International Journal of Immunopathology and Pharmacology最新文献

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by damage to alveolar epithelial cells and pulmonary capillary endothelial cells. Compared with ARDS caused by other causes, the subtypes of ARDS caused by sepsis are more serious and lead to poor prognosis and higher mortality. Agmatine (AGM) is a biological metabolite of L-arginine decarboxylation, proven to ameliorate sepsis-induced acute lung injury (SALI), but the mechanism remains unclear. Therefore, this study aims to explore the role of AGM in SALI, clarify the relationship between the I₂R/RSK2/NF-κB signaling pathway regulated by AGM and macrophage polarization, and provide a theoretical basis for the clinical treatment of SALI. Cellular and animal models of lung injury in sepsis were established with lipopolysaccharide (LPS). We conducted a series of experiments to examine the oxygenation index (OI), wet/dry ratio (W/D) of the lung, pathological changes, levels of inflammation, Apoptosis and related protein expression in different groups of mice. Finally, we found that AGM can ameliorate sepsis-induced acute lung injury by suppressing the I₂R/RSK2/NF-κB signaling pathway and modulating polarization of alveolar macrophage.

Hepatitis C virus (HCV) infection is a major global public health problem. Although it has traditionally been linked to liver damage, several studies have demonstrated its extrahepatic impact, specifically in the oral cavity. Oral manifestations can be considered early signs of infection or contribute to clinical progression. This narrative review aims to describe the oral alterations associated with HCV, integrating the pathophysiological mechanisms and clinical implications for dental management. The most prevalent manifestations include periodontal disease, oral lichen planus, Sjögren's syndrome-like sialadenitis, and squamous cell carcinoma of the oral cavity. Recent findings suggest that HCV triggers dysbiosis of the oral microbiome, promotes exacerbated immune responses with overproduction of pro-inflammatory cytokines, and disrupts the homeostatic environment, thereby promoting the progression of inflammatory and neoplastic diseases. In addition, viral RNA has been identified in saliva and gingival crevicular fluid, which could be considered a non-parenteral route of transmission, particularly important in dental interventions. In parallel, direct-acting antiviral therapy, in addition to achieving virus elimination, could also partially correct immunological and microbial disruptions in the cavity, with favorable clinical responses. Understanding these oral alterations can guide dentists in early detection and improve systemic outcomes.

The spectrum of pathological conditions affecting the nasopharynx includes infections, congenital anomalies, and tumoral lesions, particularly angiofibroma, nasopharyngeal carcinoma, and lymphoma. Hypertrophy of adenoid tissue is a frequent phenomenon in children, but it is less common in the adult population. With this case report, we wanted to point out the importance of rhinological and otological manifestations of adenoid hypertrophy in adult patients. A 48-year-old man presented with impaired hearing in both ears, difficulty breathing through the nose, impaired sense of smell, hyponasal speech, and occasional scanty bleeding from the right side of the nose. After taking detailed data, the diagnostics included a classic ENT examination, endoscopy of the nasal cavity and nasopharynx, audiological diagnostics, allergy tests, computerized tomography of the paranasal sinuses and the skull base, and serological analysis for viruses and protozoa. A soft tissue lesion that filled the entire nasopharynx was surgically removed, and the pathohistological analysis indicated B-cell small lymphocytic lymphoma (SLL) with polyclonal plasma cell differentiation. Serological analyses showed that it was a human immunodeficiency virus (HIV)-positive patient, who also had a high blood titer of IgG to the Epstein-Barr virus. The patient was admitted to another institution for oncology treatment under the supervision of an infectious disease specialist. Although rare, malignant transformation of nasopharyngeal lymphoid tissue is possible. B-cell SLL with polyclonal plasma cell differentiation represents a minority of malignancies originating from the nasopharynx, and there are limited data regarding epidemiologic and treatment outcomes. Early recognition and thorough evaluation are essential to distinguish benign enlargement from more serious conditions.

Objective: Cannabidiol (CBD) administration (5 mg/kg) in healthy rats has been shown to significantly decrease lymphocyte subset numbers in peripheral blood without involvement of natural killer cells. The aim was to evaluate whether lymphocyte numbers also decrease in the spleen.

Introduction: CBD, the major non-psychotropic compound of Cannabis sp., is an effective treatment for inflammatory and autoimmune diseases with various anti-tumor effects, but the mechanisms of its long-term actions in vivo remain unclear.

Methods: To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days, and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, the effect was similar to a decrease in lymphocytes caused by treatment with the selective receptor antagonist AM630 (1 mg/kg).

Results: The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day decreased splenic lymphocyte numbers, involving T and non-T/NK CD45RA+ lymphocytes but not NK cells. The effects of CB₂ receptor antagonist were not significant, but it had a significant interaction with CBD. No changes in NKCC were observed following CBD administration.

Conclusion: These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood without affecting NK cell counts or cytotoxicity.

The oral epithelium is a dynamic interface between host and environment, where keratinocytes not only serve as structural components but also actively modulate immune responses. Emerging research identifies IRF6 as a pivotal regulator of epithelial differentiation and immune signaling within chronic inflammatory contexts. This narrative review explores the role of IRF6 and its downstream effects in oral keratinocytes, particularly in relation to Toll-like receptor (TLR) activation, CCL5-mediated inflammation, hypoxic signaling, and the epithelial-mesenchymal transition (EMT). It proposes a mechanistic framework for understanding the progression from chronic inflammation to epithelial disruption and malignant transformation in oral mucosal disorders. Modulation of IRF6 signaling represents a promising therapeutic target for restoring epithelial integrity and halting disease progression in chronic inflammatory oral diseases. This model lays groundwork for future research integrating molecular biomarkers and immune modulation strategies in oral pathology.

Objective: To evaluate the safety and effectiveness of isoniazid preventive therapy (IPT) in pregnant women living with HIV (WLWH) through a systematic review and meta-analysis.

Introduction: Isoniazid preventive therapy (IPT) is recommended for preventive treatment of tuberculosis in high risk groups. However, evidence on its role in pregnant WLWH remains scarce.

Methods: We performed a systematic review and meta-analysis to pool randomized controlled trials (RCTs) as well as non-randomized studies (NRS) where IPT was administered to pregnant WLWH (PROSPERO ID: CRD42024618836). PubMed, Embase, and Cochrane Central databases were searched for relevant articles, until November 15, 2024. Statistical analysis was performed using R Software v4.4.1 and a random-effects model was applied to pool risk ratios (RRs) along with 95% confidence intervals.

Results: Five studies with a total of 45,402 patients (mean age = 30 years) were included. The risk of maternal mortality was significantly decreased in pregnant WLWH exposed to IPT compared with the control group (RR 0.42; 95% CI 0.20-0.92; p = 0.03). However, the risks of other outcomes including composite adverse pregnancy outcome (RR 0.90; 95% CI 0.56-1.43; p = 0.66), prematurity (RR 0.86; 95% CI 0.46-1.60; p = 0.63), low birthweight (RR 0.99; 95% CI 0.69-1.42; p = 0.95), very low birthweight (RR 1.28; 95% CI 0.39-4.23; p = 0.55), congenital anomalies (RR 1.48; 95% CI 0.59-3.75; p = 0.41), and hepatotoxicity (RR 0.99; 95% CI 0.71-1.37; p = 0.93) were comparable between the two groups.

Conclusion: IPT in pregnant WLWH significantly reduces maternal mortality without increasing adverse pregnancy outcomes. These findings support the continued use of IPT during pregnancy, with careful monitoring for hepatotoxicity, and highlight its potential role as an important maternal health intervention in high TB/HIV burden regions.

Shikonin has been reported to regulate caudal-type homeobox 2 (CDX2)-mediated intestinal epithelial cell (IEC) differentiation, and ferroptosis has been identified a critical event during this process. However, the exact role of ferroptosis in shikonin-induced IEC differentiation remains unclear. Accordingly, the aim of this study was to elucidate the involvement of ferroptosis in CDX2-mediated IEC differentiation induced by shikonin. Real-time polymerase chain reaction, western blotting, luciferase assay, immunoprecipitation, and chromatin immunoprecipitation were used to reveal the mechanism underlying shikonin-modulated ferroptosis-dependent IEC differentiation in HT-29 and Caco-2 cells. Shikonin treatment reduced ferroptosis in IECs, as evidenced by the increased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 (cationic amino acid transporter) member 11, which enhanced CDX2 expression and improved IEC barrier function. Mechanistically, shikonin activated the protein kinase A (PKA)/cAMP-responsive element-binding protein (CREB) signaling cascade, promoting CREB binding to the GPX4 promoter and initiating GPX4 transactivation. GPX4 inhibition reversed the effects of shikonin on CDX2 expression. Endogenous pyruvate kinase isozyme M2 interacted with phosphodiesterase 4; this interaction was disrupted by shikonin, leading to the activation of PKA/CREB signaling. The findings of this study indicate that a low dose of shikonin improves IEC barrier function through GPX4-mediated inhibition of ferroptosis, highlighting its potential as a therapeutic agent for intestinal mucosal injury.

Objective: This study aims to comprehensively investigate the expression profiles of interleukins in prostate adenocarcinoma (PRAD) and their relationship with immune cell infiltration, tumor progression, and patient prognosis. By establishing an interleukin-related risk score, we seek to enhance the understanding of the tumor immune microenvironment and facilitate the development of tailored immunotherapeutic strategies for PRAD patients.

Introduction: Interleukins can nurture a tumor promoting environment and simultaneously regulate immune cell infiltration. However, the potential roles of interleukins in the prostate adenocarcinoma immune landscape remain abstruse.

Methods: We comprehensively investigated the interleukin expression patterns and tumor immune landscape of prostate adenocarcinoma patients. And explored the interleukin expression patterns with immune infiltration landscape. The interleukin score was established using LASSO cox regression analysis. Multivariate Cox regression analysis was employed to assess the prognostic value of the interleukin score.

Results: We identified two distinct interleukin clusters, characterized by different immune cell infiltration, tumor promoting signaling pathways activation and prognosis. The interleukin score was established to estimate the prognosis of individual prostate adenocarcinoma (PRAD) patient. Further analysis demonstrated that the interleukin score was an independent prognostic factor of PRAD. Finally, we investigated the predictive value of interleukin score in the programmed cell death protein (PD-1) blockade therapy of patients with prostate adenocarcinoma. At the same time, the differences in related genes among different prostate cell lines were also identified.

Conclusions: This study demonstrated the correlation between interleukin and tumor immune landscape in prostate adenocarcinoma. The comprehensive evaluation of interleukin expression patterns in individual prostate patients contribute to our understanding of the immune landscape and helps clinicians selecting proper immunotherapy strategies for prostate patients.

Systemic lupus erythematosus (SLE) patients are at greater risk of developing osteoporosis (OP) than the general population. This study aimed to identify crosstalk genes between SLE and OP and to validate their diagnostic accuracy as biomarkers. Data analysis based on Gene Expression Omnibus (GEO) datasets was conducted. We utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and differential expression analysis to identify crosstalk genes (CGs). Machine learning algorithms and consensus clustering were applied to screen shared diagnostic biomarkers and construct two predictive models featuring key genes. We also investigated potential subgroups, immune infiltration across different subtypes, and validated hub mRNAs using quantitative real-time PCR (qPCR). Molecular docking was performed to simulate the interaction of a small molecule compound with its target. We identified 19 CGs and developed two predictive models: the IL1R2-GADD45B and CHI3L1-IL1R2-SPTLC2 diagnostic score thresholds. The CHI3L1-IL1R2-SPTLC2 model showed improved predictive accuracy for lupus-associated osteoporosis. The C2 subtype was found to potentially regulate bone metabolism in SLE patients. Immune infiltration analysis indicated a strong association between CGs and multiple immunocytes, with IL1R2 being a common element in both models. Molecular docking suggests that Anakinra's therapeutic effect may involve IL1R2. Our study introduces novel diagnostic biomarkers and predictive models for lupus-associated osteoporosis, with a particular focus on IL1R2 as an innovative biomarker and therapeutic target. These are anticipated to aid early screening and risk assessment in SLE patients, pending large-scale clinical validation.

Objective: This study aimed to investigate the effect of rapamycin on inflammatory pain in rats.

Introduction: Inflammatory pain is a kind of pathological pain caused by inflammatory mediators or factors such as TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin-1β), and IL-6 (Interleukin-6). NSAIDs and opioid analgesics are commonly used for relieving inflammatory pain, but the side effects limit their clinical application. New drugs based on new mechanisms for inflammatory pain are urgently needed. Autophagy is an evolutionarily conserved homeostatic process for lysosomal degradation of intracellular components. Recent reports indicate the involvement of autophagy in the development and maintenance of neuropathic pain, but the role of autophagy in inflammatory pain still needs to be explored.

Methods: The pain-related behaviors of rats were studied by paw withdrawal threshold and paw withdrawal latency. The autophagy level of the rat spinal cord was detected by western blots. The concentrations of TNF-α, IL-1β, and IL-6 were detected by ELISA.

Results: We found that the paw withdrawal threshold and paw withdrawal latency were both significantly decreased after CFA (Complete Freund's Adjuvant) injection, accompanied by the activation of mTOR signaling pathway and the inhibited autophagy flux in the spinal cord. And inflammatory cytokines were increased in the spinal cord after CFA injection. Then, we studied the effect of rapamycin on CFA-induced inflammatory pain in rats, and found that rapamycin restored the autophagy flux and significantly reduced mechanical allodynia and thermal hyperalgesia. In addition, rapamycin significantly decreased the levels of TNF-α, IL-1β, and IL-6 after CFA injection in the spinal cord.

Conclusion: Our results suggested that rapamycin might be a promising candidate for the treatment of inflammatory pain by restoring the autophagy flux in the spinal cord.