Immunopharmacology and Immunotoxicology最新文献

Background: Albiflorin isolated from Paeoniae Alba Radix can cross the blood-brain barrier (BBB) and possesses analgesia, anticonvulsant, anti-inflammatory, and hepatoprotective properties. This study investigates albiflorin functions and related mechanisms in Parkinson's disease (PD) pathogenesis.

Methods: Cellular and animal models of PD were constructed. Cell viability and apoptosis were detected by CCK-8 assays. Levels of Iba-1 and TH were measured by immunofluorescence staining, western blotting, and immunohistochemistry staining. Levels of pro-inflammatory mediators and pathway-related genes were measured by western blotting and RT-qPCR. Locomotor activity of mice was examined by open field test, rod climbing test, and rod rotating test.

Results: For in vitro analysis, albiflorin inhibited LPS-induced microglial activation and neuroinflammation. Additionally, albiflorin inactivated NF-κB and MAPK pathways in LPS-treated BV2 cells. Moreover, albiflorin attenuated neurotoxicity mediated by LPS-stimulated microglia. For in vivo analysis, albiflorin improved MPTP-induced locomotor activity deficits and reduced MPTP-induced dopaminergic neuron loss. In parallel, albiflorin inhibited activated microglia-mediated neuroinflammation in MPTP-treated mice.

Conclusion: Albiflorin mitigates neuronal apoptosis and improves behavioral impairments in MPTP-induced PD mouse model through inhibition of activated microglia-mediated neuroinflammation via the NF-κB and MAPK pathways.

Objectives: Traumatic brain injury (TBI) precipitates a neuroinflammatory cascade, with the NLRP3 inflammasome emerging as a critical mediator. This review scrutinizes the complex activation pathways of the NLRP3 inflammasome by underscoring the intricate interplay between calcium signaling, mitochondrial disturbances, redox imbalances, lysosomal integrity, and autophagy. It is hypothesized that a combination therapy approach-integrating NF-κB pathway inhibitors with NLRP3 inflammasome antagonists-holds the potential to synergistically dampen the inflammatory storm associated with TBI.

Methods: A comprehensive analysis of literature detailing NLRP3 inflammasome activation pathways and therapeutic interventions was conducted. Empirical evidence supporting the concurrent administration of MCC950 and Rapamycin was reviewed to assess the efficacy of dual-action strategies compared to single-agent treatments.

Results: Findings highlight potassium efflux and calcium signaling as novel targets for intervention, with cathepsin B inhibitors showing promise in mitigating neuroinflammation. Dual therapies, particularly MCC950 and Rapamycin, demonstrate enhanced efficacy in reducing neuroinflammation. Autophagy promotion, alongside NLRP3 inhibition, emerges as a complementary therapeutic avenue to reverse neuroinflammatory damage.

Conclusion: Combination therapies targeting the NLRP3 inflammasome and related pathways offer significant potential to enhance recovery in TBI patients. This review presents compelling evidence for the development of such strategies, marking a new frontier in neuroinflammatory research and therapeutic innovation.

Objective: C-Phycocyanin (C-PC) is a photosynthetic pigment with interesting therapeutic properties. However, its effectiveness in modulating the immune system cell populations has not been elucidated. We analyzed the action of C-PC on the modulation of mice immune system.

Methods: The animals were treated subcutaneously with C-PC for 3 consecutive days. On the fourth day, the animals were euthanized and cells from different organs were analyzed by flow cytometry. Cytotoxicity was analyzed using biochemical parameters.

Results: The results showed that C-PC increased the total cellularity in percentage and absolute number in the inguinal lymph node as well as the absolute number of B cells, CD4+ and CD8+ T cells and myeloid cells. The percentage of B cells was also increased in the lymph node. In the bone marrow, there was a reduction in immature and mature B cells. In contrast, C-PC increased the percentage and absolute number of myeloid cells in the bone marrow. C-PC administration also promoted an increase of CD4+ and CD8+ T cells in the thymus, and a reduction in these populations in the spleen.

Conclusion: The data show for the first time the positive immunomodulatory role of C-PC by recruiting distinct populations of immune system cells to the treatment-draining lymphoid organ.

Objective: Osteoimmunology is an emerging field that explores the interplay between bone and the immune system. The immune system plays a critical role in the pathogenesis of diabetes and significantly affects bone homeostasis. Artesunate, a first-line treatment for malaria, is known for its low toxicity and multifunctional properties. Increasing evidence suggests that artesunate possesses anti-inflammatory, immunoregulatory, and osteogenic effects. This review aims to explore the relationship between immune regulation and bone metabolism in type 2 diabetes (T2DM) and to investigate the potential therapeutic application of artesunate.

Methods: This review systematically examines literature from PubMed/Medline, Elsevier, Web of Science, Embase, the International Diabetes Federation, and other relevant databases.

Results: This review synthesizes evidence from multiple sources to delineate the relationship between T lymphocytes and T2DM, the regulation of T lymphocyte subsets in bone metabolism, and the effects of artesunate on both T lymphocytes and bone metabolism. Recent studies suggest a bidirectional regulatory relationship between T2DM and T lymphocytes (CD4⁺ T and CD8⁺ T) during the onset and progression of the disease, with inflammatory and anti-inflammatory cytokines serving as key mediators. T lymphocyte subsets and their cytokines play a pivotal role in regulating osteogenesis and osteoclastogenesis in pathological conditions. Furthermore, artesunate has shown promise in modulating inflammatory infiltration and bone metabolism.

Conclusion: The accumulated evidence indicates that artesunate exerts regulatory effects on bone metabolism in T2DM by influencing T lymphocyte differentiation.

Objectives: This study investigates the effects of birinapant, a novel compound, on psoriasis-like symptoms induced by imiquimod in Balb/c mice.

Material and methods: Male Balb/c mice were treated with imiquimod (IMQ) to induce psoriasis-like symptoms. The clinical characteristics of psoriasis were assessed using the Psoriasis Area and Severity Index, as well as back skin thickness, skin length and mass, and body weight alterations. The treatment groups included those receiving birinapant, with the assessment on the levels of interleukin-17 and tumor necrosis factor -α, two key cytokines involved in the inflammatory process of psoriasis. The study found that birinapant significantly reduced the levels of these cytokines, providing reassurance about its potential to combat psoriasis. Additionally, the study evaluated the effect of birinapant on oxidative stress levels to determine its role in maintaining skin homeostasis.

Result and discussion: The findings from this study revealed that mice subjected to IMQ-induced psoriasis exhibited positive responses to 21 days of treatment with birinapant (50 mg/kg). The levels of interleukin-17 and tumor necrosis factor-alpha, in the skin of IMQ-treated mice significantly decreased, indicating its effectiveness in reducing inflammation associated with psoriasis. Furthermore, Birinapant positively affected oxidative stress maintenance, suggesting its potential role in promoting skin health and homeostasis.

Conclusion: By demonstrating birinapant's efficacy, this research paves the way for further studies that could lead to the development of more effective therapies for psoriasis.

Background: Nivolumab has been linked to occurrences of uveitis, yet the clinical features associated with these episodes remain unclear. This study aimed to explore the clinical characteristics of uveitis induced by nivolumab and to offer guidance for its prevention, diagnosis, and treatment.

Methods: We conducted a retrospective analysis by gathering case reports related to nivolumab-induced uveitis from both Chinese and English databases, covering the period from inception until 30 September 2024.

Results: A total of 38 patients with uveitis were included, with a median age of 63 years (range 35 and 92). The onset of uveitis occurred between 1 week and 24 months post-administration, with a median onset time of 1.4 months. Blurred vision was the primary complaint among patients. Sixteen patients (42.1%) exhibited uveitis resembling Vogt-Koyanagi-Harada (VKH) disease. Bilateral uveitis was the most prevalent form (89.2%), followed by unilateral uveitis (8.1%). Anterior uveitis was the most frequently observed type (52.6%), succeeded by posterior uveitis (23.7%), panuveitis (21.1%), and intermediate uveitis (2.6%). Uveitis showed significant improvement or resolution following treatment with topical or systemic corticosteroids, with a median improvement time of 4 weeks post-therapy.

Conclusions: Uveitis is a relatively uncommon adverse effect of nivolumab, typically manifesting within 5 months of treatment. Prompt recognition of nivolumab-induced uveitis and appropriate management are crucial, as most cases are treatable.

Background: Bisphenol A (BPA) is an industrial chemical used in manufacturing epoxy resins, polycarbonate plastics. We aimed to evaluate the possible protective effect of modafinil (MOD) in BPA-induced lung injury.

Materials and methods: Twenty-four adult male albino Wistar rats were divided into four groups: Control group, MOD group: rats received modafinil 10 mg/kg/day for 4 weeks, BPA group: rats received Bisphenol A (500 mg/kg/day) for 4 weeks, MOD/BPA group: rats received MOD+ BPA. We measured arterial blood gas (ABG), malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), interlukin-1b (IL-1b), Sirtuin type 1 (SIRT1), Keap1, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), caspase-3 and forkhead-box transcription factor1 (FOXO1) levels, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) and Heme Oxygenase-1 (HO-1) gene expression. Furthermore; histological changes, interlukin-6 (IL-6) immuno-expression were evaluated.

Results: BPA group showed significant increase in the partial pressure of carbon dioxide (PaCO2), MDA, NOx, IL-1b, keap1 and FOXO1, caspase-3 levels; TNF-α and NF-Κb, Bax and HO-1 gene expression, IL-6 exhibited a notable rise in immune-expression in the alveolar wall cells, interstitial cells, and infiltrating inflammatory cells. Moreover; it showed toxic histological changes of marked lung injury. Meanwhile, there is a significant decrease in the partial pressure of oxygen (PaO2), TAC, SIRT1, Nrf2 levels, and Bcl2 gene expression. MOD showed a significant improvement in all parameters.

Conclusion: MOD possesses potent ameliorative effects against lung injury caused by BPA via reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.

Background: The management of hypersensitivity to excipients and food additives remains a significant issue for healthcare professionals and patients. Avoiding carboxymethylcellulose (CMC) can be a considerable challenge for patients allergic to CMC due to its widespread use. We assessed the tolerance of CMC through different route of administration in a patient with a confirmed CMC allergy. We conducted a literature review to analyze all relevant cases of patients allergic to CMC, focusing on tolerance through non-injectable routes.

Methods: Skin tests, basophil activation tests, oral and nasal provocation tests with CMC were performed to evaluate patient's hypersensitivity.

Results: Skin tests and basophil activation tests with CMC were positive and confirmed IgE-mediated hypersensitivity to CMC in the patient. While the patient tolerated oral administration of CMC and CMC-containing eye drops, nasal provocation test resulted in asthma exacerbation and rhinitis.

Conclusion: Tolerance of CMC appears to be route-dependent. Provocation tests with CMC through various routes of administration are essential for assessing tolerance and providing appropriate recommendations for patients with CMC allergy.

Background: The incidence of hepatic immune-related adverse events has increased with the wide use of immune checkpoint inhibitors (ICIs), some immune-mediated hepatotoxicity (IMH) cases are severe and lack of clinical recommendations.

Objective: This study aimed to evaluate the efficacy of artificial liver support systems (ALSSs) in the treatment of IMH.

Methods: This retrospective case series included six patients with grade 4 hepatotoxicity with high bilirubin induced by ICIs treated between 1 January 2019 and 31 December 2021. All patients received ALSS treatment.

Results: After treatment and recovery, four of the six patients experienced improvement in hepatotoxicity, with total bilirubin (TBIL) levels reduced to ≤ grade 2, and two patients achieved complete recovery (TBIL grade = 0).

Conclusion: ALSS serve as a therapeutic option for severe IMH.

Objective: Multiple sclerosis (MS) is a prevalent autoimmune disorder characterized by neuroinflammation and demyelination in the central nervous system (CNS), leading to neurological dysfunction. Despite advances in treatment, there remains an unmet need for safe and effective therapies. Crocin, a bioactive constituent of saffron, has demonstrated anti-inflammatory and immunoregulatory properties in various disease models. This study investigates the therapeutic potential of Crocin in a murine model of MS, experimental autoimmune encephalomyelitis (EAE).

Methods and results: Female C57BL/6 mice were induced with EAE and treated with different doses of Crocin. Clinical severity, CNS pathology, T cell proliferation, cytokine production, and transcription factor expression were assessed. Crocin-treated mice showed reduced clinical severity, inflammation, and demyelination in the CNS compared to controls. Moreover, Crocin attenuated T cell proliferation and modulated cytokine production, promoting an anti-inflammatory cytokine profile while suppressing pro-inflammatory cytokines. Additionally, Crocin altered the expression of transcription factors associated with T cell differentiation, favoring regulatory T cell responses.

Discussion: These findings suggest that Crocin exerts therapeutic effects in EAE by modulating neuroinflammation and immune responses. Further studies are warranted to elucidate the mechanisms underlying Crocin's immunomodulatory properties and its potential as a treatment for MS.