Inflammation-related Diseases Research Articles

Self-Driven Janus Ga/Mg Micromotors for Reducing Deep Bacterial Infection in the Treatment of Periodontitis.

A self-propulsion Janus gallium (Ga)/magnesium (Mg) bimetallic micromotor is designed with favorable biocompatibility and antimicrobial properties as a therapeutic strategy for periodontitis. The Janus Ga/Mg micromotors are fabricated by microcontact printing technique to asymmetrically modify liquid metallic gallium onto magnesium microspheres. Hydrogen bubbles produced by the magnesium-water reaction can provide the driving performance of up to 31.03 µms-1 (pH 6.8), prompting the micromotor to actively breakthrough the biological barrier of saliva and gingival crevice fluid (GCF) into the bottom of periodontal pockets. In addition, the Janus Ga/Mg micromotors are effectively converted by degradation into the built-in antimicrobial ion Ga(III) to eliminate deep-seated Porphyromonas gingivalis (P.gingivalis), with bactericidal efficiencies of over 99.8%. The developed Janus Ga/Mg micromotors have demonstrated potent antimicrobial and anti-inflammatory activity both in vitro and in vivo studies. Crucially, it reduces alveolar bone resorption, demonstrating the superior efficacy of liquid metal gallium in treating periodontitis. Therefore, Ga/Mg bimetallic micromotors hold great promise to be an innovative and translational drug delivery system to treat periodontitis or other inflammation-related diseases in the near future.

Fishroesomes show intrinsic anti-inflammatory bioactivity and ability as celecoxib carriers in vivo.

According to the World Health Organization (WHO), chronic inflammatory-related diseases represent the greatest threat to human health. Indeed, failure in the resolution of inflammation leads to serious pathological conditions, such as cardiovascular diseases, arthritis, cancer, diabetes, autoimmune diseases, and neurodegenerative disorders that are often associated with extremely high human suffering and societal and economic burdens. Despite the number and efficacy of available therapeutic agents have been increased, the serious side effects associated with some of them often create a very high risk/benefit ratio for patients. Therefore, herein, a drug delivery system was engineered to overcome important drawbacks of conventional therapies and to have a synergistic action with the incorporated drug. Indeed, it will have an added beneficial role in controlling inflammation. For that, sardine (Sardina pilchardus) roe was used as the lipidic source to produce bioactive liposomes, namely fishroesomes. These spherical vesicles with ≈326 nm in size and a significant negative surface charge (≈-31 mV) were able to encapsulate and control the release of the anti-inflammatory drug celecoxib. Moreover, fishroesomes were cytocompatible for different cell types (chondrocytes and macrophages), at concentrations in which they present anti-inflammatory properties. Importantly, fishroesomes were more effective in reducing pro-inflammatory mediators than the free drug. We also demonstrated that a single intra-articular injection of the fishroesomes encapsulating or not celecoxib in an experimental rat model of inflammatory arthritis was safe and more effective in controlling the pain and reducing the synovial inflammation compared to the free drug. Notably, as the celecoxib concentration in the sardine roe-derived liposomes was less than half of the amount of free drug, this study demonstrates the value of fishroesomes in counteracting inflammation. Therefore, the developed formulations may be considered a promising therapeutic option for inflammatory conditions.

Exploring the unique antioxidative and anti-inflammatory properties of aging black lemon (Citrus limon L. Brum. F.)

The aging black lemon is a dried citrus fruit, generally made from lemon, which is lightly thermal processed until it takes on the appearance of blackish-brown leather. This study aimed to determine the phenolic and flavonoid components in aqueous black lemon extract (ABLE). FRAP was used to determine the antioxidant capacity of ABLE. The effects of ABLE on LPS-induced NO production in macrophages (RAW264.7) were investigated by measuring the amount of nitrite released into the culture medium using the Griess reaction. For the anti-inflammatory effects, pro-inflammatory mediators, including iNOS, TNF-α, and NF-κB, were examined by Western blotting. In addition, UPLC/MS/MS data of ABLE presented higher concentrations of gallic acid, protocatechuic acid, vanillic acid, p-coumaric acid, ferulic acid, luteolin, naringenin, hesperetin, and diosmetin than fresh lemon. Based on the results, we consider ABLE to have outstanding anti-inflammation properties by polyphenols and flavonoids and is a great functional food for inflammation-related diseases.

Neuronal PLPP/CIN exaggerates the immune response of hippocampal microglia to LPS challenge dependent on PAK1-NF-κB-COX-2 signaling pathway

Recently, we have reported that pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN) selectively dephosphorylates neurofibromin 2 (NF2, also known as merlin) at serine (S) 10 site. Since NF2 inhibits p21-activated kinase 1 (PAK1)-mediated nuclear factor-κB (NF-κB) activation, in the present study, we investigated the role of PLPP/CIN-mediated NF2 S10 dephosphorylation in lipopolysaccharide (LPS)-induced neuroinflammation and explored its related signaling pathways in the mouse hippocampus. PLPP/CIN overexpression increased NF2 S10 dephosphorylation and PAK1 S204 autophosphorylation under physiological condition, which were reversed by PLPP/CIN deletion. Following LPS injection, PLPP/CIN overexpression exacerbated microglial activation, although microglial PLPP/CIN expression was undetectable. In addition, PLPP/CIN overexpression enhanced PAK1 and NF-κB phosphorylations, and upregulated cyclooxygenase-2 (COX-2) and prostaglandin E synthase 2 (PTGES2) expressions in CA1 neurons. PLPP/CIN overexpression also augmented microglial interleukin-1β induction. PLPP/CIN ablation and 1,1′-dithiodi-2-naphthtol (IPA-3, a PAK1 inhibitor) pretreatment ameliorated these LPS-induced neuroinflammatory responses. These findings indicate that PLPP/CIN-mediated NF2 S10 dephosphorylation may facilitate PAK1-NF-κB-COX-2-PTGES2 signaling pathway in CA1 neurons, which would subsequently exaggerate immune response of microglia following LPS treatment. Therefore, our findings suggest that this PLPP/CIN-mediated neuron-microglia interaction may play an important role in the pathogenesis of inflammation-related neurological diseases.

Hyaluronan-Cholesterol nanogels embedding betamethasone for the treatment of skin inflammatory conditions

Topical application of the glucocorticoid betamethasone (BM) is a common treatment for inflammatory-related skin diseases, such as psoriasis. However, enhancing its bioavailability remains challenging due to poor skin permeability. Herein, we developed and evaluated hyaluronan-cholesterol (HACH) based nanohydrogel systems (NHs) and NHs-Carbopol formulation for dermal delivery of BM. Various parameters were investigated including particle size, surface charge, encapsulation efficiency, in vitro drug release kinetics and stability. The HACH-based NHs demonstrated high encapsulation efficiency, with apparent solubility improved up to 9-fold, small size (∼190 nm) and good stability at 4 ℃ and during long-term storage. Besides, the NHs-Carbopol formulation exhibited excellent rheological properties and an occlusive effect suitable for cutaneous application. Both in-vitro (using Strat-M® membrane) and ex-vivo (using pig ear skin) permeation studies revealed that these formulations significantly improved skin permeation and drug retention in the deeper layers of the epidermis and dermis, making it advantageous for the topical delivery of BM in psoriasis treatment. Moreover, the NHs system demonstrated potential anti-psoriatic activity by downregulating the proinflammatory cytokines in vitro in human keratinocytes (HaCaT cell line) and in an ex vivo 3D skin tissue model (EpiDerm-FT™).

Proinflammatory Cytokines Enhance the Mineralization, Proliferation, and Metabolic Activity of Primary Human Osteoblast-like Cells.

Osteoporosis is a progressive metabolic bone disease characterized by decreased bone density and microarchitectural deterioration, leading to an increased risk of fracture, particularly in postmenopausal women and the elderly. Increasing evidence suggests that inflammatory processes play a key role in the pathogenesis of osteoporosis and are strongly associated with the activation of osteoclasts, the cells responsible for bone resorption. In the present study, we investigated, for the first time, the influence of proinflammatory cytokines on the osteogenic differentiation, proliferation, and metabolic activity of primary human osteoblast-like cells (OBs) derived from the femoral heads of elderly patients. We found that all the proinflammatory cytokines, IL-1β, TNF-α, IL-6, and IL-8, enhanced the extracellular matrix mineralization of OBs under differentiation-induced cell culture conditions. In the cases of IL-1β and TNF-α, increased mineralization was correlated with increased osteoblast proliferation. Additionally, IL-1β- and TNF-α-increased osteogenesis was accompanied by a rise in energy metabolism due to improved glycolysis or mitochondrial respiration. In conclusion, we show here, for the first time, that, in contrast to findings obtained with cell lines, mesenchymal stem cells, or animal models, human OBs obtained from patients exhibited significantly enhanced osteogenesis upon exposure to proinflammatory cytokines, probably in part via a mechanism involving enhanced cellular energy metabolism. This study significantly contributes to the field of osteoimmunology by examining a clinically relevant cell model that can help to develop treatments for inflammation-related metabolic bone diseases.

Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases: a two-sample Mendelian randomization study.

To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

Evaluation of cytotoxicity, chemical composition, antioxidant potential, apoptosis relationship, molecular docking, and MM-GBSA analysis of Rumex crispus leaf extracts

Medicinal plants have been used in the treatment of diseases for centuries due to their pharmaceutical activities. It is known that a significant majority of medicinal plants have antimicrobial, antiplasmodial and antitrypanosomal activities and are also effective in the treatment of infections. Medicinal plants also make significant contributions to cancer treatment. Medicinal plants of the Rumex genus are widely used in the treatment of skin, liver inflammation-related diseases as well as cancer. Rumex crispus, a sub-class of the Rumex genus, is a perennial plant known for its wavy and curly leaves and is used as a useful alternative in traditional medicine. In this study, cytotoxicity of Rumex crispus plant extracts was determined by MTT method. Extract contents of the plant were determined by GC-MS, antioxidant capacity by kit and relationship with apoptosis genes by RT-PCR. Finally, the molecular interactions between Rumex crispus leaf extracts and certain proteins associated with colon cancer (PDB ID: 3DTC and 4UYA) and lung cancer (PDB ID: 4ZXT and 5ZMA) were investigated and their respective activity were compared. The binding free energy of the molecule with the highest docking score is computed using MM/GBSA techniques.

Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion

Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl-) and hydrogen peroxide (H2O2). Endogenous HOCl has recently been studied as a potential biomarker of psoriasis underlying the necessity for the development of efficient analytical tools for its detection and real time monitoring. Herein, we designed a novel highly sensitive and selective coumarin-based fluorescent probe for HOCl detection, named CN2-CF3-S. The probe itself featured negligible fluorescence because of the heavy atom effect of the thiocarbonyl group. However, upon responding to HOCl a conversion to sulfur-free derivative CN2-CF3-O occurs, resulting in a dramatical fluorescent enhancement setting the detection limit for HOCl of 3.2 nM. The HOCl-recognition mechanism could be ascribed to the HOCl-triggered oxidative desulfurization process that agrees with liquid chromatography-mass spectrometry (LC-MS) analysis and density functional theory (DFT) computations. The probe’s design incorporated a synergistic combination of two structural features for efficient lipid droplets (LDs)-targeting imaging. An efficient push–pull system reinforced by the presence of two strongly electron-donating dimethylamino groups equipped CN2-CF3-O with pronounced solvatochromism realized through the enhanced blue-shifted emission in non-polar media. Meanwhile, the presence of trifluormethylphenyl moiety at the acceptor side led to an increased lipophilicity. The CN2-CF3-S probe has been successfully utilized to track the endogenous HOCl in cells and on skin of the psoriatic mice in a wash-free manner. As a result, we have demonstrated that the concentration of HOCl in skin might correlate positively with the degree of inflammation in psoriasis. Thus, CN2-CF3-S constitutes the first example of LDs-imaging fluorescent probe for detecting the psoriasis-linked HOCl, offering a convenient tool for further in-depth investigation of psoriasis pathophysiology.

Exosomes from Limosilactobacillus fermentum Ameliorate Benzalkonium Chloride-Induced Inflammation in Conjunctival Cells.

Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the L. fermentum KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including interleukin (IL)-20, IL-8, IL-6, and IL-1B, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including TJP1, TJP2, and occludin-1, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of IL1B, IL20, IL6, IL8, and NFAT5 in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut-eye axis communication via exosomes.

Mechanism of Resveratrol on LPS/ATP-induced pyroptosis and inflammatory response in HT29 cells

Pyroptosis plays an important role in maintenance of intestinal homeostasis, the abnormal activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome can promote the event and development of ulcerative colitis (UC). Its protective effects such as inhibiting pyroptosis in various inflammation-related diseases have been demonstrated, but whether resveratrol (RES) can also alleviate the progression of the disease by inhibiting pyroptosis in UC and the mechanism have rarely been studied. In this study, lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP) was used to induce HT29 human colon cancer cells to construct an intestinal epithelial cell pyroptosis and inflammation model in vitro to investigate the anti-inflammatory effect of RES, reveal the regulatory mechanism of RES on pyroptosis, and provide a new theoretical basis for the treatment of UC. In vitro experiences, HT29 cells were dividing into control group, LPS/ATP group, RES low-dose group, RES high-dose group, NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), and LPS/ATP+PDTC group. The mRNA expressions of pyroptosis-related indicators such as NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1(CASP1), IL-18, IL-1β, and inflammatory factors such as TNF-α and IL-6 were detected by qRT-PCR. The protein expressions of pyroptosis-related indicators NLRP3, ASC, CASP1, IL-18, IL-1β, NF-κB-p65 in the nucleus, and IκBα and p-IκBα in the cytoplasm were detected by Western blot. Immunofluorescence saw the distribution and expression of NLRP3, ASC and NF-κB-p65 protein in each group. The morphology and degree of pyroptosis in each group were observed by transmission electron microscope. The results showed that compared with the control group, the pyroptosis-related proteins including NLRP3, ASC, CASP1, IL-18, IL-1β, and inflammatory factors including TNF-α and IL-6 in the LPS/ATP group were increased, and LPS/ATP activated the activity of NF-κB signaling pathway. Compared with the LPS/ATP group, RES downregulated the expression of pyroptosis-related proteins and inflammatory factors in HT29 cells, and inhibited the activation of the NF-κB signaling pathway in HT29 cells pyroptosis. RES down-regulates the pyroptosis of HT29 cells induced by LPS/ATP and the expression of pyroptosis-related indicators NLRP3, ASC, CASP1, IL-18, IL-1β and inflammatory factors TNF-α and IL-6 in the inflammatory response and inhibits the occurrence of pyroptosis. The mechanism is related to the inhibition of NF-κB pathway activity.

Abstract 4134249: Cardiovascular Risk Factors and Associations of Chronic Inflammatory-Related Disease in the Multi-Ethnic Study of Atherosclerosis

Background: Inflammation plays a role in the development of cardiovascular disease (CVD). We have defined various non-cardiovascular and non-cancer conditions, both infectious and non-infectious, with a common basis of inflammation; collectively termed Chronic Inflammatory-Related Disease (ChrIRD). We have previously described that ChrIRD is common, associated with baseline inflammatory marker levels, associated with high mortality, and has a bidirectional association with CVD. The clinical implications of these data require further study. Aims: We hypothesize that many traditional risk factors for CVD are also associated with ChrIRD and that ChrIRD has additional unique risk factors. We also hypothesize that the treatment of traditional CVD risk factors is associated with a decreased likelihood of ChrIRD. Methods: We studied MESA participants free of overt CVD or significant illness at baseline. ChrIRD was determined based on review of ICD codes for hospitalizations and deaths. Incident CVD was adjudicated by review of medical records. We performed proportional hazards regression (time-dependent for CVD) to identify factors associated with a first diagnosis of ChrIRD. All variables were simultaneously entered into the model. Results: Participants (n=6155) had mean age 62±10 years and 47% male gender. ChrIRD was observed in 24% and CVD in 18%; including 8% with both conditions. Participants with a diagnosis of CVD, older age, higher heart rate, higher BMI, current or ever smoking status, higher HDL, higher baseline IL6 and GlycA levels, and NSAID use had increased likelihood of ChrIRD. Whereas those with female sex, higher total cholesterol, and statin use had a decreased likelihood of ChrIRD. Participant race/ethnicity, blood pressure, diabetes status, antihypertensive use, aspirin use, baseline CRP level, and baseline D-dimer level were not associated with ChrIRD. Regression results are summarized in Table 1. Conclusions: ChrIRD shares some risk factors with CVD, while other risk factors are opposite. Better understanding of ChrIRD could eventually lead to improved patient care.

Innate Immunity and Synovitis: Key Players in Osteoarthritis Progression.

Osteoarthritis (OA) is a chronic progressive disease of the joint. Although representing the most frequent cause of disability in the elderly, OA remains partly obscure in its pathogenic mechanisms and is still the orphan of resolutive therapies. The concept of what was once considered a "wear and tear" of articular cartilage is now that of an inflammation-related disease that affects over time the whole joint. The attention is increasingly focused on the synovium. Even from the earliest clinical stages, synovial inflammation (or synovitis) is a crucial factor involved in OA progression and a major player in pain onset. The release of inflammatory molecules in the synovium mediates disease progression and worsening of clinical features. The activation of synovial tissue-resident cells recalls innate immunity cells from the bloodstream, creating a proinflammatory milieu that fuels and maintains a damaging condition of low-grade inflammation in the joint. In such a context, cellular and molecular inflammatory behaviors in the synovium could be the primum movens of the structural and functional alterations of the whole joint. This paper focuses on and discusses the involvement of innate immunity cells in synovitis and their role in the progression of OA.

Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update.

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.

17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7.

Macrophages are major effectors in regulating immune response and inflammation. The pro-inflammatory phenotype (M1) is induced by the activation of the Toll-like receptor 4 (TLR4) on the macrophage surface, which recognizes lipopolysaccharide (LPS), a component of Gram-negative bacterial wall, and by the binding of interferon-gamma (IFNγ), a cytokine released by activated T lymphocytes, to its receptor (IFNGR). Among the pathways activated by LPS/IFNγ is the Notch pathway, which promotes the M1 phenotype. Conversely, 17β-estradiol (E2) has been shown to blunt LPS-mediated inflammatory response. While it has been shown that E2 regulates the activity of the Notch1 receptor in human endothelial cells, there is no evidence of estrogen-mediated regulation of Notch1 in macrophages. In this study, RAW 264.7 cells were stimulated with LPS/IFNγ in the presence or absence of E2 and/or N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of γ-secretase, the enzyme involved in Notch activation. The effects of treatment on inducible nitric oxide synthase (iNOS), on components of the Notch pathway, and MAPK (mitogen-activated protein kinase) were assessed by quantitative PCR and Western blotting. We found that E2, through a mechanism involving the inhibition of p38 phosphorylation, reduces the activation of Notch1 induced by LPS/IFNγ. On the contrary, Notch1 exerts a negative control on the estrogen receptor α (ERα) since Notch1 inhibition increases the protein levels of this receptor. In conclusion, we report for the first time a Notch-ERα interaction in macrophages. Our data suggest that E2 may reduce LPS/IFNγ-mediated M1 pro-inflammatory phenotype in macrophages by inhibiting Notch1. This finding encourages further studies on Notch1 inhibitors as novel treatments for inflammation-related diseases.

Nanomotors as Therapeutic Agents: Advancing Treatment Strategies for Inflammation-Related Diseases.

Inflammation is a physiological response of the body to harmful stimuli such as pathogens, damaged cells, or irritants, involving a series of cellular and molecular events. It is associated with various diseases including neurodegenerative disorders, cancer, and atherosclerosis, and is a leading cause of global mortality. Key inflammatory factors, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), RANTES (CCL5), and prostaglandins, play central roles in inflammation and disease progression. Traditional treatments such as NSAIDs, steroids, biologic agents, and antioxidants have limitations. Recent advancements in nanomaterials present promising solutions for treating inflammation-related diseases. Unlike nanomaterials that rely on passive targeting and face challenges in precise drug delivery, nanomotors, driven by chemical or optical stimuli, offer a more dynamic approach by actively navigating to inflammation sites, thereby enhancing drug delivery efficiency and therapeutic outcomes. Nanomotors allow for controlled drug release in response to specific environmental changes, such as pH and inflammatory factors, ensuring effective drug concentrations at disease sites. This active targeting capability enables the use of smaller drug doses, which reduces overall drug usage, costs, and potential side effects compared to traditional treatments. By improving precision and efficiency, nanomotors address the limitations of conventional therapies and represent a significant advancement in the treatment of inflammation-related diseases. This review summarizes the latest research on nanomotor-mediated treatment of inflammation-related diseases and discusses the challenges and future directions for optimizing their clinical translation.

Tanshinone IIA, a component of Salvia miltiorrhiza Bunge, attenuated sepsis-induced liver injury via the SIRT1/Sestrin2/HO-1 signaling pathway

Ethnopharmacological relevanceAs a traditional Chinese medicine, Salvia miltiorrhiza Bunge has been widely used to treat ischemic and inflammation-related diseases for more than 2000 years. S. miltiorrhiza Bunge has hepatoprotective effects, but the underlying mechanism is not fully understood. ObjectiveTo verify the effect of tanshinone IIA (Tan IIA), the main fat-soluble component of S. miltiorrhiza Bunge, on liver damage induced by sepsis/LPS-induced inflammation and further explore the underlying mechanisms. Materials and methodsMice were administered Tan IIA 2 h before cecal ligation and puncture (CLP). Liver damage was evaluated by hematoxylin-eosin staining and changes in related serum factor levels. The expression of silent information regulator sirtuin 1 (SIRT1), Sestrin2, HO-1 and inflammatory cytokines was examined by immunohistochemistry or western blotting. LPS was used to induce the inflammatory response in vitro, and the activity of the related signaling pathway in response to Tan IIA was detected by western blotting. The SIRT1 inhibitor EX-527 and small interfering RNAs (siRNAs) were employed to determine the key roles of SIRT1 and Sestrin2 in Tan IIA's function. ResultsWe found that Tan IIA significantly improved the pathological changes and function of the liver, and alleviated liver damage in CLP mice. Additionally, SIRT1, Sestrin2, and HO-1 expression was significantly elevated after Tan IIA treatment compared with that in the CLP group both in vivo and in vitro, and Tan IIA treatment additionally suppressed pro-inflammatory cytokine release. However, inhibition of either SIRT1 or Sestrin2 remarkably abrogated the protective effects of Tan IIA. Most importantly, Sestrin2 appeared to function downstream of SIRT1 based on their expression changes after EX-527 or siRNA treatment. ConclusionTan IIA inhibited sepsis/LPS-induced inflammation through the SIRT1/Sestrin2/HO-1 pathway, thereby protecting against sepsis-induced liver injury (SLI). This study suggests that Tan IIA has therapeutic potential against SLI and that the SIRT1/Sestrin2/HO-1 signaling pathway might be a viable target for SLI treatment.

Melissa officinalis Regulates Lipopolysaccharide-Induced BV2 Microglial Activation via MAPK and Nrf2 Signaling.

Neuroinflammation and microglial activation play critical roles in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Modulating microglial activation may help prevent the progression of these disorders. This study aimed to investigate the effects and mechanisms of Melissa officinalis ethanol extract on lipopolysaccharide (LPS)-induced microglial activation in BV2 cells. Cell viability and nitric oxide (NO) production were assessed using MTT assay and Griess reagent, while inflammatory cytokine levels were measured by qPCR. Key inflammatory pathways, including MAPK, TLR4, and antioxidant biomarkers, were analyzed through western blot and immunofluorescence. Rosmarinic acid content in M. officinalis was determined using high-performance liquid chromatography (HPLC). The results demonstrated that M. officinalis ethanol extract significantly inhibited LPS-induced NO production and reduced inflammatory cytokine expression. Additionally, it downregulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TLR4, NF-κB, and MAPK signaling pathways (p38, JNK, ERK), while increasing the expression of antioxidant markers, including Nrf2, HO-1, catalase, and SOD2. In conclusion, M. officinalis ethanol extract exerts neuroprotective effects by modulating inflammation and enhancing antioxidant defenses, suggesting its potential in the prevention and treatment of inflammation-related neurodegenerative diseases.

Predictive Value of Red Blood Cell Distribution Width-to-Platelet Ratio for Severity in Pyogenic Liver Abscess: A Retrospective Observational Study.

Background: The ratio of red blood cell distribution width (RDW) to platelet ratio (RPR) may have prognostic value in several inflammation-related diseases. However, few studies have been conducted on the value of RPR for predicting the severity of pyogenic liver abscess (PLA). Methods: Patients receiving the diagnosis of PLA from February 2013 to December 2022 were enrolled in this retrospective study. We collected data related to baseline characteristics and laboratory results within the first 24 hours the of admission. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate the predictive ability of different indicators for severity in PLA. Results: A total of 278 patients were enrolled. For the prediction of sepsis in PLA, RPR had the highest AUC (0.83; 95% confidence interval [CI], 0.78-0.89) with a sensitivity of 0.78 and specificity of 0.82. For the prediction of septic shock, RPR also had the highest AUC (0.74; 95% CI, 0.60-0.88) with a sensitivity of 0.67 and specificity of 0.79. The best cutoff value for RPR to predict sepsis was 0.08 and to predict septic shock was 0.11. Conclusions: An increase in RPR level serves as a useful indicator with a predictive capacity for severity in PLA.

Virtual screening-led design of inhibitor scaffolds for the NLRP3 inflammasome

The NLRP3 inflammasome is a key target for drug discovery due to its implication in a range of inflammation-related diseases. In this work, we identify new inhibitors of the NLRP3 inflammasome via a hierarchical virtual screening strategy using molecular similarity, docking and MD simulation. The most potent inhibitors identified from a subsequent biological assay (IC50 of 1 – 4 μM) feature a sulfonamide group, a motif known to favour NLRP3 inhibition, in conjunction with an indole, benzofuran or tricyclic 6,7-dihydro-5H-indeno[5,6-b]furan ring, yielding novel scaffolds. These structures provide a basis for the design of more potent, selective NLRP3 inhibitors.