IL-1β Levels Research Articles

The correlation of GluR3B antibody with T lymphocyte subsets and inflammatory factors and their role in the progression of epilepsy

ObjectiveTo investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated.MethodsPatients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed.ResultsIn this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1β (IL-1β), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1β levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1β and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1β, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409–8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756–8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy.ConclusionsThis study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.

Sea Buckthorn Oil Promotes the PI3K-Akt-ERK Signaling Pathway and Macrophage M2 Polarization to Reduce Radiation-induced Skin Injury.

In this work, we explored the role and mechanism of sea buckthorn oil in reducing radiation-induced skin damage. The radiation-induced rat skin injury model was established using strontium-90. Rats were treated with sea buckthorn oil twice a day postirradiation, and skin damage was observed at different times and evaluated using an injury score. Skin pathological changes were observed using hematoxylin and eosin (H&E) staining. Western blotting and immunohistochemistry were used to detect the expression of vascular growth and pathway proteins. ELISA was used to detect the secretion level of inflammatory factors. Immunohistochemistry was used to detect macrophage polarization marker proteins. We found that sea buckthorn oil can alleviate radiation-induced skin damage, accelerate skin vascular regeneration, and promote the up-regulation of vascular endothelial growth factor (VEGF) and its receptor (VEGFR). These results demonstrate the beneficial effects of sea buckthorn oil on radiation-induced skin damage. Furthermore, the levels of IL-1β and TNF-α in the sea buckthorn oil treatment group were significantly lower than those in the control group, while the levels of IL-4 and IL10 were significantly higher (P < 0.05). CD206 expression also increased in the sea buckthorn oil treatment group, while CD16 expression decreased compared to the control group (P < 0.05). Western blotting showed that PI3K, Akt and ERK expression increased in the sea buckthorn oil treatment group (P < 0.05). The beneficial effect of sea buckthorn oil in reducing the inflammatory response in irradiated rats was diminished when they were treated with PI3K inhibitor. We conclude that sea buckthorn oil may regulate macrophage M2 polarization by increasing the PI3K-Akt-ERK signaling pathway, thereby inhibiting the inflammatory response and promoting skin vascular regeneration to prevent and treat radiation-induced skin damage.

Systemic cytokines related to memory function 6–9 months and 12–15 months after SARS-CoV-2 infection

Cognitive symptoms persisting beyond the acute phase of COVID-19 infection are commonly described for up to 2 years after infection. The relationship between cognitive performance, in particular episodic memory processes observed chronically after infection, and cytokine levels in the acute phase of COVID-19 has not yet been identified in humans. To determine whether the levels of cytokines IL1β, IL-6 and TNFα secreted in the acute phase of SARS-CoV-2 infection are associated and predict verbal and visuospatial episodic memory performance in humans 6 to 9 months and 12 to 15 months post-infection. The associations and predictive value of the concentration of cytokines measured in acute phase (IL-1β, IL-6, TNFα) from plasma samples of N = 33 hospitalized COVID-19 patients (mean age 61 years, 39–78, 65% in intensive care) in relation to their verbal and visuospatial episodic memory performance measured at 6–9 months and 12–15 months post-infection were analyzed. To do this, we used Spearman correlations and generalised linear mixed models. IL-1β levels were associated with verbal episodic memory total recall scores 6–9 months post-infection. At 12–15 months post-infection IL-6 predicted verbal episodic memory score. This study demonstrated that the severity of inflammatory reaction at acute phase of SARS-CoV-2 infection predicts verbal episodic memory performance in the long-term post-infection.

The Alpha-7 Nicotinic Receptor Positive Allosteric Modulator PNU120596 Attenuates Lipopolysaccharide-Induced Depressive-Like Behaviors and Cognitive Impairment by Regulating the PPAR-α Signaling Pathway in Mice.

The brain α7 nicotinic acetylcholine receptor (α7 nAChR) has a critical role in the pathophysiology of Major Depressive Disorder (MDD) involving neuroinflammation. The α7 nAChR stimulation has been shown to modulate the anti-inflammatory effects of nuclear peroxisome proliferator-activated receptor-α (PPAR-α) via its endogenous ligands in the brain. The present study determined the effects of α7 nAChR modulator PNU120596 on PPAR-α, an inhibitor of κB (IκB) and nuclear factor-κB (NF-κB) expression and interleukin-1β (IL-1β) level in the hippocampus and prefrontal cortex (PFC) in an inflammatory mouse model of MDD induced by lipopolysaccharide (LPS). We also evaluated the combined effects of PNU120596 and GW6471, a PPAR-α antagonist, on depressive-like and cognitive deficit-like behaviors in mice. Male C57BL/6J mice were treated with PNU120596, followed by systemic LPS (1 mg/kg, i.p.) administration. The effects of PNU120596 on the mRNA expression of PPAR-α and IκB were assessed in the hippocampus and PFC using qRT-PCR following LPS administration. Similarly, the effects of PNU120596 on the immunoreactivity of PPAR-α and NF-κB were measured in the hippocampus and PFC using an immunofluorescence assay. Furthermore, the effects of PNU120596 on pro-inflammatory cytokine IL-1β levels were measured in the hippocampus and PFC using ELISA. The combined effects of PNU120596 and GW6471 were also assessed against LPS-induced depressive-like and cognitive deficit-like behaviors using the Tail Suspension Test (TST), Forced Swim Test (FST), and Y-maze test. PNU120596 (4 mg/kg) significantly prevented LPS-induced dysregulation of PPAR-α, IκB, p-NF-κB p65, and IL-1β in the hippocampus and PFC. Pretreatment with PNU120596 showed significant antidepressant-like effects by reducing immobility time in the TST and FST. Similarly, pretreatment with PNU120596 significantly reduced cognitive deficit-like behavior in the Y-maze test. The antidepressant and pro-cognitive-like effects of PNU120596 were reversed by PPAR-α antagonist GW6471 (2 mg/kg). These results suggest that PNU120596 prevented LPS-induced MDD and cognitivelike behavior by regulating α7 nAChR/PPAR-α signaling pathway in the hippocampus and PFC.

The relationship between interleukin 1-B and calprotecin in periodontal Disease

Backgrounds: One of the most common diseases affecting the oral cavity in humans is periodontitis. Researchers looked at the effects of calprotectin and IL-1B in human gingival Among the cytokines involved in the pathogenesis of periodontal disease, IL-1β, an inflammatory cytokine, can be highlighted for its contribution to stimulating the recruitment and differentiation of osteoblasts in tissues. Calprotectin is a heterodimer protein consisting of two calcium-bindinglinkages, belonging to the S-100 family.Materials and method: Ninety samples (patient and control) were obtained for the study between July 2023 and December 2024. Of them, sixty samples came from patients who saw periodontists in outpatient clinics and at Balad General Hospital. A sterile cotton swab (transport cotton swab) was used to obtain the sample. Using a syringe and a 5-milliliter Slim syringe, blood was drawn for 79 medical devices and then put into gelatinous gel tubes. The blood was then allowed to clot for fifteen minutes, sediment on the central computer at 3500 for one minute, and the serum was separated and kept in Eppendorf tubes with a 2-milliliter top at room temperature. The bacterial isolates were identified using physiological and biochemical assays, and the sample was held for 20 AD before being employed in the decimal filter. immunological examination The levels of immunological proteins calprotectin and human interleukin (IL-1β) were measured using ELISA technique. Results: IL-1B level in patients with Periodontitis recorded that (50.3±26.7) in comparison with control group that were (49.8±21.8,9.85±4.28) .While calprotectin level in patients with Periodontitis recorded that (10.79±2.69) in comparison with control group that were (9.85±4.28). Conclusion: Most common causes of Periodontitis was Prophyromonas gingivalis ,Staph. Aureus, Strep. Pyogenes. functional polymorphisms in the IL-1 B were not related to the calprotectin in development in Periodontitis prevalent diseases.

Dual anti-inflammatory effects of curcumin and berberine on acetaminophen-induced liver injury in mice by inhibiting NF-κB activation via PI3K/AKT and PPARγ signaling pathways

Acetaminophen (APAP) overdose is still a leading cause of drug-induced liver injury (DILI), accompanied with severe inflammatory response. However, the therapy for APAP-induced DILI is rather limited. The combined application of natural products to treat DILI induced by APAP may be a new direction of the research. This study was conducted to evaluate the dual anti-inflammatory activity of curcumin (CUR) combined with berberine (BBR) against APAP-mediated DILI. Network pharmacology found that PI3K-Akt and PPAR signaling pathways were primarily involved in anti-DILI of the combination of CUR and BBR. APAP injection enhanced the levels of ALT, AST, IL-1β, IL-6, and TNF-α in mice, while such phenomenon was significantly reversed by the cotreatment of CUR and BBR, which was more effective than either single treatment. The increase of p-NF-κB and p-IKKα/β protein expression and the decrease of p-PI3K, p-AKT, and PPARγ protein expression in APAP-treated mice were markedly inhibited by the coadministration of CUR and BBR. Molecular docking further demonstrated that both CUR and BBR could stably bind to PI3K, AKT, and PPARγ protein. In conclusion, the combination of CUR and BBR more effectively protected liver from APAP-triggered DILI than individual treatment. The mechanism is to alleviate hepatic inflammation by inhibiting NF-κB activation, which is possibly mediated by PI3K/Akt and PPARγ signaling pathways.

Sinomenine Hydrochloride Regulates the Apoptosis of Endothelial Cells through PPAR-γ to Alleviate PAH.

Pulmonary arterial hypertension is a progressive heart and lung disease that is caused by irreversible pulmonary vascular remodeling. Sinomenine hydrochloride is an alkaloid that is extracted from sinomenium acutum, which has strong anti-inflammatory effects. In this study, male rats were injected with monocrotaline, and endothelial cells were exposed to hypoxia for 24 hours to induce pulmonary arterial hypertension. Apoptosis, inflammation, and oxidative stress pathways were observed the in lungs and cells. Sinomenine hydrochloride repressed the increased right ventricular systolic pressure and attenuated the right ventricular hypertrophy and pulmonary artery remodeling in model rats. It reversed the expression of BCL2 and BAX and prevented the apoptosis of endothelial cells. Additionally, it increased the contents of IKBα and NRF2. P65, P-P65, TNFα, IL1β, and IL6 levels in the lungs decreased by it. Malondialdehyde contents decreased, and the superoxide dismutase and glutathione peroxidase activity and HO-1 level increased in the treatment group. In vivo, it promoted apoptosis of pulmonary artery endothelial cells. Moreover, by activating PPAR-γ, sinomenine hydrochloride attains the above effects. These data suggested that sinomenine hydrochloride could protect endothelial cells, restrain inflammation and oxidative stress, and enhance pulmonary vascular remodeling.

Measures of spatial memory, peripheral inflammation and negative emotional state predict social-cognitive skills in healthy aging cats

Aging is a complex, multidimensional process. Normative aging is typically accompanied by declines in several cognitive domains, including memory and social cognition. As aging progresses, the often-overlooked early manifestations of cognitive decline can advance, leading to an inability to adapt to new situations and environments. Potential mechanisms influencing cognitive decline remain elusive, but, among other mechanisms, inflammaging, an age-related increase in the chronic production of pro-inflammatory mediators, and emotional stress are implicated. Cognitive function in cats is under-researched, with no studies on the link between potential risk factors and cognitive signs in aging subjects. Understanding this link is essential as it may facilitate the early identification of cognitive decline and encourage preventative, individualized interventions. We carried out a citizen science study to investigate, for the first time, the relationship between cognitive functions, stress, and the inflammatory markers interleukin (IL)-1β and IL-10 in 44 healthy, privately owned pet cats (7–14 years of age), who underwent standardized testing in their home environment. A task was employed to test spatial memory, requiring the cat to recall the location of a food-baited container. An unsolvable task was used to assess cats' social cognition and cognitive flexibility by measuring how they used referential communication (i.e., gaze alternation between the apparatus and the caregivers) compared to their persistence in trying to obtain food which was out of reach. Generalized linear regression analysis, conducted while adjusting for demographic factors and stress behaviors, revealed: 1) a predictive positive relationship connecting spatial memory and the use of social referencing with the caregiver (more gaze alternation) in the unsolvable task, highlighting the importance of the interplay between cognitive domains in sustaining complex behaviors, and 2) a reduced engagement in social referencing toward caregivers (less gaze alternation) in the presence of higher serum levels of IL-1β in the unsolvable task, especially as cats get older. A cat’s social cognitive performance was also negatively predicted by stress-related behaviors, which is not surprising given that cats are sentient creatures whose everyday behavior is also influenced by emotional states. These findings provide new insights into the crosstalk between different cognitive domains during aging and the potential contributions of emotions and inflammation to cognitive changes in healthy aging cats. Further research using this multidimensional approach will help explore these mechanisms of cognitive aging and potential markers for early detection of cognitive changes in older cats, which is critical for timely interventions.

Codonopsis pilosula polysaccharide suppresses the progression of non-small cell lung cancer by triggering NLRP3/GSDMD-dependent pyroptosis

BackgroundNon-small cell lung cancer (NSCLC) represents a prevalent and challenging malignancy, often posing difficulties in treatment due to late-stage diagnosis and limited therapeutic options.ObjectiveThis study aims to elucidate the impact of Codonopsis pilosula polysaccharide (CPP) on NSCLC, exploring its potential anticancer molecular mechanisms.Materials and methodsPurchase A549 cells and treat them with varying concentrations of CPP, dividing them into groups. Use CCK-8 assays for cell proliferation and TUNEL assays for apoptosis detection. Perform Western blot (WB) to detect NF-κB p65, pNF-κB p65, and pyroptosis-related proteins. Measure ROS, inflammatory factors, and LDH levels using kits. Observe pyroptosis morphology under a microscope. Inoculate A549 cells subcutaneously into nude mice to create a xenograft model and treat them with daily CPP injections. Collect tumor tissues, measure tumor volume and mass. Perform TUNEL immunohistochemistry for apoptosis and H&E staining for tumor histology. Detect pyroptosis-related proteins with Western blot and immunohistochemistry, and assess inflammatory factors using ELISA and immunohistochemistry.ResultsThe research reveals a concentration-dependent inhibitory effect of CPP on A549 cell viability, with optimal efficacy observed at 40 μmol/L CPP. CPP demonstrates the capacity to induce apoptosis, mediate NF-κB activation, and accumulate reactive oxygen species (ROS). Notably, CPP promotes pyroptosis in A549 cells and in vivo, upregulating pyroptosis-related proteins. In vivo administration of CPP significantly inhibits tumor growth, accompanied by notable morphological and histological alterations. Additionally, both in vitro and in vivo studies confirm elevated levels of IL-1β and IL-18 in tumor tissues following CPP treatment.Discussion and conclusionIn conclusion, CPP, as a multifaceted agent, suppresses the progression of NSCLC by inducing NLRP3/GSDMD-dependent pyroptosis. This research provides valuable insights into the therapeutic potential of CPP and stimulates further exploration for its integration into future NSCLC treatments.

Interleukin one beta (IL-1B) gene polymorphisms in Iraqi patients with susceptibility to develop hepatitis C infections

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. This study aimed to find an associated relationship between HCV susceptibility and Polymorphic gene of IL‐1B targeting a total of 45 individuals: 30 patients with chronic hepatitis C and 15 healthy control from different cities of Iraqi recruited the Hospital for diseases of the digestive system and liver in Baghdad between November 2022 to February 2023. Genomic DNA was extracted and specific promotor sequence was amplified by polymerase chain reaction (PCR) followed by sequencing then measuring serum concentrations of IL-1β by Enzyme-Linked Immunosorbent Assay (ELISA). The results revealed significant difference in serum levels of IL-1B (P≤0.01), from 1.10-+0.09 in Chronic HCV patients in comparison with its level in healthy controls 7.58± 0.28. Molecular results suggested that single nucleotide polymorphisms in the promoter of IL-1B is probably associated with susceptibility to HCV chronic infection according to this sample of Iraqi patients. In conclusion, the results suggested that variation in serum level and polymorphism in IL-1B is probably associated with susceptibility to hepatitis C virus chronic infection.

IL-37 Inhibits Inflammation of Lacrimal Gland in Dry Eye Mice via the IL-37-PTEN-NFκB Signaling Pathway

ABSTRACT Purpose This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye. Methods Two murine models of dry eye were employed in this investigation. The evaluation of the anti-inflammatory impact of IL-37 (200 μl, 10 μg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1β, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence. Results Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1β, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice. Conclusion IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.

Bovine Neutrophil β-Defensin-5 Provides Protection against Multidrug-Resistant Klebsiella pneumoniae via Regulating Pulmonary Inflammatory Response and Metabolic Response.

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage.

Obesity modulates hematopoietic stem cell fate decision via IL-1β induced p38/MAPK signaling pathway

BackgroundObesity is accompanied by inflammation, which significantly affects the homeostasis of the immune microenvironment. Hematopoietic stem cells (HSCs), residing primarily in the bone marrow, play a vital role in maintaining and producing diverse mature blood cell lineages for the adult hematopoietic and immune systems. However, how HSCs development is affected by obese-promoting inflammation, and the mechanism by which HSC hematopoietic potency is affected by inflammatory signals originating from the obese-promoting changes on bone marrow niche remain unclear. This study elucidates the relationship between obesity-promoting inflammation and HSC fate determination.MethodsThe obesity mice model was established by feeding C57BL/6J mice a high-fat diet (HFD) containing 60% kcal fat. After 6 weeks, HSCs were analyzed using flow cytometry and identified key inflammation cytokine. Transcriptome sequencing techniques were used to discern the distinct pathways in HSCs. Ultimately, confirming the biological mechanism of obesity-induced HSC fate changes via Anakinra blocking specific inflammatory signals.ResultsObesity caused by HFD changed the physical and biochemical properties of the bone marrow niche. In the HFD mice, the population of long-term HSCs in the bone marrow was decreased and facilitated HSCs differentiation towards the myeloid lineage. In addition, HFD increased expression of the inflammatory factor IL-1β in the bone marrow, and a significantly increased expression of IL-1r1 and active p38/MAPK signaling pathway were detected in the HSCs. Inhibition of IL-1β further normalized the expression of genes in p38/MAPK pathway and reversed HSC fate.ConclusionsThese findings have been demonstrated that the p38/MAPK signaling pathway in HSCs is activated by elevated levels of IL-1β within the HSC niche in obese models, thereby regulating HSC differentiation. It suggested a direct link between obesity-promoting inflammation and myeloid differentiation bias of HSCs in the HFD mice.Graphical abstract

Phytochemistry and Evaluation of the Anti-Inflammatory Activity of the Hydroethanolic Extract of Virola elongata (Benth.) Warb. Stem Bark.

Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluated its anti-inflammatory potential. HEVe was obtained by maceration and phytochemically analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulting from croton-oil-induced dermatitis in mice. A cell viability assay was conducted to determine the non-cytotoxic concentrations of the HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production. A phytochemical analysis of the HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. The oral treatment of acute peritonitis with HEVe reduced the total leukocytes, neutrophils, TNF-α, and IL-1β and elevated IL-10 levels. The application of the HEgVe reduced local edema. The HEVe on the RAW 264.7 cells exhibited no cytotoxicity, and the cells with HEVe displayed reduced TNF-α, IL-1β, and NO levels and increased IL-13 levels. HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance.

Investigation of the Effects of Boric Acid against Post Operative Testicular Adhesion Caused by Experimental Laporotomy in Rats.

Post-operative intra-abdominal adhesions, significantly affecting testicular tissue, are a prevalent and serious complication following laparoscopic surgery. This study investigated the efficacy of boric acid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, in preventing post-operative testicular adhesions. Forty rats, were divided into four groups: control, laparoscopy (LA), boric acid (BA), and LA + BA. Following laparoscopic surgery, BA treatment was administered for seven days. While the adhesion score was around 3 in the LA group, it was 1 or below in the LA + BA group. Testicular tissues were examined by histopathological and biochemical methods. In testis tissues, in the LA group, malondialdehyde (MDA) levels increased while superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels decreased; these parameters normalized with BA treatment. Additionally, the LA group exhibited reduced levels of IL-10, Bcl-2, Kisspeptin-1, and GnRH, alongside elevated levels of inflammatory markers IL-1β, IL-6, TNF-α, JNK, BAX, and Caspase 3. BA treatment significantly restored these levels to normal. In conclusion, oxidative stress, inflammation, and apoptosis in testicular tissues were associated with post-operative testicular adhesions. BA demonstrated potential as an anti-adhesive agent, reducing testicular adhesions and normalizing biochemical and histological parameters following laparoscopic surgery.

Role of caspase-11 non-canonical inflammasomes in retinal ischemia/reperfusion injury

BackgroundRetinal ischemia/reperfusion (IR) injury is a common pathological process in many ophthalmic diseases. Interleukin-1β (IL-1β) is an important inflammatory factor involved in the pathology of retinal IR injury, but the mechanism by which IL-1β is regulated in such injury remains unclear. Caspase-11 non-canonical inflammasomes can regulate the synthesis and secretion of IL-1β, but its role in retinal IR injury has not been elucidated. This study aimed to evaluate the role of caspase-11 non-canonical inflammasomes in retinal IR injury.MethodsRetinal IR injury was induced in C57BL/6J mice by increasing the intraocular pressure to 110 mmHg for 60 min. The post-injury changes in retinal morphology and function and in IL-1β expression were compared between caspase-11 gene knockout (caspase-11−/−) mice and wild-type (WT) mice. Morphological and functional changes were evaluated using hematoxylin–eosin staining and retinal whole mount staining and using electroretinography (ERG), respectively. IL-1β expression in the retina was measured using enzyme-linked immunosorbent assay (ELISA). The levels of caspase-11-related protein were measured using western blot analysis. The location of caspase-11 in the retina was determined via immunofluorescence staining. Mouse type I astrocytes C8-D1A cells were used to validate the effects of caspase-11 simulation via hypoxia in vitro. Small-interfering RNA targeting caspase-11 was constructed. Cell viability was evaluated using the MTT assay. IL-1β expression in supernatant and cell lysate was measured using ELISA. The levels of caspase-11-related protein were measured using western blot analysis.ResultsRetinal ganglion cell death and retinal edema were more ameliorated, and the ERG b-wave amplitude was better after retinal IR injury in caspase-11−/− mice than in WT mice. Further, caspase-11−/− mice showed lower protein expressions of IL-1β, cleaved caspase-1, and gasdermin D (GSDMD) in the retina after retinal IR injury. Caspase-11 protein was expressed in retinal glial cells, and caspase-11 knockdown played a protective role against hypoxia in C8-D1A cells. The expression levels of IL-1β, cleaved caspase-1, and GSDMD were inhibited after hypoxia in the si-caspase-11 constructed cells.ConclusionsRetinal IR injury activates caspase-11 non-canonical inflammasomes in glial cells of the retina. This results in increased protein levels of GSDMD and IL-1β and leads to damage in the inner layer of the retina.

Preparation of cubic liquid crystal nanoparticles of puerarin and its protective effect on ischemic stroke

The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).

Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling.

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our prior research has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17-20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the gene) were subjected to a 60-min middle cerebral artery occlusion (MCAO). Gene floxed females (two alleles) and males (one allele) were included as controls. Infarct volume and behavioral deficits were quantified 3 days after stroke. Immune responses including microglial activation and infiltration of peripheral leukocytes in the ischemic brain were assessed by flow cytometry. Epigenetic modification of IRF5/4 by Kdm6a/5c were analyzed by CUT&RUN assay. The demethylation of H3K27Me3 by kdm6a increased IRF5 transcription; meanwhile Kdm5c demethylated H3K4Me3 to repress IRF5. Both Kdm6a fl/fl and Kdm5c fl/fl mice had worse stroke outcomes compared to fl/y and CKO mice. Gene floxed females showed more robust expression of CD68 in microglia, elevated brain and plasma levels of IL-1β or TNF-α, after stroke. We concluded that IRF5 signaling plays a critical role in mediating the deleterious effect of Kdm6a; whereas Kdm5c's effect is independent of IRF5.

Harmaline attenuates chemotherapy-induced peripheral neuropathy: Modulation of Nrf-2 pathway and NK-1 receptor signaling

Peripheral neuropathy, resulting from damage to peripheral nerves, manifests as weakness, numbness, and pain, primarily affecting extremities and significantly impairing quality of life, especially in the elderly. Current treatments often entail severe side effects, necessitating the exploration of alternative therapies. Harmaline, a β-carboline alkaloid derived from Peganum harmala, exhibits promising antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of harmaline in a vincristine-induced mouse model of peripheral neuropathy. Swiss albino mice received vincristine (0.1 mg/kg, i.p.) for 10 days to induce neuropathy. Harmaline (5 and 10 mg/kg, i.p.) was administered 30 min before vincristine and continued until day 14 to evaluate its protective effects. Behavioral assessments were conducted on days 7 and 14. Vincristine treatment significantly heightened sensitivity to cold, measured by cold plate and acetone drop tests, and to heat, assessed via the hot plate test, while also impairing motor coordination. Biochemical analyses revealed decreased levels of GSH and Nrf-2, alongside elevated TBARS and IL-1β levels in sciatic nerve tissue. Harmaline administration markedly alleviated both behavioral and biochemical alterations induced by vincristine, with the 10 mg/kg dose exhibiting the most pronounced effects. Notably, harmaline treatment elevated GSH and Nrf-2 levels while reducing TBARS and IL-1β. Furthermore, substance-P treatment reversed the protective effects of harmaline, implicating the NK-1 receptor in its mechanism of action. In conclusion, harmaline demonstrates significant potential in mitigating vincristine-induced peripheral neuropathy by reducing oxidative stress through Nrf-2 activation and lowering IL-1β levels, likely via NK-1 receptor inhibition.

The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

Aim: To study the relationship between NLRP3 (nucleotide oligomerization domain [NOD]-, leucine-rich repeats [LRR]-, and pyrin domain-containing protein 3) inflammasome and its downstream inflammatory factors in obstructive sleep apnea (OSA) patients with carotid atherosclerosis (CAS) under cigarette exposure, further exploring the risk factors of CAS in OSA patients. Methods: A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected. According to the detection results, they were divided into the OSA group, the CAS group, and the OSA combined CAS group; additionally, 29 healthy subjects who underwent a physical examination were also included. According to whether they were smoking, the groups were further divided into smoking and non-smoking groups. The age, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), lowest blood oxygen saturation (LSaO2), carotid intima-media thickness (CIMT), levels of blood sugar, blood low-density lipoprotein cholesterol (LDLc), and serum NLRP3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) of all subjects were recorded. Results: The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group. The levels of serum NLRP3, IL-1β, and IL-18 in the OSA group were higher than those in the normal control group (P &lt; 0.05); and those in the OSA combined CAS group were higher than the OSA group and CAS group (P &lt; 0.05), regardless of cigarette exposure. Considering cigarette exposure, serum NLRP3, IL-1β, and IL-18 levels were higher in the OSA, CAS, and OSA combined CAS smoking groups than those in the non-smoking group (P &lt; 0.05). Under cigarette exposure, AHI, LDLc, NLRP3, IL-1β, and IL-18 were significantly positively correlated (P &lt; 0.05), and LSaO2 was negatively correlated with CAS in OSA (P &lt; 0.05). AHI, LSaO2, LDLc, NLRP3, and IL-1β are the risk factors for OSA combined with CAS. Conclusion: LSaO2, AHI, LDLc, NLRP3, and IL-1β are the important risk factors for OSA combined with CAS under cigarette exposure, and their levels can be used to predict the occurrence of CAS in OSA.