Release Of Inflammatory Factors Research Articles

The therapeutic effect of different cumin essential oil fractions against gastric ulcer in rats.

Cumin, a popular spice, is widely used to treat stomach ailments in Central Asia and Xinjiang, China. Cumin essential oil has been found to effectively treat gastric ulcers, but its pharmacodynamic basis remains unclear. In this study, cumin essential oil was directly separated using column chromatography, and its components were identified through multi-dimensional gas chromatography-mass spectrometry. Finally, the cumin essential oil was fractionated into E1, E2, and E3. The effects of these fractions on gastric ulcers were studied using an anhydrous ethanol-induced rat model. The results indicated that the three fractions decreased ulcer index, gastric fluid pH, and pepsin activity to different extents. They lowered the levels of prostaglandin E2, gastrin, and epidermal growth factor in rat serum. According to an analysis of the above indices, E3 fraction had the best anti-ulcer effect. The detection results of the oxidative stress and inflammatory factors showed that all three fractions relieved the ethanol-induced oxidative stress and reduced the release of inflammatory factors to varying degrees. The E3 fraction played the most significant role. The E3 fraction was selected to explore the relevant mechanism, and the results showed that E3 fraction significantly prevented the cleaved caspase-3 and Bax protein levels that were ethanol-induced and resisted apoptosis induced by ethanol injury. The western blot results for detecting the NF-κB-related pathway protein showed that E3 fraction significantly inhibited the activation of p-p65, p-IKKβ, and p-IκBα. The study found that the E3 fraction of cumin essential oil had the most effective anti-ulcer effect by inhibiting NF-κB activation and apoptosis, thus reducing inflammation.

Potential shared mechanisms in atopic dermatitis and type 2 diabetes identified via transcriptomic and machine learning approaches

Although atopic dermatitis (AD) and type 2 diabetes mellitus (T2DM) may appear clinically and pathophysiologically unrelated, AD is a common skin disease characterized by chronic inflammation and skin barrier dysfunction, whereas T2DM is a metabolic disorder marked by hyperglycemia and chronic inflammation, which further exacerbates insulin resistance (IR) through the release of systemic inflammatory factors. Despite their apparent differences, the molecular mechanisms shared between AD and T2DM remain relatively unexplored. In this study, we integrated transcriptomic data from both AD and T2DM using differential gene expression analyses (DEGs), gene set variation analysis (GSVA), and machine learning algorithms to uncover common features of these diseases. We identified several characteristic genes, including LTF, LTB4R, and CCR1, which are significantly upregulated in both conditions and may serve as potential biomarkers. Furthermore, virtual screening revealed that Dioscin, Camptothecin, and Albamycin exhibit strong affinity for the CCR1 binding site, indicating their potential as therapeutic candidates. In summary, this study elucidates the shared molecular mechanisms of AD and T2DM and introduces new potential targets and drugs for the diagnosis and treatment of these diseases.

Evaluation of the effect of phellodendrin application on rats creating an experimental model of non-compression lumbar disc herniation on the NF-κB-related inflammatory signaling pathway

ObjectiveTo explore the therapeutic effects of phellodendrine on non-compression lumbar disc herniation (NCLDH).MethodsThe Sprague Dawley rat model of NCLDH was established via autologous caudal nucleus pulposus transplantation. Behavioral observations and neurological function scoring were conducted in Sprague Dawley rats, and the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured via enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (RT‒qPCR) was used to detect the expression of nuclear factor kappa-B (NF-κB) p65 mRNA in L5 nerve roots and surrounding tissues. Western blotting was used to assess the protein expression of NF-κB p65 and TNF-α. Immunofluorescence and immunohistochemical analyses were performed to investigate the distribution and expression of the NF-κB p65 protein in the L5 nerve and its surrounding tissues.ResultsIn this animal study, phellodendrine was found to downregulate the expression of p65 mRNA, decrease the release of inflammatory factors, and alleviate motor dysfunction caused by lumbar disc herniation(LDH). Therefore, the phellodendrine technique has potential value for the treatment of NCLDH.ConclusionIn this animal experiment, phellodendrine was found to significantly reduce the expression level of p65 mRNA, decrease the release of inflammatory cytokines, and alleviate lumbar disc pain.Clinical trial numberNot applicable.

Mechanism of Saikosaponin D on Lipopolysaccharide-Induced Acute Lung Injury in Neonatal Rats

This study investigates the mechanism of saikosaponin D on lipopolysaccharide (LPS) aspiration pneumonia in neonatal rats. Inhalation lung injury model was constructed and rats were assigned into control group, model group, saikosaponin D (5, 10 or 20 mg/kg) group and dexamethasone 2 mg/kg group (positive control group). The dry and wet mass ratio of lung tissue was measured by wet and dry method. Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), IL-6, IL-1β and TNF-α were measured by ELISA. HMGB1, TLR4 and p-NF-κB p65 protein expressions were detected by Western blot. Compared with control group, model group had significantly higher wet and dry mass ratio of lung tissue, lower SOD and GSH contents, higher MDA content, higher IL-6/IL-1β/TNF-α levels, higher HMGB1 and TLR4 levels and higher p-NF-κB p65 to NF-κB p65 ratio (P <0.05). Compared with model group, dry and wet mass ratios of lungs in saikosaponin D groups and dexamethasone group were reduced, SOD and GSH contents were increased, and MDA contents were reduced. Meanwhile, IL-6/IL-1β/TNF-α levels were reduced and HMGB1 and TLR4 levels and p-NF-κB p65 ratio were reduced (P < 0.05). In conclusion, saikosaponin D inhibited release of inflammatory factors, improved oxidative stress and HMGB1/TLR4/NF-κB signaling in LPS-induced inhalational lung injury.

Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.

Morphine has a crucial role in treating both moderate to severe pain and chronic pain. However, prolonged administration of morphine can lead to tolerance of analgesia, resulting in increased doses and poor treatment of pain. Many patients, such as those with terminal cancer, require high doses of morphine for long periods. Addressing morphine tolerance can help this group of patients to escape pain, and the mechanisms behind this need to be investigated. Microglia are the key cells involved in morphine tolerance and chronic morphine administration leads to microglia activation, which in turn leads to activation of internal microglia signalling pathways and protein transcription, ultimately leading to the release of inflammatory factors. Inhibiting the activation of microglia internal signalling pathways can reduce morphine tolerance. However, the exact mechanism of how morphine acts on microglia and ultimately leads to tolerance is unknown. This article discusses the mechanisms of morphine induced microglia activation, reviews the signalling pathways within microglia and the associated therapeutic targets and possible drugs, and provides possible directions for clinical prevention or retardation of morphine induced analgesic tolerance.

Progress in the mechanism of functional dyspepsia: roles of mitochondrial autophagy in duodenal abnormalities.

Mitochondria are the main source of energy for cellular activity. Their functional damage or deficiency leads to cellular deterioration, which in turn triggers autophagic reactions. Taking mitochondrial autophagy as a starting point, the present review explored the mechanisms of duodenal abnormalities in detail, including mucosal barrier damage, release of inflammatory factors, and disruption of intracellular signal transduction. We summarized the key roles of mitochondrial autophagy in the abnormal development of the duodenum and examined the in-depth physiological and pathological mechanisms involved, providing a comprehensive theoretical basis for understanding the pathogenesis of functional dyspepsia. At present, it has been confirmed that an increase in the eosinophil count and mast cell degranulation in the duodenum can trigger visceral hypersensitive reactions and cause gastrointestinal motility disorders. In the future, it is necessary to continue exploring the molecular mechanisms and signaling pathways of mitochondrial autophagy in duodenal abnormalities. A deeper understanding of mitochondrial autophagy provides important references for developing treatment strategies for functional dyspepsia, thereby improving clinical efficacy and patient quality of life.

Acupoint injection inhibiting abnormal secretion of mucin and inflammatory reaction of nasal mucosa in rats with allergic rhinitis through the p38 mitogen-activated protein kinase pathway

To observe the effects of acupoint injection on the expression of p38 mitogen-activated protein kinase (MAPK), phosphorylated (p)-p38 MAPK, mucin 5 subtype AC (MUC5AC) in the nasal mucosa, and serum inflammatory factors of rats with allergic rhinitis, so as to explore the mechanism of acupoint injection in improving inflammatory reactions in the nasal mucosa of rats with allergic rhinitis. SD rats were randomly divided into the normal group, model group, acupoint injection group, and non-acupoint group, with 7 rats in each group. The allergic rhinitis rat model was established using ovalbumin sensitization. Intervention was performed by injecting dexamethasone and 1% lidocaine mixture (0.05 mL) into the bilateral "Yingxiang"(LI20) and "Yintang"(GV24+) acupoints, with injection at non-acupoints for non-acupoint group as the control, once every 3 days for a total of 4 times. Allergic symptoms in the rat nose were evaluated using a cumulative scoring method；histopathological changes in the nasal mucosa were observed after HE staining；serum histamine (HA), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-α) contents were detected using ELISA；real-time fluorescent quantitative PCR was used to detect the expression of MUC5AC mRNA in the nasal mucosa；Western blot was used to detect the expression of p38 MAPK, p-p38 MAPK, and MUC5AC protein in the nasal mucosa. Compared with the normal group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK, p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly increased(P<0.01) in the model group. Compared with the model group and non-acupoint group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK and p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly reduced (P<0.01, P<0.05) in the acupoint injection group. Acupoint injection can reduce nasal allergic symptom, and MUC5AC secretion in rats with allergic rhinitis, alleviate nasal mucosal inflammatory reactions, and its mechanism of action may be related to the inhibition of p38 MAPK phosphorylation, thereby reducing the release of inflammatory factors.

Paeonol attenuates LPS-induced inflammatory injury in mastitis by regulating the MAPK and Nrf2 signaling pathways

Mastitis is an inflammatory udder disease that causes important economic losses in the animal breeding and dairy product industries. While antibiotics have contributed to disease control, their use presents risks due to drug residues in livestock products that can potentially threaten human health. Paeonol, an active ingredient extracted from the dried root bark of paeonia suffruticosa, exhibits various pharmacological effects, including anti-inflammatory and antibacterial properties, but its role in mastitis remains unclear. In this study, we first evaluated the effects of paeonol on LPS-induced mastitis in mice and further explored the potential anti-inflammatory mechanism of paeonol on bovine mammary epithelial cells (BMECs). The results showed that paeonol alleviated LPS-induced mouse mastitis by inhibiting the infiltration of inflammatory cells and the release of inflammatory factors. Cellular assays further demonstrated that paeonol reduced apoptosis and inhibited inflammation and oxidative stress injury by mechanisms involving activation of Nrf2 signaling and inhibition of MAPK signaling in BMECs. Collectively, our results suggest that paeonol holds promise as a therapeutic agent for alleviating LPS-induced mastitis injury while providing novel insights into potential drug targets for mastitis treatment.

Ethanol extracts of Cinnamomum migao H.W. Li attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways

Ethnopharmacological relevanceCinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), activating blood circulation (Huoxue in Chinese), and promoting Qi circulation (Tongqi in Chinese) properties. However, its therapeutic potential for ischemic stroke (IS) remains unexplored. Therefore, this study was to explore the protective effect of MG against cerebral ischemia-reperfusion injury caused by IS. Aim of the studyThe aim of this study was to investigate whether ethanol extract of MG (EEMG) attenuates cerebral ischemia-reperfusion injury, and explored the underlying mechanisms. Materials and methodsMiddle cerebral artery occlusion and reperfusion (MCAO/R) was established, and the efficacy of EEMG was evaluated using triphenyltetrazolium chloride (TTC), immunofluorescence, hematoxylin-eosin (HE) staining, and real-time quantitative PCR (qRT-PCR). Qualitative analysis of EEMG was analyzed for chemical composition by liquid chromatography-mass spectrometry (LC-MS). The molecular mechanism of EEMG was explored by metabolomics, network pharmacology, immunoblotting, immunofluorescence staining, gene knockdown, and agonist treatment. ResultsThe results showed that EEMG alleviates ischemic injury in MCAO/R-operated rats and reduces neuronal damage of OGD/R-treated SH-SY5Y cells. Specifically, EEMG inhibited the release of inflammatory factors and reversed serum metabolic profile disorders of MCAO/R rats. Network pharmacology analysis showed that the PI3K-Akt and NF-κB signaling pathways play a role in the neuroprotective effects of EEMG against ischemic injury and in mitigating the inflammatory response. Consistent with our expectations, EEMG activated PI3K-AKT and suppressed NF-kB signaling pathways both in MCAO/R-operated rats and OGD/R-treated BV2 cells. The results showed that knockdown of TLR4 abolished the EEMG-mediated inhibition on neuroinflammation in OGD/R-treated BV2 cells. After treating BV2 cells with the TLR4 agonist neoseptin 3, EEMG showed a trend toward inhibiting neuroinflammation, though the effect was not statistically significant. Additionally, EEMG was found to improve liver injury caused by cerebral ischemia-reperfusion, which is associated with NF-κB signaling pathway in this study. ConclusionsCollectively, this study demonstrated that EEMG attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.

Glia-related Acute Effects of Risperidone and Haloperidol in Hippocampal Slices and Astrocyte Cultures from Adult Wistar Rats: A Focus on Inflammatory and Trophic Factor Release.

Antipsychotics are drugs commonly prescribed to treat a variety of psychiatric conditions. They are classified as typical and atypical, depending on their affinity for dopaminergic and serotonergic receptors. Although neurons have been assumed to be the major mediators of the antipsychotic pharmacological effects, glia, particularly astrocytes, have emerged as important cellular targets for these drugs. In the present study, we investigated the effects of acute treatments with the antipsychotics risperidone and haloperidol of hippocampal slices and astrocyte cultures, focusing on neuron-glia communication and how antipsychotics act in astrocytes. For this, we obtained hippocampal slices and primary astrocyte cultures from 30-day-old Wistar rats and incubated them with risperidone or haloperidol (1 and 10μM) for 30min and 24h, respectively. We evaluated metabolic and enzymatic activities, the glutathione level, the release of inflammatory and trophic factors, as well as the gene expression of signaling proteins. Haloperidol increased glucose metabolism; however, neither of the tested antipsychotics altered the glutathione content or glutamine synthetase and Na+K+-ATPase activities. Haloperidol induced a pro-inflammatory response and risperidone promoted an anti-inflammatory response, while both antipsychotics seemed to decrease trophic support. Haloperidol and risperidone increased Nrf2 and HO-1 gene expression, but only haloperidol upregulated NFκB and AMPK gene expression. Finally, astrocyte cultures confirmed the predominant effect of the tested antipsychotics on glia and their opposite effects on astrocytes. Therefore, antipsychotics cause functional alterations in the hippocampus. This information is important to drive future research for strategies to attenuate antipsychotics-induced neural dysfunction, focusing on glia.

VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages

Macrophages are present in all tissues and body compartments under homeostatic physiological conditions. Importantly, they play a key role in pathological inflammatory processes when disturbed. They can quickly produce large amounts of inflammatory cytokines in response to danger signals. Macrophages can recognize muramyl dipeptide (MDP) through nucleotide-binding oligomerization domain (NOD)-like receptors, subsequently activating the NF-κB signaling pathway and producing proinflammatory cytokines. Erbin can bind to NOD2 and inhibit MDP-induced NF-κB activation, thus participating in the regulation of inflammatory response. Stabilizing or enhancing Erbin expression is essential for suppressing inflammatory responses. In this study, we used a deubiquitination enzyme plasmid library to screen for a key deubiquitinase, VCPIP1, which interacts with Erbin and influences its stability through deubiquitination modification. We investigated whether VCPIP1 affects inflammation using MDP-stimulated RAW 264.7 and BMDMs cells. The results showed that VCPIP1 deficiency reduced Erbin expression and increased NF-κB phosphorylation. Additionally, VCPIP1 deficiency promoted the release of inflammatory factors (IL-1β, IL-6, and TNF-α) in RAW 264.7 cells and BMDMs. This study further expands the role of deubiquitinases (DUBs) in inflammation, providing new insights for the prevention and treatment of sepsis, tumors, immune diseases, and other inflammatory reactions.

Metformin as a strategy against false positives in 18F-FDG PET/CT due to inflammation

Lung cancer is the leading cause of cancer-related deaths globally. Despite recent improvements in incidence and mortality rates, the prognosis of lung cancer remains dire.18F-FDG PET/CT plays a vital role in diagnosing, staging, and monitoring the therapeutic efficacy of lung cancer. However, the high glucose metabolism in inflammatory lesions, driven by macrophage activation, aggregation, and the release of inflammatory factors, is a primary source of false-positive results in FDG PET/CT oncology. This significantly diminishes the specificity and accuracy of PET/CT in diagnosing and staging lung cancer.Here we show FoxO1 plays a role in glucose metabolism in macrophages.We found that metformin regulated FoxO1 expression in macrophages, regulated the expression of inflammatory mediators and apoptosis of macrophages, thus reducing inflammatory glucose metabolism and improving the diagnostic accuracy of 18F-FDG PET/CT in lung cancer.We anticipate that our study could provide a credible approach to improve tumor diagnostic accuracy with PET/CT.

20-Hydroxyeicosatetraenoic Acid Regulates the Src/EGFR/NF-κB Signaling Pathway Via GPR75 to Activate Microglia and Promote TBI in the Immature Brain.

20-Hydroxyeicosatetraenoic acid (20-HETE) is associated with secondary damage in traumatic brain injury (TBI) of the immature brain. Microglial activation is pivotal in this process. However, the underlying mechanism of action remains unknown. While 20-HETE interacts with G protein-coupled receptor 75 (GPR75) in some pathological processes, their interaction in brain tissue remains uncertain. This study aimed to investigate whether 20-HETE can activate microglia by binding to GPR75 in TBI of the immature brain. Drug affinity responsive molecular target stability (DARTS) assays, cycloheximide (CHX) chase assays, and auto-dock assays were employed to analyze the interaction between 20-HETE and GPR75. The expression levels of cytochrome P450 4A (CYP4A) and GPR75 in activated microglia in an immature brain TBI model were observed by western blot and multiple immunofluorescence staining. The effects of different levels of 20-HETE expression and lentivirus-mediated GPR75 gene silencing on 20-HETE-induced inflammatory factor release from BV-2 cells were observed by enzyme-linked immunoassay (ELISA). The phosphorylation levels of the downstream Src kinase, epidermal growth factor receptor (EGFR), and nuclear factor (NF)-κB were assessed using western blot. Cell viability and apoptosis were detected by CCK-8 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. 20-HETE bound to the GPR75 protein and inhibited its degradation. GPR75 gene silencing reversed the 20-HETE-induced inflammatory activation of BV-2 cells, effectively inhibiting the activation of the Src/EGFR/NF-κB pathway and the effects of 20-HETE on cell viability and the apoptosis rate. In contrast, overexpression of GPR75 had the opposite effect. In addition, after immature brain TBI, the 20-HETE and GPR75 expression levels were upregulated in microglia, with significant activation of the Src/EGFR/NF-κB pathway. Inhibition of 20-HETE synthesis with N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) produced the opposite effect. 20-HETE regulates the Src/EGFR/NF-κB signaling pathway via GPR75 to activate microglia, promoting immature brain TBI. These findings offer a novel target for promoting the brain injury effect of 20-HETE.

Bendamustine–rituximab elicits dual tumoricidal and immunomodulatory responses via cGAS–STING activation in diffuse large B-cell lymphoma

BackgroundBendamustine–rituximab (BR) therapy stands out as a promising alternative for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating notable efficacy when conventional regimens pose challenges. Despite its clinical success,...

MiR-146a-5p-enriched exosomes inhibit M1 macrophage activation and inflammatory response by targeting CD80.

Previous studies have demonstrated that miR-146a-5p negatively regulated the intrinsic immune and inflammatory responses, whether the miR-146a-5p-enriched exosomes possess the anti-inflammation effect remains unclear. This study aimed to investigate the effect of miR-146a-5p-enriched exosomes on M1 macrophage activation and inflammatory response and the potential molecular mechanism. GEO database was used to analyze the expression of miR-146a-5p in serum exosomes of MASH patients. MiR-146a-5p levels in primary hepatocytes, macrophages, and serum exosomes of MASH mice were measured. MiR-146a-5p-enriched exosomes were constructed and the effects on M1 macrophages activation and inflammatory factors release were investigated. The target gene of miR-146a-5p was predicted and verified. Serum exosomal miR-146a-5p level was decreased in MASH patients analyzed by GEO database. The miR-146a-5p levels in primary cultured hepatocytes and macrophages of MASH mice were decreased. Serum exosomal miR-146a-5p level was decreased and negatively correlated with the concentrations of IL-6 in MASH mice. Furthermore, miR-146a-5p-enriched exosomes inhibited the M1 macrophages activation and the expression of pro-inflammatory factors MCP-1, IL-6, and TNF-α. CD80 was predicted as the potential target gene of miR-146a-5p, and the expression of CD80 was regulated by miR-146a-5p. In addition, the inhibitory effect of miR-146a-5p on M1 macrophages activation and inflammatory factors release was restored when CD80 was over-expressed. This study demonstrated that miR-146a-5p-enriched exosomes can inhibit the M1 macrophages activation and reduce the release of pro-inflammatory factors by targeting CD80.

Tinosporae Radix attenuates acute pharyngitis by regulating glycerophospholipid metabolism and inflammatory responses through PI3K-Akt signaling pathway.

With the onset of the COVID-19 pandemic, the incidence and prevalence of acute pharyngitis (AP) have increased significantly. Tinosporae Radix (TR) is a vital medication utilized in the treatment of pharyngeal and laryngeal ailments, especially AP. The study endeavors to explore unclear molecular mechanisms of TR in addressing AP. Network pharmacology and metabolomics analyses of effect of TR on AP were conducted, and apossible pathway was validated both in vivo using the acute pharyngitis rat model and in vitro using the LPS-induced RAW264.7 cells model, through techniques such as histopathological examinations, immunohistochemical technology, ELISA, RT-qPCR, and Western blotting to systematically explore the possible mechanisms underlying the inhibition of AP by TR. Network pharmacology analysis identified several key targets, including PIK3CA, IL6, AKT1, TNF, and PTGS2, alongside pivotal signaling pathways such as IL-17, TNF, Hepatitis B, nuclear factor kappa B (NF-κB), Influenza A, and the PI3K-Akt pathway. Most of them are closely associated with inflammation. Then, wide-target metabolomics analysis showed that TR downregulated substances within the glycerophospholipid metabolic pathway, and modulated the PI3K-Akt pathway. The integrated findings from network pharmacology and metabolomics underscored the pivotal role of the PI3K-Akt signaling pathway and the attenuation of inflammatory responses. Finally, in vitro and in vivo experiments have shown that TR can inhibit inflammatory factors such as IL-6, TNF - α, and COX-2, downregulate targets such as PI3K and AKT on the PI3K-Akt signaling pathway, and thereby alleviate the inflammatory response of AP. Our study demonstrated that TR exerts an anti-AP effect through suppression of release of inflammatory factors and modulation of glycerophospholipid metabolism via suppressing the PI3K-Akt signaling pathway.

Gypenosides alleviates HaCaT keratinocyte hyperproliferation and ameliorates imiquimod-induced psoriasis in mice.

Psoriasis is an autoimmune skin condition characterized by hyperproliferation of keratinocytes and chronic immune responses. Gypenosides (Gyp) exhibits anti-proliferative and anti-inflammatory effects on different diseases. However, its functioning and mechanism of Gyp on psoriasis remains unknown. To explore the effect and mechanism of Gyp on psoriasis. The impact and mechanism of Gyp on psoriasis in vitro and in vivo were probed through cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, reverse transcription quantitative polymerase chain reaction, hematoxylin and eosin staining, enzyme-linked immunosorbent serologic assay, immunofluorescence, and Western Blotting assays. Gyp inhibited cell proliferation and the release of inflammatory cytokinesin interleukin (IL-22)-induced spontaneously transformed human aneuploid immortal keratinocyte cell line (HaCaT). In addition, Gyp demonstrated enhancement in erythema and scaling as well as reductions in the thickness of epidermal layers, release of inflammatory factors, and Ki-67 (a nuclear protein) level in imiquimod (IMQ)-induced mice. Mechanistically, Gyp upregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) expression and diminished the level of p-p65/p65 and p-STAT3/STAT3 in skin tissues from IMQ-induced mice and IL-22-induced HaCaT cells, which were reversed with the application of ML385, an inhibitor of Nrf2. In addition, the administration of ML385 reversed decrease in cell viability and reduced the expressions of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in IL-22-induced HaCaT cells caused by Gyp. In summary, Gyp reduced excessive cell growth and inflammation in psoriasis by suppressing nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) through activation of Nrf2.

Unveiling the nexus: pyroptosis and its crucial implications in liver diseases.

Pyroptosis, a distinctive form of programmed cell death orchestrated by gasdermin proteins, manifests as cellular rupture, accompanied by the release of inflammatory factors. While pyroptosis is integral to anti-infection immunity, its aberrant activation has been implicated in tumorigenesis. The liver, as the body's largest metabolic organ, is rich in various enzymes and governs metabolism. It is also the primary site for protein synthesis. Recent years have witnessed the emergence of pyroptosis as a significant player in the pathogenesis of specific liver diseases, exerting a pivotal role in both physiological and pathological processes. A comprehensive exploration of pyroptosis can unveil its contributions to the development and regression of conditions such as hepatitis, cirrhosis, and hepatocellular carcinoma, offering innovative perspectives for clinical prevention and treatment. This review consolidates current knowledge on key molecules involved in cellular pyroptosis and delineates their roles in liver diseases. Furthermore, we discuss the potential of leveraging pyroptosis as a novel or existing anti-cancer strategy.

Avicularin Treatment Ameliorates Ischemic Stroke Damage by Regulating Microglia Polarization and its Exosomes via the NLRP3 Pathway.

Avicularin (AL), an ingredient of Banxia, has anti-inflammatory properties in cerebral disease and regulates polarization of macrophages, but its effects on ischemic stroke (IS) damage have not been studied. In vivo, AL was administered by oral gavage to middle cerebral artery occlusion/reperfusion (MCAO/R) C57BL/6J mice in doses of 1.25, 2.5, and 5 mg/kg/day for seven days, and, in vitro, AL was added to treat oxygen-glucose deprivation (OGD)-BV2 cells. Modified neurological severity score, Triphenyltetrazolium chloride (TTC) staining, brain-water-content detection, TdT-mediated dUTP nick-end labeling (TUNEL) assay, flow cytometry, immunofluorescence assay, Enzyme linked immunosorbent assay (ELISA), and Western-blot analysis were used to investigate the functions and mechanism of the effect of AL treatment on IS. The exosomes of AL-treated microglia were studied by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and Western-blot analysis. AL treatment reduced the neurological severity score, infarct volume, brain-water content, neuronal apoptosis, and the release of inflammatory factors, that were induced by MCAO/R. Notably, M2 microglia polarization was promoted but M1 microglia polarization was inhibited by AL in the ischemic penumbra of MCAO/R mice. Subsequently, anti-inflammatory and polarization-regulating effects of AL were verified in vitro. Suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation was found in the ischemic penumbra of animal and Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) cells treated with AL, as evidenced by decreasing NLRP3-inflammasome-related protein and downstream factors. After AL treatment, the anti-apoptosis effect of microglial exosomes on OGD/R primary cortical neurons was increased. AL reduce inflammatory responses and neuron death of IS-associated models by regulating microglia polarization by the NLRP3 pathway and by affecting microglial exosomes.

Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress Induced Neuroinflammation and Depression-like Behavior.

Growing evidence suggests that glucose metabolism plays a crucial role in activated immune cells, significantly contributing to the occurrence and development of neuroinflammation and depression-like behaviors. Chronic stress has been reported to induce microglia activation and disturbances in glucose metabolism in the hippocampus. This study aims to investigate how chronic stress-mediated glycolysis promotes neuroinflammation and to assess the therapeutic potential of the glycolysis inhibitor, 2-deoxy-D-glucose (2-DG), in a model of chronic stress-induced neuroinflammation and depression-like behavior. In in vitro studies, we first explored the effects of 2-DG on the inflammatory response of microglia cells. The results showed that corticosterone (Cort) induced reactive oxygen species (ROS) production, increased glycolysis, and promoted the release of inflammatory mediators. However, these effects were reversed by intervention with 2-DG. Subsequently, we examined changes in depression-like behavior and hippocampal glycolysis in mice during chronic stress. The results indicated that chronic stress led to prolonged escape latency in the Morris water maze, increased platform-crossing frequency, reduced sucrose preference index, and extended immobility time in the forced swim test, all of which are indicative of depression-like behavior in mice. Additionally, we found that the expression of the key glycolytic enzyme hexokinase 2 (HK2) was upregulated in the hippocampus of stressed mice, along with an increased release of inflammatory factors. Further in vivo experiments investigated the effects of 2-DG on glycolysis and pro-inflammatory mediator production, as well as the therapeutic effects of 2-DG on chronic stress-induced depression-like behavior in mice. The results showed that 2-DG alleviated chronic stress-induced depression-like behaviors, such as improving escape latency and platform-crossing frequency in the Morris water maze, and increasing the time spent in the center of the open field. Additionally, 2-DG intervention reduced the level of glycolysis in the hippocampus and decreased the release of pro-inflammatory mediators. These findings suggest that 2-DG can mitigate neuroinflammation and depressive behaviors by inhibiting glycolysis and inflammatory responses. Overall, our results highlight the potential of 2-DG as a therapeutic agent for alleviating chronic stress-induced neuroinflammation through the regulation of glycolysis.