Immunopharmacology and Immunotoxicology最新文献

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.

Background: One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc.

Methods: We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect in-vitro on T lymphocytes and their functional responses.

Results: We found higher levels of hexachlorocyclohexane (HCH- α-, β-, and γ) and o,p'-dichlorodiphenyltrichloroethane (DDT) metabolite (p,p΄-DDE) in blood of SSc patients. In vitro treatment of SSc patient PBMCs with either of HCH (100 mM) or DDT (50 µM) caused a significant increase merely in CD8⁺ memory (CD8⁺CD45RO⁺) T lymphocytes. We also observed reduced FoxP3 expression in CD4⁺CD25⁺ (regulatory T cells) of SSc patients. Neither HCH nor DDT exposure of SSc PBMCs altered significantly the secretion of IL-2, IL-10, or IFN-γ, but both of these pesticides elevated their IL-4 (a pro-fibrotic cytokine) secretion.

Conclusion: Taken together, our findings indicate that persistent exposure to these OCPs results in decreased lymphoproliferative activity which promotes disease activity by producing pro-fibrotic cytokine(s). Thus, SSc patients are less able to initiate or augment an immune response to foreign antigens, when there is substantial suppression of lymphocyte function, which increases their susceptibility to infection. Strategies to prevent and control pesticide exposure may play an important role in reducing the morbidity and mortality associated with this disease.

Objective: Triple-Negative Breast Cancer (TNBC), the most challenging subtype of Breast Cancer (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play a significant role in TNBC progression and could be targeted by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), a plant lignan, has been shown to exhibit anticancer, anti-inflammatory and immunomodulatory activities. In this study, we explored how MAT-induced repolarization of THP-1-derived M2 macrophages towards the M1 phenotype, which could effectively target the TNBC cell line, MDA-MB-231.

Methods: The differential expression of genes in THP-1-derived macrophages at mRNA levels was evaluated by RNAseq assay. An inverted microscope equipped with a CMOS camera was utilized to capture the morphological variations in THP-1 cells and THP-1-derived macrophages. Relative mRNA expression of M1 and M2 specific marker genes was quantified by qRT-PCR. Cell viability and induction of apoptosis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1 dye) assays, respectively.

Results: MAT reduced the viability of M2a and M2d macrophages and repolarized them to M1 phenotype. Conditioned medium (CM) from MAT-treated M2a and M2d macrophages significantly reduced the viability of TNBC cells by apoptosis.

Conclusion: Targeting M2 macrophages is an important strategy to regulate cancer progression. Our study provides evidence that MAT may be a promising drug candidate for developing novel anti-TNBC therapy. However, further studies are warranted to thoroughly elucidate the molecular mechanism of action of MAT and evaluate its therapeutic potential in TNBC in vitro and in vivo models.

Background: Ulcerative colitis (UC) is a frequent inflammatory bowel disease (IBD) that causes long-lasting inflammation in the innermost lining of the rectum and colon.

Objective: The aim of this study was to evaluate the therapeutic effect of Cannabis sativa (C. sativa) on the amelioration of acetic acid-induced colitis in rats.

Materials and methods: Group 1: normal control group was intrarectally administered saline solution (0.9%); group 2: acetic acid (AA) group was given AA intra-rectally (2 mL of 4% (v/v) in 0.9% NaCl) once.; group 3&4: This group represented the ulcerative colitis-induced rats that were injected with acetic acid intra-rectally, then s.c. injection with C. sativa (20 and 40 mg/kg daily for 8 days).

Results: Colonic architectural abnormality significantly improved after pretreatment with C. sativa. Additionally, it significantly reduced the MDA level and prevented the depletion of GSH content. Moreover, C. sativa administration showed suppressive activities on pro-inflammatory cytokines, including NF-κB, MAPK, ERK, PI3K, AKT, HIF-1α, and TLR4. Moreover, it significantly upregulated the level of SIRT and CB1 in the colon tissue.

Conclusion: This study provided a novel impact for CB1 receptor activation produced by C. sativa against AA-induced UC in rats through inhibiting the TLR-4 MAPK/ERK, PI3K, and NFκB signaling pathways.