Modulation Of Inflammatory Response Research Articles

Scalp acupuncture alleviates remote hippocampal damage in MCAO rats by inhibiting neuroinflammation: A TMT-based proteomics analysis

While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO). Moreover, 74 upregulated and 50 downregulated proteins were identified in the MCAO group compared to the sham group, whilst 52 up-regulated and 50 down-regulated proteins were identified in the SA group compared to the MCAO group. Bioinformatics analysis indicated that SA may exert neuroprotective effects by modulating the acute inflammatory response and microglial activation. Additionally, SA down-regulated the expression levels of Iba-1, TNF-α, IL-1β, and IL-6, while up-regulating those of IL-4 and IL-10. Likewise, it downregulated the expression levels of three key proteins identified via proteomics analysis (Kng1, Brd9, and Magl) that may mediate the anti-inflammatory effects of SA. Overall, these results indicate that SA attenuates neuronal damage in the hippocampus and ischemic penumbra and ameliorates neurological deficits. Proteomic analysis suggested that this effect is related to the modulation of the acute inflammatory response. SA attenuated remote hippocampal damage after IS by inhibiting microglia activation and neuroinflammation. Lastly, Kng1, Brd9, and Magl were identified as potential targets that mediate the anti-inflammatory effects of SA.

B cell c-Maf signaling promotes tumor progression in animal models of pancreatic cancer and melanoma

BackgroundThe role of B cells in antitumor immunity remains controversial, with studies suggesting the protumor and antitumor activity. This controversy may be due to the heterogeneity in B cell populations,...

Xanthohumol: Anti-Inflammatory Effects in Mechanically Stimulated Periodontal Ligament Stem Cells

Background/Objectives: Initial sterile inflammation is an essential molecular process in the periodontium during orthodontic tooth movement. A better understanding and possible modulations of these processes are of great interest to develop individual therapies for special patient groups. The prenylated plant polyphenol xanthohumol (XN) could have modulating effects as it has shown anti-inflammatory and angiogenesis-inhibiting effects in various cell lines. This study investigated the anti-inflammatory properties of XN in an in vitro model of compressively stimulated human periodontal ligament stem cells (hPDLSCs), which have a different function in the periodontium than the previously used cementoblasts. Methods: The expression of inflammatory markers at the mRNA and protein levels and the regulation of central kinases were investigated. Results: XN showed a dose-dependent influence on cell viability. Low concentrations between 0.2 and 4 µM showed positive effects, while 8 µM caused a significant decrease in viability after 24 h. Mechanical stimulation induced an upregulation of pro-inflammatory gene (IL-6, COX2) and protein (IL-6) expression. Here, XN significantly reduced stimulation-related IL-6 mRNA and gene expression. Furthermore, the phosphorylation of AKT and ERK was upregulated by mechanical stimulation, and XN re-established phosphorylation at a level similar to the control. Conclusions: We demonstrated a selective anti-inflammatory effect of XN in hPDLSCs . These findings provide the basis for further investigation of XN in the modulation of inflammatory responses in orthodontic therapy and the treatment of periodontal inflammation.

Impact of Immunosenescence on Vaccine Immune Responses and Countermeasures.

The biological progression of aging encompasses complex physiological processes. As individuals grow older, their physiological functions gradually decline, including compromised immune responses, leading to immunosenescence. Immunosenescence significantly elevates disease susceptibility and severity in older populations while concurrently compromising vaccine-induced immune responses. This comprehensive review aims to elucidate the implications of immunosenescence for vaccine-induced immunity and facilitate the development of optimized vaccination strategies for geriatric populations, with specific focus on COVID-19, influenza, pneumococcal, herpes zoster, and respiratory syncytial virus (RSV) vaccines. This review further elucidates the relationship between immunosenescence and vaccine-induced immunity. This review presents a systematic evaluation of intervention strategies designed to enhance vaccine responses in older populations, encompassing adjuvant utilization, antigen doses, vaccination frequency modification, inflammatory response modulation, and lifestyle interventions, including physical activity and nutritional modifications. These strategies are explored for their potential to improve current vaccine efficacy and inform the development of next-generation vaccines for geriatric populations.

Research progress in molecular mechanism of acupuncture for diabetes mellitus

This paper discusses the mechanism of acupuncture for diabetes mellitus from the perspective of molecular biology, aiming to reveal the potential rules of restoring the balance in the body and fighting against diabetes mellitus (DM). By searching the basic research literature of acupuncture treatment for DM, it is found that the molecular biological mechanism of acupuncture treatment for DM is closely related to the regulation of insulin signaling pathway, the modulation of inflammatory response, the protection and regeneration of islet β-cells, fat metabolism and energy balance. It points out that there are few studies of acupuncture on the type 1 diabetes mellitus and the large-scale randomized controlled trials, as well as the studies on the upstream regulation mechanism, the specific cellular molecules and the interaction mechanism of various molecules. It needs to deepen the multi-level, multi-target and multi-dimensional exploration on the molecular biological mechanism of acupuncture for diabetes mellitus.

The ketogenic diet modulates tumor-associated neutrophil polarization via the AMOT-YAP/TAZ axis to inhibit colorectal cancer progression

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), the prognosis for late-stage patients remains poor, highlighting the urgent need for new preventive and therapeutic strategies. Recent studies have focused on the ketogenic diet (KD) and its metabolite, β-hydroxybutyrate (BHB), for their tumor-suppressive effects and modulation of inflammatory responses. Using the azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced mouse CRC model, we found that the ketogenic diet and BHB inhibit pro-tumor N2-type tumor-associated neutrophils (TANs) while promoting the polarization of TANs towards the anti-tumor N1 type. This shift in TANs polarization affects tumor growth and metastasis. The underlying mechanism involves BHB acting on the intracellular receptor histone deacetylases 3 (HDAC3), which modulates the activation of the AMOT-YAP/TAZ axis, leading to the inhibition of pro-carcinogenic factor transcription and release. Moreover, clinical cohort data corroborate these findings, showing that CRC patients with elevated BHB levels have significantly lower rates of lymph node involvement, which is associated with a higher infiltration ratio of anti-carcinogenic N1-type TANs in the tumor microenvironment (TME). These results suggest that BHB levels could serve as a prognostic biomarker for CRC. In conclusion, our findings indicate that BHB derived from KD regulates TANs polarization in CRC via the HDAC3-AMOT-YAP/TAZ axis, effectively inhibiting tumor growth and metastasis. These insights establish a novel theoretical basis for employing the KD in the treatment of CRC and for developing cancer adjuvant immunotherapy strategy based on the polarization of neutrophils.

Aquaporins in sepsis- an update.

Aquaporins (AQPs), a family of membrane proteins that facilitate the transport of water and small solutes, have garnered increasing attention for their role in sepsis, not only in fluid balance but also in immune modulation and metabolic regulation. Sepsis, characterized by an excessive and dysregulated immune response to infection, leads to widespread organ dysfunction and significant mortality. This review focuses on the emerging roles of aquaporins in immune metabolism and their potential as therapeutic targets in sepsis, with particular attention to the modulation of inflammatory responses and organ protection. Additionally, it explores the diverse roles of aquaporins across various organ systems, highlighting their contributions to renal function, pulmonary gas exchange, cardiac protection, and gastrointestinal barrier integrity in the context of sepsis. Recent studies suggest that AQPs, particularly aquaglyceroporins like AQP3, AQP7, AQP9, and AQP10, play pivotal roles in immune cell metabolism and offer new therapeutic avenues for sepsis treatment. In the context of sepsis, immune cells undergo metabolic shifts to meet the heightened energy demands of the inflammatory response. A key adaptation is the shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, where pyruvate is converted to lactate, enabling faster ATP production. AQPs, particularly aquaglyceroporins, may facilitate this process by transporting glycerol, a substrate that fuels glycolysis. AQP3, for example, enhances glucose metabolism by transporting glycerol and complementing glucose uptake via GLUT1, while also regulating O-GlcNAcylation, a post-translational modification that boosts glycolytic flux. AQP7 could further contributes to immune cell energy production by influencing lipid metabolism and promoting glycolysis through p38 signaling. These mechanisms could be crucial for maintaining the energy supply needed for an effective immune response during sepsis. Beyond metabolism, AQPs also regulate key immune functions. AQP9, highly expressed in septic patients, is essential for neutrophil migration and activation, both of which are critical for controlling infection. AQP3, on the other hand, modulates inflammation through the Toll-like receptor 4 (TLR4) pathway, while AQP1 plays a role in immune responses by activating the PI3K pathway, promoting macrophage polarization, and protecting against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). These insights into the immunoregulatory roles of AQPs suggest their potential as therapeutic targets to modulate inflammation in sepsis. Therapeutically, AQPs present promising targets for reducing organ damage and improving survival in sepsis. For instance, inhibition of AQP9 with compounds like HTS13286 or RG100204 has been shown to reduce inflammation and improve survival by modulating NF-κB signaling and decreasing oxidative stress in animal models. AQP5 inhibition with methazolamide and furosemide has demonstrated efficacy in reducing immune cell migration and lung injury, suggesting its potential in treating acute lung injury (ALI) in sepsis. Additionally, the regulation of AQP1 through non-coding RNAs (lncRNAs and miRNAs) may offer new strategies to mitigate organ damage and inflammatory responses. Moreover, AQPs have emerged as potential biomarkers for sepsis progression and outcomes. Altered expression of AQPs, such as AQP1, AQP3, and AQP5, correlates with sepsis severity, and polymorphisms in AQP5 have been linked to better survival rates and improved outcomes in sepsis-related acute respiratory distress syndrome (ARDS). This suggests that AQP expression could be used to stratify patients and tailor treatments based on individual AQP profiles. In conclusion, AQPs play a multifaceted role in the pathophysiology of sepsis, extending beyond fluid balance to crucial involvement in immune metabolism and inflammation. Targeting AQPs offers novel therapeutic strategies to mitigate sepsis-induced organ damage and improve patient survival. Continued research into the metabolic and immune functions of AQPs will be essential for developing targeted therapies that can be translated into clinical practice.

Rodent Model of Cardiopulmonary Bypass Demonstrates Systemic Inflammation and Neuromarker Changes

IntroductionThe physiologic derangements imposed by cardiopulmonary bypass (CPB) can result in complications such as postoperative delirium. We aim to validate a rodent survival model of CPB demonstrating a systemic inflammatory response and hypothesize that this contributes to post-CPB delirium. MethodsAdult Sprague–Dawley rats were randomized to three groups: 1) Sham peripheral surgical cannulation, 2) CPB followed by acute phase harvest, or 3) CPB followed by 24-h survival. CPB was carried out for 60 min before decannulation and weaning from mechanical ventilation. Physiological and biochemical endpoints were compared between groups. Gene expression analysis of hippocampal tissue was performed using quantitative RT-PCR panels and protein expression levels were confirmed with Western blot. ResultsSixteen animals underwent cannulation and were successfully decannulated without transfusion requirement or inotrope use with one procedure-related mortality. Serum acute phase proinflammatory chemokines cytokine-induced neutrophil chemoattractant 1, cytokine-induced neutrophil chemoattractant 3, fractalkine, and lipopolysaccharide-induced CXC chemokine as well as interleukin (IL)-10 were increased 1 h following CPB compared to sham (P < 0.05). Significant changes in hippocampal expression of biomarkers apolipoprotein 1, vascular epithelial growth factor A, and synapsin 1 were demonstrated following CPB. ConclusionsThis study validated a model of CPB that captures the resultant systemic inflammatory response, and identified differentially expressed proteins that may be associated with brain injury. Modulation of the CPB-induced inflammatory response may be a promising therapeutic target to attenuate post-CPB delirium, and this survival rat model of CPB with low surgical attrition will allow for more comprehensive evaluations of the short- and long-term effects of both CPB and potential therapeutic interventions.

1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.

Sepsis is a complex disorder caused by a dysregulated host response to infection, with high levels of morbidity and mortality. Treatment aimed to modulate immune response and maintain vascular function is still one of the major clinical challenges. This study was designed to test the effect of the small molecule 1-Piperidine Propionic Acid (1-PPA) as molecular targeted agent to block protease-activated receptor 2 (PAR2), one of the major modulators of inflammatory response in LPS-induced experimental endotoxemia. In the THP-1 cell line, LPS-induced cytokine expression was inhibited by 1-PPA in a dose-dependent manner. In LPS-injected mice, treatment with 1-PPA was effective in reducing mortality and sepsis-related symptoms and improved cardiac function parameters. After 6 h from LPS injection, a significant decrease in IL-6, IL-1β, and IL-10 was observed in the lung tissue of 1-PPA-treated mice, compared to controls. In these mice, a significant decrease in vasoactive molecules, especially kininogen-1, was also observed, mainly in the liver. Histopathological analysis confirmed typical features of sepsis in different organs and these findings were markedly reduced in mice treated with 1-PPA. These data demonstrate the effectiveness of 1-PPA in protecting the whole organism from sepsis-induced damage.

Research Progress of Acupuncture in the Treatment of Post-Stroke Depression

Post-stroke depression (PSD) is a prevalent complication in stroke survivors, characterized by persistent mood disorders that hinder rehabilitation and reduce quality of life. This study examines recent scholarly endeavors focusing on acupuncture (AC) as a feasible therapeutic approach for PSD. By analyzing contemporary literature, it elucidates the Traditional Chinese Medicine (TCM) perspective on PSD and evaluates AC's effectiveness. AC stands out as a promising modality of treatment owing to its potency and negligible side effects, with mechanisms including neurotransmitter modulation, neurotrophic factor regulation, neuronal apoptosis inhibition, inflammatory response modulation, and so on. This review offers valuable insights into PSD from a TCM perspective and highlights AC's potential as a therapeutic intervention, contributing to knowledge advancement and informing clinical practice in PSD management.

Regenerative Inflammation: The Mechanism Explained from the Perspective of Buffy-Coat Protagonism and Macrophage Polarization.

The buffy-coat, a layer of leukocytes and platelets obtained from peripheral blood centrifugation, plays a crucial role in tissue regeneration and the modulation of inflammatory responses. This article explores the mechanisms of regenerative inflammation, highlighting the critical role of the buffy-coat in influencing macrophage polarization and its therapeutic potential. Macrophage polarization into M1 and M2 subtypes is pivotal in balancing inflammation and tissue repair, with M1 macrophages driving pro-inflammatory responses and M2 macrophages promoting tissue healing and regeneration. The buffy-coat's rich composition of progenitor cells, cytokines, and growth factors-such as interleukin-10, transforming growth factor-β, and monocyte colony-stimulating factor-supports the transition from M1 to M2 macrophages, enhancing tissue repair and the resolution of inflammation. This dynamic interaction between buffy-coat components and macrophages opens new avenues for therapeutic strategies aimed at improving tissue regeneration and managing inflammatory conditions, particularly in musculoskeletal diseases such as osteoarthritis. Furthermore, the use of buffy-coat-derived therapies in conjunction with other regenerative modalities, such as platelet-rich plasma, holds promise for more effective clinical outcomes.

Isoorientin Improves Excisional Skin Wound Healing in Mice

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p &lt; 0.01) and control (p &lt; 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p &lt; 0.001) and increased collagen deposition (p &lt; 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response.

Bothrops atrox snake venom decreased MHC-II and CD86 expression in bone marrow-derived dendritic cells

The effect of Bothrops atrox venom (BaV) on the maturation of bone marrow-derived dendritic cells (BMDCs) from mice was investigated, with a focus on selected cell markers, TAP1 expression, and the release of pro-inflammatory cytokines during this process. The objective was to evaluate BaV's impact on dendritic cell (DC) function, as DCs are pivotal in antigen presentation and responsible for initiating the immune response mediated by naïve T cells, as well as regulating the immune system. Bone marrow cells were obtained from Swiss mice, and hematopoietic precursors were differentiated into BMDCs using GM-CSF and IL-4. On the 7th day, BaV and LPS were introduced into the culture, and the cells were analyzed 24 h later. BaV's ability to stimulate BMDC maturation was assessed through the analysis of surface marker expression. The findings demonstrated that BMDCs are highly influenced by culture environment factors, such as GM-CSF and IL-4, and are sensitive to additional stimuli like LPS and BaV. Mature DCs exhibited elevated levels of critical markers for T cell activation, such as MHC-II, CD80, and CD86, displaying specific phenotypic characteristics. However, the observed reduction in MHC-II and CD86 expression following BaV exposure suggests a substantial impact on the immunological activation capacity of these cells, potentially interfering with the adaptive immune response. Furthermore, the selective release of cytokines, such as IL-6, but not TNF-α or IL-1β, indicates differentiated modulation of inflammatory responses by DCs under various stimulation conditions.

Juruaça virus taxonomy, tolerance and resistance to infection, and inflammatory response modulation in murine model

Juruaça virus (JUAV), previously unclassified, was isolated from bats and administered to neonatal and adult BALB/c mice to investigate acute and chronic disease progression. In this study, we conducted genomic sequencing to achieve taxonomic classification and utilized these models to explore the inflammatory response and sickness behavior in both neonatal and adult mice. Neonates received a single intranasal instillation of infected brain homogenate (20 µL), whereas 31-day-old mice were given the same volume intranasally for three consecutive days. Control groups were administered equal volumes of uninfected brain homogenate. Our findings reveal that intranasal JUAV infection-induced acute meningoencephalitis and death in neonates, while adult mice exhibited chronic infection with variable clinical signs, inflammatory mediator production, histopathological changes, and neuropathological features. Interestingly, only some adult mice showed sickness behavior post-infection, and among these, a subset continued to decline and die. The differential tissue damage observed in mice with and without overt disease symptoms suggests mechanisms of resistance or tolerance, where exceeding tolerance capacity resulted in pathological outcomes, including chronic dysfunction or death. This study provides the first evidence of JUAV’s capability to infect mammals, demonstrating its distinct impact on bats and variable effects in neonatal and adult mice. We provisionally classified JUAV as closely related to the clade containing tombus-like virus 6 found in mute swan feces. Our research highlights the importance of understanding viral–host interactions and the inflammatory responses that contribute to disease variability, offering insights into tolerance and resistance mechanisms based on inflammatory response modulation.

Role of Mesenchymal Stem Cells Exosomes in Lipopolysaccharide-induced Acute Lung Injury in Rats, A Histological Study

Abstract Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a substantial disease burden in terms of both morbidity and mortality. And since 2019 this condition represented the leading cause of mortality in patients with severe COVID-19. Mesenchymal stem cells (MSCs) and their exosomes have shown promising results in the modulation of inflammatory responses. Exosomes, have been offering a powerful cell-free therapeutic modality, bypassing most of the safety concerns related to cell-based therapy. Lipopolysaccharide (LPS), a glycoprotein present in the cell wall of gram negative bacteria, could induce ALI in experimental animals, mimicking ARDS in humans. Aim Histological assessment of the potential role of exosomes derived from bone marrow MSCs in treatment of LPS-induced acute lung injury model in adult male albino rats. Materials &amp; Methods Thirty-five rats were used including 5 young aged albino rats that were sacrificed to harvest their bone marrow-derived MSCs and their exosomes. The remaining 30 adult male albino rats were divided into 3 groups. Group I (control group), Group II (LPS group): received a single intraperitoneal injection of LPS dissolved in PBS (6mg/kg). Group III (LPS+Exosomes group): received LPS as in group II followed by intravenous injection of Exosomes (30uL/rat), one hour later. Twenty-four hours later, lung specimens were processed for light &amp; electron microscopic examination, as well as morphometric and statistical analysis. Results H&amp;E-stained sections of Group II revealed marked inflammatory changes as interalveolar septa were significantly thickened by infiltrating inflammatory cells and extravasated red blood cells. Many alveoli appeared narrowed and collapsed while other alveolar spaces were dilated with destruction of the alveolar walls. Blood vessels were congested with thickened walls. The lining epithelium of bronchioles appeared occasionally desquamated and necrotic. Masson’s Trichrome-stained sections showed an apparent increase of collagen fibers around the bronchioles and in the interalveolar septa. Immunohistochemical stain showed a significantly increased reaction to iNOS antibodies in addition to a significantly increased Caspase-3 immune reactivity. Examination with Transmission electron microscopy showed Type I Pneumocyte having an electron dense nucleus and cytoplasmic vacuolations. Type II pneumocytes had degenerated lamellar bodies, many lysosomes and lost microvilli. Eosinophils were seen infiltrating the interstitium with their bilobed nucleus and specific granules with crystalline cores in addition to macrophages with large eccentric nucleus and many lysosomes. On the other hand, the lung structure in Group III showed significant improvement in all parameters. Conclusion The study showed that MSCs exosomes could help in treatment of ALI caused by LPS in rats. Group II showed signs of inflammation and lung damage in addition to increased inflammatory and apoptotic immune reactivity. However, in Group III, treatment with exosomes resulted in significant improvement in all previous parameters. This study highlights the potential of using mesenchymal stem cell exosomes as a treatment for ALI in animals and as a clinical trial.

The Impact of Preoperative and Postoperative Nutritional Interventions on Treatment Outcomes and Quality of Life in Colorectal Cancer Patients-A Comprehensive Review.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with high morbidity and mortality rates. Nutritional status has emerged as a significant factor influencing the prognosis and survival of CRC patients. This comprehensive literature review examines the role of nutritional support in improving treatment outcomes, including the efficacy of interventions, patient quality of life (QoL), and the modulation of inflammatory responses. The findings suggest that tailored nutritional interventions improve clinical outcomes, enhance QoL, and reduce treatment-related complications, particularly by attenuating inflammation. Furthermore, the review highlights the cost-effectiveness of nutritional strategies and identifies key methods to enhance patient compliance with dietary recommendations. In conclusion, integrating nutritional support into CRC treatment plans is crucial for optimizing clinical management and improving patient well-being.

Yeast β-glucan attenuates dextran sulfate sodium-induced colitis: Involvement of gut microbiota and short-chain fatty acids

Yeast β-glucan intervention offers a promising strategy for managing colitis; however, the mechanisms remain unknown. In the present work, the protective effects of yeast β-glucan on DSS-induced colitis in mice was evaluated, focusing on its interaction with gut microbiota. The result showed yeast β-glucan significantly alleviated colitis symptoms, evidenced by reduced weight loss, lower disease activity index (DAI) scores, and minimized intestinal damage. It enhanced intestinal barrier integrity via upregulation of tight junction proteins, suppressed lipopolysaccharide (LPS) release, and decreased pro-inflammatory cytokines production. Additionally, yeast β-glucan boosted short-chain fatty acids (SCFAs) production, and activated their receptors, increased the relative abundances of beneficial microbes like Lactobacillus and Lachnospiraceae_UCG-006. Transcriptomic analyses suggest that yeast β-glucan mitigates inflammation by downregulating gene expression related to IL-17 pathway. Our findings highlight potential of yeast β-glucan as a therapeutic agent for colitis through modulation of gut microbiota and inflammatory responses.

Mesenchymal Stem Cell-Conditioned Media-Loaded Microparticles Enhance Acute Patency in Silk-Based Vascular Grafts.

Coronary artery disease leads to over 360,000 deaths annually in the United States, and off-the-shelf bypass graft options are currently limited and/or have high failure rates. Tissue-engineered vascular grafts (TEVGs) present an attractive option, though the promising mesenchymal stem cell (MSC)-based implants face uncertain regulatory pathways. In this study, "artificial MSCs" (ArtMSCs) were fabricated by encapsulating MSC-conditioned media (CM) in poly(lactic-co-glycolic acid) microparticles. ArtMSCs and control microparticles (Blank-MPs) were incubated over 7 days to assess the release of total protein and the vascular endothelial growth factor (VEGF-A); releasates were also assessed for cytotoxicity and promotion of smooth muscle cell (SMC) proliferation. Each MP type was loaded in previously published "lyogel" silk scaffolds and implanted as interposition grafts in Lewis rats for 1 or 8 weeks. Explanted grafts were assessed for patency and cell content. ArtMSCs had a burst release of protein and VEGF-A. CM increased proliferation in SMCs, but not after encapsulation. TEVG explants after 1 week had significantly higher patency rates with ArtMSCs compared to Blank-MPs, but similar to unseeded lyogel grafts. ArtMSC explants had lower numbers of infiltrating macrophages compared to Blank-MP explants, suggesting a modulation of inflammatory response by the ArtMSCs. TEVG explants after 8 weeks showed no significant difference in patency among the three groups. The ArtMSC explants showed higher numbers of SMCs and endothelial cells within the neotissue layer of the graft compared to Blank-MP explants. In sum, while the ArtMSCs had positive effects acutely, efficacy was lost in the longer term; therefore, further optimization is needed.

Exploration of compounds to inhibit the Panton-Valentine leukocidin of Staphylococcus aureus

The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus is associated with necrotizing infections. After binding to complement 5a receptor (C5aR/CD88) and CD45 it causes cytolysis in polymorphonuclear neutrophils (PMNs) as well as inflammasome activation in monocytes. The objective of this study was to test if (ant)agonists of C5aR and CD45 can attenuate the effect of PVL on PMNs and monocytes. We tested the effect of various concentrations of six C5aR (ant)agonists (avacopan, BM213, DF2593A, JPE-1375, PMX205 and W-54011) and one CD45 antagonist (NQ301) to attenuate the cytotoxic effect of PVL on human PMNs and monocytes in vitro. Shifts in the half-maximal effective concentration (EC50) of PVL to achieve a cytotoxic effect on PMNs and modulation of inflammatory cytokine response from monocytes were determined by flow cytometry and IL-1β detection. Pre-treatment of PMNs with avacopan, PMX205 and W-54,011 resulted in 3.6- to 4.3-fold shifts in the EC50 for PVL and were able to suppress IL-1β secretion by human monocytes in the presence of PVL. BM213, DF2593A and NQ301 were unable to change the susceptibility of PMNs towards PVL or reduce inflammasome activation in monocytes. Avacopan, PMX205 and W-54,011 showed protection against PVL-induced cytotoxicity and suppressed IL-1β secretion by monocytes. Clinical studies are needed to prove whether these substances can be used therapeutically as repurposed drugs.

Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses

Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses