PPAR-γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting.

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.

Gene-Engineered Cerium-Exosomes Mediate Atherosclerosis Therapy Through Remodeling of the Inflammatory Microenvironment and DNA Damage Repair.

The pro-inflammatory immune microenvironment in the localized lesion areas and the absence of DNA damage repair mechanisms in endothelial cells serve as essential accelerating factors in the development of atherosclerosis. The lack of targeted therapeutic strategies represents a significant limitation in the efficacy of therapeutic agents for atherosclerosis. In this study, Genetically engineered SNHG12-loaded cerium-macrophage exosomes (Ce-Exo) are designed as atherosclerosis-targeting agents. In vivo studies demonstrated that Ce-Exo exhibited multivalent targeting properties for macrophages, with a 4.1-fold higher atherosclerotic plaque-aggregation ability than that of the control drugs. This suggests that Ce-Exo has a higher homing capacity and deeper penetration into the atherosclerotic plaque. In apolipoprotein E-deficient mice, Ce-Exo found to effectively remodel the immune microenvironment in the lesion area, repair endothelial cell damage, and inhibit the development of atherosclerosis. This study provides a novel approach to the treatment of atherosclerosis and demonstrates the potential of cell-derived drug carriers in biomedicine.

Engineered Macrophage Membrane-Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death.

Spinal cord injury (SCI) is a severe neurological disorder characterized by significant disability and limited treatment options. Mitigating the secondary inflammatory response following the initial injury is the primary focus of current research in the treatment of SCI. CCL2 (C─C motif chemokine ligand 2) serves as the primary regulator responsible for inflammatory chemotaxis of the majority of peripheral immune cells, blocking the CCL2-CCR2 (C─C chemokine receptor type 2) axis has shown considerable therapeutic potential for inflammatory diseases, including SCI. In this study, it presents a multifunctional biomimetic nanoplatform (CCR2-MM@PLGA/Cur) specifically designed to target the CCL2-CCR2 axis, which consisted of an engineered macrophage membrane (MM) coating with enhanced CCR2 expression and a PLGA (poly (lactic-co-glycolic acid)) nanoparticle that encapsulated therapeutic drugs. CCR2 overexpression on MM not only enhanced drug-targeted delivery to the injury site, but also attenuated macrophage infiltration, microglia pro-inflammatory polarization, and neuronal apoptosis by trapping CCL2. Consequently, it facilitated neural regeneration and motor function recovery in SCI mice, enabling a comprehensive treatment approach for SCI. The feasibility and efficacy of this platform are confirmed through a series of in vitro and in vivo assays, offering new insights and potential avenues for further exploration in the treatment of SCI.

Vagus nerve stimulation (VNS) preventing postoperative cognitive dysfunction (POCD): two potential mechanisms in cognitive function.

Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.

Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis.

AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.

Lockd Enhances Mandibular Mesenchymal Stem Cell Proliferation While Inhibiting Osteogenic Capability via Binding With SUZ12 in the Inflammatory Microenvironment.

AIM: To investigate the role of lncRNA Lockd in mandibular mesenchymal stem cell (M-MSC) proliferation and osteogenic capability in the inflammatory microenvironment, focusing on its interaction with SUZ12. MATERIALS AND METHODS: Using lncR Lockd knockdown/overexpression cell models and a murine periodontitis model, we explored Lockd's effects on M-MSC proliferation and osteogenic capability in the inflammatory microenvironment. Predictions from multiple databases and a series of rescue experiments revealed the regulatory role of the Lockd/SUZ12 signalling axis of M-MSC in the inflammatory microenvironment. RESULTS: Lockd was found to stimulate M-MSC proliferation but impair osteogenic differentiation. The in vitro studies suggested that the activation of Lockd negatively inhibited the osteogenic differentiation process and may ultimately impact bone formation in periodontitis. Mechanistically, it was elucidated that Lockd interacts with SUZ12, a core component of the polycomb repressive complex 2 (PRC2), and may affect the PRC2 complex's role in osteogenic gene expression. CONCLUSIONS: Lockd boosts the proliferation of M-MSCs but inhibits their osteogenic differentiation by interacting with SUZ12, potentially inhibiting osteogenic capability in the inflammatory microenvironment.

CircRNAs regulate the crosstalk between inflammation and tumorigenesis: The bilateral association and molecular mechanisms.

Inflammation, a hallmark of cancer, has been associated with tumor progression, transition into malignant phenotype and efficacy of the chemotherapeutic agents in cancer. Chronic inflammation provides a favorable environment for tumorigenesis by inducing immunosuppression, whereas acute inflammation prompts tumor suppression by generating anti-tumor immune responses. Inflammatory factors derived from interstitial cells or tumor cells can stimulate cell proliferation and survival by modulating oncogenes and/or tumor suppressors. Recently, a new class of RNAs, i.e., circular RNAs (circRNAs), has been implicated in inflammatory diseases. Although there are reports on circRNAs imparting functions in inflammatory insults, whether these circularized transcripts hold the potential to regulate inflammation-induced cancer or tumor-related inflammation, and modulate the interactions between tumor microenvironment (TME) and the inflammatory stromal/immune cells, awaits further elucidation. Contextually, the current review describes the molecular association between inflammation and cancer, and spotlights the regulatory mechanisms by which circRNAs can moderate TME in response to inflammatory signals/triggers. We also present comprehensive information about the immune cell(s)-specific expression and functions of the circRNAs in TME, modulation of inflammatory signaling pathways to drive tumorigenesis, and their plausible roles in inflammasomes and tumor development. Moreover, the therapeutic potential of these circRNAs in harnessing inflammatory responses in cancer is also discussed.

Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy.

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.

BACKGROUND: Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery. RESULTS: We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice. CONCLUSION: Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.

The Role of Autophagy on Osteogenesis of Dental Follicle Cells Under Inflammatory Microenvironment.

OBJECTIVE: This study investigated the role of autophagy on osteogenesis of DFCs under inflammatory microenvironment during tooth eruption. METHODS: DFCs were isolated and identified. Lipopolysaccharide (LPS) was used to construct the inflammatory microenvironment in vitro and in vivo. Cell viability was examined by CCK-8 assay. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining. The gene and protein levels were examined using qRT-PCR and western blot analysis, respectively. We observed the process of tooth eruption after local LPS injection by micro-CT and HE staining. Osteogenesis and autophagy were monitored through qRT-PCR, western blot and histological staining of specific markers. RESULTS: LPS at the indicated concentrations did not produce toxic effects on DFCs, and significantly promoted the inflammatory gene expression. LPS inhibited osteogenic differentiation and activated autophagy in DFCs. Blocking autophagy with 3-MA reversed the expression of osteogenic markers in LPS-treated DFCs. Additionally, the eruption of LPS-treated teeth was accelerated and their DFs exhibited an increased expression of TNF-α and Beclin1, and decreased expression of ALP and RUNX2. CONCLUSIONS: Autophagy was involved in the suppression of the DFCs osteogenesis in an LPS-induced inflammatory condition, suggesting the pivotal role of autophagy in inflammation-induced premature tooth eruption.

uPAR (PLAUR) Marks Two Intra-Tumoral Subtypes of Glioblastoma: Insights from Single-Cell RNA Sequencing.

Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell.

Trends and challenges on inflammatory microenvironment in diabetic wound from 2014 to 2023: A bibliometric analysis.

The disturbance of the inflammatory microenvironment is a frequent pathological trait of diabetic wounds, contributing to the emergence of numerous chronic illnesses. This is crucial in both the development and recovery of wounds caused by diabetes. This study aims to perform a bibliometric analysis of research on the inflammatory microenvironment within the domain of diabetic wounds (DW) over the past 10 years. The objective is to map out the current global research landscape, pinpoint the most significant areas of study and offer guidance for future research avenues. Our research involved querying the Web of Science Core Collection (WoSCC) database for all pertinent studies on the inflammatory microenvironment in diabetic wounds (DW). We utilized bibliometric tools such as CiteSpace, VOSviewer and R (version 4.3.1) to identify and highlight the most impactful studies in the field. The study encompassed a review of 1454 articles published from 2014 to 2023, highlighting China and the United States as pivotal nations in the research of the inflammatory microenvironment in diabetic wounds (DW). Within this sphere, the University of Michigan and Harvard University in the United States, along with Shanghai Jiaotong University in China, emerged as the most prolific institutions. WANG Y from China was identified as the most productive author, while KUNKEL SL from the United States received the most citations. The research primarily focuses on topics such as wound healing, repair processes, angiogenesis, oxidative stress and macrophage activity. Additionally, "macrophage" and "delivery" were pinpointed as the leading subjects with promising research potential in this area. Research on the inflammatory microenvironment of diabetic wounds is rapidly advancing through active international collaboration. The study of new mechanisms related to the inflammatory microenvironment and the development of novel materials for repair based on this microenvironment represent emerging fields of future research, particularly in terms of translational applications. This may offer guidance and novel perspectives for further research in the area of the diabetic wound inflammatory microenvironment.

[Potential pathways for traditional Chinese medicine intervention in diabetic kidney disease: macrophage polarization].

Diabetic kidney disease(DKD) is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM). Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals. Macrophages play a crucial role in immune-inflammatory responses, and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences. The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium. Therefore, restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD. Macrophage polarization is a complex and dynamic process. Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD. They are closely related to various mechanisms such as metabolism, inflammation, fibrosis, and mitochondrial autophagy in DKD. By coordinating the inflammatory responses through polarization, they play a key role in regulating inflammation in metabolic-related diseases. The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway, multi-target treatment model of traditional Chinese medicine(TCM). Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization. Studies on relieving renal inflammation, repairing renal tissues, and promoting renal function recovery through macrophage polarization modulation are not uncommon. Therefore, based on exis-ting evidence, this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD, aiming to explore the potential of macrophage polarization in regulating DKD, which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.

Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.

BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS: The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. RESULTS: The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. CONCLUSIONS: This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.

Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo.

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

Intervertebral disc degeneration and inflammatory microenvironment: expression, pathology, and therapeutic strategies.

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of low back pain (LBP), posing a significant socioeconomic burden. Recent studies highlight the crucial role of inflammatory microenvironment in IDD progression. METHOD: A keyword-based search was performed using the PubMed database for published articles. RESULTS AND CONCLUSIONS: Dysregulated expression of inflammatory cytokines disrupts intervertebral disc (IVD) homeostasis, causing atrophy, fibrosis, and phenotypic changes in nucleus pulposus cells. Modulating the inflammatory microenvironment and restoring cytokine balance hold promise for IVD repair and regeneration. This comprehensive review systematically examines the expression regulation, pathological effects, therapeutic strategies, and future challenges associated with the inflammatory microenvironment and relevant cytokines in IDD. Key inflammatory cytokines, including interleukins (IL), tumor necrosis factor-alpha (TNF-α), and chemokines, exhibit significant pathological effects in IDD. Furthermore, major therapeutic modalities such as chemical antagonists, biologics, plant extracts, and gene transcription therapies are introduced to control and ameliorate the inflammatory microenvironment. These approaches provide valuable insights for identifying potential targets in future anti-inflammatory treatments for IDD.

Microenvironment of pancreatic inflammation: calling for nanotechnology for diagnosis and treatment.

Acute pancreatitis (AP) is a common and life-threatening digestive disorder. However, its diagnosis and treatment are still impeded by our limited understanding of its etiology, pathogenesis, and clinical manifestations, as well as by the available detection methods. Fortunately, the progress of microenvironment-targeted nanoplatforms has shown their remarkable potential to change the status quo. The pancreatic inflammatory microenvironment is typically characterized by low pH, abundant reactive oxygen species (ROS) and enzymes, overproduction of inflammatory cells, and hypoxia, which exacerbate the pathological development of AP but also provide potential targeting sites for nanoagents to achieve early diagnosis and treatment. This review elaborates the various potential targets of the inflammatory microenvironment of AP and summarizes in detail the prospects for the development and application of functional nanomaterials for specific targets. Additionally, it presents the challenges and future trends to develop multifunctional targeted nanomaterials for the early diagnosis and effective treatment of AP, providing a valuable reference for future research.

Pleiotrophin inhibited chondrogenic differentiation potential of dental pulp stem cells.

OBJECTIVE: Studies have shown that the levels of pleiotrophin (PTN) are greatly elevated in the synovial fluid and cartilage in osteoarthritis. Therefore, the purpose of this study was to investigate the effect and mechanism of PTN on the chondrogenic differentiation of DPSCs in inflammatory and normal microenvironments. MATERIALS AND METHODS: A lentiviral vector was used to deplete or overexpress PTN in DPSCs. The inflammatory microenvironment was simulated in vitro by the addition of IL-1ß to the culture medium. The chondrogenic differentiation potential was assessed using Alcian Blue staining and the main chondrogenic markers. A dual-luciferase reporter assay was used to explore the relationship between miR-137 and PTN. RESULTS: The results showed that 0.1 ng/mL IL-1ß treatment during chondrogenic induction greatly impaired the chondrogenic differentiation of DPSCs. Supplementation with PTN and PTN overexpression inhibited chondrogenic differentiation of DPSCs, while PTN depletion promoted chondrogenic differentiation. MiR-137 negatively regulated the expression of PTN by binding to the 3'UTR of its mRNA. Moreover, miR-137 promoted chondrogenic differentiation of DPSCs in normal and inflammatory microenvironments. CONCLUSION: Our results suggest that PTN may play an inhibitory role in the chondrogenic differentiation of DPSCs in normal and inflammatory microenvironments, which is regulated by miR-137.

PM2.5 exposure aggravates acute liver injury by creating an inflammatory microenvironment through Kupffer cell.

AIM: This work aimed to investigate the impact of PM2.5 exposure on acute liver injury METHODS: C57BL/6 mice were used to examine the hepatic histopathological changes in PM2.5-exposed mice, as well as in CCl4-mediated acute liver injury mice after long-term exposure to PM2.5. During in vitro experiments, Kupffer cells were detected for M1 polarization level after treating with PM2.5, and the activation level of NLRP3 inflammasomes were assessed. RESULTS: According to our findings, PM2.5 can induce M1 polarization of Kupffer cells in the liver to create an inflammatory microenvironment. Long-term exposure to PM2.5 can aggravate acute liver injury in mice. Treatment with MCC950, an NLRP3 inhibitor, can inhibit the effect of PM2.5. As demonstrated by in vitro analysis, PM2.5 can promote M1 polarization of Kupffer cells. CONCLUSION: As suggested by our results, long-term exposure to PM2.5 can create an inflammatory microenvironment to aggravate mouse acute liver injury. The effect is related to NLRP3-mediated M1 polarization in Kupffer cells.

LINC00702-mediated DUSP1 transcription in the prevention of bladder cancer progression: Implications in cancer cell proliferation and tumor inflammatory microenvironment.

BACKGROUND: Long noncoding RNAs (lncRNAs) can mediate the biological processes during tumorigenesis which may be affected by tumor associated macrophages (TAMs). Hence, we aim to identify the functionality of LINC00702 in regulation of bladder cancer cells and M2-TAMs. METHODS: After induction of M2-TAMs from THP-1 monocyte, we evaluated effects of LINC00702 on bladder cancer cells and M2-TAMs, which were validated in a xenograft tumor mouse model. RESULTS: Low LINC00702 expression was determined in bladder cancer tissues. LINC00702 could promote DUSP1 transcription by recruiting JUND to its promoter. Ectopic LINC00702 expression suppressed the bladder cancer cell proliferation and secretion of inflammatory cytokines by M2-TAMs through up-regulation of DUSP1. The anti-tumor activity of LINC00702 was ultimately validated in vivo. CONCLUSION: LINC00702 promoted DUSP1 by recruiting JUND to inhibit the proliferation of bladder cancer cells and the secretion of inflammatory factors, thus modulating bladder cancer inflammatory microenvironment.