Anti-inflammatory Functions Research Articles

Regulation of Immune Inflammation and Promotion of Periodontal Bone Regeneration by Irisin-Loaded Bioactive Glass Nanoparticles.

Clinical solutions of bone defects caused by periodontitis involve surgical treatment and subsequent anti-infection treatment using antibiotics. Such a strategy faces a key challenge in that the excessive host immune response results in the damage of periodontal tissues. Consequently, it is of great importance to develop novel periodontitis treatment that allows the regulation of the host immune response and promotes the generation of periodontal tissues. Irisin has a good bone regeneration ability and could reduce the inflammatory reaction by regulating the differentiation of macrophages. In this study, we loaded irisin onto bioactive glass nanoparticles (BGNs) to prepare a composite, irisin-BGNs (IR-BGNs) with anti-inflammatory, bacteriostatic, and tissue regeneration functions, providing a novel idea for the design of ideal materials for repairing oral tissue defects caused by periodontitis. We also verified that the IR-BGNs had better anti-inflammatory properties on RAW264.7 cells compared to irisin and BGNs alone. Strikingly, when hPDLCs were stimulated with IR-BGNs, they exhibited increased expression of markers linked to osteogenesis, ALP activity, and mineralization ability in comparison to the negative control. Furthermore, on the basis of RNA sequencing results, we validated that the p38 pathway can contribute to the osteogenic differentiation of the IR-BGNs. This work may offer new thoughts on the design of ideal materials for repairing oral tissue defects.

A double-blinded, placebo-controlled, cross-over pilot trial in healthy men to study the effects of Angelica gigas herbal supplement on prostate cancer–relevant inflammatory cytokines.

170 Background: The ethanol extract of the root of Angelica gigas Nakai (AGN) dose-dependently inhibits animal models of prostate cancer. Multi-omic analyses have implicated immune and anti-inflammatory responses in the anti-cancer action. In our single dose-PK study (NCT02114957) in healthy volunteers with AGN dietary supplement CognI.Q, we observed a near doubling of the natural killer (NK) mRNA signature in peripheral blood mononuclear cells (PBMC) at 24 h after dosing while the inflammatory cytokine IL-8 mRNA was decreased by one half over the pre-dose baseline. Given NK incapacitation and inflammation have been linked to prostate cancer, the current trial (NCT03630328) was designed to assess safety and to delineate CognI.Q-specific immune and anti-inflammation functions. Methods: We used a double-blinded, placebo-controlled and crossover trial design to monitor hepatic and renal safety metrics based on Comprehensive Metabolic Panel (CMP) and compare the immune cell and cytokine responses to CognI.Q and placebo. Supplement period of 3 weeks was followed with a 2-week washout period. We employed the Ella microfluidic multiplex immunoassay to evaluate select plasma cytokines. Results: Fourteen healthy men completed the trial protocol. Physical examination on study visit days did not reveal any adverse events. Blood CMP monitoring detected abnormal hepatic integrity values in three subjects, all in the second washout period and were attributed to use of anti-allergy medication, an herbal tea for tooth ache, and excessive alcohol, respectively. Analysis of plasma cytokines detected corresponding elevation of MIG, CCL4, CXCL10 and IL-8 with these hepatic damage events. With the exclusion of these subjects or time point, the plasma cytokine measurement did not reveal a significant response to CognI.Q supplement vs. placebo. Conclusions: CognI.Q supplement at the current recommended dose (400 mg, twice per day) did not impair hepatic integrity or renal function, nor did it modulate select plasma cytokines in healthy men. Phase I dose-escalation trials should be implemented to establish safety profile and assess immune and inflammation modulatory effects of AGN supplement beyond the current dose. Clinical trial information: NCT03630328 .

Quercetin attenuates inflammation in LPS-induced lung epithelial cells via the Nrf2 signaling pathway.

Pneumonia is the leading cause of death among children under five, and kill almost two million children each year. Quercetin, a flavonoid polyphenolic compound, exerts many beneficial biological activities, including anti-inflammatory functions. Our study aimed to investigate the possibility of quercetin as a therapeutic agent for pneumonia and its role in the inflammatory response induced by lipopolysaccharide (LPS). LPS induced human alveolar epithelial cell A549 as a lung inflammation model in vitro. The effects of quercetin on the production of cytokines and the expression of related-proteins were detected by Enzyme-Linked ImmunoSorbent Assay and Western Blot, respectively. Cell Counting Kit-8 assay was used to detect cell viability. flow cytometry was used to measure cell apoptosis. NO levels were also analyzed through NO kit. Our results found that quercetin attenuated the release of IL-1β, IL-6, PGE2, and nitrite in LPS-induced A549 cells. In addition, quercetin inhibits cell apoptosis and relieves ROS generation in LPS-induced A549 cells. Quercetin also inhibits LPS-induced NF-κB activation. They have upregulated the expression of nuclear factor erythroid 2 (Nrf2) and HO-1. In conclusion, these results suggested that quercetin attenuates LPS-induced inflammation in A549 by activating the Nrf2 signaling pathway.

P179 Decrease in Butyric Acid in fecal matter in patients with Inflammatory Bowel Disease is associated with the levels of secretory Immunoglobulin A and fecal calprotectin

Abstract Background Accumulating evidence shows that the development of IBD is always accompanied by dysbiosis of the intestinal microbiota. Short-chain fatty acids (SCFAs) are produced by prebiotic intestinal bacteria, with mportant anti-inflammatory functions, delaying the clinical progression of IBD. The aim of this study is to compare SCFA levels in fecal matter in patients with IBD versus patients with Spondyloarthritis (SpA) and healthy controls. Methods 24 patients were evaluated for the presence of gastrointestinal symptoms, demographic data and inflammatory markers: fecal calprotectin, C-reactive protein (CRP), secretory IgA (SIgA) and erythrocyte sedimentation rate (ESR). The quantification of SCFAs (acetic-AC, propionic-AP, butyric-AB and total SCFAs-ACCC-T) from fecal matter was analyzed by ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-Q/ TOFMS). Results 33.3% of patients with IBD were men, with body mass index >25 in 16.7%; 83.3% presented more than 2 gastrointestinal symptoms at the time of sample collection, 33.3% had high levels of fecal calprotectin, 50% had CRP levels higher than 3mg/L and high ESR in 33.3% and a mean SIgA. of 27.73±5.03 g/mL. Very decreased levels of butyric acid (BA)ug/mL and T-SCFA were observed in IBD (9.45±4.89 and 121.73±65.94, respectively), compared to CS (BA 20.84±8.83 and total SCFA.12±122.09)., SpA SG (AB 13.35±10.44 and total AGCC 150.73±128.52) and SpA without OS (AB 21.13±5.68 and AGCC-T 219.51±229.65). Significant differences were found in fecal BA levels between the study groups (p=0.027). Interestingly, this metabolite in the CS group and the SpA group without OS did not show differences between them, but compared to the IBD group p=0.015 and 0.009 respectively, with a decrease in IBD. And interestingly, no differences were evident between fecal SCFA levels between the IBD group and the SpA group with OS even without a diagnosis of IBD. A principal component analysis was performed for the IBD group where two components were identified that group where COMP.1 was defined by a high correlation between the levels of each of the ACCC (AB CCF= 0.994, AA CCF= 0.935, AP= 0.610 and AGCC-TCCF= 0.910) that had an inverse relationship with COMP.2 which was made up of SIgA (CCF=0.988) and fecal calprotectin (CCF= 0.988). Conclusion SCFAs play a key role in maintaining immune homeostasis both locally and systemically. BA levels were significantly lower in patients with IBD compared to CS and those with SpA. This evidence clearly supports the hypothesis that relates the lack of BA with an exacerbated inflammatory response that could give rise to a dysfunctional intestinal epithelial barrier by regulating the production of mucosal antibodies such as SIgA.

Incomplete accumulation of perilesional reactive astrocytes exacerbates wound healing after closed-head injury by increasing inflammation and BBB disruption

Wound healing after closed-head injury is a significant medical issue. However, conventional models of focal traumatic brain injury, such as fluid percussion injury and controlled cortical impact, employ mechanical impacts on the exposed cerebral cortex after craniotomy. These animal models are inappropriate for studying gliosis, as craniotomy itself induces gliosis. To address this, we developed a closed-head injury model and named “photo injury”, which employs intense light illumination through a thinned-skull cranial window. Our prior work demonstrated that the gliosis of focal cerebral lesion after the photo injury does not encompass artificial gliosis and comprises two distinct reactive astrocyte subpopulations. The reactive astrocytes accumulated in the perilesional recovery area actively proliferate and express Nestin, a neural stem cell marker, while those in distal regions do not exhibit these traits. The present study investigated the role of perilesional reactive astrocytes (PRAs) in wound healing using the ablation of reactive astrocytes by the conditional knockout of Stat3. The extensive and non-selective ablation of reactive astrocytes in Nestin-Cre:Stat3f/f mice resulted in an exacerbation of injury, marked by increased inflammation and BBB disruption. On the other hand, GFAP-CreERT2:Stat3f/f mice exhibited the partial and selective ablation of the PRAs, while their exacerbation of injury was at the same extent as in Nestin-Cre:Stat3f/f mice. The comparison of these two mouse strains indicates that the PRAs are an essential astrocyte component for wound healing after closed-head injury, and their anti-inflammatory and regenerative functions are significantly affected even by incomplete accumulation. In addition, the reporter gene expression in the PRAs by GFAP-CreERT2 indicated a substantial elimination of these cells and an absence of differentiation into other cell types, despite Nestin expression, after wound healing. Thus, the accumulation and subsequent elimination of PRA are proposed as promising diagnostic and therapeutic avenues to bolster wound healing after closed-head injury.

Tumor necrosis factor receptor 2 activation elicits sex-specific effects on cortical myelin proteins and functional recovery in a model of multiple sclerosis

Multiple sclerosis (MS), a demyelinating autoimmune disease of the central nervous system (CNS), predominately affects females compared to males. Tumor necrosis factor (TNF), a pro-inflammatory cytokine, signaling through TNF receptor 1 contributes to inflammatory disease pathogenesis. In contrast, TNF receptor 2 signaling is neuroprotective. Current anti-TNF MS therapies are shown to be detrimental to patients due to pleiotropic effects on both pro- and anti-inflammatory functions. Using a non-pertussis toxin (nPTX) experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice, we systemically administered a TNFR2 agonist (p53-sc-mTNFR2) to investigate behavioral and pathophysiological changes in both female and male mice. Our data shows that TNFR2 activation alleviates motor and sensory symptoms in females. However, in males, the agonist only alleviates sensory symptoms and not motor. nPTX EAE induction in TNFR2 global knockout mice caused exacerbated motor symptoms in females along with an earlier day of onset, but not in males. Our data demonstrates that TNFR2 agonist efficacy is sex-specific for alleviation of motor symptoms, however, it effectively reduces mechanical hypersensitivity in both females and males. Altogether, these data support the therapeutic promise TNFR2 agonism holds as an MS therapeutic and, more broadly, to treat central neuropathic pain.

Endothelial Protein C Receptor and 3K3A-Activated Protein C Protect Mice from Allergic Contact Dermatitis in a Contact Hypersensitivity Model.

Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (aPC). It mediates the anti-inflammatory and barrier-protective functions of aPC through the cleavage of protease-activated receptor (PAR)1/2. Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. This study investigated the effect of EPCR and 3K3A-aPC on allergic contact dermatitis using a contact hypersensitivity (CHS) model. CHS was induced using 1-Fluoro-2,4-dinitrobenzene in EPCR-deficient (KO) and matched wild-type mice and mice treated with 3K3A-aPC, a mutant form of aPC with diminished anti-coagulant activity. Changes in clinical and histological features, cytokines, and immune cells were examined. EPCRKO mice displayed more severe CHS, with increased immune cell infiltration in the skin and higher levels of inflammatory cytokines and IgE than wild-type mice. EPCR, aPC, and PAR1/2 were expressed by the skin epidermis, with EPCR presenting almost exclusively in the basal layer. EPCRKO increased the epidermal expression of aPC and PAR1, whereas in CHS, their expression was reduced compared to wild-type mice. 3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.

Restoration of autophagy activity by dipsacoside B alleviates exhaustive exercise-induced kidney injury via the AMPK/mTOR pathway

Exhaustive exercise (EE) induces kidney injury, but its concrete mechanism has not been fully elucidated. Hepatoprotective effects of dipsacoside B (DB) have been found previously, involving in autophagy induction. However, whether DB exerts renal protective effect and its potential mechanism are still unknown. The present study aimed to investigate the benefit of DB in EE-induced kidney injury and decipher its underlying mechanism. Here, we found that DB ameliorated EE-induced renal dysfunction and renal histopathological injury in rats. DB possessed anti-inflammatory, anti-oxidative, and anti-apoptotic functions in kidneys of exercise-induced exhausted rats. Besides, DB improved autophagy function in kidneys of EE rats. Mechanically, activation of the adenylate-activating protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was implicated in the kidney injury-relieving effects and autophagy restoration induced by DB. Collectively, these findings provide reference for the clinical application of DB in preventing and managing EE-induced kidney injury.

The Genus Bryonia L. (Cucurbitaceae): A Systematic Review of Its Botany, Phytochemistry, Traditional Uses, and Biological Activities

The Bryonia genus (Cucurbitaceae) is divided into 13 plants considered medicinal species with a significant pharmacological value fortreating as well as preventing various ailments. The current systematic review aims to present useful and updated findings published onthis genus inthe last two decades. Based on PubMed, Science Direct, JSTOR, and Google Scholar, 42 of the available previous studies on Bryonia have been selected from 2000 to 2022. Thereafter, these studies were analyzed, summarized, and separately recorded according to the topic or section, adding some comments foreach. Our review provided a botanical description of the genus, followed by itsindigenous uses. Furthermore, more than 150 reported phytochemical compounds were grouped into families such as terpenoids, alkaloids, flavonoids, glycosides, saponins, and volatile oils. Hereby, thebiological activities part of this genus wereexposed, including itsantimicrobial, antioxidant, antidiabetic, antinociceptive, and anti-inflammatory functions, along with an interesting anticancer efficiency. Overall, our findings could contribute to forthcoming investigations that may lead to determining the responsible phytoconstituents for Bryonia’s efficiency.

Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43

PurposeShort chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye. MethodsBoth human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount. ResultsGPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells. ConclusionsThis is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.

Dual-Drug-Loaded Core-Shell Electrospun Nanofiber Dressing for Deep Burns.

The epidermis of a deep burn wound is entirely absent and the dermal tissue sustains significant damage, accompanied by a substantial amount of tissue exudate. Due to the excessively humid environment, the formation of a scab on the wound becomes challenging, leaving it highly vulnerable to external bacterial invasion. In this work, a core-shell dual-drug-loaded nanofiber dressing was prepared by electrospinning technology for the synergistic treatment of a deep burn. The shell layer consists of polycaprolactone and chitosan encapsulating asiaticoside, with the core layer comprising the clathrate of 2-hydroxypropyl-β-cyclodextrin and curcumin. Upon application to the wound, the dual-drug-loaded nanofiber dressing exhibited rapid release of asiaticoside, stimulating collagen deposition and promoting tissue repair. The core-shell structure and clathrate configuration ensured sustained release of curcumin, providing antibacterial and anti-inflammatory functions for the wound. The mechanical strength, broad-spectrum antibacterial ability, cell proliferation, and adhesion ability of the nanofiber dressing showed its potential as a medical dressing. This dressing also exhibited excellent wound healing promoting effects in the SD rat burn model. This paper provides a strategy for burn wound healing.

Grape seed proanthocyanidin extract alleviates inflammation in experimental colitis mice by inhibiting NF-κB signaling pathway.

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.

Zerumbone reduces TLR2 stimulation-induced M1 macrophage polarization pattern via upregulation of Nrf-2 expression in murine macrophages

Hyperuricemia contributes significantly to gout arthritis pathogenesis, which promotes urate crystal deposition in the joints and activates joint-resident macrophages and circulating monocytes to initiate a state of inflammatory arthritis. In the joint, macrophages have an immune defense role where the presence of urate crystals results in the inflammatory mediators secretion, inflammatory cells recruitment to the joint, and shift macrophage population toward M1 pro-inflammatory phenotypes. Current treatment modalities of gout arthritis have side effects that limit their use in the elderly. A novel treatment that targets macrophage polarization to re-establish homeostasis may initiate a drug discovery program of novel disease-modifying agents for gout. Zerumbone (Zer) is a sesquiterpenoid bioactive compound found in the rhizome of Zingiberaceae family and possesses anti-inflammatory, antioxidant, and anti-proliferative activity. Our study hypothesized that soluble uric acid (sUA) and Pam3CSK4 (TLR2 agonist) reduce the anti-inflammatory function of murine M2 bone marrow-derived macrophages and change the expression of M2 genetic markers toward M1 phenotypes. We observed that priming of M2 macrophages with sUA and Pam3CSK4 significantly decreased M2 specific markers expression, e.g., Arg-1, Ym-1, and Fizz-1, enhanced mRNA expression of IL-1β, TNF-α, CXCL2, and iNOS and increased oxidative stress in M2 macrophages, as exhibited by a reduction in Nrf2 expression. We also aimed to study the impact of Zer on reducing the pro-inflammatory effect of sUA in TLR2-stimulated M2 macrophages. We noticed that Zer treatment significantly reduced L-1β and TNF-α production following Pam3CSK4 + sUA treatment on M2 macrophages. Furthermore, Zer reduced the caspase-1 activity without altering cytosolic NLRP3 content in challenged M2 BMDMs. We also observed that Zer significantly enhanced M2-associated marker’s expression, e.g., Arg-1, Ym-1, and Fizz-1, and augmented Nrf-2 and other antioxidant proteins, including HMOX1 and srxn1expression following Pam3CSK4 + sUA treatment. We draw the conclusion that Zer is a potentially effective anti-inflammatory treatment for gout arthritis linked to hyperuricemia.

Astrocyte DNA damage and response upon acute exposure to ethanol and corticosterone.

Introduction: Astrocytes are the glial cells responsible for brain homeostasis, but if injured, they could damage neural cells even deadly. Genetic damage, DNA damage response (DDR), and its downstream cascades are dramatic events poorly studied in astrocytes. Hypothesis and methods: We propose that 1h of 400mmol/L ethanol and/or 1μmol/L corticosterone exposure of cultured hippocampal astrocytes damages DNA, activating the DDR and eliciting functional changes. Immunolabeling against γH2AX (chromatin DNA damage sites), cyclin D1 (cell cycle control), nuclear (base excision repair, BER), and cytoplasmic (anti-inflammatory functions) APE1, ribosomal nucleolus proteins together with GFAP and S100β plus scanning electron microscopy studies of the astrocyte surface were carried out. Results: Data obtained indicate significant DNA damage, immediate cell cycle arrest, and BER activation. Changes in the cytoplasmic signals of cyclin D1 and APE1, nucleolus number, and membrane-attached vesicles strongly suggest a reactivity like astrocyte response without significant morphological changes. Discussion: Obtained results uncover astrocyte genome immediate vulnerability and DDR activation, plus a functional response that might in part, be signaled through extracellular vesicles, evidencing the complex influence that astrocytes may have on the CNS even upon short-term aggressions.

Effects of ADSC-Derived Exosome LRRC75A-AS1 on Anti-inflammatory Function After SCI.

Spinal cord injury (SCI) is a highly debilitating disorder of the central nervous system that can severely impact an affected patient's quality of life. This study aimed to examine how adipose-derived mesenchymal stem cell exosomes (ADSC-exos) can be used to treat spinal cord injury. We analysed differentially expressed mRNAs in SCI using bioinformatics data, gene expression profiles in inflammatory cell models, RT-qPCR and WB. Apoptosis was detected with flow cytometry. Starbase provides the control mechanism for FDFT1. Target interactions were detected with dual-luciferase reporter and RIP assays. Exosomes were isolated from adipose tissue-derived mesenchymal stem cells and subsequently characterized with western blot analysis, transmission electron microscopy and nanoparticle tracking analysis. By analysing the GSE102964 database, we found that FDFT1 was significantly downregulated as SCI progressed. Overexpression of FDFT1 can significantly reverse the inflammatory response and apoptosis of BV2 cells induced by hemin. Mechanically, ADSC-exos can affect the expression of FDFT1 through the ceRNA mechanism mediated by LRRC75A-AS1 and in an RBP-dependent manner mediated by IGF2BP2. The overexpression of LRRC75A-AS1 significantly enhances BV2 apoptosis and can be reversed by FDFT1 knockdown. ADSC-exos LRRC75A-AS1 inhibits inflammation and reduces SCI by increasing the expression and stability of FDFT1 mRNA in a ceRNA and RBP-dependent manner.

Effect of the Combination of Clostridium butyricum and Mycelium of Phellinus igniarius on Intestinal Microbiota and Serum Metabolites in DSS-Induced Colitis.

Clostridium butyricum (CB) and Phellinus igniarius (PI) have anti-inflammatory, immune regulation, anti-tumor, and other functions. This study aimed to explore the therapeutic effect of CB and mycelium of PI (MPI) alone and in combination on colitis mice induced by dextran sodium sulfate (DSS). Mice were randomly assigned to five groups: (1) control (CTRL), (2) DSS, (3) CB, (4) MPI, and (5) CB + MPI (CON). The weight of the mice was recorded daily during the experiment, and the length of the colon was measured on the last day of the experiment. The colons were collected for hematoxylin and eosin staining, colon contents were collected for intestinal flora analysis, and serum was collected for metabolite analysis. The results showed that compared with the DSS group, CB, MPI, and CON treatments inhibited the weight loss and colon length shortening caused by DSS, significantly increased the concentrations of interleukin (IL)-4, IL-10, and superoxide dismutase, and significantly decreased the concentrations of IL-6, tumor necrosis factor-α, and myeloperoxidase. Gene sequence analysis of 16S rRNA showed that CB, MPI, and CON treatments changed the composition and structure of intestinal microorganisms. Metabolome results showed that CB, MPI, and CON treatments changed serum metabolites in DSS-treated mice, including dodecenoylcarnitine, L-urobilinogen, and citric acid. In conclusion, CB, MPI, and CON treatments alleviated DSS-induced colitis in mice by regulating intestinal flora and metabolites, with the CON group having the best effect.

CD317+ MSCs expanded with chemically defined media have enhanced immunological anti-inflammatory activities

BackgroundAlthough both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity.MethodsCell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo.ResultsOur data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317+ MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317+ MSCs.ConclusionsThus, CD317+ MSCs might be a promising candidate for treating immunological disorder-related diseases.

From Bronchial Asthma to Tuberculosis: Unravelling the Cytokine-Macrophage Axis in Diverse Diseases

Cytokines, tiny proteins secreted by cells, play a critical role in mediating communication and interactions between cells. They also function as immunomodulating agents, adjusting immune responses. When released into the bloodstream or tissues, cytokines bind to specific receptors on target immune cells, triggering cellular responses. Cytokines are implicated in various diseases, including asthma, COPD, HIV infection, and multiple sclerosis. This review delves into the intricate interplay between cytokines and macrophages, focusing on their roles in inflammation and the immune response. Macrophages, which are scavenger cells of the immune system, exhibit remarkable heterogeneity, reside in diverse tissues, and play crucial roles in both innate and acquired immunity. They can be activated for proinflammatory or anti-inflammatory functions, contributing to tissue destruction or regeneration. Cytokines influence macrophage activation and polarization, impacting the inflammatory process. Dysregulated cytokine production and macrophage activation are observed in various diseases. For example, in asthma, an imbalance in macrophage phenotypes contributes to airway hyperresponsiveness. Understanding the complex interplay between cytokines and macrophages is crucial for developing novel therapeutic strategies for inflammatory diseases. Future research directions include utilizing humanized animal models, single-cell sequencing, and immunomodulatory therapies to further decipher the intricate roles of cytokines and macrophages in health and disease. Ultimately, elucidating these interactions holds immense potential for improving human health outcomes.

Integrated cellular 4D-TIMS lipidomics and transcriptomics for characterization of anti-inflammatory and anti-atherosclerotic phenotype of MyD88-KO macrophages.

Introduction: Recent progress in cell isolation technologies and high-end omic technologies has allowed investigation of single cell sets across multiple omic domains and a thorough exploration of cellular function and various functional stages. While most multi-omic studies focused on dual RNA and protein analysis of single cell population, it is crucial to include lipid and metabolite profiling to comprehensively elucidate molecular mechanisms and pathways governing cell function, as well as phenotype at different functional stages. Methods: To address this gap, a cellular lipidomics and transcriptomics phenotyping approach employing simultaneous extraction of lipids, metabolites, and RNA from single cell populations combined with untargeted cellular 4 dimensional (4D)-lipidomics profiling along with RNA sequencing was developed to enable comprehensive multi-omic molecular profiling from the lowest possible number of cells. Reference cell models were utilized to determine the minimum number of cells required for this multi-omics analysis. To demonstrate the feasibility of higher resolution cellular multi-omics in early-stage identification of cellular phenotype changes in pathological and physiological conditions we implemented this approach for phenotyping of macrophages in two different activation stages: MyD88-knockout macrophages as a cellular model for atherosclerosis protection, and wild type macrophages. Results and Discussion: This multi-omic study enabled the determination of the lipid content remodeling in macrophages with anti-inflammatory and atherosclerotic protective function acquired by MyD88-KO, hence expedites the understanding of the molecular mechanisms behind immune cells effector functionality and of possible molecular targets for therapeutic intervention. An enriched functional role of phosphatidylcholine and plasmenyl/plasmalogens was shown here to accompany genetic changes underlying macrophages acquisition of anti-inflammatory function, finding that can serve as reference for macrophages reprogramming studies and for general immune and inflammation response to diseases.

Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.