. Several key cytokines have been considered potential targets for the reduction of chronic inflammation in SLE. Recent studies indicated that dysregulated production of several cytokines, including those of the IL‐1 family and IL‐10 family, orchestrate immune activation and self‐tolerance, play critical roles in the pathogenesis of SLE. Among IL‐1 family cytokines, IL‐1, IL‐18, IL‐33, IL‐36, IL‐37, and IL‐38 had been the most thoroughly investigated in SLE. Additionally, IL‐10 family cytokines, IL‐10, IL‐20, IL‐22, IL‐26, IL‐28, and IL‐29 are dysregulated in SLE. Therefore, a better understanding of the initiation and progression of SLE may provide suitable novel targets for therapeutic intervention. In this review, we discuss the involvement of inflammation in the pathogenesis of SLE, with a focus on IL‐1 family and IL‐10 family cytokines, and highlight pathophysiological approaches and therapeutic potential for treating SLE.
Interferons (IFNs) are pleiotropic cytokines originally identified for their antiviral activity. IFN-α and IFN-β are both type I IFNs that have been used to treat neurological diseases such as ...multiple sclerosis. Microglia, astrocytes, as well as neurons in the central and peripheral nervous systems, including spinal cord neurons and dorsal root ganglion neurons, express type I IFN receptors (IFNARs). Type I IFNs play an active role in regulating cognition, aging, depression, and neurodegenerative diseases. Notably, by suppressing neuronal activity and synaptic transmission, IFN-α and IFN-β produced potent analgesia. In this article, we discuss the role of type I IFNs in cognition, neurodegenerative diseases, and pain with a focus on neuroinflammation and neuro-glial interactions and their effects on cognition, neurodegenerative diseases, and pain. The role of type I IFNs in long-haul COVID-associated neurological disorders is also discussed. Insights into type I IFN signaling in neurons and non-neuronal cells will improve our treatments of neurological disorders in various disease conditions.
This meta-analysis aimed at exploring the impact of intravenous ketamine on pain relief and analgesic consumption in patients undergoing bariatric surgery (BS). Literature searches identified nine ...eligible trials with 458 participants. Forest plot revealed a significantly lower pain score mean difference (MD) = − 1.06,
p
= 0.005; 390 patients) and morphine consumption (MD = − 3.85 mg,
p
= 0.01; 212 patients) immediately after BS in patients with intravenous ketamine than in those without. In contrast, pooled analysis showed comparable pain score (
p
= 0.28), morphine consumption (
p
= 0.45) within 24 h, and risk of postoperative nausea/vomiting (
p
= 0.67) between the two groups. In conclusion, the meta-analysis demonstrated improvements in pain outcomes immediately after surgery through perioperative intravenous ketamine administration despite the absence of analgesic benefit in the late postoperative period and a positive impact on postoperative nausea/vomiting.
Graphical abstract
Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex) has anti-inflammatory effect. ...We investigated the effects of Dex on lipopolysaccharide (LPS)-induced neuroinflammation and sickness behavior in mice.
BALB/c mice were intraperitoneally (i.p.) injected with Dex (50 ug/kg) or vehicle. One hour later, the mice were injected (i.p.) with Escherichia coli LPS (0.33 mg/kg) or saline (n = 6 in each group). We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment.
In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal) were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO), caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle.
Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Patients with chronic kidney diseases (CKD) are often treated with antiplatelets due to aberrant haemostasis. This study aimed to evaluate the bleeding risk with CKD patients undergoing ...pentoxifylline (PTX) treatment with/without aspirin. In this retrospective study, we used Taiwan’s National Health Insurance Research Database to identify PTX treated CKD patients. Patients undergoing PTX treatment after CKD diagnosis were PTX group. A 1:4 age, sex and aspirin used condition matched CKD patients non-using PTX were identified as controls. The outcome was major bleeding event (MBE: intracranial haemorrhage (ICH) and gastrointestinal tract bleeding) during 2-year follow-up period. Risk factors were estimated using Cox regression for overall and stratified analysis. The PTX group had higher MBE risk than controls (hazard ratio (HR) 1.19; 95% confidence interval (CI) 0.94–1.50). In stratified analysis, hyperlipidaemia was a significant risk factor (HR: 1.42; 95% CI 1.01–2.01) of MBE. A daily PTX dose larger than 800 mg, females, non-regular aspirin usage, and ischaemic stroke were risk factors for MBE in PTX group. When prescribing PTX in CKD patients, bleeding should be closely monitored, especially in those with daily dose more than 800 mg, aspirin users, and with a history of ischaemic stroke.
Glucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs, are also effective, alone or combined with other antiemetics, for preventing nausea and vomiting. Dexamethasone, one of ...the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting, and in patients with only one or two risks for postoperative nausea and vomiting (PONV). Dexamethasone combined with 5-HT3 or tachykinin NK1 antagonists is also suggested for higher-level emetogenic chemotherapy and radiotherapy and for patients at high risk for PONV. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting.
This nationwide retrospective case-control study was aimed at elucidating the risk from cataract surgery in end-stage renal disease (ESRD) patients. Cataract surgery patients were identified using ...the diagnostic and procedural codes for International Classification of Diseases, 9
Revision, Clinical Modification from Taiwan's National Health Insurance Research Database. ESRD patients were selected as cases, while propensity scores for age, sex, comorbidities and year-of-surgery-matched patients without chronic kidney disease constituted the controls. Patients who had undergone eye surgery within 3 years before cataract surgery were excluded. The main outcome measures were target cataract surgery-related complications within 3 months after surgery. A total of 352 cases and 1,760 controls were analysed. Patients with ESRD had a 5.06-fold (95% CI: 2.36-10.87; p < 0.001) risk of vitreous haemorrhage and a 2.74-fold (95% CI: 1.20-6.27; p = 0.017) risk of re-operation for dropped nucleus or vitreous complications. Non-diabetic ESRD patients had a 3.49-fold (95% CI: 1.36-8.91; p = 0.009) risk of corneal oedema. In conclusion, ESRD patients have a higher risk of vitreous haemorrhage, re-operation for dropped nucleus or vitreous complications and corneal oedema (non-diabetic patients) after cataract surgery. Pre-surgery corneal examination, surgery procedure and medication adjustment, closer and longer post-surgery follow-up may lower the risk and improve the visual outcome.
Abstract
Background
Vision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of ...irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.
Methods
We established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.
Results
In the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3
+
CD4
+
RORγt
+
T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro
,
IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.
Conclusions
Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.
To evaluate the impact of high flow nasal oxygenation (HFNO) on the risk of hypoxemia during gastrointestinal endoscopic procedures (GEPs) under sedation.
Meta-analysis of randomized controlled ...trials.
Gastrointestinal endoscopy.
HFNO.
Adults patients undergoing GEPs under sedation.
The primary outcome was risk of hypoxemia, while the secondary outcomes included risks of severe hypoxemia, hypercapnia, need for jaw thrust or other airway interventions, and procedural interruption as well as procedure time, minimum SpO2, and level of carbon dioxide (CO2). Analyses based on age, gender, flow rate, risk status of patients were performed to investigate subgroup effects.
Medline, Google scholar, Cochrane Library, and EMBASE databases were searched from inception to July 2021. Seven randomized controlled trials (RCTs) involving 2998 patients published from 2019 to 2021 were included. All GEPs were performed under propofol sedation. Pooled results revealed significantly lower risks of hypoxemia relative risk (RR) = 0.31, 95% CI:0.13–0.75; 2998 patients, severe hypoxemia (RR = 0.38, 95% CI:0.2–0.74; 2766 patients), other airway interventions (RR = 0.34, 95% CI:0.22–0.52; 2736 patients), procedural interruption (RR = 0.12, 95% CI:0.02–0.64, 451 patients) and a lower CO2 level standard mean difference (MD) = −0.21, 95% CI: −0.4 to −0.03; 458 patients in HFNO group compared to control group. Subgroup analysis focusing on risk of hypoxemia showed no significant subgroup effects, indicating consistent benefits of HFNO in different clinical settings. There were no difference in minimum SpO2 (p = 0.06; 262 patients), risk of hypercapnia (p = 0.09; 393 patients), need for jaw thrust (p = 0.28; 2256 patients), and procedure time (p = 0.41, 1004 patients) between the two groups.
Our results demonstrated the efficacy of high flow nasal oxygenation for reducing the risk of hypoxemia in patients receiving elective gastrointestinal endoscopic procedures under sedation. Further studies are warranted to verify its cost-effectiveness in the gastrointestinal endoscopy setting.
•Hypoxemia related to sedated endoscopic procedures is associated with cardiac risks.•Benefits of high flow nasal oxygenation (HFNO) remain unclear in this setting.•HFNO was associated with reduced risks of severe hypoxemia and airway interventions.•HFNO was related to a reduced blood CO2 level and risk of procedure interruption.•Beneficial impacts of HFNO unaffected by age, gender, flow rate, and risk status.
MicroRNAs (miRNAs) can regulate cell survival and death by targeting apoptosis-related gene expression. miR-210 is one of the most hypoxia-sensitive miRNAs. In this study, we evaluated the roles of ...miR-210 in hypoxia-induced insults to neural cells. Treatment of neuro-2a cells with oxygen/glucose deprivation (OGD) induced cell apoptosis in a time-dependent manner. In parallel, OGD time-dependently increased cellular miR-210 levels. Knocking down miR-210 expression using specific antisenses significantly attenuated OGD-induced neural apoptosis. Concurrently, OGD increased hypoxia-inducible factor (HIF)-1α mRNA and protein syntheses. Pretreatment with YC-1, an inhibitor of HIF-1α, reduced OGD-caused cell death. Sequentially, OGD specifically decreased antiapoptotic Bcl-2 mRNA and protein levels in neuro-2a cells. A search by a bioinformatic approach revealed that miR-210-specific binding elements exist in the 3′-untranslated region of Bcl-2 mRNA. Application of miR-210 antisenses simultaneously alleviated OGD-involved inhibition of Bcl-2 mRNA expression. In comparison, overexpression of miR-210 synergistically diminished OGD-caused inhibition of Bcl-2 mRNA expression and consequently induced greater cellular insults. Taken together, this study shows that OGD can induce miR-210 expression through activating HIF-1α. And miR-210 can mediate hypoxia-induced neural apoptosis by targeting Bcl-2.
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