Downregulation Of Cytokines Research Articles

Assessment of Lactobacillus acidophilus (L. acidophilus) therapeutic and prophylactic role in rats experimentally infected with Blastocystis subtype 3 (ST3).

Blastocystis, an eukaryote, inhabits the intestinal tract of humans and animals worldwide. Lactobacillus acidophilus (L. acidophilus), a probiotic, has been reported to be effective against blastocystosis. The present study evaluated the therapeutic and prophylactic effectiveness of L. acidophilus compared to metronidazole (MTZ) in rats experimentally infected with Blastocystis subtype 3 (ST3). Four groups of Blastocystis ST3-infected rats received MTZ, L. acidophilus, both MTZ and L. acidophilus, or prophylactic L. acidophilus. Non-infected and infected control groups were included. The effectiveness of treatment and prevention was evaluated using parasitological monitoring, histopathological examination, immunohistochemical staining for TNF-α and IgA expression, and immunological testing for TNF-α and IL-10. In the L. acidophilus-treated group, a 76% reduction in the mean fecal parasitic count and a 67% clearance in the intestinal wash were achieved aligning closely with outcomes observed in the MTZ-treated group. An immunomodulatory impact via upregulation of the anti-inflammatory cytokine IL-10 and downregulation of the pro-inflammatory cytokine TNF-α was demonstrated as well. Combined administration of MTZ and L. acidophilus exhibited superior efficacy with a 99% decrease in the mean fecal parasitic count and a 98% decrease in the intestinal fluid parasitic count. Additionally, the lowest TNF-α and the highest IL-10 serum levels. Prophylactic use of L. acidophilus for 7 days neither prevented infection nor reduced its severity. Furthermore, no significant differences were detected in serum levels of TNF-α and IL-10 following post-prophylaxis andpost-treatmentwith L. acidophilus. Accordingly, L. acidophilus might be recommended as an adjuvant treatment alongside MTZ for improved efficacy against blastocystosis.

P0852 Influence of a gluten-free dietary intervention on the gut microbiome and inflammation in inflammatory bowel disease: results from murine experiments and protocol of a prospective proof-of-concept human study as part of the miGut-Health project

Abstract Background A significant number of inflammatory bowel disease (IBD) patients report an improvement of gastrointestinal symptoms under a gluten-free diet (GFD), despite not suffering from celiac disease. In a recent prospective pilot study, we detected a significant downregulation of proinflammatory cytokines and chemokines on the mucosal level, as well as slight compositional changes of the luminal microbiome after implementation of an eight-week GFD intervention in PSC-IBD patients (1). For a further characterization, we established murine models of IBD, investigating the influence of a GFD on colitis susceptibility, gut microbiota, and intestinal inflammation (Part A). Subsequently, a proof-of-concept human study was implemented as part of the miGut Health project for clinical correlation (Part B). Methods A) C57BL/6 mice are either bred and kept under standard diet (SD, containing wheat) or GFD followed by induction of dextran sodium sulfate (DSS) colitis, a murine model for ulcerative colitis. Relative loss of bodyweight and mean endoscopic colitis score are measured. For characterization of the microbiota impact, murine stool transplantation into germ free mice and 16s RNA analyzes are performed. B) An investigator-initiated prospective clinical trial with one interventional arm in IBD patients will be performed at the University Medical Center Hamburg-Eppendorf to investigate a 1.5-year long wheat protein-free diet in patients with inflammatory bowel disease (IBD) including ulcerative colitis (UC), Crohn’s disease (CD) and PSC-associated IBD (PSC-IBD), n=20 each. Effects of the GFD on intestinal cell composition and state, intestinal fecal and mucosal microbiota composition will be assessed as well as the dietary impact on IBD activity using colonoscopy and biomarkers of intestinal inflammation and on symptoms and health-related quality of life. Results A) Gluten aggravates murine DSS-colitis and long-term GFD (LT-GFD) protects mice from gluten aggravated colitis susceptibility. More importantly, preliminary data in germ-free settings support that this effect is mediated through microbiota alterations during the LT-GFD. 16s RNA sequencing data from murine stool showed different relative bacterial abundance. B) The study protocol received formal ethical approval by the ethics committee of the Hamburg Medical Association, Hamburg, Germany. Patient recruitment has started and is ongoing. Conclusion These primary results underline a potential role of gut microbiota modulation for the positive effect of a GFD on gastrointestinal symptoms in IBD. Long-term tolerability and efficacy of the dietary intervention in IBD patients remain to be seen.

In vitro evaluation of the immunomodulatory and antibacterial activities of calcitriol (1,25-dihydroxy-vitamin D3) as a potential application for aerobic vaginitis treatment - preliminary study results

BackgroundAerobic vaginitis (AV) is a state of abnormal vaginal microbiota, which is associated with increased numbers of aerobic, enteric bacteria and inflammation of the vaginal epithelium. Anti-microbial treatment combined with anti-inflammatory therapy could be useful in the treatment of this condition. It is known that calcitriol, the active form of vitamin D, plays an important role in modulating the immune response in several inflammatory diseases. The aim of this preliminary study was to evaluate in vitro the influence of calcitriol on the immune response of human vaginal epithelial cells to bacterial infection. Moreover, we assessed the anti-bacterial properties of calcitriol, as well as its synergistic activity with antibiotics that are used for the treatment of AV.ResultsHuman vaginal A431 epithelial cells were treated with calcitriol (100 nM) and then stimulated with thermally inactivated strains of AV-associated bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus agalactiae), or first stimulated with heat-treated bacteria and then incubated with calcitriol (30 nM). After 24 h, 48 h, and 72 h post-infection, culture supernatants were collected, and levels of pro-inflammatory cytokines IL-6 and IL-1β were analyzed using enzyme-linked immunosorbent assays (ELISA). As it turned out, calcitriol treatment pre- or post-bacterial stimulation of vaginal epithelial cells significantly decreased the levels of IL-6 and IL-1β compared to cells stimulated only with bacteria. Downregulation of pro-inflammatory cytokines was more frequently significant when cells were pre-treated with calcitriol. Additionally, this study evaluated the anti-bacterial properties and synergistic activity of calcitriol with antibiotics by determining the Minimal Inhibitory Concentration (MIC) using colorimetric, Resazurin-based microdilution method detecting the active metabolism of bacteria. As a result, calcitriol by itself did not exhibit clinically relevant anti-bacterial activity; however, when combined with antibiotics, calcitriol significantly reduced the MIC values.ConclusionsThe results of this preliminary study confirm that calcitriol treatment influences cytokine-mediated immune response during infection and indicate that it can be effective in enhancing antibiotic activity. Such properties could be very useful in the treatment of inflammatory diseases. However, conclusions regarding the potential use of calcitriol in the treatment of AV require further confirmation in in vivo studies as well as in well-designed clinical trials.

Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice.

Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases.

Downregulation of proinflammatory cytokines and dynamic expression of TGF-β1 molecules induced by anti-IL-17 mAb in murine schistosomiasis mansoni

Hepato-intestinal schistosomiasis is characterized by severe pathological changes at advanced chronic stages, including granulomatous lesions and liver fibrosis. The objective of our research was to assess the dynamic expression of profibrotic molecules, the transforming growth factor beta 1 (TGF-β1), and proinflammatory cytokines immunomodulation induced by interleukin 17 (IL-17) neutralization in murine Schistosomiasis mansoni. The study included 56 specific pathogen-free male C57BL/6 mice, divided into 3 main groups: GI uninfected normal controls, GII S. mansoni infected with 70±5 cercariae/non-treated, GIII S. mansoni infected and treated with anti-IL-17 monoclonal antibody (mAb), GIV S. mansoni infected and isotype-matched IgG2a mAb was given as a challenge. Mice were sacrificed at 6, 8, and 10 weeks after infection, then their liver enzymes and cytokines assessed, histopathological and immunohistochemical tested. The present study demonstrated a statistically significant elevation in serum levels of IL-17 (p<0.01), TGF-β1 (p<0.01), IL-1β (p≤0.001), IL-4 (p≤0.003), IL-6 (p≤0.05), and liver enzymes (ALT: p≤0.001; AST: p≤0.002). Additionally, granulomatous lesions and TGF-β1 expression were significantly increased (p<0.001) in infected mice at 6, 8, and 10 weeks after infection. All showed significant reduction by neutralization with anti-IL-17 mAb. Finally, IL-17 exhibited potent profibrogenic activity, and anti-IL-17 mAb can be used to alleviate and counteract this impact in murine S. mansoni.

An Oral H2S Responsive Cu5.4O Nanozyme Platform with Strong ROS/H2S Scavenging Capacity for the Treatment of Colitis.

Inflammatory bowel disease involves excess reactive oxygen species (ROS) and hydrogen sulfide (H2S) at inflammatory sites. Nanozyme-mediated ROS and H2S scavenging therapy is promising for colitis treatment. Here, we synthesized a multiple ROS scavenging Cu5.4O nanoparticle and first explored its H2S scavenging capacity. Chitosan oligosaccharide modified with alpha-lipoic acid was coated on the nanoparticles to further enhance the H2S scavenging capacity. Furthermore, calcium alginate was coated on the surface to develop an oral nanoplatform (Cu5.4O@SAG) possessing dual-pH/H2S-responsive release characteristics. Importantly, Cu5.4O@SAG exhibited enrichment at the colonic inflammation site and relieved the inflammatory index, containing the recovery of colon length, spleen index, liver index, and body weight, as well as inflammatory cell infiltration. In vivo and in vitro experiments revealed the dual ROS and H2S scavenging capacities of the nanoplatform. Additionally, Cu5.4O@SAG regulated tight junctions, mucus layers, and gut microbiota, which was accompanied by the downregulation of inflammatory cytokines. Notably, Cu5.4O@SAG also had excellent biocompatibility. In conclusion, this oral multiple-scavenging nanozyme platform provides a new and safe paradigm for the development of nanozymes for colitis treatment.

Omega-3 long chain fatty acids and their metabolites in pregnancy outcomes for the modulation of maternal inflammatory- associated causes of preterm delivery, chorioamnionitis and preeclampsia

Preterm birth is a major cause of perinatal complications and neonatal deaths. Furthermore, in the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre- eclampsia remain to be serious complications during pregnancy and represent a major psychological, financial, and economic burden for society. Several published guidelines, studies and recommendations have highlighted the importance of supplementation of omega-3 long chain polyunsaturated fatty acids (PUFAs) during pregnancy. This narrative review aims at giving an overview on the modern perception of inflammatory processes and the role of specialized pro-resolving mediators (SPMs) in their resolution, especially in obstetrics. Additionally, we highlight the possible role of SPMs in the prevention of obstetric complications through oral supplementation using enriched marine oil nutritional’s. The intake of PUFAs may result in an overall improvement of pregnancy outcomes by contributing to fetal brain growth and neurological development but more importantly though modulation of inflammation-associated pathologies. Especially the use of SPMs represents a promising approach for the management of obstetric and perinatal complications. SPMs are monohydroxylates derived from enriched marine oil nutritional’s that involve certain pro-resolutive metabolites of omega-3 long chains PUFAs and may contribute to an attenuation of inflammatory diseases. This may be obtained through various mechanisms necessary for a proper resolution of inflammation such as the termination of neutrophil tissue infiltration, initiation of phagocytosis, downregulation of pro-inflammatory cytokines or tissue regeneration. In this way, acute and chronic inflammatory diseases associated with serious obstetrical complications can be modulated, which might contribute to an improved pregnancy outcome.

Curcumin: a potent anti-inflammatory agent for the management of chronic inflammatory diseases

Chronic inflammation plays a critical role in the progression of several debilitating conditions, including diabetes, cancer, cardiovascular diseases, neurological disorders, and autoimmune diseases. As a result, targeting inflammation has become a key therapeutic approach for managing these diseases. Curcumin, a bioactive compound derived from turmeric (Curcuma longa), has garnered significant interest due to its potent anti-inflammatory and antioxidant properties.Curcumin exerts its effects by modulating various molecular pathways involved in inflammation, including the downregulation of pro-inflammatory cytokines and transcription factors such as NF-?B. Its ability to inhibit oxidative stress further enhances its therapeutic potential. Preclinical and clinical studies have shown promising results in the use of curcumin for managing inflammatory conditions like arthritis, inflammatory bowel disease, and metabolic syndrome.Despite its potential, curcumin’s clinical applicability is limited by its low bioavailability, which has led to the development of novel delivery systems such as nanoparticles, liposomes, and curcumin analogs to enhance absorption and efficacy.This review aims to summarize the current evidence on curcumin’s anti-inflammatory properties and its medical applications, highlighting its role as a natural and safe therapeutic agent for combating chronic inflammatory diseases. Future research is warranted to further optimize its clinical efficacy and formulations.

Carvone-loaded chitosan nanoparticles alleviate joint destruction by downregulating the expression of pro, inflammatory cytokines and MMP-13 in adjuvant-induced rat model.

Rheumatoid arthritis is an autoimmune illness causing deformity, edema, and joint tenderness. Its long-term treatment burdens the healthcare system and leads to toxicity, and thus, finding safe, effective, and affordable therapies is essential. The current study aimed to exhibit the anti-arthritic activity of Carvone-loaded chitosan nanoparticles to treat Freund's complete adjuvant (FCA) arthritis in rats. Healthy albino rats (n = 35) were distributed into seven groups. The 1st group worked as normal control, while the 2nd was arthritic control. The 3rd group received methotrexate (10mg/kg/week). The 4th group received Carvone (60mg/kg/day), while the 5th (30mg/kg/day), 6th (45mg/kg/day), and 7th (60mg/kg/day) groups received Carvone-C-NPs, respectively. Nanoparticles, prepared by the ion gelation method, were characterized by zeta size, potential, scanning electron microscopy, and Fourier transform infrared microscopy. NPs have zeta size (78.82 ± 0.02nm) and potential (19.96 ± 0.02mV). A significant reduction was shown in paw swelling (5.52 ± 0.05mm), arthritic score (2.81 ± 0.23), and rheumatoid factor (14.56 ± 0.68IU/L) by Carvone-C-NPs. qRT-PCR results showed significant down-regulation of pro-inflammatory cytokines [TNF-α (0.25 ± 0.03), IL-1β (0.21 ± 0.06), IL-17a (0.16 ± 0.12), and IL-33 (0.15 ± 0.01)] and up-regulation of anti-inflammatory cytokines [IL-4 (0.85 ± 0.06) and IL-10 (0.66 ± 0.04)] in ankle joint of Carvone-C-NPs treated group. The radiographical and histopathological findings showed reduced pannus formation, joint swelling, and synovial hyperplasia in the Carvone-C-NPs treated group. Overall, it is concluded that Carvone-C-NPs have remarkable anti-arthritic activity and promising anti-inflammatory properties.

Oligochitosan Mitigates Vibrio harveyi Infection in Hybrid Groupers (Epinephelus lanceolatus ♂ × Epinephelus fuscoguttatus ♀) by Modulating Immune Responses and Disease-Related Pathways

Vibrio harveyi is an important pathogen causing enteritis in hybrid groupers. However, its effects on the intestinal microbiota and the regulatory effects of oligochitosan on Vibrio-infected groupers are unclear. In this study, we investigated the effects of infection with V. harveyi and oligochitosan administration on the growth performance, immune responses, and intestinal transcriptome profiles of hybrid groupers during a 60-day rearing period. Growth parameters were reduced in Vibrio-infected groupers, while oligochitosan improved the body weight. Biochemical analysis showed reduced antioxidant enzyme activity and increased lipid peroxidation in Vibrio-infected groupers, which were consequently improved by oligochitosan. Transcriptome analysis was used to identify differentially expressed genes in the disease-related and immune system pathways that significantly accumulated in the treatment groups. An evaluation of the immune response showed a significant down-regulation of proinflammatory cytokines, antioxidant genes, and tight-junction proteins in Vibrio-infected groupers, which was partially restored by oligochitosan. Additionally, intestinal apoptosis, indicated by TUNEL signaling, was observed to significantly increase in Vibrio-infected groupers and was subsequently alleviated by oligochitosan supplementation. These results demonstrate the detrimental effects of V. harveyi infection on the growth and immune function of hybrid groupers and the potential of oligochitosan to attenuate these effects.

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Broad-spectrum downregulation of inflammatory cytokines by polydopamine nanoparticles to protect the injured spinal cord.

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

Gene expression profiling of indigenous Tharparkar and crossbred Vrindavani cattle affected with lameness using PBMC model.

Lameness is an economically significant, production-limiting syndrome that adversely affects the (re)production performance of animals besides deteriorating the quantity and quality aspects of milk in dairy cattle. The present study aimed to explore the potential biomarkers for painful foot lesions in indigenous Tharparkar and crossbredVrindavani cattle affected with lameness. The differentially expressed genes in lame versus healthy animals were elucidated using microarray analysis and validated them by qRT-PCR. On microarray analysis, 504 genes were differentially expressed in lame crossbred cattle as compared to healthy counterparts. Similarly, 991 genes were differentially expressed in lame crossbred cattle as compared to the healthy Tharparkar animals. Various genes such as BOLA-DQA3, BOLA-DQA1, CCL4, CCR1, CCRL2, CXCL2, CXCL3, CXCL8, IL1A, IL1B, MMP-9 and SLC11A1 were common between both the comparisons (crossbred lame vs. crossbred normal cattle; and crossbred lame vs. normal Tharparkar cattle). The results revealed downregulation of multiple pro-inflammatory cytokines. Validation using qRT-PCR showed high correlation with the microarray results, except for the IRAK1 gene. The functional annotation and gene network analysis revealed involvement of various processes including inflammation, immunology, apoptosis, cell proliferation and cytoskeleton organization. The Ingenuity pathway analysis revealed three inhibited pathways in the comparison between lame and normal (healthy) crossbred cattle i.e., HMGB1-signalling pathway, Aryl hydrocarbon receptor signalling pathway, and Mitotic roles of pol-like kinase. Whereas, on comparison of lame crossbred with healthy Tharparkar cattle, the Situin signalling pathway was inhibited; the LxR/RxR activation pathway was activated. The results from microarray analysis, identifying differential expressed genes provides valuable insights into the development of molecular biomarkers for early detection of lameness-affected animals.

Stilbene-enriched extract from the leaves of Cajanus cajan attenuates psoriasis in imiquimod-induced psoriatic mice by targeting aryl hydrocarbon receptor and chemokines

Ethnopharmacological relevanceThe leaves of Cajanus cajan (L.) Millsp., an Asian traditional folkloric medicine, have been used to treat inflammatory conditions since ancient times. In Southern China, these leaves have been employed to alleviate the symptoms associated with various skin diseases. However, the therapeutic effects and the underlying mechanisms of Cajanus cajan leaves in the treatment of psoriasis remain poorly understood. Aim of the studyThis study aims to investigate the efficacy of stilbene-enriched extract from C. cajan leaves (termed as “EXT”) in treating imiquimod (IMQ)-induced psoriatic mice and to elucidate its possible underlying mechanism in psoriasis treatment. Materials and methodsThe coumpounds of EXT was analyzed through a UPLC-MS system, the MS survey scan was conducted across the mass range of m/z 100–1000 Da. The activation of aryl hydrocarbon receptor (AhR), a potential therapeutic target, by EXT in HaCaT cells was assessed using RT-qPCR and immunofluorescence. Subsequently, EXT was administrated to IMQ-induced psoriatic mice once daily for 10 days. The efficacy of EXT in treating psoriasis was evaluated through pathological analysis including change of weight, PASI score, Baker score, epidermal thickness, and H&E staining of lesion skin. Additionally, transcriptomic analysis of lesion skins was conducted to identify the potential therapeutic targets and possible mechanisms of EXT in psoriasis treatment. ResultsIt was identified that the primary stilbenes present in EXT were 3.10% pinosylvin monomethyl ether (PME), 12.32 % cajaninstilbene (CSA), 4.54 % ongistylin A (LGA) and 2.43 % longistylin C (LGC). In cellular tests, the addition of 2.5 μg/mL EXT to HaCaT cells enhanced the expression of AhR and its nuclear translocation. In vivo tests of EXT in IMQ-induced psoriasis mouse model, 50 mg 1.0 % EXT reduced PASI and Baker score of lesion skin to 2.67 and 4.5, respectively. In addition, the epidermis thickness of lesion skin induced by IMQ returned to normal following the application of 50 mg 1.0 % EXT in psoriatic mice. Transcriptomic profiling revealed significant downregulation of numerous chemokines (Ccl2, Ccl20, and Cxc5, etc.), pro-inflammatory cytokines (Il17a, Il19, Il22, and Il23, etc.), and genes associated with keratinocyte differentiation (Lce and Sprr family genes). Conversely, AhR and genes of the cytochrome P450 family were activated. ConclusionsThis study is the first to demonstrate that the ethyl acetate (EtOAc) extract enriched with stilbenes from Cajanus cajan leaves (EXT) effectively alleviates symptoms in IMQ-induced psoriatic mice. The mechanism involves the activation of the aryl hydrocarbon receptor (AhR) and a subsequent reduction in the production of various inflammatory chemokines and cytokines. These findings suggest that EXT holds significant potential as a plant-derived therapeutic agent for the treatment of psoriasis.

Broad-Spectrum Bactericidal Multifunctional Tiny Silicon-Based Nanoparticles Modified with Tannic Acid for Healing Infected Diabetic Wounds.

Infected chronic wounds, in particular, diabetic wounds, are hard to heal, posing a global health concern with high morbidity and mortality rates. Diabetic full-thickness wounds infected with E. coli belong to the most difficult to heal chronic infected wounds. Here, we introduced tannic acid-modified silicon-based nanoparticles (TA-SiNPs) with broad-spectrum bactericidal activity that bacteria develop minimal resistance to, and they can effectively treat full-thickness wounds in diabetic mice infected with E. coli. Our findings indicate that these TA-SiNPs could achieve 100% antibacterial efficiency against S. aureus and 99.83% against E. coli, underlied by a positive surface charge and tannic acid groups facilitating bacterial membrane chemical composition depletion and depolarization of the membrane. In addition, we showed that spraying TA-SiNPs onto the skin wound of diabetic mice infected with E. coli resulted in wound healing with 98% closure after 12 days, in stark contrast to 49% of the control (PBS) and 68% of the one treated with Ofloxacin. Along with infection inhibition and ROS scavenging, we identified cell proliferation stimulation, inflammatory cytokine downregulation, and healing cytokine upregulation in the lesion, favoring the healing process. This study not only demonstrates the feasibility of employing silicon-based nanoparticles in diabetic wound healing for the first time, but also reports the first broad-spectrum bactericidal silicon nanodots. Furthermore, this provides novel insights into the mechanism of tannin-based nanoparticles disrupting bacterial membranes by depleting their chemical constituents. Our results highlighted that the developed TA-SiNPs are an effective nanomaterial for treating the infected chronic wounds.

Enriched marine oil supplements in pregnancy for the modulation of maternal inflammatory- associated causes of preterm delivery

Preterm birth is a major cause of perinatal complications and neonatal deaths. Furthermore, in the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre- eclampsia remain to be serious complications during pregnancy and represent a major psychological, financial, and economic burden for society. Several published guidelines, studies and recommendations have highlighted the importance of supplementation of omega-3 long chain polyunsaturated fatty acids (PUFAs) during pregnancy. This narrative review aims at giving an overview on the modern perception of inflammatory processes and the role of specialized pro-resolving mediators (SPMs) in their resolution, especially in obstetrics. Additionally, we highlight the possible role of SPMs in the prevention of obstetric complications through oral supplementation using enriched marine oil nutritional’s. The intake of PUFAs may result in an overall improvement of pregnancy outcomes by contributing to fetal brain growth and neurological development but more importantly though modulation of inflammation-associated pathologies. Especially the use of SPMs represents a promising approach for the management of obstetric and perinatal complications. SPMs are monohydroxylates derived from enriched marine oil nutritional’s that involve certain pro-resolutive metabolites of omega-3 long chains PUFAs and may contribute to an attenuation of inflammatory diseases. This may be obtained through various mechanisms necessary for a proper resolution of inflammation such as the termination of neutrophil tissue infiltration, initiation of phagocytosis, downregulation of pro-inflammatory cytokines or tissue regeneration. In this way, acute and chronic inflammatory diseases associated with serious obstetrical complications can be modulated, which might contribute to an improved pregnancy outcome.

Alginate from Ericaria crinita Possesses Antioxidant Activity and Attenuates Systemic Inflammation via Downregulation of Pro-Inflammatory Cytokines.

Alginates are anionic polysaccharides present in the cell walls of brown seaweeds. Various biological activities of alginate and its derivatives have been described. In this study, we assessed the potential of alginate obtained from Ericaria crinita (formerly Cystoseira crinita) to scavenge free radicals and function as a ferric ion reductor. The anti-inflammatory effect on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment was also examined. Ericaria crinita alginate showed antioxidant activities of IC50 = 505 µg/mL (DPPH) and OD700 > 2 (ferric reducing power). A significant decrease in serum levels of IL-1β was observed only in animals treated with the polysaccharide at a dose of 100 mg/kg bw. Both doses of E. crinita alginate (25 and 100 mg/kg bw) significantly reduced the serum concentrations of pro-inflammatory cytokines TNF-α and IL-6, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. Our findings show the potential of E. crinita alginate to act as an antioxidant and anti-inflammatory agent. It is likely that the exhibited antioxidant ability of the polysaccharide contributes to its antiphlogistic effects. More in-depth studies are needed to fully understand the specific mechanisms and the molecular pathways involved in these activities.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

A Synbiotic Combining Chitin-Glucan and Lactobacillus acidophilus NCFM Induces a Colonic Molecular Signature Soothing Intestinal Pain and Inflammation in an Animal Model of IBS.

Chitin-glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1β, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes.

The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE2 synthesis by keratinocytes.

Erythema, characterized by the redness of the skin, is a common skin reaction triggered by various endogenous and exogenous factors. This response is often a result of the activation of underlying inflammatory mechanisms within the skin. The objective of this study is to investigate the potential benefits of applying a combination of skincare ingredients, namely allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate (AB5D), in the modulation of inflammatory factors associated with erythema. Additionally, the study aims to elucidate the mechanisms by which these ingredients exert their combined actions to alleviate erythema-associated inflammation. Human epidermal keratinocytes were exposed to UVB and subsequently treated with AB5D. Transcriptomics profiling was performed to analyse the dose-response effect of AB5D treatment on keratinocytes. The quantitation of inflammatory mediators, including PGE2, IL-1α, IL-6, IL-8, IL-1RA and TNFα, was performed on cultured media. Additionally, the oxygen radical absorbance capacity (ORAC) assay was carried out to evaluate the total antioxidant capacity of both individual ingredients and the AB5D combination. To assess the in-vitro antioxidant effects of AB5D against UVB-induced oxidative stress in hTERT keratinocytes, real-time quantitation of mitochondrial superoxide was measured through live-cell imaging. The application of AB5D to UVB-exposed keratinocytes downregulated gene sets associated with inflammatory responses, highlighting the anti-inflammatory properties of AB5D. Specifically, AB5D effectively reduced the production of PGE2, leading to the downregulation of inflammatory cytokines. Moreover, our findings indicate that AB5D exhibits antioxidative capabilities, functioning as both an antioxidant agent and a regulator of antioxidant enzyme expression to counteract the detrimental effects of cellular oxidative stress. We demonstrated that AB5D can reduce UVB-induced PGE2, IL-1α, IL-6, IL-8, IL-1RA and TNFα as well as mitochondrial superoxide. These findings suggest that AB5D may alleviate erythema by modulating inflammation via PGE2 and through antioxidation mechanisms.