American journal of clinical and experimental immunology最新文献

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease primarily affecting the elderly, marked by lung tissue scarring and impaired function. Current treatments, such as pirfenidone and nintedanib, slow disease progression but do not halt it and are associated with side effects. Lung transplantation is limited by donor shortages and surgical risks. Stem cell-based therapies, particularly mesenchymal stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord, offer promise due to their low immunogenicity, homing capacity, and paracrine signaling. Preclinical models show that MSCs or their miRNA-bearing extracellular vehicles (EVs) can inhibit the TGFβ/Smad pathway, reprogram macrophage polarization, and promote tissue regeneration through anti-inflammatory and repair factors (e.g., IL-10, HGF, VEGF). Genetic modifications like CXCR4 overexpression may enhance MSC efficacy. Early clinical trials suggest favorable safety and preliminary efficacy, though long-term validation is needed. Additionally, alveolar type 2 (AT2) cells derived from induced pluripotent stem cells (iPSCs) and lung epithelial cells from embryonic stem cells (ESCs) offer potential for alveolar repair. Bioengineering advancements, including hydrogel scaffolds and 3D lung organoids, enhance stem cell retention and provide platforms for IPF research and drug screening. This review explores the therapeutic potential of stem cell therapies in IPF, integrating recent bioengineering developments and clinical prospects.

Diabetes-associated infertility results from interconnected immunometabolic, oxidative, inflammatory, and endocrine disturbances that impair reproductive function in both sexes. Conventional therapies address individual symptoms but often fail to target this systemic, immune-mediated complexity. This narrative review summarizes preclinical and clinical evidence on the role of Traditional Chinese Medicine (TCM) in managing diabetic infertility, with a focus on immune-endocrine interactions, cytokine modulation, and inflammatory signaling. TCM interventions - including single-herb extracts, multi-herb formulations, and non-pharmacological approaches such as acupuncture and mind-body interventions-enhance insulin sensitivity, suppress pro-inflammatory cascades (NF-κB, TNF-α, IL-6), and regulate key immunometabolic pathways such as PI3K/Akt and AMPK. Mechanistic studies have also demonstrated improved nitric oxide bioavailability, endothelial function, and mitochondrial protection in gametogenic cells. They further show stabilization of hypothalamic-pituitary-gonadal and immune signaling, along with modulation of the gut-microbiota-immune axis. These immunomodulatory effects contribute to better spermatogenesis, semen quality, ovulation, endometrial receptivity, implantation, and pregnancy outcomes, particularly in individuals with insulin resistance or polycystic ovary syndrome. Overall, TCM shows promise as an adjunctive immunomodulatory strategy for diabetic infertility, supported by preliminary evidence of reproductive benefits. However, current evidence remains limited, and well-designed multicenter, immunology-informed clinical trials are required to confirm its efficacy.

Background: Previous studies have found associations between dietary habits, physical activity (PA) and a variety of renal/urinary disorders. However, only a few studies have used Mendelian randomisation analyses to explore the causal relationship between dietary habits, physical activity and a range of renal/urinary diseases.

Methods: The exposure and outcome datasets were sourced from the BioBank, FinnGen, and the NHGRI-EBI databases. The exposure dataset comprised of 20 dietary patterns and 4 PA modalities, while the outcome dataset included 19 renal/urological disorders. The primary methods employed for MR analyses were inverse variance weighted. Heterogeneity and multiplicity analyses were conducted to ensure the validity of the results.

Results: In terms of dietary habits, studies have found that consumption of soya-based sweets reduces the risk of chronic kidney disease (CKD). Consumption of fresh fruits prevented benign adrenal tumours and immunoglobulin A nephropathy (IgA-N). Consumption of paneer helps to reduce the risk of developing type 2 diabetes (T2D) nephropathy and immunoglobulin A nephropathy (IgA-N). In addition, consumption of nuts is a protective factor against type 2 diabetic nephropathy. Consumption of nuts, lean fish and fatty fish reduces the incidence of acute tubulointerstitial nephritis (ATIN). Among various forms of physical activity, recreational hiking was inversely associated with IgA-N nephritis and T2D nephritis. Other physical activities, including swimming, cycling, fitness and bowling, also reduced the risk of developing IgA-N. In contrast, leisure screen time (LST) was considered a risk factor.

Conclusion: This study suggests that a sensible diet and increased leisure time walking may prevent chronic kidney diseases such as chronic renal insufficiency, chronic renal failure, type 2 kidney disease and IgA nephropathy. This study deepens the understanding of the association between diet, physical activity and renal/urinary abnormalities and provides practical recommendations for reducing the risk of developing these diseases.

Objective: To analyze the expression of Aryl Hydrocarbon Receptor Nuclear Translocator-Like 2 (ARNTL2) and miR-204-5p in non-small cell lung cancer (NSCLC) patients and their correlation with clinicopathological characteristics.

Methods: Respiratory department cases from April 2020 to April 2022 were selected, and patients were divided into an NSCLC group (80 cases) and a non-NSCLC group (60 cases). The expression levels of ARNTL2 and miR-204-5p and the survival status were compared between the two groups. The predictive value of ARNTL2 and miR-204-5p for mortality in NSCLC patients was analyzed.

Results: TCGA data showed ARNTL2 expression was significantly higher and hsa-miR-204-5p significantly lower in cancer versus normal tissues (P<0.05). Patients with high ARNTL2 or miR-204-5p expression had shorter survival than those with low expression (P<0.05). In NSCLC patients, ARNTL2 was elevated and miR-204-5p reduced compared to non-NSCLC (P<0.05). High ARNTL2 or low miR-204-5p expression correlated with older age, larger tumor size, higher malignancy, lymph node metastasis, advanced stage, and smoking history (P<0.05). Over 36 months, survival was lower with high ARNTL2 but higher with high miR-204-5p (P<0.05). Pearson analysis showed ARNTL2 positively and miR-204-5p negatively correlated with mortality (P<0.05). ROC analysis yielded AUCs, sensitivities, and specificities of 0.914/86.7%/86.2% for ARNTL2, 0.934/81.7%/96.2% for miR-204-5p, and 0.920/89.8%/97.7% for combined detection.

Conclusion: The expression levels of ARNTL2 and miR-204-5p in NSCLC are closely associated with patient age, tumor differentiation, and lymph node metastasis, and they have high predictive value for NSCLC-related mortality.

Background: Preterm birth poses significant risks to neonatal health. Although immune dysregulation has been implicated in its etiology, the causal roles of specific immune cell phenotypes and the potential mediating effects of metabolites remain unclear. This study applied Mendelian randomization (MR) to investigate causal relationships between immune cell phenotypes and preterm birth, and to assess whether plasma metabolites mediate these associations.

Methods: Two-sample and mediation MR analyses were performed using genetic variants from genome-wide association studies (GWAS) of immune cells and plasma metabolites. Causal estimates were primarily derived using inverse variance weighting (IVW), with sensitivity analyses conducted via MR-Egger, MR-PRESSO, and leave-one-out validation.

Results: A total of 28 immune cell phenotypes and 47 metabolites were robustly associated with preterm birth (P < 0.05). Reverse MR analysis revealed no evidence of reverse causality for the identified immune phenotypes. Among these, CD28^- CD8^br AC exhibited the strongest association with increased preterm birth risk. Mediation analysis demonstrated that the effect of CD28^- CD8^br AC on preterm birth (total effect: 0.148; IVW OR [95% CI]: 1.160 [1.056-1.274], P = 0.002) was partially mediated by isoleucine levels (mediation proportion: 6.79%; P = 0.027) and the acetylcarnitine-to-propionylcarnitine (C2/C3) ratio (mediation proportion: 7.35%; P = 0.029). Sensitivity analyses confirmed the robustness of these findings.

Conclusion: This study establishes causal links between immune cell phenotypes, metabolites, and genetic susceptibility to preterm birth. Specifically, CD28^- CD8^br AC may elevate preterm birth risk through modulation of isoleucine and the C2/C3 ratio, providing novel insights into disease mechanisms and potential therapeutic targets.

Objective: To perform a meta-analysis on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy.

Methods: Relevant literature on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy was searched in both Chinese and English databases.

Results: A total of 19 studies published between 2012 and 2024 were included, involving 38 groups and 2,339 patients. Meta-analysis of continuous variables from fifteen studies reported no statistically significant difference in systolic blood pressure between the study group and the control group (MD = -0.27, 95% CI: -2.16 to 1.61, Z = -0.28, P = 0.78). Similarly, eight studies showed no significant difference in heart rate between the study group and the control group (MD = -0.62, 95% CI: -2.67 to 1.43, Z = -0.59, P = 0.55). Twelve studies demonstrated significantly higher oxygen saturation (SaO2) levels in the study group compared to the control group (MD = 1.88, 95% CI: 0.56 to 3.20, Z = 2.79, P = 0.01). Nine studies indicated that sedation satisfaction was significantly higher in the study group than in the control group (MD = 2.93, 95% CI: 1.16 to 4.70, Z = 3.25, P < 0.01). Ten studies assessed sedation scores, showing no statistically significant difference between groups (MD = 0.32, 95% CI: -0.02 to 0.67, Z = 1.82, P = 0.07). Awakening time, reported in eight studies, also showed no significant difference (MD = -2.70, 95% CI: -5.50 to 0.09, Z = -1.89, P = 0.06). Six studies reported VAS (Visual Analogue Scale) scores, showing a statistically significant difference (MD = -0.46, 95% CI: -0.83 to -0.08, Z = -2.39, P = 0.02). Meta-analysis of dichotomous variables from fourteen studies showed no significant difference in the incidence of adverse events between the groups (OR = -0.10, 95% CI: -0.49 to 0.29, Z = -0.49, P = 0.62). Meta-regression analysis suggested that heterogeneity mainly originated from differences in study type and methodology (P < 0.05).

Conclusion: Both midazolam and dexmedetomidine demonstrate good sedative effects during bronchoscopy, and their use should be tailored to individual patient conditions.

Granzyme B (GrB)-producing B cells have dual roles in tumor immunity, either killing tumor cells or suppressing antitumor responses by eliminating effector T cells. In this study, we aimed to investigate how breast cancer cells influence GrB-producing B cells from tumor-draining lymph nodes and whether B cell activation enhances their cytotoxic potential. Mononuclear cells were isolated from 14 fresh axillary lymph node samples by density gradient centrifugation using Ficoll-Hypaque. Lymphocytes were co-cultured with breast tumor cell lines (MCF-7 and MDA-231) in the presence of recombinant interleukin-21 (rIL-21) and anti-B cell receptor (BCR). B cell granzyme B production was measured by flow cytometry, while tumor cell (MCF-7) apoptosis was assessed using calcein AM release assays. Direct co-culture of lymphocytes with MCF-7 or MDA-MB-231 significantly reduced the frequency of GrB-producing B cells (P=0.001 and P=0.031, respectively), while tumor supernatants alone had no effect. When B cells were pre-stimulated with IL-21 and anti-BCR for 24 hours before direct co-culture, GrB expression was maintained at baseline levels (no significant difference vs. control). Additionally, B cells activated with IL-21 and anti-BCR caused significant apoptosis in MCF-7 cells (38±8.9%, P=0.023). In conclusion, breast cancer cells suppress GrB⁺ B cell responses via direct contact, but this suppression is reversible through B cell activation. Importantly, pre-activated B cells exhibit direct cytotoxic activity against tumor cells, highlighting their potential as an effector population for breast cancer immunotherapy.

Despite advances in screening and therapy, colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for early detection and for predicting treatment efficacy. This review highlights circulating cell-free DNA (cfDNA) fragmentomics as a promising non-invasive approach for tumor detection and disease monitoring. We focus on fragmentomic features - such as fragment size distributions, fragment-end motifs, and epigenetic signals - which, when integrated into machine-learning models, have shown strong performance in distinguishing patients with CRC from healthy controls. Emerging evidence indicates that, these signatures may support early-stage detection, track disease progression, and predict pathologic complete response (pCR), thereby enabling more personalized treatment strategies. We also discuss the potential role of fragmentomics in non-operative management, including "watch-and-wait" approaches. However, important gaps remain in clinical translation; prospective trials and standardized assays/analysis pipelines are required to validate these findings and define their real-world utility.

This study was carried out to analyze the time-dependent changes of Wnt3a/β-catenin signaling during lupus nephritis (LN). At the age of 5 weeks, 30 female MRL/lpr mice and C57BL/6 (C57) mice were randomly grouped. Moreover, 12 females MRL/lpr mice were split into two groups, cyclophosphamide treatment (LN-CTX) and one was untreated. Mice in the LN-CTX group were injected intraperitoneally with cyclophosphamide (CTX) from the age of 16 wk. Urinary protein, serum antinuclear antibodies (ANA), and anti-double-stranded DNA (dsDNA) antibody levels were measured. The detection of renal injury was later confirmed through histopathology, and immunofluorescence analysis. Compared with C57 mice, LN mice had much higher levels of 24-hour urinary protein, ANA and dsDNA antibodies (P<0.05). Histological examination exhibited the proliferation of mesangial cells with the invasion of inflammatory cells, while deposition of immune complex was shown to reach the peak at 28 weeks. The production of Wnt3a and β-catenin proteins and mRNA was significantly increased in the kidneys of LN mice. In contrast, 24-hour urinary protein, ANA and dsDNA antibodies levels decreased significantly and CTX treatment caused a drop in the aforementioned immune response (P<0.05). Renal histopathological changes and immune complex deposition were ameliorated by CTX treatment. the renal levels. Notably, the renal levels of Wnt3a/β-catenin at LN-CTX were found to be lower than that in the untreated LN group. The abnormal activation of the Wnt/β-catenin signaling pathway may play a role in LN formation and thus important molecular target for CTX drug. This research shows that CTX inhibits renal Wnt3a/β-catenin activation in LN mice for the first time, offering a potential molecular mechanism for its renoprotective effects.

Background: This study investigated whether the combined treatment of melatonin and tofacitinib offers enhanced protection against dextran sulfate sodium-induced acute colitis (AC) in rats. Using CCD-18Co fibroblasts and a rat colitis model, we assessed the anti-inflammatory, anti-apoptotic, and immunomodulatory effects of the combination therapy.

Methods: CCD-18Co cells were grouped as A1 (CCD-18Co), A2 (CCD-18Co + lipopolysaccharide (LPS)), A3 (CCD-18Co + LPS + Melatonin), A4 (CCD-18Co + LPS + Tofacitinib), or A5 (CCD-18Co + LPS + melatonin + tofacitinib). Sprague-Dawley rats were categorized into groups 1 (normal control), 2 (AC), 3 (AC + melatonin), 4 (AC + tofacitinib), and 5 (AC + melatonin + tofacitinib), and the colons were harvested 14 days after AC induction.

Key findings: Cell viability at time points of 24, 48, and 72 h was the highest in A1, lowest in A2, and progressively increased from A3 to A5 (all P < 0.0001). The protein expression levels of inflammatory, DNA-damaged, and autophagic (ratio of LC3-BII to LC3-BI) biomarkers displayed identical patterns of apoptosis among the groups (all P < 0.0001). Additionally, the blood stool, colon leakage, and colon injury scores were the lowest in group 1, highest in group 2, and significantly progressively reduced from groups 3 to 5 (all P < 0.0001). The protein expression of the Janus kinase family-signal transducer and activator of transcriptions/cell-stress signaling, inflammation, oxidative stress, DNA-damaged, apoptotic biomarkers, and cellular expression of immune and inflammatory factors exhibited an identical pattern of colon injury scores among the groups.

Conclusions: Combined melatonin-tofacitinib treatment effectively protected the colon against dextran sulfate sodium-induced damage, mainly through the suppression of Janus kinase family-signal transducer and activator of transcriptions/cell-stress signaling, inflammation, and oxidative stress.