BMC Immunology最新文献

Aim: IBD is a condition that may result from the presence of oxidative stress. The objective of this research is to evaluate and compare the potency of probiotics and paraprobiotics to modulate oxidative stress and inflammation.

Methods and results: In the initial phase, the antioxidant capabilities of 88 strains from Lactobacillus and Bifidobacterium were evaluated. In the subsequent phase, during the in-vivo stage, four experimental groups were established, consisting of a high-fat diet (HFD) + PBS, HFD + DSS, HFD + DSS + 10^⁹ cfu/ml of 6 selected native probiotic, and HFD + DSS + 10^⁹ cfu/ml of paraprobiotic (from 6 selected strains), with male wild-type C57BL/6 mice being assigned to these groups. The phenotypical indices and pathological scores along with the evaluation of the expression of genes associated with the NF-kB and Nrf2 signaling pathways, as well as enzymes linked to oxidant/anti-oxidant activities, and proinflammatory/inflammatory cytokines were performed. A significant difference was noted among the groups exposed to DSS and groups that given our native agents. The mice receiving a blend of probiotics and paraprobiotics alongside DSS demonstrated a mitigation of the harmful impacts caused by DSS, both regarding phenotypic traits, including pathological scores and also the level of cytokines and antioxidant markers and also molecular indicators like the Nrf2 and NF-kB associated genes. Also, there was no notable difference between our native probiotic and paraprobiotic.

Conclusion: The study's findings provide evidence that the expression of inflammation can be successfully alleviated by utilizing our native probiotics and paraprobiotics, with a greater emphasis on the latter due to its inherent safety.

Impact statements: This study highlighted the anti-inflammatory and antioxidant properties of probiotic and paraprobiotic that could be useful for patients with inflammatory status.

Purpose: Immunotherapy is a promising treatment for cancers but should be optimized for malignant gliomas. Because of immune privilege feature of the brain, local administration of immunotherapy may be a promising strategy for malignant glioma treatment. Identification of patients who may benefit from local immunotherapy is essential.

Methods: We retrospectively reviewed the clinicopathological characteristics and outcomes of six malignant glioma patients who received local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor resection cavity. Profiles of tumor genome, transcriptome and immune microenvironment were also investigated by genomic target sequencing, RNA sequencing, electrochemiluminescence assay and immunohistochemistry (IHC) staining.

Results: Four patients died from tumor progression and the overall survival ranged from 10.0 to 33.9 months. Remarkably, two patients, including one diagnosed as diffuse hemispheric glioma H3 G34-mutant (G34-DHG, WHO grade 4) and the other diagnosed as astrocytoma (IDH1 mutation, WHO grade 3) survived more than 20 years without evidence of recurrence. The distinctive clinical feature of the two long-term survivors was tumor gross total resection (GTR) before CIK therapy. NTRK1 mutation was uniquely present and 353 genes were differentially expressed in the long-term survivors compared with the short-term survivors. These differential expression genes were highly associated with immune function. Electrochemiluminescence assay and IHC staining revealed higher expressions of cytokines and lower infiltrations of tumor-associated macrophages in the tumors of the long-term survivors.

Conclusion: These findings suggest that certain patients diagnosed as malignant gliomas, including G34-DHG (WHO grade 4), can acquire long-term survival after local immunotherapy. Tumor GTR before local immunotherapy and relatively weaker immunosuppressive tumor microenvironment are the favorable factors for long-term survival. Larger, controlled studies with standardized treatment protocols, including consistent use of GTR, are warranted to further evaluate the potential benefits of locally delivered immunotherapy.

Background: HIV-exposed uninfected (HEU) children are at increased risk of morbidity during the first years of life. Although the immune responses of HEU infants in early-life are relatively well described, studies of natural killer (NK) cells in older HEU children are lacking. NK cell subsets were analysed in HEU children and compared to those in HIV unexposed uninfected (HUU) children aged ~ five years.

Methods: Multi-parametric flow cytometry was used to characterize peripheral blood-derived NK cell CD56, CD16, CD57, NKG2A and KIR3DL1/KIR2DL2/L3 expression, including intracellular perforin and granzyme B. NK cell subsets were compared between HEU children exposed to prenatal antiretroviral therapy (ART) from conception [long-term (HEULT)]; those exposed to ART during pregnancy [medium-term (HEUMT)] with continued exposure throughout the breastfeeding period and HUU peers. Furthermore, clinical data of the children, including sick clinic visits and hospitalizations documented in morbidity diaries from birth to 5 years were compared between HEU and HUU groups. Frequencies of CD56^bright and CD56^dim NK cell were correlated with these clinical parameters.

Results: 139 children were enrolled however, 133 comprising 43 HEULT, 38 HEUMT and 52 HUU were included in the main analyses. Total NK cell, CD56^bright nor CD56^dim NK cell proportions differed between HEU and HUU children. However, HEULT children had lower frequencies of CD56^dim NK cells compared to HEUMT children, (p = 0.002) which maintained significance after controlling for preterm birth, p = 0.012. No differences were observed between HEULT and HUU. The expressions of NKG2A, KIR3DL1/KIR2DL2/L3 and CD57 on CD56^bright and CD56^dim NK cells were similar between the three groups. Furthermore, the frequencies of granzyme B and perforin double positive NK cells were similar between the HUU with HEULT and HEUMT children. CD56^dim NK cell counts had a significant moderate negative correlation with recurrent respiratory infections (rho=-0.38; p = 0.010) in HUU children and negatively correlated with total sick clinic visits in HEUMT (rho=-0.40, p = 0.064).

Conclusion: The proportions of total NK cell, CD56^bright and CD56^dim NK cells, NK cells inhibitory and differentiation surface marker expression and cytolytic granule-positive cells were similar between HEU and HUU children. These data suggest that early-life HIV/ART exposure may not result in major changes in NK cell subsets at 5 years of age.

Background: The relationship of serum 25-hydroxyvitamin D concentrations and ANA positivity according to sex stratification is unclear. The propose of this study was to reveal the sex-specific relationship of serum 25-hydroxyvitamin D concentrations and ANA positivity in American people.

Methods: The study was conducted in 2757 subjects from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. The logistic regression models were used to assess the correlation between the risk of ANA positivity and serum 25-hydroxyvitamin D concentrations. Generalized additive models and smooth fitting curves were used to evaluate the non-linear relationship of the risk of ANA positivity and serum 25-hydroxyvitamin D levels.

Results: Following multivariable adjustment, we observed a negative correlation between serum 25-hydroxyvitamin D concentrations and the risk of ANA positivity in male participants, particularly in men non-white individuals and those exposed to second-hand smoke. However, there was no significant relationship observed in the female participants. Additionally, the relationship between serum 25-hydroxyvitamin D concentrations and the risk of ANA positivity followed an L-shaped pattern, with an inflection point at 18 ng/mL. When serum 25-hydroxyvitamin D levels fell below this inflection point, decrease of 1 unit in serum 25-hydroxyvitamin D concentrations was linked to an 8% increase in the adjusted OR of ANA positivity (OR 0.92; 95% CI 0.87, 0.97; p 0.0026).

Conclusions: In American men, nonlinear relationships were observed between serum 25-hydroxyvitamin D concentrations and the risk of ANA positivity.

Purpose: This research probes into genes related to the risk of concurrent kidney injury in septic patients to provide reliable targets for early identification of sepsis-associated kidney injury and prognosis research.

Methods: Peripheral blood samples were isolated from 10 healthy individuals and 22 septic patients for RNA sequencing and differential analyses. Meanwhile, the top 1000 kidney-associated genes were chosen from the GTEx website. Subsequently, DEGs in sepsis were intersected with kidney-specific genes, followed by GO and KEGG analyses on these intersection genes. The predictive ability of hub genes for prognosis was evaluated using survival analysis. A meta-analysis was carried out to determine the differential expression profiles of hub genes between the sepsis surviving and dead groups. ROC curves were plotted to screen hub genes and clarify their diagnostic value. Cell line localization of hub genes was further clarified through single-cell RNA sequencing.

Results: There were 40 targets in the intersection between 1328 DEGs in sepsis and 1000 kidney-associated genes. These intersection genes were mainly engaged in functions and signaling pathways .Survival curves linked the higher levels of CD74 and IL32 to raised survival rates of patients, indicating positive correlations of CD74 and IL32 with patient prognosis. Meta-analysis revealed that CD74 and IL32 were highly expressed in the sepsis surviving group but poorly expressed in the sepsis dead group, showing statistically significant differences between these two groups. In the ROC analysis of hub genes, AUC values of CD74 (0.983) and IL32 (0.980) suggested their high diagnostic value. Lastly, CD74 was principally expressed in macrophages, while IL32 was mainly presented in T cells.

Conclusion: CD74 and IL32, as biomarkers for early diagnosis and prognostic evaluation of sepsis complicated with kidney injury, are highly expressed in macrophages and T cells, respectively, providing new diagnostic and prognostic targets for sepsis complicated with acute kidney injury.

Background: Psoriasis is a chronic inflammatory skin disease. The Wnt/β-catenin signaling pathway is essential for the regulation of adult stem cells, homeostasis, and tissue regeneration; however, the relationship between this pathway and interleukin (IL)-36γ in the pathogenesis of psoriasis remains unclear.

Methods: In this study, psoriasiform model mice were established using imiquimod (IMQ) induction. Hematoxylin and eosin (H&E) staining was used to evaluate pathological morphologies, while immunohistochemistry was used to verify the expression patterns of β-catenin and the inflammatory factors IL-6, IL-17 A, and interferon (IFN)-γ.

Results: IL-36γ treatment increased psoriasis area and severity index scores, and enhanced proliferation of keratinocytes in IMQ-induced psoriatic mice. The effects of IL-36γ on the severity of psoriasiform lesions and epidermal hyperplasia were partly inhibited by IWR-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. Furthermore, the levels of proinflammatory cytokines and molecules involved in the Wnt/β-catenin signaling pathway in psoriatic mouse skin, including IL-6, IL-17 A, IFN-γ, β-catenin, and Dickkopf-1 (DKK1), were upregulated by treatment with IL-36γ. Consistently, the effects of IL-36γ on the inflammatory response and the Wnt/β-catenin signaling pathway were alleviated by IWR-1.

Conclusions: Taken together, our findings suggested that inhibition of the Wnt/β-catenin signaling pathway may be useful in the alleviation of IL-36γ-induced psoriasis-like lesions.

The Mokola Virus belongs to the family Rhabdoviridae and is genotype 3 of the Lyssavirus genera. A small number of cases of animal and human encephalomyelitis, mainly scattered over sub-Saharan Africa, have been linked to the Mokola Virus (MOKV). Currently there is no vaccine to protect against MOKV infection in people or animals. It has been proven that rabies vaccination does not confer immunity against MOKV infection, even though MOKV and the rabies virus are related. Using immunoinformatics approaches, this study designed an mRNA vaccine that can protect against all the five glycoproteins of the Mokola virus. NCBI was used to obtain the viral sequences, which were then screened for antigenicity, allergenicity, toxicity, B-cell epitopes, CD8 + T lymphocytes (CTL), and CD4 + T lymphocytes (HTL). These epitopes were used in the construction of the vaccine. Some extra co-translational residues were added to the mRNA vaccine construct. Its molecular weight is 129.19083 kDa, and its estimated pI is 8.58. It interacts rather steadily and with limited deformability with TLR 3, among other human innate immune receptors. Overall, the results show that the produced candidate vaccine is non-allergen, non-toxic, and can elicit T-cell and B-cell immune responses. These findings can further be subjected to in-vivo and in-vitro techniques for validation.

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Four types of RNA modification writers (m6A, m1A, A-I editing, and APA) are widely involved in tumorigenesis and the TME. We aimed to comprehensively explore the role of the four RNA modification writers in the progression and immune microenvironment of HNSCC.

Materials and methods: We first obtained transcription profile data and transcriptional variation of the four types of RNA modification writers from The Cancer Genome Atlas (TCGA) database. HNSCC patients in TCGA dataset were divided into different clusters based on the four types of RNA modification writers. Univariate Cox and Least absolute shrinkage and selection operator (LASSO) analyses were performed to conduct a Writer-score scoring system, which was successfully verified in the GSE65858 dataset and our clinical sample dataset. Finally, we evaluated the relationship between different RNA modification clusters (Writer-score) and immunological characteristics of HNSCC.

Results: Two different RNA modification clusters (A and B) were obtained. These RNA modification clusters (Writer-score) were strongly associated with immunological characteristics (immunomodulators, cancer immunity cycles, infiltrating immune cells (TIICs), inhibitory immune checkpoints, and T cell inflamed score (TIS)) of HNSCC.

Conclusions: This study identified two different RNA modification clusters and explored the potential relationship between RNA modification clusters (Writer-score) and immunological characteristics, offering a new theoretical basis for precision immunotherapy in patients with HNSCC.

Aims: We aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.

Methods: Forty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.

Results: DEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.

Conclusion: Darbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.