IL-6 Gene Expression Research Articles

Abstract Tu084: Endothelial Cell STING contributes to Systolic Dysfunction by modulating cardiomyocyte hypertrophy and capillary density in pressure overload-induced heart failure

Introduction: Cardiomyocyte (CM) hypertrophy, endothelial cell (EC) dysfunction and cardiac inflammation are hallmarks of adverse cardiac remodeling that contribute to heart failure (HF) progression. The “Stimulator of Interferon Genes” (STING) is highly expressed in ECs, the dominant non-CM cell in the heart and contributes to vascular inflammation, yet its role in adverse cardiac remodeling is unknown. We hypothesized that EC STING contributes to systolic dysfunction by modulating adverse remodeling in HF. Methods: Wildtype (WT), global deficient (STING-/-) and inducible EC STING-/- mice or EC STING+/+ littermate controls (Cad5ERTCre2+/–Stingfl/fl treated with Tamoxifen or oil, respectively) were subjected to transverse aortic constriction (TAC) or Sham surgery for 2-8 weeks. Cardiac function was analyzed by echocardiography. Left ventricular (LV) sections were stained with wheat germ agglutinin and isolectin to analyze CM hypertrophy and capillary density. Cardiac leukocytes were analyzed by flow cytometry and gene expression by qPCR. Bulk RNA Sequencing was performed on sorted CD45- CD31+ mouse heart ECs (MHEC) from EC STING+/+ and EC STING-/- after 4 weeks of TAC or sham surgery. ELISA was performed on MHEC supernatant. Results: STING-/- mice did not show a decline in fractional shortening (FS), capillary density or develop LV hypertrophy and had decreased intramyocardial CD45+ leukocytes in response to TAC, compared to WT mice. EC STING-/- mice also showed preserved FS, capillary density, and ameliorated CM hypertrophy over the course of 2, 4 and 8 weeks of TAC, compared to EC STING+/+ mice, despite having similar numbers of myocardial CD45+ leukocytes. RNASeq revealed decreased IL6 transcription, a pro-hypertrophic cytokine, in TAC STING-/- MHECs compared to WT MHECs. Myocardial IL6 gene expression was also reduced in EC STING-/- TAC hearts compared to EC STING+/+. In vitro, STING-/- MHECs had decreased secretion of IL6 protein compared to WT MHECs. Conclusions: Our data demonstrate that EC STING modulates both the EC and cardiac expression of the pro-hypertrophic cytokine IL6, suggesting a mechanism contributing to cardiomyocyte hypertrophy, capillary rarefaction, and systolic dysfunction in response to cardiac pressure overload.

CysLT receptor-mediated NOX2 activation is required for IL-8 production in HMC-1 cells induced by Trichomonas vaginalis-derived secretory products.

Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B4 (LTB4) and various cysteinyl leukotrienes (CysLTs) which included LTC4, LTD4, and LTE4. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.

Desaminotyrosine is a redox-active microbial metabolite that bolsters macrophage antimicrobial functions while attenuating IL-6 production.

Intestinal microbiota contributes to host defense against pathogens while avoiding the induction of inflammation in homeostatic conditions, but the mechanism is not fully understood. To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow-derived macrophages (BMDMs) with DAT for 12 hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming-enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)-6 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell-free system. DAT-primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP+ to cells reversed DAT's effect on LPS-induced Il-6 and interferon-stimulated gene expressions. DAT-primed cells also were more resistant to oxidative stress-induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox-dependent manner, leading to enhanced macrophage antimicrobial activity during Salmonella enterica infection. Our data suggest that DAT acts as a host-microbiota crosstalk signal in shaping host immune defense and inflammatory response.

Exploring the role of mesenchymal stem cells in modulating immune responses via Treg and Th2 cell activation: insights from mouse model of multiple sclerosis.

Multiple sclerosis is a demyelinating neurodegenerative disease, and its animal model, experimental autoimmune encephalomyelitis (EAE), exhibits immunological and clinical similarities. The study aimed to examine mechanisms underlying therapeutic effects of mesenchymal stem cell administration in EAE. C57BL/6 mice were separated into control and treatment groups (T1, T2, and T3); EAE was induced in all animals. Clinical examinations were conducted daily, and on 25th day, animals were sacrificed, and spinal cord was stained for histological analysis. Additionally, spleen cell proliferation assay, assessments of cytokine, and gene expression in both spinal cord and spleen cells were performed. The results indicated a significant reduction in clinical symptoms among treatment groups compared to control group. Histological analyses revealed decreased infiltration of lymphocytes into the spinal cord and reduced demyelinated areas in treatment groups compared to control group. Cytokine production of IL-10, TGF-β, and IL-4 were significantly enhanced and IFN-γ and TNF-α in treatment groups were decreased relative to control group. Also, gene expression of CTLA-4, PD-1, IL-27, and IL-33 indicated a significant increase in treatment groups. The administration of MSCs significantly improved clinical symptoms, attenuated inflammation, and reduced spinal cord demyelination in EAE, suggesting a potential protective effect on disease progression.

Fevogrit, a polyherbal medicine, mitigates endotoxin (lipopolysaccharide)-induced fever in Wistar rats by regulating pro-inflammatory cytokine levels.

Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)-induced fever model in Wistar rats. Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography (UHPLC) platform. For the in-vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6-h time point, levels of TNF-α, IL-1β and IL-6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post-LPS administration. UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti-inflammatory properties. Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals. The levels and gene expression of TNF-α, IL-1β and IL-6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment. The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.

Mechanism analysis of essential oil from Radix Bupleuri for the treatment of asthma through regulation of ectopic olfactory receptor

Ethnopharmacological relevanceRadix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. Aim of the studyStudies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. Materials and methodsFirstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. ResultsOral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. ConclusionsThe mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

Insights into bioactive constituents of onion (Allium cepa L.) waste: a comparative metabolomics study enhanced by chemometric tools

BackgroundOnion waste was reported to be a valuable source of bioactive constituents with potential health-promoting benefits. This sparked a surge of interest among scientists for its valorization. This study aims to investigate the chemical profiles of peel and root extracts of four onion cultivars (red, copper-yellow, golden yellow and white onions) and evaluate their erectogenic and anti-inflammatory potentials.MethodsUPLC-QqQ-MS/MS analysis and chemometric tools were utilized to determine the chemical profiles of onion peel and root extracts. The erectogenic potential of the extracts was evaluated using the PDE-5 inhibitory assay, while their anti-inflammatory activity was determined by identifying their downregulating effect on the gene expression of IL-6, IL-1β, IFN-γ, and TNF-α in LPS-stimulated WBCs.ResultsA total of 103 metabolites of diverse chemical classes were identified, with the most abundant being flavonoids. The organ’s influence on the chemical profiles of the samples outweighed the influence of the cultivar, as evidenced by the close clustering of samples from the same organ compared to the distinct separation of root and peel samples from the same cultivar. Furthermore, the tested extracts demonstrated promising PDE-5 and anti-inflammatory potentials and effectively suppressed the upregulation of pro-inflammatory markers in LPS-stimulated WBCs. The anti-inflammatory activities exerted by peel samples surpassed those of root samples, highlighting the importance of selecting the appropriate organ to maximize activity. The main metabolites correlated with PDE-5 inhibition were cyanidin 3-O-(malonyl-acetyl)-glucoside and quercetin dimer hexoside, while those correlated with IL-1β inhibition were γ-glutamyl-methionine sulfoxide, γ-glutamyl glutamine, sativanone, and stearic acid. Taxifolin, 3’-hydroxymelanettin, and oleic acid were highly correlated with IL-6 downregulation, while quercetin 4’-O-glucoside, isorhamnetin 4’-O-glucoside, and p-coumaroyl glycolic acid showed the highest correlation to IFN-γ and TNF-α inhibition.ConclusionThis study provides a fresh perspective on onion waste as a valuable source of bioactive constituents that could serve as the cornerstone for developing new, effective anti-PDE-5 and anti-inflammatory drug candidates.

Penetration capacity and local anti-inflammatory effect of a methyl salicylate gel with turpentine essence, camphor, and menthol for the symptomatic local treatment of muscular and joint pains

Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective in managing musculoskeletal pain, but often are associated with side effects. Therefore, topical anti-inflammatory drugs are considered a suitable alternative for certain patients. To determine the skin penetration capacity and anti-inflammatory efficacy of a methyl salicylate gel (MS) with turpentine essence, camphor and menthol (GelSMETAM). Human skin explants were used (three biological replicates with 3 technical replicates each were performed). To assess penetration capacity, methyl salicylate (MS) levels were quantified at different intervals using liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the anti-inflammatory effect, the gene expression of major pro-inflammatory factors was quantified 30 minutes, 8 hours, and 12 hours after an impact; comparing GelSMETAM application with untreated controls. The results showed that approximately 0.8% of the total applied methyl salicylate penetrated the skin with a time-dependent concentration increase. The anti-inflammatory effect demonstrated a significant reduction in the gene expression of TNFα, IL1α, IL6, IL8, and NFKβ at 30 minutes (between -39% and -53.6% compared to control), which was maintained at 8 hours except for TNFα (between -59% and -92.6%) and persisted even at 12 hours (-69.4%) for IL1α. The results support the hypothesis that GelSMETAM provides an effective and prolonged anti-inflammatory response, positioning it as a suitable option for the management of musculoskeletal pain.

Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways

We aimed to determine the chemical profile and unveil Anadenanthera colubrina (Vell.) Brenan standardized extract effects on inflammatory cytokines expression and key proteins from immunoregulating signaling pathways on LPS-induced THP-1 monocyte. Using the RT-PCR and Luminex Assays, we planned to show the gene expression and the levels of IL-8, IL-1β, and IL-10 inflammatory cytokines. Key proteins of NF-κB and MAPK transduction signaling pathways (NF-κB, p-38, p-NF-κB, and p-p38) were detected by Simple Western. Using HPLC-ESI-MSn (High-Performance Liquid-Chromatography) and HPLC-HRESIMS, we showed the profile of the extract that includes an opus of flavonoids, including the catechins, quercetin, kaempferol, and the proanthocyanidins. Cell viability was unaffected up to 250 µg/mL of the extract (LD50 = 978.7 µg/mL). Thereafter, the extract's impact on the cytokine became clear. Upon LPS stimuli, in the presence of the extract, gene expression of IL-1β and IL-10 were downregulated and the cytokines expression of IL-1β and IL-10 were down an upregulated respectively. The extract is involved in TLR-4-related NF-κB/MAPK pathways; it ignited phosphorylation of p38 and NF-κB, orchestrating a reduced signal intensity. Therefore, Anadenanthera colubrina's showed low cytotoxicity and profound influence as a protector against the inflammation, modulating IL-1β and IL-10 inflammatory cytokines gene expression and secretion by regulating intracellular NF-κB and p38-MAPK signaling pathways.

Th17 pathway‐related immune signatures in the pathobiology of myasthenia gravis: Integrating the roles of regulatory/effector cytokines and transcription factors

AbstractObjectivesMyasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acetylcholine receptor (AChR), muscle specific kinase (MuSK), and other antigens in the neuromuscular junction. Antibody production is influenced by T lymphocytes. The T helper 17 (Th17) subset, an inflammatory lineage of Th cells, is associated with several autoimmune diseases. Functional interactions between T lymphocytes and pathogenic antibody responses including aberrant Th17 cell responses have been reported in MG. However, the precise mechanism(s) underlying the activation and/or pathogenic transformation of Th17 cells are not clearly known. The current study aimed at simultaneously exploring the roles of the inducers, master regulator transcription factors, and effectors of Th17 cells in patients with MG.MethodsIn this cross‐sectional study, quantification of gene expression of IL6, IL17A, STAT3, and RORC in the peripheral mononuclear cells by quantitative polymerase chain reaction (qPCR) as well as estimation of plasma levels of IL‐1β, IL‐6, and IL‐17A cytokines by multiplex suspension assay were carried out in 59 patients with MG and 61 healthy controls.ResultsGene expression levels of IL17A were significantly upregulated in patients as compared to healthy controls. The plasma levels of IL‐1β, IL‐6, and IL‐17A were significantly elevated in patients compared to healthy controls. IL17A as well as RORC gene expressions correlated with the clinical features. IL17A gene expression levels were higher in AChR‐MG patients.ConclusionThe present study supports the crucial role of the Th17 pathway in the pathobiology of MG, including its potential influence on disease severity.

Association between host defence peptide IDR-1002 and ciprofloxacin: Effects on human dental pulp cells.

To evaluate the effects of the association of host defence peptide IDR-1002 and ciprofloxacin on human dental pulp cells (hDPSCs). hDPSCs were stimulated with ciprofloxacin and IDR-1002. Cell viability (by MTT assay), migration capacity (by scratch assay), production of inflammatory and anti-inflammatory mediators by hDPSCs (RT-PCR) and osteogenic differentiation (alizarin red staining) were evaluated. Phenotypic profile of hDPSCs demonstrated 97% for positive marked mesenchymal stem cell. Increased pulp cell migration and proliferation were observed after 24 and 48 h of exposure to IDR-1002 with ciprofloxacin. Mineral matrix formation by hDPSCs was observed of the association while its reduction was observed in the presence of peptide. After 24 h, the association between ciprofloxacin and IDR-1002 significantly downregulated TNFRSF-1, IL-1β, IL-8, IL-6 and IL-10 gene expression (p ≤ 0.0001). The association between the IDR-1002 and ciprofloxacin showed favourable immunomodulatory potential, emerging as a promising option for pulp revascularisation processes.

UPLC-QTOF-MS characterized, herbal medicine, pancogrit modulates NF-κB and JAK2/STAT3 signaling pathways in cell-based model of TNF-α dependent acute pancreatitis

Acute pancreatitis develops as a local inflammatory condition of the pancreas due to a wide range of factors including overdose of alcohol or drugs, gall stones, etc. At present, medications based on herbal formulations have gained importance due to their better safety profile. Current study assessed the pharmacological effects of Pancogrit, an herbal medicine, in caerulein and TNF-α-induced in vitro pancreatitis models. A comprehensive evaluation of phytometabolites present in Pancogrit was conducted and 85 phytometabolites were identified through UPLC-QTOF-MS and UPLC-UV. The bioactivity and mode of action of Pancogrit were assessed in caerulein-induced AR42J (rat pancreatic acinar) cells, TNF-α-induced PANC-1 (human pancreatic duct) cells, and NF-κB reporter cells. Pancogrit was found to decrease the elevated amylase and lipase activity in caerulein-induced AR42J cells. It ameliorated the increased ROS levels, IL-6, IL-8 release and NF-κB activity in TNF-α-induced PANC-1 and NF-κB reporter cells. Pancogrit also downregulated IL-6, IL-1β, ICAM-1, and STAT3 gene expression in PANC-1 cells. Moreover, Pancogrit inhibited the protein expression levels of phosphorylated STAT3, phosphorylated and total JAK2 in TNF-α-induced PANC-1 cells. Taken together, Pancogrit is a clinically relevant therapeutic agent for mitigation of pancreatitis.

Direct Current Electrical Stimulation Shifts THP-1-Derived Macrophage Polarization towards Pro-Regenerative M2 Phenotype.

A macrophage shift from the M1 to the M2 phenotype is relevant for promoting tissue repair and regeneration. In a previous in vivo study, we found that direct current (DC) electrical stimulation (EStim) increased the proportion of M2 macrophages in healing tissues and directed the balance of the injury response away from healing/scarring towards regeneration. These observations led us to hypothesize that DC EStim regulates macrophage polarization towards an M2 phenotype. THP-1-derived M0, M1 (IFN-γ and LPS), and M2 (IL-4 and IL-13) macrophages were exposed (or not: control group) to 100 mV/mm of DC EStim, 1 h/day for three days. Macrophage polarization was assessed through gene and surface marker expressions and cytokine secretion profiles. Following DC EStim treatment, M0 cells exhibited an upregulation of M2 marker genes IL10, CD163, and PPARG. In M1 cells, DC EStim upregulated the gene expressions of M2 markers IL10, TGM2, and CD206 and downregulated M1 marker gene CD86. EStim treatment also reduced the surface expression of CD86 and secretion of pro-inflammatory cytokines IL-1β and IL-6. Our results suggest that DC EStim differentially exerts pro-M2 effects depending on the macrophage phenotype: it upregulates typical M2 genes in M0 and M1 cells while inhibiting M1 marker CD86 at the nuclear and protein levels and the secretion of pro-inflammatory interleukins in M1 cells. Conversely, M2 cells appear to be less responsive to the EStim treatment employed in this study.

Black cumin seed oil and its nano-form ameliorate lipopolysaccharide-induced brain inflammatory injury in mice

Backgrounds and objectives Microglia play a regulatory role in central nervous system inflammatory diseases, such as Alzheimer’s, Parkinson’s, and multiple sclerosis. Natural remedies like black cumin seeds (Nigella sativa) are rich in bioactive compounds that potentially can modulate inflammatory processes in the brain. In the current work, we studied the protective and anti-inflammatory properties of black cumin seed oil (BCSO) and its nano-form on lipopolysaccharide (LPS)-induced neurotoxicity in mice. Materials and methods Forty-eight mice were divided randomly into eight groups (n=6), three control groups (negative control, BCSO control, nano-BCSO control), LPS group, and four treatment groups [BCSO+LPS, nano-BCSO+LPS, indomethacin (5 mg/kg)+LPS, BCSO+indomethacin(2.5 mg/kg)+LPS]. At the end of the experiment, the brain tissues were removed for histopathological and biochemical assessments. Malondialdehyde and interleukin (IL)-10 were assessed using enzyme-linked immunosorbent assay while the gene expression of IL-6, toll-like receptor-4, brain-derived neurotrophic factor, nerve growth factor, cyclooxygenase-2, and B-cell lymphoma-2 were assessed by real-time PCR. IL-1β was quantified immunohistochemically along with the histopathological studies of the cerebral cortex of mice brains. Results and conclusions In our study, BCSO and its nano-form demonstrated a reduction in LPS-induced neurotoxicity, exhibiting comparable or better anti-inflammatory effects to indomethacin. These treatments significantly elevated the gene expression levels of neuroprotective factors brain-derived neurotrophic factor and nerve growth factor in LPS-treated mice. Pretreatment with BCSO and its nano-form reduced the malondialdehyde levels, in addition to gene expressions of cyclooxygenase-2, toll-like receptor-4, IL-6, and B-cell lymphoma-2. Immunohistochemical analysis indicated a decrease in IL-1β with BCSO and the lowering effect of the nano-form was superior. The histopathological studies corroborated with biochemical and molecular findings, suggesting that BCSO and its nano-form attenuated the inflammation and enhanced the microglial antioxidative and anti-inflammatory status. BCSO could enhance the anti-inflammatory activity of indomethacin, so lower doses of indomethacin with BCSO may be suggested for protecting against the adverse effects of high doses of NSAIDs as gastritis. Consequently, BCSO can serve a potential stimulatory supplement of the immunity for neurodegenerative conditions.

Effect of ASC Injection in the Inflammatory Reaction in Silicone Implant Capsule: Animal Model.

Capsular contracture is a common complication affecting about 80% of patients who receive radiotherapy after breast reconstruction with silicone prostheses. This study examines the use of adipocyte stem cells (ASCs) to treat capsular contracture. Thirty rats were operated on to implant a minisilicone prosthesis in the dorsal region. The rats were divided into three groups: control (saline solution injection), radiotherapy (RDT), and RDT + ASC. After 3 months, the capsules were collected and submitted to histological analysis for inflammatory cell presence, vascular density, and collagen fibers, and gene expression of Tnf, Il1rap, Il10, Cd68, Mmp3, and Mmp9 by qPCR. In macroscopic analysis, the RTGO score showed a two-point reduction in RDT + ASC compared with the RDT (P = 0.003). In histological analysis, ASC exhibited less than 50% of inflammatory cells compared with RDT (P = 0.004), which was similar to control. This study demonstrated that Il1rap gene expression was identical in both RDT and RTD + ASC. Compared with control, treatment with ASC reduced Il1rap expression by 30%. Cd68 and Mmp3 expression levels were similar in both the control and RTD + ASC. This study suggests that ASC treatment decreases silicone prosthesis capsule inflammation.

Regulatory effect of Balanites aegyptiaca ethanol extract on oxidant/antioxidant status, inflammatory cytokines, and cell apoptosis gene expression in goat abomasum experimentally infected with Haemonchus Contortus

This experiment aimed to assess the regulatory effects of treatment with Balanites aegyptiaca fruit ethanol extract (BA-EE) on oxidant/antioxidant status, anti-inflammatory cytokines, and cell apoptosis gene expression in the abomasum of Haemonchus contortus–infected goats. Twenty goat kids were assigned randomly to four equal groups: (G1) infected-untreated, (G2) uninfected-BA-EE-treated, (G3) infected-albendazole-treated, (G4) infected-BA-EE-treated. Each goat in (G1), (G3), and (G4) was orally infected with 10,000 infective third-stage larvae. In the fifth week postinfection, single doses of albendazole (5 mg/kg.BW) and BA-EE (9 g/kg.BW) were given orally. In the ninth week postinfection, the animals were slaughtered to obtain abomasum specimens. The following oxidant/antioxidant markers were determined: malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT). The mRNA gene expression of cytokines (IL-3, IL-6, IL-10, TNF-α) and cell apoptosis markers (Bax, Bcl-2) were estimated. (G1) showed significantly reduced GSH content and GST and SOD activities but a markedly increased MDA level. (G3) and (G4) revealed a markedly lower MDA level with pronouncedly elevated GSH, SOD, and GST levels. The antioxidant properties of BA-EE were superior to those of albendazole. The mRNA gene expressions of IL-3, IL-6, IL-10, TNF-α, and Bax-2 were upregulated in (G1) but downregulated in (G3) and (G4). Bcl-2 and Bcl-2/Bax ratio expression followed a reverse course in the infected and both treated groups. We conclude that BA-EE treatment has a protective role in the abomasum of H. contortus–infected goats. This could be attributed to its antioxidant properties and ability to reduce pro-inflammatory cytokines and cell apoptosis.

Deciphering the mechanism of cimifugin in mitigating LPS-induced neuroinflammation in BV-2 cells.

Sepsis often triggers a systemic inflammatory response leading to multi-organ dysfunction, with complex and not fully understood pathogenesis. This study investigates the therapeutic effects of cimifugin on BV-2 cells under sepsis-induced stress conditions. We utilized a BV-2 microglial cell model treated with lipopolysaccharide (LPS) to mimic sepsis. Assessments included cellular vitality, inflammatory cytokine quantification (6 interleukin [6IL]-1β, interleukin 6 [IL-6], and tumor necrosis factor-α [TNF-α]) via enzyme-linked-immunosorbent serologic assay, and analysis of mRNA expression using real-time polymerase chain reaction. Oxidative stress and mitochondrial function were also evaluated to understand the cellular effects of cimifugin. Cimifugin significantly attenuated LPS-induced inflammatory responses, oxidative stress, and mitochondrial dysfunction. It enhanced cell viability and modulated the secretion and gene expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, cimifugin activated the deacetylase sirtuin 1-nuclear factor erythroid 2-related factor 2 pathway, contributing to its protective effects against mitochondrial damage. Cimifugin demonstrates the potential of being an effective treatment for sepsis--induced neuroinflammation, warranting further investigation.

Research on the mechanism of Ursolic acid for treating Parkinson's disease by network pharmacology and experimental verification

The objective of this study was to investigate the potential targets and mechanisms of UA in the treatment of PD. The efficacy of UA in PD was assessed through network pharmacology, molecular docking, and experimental methods. Common target protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape. As a result, 9 key genes, namely CASP3, IL6, IL1B, PTGS2, CREB1, TNF, MAPK3, JUN, and CASP8, were selected. Molecular docking simulations were performed using Discovery Studio 2019 to validate the correlation between UA and the core targets. The results demonstrated a favorable binding affinity between UA and CASP8, IL1B, CASP3, TNF, MAPK3 and IL6. In vivo studies showed UA ameliorated motor dysfunction, and UA can significantly increase the protein expression of tyrosine hydroxylase (TH) in PD mice model. In addition, in vitro experiments confirmed that UA effectively reduced the protein expression of CASP8, CASP3 and MAPK3 in PD cell models and suppressed the gene expression of TNF-α, IL-6, and IL-1β. These findings indicate that the therapeutic effects of UA on PD could be due to its influence on various targets within both the apoptosis and neuroinflammatory signaling pathways. Consequently, this study provides a methodological and theoretical foundation for further elucidating the pharmacological mechanism of UA.

Expression of IL-8 Gene in Rainbow Trout (Oncorhynchus mykiss) Leucocytes Fed with Uryani plum (Prunus domestica) Extract

Expression of IL-8 Gene in Rainbow Trout (Oncorhynchus mykiss) Leucocytes Fed with Uryani plum (Prunus domestica) Extract

The Effect of Propolis Extract from Sumatra, Indonesia on Escherichia coli and IL-6 Gene Expression in Male Wistar Rats Fed with a High-Fat Diet

The Effect of Propolis Extract from Sumatra, Indonesia on Escherichia coli and IL-6 Gene Expression in Male Wistar Rats Fed with a High-Fat Diet