Reduction Of Mediators Research Articles

Chondroitin sulfate alleviated lipopolysaccharide-induced arthritis in feline and canine articular chondrocytes through regulation of neurotrophic signaling pathways and apoptosis

Osteoarthritis (OA) is a pervasive degenerative joint disease affecting companion animals, characterized by chronic inflammation and cartilage degradation. However, the effectiveness of chondroitin sulfate (CS) in treating OA in dogs and cats remains controversial. This study aimed to determine the therapeutic effects and molecular mechanisms of CS on lipopolysaccharide (LPS)-induced inflammation in feline and canine articular chondrocytes (FAC and CAC) at the cellular level in vitro. Our findings demonstrated that CS treatment (800 µg/mL) significantly enhanced cell viability and reduced oxidative stress in FAC and CAC, as evidenced by decreased levels of reactive oxygen species and increased activities of antioxidant enzymes. Furthermore, CS treatment effectively suppressed LPS-induced secretion of pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, interleukin-8, interleukin-10, and matrix metalloproteinases-3, and reduced apoptosis, as confirmed by fluorescence staining and flow cytometry. Transcriptomic analysis revealed that CS upregulated neurotrophic signaling pathways, promoting cell survival and proliferation. Metabolomic analysis indicated that CS treatment upregulated metabolites associated with glycerophospholipid and purine metabolism, suggesting enhanced membrane integrity and energy metabolism. Conversely, pathways involved in protein catabolism and arachidonic acid metabolism were downregulated, indicating a reduction in inflammatory mediators. Collectively, these findings elucidate the multifaceted role of CS in modulating chondrocyte metabolism and inflammatory responses, highlighting its potential to alleviate OA.

Traditional Chinese Medicine: A Promising Treatment Option for Intestinal Fibrosis.

Intestinal fibrosis, a common complication of inflammatory bowel disease, in particular in Crohn's disease, arises from chronic inflammation, leading to intestinal narrowing, structural damage, and functional impairment that significantly impact patients' quality of life. Current treatment options for intestinal fibrosis are limited, with surgery being the primary intervention. Traditional Chinese Medicine (TCM) has emerged as a promising approach in preventing and treating intestinal fibrosis. However, there is a scarcity of literature summarizing the mechanisms underlying TCM's efficacy in this context. To address this gap, we conducted a comprehensive review, uncovering multiple mechanisms through which TCM mitigates intestinal fibrosis. These mechanisms include immune cell balance regulation, suppression of inflammatory responses, reduction of inflammatory mediators, alleviation of colon tissue damage, restoration of intestinal function, modulation of growth factors to inhibit fibroblast activation, dynamic regulation of TIMPs and MMPs to reduce extracellular matrix deposition, inhibition of epithelial-mesenchymal transition and endothelial-mesenchymal transition, autophagy modulation, maintenance of the intestinal mucosal barrier, prevention of tissue damage by harmful factors, and regulation of cell proliferation and apoptosis. This study aims to bridge existing knowledge gaps by presenting recent evidence supporting the utilization of TCM in both clinical and experimental research settings.

Endodontic treatment modifies circulatory inflammatory mediator levels: A systematic review with meta-analysis.

There is limited and conflicting data on the reduction of circulatory inflammatory mediators in patients with apical periodontitis (AP) following endodontic treatment. To answer the following research question: in adult healthy patients with AP [Population (P)], is there a difference before [Comparator (C)] and after various endodontic treatments (nonsurgical, surgical or retreatment) [Intervention (I)] on systemic levels of inflammatory biomarkers [Outcome (O)] in the follow-up period[Time (T)]? An electronic literature search was conducted in the databases Scopus, PubMed, Clarivate Analytics' Web of Science, Cochrane Database of Systematic Reviews and Grey literature from inception to July 2024 with no language restrictions. Observational studies examining changes in serum levels of inflammatory mediators were included. Two independent reviewers selected studies, extracted data and critically appraised the included studies. Qualitative and quantitative (meta-analysis) data synthesis methods were employed. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Sixteen studies met the inclusion criteria, of which six were included in the meta-analysis. These studies were published between 1992 and 2024, involving a total of 596 patients (54% females) aged between 16 and 75 years. The meta-analysis of pooled data showed a significant decrease in high-sensitive C-reactive protein (hs-CRP) levels in the serum of patients with AP 6 months after treatment [2.26 ± 1.76 versus 1.28 ± 1.06 mg/L, (Z = 2.03, p = .04)] and a decrease in interleukin-1β (IL-1β) levels 12 months after treatment [13.01 ± 5.95 versus 10.86 ± 3.52 pg/mL, (Z = 3.72, p < .01)]. One study was assessed as poor quality, while all others were considered high quality. Despite the differences in methodologies across the included studies, it has been established that effective endodontic treatment leads to a reduction in systemic inflammatory biomarkers in the body. Following effective endodontic treatment in patients with AP, the systemic levels of hs-CRP and IL-1β exhibit a significant reduction at 6 and 12 months, respectively. Further clinical studies should investigate whether effective endodontic treatment and reduced levels of investigated biomarkers may change the clinical presentation of systemic diseases. PROSPERO database (CRD42024559271).

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

A Selective Nuclear Factor-κB Inhibitor, JSH-23, Exhibits Antidepressant-like Effects and Reduces Brain Inflammation in Rats.

Accumulating evidence suggests that nuclear factor (NF)-κB is involved in the pathophysiology of mood disorders. We conducted two experimental protocols in rats to investigate the effects of a selective NF-κB inhibitor (JSH-23) on (i) lipopolysaccharide (LPS)-induced inflammation and (ii) on behavioral phenotypes in rat models of depression (sucrose consumption test and forced swim test) and mania (amphetamine-induced hyperactivity test). Additionally, we tested the effects of JSH-23 on levels of inflammatory components (interleukin-6, prostaglandin E2, nuclear phospho-p65, and tumor necrosis factor-α) in the brain. Acute treatment with JSH-23 (10 mg/kg, intraperitoneally [ip]) led to potent anti-inflammatory effects in LPS-treated rats, including a diminished hypothermic response to LPS and a reduction in pro-inflammatory mediators' levels in the brain. Chronic treatment with JSH-23 (3 mg/kg, ip, once daily, for 14 days) resulted in robust antidepressant-like effects (increased sucrose consumption and decreased immobility time). The antidepressant-like effects of JSH-23 were mostly accompanied by a reduction in levels of pro-inflammatory mediators in the brain. On the other hand, JSH-23 did not reduce amphetamine-induced hyperactivity. Altogether, these data suggest that NF-κB may be a potential therapeutic target for pharmacological interventions for depression.

Anisakis extracellular vesicles elicit immunomodulatory and potentially tumorigenic outcomes on human intestinal organoids

BackgroundAnisakis spp. are zoonotic nematodes causing mild to severe acute and chronic gastrointestinal infections. Chronic anisakiasis can lead to erosive mucosal ulcers, granulomas and inflammation, potential tumorigenic triggers. How Anisakis exerts its pathogenic potential through extracellular vesicles (EVs) and whether third-stage infective larvae may favor a tumorigenic microenvironment remain unclear.MethodsHere, we investigated the parasite's tumorigenic and immunomodulatory capabilities using comparative transcriptomics, qRT-PCR and protein analysis with multiplex ELISA on human intestinal organoids exposed to Anisakis EVs. Moreover, EVs were characterized in terms of shape, size and concentration using classic TEM, SEM and NTA analyses and advanced interferometric NTA.ResultsAnisakis EVs showed classic shape features and a median average diameter of around 100 nm, according to NTA and iNTA. Moreover, a refractive index of 5–20% of non-water content suggested their effective biological cargo. After treatment of human intestinal organoids with Anisakis EVs, an overall parasitic strategy based on mitigation of the immune and inflammatory response was observed. Anisakis EVs impacted gene expression of main cytokines, cell cycle regulation and protein products. Seven key genes related to cell cycle regulation and apoptosis were differentially expressed in organoids exposed to EVs. In particular, the downregulation of EPHB2 and LEFTY1 and upregulation of NUPR1 genes known to be associated with colorectal cancer were observed, suggesting their involvement in tumorigenic microenvironment. A statistically significant reduction in specific mediators of inflammation and cell-cycle regulation from the polarized epithelium as IL-33R, CD40 and CEACAM1 from the apical chambers and IL-1B, GM-CSF, IL-15 and IL-23 from both chambers were observed.ConclusionsThe results here obtained unravel intestinal epithelium response to Anisakis EVs, impacting host’s anthelminthic strategies and revealing for the first time to our knowledge the host-parasite interactions in the niche environment of an emerging accidental zoonosis. Use of an innovative EV characterization approach may also be useful for study of other helminth EVs, since the knowledge in this field is very limited.Graphical

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting.

Aim: Amitriptyline (AMI) has been used to treat neuropathic pain. However, the clinical outcomes remain unsatisfactory, presumably due to a limited understanding of the underlying molecular mechanisms. Here, we investigated a drug repositioning strategy using a low-dose of AMI encapsulated in poly (D, L lactic-co-glycolic acid) (PLGA) nanoparticles (AMI NPs) for neuropathic pain, since PLGA nanoparticles are known to enhance delivery to microglia.Methods: We evaluated the anti-allodynic effects of AMI and AMI NPs on neuropathic pain by assessing behaviors and inflammatory responses in a rat model of spinal nerve ligation (SNL). While the anti-allodynic effect of AMI (30μg) drug injection on SNL-induced neuropathic pain persisted for 12h, AMI NPs significantly alleviated mechanical allodynia for 3days.Results: Histological and cytokine analyses showed AMI NPs facilitated the reduction of microglial activation and pro-inflammatory mediators in the spinal dorsal horn. This study suggests that AMI NPs can provide a sustained anti-allodynic effect by enhancing the targeting of microglia and regulating the release of pro-inflammatory cytokines from activated microglia.Conclusion: Our findings suggest that the use of microglial-targeted NPs continuously releasing AMI (2μg) as a drug repositioning strategy offers long-term anti-allodynic effects.

Effects of Photobiomodulation Associated with Platelet-Rich Plasma in Acute Rheumatoid Arthritis Induced in Female Wistar Rats' Knee.

Objective: Rheumatoid arthritis causes inflammation, pain, and joint degradation, necessitating treatment with anti-inflammatory drugs and corticosteroids, posing various challenges. We aimed to evaluate the effects of photobiomodulation (PBM) at two different doses associated to platelet-rich plasma (PRP) in an invivo model of induced acute arthritis in Wistar rats' knee. Methods: Eighty-four Wistar rats were assigned into seven groups, including animals treated with PBM and/or PRP. On day 0, arthritis was induced in sham and treated groups through the intra-articular injection of zymosan (200 μg). Twenty-four hours after induction, the PBM groups were treated with an AsGaAl laser, whereas the PRP-treated groups received intra-articular injections with a concentration of 8 × 105 platelets obtained from another four animals. After 3 days, the animals were euthanized, and the interleukin (IL)-6 and complement C3 gene and protein expression levels were analyzed. Statistical analysis was performed using the mean ± SD with analysis of variance and Tukey's posttest, with a significance level set at 5% (p < 0.05). Results: Synovial inflammation decreased in PBM-treated groups; however, PRP alone showed no significant difference. Gene expression analysis revealed a significant difference in IL-6 and C3 levels in the PBM and PBM+PRP-treated groups. Meanwhile, the PRP alone group exhibited significance for IL-6. Moreover, the PBM and PBM+PRP-treated groups showed a significant difference in C3 protein expression levels, whereas the PRP alone group showed no difference. Conclusion: The increase in cellular activity in the synovial membrane and the decrease protein expression levels are owing to the reduction in proinflammatory mediators following PBM therapy.

Anti-pneumoconiosis effect of schisantherin A in PMA-induced A549 cells and SiO2/TiO2nanoparticles-induced acute pulmonary injury in mice

There has been significant global interest in respiratory health driven by the coronavirus disease (COVID-19) and severe environmental pollution. This study explored the potential of schisantherin A (SchA), a compound derived from Schisandra chinensis, to protect against acute pneumoconiosis. We assessed the effects of SchA on phorbol 12-myristate 13-acetate (PMA)-stimulated A549 alveolar epithelial cells and SiO2/TiO2-induced pulmonary injury in mice. In A549 cells, SchA significantly decreased pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-8 levels. SchA-mediated reduction in inflammatory mediators was associated with the downregulation of PMA-stimulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling activation. In SiO2/TiO2-induced lung-injured mice, SchA administration significantly reduced MUC5AC production in lung tissue. SchA administration significantly downregulated the overexpression of NK-κB and the subsequent production of COX-2, iNOS, and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes. It significantly suppressed expected increases in total cell numbers and pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and IL-1β in the bronchoalveolar lavage fluid (BALF) in SiO2/TiO2-stimulated mice. In contrast, the SiO2/TiO2-mediated decrease in IL-10 levels was significantly improved by SchA treatment. These fundamental results can be used to develop potential treatments involving SchA for acute pneumoconiosis.

Artemisinin and deoxyartemisinin isolated from Artemisia annua L. promote distinct antinociceptive and anti-inflammatory effects in an animal model

Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55 %) and inflammatory pain (45.43 %). These findings were superior to the effect of artemisinin (reduction of 28.66 % and 33.35 %, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57 %) compared to morphine (75.94 %) in 0.5 h. After 1.5 h, the MPE of deoxyartemisinin (87.99 %) exceeded the effect of morphine (47.55 %), without reversal with naloxone. The MPE of artemisinin (23.3 %) observed after 2 h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37 % and 48.19 %, respectively, higher than the effect of deoxyartemisinin (33.64 %). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96 %) more selectively when compared to interleukin-1beta (IL-1β) (48.23 %) and interleukin-6 (IL-6) (44.49 %). Lac-FR showed greater selectivity in IL-6 reduction (56.49 %) in relationship to TNF-α (46.71 %) and IL-1β (45.12 %), whereas deoxyartemisinin selectively reduced TNF-α (37.37 %). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome.

Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson’s disease in mice

Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson’s disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1–7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by 1H and 13C nuclear magnetic resonance and ESI–MS spectral data. Compound 1 (6β,7β-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.

Unraveling the Electron Transfer in Cupriavidus necator – Insights Into Mediator Reduction Mechanics

AbstractCupriavidus necator, despite lacking direct electron transfer capabilities, demonstrates efficient reduction of various redox mediators in oxygen‐free cultivation within bioelectrochemical systems. This study investigates the reduction site of ferricyanide through inhibition and expression rate analysis of oxygen and nitrate respiration chain complexes, comparing aerobic cultivation conditions with fructose as carbon and electron donor to autotrophic (CO2/H2/O2) and anodic cultivation conditions (fructose/anode). Azide inhibition identified cytochrome c oxidase as the primary complex facilitating electron transfer to ferricyanide, with a secondary role proposed for nitrite reductase NirS, demonstrating a 3.9±1.1‐fold higher expression when exposed to anodic conditions. The 2.9±0.6‐fold increase in the expression of the natural porin OmpA under anodic conditions implies its potential involvement in ferricyanide uptake. Additionally, chemically permeabilizing cell membranes with cetyltrimethylammonium bromide doubles ferricyanide reduction rates without an anode present, offering insights for optimizing redox mediation in C. necator based bioelectrochemical systems. This study opens up new possibilities for the targeted optimization of mediated electron transfer in C. necator and other organisms.

A review of the efficacy of popular eye cream ingredients.

Due to the periorbital region's high susceptibility to damage from external factors, along with its tendency to demonstrate early signs of aging, periorbital skin is a common target for antiaging therapy. This review aims to evaluate the efficacy of active ingredients commonly found in eye creams, particularly focusing on their impact on periorbital skin concerns. A comprehensive review of the literature on active ingredients in eye creams, including retinoids, vitamins C and E, peptides, ceramides, hyaluronic acid, caffeine, and niacinamide, was conducted. Clinical studies assessing the efficacy of these ingredients in addressing periorbital concerns were examined. Studies demonstrate the potential of these ingredients to improve various aspects of periorbital skin, including hydration, elasticity, collagen synthesis, and reduction of inflammatory mediators. Ingredients such as retinoids, vitamin C, and caffeine show promise in addressing wrinkles and hyperpigmentation, while peptides and hyaluronic acid aid in collagen production and hydration. Niacinamide and ceramides offer benefits in reducing wrinkles and enhancing the skin barrier function. The lack of clinical trials specifically targeting eye cream formulations and periorbital skin is a notable limitation. Furthermore, the variability in study designs, sample sizes, and concentrations of active ingredients across studies complicates direct comparisons. The reviewed studies highlight the potential of active ingredients in eye creams to address various periorbital concerns. Further research, particularly large-scale clinical trials focusing on eye cream formulations and their efficacy on periorbital skin, is warranted to establish their significance and comparability with other dermatologic products.

Effects of minimally invasive non-surgical therapy on C-reactive protein, lipoprotein-associated phospholipase A2, and clinical outcomes in periodontitis patients: A 1-year randomized, controlled clinical trial.

Growing evidence suggests the type of periodontal treatment could differentially influence the reduction of key cardiovascular risk mediators in periodontitis patients. This randomized, controlled clinical trial compared the impact of minimally invasive non-surgical therapy (MINST) with quadrant-wise subgingival instrumentation (Q-SI) on C-reactive protein (CRP) together with lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, and clinical periodontal outcomes in patients with periodontitis. Moreover, it was evaluated if baseline CRP levels impacted the efficacy of non-surgical periodontal therapy protocols. Forty-two periodontitis patients were enrolled and randomly treated by means of MINST (n=21) or Q-SI (n=21). The outcomes assessed were serum CRP and Lp-PLA2, and periodontal parameters (probing depth [PD], clinical attachment level [CAL], full-mouth bleeding score [FMBS]), at baseline and at follow-ups at 1, 3, and 6 months and at 1 year after treatment. At 1 year, MINST significantly reduced, among others, mean PD (p=0.007), mean CAL (p=0.007), the number of pockets>4mm (p=0.011) and ≥6mm (p=0.005), and FMBS (p=0.048) compared to Q-SI. Generalized multivariate analysis evidenced that high baseline CRP (p=0.039) and FMBS (p=0.046) levels, together with MINST treatment (p=0.007) were significant predictors of PD reduction at 1-year follow-up. Moreover, the Jonckheere-Terpstra test showed that patients with high baseline CRP levels gained more benefits from MINST treatment at 1-year follow-up than they did from Q-SI. Patients receiving MINST showed a greater reduction in CRP levels than patients with Q-SI after 1 year of follow-up. Moreover, patients with high baseline levels of CRP and Lp-PLA2 gained more benefits from the MINST approach at 1-year follow-up.

Immunomodulatory and antioxidant properties of Sarcophaga argyrostoma larval hemolymph: utilizing the Biomphalaria alexandrina snail as a model

In recent years, there has been a growing interest in exploring novel natural sources for antioxidant and anti-inflammatory agents, driven by the need for alternative therapeutic strategies with fewer side effects. This study investigates the potential of the Biomphalaria alexandrina snail as a valuable model organism to evaluate the antioxidant and anti-inflammatory properties of Sarcophaga argyrostoma larval hemolymph. The choice of B. alexandrina snails as a model is based on its ecological relevance and physiological similarities to other organisms, supporting well-established use in ecological and physiological research, as well as it provides a valuable platform for such investigations. Ultimately, this study may open avenues for the development of innovative and sustainable therapeutic interventions rooted in the rich biodiversity of the natural world. The experimental design involves the extraction of hemolymph from S. argyrostoma larvae, followed by a comprehensive analysis of its antioxidant capacity and anti-inflammatory effects using adult snails. Various biochemical assays, including total antioxidant capacity, immunomodulatory markers and histological investigation, will be employed to assess the bioactive potential of the hemolymph. The outcomes of this research can be attributed to the identification of the anti-oxidant and anti-inflammatory effects of hemolymph. This effect was observed through the reduction of oxidative stress and proinflammatory mediators, impacting the biological activities of the snails. The study is the first to shed light on the potential benefits of S. argyrostoma larval hemolymph using an animal model, showcasing its ability to mitigate oxidative and inflammatory responses within the biological context of the snails.

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

Bioactive compounds and pharmacological properties of some date cultivars (Phoenix dactylifera L.)

In this study, five Algerian date cultivars (Phoenix dactylifera L.) were investigated for their antioxidant contents, phenolic profiles, and some pharmacological properties (anti-inflammatory, anti-diabetic, and antioxidant activities). The results showed that the Tanslit cultivar was the most concentrated in total phenolic compounds and flavonoids with 433.03±0.47 96 mg QE/100g DM and 102.5±3.96 mg QE/100g DM, respectively. The Tamdjohert cultivar was the richest on anthocyanins (9.83±0.07mg CE/100g DM). HPLC analysis indicated that the Tamdjohert cultivar contained a high flavonoids concentration (8.22 ± 0.53mg/100g DM), and the Takarmoust cultivar displayed the highest concentration of phenolic acids (15.64±0.41mg/100g DM). The results indicated that the Litim cultivar exhibited strong hydroxyl radical inhibition (134.95±18.07mg GAE/100g DM), and also potently inhibited α-amylase activity (35.19±4.98%). The Tamdjohert cultivar exerted the highest reduction of inflammatory mediators (255.87±18.47mg GAE/100g DM). This study demonstrated that date fruit was a good source of bioactive compounds with important pharmacological properties and can be considered as functional food.

Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial

We assessed the joint effects of omega (n)-3 fatty acid supplementation and dietary fish intake on systemic lipid mediators of inflammation among adults. Within VITAL, a double-blind randomized controlled trial, adults were randomized to ω-3 fatty acids (460 mg EPA + 380 mg DHA/d) or placebo. We selected participants who reported low (<1 serving/mo) baseline dietary fish intake and matched them by age, sex, race, and trial arm to participants with self-reported highest fish intake (≥3.9 servings/wk). Baseline and 1-y plasma samples were tested for 9 ω-3 fatty acid-derived lipid mediators. Multivariable linear models assessed lipid mediator changes and joint effects of ω-3 fatty acid supplementation and dietary fish intake. Forty-eight participants with low baseline fish intake were matched to 48 with high fish intake. Mean age was 64.6 (±7.26), 50% were female, and 85% non-Hispanic white. One-year lipid mediator changes in expected directions were observed in those receiving ω-3 fatty acids versus placebo: reductions in proinflammatory mediators, PGD2, 5-HETE, and 12-HETE; increases in proresolving mediators, EPA and DHA. Larger 1-y lipid biomarker changes were seen in those with low baseline fish intake randomized to active ω-3 fatty acids for DHA, EPA, PGD2, Resolvin D1, and Resolvin D4 were observed, although no significant multiplicative interactions were detected. Beneficial changes in circulating proresolving and proinflammatory mediators were found with 1-y of ω-3 fatty acid supplementation versus placebo for all participants, with a trend toward larger effects among those with low baseline fish intake, although interactions were not significant.

Involvement of TNFα, IL-1β, COX-2 and NO in the anti-inflammatory activity of Tamarix aphylla in Wistar albino rats: an in-vivo and in-vitro study

BackgroundWith the emergence of many side effects from synthetic drugs, there is an urgent need to find a natural alternative to these products. Therefore, our primary aim was to evaluate the anti-inflammatory activity of Tamarix aphylla (TA) and investigate the potential mechanism underlying this action.MethodsInitially, to ensure the safety of the extract and for dose selection, we performed an acute oral toxicity Assay through the oral administration of graded doses up to 4 g\\kg in Wistar rats. then, we used the carrageenan-induced edema model to elucidate the anti-inflammatory activity. Using specific ELISA kits, we measured the levels of TNF-α, IL-1β, COX-2 and NO inside the inflamed paw tissue. Finally, for the in-vitro anti-inflammatory experiment, we used the erythrocyte membrane stability test.ResultsBased on the acute oral toxicity assay, T. aphylla was considered generally safe and three different doses of 100, 200, and 400 mg/kg were chosen for further experiments. Additionally, TA expressed a significant (P < 0.05) anti-inflammatory activity, showing the maximum inhibition percentage at the fifth hour of measurement at 53.47% and 70.06%, at doses of 200 and 400 mg/kg respectively, compared to 63.81% for the standard drug. Similarly, we found that TA effectively reduced the levels of TNF-α and IL-1β at all tested doses (100-200-400 mg/kg) to a greater extent than the standard drug. Moreover, at 400 mg/kg, TA was able to significantly lower the levels of COX-2 and NO inside the inflamed tissue to a level comparable (P < 0.05) with that measured inside the paw tissue of normal rats. Finally, Tamarix aphylla at 100, 200 and 400 mg/kg doses significantly (P < 0.05) inhibited the heat-induced hemolysis of RBCs membrane by 67.78, 74.82 and 82.08%, respectively, compared to 83.89% produced by Aspirin.ConclusionT. aphylla produced a significant (P < 0.05) anti-inflammatory activity compared to the standard drugs either through the reduction of pro-inflammatory mediators or the protection of the lysosomal membrane.

Possible protective anticancer effect of chloroform fraction of Iraqi Hibiscus tiliaceus L. leaves extract on diethylnitrosamine-induced hepatocarcinogenesis in male rats.

We aimed to examine the potential protective effects of IraqiH. tiliaceus L. chloroform leaves extract on DEN-induced HCC in male Wistar Albino rats. Rats were assigned to four groups, six in each group. Group I: rats were administered a daily oral dose of 1 mL/kg/day of distilled water. Group II: rats were intraperitoneally injected with 70 mg/kg DEN once per week for 10 consecutive weeks. Group III: rats received 250 mg/kg of chloroform leaves extract. Groups IV: the rats were administered 500 mg/kg of chloroform leaves extract, along with their food, for five days per week over 20weeks, with a subsequent dose of DEN once per week for 10 consecutive weeks. The results indicate that the extract demonstrated a significant reduction (p<0.05) in oxidative stress, pro-inflammatory mediators, and HCC parameters, the extract also had a beneficial effect on liver function tests, and there was a significant elevation (p<0.05) of antioxidant parameters in a dose-dependent manner. This study supports the protective properties of the chloroform extract of Iraqi H.tiliaceus L. leaves in HCC.