Immunopharmacology and Immunotoxicology最新文献

Objective: Inflammatory diseases are influenced by oxidative stress. Oxidatively damaged 8-oxoG in DNA is linked to inflammation. The enzyme OGG1 is responsible for repairing the damaged base in the DNA which is linked to pro-inflammatory signaling and severe inflammation. This study aims to explore the potential of targeting OGG1 as a therapeutic strategy in inflammatory disease conditions.

Methods: A comprehensive search and review of literature were conducted using appropriate scientific databases such as Google Scholar, Scopus, PubMed, Web of Science, and other references to obtain relevant information that suited the title and content of this article.

Results: Compelling pieces of evidence from many previous studies have shown the crucial role of the OGG1/8oxoG pathway in inflammatory disease conditions, leading to severe inflammatory response and death. Therefore, based on these pieces of evidence, targeting this enzyme (OGG1) using specific pharmacological inhibitors or interventions might lead to downregulation and amelioration of severe inflammation to reduce the morbimortality related to several disease conditions.

Conclusion: This review highlighted the molecular mechanism of OGG1 activity via the 8-oxo/OGG1 pathway and its role in inflammation and inflammatory disease conditions. Due to the paucity of studies involving OGG1in inflammatory infectious diseases, further research projects are needed to explore the therapeutic potential of various OGG1 inhibitors to serve as novel therapeutic strategies in infectious inflammatory diseases of medical importance in developing countries such as malaria, meningitis, tuberculosis among others.

Objective: Inulicin is a sesquiterpene lactone in Inulae Flos which is clinically used for the treatment of inflammatory diseases, such as cough, sputum production, and vomiting. This study aimed to demonstrate the anti-inflammatory activity and the underlying mechanism of inulicin by using lipopolysaccharide (LPS)-induced in vitro and in vivo models.

Methods: LPS-stimulated RAW264.7 macrophages and mouse peritoneal macrophages (MPMs) were used for evaluating the in vitro anti-inflammatory activity of inulicin, while endotoxemia mice were used for evaluating its in vivo action. Cytokines' levels were determined by ELISA. RT-qPCR and western blot were used for assaying the mRNA and protein levels of target genes. RAW264.7 macrophages transfected with reporter plasmid pNFκB-TA-luc or pAP1-TA-luc were used for assaying the activation of NF-κB or AP-1 signaling.

Results: Inulicin significantly inhibited LPS-induced production of NO, IL-6, c-c motif chemokine ligand 2 (CCL2), and IL-1β in both RAW264.7 cells and MPMs. Mechanism study indicated that it could suppress inducible nitric oxide synthase, IL-6, CCL2, and IL-1β mRNA levels in LPS-stimulated RAW264.7 cells. Moreover, inulicin inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating NF-κB signaling. Concurrently, it also inhibited AP-1 signaling by reducing the phosphorylation of C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). In endotoxemia mice, a single intraperitoneal administration of inulicin could decrease the production of pro-inflammatory cytokines in serum and peritoneal lavage fluid.

Conclusions: The present study demonstrates that inulicin possesses anti-inflammatory effects in vitro and in vivo, which suggests that inulicin might be a promising candidate for the treatment of inflammatory diseases.

Introduction: Bone marrow mesenchymal stem cell (BMMSC) transplantation is beneficial in treating Systemic lupus erythematosus (SLE); however, the underlying mechanism remains elusive. This study investigates the role of BMMSCs in regulating lymphocyte proliferation and cell cycle progression during SLE and delves into the contribution of BMMSC-produced galectin-1.

Methods: BMMSCs were co-cultured with T lymphocytes to assess their impact on suppressing CD4+ T cells in SLE patients. Proliferation and cell cycle distribution of CD4+ T cells were analyzed using flow cytometry. The expression of cell cycle-related proteins, including p21, p27, and cyclin-dependent kinase 2 (CDK2), was investigated through western blotting. Extracellular and intracellular galectin-1 levels were determined via ELISA and flow cytometry. The role of galectin-1 in CD4+ T cell proliferation and cell cycle was evaluated through RNAi-mediated galectin-1 expression disruption in BMMSCs.

Results and discussion: BMMSCs effectively inhibited CD4+ T cell proliferation and impeded their cell cycle progression in SLE patients, concurrently resulting in a reduction in CDK2 levels and an increase in p21 and p27 expression. Moreover, BMMSCs expressed a high level of galectin-1 in the co-culture system. Galectin-1 was found to be critical in maintaining the suppressive activity of BMMSCs and restoring the cell cycle of CD4+ T cells.

Conclusion: This study demonstrates that BMMSCs suppress the proliferation and influence the cell cycle of CD4+ T cells in SLE patients, an effect mediated by the upregulation of galectin-1 in BMMSCs.

Background: Pulmonary surfactant (PS) plays an important role in the treatment of sepsis-induced acute lung injury (ALI). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, improves the secretion and function of PS in ALI, but the underlying mechanism remains unknown. This study aimed to investigate how liraglutide regulates PS secretion in ALI.

Methods: C57BL/6 mice were injected subcutaneously with normal saline containing different concentrations of liraglutide after the establishment of the ALI model. MLE-12 cells were treated with liraglutide after LPS stimulation. The survival rate of mice, wet/dry weight ratio, inflammatory factors in bronchoalveolar lavage fluid (BALF), pulmonary injury, and apoptosis were analyzed. Cell viability, proliferation, apoptosis, the expression of SP-A, SP-B, and expression of autophagy-related proteins in cells were measured.

Results: ALI mice showed reduced pulmonary injury, less apoptosis, and less inflammation compared to the controls. Liraglutide prolonged survival, decreased the wet/dry weight ratio, reduced inflammatory responses, and attenuated pulmonary edema compared with the ALI group. Moreover, LPS-induced cell damage and reduction of SP-A and SP-B expression were markedly reversed by liraglutide in MLE-12 cells. Furthermore, the protective effects of liraglutide were reversed by rapamycin.

Conclusion: Liraglutide alleviate sepsis-induced ALI by inhibiting autophagy and regulating PS.

Objective: Polyphenols are organic compounds with diverse biological activities such as anti-inflammatory and antioxidant effects, making them important candidates for the development of anti-aging drugs. In this systematic review, we aimed to answer the question: can plant-derived polyphenols have an immunomodulatory effect in experimental models of aging?

Methods: We systematically searched Web of Science, MEDLINE/Pubmed, and Embase to select articles using the following combinations of terms and synonyms: polyphenols, phenols, senescence, aging, and immune. The selected articles were evaluated for reporting quality and risk-of-bias according to standard guidelines.

Results: The most used polyphenol was resveratrol, followed by curcumin, salidroside, and gallic acid. These molecules demonstrated an ability to restore immune function both in vitro and in vivo. The mechanism of action was not completely elucidated in these studies, but inhibition of NF-kB signaling, and antioxidant properties seemed to account for the anti-aging effects. All articles included in the review had good quality of reporting but failed to describe an adequate sample size, criteria for inclusion/exclusion, randomization, and blinding.

Conclusion: We conclude that polyphenols are promising immunomodulatory substances for use in anti-aging therapies. However, more research with standardized analysis is needed to understand the role of these molecules in the prevention or reduction of damage associated with the aging process, as well as to determine the safety profile and consequences of systemic action.

Background: Skin flap transplantation is used to effectively reconstruct defects of the hand and foot skin and soft tissues. We here investigated the effect of the PF127/bleomycin (BLM) hydrogel on the extracellular matrix (ECM) remodeling of skin flaps and the underlying mechanism, thereby providing a new reference point for personalized flap modification and overcoming abrasion resistance- and stability-associated difficulties.

Methods: The appropriate PF127/BLM concentration was selected based on the gelation time and drug release curve. Migration assays, scratch assays, and live/dead staining were conducted to verify the effect of PF127/BLM on human skin fibroblasts (HSFs). The effects of PF127/BLM on the ECM were assessed through hematoxylin and eosin and Masson staining. Additionally, we examined the expression of ECM remodeling-related genes and proteins involved in their associated signaling pathway. Finally, the effects of PF127/BLM on organ fibrosis and toxicity to liver and kidney functions were assessed in mice.

Results: A 25% PF127/BLM hydrogel was selected as the study concentration. PF127/BLM augmented HSF chemotaxis and proliferation. Furthermore, PF127/BLM promoted subcutaneous ECM remodeling and fibrosis, increased the flap dermis thickness, and reduced the toxic side effects of BLM on liver/lung fibrosis and liver/kidney function. Additional studies confirmed that the PF127/BLM-mediated regulation of ECM remodeling in skin flaps was associated with TGFβ-Col signaling pathway activation.

Conclusion: The PF127/BLM hydrogel promoted subcutaneous ECM remodeling and fibrosis, which aided the construction of personalized flaps through the TGFβ-Col signaling pathway, with decreased hepatic, pulmonary, and renal toxicities.

Background: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI.

Methods: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses.

Results: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols.

Conclusion: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

Objective: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved.

Materials and method: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence.

Results: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines.

Conclusion: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

Background: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment.

Methods: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.

Results: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results.

Conclusion: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

Objective: The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye.

Methods: A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (n = 39).

Results: The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (p < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (p < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (p < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (p < 0.001). The CPR, TNF-α, IFN-γ and IL-1β levels in the joint group were notably decreased than those in other two groups (p < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (p < 0.05).

Conclusion: SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.