Expression Of Inflammatory Mediators Research Articles

Armillaria mellea Mycelia Alleviate PM2.5-Induced Pulmonary Inflammation in Murine Models

Particulate matter (PM) with an aerodynamic diameter of ≤2.5 μm (PM2.5) significantly contributes to various disease-related respiratory inflammations. Armillaria mellea, recognized for its medicinal properties, could alleviate these respiratory ailments. However, its efficacy against PM2.5-induced inflammation remains elusive. In this study, we investigated whether A. mellea mycelia could mitigate PM2.5-induced respiratory inflammation and assessed the underlying mechanisms. Our results showed that A. mellea mycelia significantly reduced PM2.5-induced nitric oxide (NO) production and nuclear factor (NF)-κB activation in macrophages. Furthermore, A. mellea mycelia suppressed the expression of inflammatory mediators, indicating their potent antioxidant and anti-inflammatory properties. In murine models, A. mellea mycelia mitigated PM2.5-induced lung inflammation and cytokine secretion, restoring lung inflammatory status. Our results highlight the potential of A. mellea mycelia to treat PM2.5-induced respiratory inflammation. The antioxidant and anti-inflammatory effects of A. mellea mycelia demonstrated in vitro and in vivo hold promising potential for developing respiratory health improvement interventions upon PM2.5 exposure.

Topical Therapies for Management of Olfactory Dysfunction in Chronic Rhinosinusitis with Nasal Polyps: Steroid-Eluting Stents.

Steroid-eluting stent implantation after endoscopic sinus surgery (ESS) effectively alleviates postoperative symptoms and polyp recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the efficacy of steroid-eluting stents for the treatment of olfactory dysfunction in CRSwNP and the influencing factors therein have not been studied. Fifty-nine patients with CRSwNP with olfactory dysfunction from Peking University Third Hospital who were hospitalized for ESS were recruited and randomly divided into a stent group (n = 30) and a control group (n = 29), and were assessed for symptom scores, olfactory function, endoscopic findings, and type 2 inflammatory mediators (IL-4, IL-5, IL-13, IL-33, eotaxin-3, periostin) expression. Postoperative olfactory Visual Analogue Scale (VAS) scores, T&T olfactometer scores, SNOT-22 scores, and Lund-Kennedy (LK) scores were reduced in patients with CRSwNP (P < .01). Postoperative olfactory VAS scores, T&T olfactometer scores, SNOT-22 scores, and LK scores, IL-5, IL-13, and periostin were significantly lower in the stent group than in the control group (P < .05). Correlation analysis was performed and found that the postoperative olfactory VAS scores were strongly correlated with IL-5 and IL-13 (r = .496, P < .001 and r = .289, P = .026), and the postoperative T&T olfactometer scores were strongly correlated with IL-5 and IL-13 (r = .553, P < .001 and r = .398, P = .002). Steroid-eluting stent implantation after ESS is an effective treatment for olfactory deficits in patients with CRSwNP and may be related to the stent's more effective reduction of local type 2 inflammatory mediators in the nasal cavity.

Lactobacillus rhamnosus modulates murine neonatal gut microbiota and inflammation caused by pathogenic Escherichia coli

BackgroundPathogenic Escherichia coli strains produce neonatal septicemia after colonizing the neonatal gut. While the probiotic Lactobacillus rhamnosus GG (LGG) effectively reduces neonatal sepsis, LGG’s effects on the neonatal intestinal microbiota alterations and inflammation triggered by E. coli are incompletely understood. We hypothesized that LGG significantly modulates the specific neonatal gut microbial populations changes and the inflammatory response elicited by the enteral introduction of septicemia-producing E. coli. To test this hypothesis, newborn rats were pretreated orally with LGG or placebo prior to infection with the neonatal E. coli septicemia clinical isolate SCB34. Amplicon 16S rRNA gene sequencing was performed on intestinal samples. Intestinal injury and expression of inflammatory mediators and apoptosis were determined.ResultsAlpha diversity of gut microbiota was greater in SCB34-infected pups in comparison to sham-infected pups, these changes were not modified by LGG pretreatment. Beta diversity analyses also showed differences between SCB34-infected vs. uninfected pups. LGG pretreatment before SCB34 infection did not result in significant beta diversity changes compared to placebo. Moreover, individual genera and species abundance analyses by linear discriminant analysis effect size (LEfSe) showed significant changes in Gram-negative, Gram-positive, and anaerobic populations resulting from LGG pretreatment and SCB34 infection. LGG significantly suppressed the expression of inflammatory cytokines but did not attenuate SCB34-induced apoptosis or histologic injury.ConclusionsLGG modulates clinically significant microbiota features and inflammation triggered by pathogenic E. coli intestinal infection shortly after birth. This new knowledge can potentially be harnessed to design novel interventions against gut-derived neonatal sepsis.

Microglia-Dependent Peripheral Neuropathic Pain in Adulthood Following Adolescent Exposure to Morphine in Male Rats

Persistent effects of adolescent morphine exposure on neurobiological processes and behaviors in adulthood have been partially identified. Hypersensitivity following adolescent exposure to morphine is a complex and multifaceted phenomenon whose underlying mechanisms remain largely unknown. This study aimed to investigate the involvement of microglia in neuropathic pain sensitivity following adolescent morphine exposure, focused on hippocampal genes expression and plasticity. To achieve this, adolescent male Wistar rats received morphine, along with minocycline, to inhibit microglial activity. The allodynia and hyperalgesia of adult rats were evaluated using von-Frey filaments and the Hargreaves plantar test in both baseline and neuropathic pain conditions. Hippocampal genes expression was analyzed following the behavioral tests. The plasticity of the Schaffer-CA1 hippocampal synapses was also assessed using field potential recording following neuropathy. Results showed that adolescent morphine exposure exacerbated the allodynia and hyperalgesia in both baseline and neuropathic pain states in adult rats, which was significantly reduced by the co-administration of minocycline during adolescence. Neuropathy in adult rats was found to increase hippocampal expression of inflammatory mediators, but adolescent morphine prevented this effect. Additionally, we observed a reduction in the baseline synaptic transmission and long-term potentiation (LTP) at the Schaffer-CA1 hippocampal synapses after neuropathy in adult rats following adolescent exposure to morphine. The reduction of synaptic activity was not altered by the co-administration of minocycline with morphine during adolescence. It is concluded that microglia play an important role in mediating hypersensitivity induced by adolescent morphine exposure, although hippocampal microglia may not be directly involved in this process.

Lysimachia mauritiana Lam. Extract Alleviates Airway Inflammation Induced by Particulate Matter Plus Diesel Exhaust Particles in Mice.

The respiratory-protective effects of Lysimachia mauritiana (LM) against airway inflammation were evaluated in a mouse model exposed to a fine dust mixture of diesel exhaust particles and particulate matter with a diameter of less than 10 µm (PM10D). To induce airway inflammation, PM10D was intranasally injected into BALB/c mice three times a day for 12 days, and LM extracts were given orally once per day. The immune cell subtypes, histopathology, and expression of inflammatory mediators were analyzed from the bronchoalveolar lavage fluid (BALF) and lungs. LM alleviated the accumulation of neutrophils and the number of inflammatory cells in the lungs and the BALF of the PM10D-exposed mice. LM also reduced the release of inflammatory mediators (MIP-2, IL-17, IL-1α, CXCL1, TNF-α, MUC5AC, and TRP receptor channels) in the BALF and lungs. Lung histopathology was used to examine airway inflammation and the accumulation of collagen fibers and inflammatory cells after PM10D exposure and showed that LM administration improved this inflammation. Furthermore, LM extract inhibited the MAPK and NF-κB signaling pathway in the lungs and improved expectoration activity through an increase in phenol red release from the trachea. LM alleviated PM10D-exposed neutrophilic airway inflammation by suppressing MAPK/NF-κB activation. This study indicates that LM extract may be an effective therapeutic agent against inflammatory respiratory diseases.

The Effect of the Root Bark of Lycium chinense (Lycii Radicis Cortex) on Experimental Periodontitis and Alveolar Bone Loss in Sprague-Dawley Rats

Lycii Radicis Cortex (LRC), the dried root bark of Lycium chinese Mill., has traditionally been used as a medicinal herb in East Asia to treat fever and hyperhidrosis. In the present study, we investigated the effects of LRC extract on ligation-induced experimental periodontitis and associated alveolar bone loss in rats. Twenty-four hours after ligation placement, LRC was orally administered once daily for 10 days. Firstly, LRC administration inhibited anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissues. Additionally, LRC exhibited anti-inflammatory effects by reducing the expression of inflammatory mediators, including prostaglandin E2, interleukin-1β, and tumor necrosis factor-α. LRC treatment also downregulated mRNA expression of these inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by inhibiting the mitogen-activated protein kinases and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, LRC showed an antioxidant effect by decreasing the malondialdehyde level and inducible nitric oxide synthase activity in gingival tissues. Moreover, LRC effectively prevented the connective tissue degradation by inhibiting matrix metalloproteinase-8 expression and the loss of collagen-occupied areas in gingival tissues. LRC also decreased the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio, as well as the number and occupied areas of osteoclasts on the alveolar bone surface, thereby inhibiting alveolar bone loss. In summary, these findings suggest that LRC is a promising medicinal herb for alleviating periodontitis and related alveolar bone loss through its antimicrobial, anti-inflammatory, and antioxidant properties.

The Rhizome of Atractylodes macrocephala Koidz.: A Comprehensive Review on the Traditional Uses, Phytochemistry and Pharmacology.

Atractylodes macrocephala Koidz. (A. macrocephala) is a perennial herb of the genus Atractylodes. The rhizome of A. macrocephala (AMR) is its medicinal part. It primarily grows in Southeast Asia and function to invigorate the spleen and qi, drying dampness and removing water. It has long been used for cancer treatment, relieving inflammation, and improving gastrointestinal function, highlighting its remarkable medicinal value. This paper focuses on recent advancements in the traditional uses, phytochemistry, and pharmacology of AMR from 2018 to the present, while exploring its therapeutic and scientific potential. In recent years, more than 120 compounds have been identified in AMR. The primary active components have been identified as sesquiterpenoids, polysaccharides and polyacetylenes. Modern pharmacological studies have demonstrated that AMR has anti-inflammatory, anti-tumor, immunity enhancement, gastrointestinal function improvement, and other pharmacological effects. It is mainly employed in the clinical treatment of tumors and gastrointestinal diseases, showing promising developmental potential. Its mechanism may be related to reducing oxidative stress, inhibiting the expression of inflammatory mediators and factors, and alleviating apoptosis through related signaling pathways. It is hoped that this review can provide a theoretical reference and scientific basis for further systematic research and extensive clinical application of AMR.

TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models

Introduction: Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear. Methods: In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection. Results: TLR2-deficient (TLR2−/−) and NLRP3-deficient (NLRP3−/−) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid. Additionally, TLR2−/− and NLRP3−/− mice display heightened neutrophil recruitment and increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway. Conclusion: TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.

Intraperitoneal Injection of the Porphyromonas gingivalis Outer Membrane Vesicle (OMV) Stimulated Expressions of Neuroinflammatory Markers and Histopathological Changes in the Brains of Adult Zebrafish.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The bacteria destroy periodontal tissue through virulence factors, which are retained in the bacteria's outer membrane vesicles (OMV). This study aimed to determine the real-time effect of an intraperitoneal injection of P. gingivalis OMV on the production and expression of inflammatory markers and histopathological changes in adult zebrafishes' central nervous systems (CNS). Following the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMVs, and the control group were injected with normal saline at seven different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA, and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 min, while IL-1β and IL-6 were expressed at subsequent 12 h and 24 h time points, respectively. Histopathological changes such as blood coagulation, astrocytosis, edema, spongiosis, and necrosis were observed between the 6hour and 24 h time points. The two apoptotic enzymes, caspases 3 and 9, were not expressed at any point. In summary, the OMV-induced neuroinflammatory responses and histopathological changes in adult zebrafish were time-point dependent. This study will enrich our understanding of the mechanism of P. gingivalis OMVs in neuroinflammation in a zebrafish model, most especially the timing of the expression of inflammatory mediators in relation to observable changes in brain tissues.

Lactoferrin modulates oxidative stress and inflammatory cytokines in a murine model of dysbiosis induced by clindamycin.

Antibiotics, specifically clindamycin, cause intestinal dysbiosis, reducing the microbiota with anti-inflammatory properties. Furthermore, clindamycin can induce alterations in the immune responses and oxidative stress. Lactoferrin, among other activities, participates in the maintenance of intestinal homeostasis and reduces dysbiosis induced by antibiotic treatment. The aim of this study was to analyze the effect of native and iron-saturated bovine LF in a murine model of dysbiosis induced by clindamycin. Six groups of male C57BL/6 mice were treated with saline (control), clindamycin (Clin), native lactoferrin (nLF), iron-saturated lactoferrin (sLF), nLF/Clin or sLF/Clin. Oxidation caused in the intestinal cells of the ileum of animals subjected to different treatments was analyzed, focusing on lipid peroxidation and protein carbonyl content. The expression of inflammatory mediators was determined by qRT-PCR. Treatment with clindamycin did not modify lipid peroxidation, but significantly increased protein carbonyl levels up to almost 5-fold respect to the control, an effect that was reversed by orally administering sLF to mice. Furthermore, clindamycin increased the expression of interleukin-6 and TNF-α by 1- and 2-fold change, respectively. This effect was reversed by treatment with nLF and sLF, decreasing the expression to basal levels. In conclusion, this study indicates that lactoferrin can prevent some of the effects of clindamycin on intestinal cells and their associated immune system.

Minocycline mitigates sepsis-induced neuroinflammation and promotes recovery in male mice: Insights into neuroprotection and inflammatory modulation.

Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, was investigated in this study for its protective effects against sepsis-induced brain injury. Adult male C57 mice pretreated with minocycline (12.5, 25, and 50 mg/kg) 3 days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Septic mice exhibited significant weight loss and impaired SLA. Initially, minocycline did not attenuate the severity of weight loss (1 day) or SLA (4 h post-sepsis), but it significantly accelerated the recovery of the mice in later days. Minocycline dose-dependently mitigated sepsis-induced brain inflammation and oxidative stress. Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.

Effectiveness of 0.2% Hyaluronic Acid on Clinical, Biomolecular and Microbiological Parameters in Type 2 Diabetes Mellitus Patients with Periodontitis.

This double-blind randomized clinical trial assessed the effectiveness of 0.2% hyaluronic acid (HA) gel as an adjunct to scaling and root planning (SRP) in patients with periodontitis and type 2 diabetes mellitus (DM), focusing on changes in clinical periodontal parameters, the expression of inflammatory mediators, and oral pathogens. The randomized clinical trial involved 36 participants, 18 DM patients, and 18 healthy patients. The participants in each group were randomly assigned to receive placebo or HA gel after SRP. Gingival crevicular fluid and subgingival plaque samples were taken before treatment and at 4-week follow-up. Clinical parameters, interleukin-1β (IL-1β) and IL-10 levels, and proportions of Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) were evaluated at baseline and follow-up. Paired t-test (parametric data) or Wilcoxon signed-rank test (nonparametric data) was used for intragroup comparison between baseline and follow-up, and comparisons between groups one-way analysis of variance test (parametric data) or Kruskal-Wallis test (nonparametric data). At 4 weeks, most of the groups showed statistically significant decreases (p ≤ 0.05) in various clinical and biomolecular parameters. However, there were exceptions: the pocket probing depth (PPD) and clinical attachment loss (CAL) parameter did not significantly decrease for the placebo (p > 0.05) non-DM group, and the IL-10 parameter in the DM HA gel group (p = 0.108). Regarding bacterial proportions, the non-DM and DM placebo group exhibited significant test results for Pg after 4 weeks (p ≤ 0.05). In the case of Fn bacteria proportions, they decreased in all groups, but these results were not statistically significant (p ≥ 0.05). An intergroup analysis revealed no significant differences (p ≤ 0.05) for bleeding on probing (BOP), PPD, and both proinflammatory and anti-inflammatory cytokines. Only clinical attachment loss (CAL) exhibited a statistically significant intergroup difference 0.042. The use of 0.2% HA gel into periodontal pockets alongside SRP, for both diabetic and healthy individuals, showed no statistically significant variances in clinical, biomolecular, and microbiological measures.

Recent Insight into Herbal Bioactives-based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

Type 2 inflammation in COPD: is it just asthma?

COPD is a heterogeneous condition, with tobacco smoking being the main environmental risk factor. The presence of type 2 (T2) inflammation is a well-recognised feature of asthma; however, it is now apparent that a subset of COPD patients also displays evidence of T2 inflammation with respect to elevated eosinophil counts and altered gene and protein expression of several T2 inflammatory mediators. T2 inflammatory mediators represent an attractive therapeutic target in both COPD and asthma; however, the efficacy of pharmaceutical interventions varies between diseases. Furthermore, the nature of some shared clinical features also differs. We provide a narrative review of differences in the nature of T2 inflammation between COPD and asthma, which may partly explain phenotypic differences between diseases. We focus on evidence from studies of pulmonary histopathology, sputum and epithelial gene and protein expression, and response to pharmacological interventions targeted at T2 inflammation.

YiMu-QingGong san alleviates lipopolysaccharide-induced endometritis in mice via inhibiting inflammation and oxidative stress through regulating macrophage polarization

Ethnopharmacological relevanceEndometritis is a common reproductive disease in dairy cattle after calving, characterized by persistent inflammation of the endometrium. YiMu-QingGong San (YMQGS), a patented Chinese medicine formulation, has demonstrated efficacy in the treatment of clinical endometritis in dairy cattle. However, the potential mechanisms by which YMQGS alleviates endometritis remain unclear. Aim of the studyThe objective of this study is to elucidate the underlying therapeutic mechanisms of YMQGS in the context of endometritis. Materials and methodsThe chemical components of YMQGS were analyzed using UHPLC/MS. The anti-inflammatory capabilities of YMQGS were assessed by inducing an inflammatory response in RAW264.7 cells with lipopolysaccharide (LPS). Moreover, a clinical model of endometritis was simulated via vaginal injection of LPS into the uterine horns to investigate the therapeutic mechanisms of YMQGS. ResultsYMQGS could downregulate the expression of inflammatory mediators (TNF-α, IL-6, IL-1β) by suppressing the activation of the TLRs/MyD88/TRAF6/NF-κB signaling pathway in RAW264.7 cells. Additionally, YMQGS facilitated the polarization of RAW264.7 cells towards M2-like macrophages (Mφs) while inhibiting M1-like Mφs polarization, thereby exerting anti-inflammatory effects. Further investigation revealed that YMQGS could diminish ROS production, augment cellular antioxidant capacity, preserve mitochondrial membrane potential, and reduce intracellular [Ca2+]i accumulation, thereby minimizing cellular damage. In the mouse model of endometritis, YMQGS similarly inhibited the activation of the NF-κB signaling pathway in uterine tissues and modulated Mφ polarization in the endometrium, leading to a decrease in the expression of inflammatory factors and subsidence of the inflammatory response in the endometrium. Histological staining results showed that YMQGS reduced endometrial fibrosis, increased the expression of endometrial ZO-1, Occludin and glycoprotein, protect the endometrial barrier function, and prevent the further development of endometritis. ConclusionCollectively, the present study confirms that YMQGS possesses notable anti-inflammatory and antioxidant properties. The suppression of the NF-κB signaling pathway and the modulation of Mφ polarization emerge as the pivotal mechanisms by which YMQGS alleviates endometritis.

Investigating the potential impact of ELF3-associated SNPs on chondrocyte inflammation

Objective: Chondrocyte inflammation is a critical factor in degenerative joint diseases, such as osteoarthritis (OA), significantly impairing quality of life through chronic pain and limited mobility. Genetic predisposition is recognized as a critical factor in the progression of chondrocyte inflammation and OA, with particular focus on the role of genetic variants in the expression and regulation of inflammatory mediators. This study aimed to obtain information about the potential roles of a few genes containing ELF3-associated SNPs in the pathogenesis of chondrocyte inflammation. Materials and Methods: GVAT Database was used to select top candidate SNPs associated with ELF3, a cardinal transcription factor in chondrocyte inflammation. Inflammation was induced by IL-1β treatment in differentiated chondrocytes to analyze gene expression patterns. Transcriptome analysis was done by RNA sequencing. Results: The most important SNPs that could potentially affect the binding affinity of ELF3 transcription factor were analyzed. As a result of the analysis, 52% of ELF3-associated SNPs were found in protein-coding regions, 40% in gene-free intergenic regions, and 8% in non-coding RNA sequences. Some of these SNPs are located in regulatory regions (enhancers). A significant increase in expression levels in the ELF3 gene was detected after IL-1β administration, indicating that IL-1β promotes the activity of this transcription factor. mRNA expressions of TLN2, BABAM2, PEPD, and NUDT5 were also increased after IL-1β stimulation. Conclusion: The presence of ELF3-associated SNPs in the enhancer sequences of TLN2 and BABAM2 genes, in addition to the increased expression of these two genes upon IL-1β stimulation, suggested that TLN2 and BABAM2 genes may be associated with the severity of chondrocyte inflammation and OA.

Catechin reduces liver inflammation by regulating Kupffer cell activation in rats

The liver is a defense against infections due to its strategic location between the gastrointestinal and systemic circulations. In dogs and cats, infectious hepatitis encompasses a range of contagious diseases affecting the liver either directly or as part of a broader systemic infection, including bacterial, mycobacterial, viral, fungal, protozoal, parasitic, and rickettsial diseases. Catechins possess well-recognized natural antioxidant properties. This study investigated their therapeutic potential for applications in hepatology, evaluating whether catechins reduce hepatic inflammation in rats repeatedly exposed to carbon tetrachloride (CCl4). Sprague-Dawley rats were given catechin 50 (C50) or 100 (C100) mg/kg body weight orally daily for 3 days. This treatment was given with or without concurrent intraperitoneal injections of CCl4. Phosphate-buffered saline served as the vehicle control, while silymarin administered at 100 mg/kg was used as the positive control.Gross examination revealed significant enlargement, edema, and darker tissue in CCl4-induced livers treated with vehicle. Additionally, spotty discoloration was observed on the surface. Kupffer cell activation suppressed the expression of inflammatory mediators, including inducible nitric oxide synthase (iNOS), in groups co-treated with catechin and CCl4; this effect was reversed when catalase replaced catechin in CCl4-injured rats. Catechin alleviates hepatic inflammation in rats repeatedly exposed to CCl4; it also modulates the activation of Kupffer cells and monocytes. These results should lead to new treatments for liver inflammation in veterinary practice.

Orally Administered Ginkgolide C Alleviates MPTP-Induced Neurodegeneration by Suppressing Neuroinflammation and Oxidative Stress through Microbiota-Gut-Brain Axis in Mice.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, the etiology of which remains unclear. Studies have shown that neuroinflammation and oxidative stress (OS) play an important role in neuronal damage in patients with PD. Disturbances in the gut microbiota influence neuroinflammation and OS through the microbiota-gut-brain axis. Ginkgolide C (GC), a traditional Chinese medicine extracted from the leaves of Ginkgo biloba, has been reported to exhibit anti-inflammatory effects and the ability to modulate intestinal microbial composition. However, the potential of GC to positively impact PD by modulating the gut microbiota remains unexplored. This study aimed to explore the effects of GC on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice and elucidate its underlying mechanisms. Our findings elucidated that GC treatment significantly ameliorates behavioral deficits as well as pathological damage via restoring gut microbial homeostasis to downgrade OS and neuroinflammation in MPTP-induced PD mice. Mechanistically, GC treatment exerts antioxidant effects via activating the AKT/Nrf2/HO-1 pathway in MPP+-exposed SN4741 neuronal cells and significantly downregulates the expression of inflammatory mediators via regulating NF-κB and MAPK signaling in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Overall, our study demonstrates that GC administration alleviates MPTP-induced neurodegeneration via rebuilding gut microbial homeostasis to inhibit OS and neuroinflammation in mice, indicating that GC might serve as a promising candidate medicine for PD.

Biologically active franchetine-type diterpenoid alkaloids: Isolation, synthesis, anti-inflammatory, agalgesic activities, and molecular docking

In this study, four franchetine-type diterpenoid alkaloids (1–4) were isolated from Aconitum sinoaxillare, and fourteen diverse franchetine analogs (5–18) were synthesized. Compounds 1, 2, 7 and 16 exhibited stronger inhibitory effects on NO production when compared to celecoxib. Among them, compound 1 had the best inhibitory effect on iNOS and COX-2 inflammatory proteins. The in vitro studies displayed that the anti-inflammatory effect of the most active compound 1 was ascribed to the inhibition of the TLR4-MyD88/NF-κB/MAPKs signalling pathway. Consequently, this led to a inhibition in the expression of inflammatory factors or mediators including NO, ROS, TNF-α, IL-6, IL-1β, iNOS, and COX-2. Additionally, compound 1 had low toxicity (LD50 > 20 mg/kg) in mice, and it had notable analgesic effects on acetic acid-induced visceral pain (ED50 = 2.15 ± 0.07 mg/kg). Moreover, compound 1 exhibited a distinct reduction in the NaV1.7 and NaV1.8 channel currents during both resting and half-inactivated states at 50 μM. The present study enriches the pharmacological activities of franchetine derivatives and provides valuable insights for the development of novel anti-inflammatory and analgesic agents.

Exploring the health benefits of high amylose wheat phenolic extract in human endothelial cell model: Inhibitory effects on endothelial activation

Newly developed high amylose durum wheat genotypes, characterized by a high content of resistant starch, is gaining interest as a healthy ingredient for functional food. The objective of the present study was to investigate the effects of Svevo high amylose phenolic extracts (HAPE) on endothelial activation, the first obligatory step of the atherosclerotic process, investigating the underlying mechanisms of action. To this aim, human microvascular endothelial cells were treated with HAPE (1–10 μg/mL) and then challenged with the pro-inflammatory and pro-atherogenic cytokine TNF-α. Endothelium-leukocyte adhesion, the expression of endothelial inflammatory mediators, intracellular reactive oxygen species (ROS) levels and the activation of nuclear factor (NF)-κB were evaluated by multiple assays. The results showed that, HAPE, already at 5 μg/mL, suppressed the TNF-α stimulated expression of endothelial adhesion molecules as well as the adhesion of leukocytes to endothelial cells by more than 50% in comparison with TNF-α alone. These effects were associated with a significant (p < 0.05) reduction of intracellular ROS levels and NF-κB activation. In summary, our findings underscore the potential of Svevo high amylose as a functional food able to blunt endothelial activation, by inhibiting the concerted expression of endothelial markers involved in leukocyte recruitment and early atherogenesis.