RETRACTION: Amelioration of Ovalbumin\u2010Induced Allergic Asthma by Juglans regia via Downregulation of Inflammatory Cytokines and Upregulation of Aquaporin\u20101 and Aquaporin\u20105 in Mice

Juglans regia (J. regia) has been used traditionally to treat cough and asthma. The present study evaluates the immunomodulatory and anti-inflammatory potential of J. regia against ovalbumin (OVA)-induced allergic asthma. Intraperitoneal sensitization proceeded by intranasal challenge with OVA was used to induce allergic asthma. BALB/c mice were treated with methanol, n-hexane, and ethyl acetate extracts of J. regia and methylprednisolone one week after 2nd sensitization with OVA and continued for 7 days. mRNA expression levels of IL-4, IL-5, IL-13, AQP-1, AQP-5 TNF-α, TGF-β, and NF-kB were determined using reverse transcription polymerase chain reaction. Hematoxylin and eosin, and periodic acidic-Schiff stains were used for histopathological studies of lung tissues. The data presented all three extracts of J. regia significantly ameliorated airway inflammation by reducing expression levels of IL-4, IL-5, and IL-13 and TNF-α in OVA-treated mice. The suppression of goblet cells hyperplasia and inflammatory cells infiltration by J. regia involved low TGF-β and NF-kB levels. Pretreatment with J. regia also increased the AQP-1 and AQP-5 expression levels in mice treated with OVA. This study supported the traditional use of J. regia and proposed that J. regia ameliorated allergic asthma by suppression of proinflammatory cytokines and elevation of AQP-1 and AQP-5 expression levels.

Acute neuroinflammation, which is notably characterized by a significant elevation in pro-inflammatory cytokines and chemokines, often rapidly develops following a traumatic spinal cord injury and exacerbates damage in the lesion area. This study addresses the limitations inherent in strategies that regulate only a single or a few cytokines, which are often insufficient to counteract the progression of secondary injuries. We explore the use of polydopamine nanoparticles as a broad-spectrum immunomodulator, capable of capturing by adsorption a wide range of cytokines and thereby effectively suppressing neuroinflammation. Leveraging their adhesive properties, these nanoparticles promptly reduce levels of various excessive cytokines, including IL-1α, IL-1β, IL-6, IL-10, IL-17A, IL-18, TNF-α, MCP-1, GRO/KC, M-CSF, MIP-3α, and IFN-γ, primarily through physical adsorption. This reduction in cytokine levels contributes to the subsequent inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation, aiding in the recovery of motor functions in vivo. In summary, polydopamine nanoparticles represent a versatile and effective approach for modulating acute neuroinflammation in spinal cord injuries. By broadly down-regulating cytokines, polydopamine nanoparticles propose an innovative approach for treating spinal cord injuries. STATEMENT OF SIGNIFICANCE: The current study demonstrated the immunomodulatory potential of polydopamine nanoparticles in mitigating neuroinflammation following spinal cord injury. Both in vitro and in vivo analyses revealed significant downregulation of several key cytokines among a panel of 23 cytokines and chemokines. The potential underlying mechanisms governing these interactions were elucidated through comprehensive molecular dynamics simulations for the first time. Consequently, the downregulation of these cytokines and chemokines led to the inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation in both in vitro and in vivo models. This inhibition protected neurons within the microenvironment, resulting in improved locomotor functions. Overall, this study underscores the prominent therapeutic efficacy of polydopamine nanoparticles in alleviating neuroinflammation, highlighting their potential as broad-spectrum regulators in intricate microenvironments.

Induction profiles of mRNA of toll like receptors and cytokines in chickens pre-exposed to low pathogenic avian influenza H9N2 virus followed by challenge with highly pathogenic avian influenza H5N1 virus

Background: Juglans regia L. is renowned for its traditional use as a cure for respiratory diseases such as asthma and sinusitis.Objectives: This study was intended to assess the protective mechanism of the effects of hydroalcoholic extract of the leaf of Juglans regia L. against airway inflammation and pulmonary edema by measuring the expression levels of heme oxygenase-1 (HO-1), occludin, and Zonula occludens-1 (ZO-1) in the lung tissues.Methods: Ovalbumin (OVA) was used intraperitoneally to sensitize mice on Days 0 and 14 to induce allergic asthma by the intraperitoneal route. Animals were divided into 5 groups, consisting of normal control (NC), disease group (OVA, i.p), low-dose J. regia (LDJR) and high-dose J. regia (HDJR), methylprednisolone (MP), and reference control (RC) drug. On the 28th day, blood and bronchial alveolar lavage fluid (BALF) were collected for total leukocyte (TLC) and differential leukocyte (DLC) analysis. Hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining of the lungs were performed for the architectural changes caused by OVA-induced bronchial asthma. Tight junction proteins were assessed by measuring the expression levels of HO-1, occludin, and ZO-1 in the lung tissues by using real-time polymerase chain reaction.Results: Scores of inflammations, edema, and goblet cell hyperplasia were significantly increased (all p ≤ 0.05) in the DC group compared to the NC group, while treatment with LDJR and HDJR significantly reduced (all p ≤ 0.05) the scores of inflammations, edema, and goblet cell hyperplasia compared to the DC group. Real-time polymerase chain reaction data showed that expression levels of HO-1, occludin, and ZO-1 in lung tissues of the DC group were significantly reduced (all p ≤ 0.05), when the same was compared to the NC group, while treatment with LDJR and HDJR significantly increased (p ≤ 0.05) their expression level when compared to the DC group.Conclusion: Juglans regia L.'s hydroalcoholic extract possesses antiasthmatic activity by normalizing the TLC cells and DLC cells. Juglans regia L.'s hydroalcoholic extract resulted in the amelioration of pulmonary edema which is attributed to the upregulation of HO-1, occludin, and ZO-1 in the lung tissues of the Juglans regia L. treated groups when compared to the diseased control group. Administration of Juglans regia L.'s extract also reduces the scores of inflammation and vascular congestion by evaluation of the lungs' histopathology in the disease control group when compared to the NC group.

Asthma is a chronic inflammation of pulmonary airways associated with bronchial hyper-responsiveness. The study was aimed to validate the folkloric use of Polystichum braunii (PB) against ovalbumin (OVA)-induced asthmatic and chemical characterization OF both extracts. Allergic asthma was developed by intraperitoneal sensitization with an OVA on days 1 and 14 followed by intranasal challenge. Mice were treated with PB methanolic (PBME) and aqueous extract (PBAE) orally at 600, 300, and 150mg/kg and using dexamethasone (2mg/kg) as standard from day 15 to 26. High performance liquid chromatography-diode array detector analysis revealed the presence of various bioactive compounds such as catechin, vanillic acid, and quercetin. The PBME and PBAE profoundly (p < 0.0001-0.05) declined immunoglobulin E level, lungs wet/dry weight ratio, and total and differential leukocyte count in blood and bronchial alveolar lavage fluid of treated mice in contrast to disease control. Histopathological examination showed profoundly decreased inflammatory cell infiltration and goblet cell hyperplasia in treated groups. Both extracts caused significant (p < 0.0001-0.05) diminution of IL-4, IL-5, IL-13, IL-6, IL-1β, TNF-α, and NF-κB and upregulation of aquaporins (1 and 5), which have led to the amelioration of pulmonary inflammation and attenuation of lung edema in treated mice. Both extracts profoundly (p < 0.0001-0.05) restored the activities of SOD, CAT, GSH and reduced the level of MDA dose dependently. Both extracts possessed significant anti-asthmatic action mainly PBME 600mg/kg might be due to phenols and flavonoids and could be used as a potential therapeutic option in the management of allergic asthma.

Amelioration of allergic asthma by Ziziphora clinopodioides via upregulation of aquaporins and downregulation of IL4 and IL5

Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5

Chlamydia trachomatis (CT), a bacterial pathogen responsible for sexually transmitted infections worldwide, causes severe inflammation including but not limited to, pelvic inflammatory disease, ectopic pregnancy and infertility in women. Secretion of inflammatory mediators plays a pivotal role in its pathogenesis of disease. Our laboratory published that IL-10 can down-regulate the secretion of inflammatory cytokines triggered by CT in mouse macrophages. Our goal in this study is to decipher the mechanisms of IL-10 down-regulation of CT-induced cytokines by focusing on the intracellular negative regulatory mediators, suppressor of cytokine signaling (SOCS) 1 and 3. We show that live CT and its recombinant major outer membrane protein (rMOMP), in a dose-dependent fashion, markedly induced the transcriptional upregulation of SOCS 1 and 3 in macrophages. In the presence of exogenously added recombinant IL-10, SOCS1 expression was reduced while that of SOCS3 was enhanced, suggesting differential regulation of these regulators by IL-10 to mediate its inhibitory effect. Experiments using various concentrations of exogenously added IL-10 over several time-points further revealed the differential regulation of SOCS 1 and 3 by IL-10 in macrophages. Signal transduction pathway inhibition studies demonstrated that the MAPK pathways including p38, MEK and JNK, particularly the latter are possibly involved in inducing SOCS 1 and 3 by CT and added IL-10, correlating with down-regulation of the cytokines, IL-6 and IL-12p40. Overall, our data helps in understanding the mechanisms of IL-10 regulation of inflammation in CT-infected macrophages by shedding light on the roles of SOCS 1 and 3 in mediating this IL-10 anti-inflammatory effect.

The probiotic potential and mechanisms of Lactobacillus helveticus against Escherichia coli (ETEC) induced diarrhea remain poorly understood, despite its robust physiological traits and long history of safe use. Here, we compared the anti-diarrheal efficacy of four L. helveticus strains (H1-H4) isolated from different geographical origins to unravel the mechanisms of action in ETEC-infected mice. Surprisingly, feeding with L. helveticus strains significantly reduced pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-6 (IL-6), alleviated jejunal damage, and restored the colon length. Among them, L. helveticus H3 exhibited the best protective effects through upregulation of aquaporin 3 (AQP3) and interleukin-10 (IL-10) and downregulation of heat-stable enterotoxin (ST) and toll-like receptor 4 (TLR4). Notably, ETEC infection disrupted intestinal homeostasis of microbiota by enriching Akkermansia and Escherichia-Shigella and suppressing Lactobacillus, Odoribacter, Alistipes, Ligilactobacillus, and Bifidobacterium; whereas the supplementation with L. helveticus could effectively restore the balance of gut microbiota. Moreover, the strain H3 significantly enhanced the production of several short-chain fatty acids (SCFAs), including butyric, propionic, isobutyric, valeric, isovaleric, and caproic acids, compared to the others. Comparative genome analysis revealed that the strain H3 had more genes that likely contributed to SCFA production, toxin detoxification, and colonization capacity, which support its better efficacy in alleviating ETEC-induced diarrhea. Collectively, our study suggests that L. helveticus alleviates ETEC-induced diarrhea by rebalancing gut microbiota and is a promising probiotic for treating infectious diarrhea.

Background Ultrasound (US) is effective in knee osteoarthritis (KOA), but its therapeutic mechanism is unclear, particularly the interaction between US and peroxisome proliferator-activated receptors (PPARs). This study aims to elucidate the therapeutic mechanism of US through PPARs signaling. Methods A surgically induced KOA rabbit model evaluated the therapeutic effects of Sham US, US, Fenofibrate (PPAR-α agonist), and Rosiglitazone (PPAR-γ agonist) via MRI. Cartilage and synovium tissues were collected for immunohistochemistry, RT-PCR, and western blotting. Synovial fluid inflammatory factors were analyzed. We also developed an in vitro cultured KOA chondrocyte model to investigate the effects of US therapy on PPARs-related signaling pathways and extracellular matrix cytokines. The mechanism by which US therapy inhibits KOA was studied using GW6471 (PPAR-α antagonist) and Mifobate (PPAR-γ antagonist). Results MRI revealed that US therapy slowed cartilage thinning and improved cartilage structure in the KOA model. Concurrently, US therapy effectively reduced chondrocyte damage and degradation via modulating mRNA and protein levels of PPARs-related signaling pathways in both cartilage and synovial tissues. Additionally, US therapy suppressed synovial inflammation by downregulating pro-inflammatory cytokines such as interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting extracellular matrix homeostasis through the upregulation of aquaporin 7 and Collagen II levels in vivo and in vitro. By maintaining cartilage-chondrocyte equilibrium, US therapy prevented GW6471 or Mifobate’s KOA-promoting impact. Conclusion Our results show that US therapy could arrest the progression of KOA by reducing synovial inflammation, delaying cartilage degradation, and decreasing extracellular matrix degradation via PPARs-related signaling pathways.

Indomethacin, an anti-inflammatory agent used for pain, fever and inflammation, causes severe lesions in the gastrointestinal tract in humans and animals. For this reason, there has been an increase in the search for new compounds that can help prevent and/or alleviate these lesions caused by indomethacin. The aim of the present study is to evaluate the gastroprotective effect of Juglans regia administration against indomethacin induced gastric lesion. A total of forty rats were divided equally among four groups for the experiments. Groups were designed as Control (C), Indomethacin (IND), Juglans regia + Indomethacin (JR+IND), and Pantoprazole + Indomethacin (PAN+IND). Following the 7-day adaptation period, substance applications (pantoprazol and Juglans regia extract) were made for 10 days. In the IND, JR+IND and PAN+IND groups were administered indomethacin 100 mg/kg single dose on day 11th. Indomethacin caused significant increases in the stomach IL-6 and TNF-α levels compared with the C group (respectively, p&lt;0.001, p&lt;0.01). In the PAN+IND and JR+IND groups showed a significant lower in the IL-6 levels compared with IND group (respectively, p&lt;0.001, p&lt;0.01). The C-reactive protein (CRP) and Cyclo-oxygenase-2R (COX-2R) levels of IND group were increased compared to C group (p&lt;0.001). There was a significant decrease in CRP and COX-2R levels after PAN and JR treatment compared with IND (p&lt;0.001). COX-2, CRP and proinflammatory cytokines is seen as the main target for the treatment of inflammatory diseases. As a result; it was determined that JR has a protective effect, which may be related to decrease inflammatory markers, against of gastric damage caused by indomethacin.

Effects of chronic stress on cytokine networks in ovarian cancer ascites (268)

Purpose Overnight eye closure results in a near cessation in tear turnover and the induction of a sub‐clinical inflammation as evidenced by PMN cell recruitment and degranulation and the accumulation of pro‐inflammatory cytokines and chemokines. What prevents cytokine induced damage to the cornea was investigated.Methods Methods: Open (O) and Closed (C) tears from Ns were subjected to multiple micro well array assays to obtain quantitative data on the distribution of &gt;80 low abundance proteins. Samples were also separated by molecular sieve HPLC and the eluent profiled for the presences of chemokines, cytokines and interactive proteins. Cytokine‐protein complexes were identified using a laboratory‐developed multiplex assays.Results Micro‐well array assay reveal a marked increase in the concentrations of a wide range of inflammatory and immune modulating cytokines as well as chemokines in the closed eye tears. This was accompanied by increased levels of s‐receptors at concentrations greatly exceeding that of the targeted proteins along with the accumulation of α2‐M. Protein‐protein binding studies and analysis of the HPLC eluent reveals that most inflammatory, angiogenic and immune cytokines eluent in the form of macromolecular complexes bound to s‐receptor and α2‐M. This serves to inactivate these entities and tags them for up take by macrophages and other cells that express the α2‐M receptor. In contrast chemokines which lack s‐receptors remain free and bioactive.Conclusion s‐receptors and α2‐M co‐operatively function in the down–regulation of cytokine and growth factor induced inflammation. Data will also be presented showing its functional role in the control of inflammation elsewhere.

&lt;b&gt;Background and Objective:&lt;/b&gt; Research has demonstrated the antibacterial, anti-angiogenetic, antiviral, anti-inflammatory, anticancer and antioxidant properties of colloidal silver due to its biological, optical and electrical properties. The aim of this study was the anti-inflammatory effect of the silver bioengineered nanoparticles by using the acetonitrile-unripe fruit extract of &lt;i&gt;Juglans regia&lt;/i&gt; L., on experimental animal model. &lt;b&gt;Materials and Methods:&lt;/b&gt; The study uses various techniques to characterize nanoparticles, including ultraviolet spectra, dynamic light scattering and Fourier transform infrared. The study used carrageenan-induced rat paw edema as an induction model for inflammation and assessed its antinociceptive effects in mice using the formalin test. As well as evaluation of proinflammatory cytokines IL-6, TNF and IL-1. &lt;b&gt;Results:&lt;/b&gt; The produced AgNPs were more compact and stable, according to physical characterization methods compared to chemical prepared nanoparticles. The formulation combining unripe fruit bio-reduced nanoparticles and extract, UF, shows a greater acute anti-inflammatory effect, while leaf extract has a better late anti-inflammatory effect. These bioengineered nanoparticles show efficient &lt;i&gt;in vivo&lt;/i&gt; anti-acute inflammation, reducing skin inflammation through decreased cellular infiltrates and cytokine release. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Juglans regia&lt;/i&gt; L., extract and silver nanoparticles show notable effects in both the early and late stages of the antinociceptive formalin test. While, bioengineered NP/UF and NP/LV can be used as topical analgesics. The potent topical anti-inflammatory and analgesic effects of these medications provide a sufficient basis for the use of this plant material in dermatological products.

Juglans regia L. attenuate Psoralea corylifolia L.-induced hepatotoxicity by regulating the Nrf2 pathway and amino acid metabolism.