Although Helicobacter pylori is recognized as an extracellular infection bacterium, it can lead to an increase in the number of CD8+ T cells after infection. At present, the characteristics of H. pylori antigen-specific CD8+ T cells and the epitope response have not been elucidated. This study was focused on putative protective antigen UreB to detect specific CD8+ T-cell responses in vitro and screen for predominant response epitopes.
Methods
The PBMCs collected from H. pylori-infected individuals were stimulated by UreB peptide pools in vitro to identify the immunodominant CD8+ T-cell epitopes. Furthermore, their HLA restriction characteristics were detected accordingly by NGS. Finally, the relationship between immunodominant responses and appearance of gastric symptoms after H. pylori infection was conducted.
Results
UreB-specific CD8+ T-cell responses were detected in H. pylori-infected individuals. Three of UreB dominant epitopes (A-2 (UreB443–451: GVKPNMIIK), B-4 (UreB420–428: SEYVGSVEV), and C-1 (UreB5–13: SRKEYVSMY)) were firstly identified and mainly presented by HLA-A*1101, HLA-B*4001 and HLA-C*0702 alleles, respectively. C-1 responses were mostly occurred in H. pylori-infected subjects without gastric symptoms and may alleviate the degree of gastric inflammation.
Conclusions
The UreB dominant epitope-specific CD8+ T-cell response was closely related to the gastric symptoms after H. pylori infection, and the C-1 (UreB5-13) dominant peptides may be protective epitopes. 相似文献
Bisphenol S (BPS) is an environmental endocrine disruptor widely used in industrial production. BPS induces oxidative stress and exhibits male reproductive toxicity in mice, but the mechanisms by which BPS impairs steroid hormone synthesis are not fully understood. Nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 signaling is a key pathway in improving cellular antioxidant defense capacities. Therefore, this study explored the effects of exposure to BPS on testosterone synthesis in adult male mice and its mechanisms with regard to the Nrf2/HO-1 signaling pathway. Adult male C57BL/6 mice were orally exposed to BPS (2, 20, and 200 mg/kg BW) with sesame oil as a vehicle (0.1 ml/10 g BW) per day for 28 consecutive days. The results showed that compared with the control group, serum testosterone levels were substantially reduced in the 20 and 200 mg/kg BPS treatment groups, and testicular testosterone levels were reduced in all BPS treatment groups. These changes were accompanied by a prominent decrease in the expression levels of testosterone synthesis-related enzymes (STAR, CYP11A1, CYP17A1, HSD3B1, and HSD17B3) in the mouse testis. In addition, BPS induced oxidative stress in the testis by upregulating the messenger RNA and protein levels of Keap1 and downregulating the levels of Nrf2, HO-1, and downstream antioxidant enzymes (CAT, SOD1, and Gpx4). In summary, our results indicate that exposure of adult male mice to BPS can inhibit Nrf2/HO-1 signaling and antioxidant enzyme activity, which induces oxidative stress and thereby may impair testosterone synthesis in testicular tissues, leading to reproductive damage. 相似文献
Few approaches have been conducted in the treatment of renal cell carcinoma (RCC) after nephrectomy, resulting in a high mortality rate in urological tumours. Mitophagy is a mechanism of mitochondrial quality control that enables selective degradation of damaged and unnecessary mitochondria. Previous studies have found that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is associated with the progression of tumours such as lung cancer, colorectal cancer and oropharyngeal cancer, but the potential mechanism in RCC is still unclear. In this study, microarrays from tumour databases were analysed. The expression of GPD1L was confirmed by RT–qPCR and western blotting. The effect and mechanism of GPD1L were explored using cell counting kit 8, wound healing, invasion, flow cytometry and mitophagy-related experiments. The role of GPD1L was further confirmed in vivo. The results showed that GPD1L expression was downregulated and positively correlated with prognosis in RCC. Functional experiments revealed that GPD1L prevented proliferation, migration and invasion while promoting apoptosis and mitochondrial injury in vitro. The mechanistic results indicated that GPD1L interacted with PINK1, promoting PINK1/Parkin-mediated mitophagy. However, inhibition of PINK1 reversed GPD1L-mediated mitochondrial injury and mitophagy. Moreover, GPD1L prevented tumour growth and promoted mitophagy by activating the PINK1/Parkin pathway in vivo. Our study shows that GPD1L has a positive correlation with the prognosis of RCC. The potential mechanism involves interacting with PINK1 and regulating the PINK1/Parkin pathway. In conclusion, these results reveal that GPD1L can act as a biomarker and target for RCC diagnosis and therapy. 相似文献
Intact tropical forests are generally considered to be resistant to invasions by exotic species, although the shrub Clidemia hirta (Melastomataceae) is highly invasive in tropical forests outside its native range. Release from natural enemies (e.g., herbivores and pathogens) contributes to C. hirta invasion success where native melastomes are absent, and here we examine the role of enemies when C. hirta co-occurs with native Melastomataceae species and associated herbivores and pathogens. We study 21 forest sites within agricultural landscapes in Sabah, Malaysian Borneo, recording herbivory rates in C. hirta and related native Melastoma spp. plants along two 100-m transects per site that varied in canopy cover. Overall, we found evidence of enemy release; C. hirta had significantly lower herbivory (median occurrence of herbivory per plant = 79% of leaves per plant; median intensity of herbivory per leaf = 6% of leaf area) than native melastomes (93% and 20%, respectively). Herbivory on C. hirta increased when closer to native Melastoma plants with high herbivory damage, and in more shaded locations, and was associated with fewer reproductive organs on C. hirta. This suggests host-sharing by specialist Melastomataceae herbivores is occurring and may explain why invasion success of C. hirta is lower on Borneo than at locations without related native species present. Thus, natural enemy populations may provide a “biological control service” to suppress invasions of exotic species (i.e., biotic resistance). However, lower herbivory pressures in more open canopy locations may make highly degraded forests within these landscapes more susceptible to invasion. 相似文献
It is critical for spring wheat (Triticum aestivum L.) production in the semi-arid Loess Plateau to understand the impact of nitrogen (N) fertilizer on changes in N metabolism, photosynthetic parameters, and their relationship with grain yield and quality. The photosynthetic capacity of flag leaves, dry matter accumulation, and N metabolite enzyme activities from anthesis to maturity were studied on a long-term fertilization trial under different N rates [0 kg ha?1(N1), 52.5 kg ha?1 (N2), 105 kg ha?1 (N3), 157.5 kg ha?1 (N4), and 210 kg ha?1 (N5)]. It was observed that N3 produced optimum total dry matter (5407 kg ha?1), 1000 grain weight (39.7 g), grain yield (2.64 t ha?1), and protein content (13.97%). Our results showed that N fertilization significantly increased photosynthetic parameters and N metabolite enzymes at all growth stages. Nitrogen harvest index, partial productivity factor, agronomic recovery efficiency, and nitrogen agronomic efficiency were decreased with increased N. Higher N rates (N3–N5) maintained higher photosynthetic capacity and dry matter accumulation and lower intercellular CO2 content. The N supply influenced NUE by improving photosynthetic properties. The N3 produced highest chlorophyll content, photosynthetic rate, stomatal conductance and transpiration rate, grain yield, grain protein, dry matter, grains weight, and N metabolite enzyme activities compared to the other rates (N1, N2, N4, and N5). Therefore, increasing N rates beyond the optimum quantity only promotes vegetative development and results in lower yields.
Compared with the standard method of manual fertilizer broadcasting (MFB), mechanized hill-drilling direct-seeding with deep application of slow-release nitrogen fertilizer (MHDDF) is an efficient method to integrate both fertilization and seeding. However, there are few studies that combine the use of slow-release fertilizer with MHDDF. We sought to explore the combined effect of MHDDF with slow-release fertilizer on rice yield and nitrogen, phosphorus, and potassium utilization, compared to MFB. We compared three different MHDDF methods (D30: 450 kg ha?1, D40: 600 kg ha?1, D50: 750 kg ha?1), with one MFB method (B50: 750 kg ha?1), and one control (CK: 0 kg ha?1). We found that the yield of all MHDDF method was higher than that of both the MFB method. Yield was the highest in the D50 treatment and was 14.14–46.03% higher than that in B50 treatment. Biomass accumulation, nutrient accumulation, and nutrient use efficiency were similarly higher in MHDDF method than both MFB and CK. Compared to B50, the D50 treatment increased nitrogen recovery efficiency by 170.53–231.50%, phosphorus recovery efficiency by 480.00–724.25%, and potassium recovery efficiency by 201.55–169.59%. Overall, we found that combining MHDDF with slow-release fertilizer was an effective method to increase rice yield and nutrient use efficiency compared with MFB.