Anti-inflammatory M2 Research Articles

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as key regulators of intercellular communication, orchestrating essential biological processes by delivering bioactive cargoes to target cells. Available evidence suggests that MSC-EVs can mimic the functions of their parental cells, exhibiting immunomodulatory, pro-regenerative, anti-apoptotic, and antifibrotic properties. Consequently, MSC-EVs represent a cell-free therapeutic option for patients with inflammatory bowel disease (IBD), overcoming the limitations associated with cell replacement therapy, including their non-immunogenic nature, lower risk of tumourigenicity, cargo specificity and ease of manipulation and storage. This review aims to provide a comprehensive examination of the therapeutic efficacy of MSC-EVs in IBD, with a focus on their mechanisms of action and potential impact on treatment outcomes. We examine the advantages of MSC-EVs over traditional therapies, discuss methods for their isolation and characterisation, and present mechanistic insights into their therapeutic effects through transcriptomic, proteomic and lipidomic analyses of MSC-EV cargoes. We also discuss available preclinical studies demonstrating that MSC-EVs reduce inflammation, promote tissue repair and restore intestinal homeostasis in IBD models, and compare these findings with those of clinical trials. Finally, we highlight the potential of MSC-EVs as a novel therapy for IBD and identify challenges and opportunities associated with their translation into clinical practice. The source of mesenchymal stem cells (MSCs) strongly influences the composition and function of MSC-derived extracellular vesicles (EVs), affecting their therapeutic potential. Adipose-derived MSC-EVs, known for their immunoregulatory properties and ease of isolation, show promise as a treatment for inflammatory bowel disease (IBD). MicroRNAs are consistently present in MSC-EVs across cell types and are involved in pathways that are dysregulated in IBD, making them potential therapeutic agents. For example, miR-let-7a is associated with inhibition of apoptosis, miR-100 supports cell survival, miR-125b helps suppress pro-inflammatory cytokines and miR-20 promotes anti-inflammatory M2 macrophage polarisation. Preclinical studies in IBD models have shown that MSC-EVs reduce intestinal inflammation by suppressing pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-6) and increasing anti-inflammatory factors (e.g., IL-4, IL-10). They also promote mucosal healing and strengthen the integrity of the gut barrier, suggesting their potential to address IBD pathology.

A Core-Brush Nanoplatform with Enhanced Lubrication and Anti-Inflammatory Properties for Osteoarthritis Treatment.

Osteoarthritis (OA) is recognized as a highly friction-related joint disease primarily associated with increased joint friction and inflammation due to pro-inflammatory M1-type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core-brush nanoplatform composed of a ROS-scavenging polydopamine-coated SiO2 core and lubrication-enhancing zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti-inflammatory drug curcumin by a reactive oxygen species (ROS)-liable conjugation (named as SiO2@PP-Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono-iodoacetic acid-induced arthritis (MIA) rat model, intra-articular injection of SiO2@PP-Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro-inflammatory M1 to anti-inflammatory M2 state by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro-regenerative microenvironment. As a result, SiO2@PP-Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core-brush nanoplatform for enhanced OA therapy.

Overexpression of Chromatin Remodeling Factor SRG3 Down-Regulates IL1β-Expressing M1 Macrophages and IL17-Producing T Cells in Adipose Tissues

The SWItch3-related gene (SRG3) is a core component of ATP-dependent SWI/SNF complexes, which are crucial for regulating immune cell development and function (e.g., macrophages and CD4+ T cells), embryonic development, and non-immune cell differentiation. Notably, SRG3 overexpression has been shown to polarize macrophages in the central nervous system toward an anti-inflammatory M2 phenotype, thereby protecting against the development of experimental autoimmune encephalomyelitis in mice. However, the effect of SRG3 on immune responses in adipose tissues remains unclear. To address this issue, we examined the cellularity and inflammatory status of adipose tissue in B10.PL mice overexpressing the SRG3 gene under the ubiquitous β-actin promoter (SRG3β-actin). Interestingly, SRG3 overexpression significantly reduced adipocyte size in both white and brown adipose tissues, without affecting the overall adipose tissue weight. Such phenotypic effects might be associated with the improved glucose tolerance observed in SRG3β-actin B10.PL mice. Moreover, we found that SRG3 overexpression down-regulates IL1β-expressing M1 macrophages, leading to a significant decrease in the M1/M2 macrophage ratio. Additionally, SRG3β-actin B10.PL mice showed a dramatic reduction in neutrophils as well as IL1β- and IL17-producing T cells in adipose tissues. Taken together, our results indicate that SRG3 plays a vital role in maintaining immune homeostasis within adipose tissues.

Chitosan-based self-healing thermosensitive hydrogel loaded with siHMGB1 for treatment of rheumatoid arthritis via macrophage repolarization.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by immune cell activation, particularly macrophages. An imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages causes synovial inflammation and joint damage, worsening RA. This study presents a biomacromolecular hydrogel delivery system with apoferritin nanoparticles for effective delivery of small interfering high mobility group protein (siHMGB1). The system was designed to promote the polarization of M1 macrophages to the M2 phenotype by downregulating the HMGB1/TLR4/NF-κB-p65 signaling pathway, offering a potential therapeutic approach for the treatment of RA. The oxidized chondroitin sulfate - chitosan - sodium glycerol β - phosphate - Fn/siHMGB1 (OCF/siHMGB1) hydrogel system possessed temperature-sensitive and self-healing properties, enabling the sustained, stable, and efficient release of siHMGB1 at the affected joint. After effective uptake by macrophages, siHMGB1 could effectively repolarize M1-phenotype macrophages to M2-phenotype via the HMGB1/TLR4/NF-κB-p65 signaling pathway both in vitro and in vivo. Additionally, it suppressed the release of pro-inflammatory cytokines and upregulated anti-inflammatory cytokines, which significantly blocked the TLR4/p65-mediated inflammatory signaling. In conclusion, the siHMGB1-loaded hydrogel delivery system designed in this study is effective in treating RA and highlights the potential of gene therapy to induce repolarization of M1 to M2 macrophages for RA treatment.

The influence of interleukin-4 on transendothelial transport of low-density lipoproteins

BACKGROUND: Cytokines are important participants in the atherosclerotic process. The product of T-helpers and mast cells, interleukin-4, causes activation of endothelial cells and induces polarization of macrophages into anti-inflammatory M2 phenotype. AIM: The aim was to study the influence of interleukin-4 on the activation of transendothelial transport of low-density lipoproteins. MATERIALS AND METHODS: Low-density lipoproteins transendothelial transport was evaluated in a two-chamber model on a monolayer of human endothelial cell line EA.hy926. For that, 200 mkg/ml of low-density lipoproteins, and 1, or 10, or 100 ng/ml of interleukin-4, or 10, or 50 ng/ml of interleukin-6, or 50 ng/ml of tumor necrosis factor, or 10 ng/ml of interleukin-4 and 50 ng/ml of tumor necrosis factor, or a phosphate buffer saline were added to the cells on 24 h. The integrity of endothelial monolayer was controlled by the passage through 1 mkg/ml of fluorescein Na. The levels of mRNA and proteins in the cells were determined by reverse transcription polymerase chain reaction and Western blotting, the activity of matrix metalloproteinases-1, -2 and -9 in the culture medium — by zymography, interleukin-6 and -8 concentrations — by enzyme-linked immunosorbent assay. RESULTS: Interleukin-4 had no effect on the passage of low-density lipoproteins through the monolayer of endothelial cells in basal and tumor necrosis factor stimulation conditions. At the same time, interleukin-4 suppressed interleukin-8 secretion by cells and increased their production of interleukin-6. The latter also did not cause the changes in the permeability of endothelial monolayer. In addition, interleukin-4 did not affect the expression of CAV, SCARB1, ACVRL1 genes, encoding proteins involved in low-density lipoproteins transendothelial transport. An addition of interleukin-4 or -6 to the cells did not change the activity of the matrix metalloproteinases. CONCLUSIONS: Interleukin-4 does not affect the transendothelial transport of low-density lipoproteins, while modulating the production of other cytokines by endothelial cells. In the future, it is necessary to establish the effect of a wider range of cytokines produced by intimal cells on low-density lipoproteins transendothelial transport, as well as to clarify the molecular mechanisms of influence of tumor necrosis factor on this process in order to identify new targets for atherosclerosis therapy.

Histopathology and prognosis of new-onset atrio-ventricular block after coronary artery bypass graft surgery

Abstract Background Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact. Purpose This study explores the association of first-degree AVB in ECG and postoperative outcome of patients with either preoperative or a new-onset AVB. Furthermore, histopathological features were analyzed to distinguish the characteristics between preoperative and postoperative AVBs compared to no AVB. Methods CAREBANK is a prospective study with atrial biopsies obtained at the time of open-heart cardiac surgery and long-term follow-up focusing on the adverse events. We analyzed preoperative as well as postoperative ECGs derived after index hospitalization (1-18mo) in patients undergoing CABG. The definition of first-degree AVB was PR-interval ≥200ms. The main outcome of interest was follow-up mortality. Histopathological analysis was used to assess the amount of fibrosis, cardiomyocytes, number of nuclei and macrophages. Results Median follow up time was 4.0 (IQR 2.7 – 5.0) years. First-degree AVB was found in 84/373 (22.5%) preoperative ECGs. Altogether 25/289 (8.7%) cases where ECG was available (after excluding preop AVB, atrial fibrillation) developed first-degree AVB after index hospitalization. New-onset first-degree AVB was associated with increased mortality (aHR 4.033 (95-CI% 1.019–15.965, p=0.047). In atrial histopathological analysis, area covered by cardiomyocytes (p=0.033) as well as area covered by nuclei (p=0.047) were smaller in those with new-onset AVB after surgery, but not in those with preoperative first-degree AVB (p=0.692 and p=0.384) as compared with controls, respectively. Similarly, the total area of fibrosis was greater in those with preoperative first-degree AVB (p<0.001), but not in those with postoperative new-onset AVB (p=0.244). When compared with controls, share of CD68 positive macrophages was similar (p=0.073), but anti-inflammatory CD206 positive M2 macrophages were absent in patients with new-onset AVB (p=0.042). Conclusion Patients with new-onset AVB after CABG have increased mortality in the long-term compared to those without. Histopathology identifies marked differences in macrophage populations between those with and without new-onset AVB.

CTRP9 attenuates peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia through regulating spinal microglial polarization and neuroinflammation mediated by AdipoR1 in male mice

Peripheral nerve injury triggers rapid microglial activation, promoting M1 polarization within the spinal cord, which exacerbates the progression of neuropathic pain. C1q/TNF-related protein 9 (CTRP9), an adiponectin homolog, is known to suppress macrophage activation and exhibit anti-inflammatory properties through the activation of adiponectin receptor 1 (AdipoR1) in various disease contexts. Nevertheless, the involvement of CTRP9 in microglial polarization in the context of neuropathic pain is still unclear. Our study aimed to how CTRP9 influences spinal microglial polarization, neuroinflammation, and pain hypersensitivity, as well as the underlying mechanism, using a neuropathic pain model in male mice with spared nerve injury (SNI) of sciatic nerve. Our findings revealed SNI elevated the spinal CTRP9 and AdipoR1 levels in microglia. Furthermore, intrathecal administration of recombinant CTRP9 (rCTRP9) substantially weakened mechanical hypersensitivity and heat-related pain response triggered by SNI. On the other hand, rCTRP9 mediated a phenotypic switch in microglia, from the pro-inflammatory M1 state to the anti-inflammatory M2 state, by influencing the spinal AMPK/NF-κB mechanism in SNI mice. Additionally, treatment with AdipoR1 siRNA or an AMPK-specific antagonist both reversed the effects of CTRP9 on the phenotypic switching of spinal microglia and pain hypersensitivity. Collectively, these results indicate that CTRP9 ameliorates mechanical hypersensitivity and heat-related pain response, shifted the balance of microglia towards the anti-inflammatory M2 state, and suppresses neuroinflammatory responses by modulating the AMPK/NF-κB pathway, mediated by AdipoR1 activation, in mice with SNI.Graphical

Bilobalide ameliorates osteoporosis by influencing the SIRT3/NF-κB axis in osteoclasts and promoting M2 polarization in macrophages

Osteoporosis is a systemic disease with complex etiology and high prevalence, resulting in a huge economic burden. For a long time, the search for new therapeutic pharmaceuticals has never stopped. Bone loss is related to the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. In recent years, the role of immunity and inflammation in the development of osteoporosis has studied well. For example, various cytokines, chemokines and endocrine factors regulate osteoclastogenesis via activating different macrophage subtypes, including pro-inflammatory M1 and anti-inflammatory M2. Bilobalide (Bil), an active Ginkgo biloba ingredient, has garnered great interest because of its anti-oxidant and anti-inflammatory activities. In this study, we found that Bil can attenuate osteoclast generation induced by receptor activator of nuclear factor- kappa B ligand (RANKL) through upregulating the sirtuin 3 (SIRT3) and negatively regulating NF-κB signaling. Furthermore, Bil promotes M2 polarization of macrophages in a dose-dependent manner. In vivo studies provided evidence that Bil improves bone density in osteoporosis mice models. Based on the above results, we have reason to believe that Bil has potential therapeutic value in osteoclast-mediated bone loss and offers an effective option for long-term osteoporosis management.

Multiomics identification of ALDH9A1 as a crucial immunoregulatory molecule involved in calcific aortic valve disease

Mitochondrial dysfunction and immune cell infiltration play crucial yet incompletely understood roles in the pathogenesis of calcific aortic valve disease (CAVD). This study aimed to identify immune-related mitochondrial genes critical to the pathological process of CAVD using multiomics approaches. The CIBERSORT algorithm was employed to evaluate immune cell infiltration characteristics in CAVD patients. An integrative analysis combining weighted gene coexpression network analysis (WGCNA), machine learning, and summary data-based Mendelian randomization (SMR) was performed to identify key mitochondrial genes implicated in CAVD. Spearman’s rank correlation analysis was also performed to assess the relationships between key mitochondrial genes and infiltrating immune cells. Compared with those in normal aortic valve tissue, an increased proportion of M0 macrophages and resting memory CD4 T cells, along with a decreased proportion of plasma cells and activated dendritic cells, were observed in CAVD patients. Additionally, eight key mitochondrial genes associated with CAVD, including PDK4, LDHB, SLC25A36, ALDH9A1, ECHDC2, AUH, ALDH2, and BNIP3, were identified through the integration of WGCNA and machine learning methods. Subsequent SMR analysis, incorporating multiomics data, such as expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (mQTLs), revealed a significant causal relationship between ALDH9A1 expression and a reduced risk of CAVD. Moreover, ALDH9A1 expression was inversely correlated with M0 macrophages and positively correlated with M2 macrophages. These findings suggest that increased ALDH9A1 expression is significantly associated with a reduced risk of CAVD and that it may exert its protective effects by modulating mitochondrial function and immune cell infiltration. Specifically, ALDH9A1 may contribute to the shift from M0 macrophages to anti-inflammatory M2 macrophages, potentially mitigating the pathological progression of CAVD. In conclusion, ALDH9A1 represents a promising molecular target for the diagnosis and treatment of CAVD. However, further validation through in vivo and n vitro studies is necessary to confirm its role in CAVD pathogenesis and therapeutic potential.

An In Vitro Macrophage Response Study of Silk Fibroin and Silk Fibroin/Nano-Hydroxyapatite Scaffolds for Tissue Regeneration Application.

In recent years, silk fibroin (SF) has been incorporated with low crystallinity nanohydroxyapatite (nHA) as a scaffold for various tissue regeneration applications due to the mechanical strength of SF and osteoconductive properties of nHA. However, currently, there is a lack of understanding of the immune response toward the degradation products of SF with nHA composite after implantation. It is known that particulate fragments from the degradation of a biomaterial can trigger an immune response. As the scaffold is made of degradable materials, the degradation products may contribute to the inflammation. Therefore, in this study, the effects of the enzymatic degradation of the SF/nHA scaffold on macrophage response were investigated in comparison to the control SF scaffold. Since the degradation products of a scaffold can influence macrophage polarization, it can be hypothesized that as the SF and SF/nHA scaffolds were degraded in vitro using protease XIV solution, the degradation products can contribute to the polarization of THP-1-derived macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The results demonstrated that the initial (day 1) degradation products of the SF/nHA scaffold elicited a pro-inflammatory response, while the latter (day 24) degradation products of the SF/nHA scaffold elicited an anti-inflammatory response. Moreover, the degradation products from the SF scaffold elicited a higher anti-inflammatory response due to the faster degradation of the SF scaffold and a higher amino acid concentration in the degradation solution. Hence, this paper can help elucidate the contributory effects of the degradation products of SF and SF/nHA scaffolds on macrophage response and provide greater insights into designing silk-based biomaterials with tunable degradation rates that can modulate macrophage response for future tissue regeneration applications.

An injectable self-lubricating supramolecular polymer hydrogel loaded with platelet lysate to boost osteoarthritis treatment

Globally, osteoarthritis (OA) is the most prevalent joint disease and is characterized by infiltration of M1 macrophages in the synovium, anabolic–catabolic imbalance of the extracellular matrix (ECM), increased articular shear force and overproduction of reactive oxygen species (ROS). Disease-modifying OA drugs are not yet available, and treatments for OA focus solely on reducing pain and inflammation and have limited therapeutic effect. Herein, we developed an injectable self-lubricating poly(N-acryloyl alaninamide) (PNAAA) hydrogel loaded with platelet lysate (PL) (termed “PNAAA@PL”) for treating OA. Tribological and drug release tests revealed suitable lubrication properties and sustained release of bioactive factors in PNAAA@PL. In vitro experiments showed that PNAAA@PL alleviated interleukin-1β (IL-1β)-induced anabolic–catabolic imbalance of chondrocytes and repolarized pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype via intracellular ROS scavenging. Additionally, the PNAAA@PL hydrogel enhanced the migratory capacity and chemotaxis ability of stem cells, which are essential for chondrogenesis. In vivo, the functionalized PNAAA@PL hydrogel acted like synovial fluid following intra-articular injection into a rat OA model with anterior cruciate ligament transection, ultimately attenuating cartilage degeneration and synovitis. According to molecular mechanism studies, PNAAA@PL repairs cartilage in the OA model by inhibiting the NF-ĸB pathway. Overall, this self-lubricating PNAAA@PL hydrogel offers a comprehensive strategy for preventing OA progression by engineering a biophysiochemical microenvironment to generate high-quality hyaline cartilage.

Preparation of a chitosan/polyvinyl alcohol-based dual-network hydrogel for use as a potential wound-healing material for the sustainable release of drugs

Treating chronic wounds poses significant challenges in clinical medicine due to bacterial infection, reactive oxygen species (ROS) accumulation, and excessive inflammation. This study aimed to address these issues by developing a wound dressing with antibacterial, antioxidant, and anti-inflammatory properties. Chitosan was functionally modified with acrolein to covalently bind to epigallocatechin gallate (EGCG), enabling a high EGCG load. Subsequently, polyvinyl alcohol (PVA) and EGCG-modified chitosan were crosslinked to prepare a new double-network hydrogel with added cysteine (CSAEC/P50). CSAEC/P50 demonstrated optimal mechanical properties (low swelling rate, high water retention, and optimal flexibility), low hemolysis, high coagulation properties, and antibacterial and antioxidant activities. Cell scratch tests indicated that CSAEC/P50 can promote NIH3T3 cell migration. Immunofluorescence results showed that CSAEC/P50 promoted the transformation of proinflammatory M1 macrophages to anti-inflammatory M2 macrophages. These findings suggest that CSAEC/P50 has significant potential for use in wound dressing applications.

Intranasal Delivery of Pure Nanodrug Loaded Liposomes for Alzheimer's Disease Treatment by Efficiently Regulating Microglial Polarization.

The activated M1-like microglia induced neuroinflammation is the critical pathogenic event in Alzheimer's disease (AD). Microglial polarization from pro-inflammatory M1 toward anti-inflammatory M2 phenotype is a promising strategy. To efficiently accomplish this, amyloid-β (Aβ) aggregates as the culprit of M1 microglia activation should be uprooted. Interestingly, this study finds out that the self-reassembly of curcumin molecules into carrier-free curcumin nanoparticles (CNPs) exhibits multivalent binding with Aβ to achieve higher inhibitory effect on Aβ aggregation, compared to free curcumin with monovalent effect. Based on this, the CNPs loaded cardiolipin liposomes are developed for efficient microglial polarization. After intranasal administration, the liposomes decompose to release CNPs and cardiolipin in response to AD oxidative microenvironment. The CNPs inhibit Aβ aggregation and promote Aβ phagocytosis/clearance in microglia, removing roadblock to microglial polarization. Subsequently, CNPs are endocytosed by microglia and inhibit TLR4/NF-κB pathway for microglia polarization (M1→M2). Meanwhile, cardiolipin is identified as signaling molecule to normalize microglial dysfunction to prevent pro-inflammatory factors release. In AD transgenic mice, neuroinflammation, Aβ burden, and memory deficits are relieved after treatment. Through combined attack by extracellularly eradicating roadblock of Aβ aggregation and intracellularly inhibiting inflammation-related pathways, this nanotechnology assisted delivery system polarizes microglia efficiently, providing a reliable strategy in AD treatment.

Biomimetic Nanomodulator Regulates Oxidative and Inflammatory Stresses to Treat Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a devastating complication of sepsis, affecting approximately 70% of patients with sepsis in intensive care units (ICU). Although the pathophysiological mechanisms remain elusive, sepsis is typically accompanied by systemic inflammatory response syndrome (SIRS) and hyper-oxidative conditions. Here, we introduce a biomimetic nanomodulator (mAOI NP) that specifically targets inflammation site and simultaneously regulates oxidative and inflammatory stresses. mAOI NPs are constructed using metal-coordinated polyphenolic antioxidants (tannic acid) and flavonoid quercetin, which are then coated with macrophage membrane to enhance pharmacokinetics and enable SAE targeting. In a cecal ligation and puncture (CLP)-induced severe sepsis model, mAOI NPs effectively mitigate oxidative stress by purging reactive oxygen species, repairing mitochondrial damage and activating the Nrf2/HO-1 signaling pathway; while polarizing M1 macrophages or microglia toward anti-inflammatory M2 subtype. mAOI NPs potently inhibit sepsis progress, prolong overall survival from 25 to 66% and enhance learning and memory capabilities in SAE mice. Further proteomics analysis reveals that mAOI NPs modulate neurodevelopment processes related to learning and memory formation while also exerting anti-inflammatory and antioxidative effects on brain tissue responses associated with SAE pathology. This study offers significant potential for improving patient outcomes and revolutionizing the treatment landscape for this devastating complication of sepsis.

Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.

With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)3), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels (p < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages (p < 0.05). The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.

The Role of Macrophages in Airway Disease Focusing on Porcine Reproductive and Respiratory Syndrome Virus and the Treatment with Antioxidant Nanoparticles.

Lung macrophage cells play a critical role in various lung diseases, and their state can change depending on the progression of the disease by inducing either an inflammatory or anti-inflammatory state. In this review, the potential therapeutic effects of treatment with antioxidant nanoparticles in air-borne diseases focusing on porcine reproductive and respiratory virus (PRRSV), considering reactive oxygen species (ROS) as one of the factors that regulate M1 and M2 macrophages in the inflammatory and anti-inflammatory states, respectively, was described. In addition, the author examines the status of protein structure research on CD163 (one of the markers of anti-inflammatory M2 macrophages) in human and veterinary lung diseases.

Lactobacillus paracasei JY062 and its exopolysaccharide enhance the intestinal barrier through macrophage polarization and Th17/Treg cell balance

Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.

Anti-pyroptosis biomimetic nanoplatform loading puerarin for myocardial infarction repair: From drug discovery to drug delivery

Pyroptosis is a critical pathological mechanism implicated in myocardial damage following myocardial infarction (MI), and the crosstalk between macrophages and pyroptotic cardiomyocytes presents a formidable challenge for anti-pyroptosis therapies of MI. However, as single-target pyroptosis inhibitors frequently fail to address this crosstalk, the efficacy of anti-pyroptosis treatment post-MI remains inadequate. Therefore, the exploration of more potent anti-pyroptosis approaches is imperative for improving outcomes in MI treatment, particularly in addressing the crosstalk between macrophages and pyroptotic cardiomyocytes. Here, in response to this crosstalk, we engineered an anti-pyroptosis biomimetic nanoplatform (NM@PDA@PU), employing polydopamine (PDA) nanoparticles enveloped with neutrophil membrane (NM) for targeted delivery of puerarin (PU). Notably, network pharmacology is deployed to discern the most efficacious anti-pyroptosis drug (puerarin) among the 7 primary active monomers of TCM formulations widely applied in clinical practice and reveal the effect of puerarin on the crosstalk. Additionally, targeted delivery of puerarin could disrupt the malignant crosstalk between macrophages and pyroptotic cardiomyocytes, and enhance the effect of anti-pyroptosis by not only directly inhibiting cardiomyocytes pyroptosis through NLRP3-CASP1-IL-1β/IL-18 signal pathway, but reshaping the inflammatory microenvironment by reprogramming macrophages to anti-inflammatory M2 subtype. Overall, NM@PDA@PU could enhance anti-pyroptosis effect by disrupting the crosstalk between M1 macrophages and pyroptotic cardiomyocytes to protect cardiomyocytes, ameliorate cardiac function and improve ventricular remodeling, which providing new insights for the efficient treatment of MI.

Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 promote infected wound healing via regulation of the wound microenvironment.

Infected wounds can result in complex clinical complications and delayed healing, presenting a significant global public health challenge. This study explored the effects of topical application of two probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB-12, on the microenvironment of infected wounds and their impact on wound healing. LGG and BB-12 were applied separately and topically on the Staphylococcus aureus (S. aureus)-infected skin wounds of the rat model on a daily basis. Both probiotics significantly accelerated wound healing, demonstrated by enhanced granulation tissue formation and increased collagen deposition, with BB-12 showing superior efficacy. LGG and BB-12 both effectively inhibited neutrophil infiltration and decreased the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Notably, BB-12 markedly reduced IL-6 levels, while LGG significantly lowered TNF-α, transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF). Additionally, both probiotics promoted macrophage polarization towards the anti-inflammatory M2 phenotype. Microbiota analysis revealed that LGG and BB-12 significantly decreased the abundance of pathogenic bacteria (e.g. Staphylococcus and Proteus) and increased the proportion of beneficial bacteria (e.g. Corynebacterium). Particularly, BB-12 was more effective in reducing Staphylococcus abundance, whereas LGG excelled in promoting Corynebacterium growth. These findings suggest the ability of LGG and BB-12 to modulate the wound microenvironment, enhance wound healing and provide valuable insights for the management of infected wounds.

Sono-Catalytic Tooth Whitening and Oral Health Enhancement with Oxygen Vacancies-Enriched Mesoporous TiO2 Nanospheres: A Nondestructive Approach for Daily Tooth Care.

Tooth discoloration and the breeding of oral microorganisms pose threats to both one's aesthetic appearance and oral health. Clinical whitening agents based on H2O2 with high concentrations are effective in tooth whitening and bacterial elimination but may also cause enamel demineralization, gingival irritation, or cytotoxicity, necessitating professional supervision. Herein, leveraging sono-catalysis effects, a nondestructive and convenient tooth whitening strategy was developed, utilizing oxygen vacancies (OVs)-enriched mesoporous TiO2 nanospheres. The introduction of OVs leads to TiO2 bandgap narrowing, boosting the generation of reactive oxygen species (ROS) by TiO2 under ultrasound treatment. Additionally, through the chemocatalysis effect, the ROS yield can be further augmented by employing OVs-enriched TiO2 in conjunction with an extremely low concentration of H2O2 (1%) during ultrasound treatment. Hence, under ultrasound treatment simulating daily tooth brushing using an electronic toothbrush, the combination of OVs-enriched TiO2 and 1% H2O2 proves to be effective in whitening teeth stained by tea, coffee, and mix juice. Furthermore, the combination of OVs-enriched TiO2 and 1% H2O2 demonstrates potent bacterial-killing and biofilm-eradicating effects under ultrasound treatment within an extremely short duration (5 min). Additionally, given the mesoporous structure, curcumin, serving as an anti-inflammatory agent, can be efficiently loaded into OVs-enriched TiO2 and then controllably released through ultrasound treatment. The curcumin-loaded TiO2 facilitates the transition of macrophages to the anti-inflammatory M2 phenotype, potentially alleviating oral inflammation induced by bacterial infection without showing any biotoxicity. The OVs-enriched TiO2 based sono-catalysis tooth whitening procedure provides the convenience of whitening teeth during daily brushing without requiring professional supervision.