Changes in peripheral T-lymphocyte subsets and serum cytokines in patients with systemic sclerosis.

Objective: T cells represent a predominant cell type in autoimmune disease. However, their exact roles are not fully clear in systemic sclerosis (SSc). This study aimed to mainly investigate the alteration in the absolute numbers of T-lymphocyte subsets and the serum levels of cytokines in SSc patients. Methods: A total of 76 patients with SSc and 76 age- and sex-matched healthy controls (HCs) were enrolled. The levels of circulating T cell subsets and serum cytokines were measured by flow cytometry. T cell subsets or serum cytokines correlations with disease activity and organ involvement were analyzed. Results: The absolute numbers of Th2 and Treg cells in SSc patients were lower than those in HCs (p < 0.05), resulting in the ratios of Th1/Th2 [25.01 (12.24, 38.61) vs. 11.64 (6.38, 20.34)] and Th17/Treg [0.42 (0.17, 0.66) vs. 0.17 (0.13, 0.29)] were increased significantly (p < 0.001). The absolute numbers of total T, Th, and Treg cells were negatively correlated with CRP (r = -0.406, p = 0.002; r = -0.263, p < 0.05; r = -0.367 p < 0.01). The serum levels of IL-2, SIL-2R, IL-6, IL-10, INF-γ, and TNF-α were significantly higher than those in HCs (p < 0.001). Increasing IL-2 in the wake of the augment of ESR (r = 0.671, p = 0.004), so did IL-6 (r = 0.378, p < 0.05). The ratio of Th17/Treg in SSc-ILD patients had lower levels than that in other patients [0.35 (0.14, 0.53) vs. 0.64 (0.26, 0.93) p = 0.028]; Treg cells were lessened in patients with Raynaud's phenomenon relative to controls [3.00 (2.41, 4.28) vs. 3.55 (2.86, 4.53) p < 0.05]. The levels of IL-2, IL-10 and INF-γ [3.32 (1.05,11.73) vs. 2.32 (0.44,6.45), p = 0.045], [8.08 (3.63, 355,77) vs. 4.89 (0.78, 21.44), p = 0.02], [6.31 (2.66, 44.03) vs. 4.03 (0.22, 16.96), p = 0.009] were elevated in patients with arthralgia, while the level of Th17 was decreased [0.62 (0.20,2.16) vs. 1.26 (0.22,10.93), p = 0.026]. ROC curve analysis yielded an optimal cut-off IL-2, IL-10, and INF-γ levels of 2.67, 5.93, and 5.32 pg/ml for the presence of arthralgia. Conclusion: We exhibited abnormalities in T subsets and the production of their cytokines in SSc, as compared with those in HCs. This may allow the pathogenesis of SSc and the development of novel therapeutic interventions aimed at targeting these cells and the cytokines they produce.

Integrative Analysis of MUC4 to Prognosis and Immune Infiltration in Pan-Cancer: Friend or Foe?

MUC4, a transmembrane mucin, plays important roles in epithelial renewal and differentiation. Recent studies suggest that MUC4 has been implicated in pancreatic cancer pathogenesis and is expressed in various normal and cancer tissues. The underlying features of MUC4 across various cancer types may allow us to ensure appropriate treatment and patient monitoring. However, the contributions of MUC4 to pan-cancer have not been well characterized. In this study, we investigated the expression pattern and prognostic value of MUC4 across multiple databases. We further explored genomic and epigenetic alterations of MUC4, its association with proliferation and metastasis, and the correlation with immune infiltration in different cancers. Our results characterized the distinct expression profile and prognostic values of MUC4 in pan-cancer. Through examining its association with genomic alteration, tumor proliferation, and metastasis, as well as tumor infiltration, we revealed multiple function effects of MUC4. MUC4 may influence prognosis, proliferation, metastasis, and immune response in opposite directions. In conclusion, our findings suggested the necessity to more carefully evaluate MUC4 as a biomarker and therapeutic target and develop the new antibodies for cancer detection and intervention.

[Research progress on the monitoring methods of atmospheric nitrogen deposition]. / å¤§æ°”æ°®æ²‰é™ç›‘æµ‹æ–¹æ³•ç ”ç©¶è¿›å±•.

As an important component of global nitrogen (N) biogeochemical cycle, atmospheric N deposition refers to the removal process of reactive N, including oxidized N (NOy) and reduced N (NHx), from the atmosphere to earth surface through dry and wet deposition. Nitrogen deposition can exert important impacts on the structure and functioning of both terrestrial and aquatic ecosystems. Increasing N deposition poses a potential threat to natural ecosystems and human health. It is a challenge to accurately monitor the composition and flux of dry and wet N deposition in different ecosystems, using a unified technology. Here, we reviewed the research progress on monitoring methods of dry and wet N deposition in China and aboard, including micrometeorology, inferential method, model estimation, surrogate surface, precipitation collection, and ion exchange resin methods. We further discussed the advantages and disadvantages of each method in terms of its applications at regional, national, and global scales. This review would provide a methodological support to establish national monitoring network for atmospheric N deposition.

microRNA-542-5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen-activated protein kinase signaling pathway through the negative regulation of P21-activated kinase 1.

Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

MicroRNA-339-3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis-associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway.

Severe acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP-ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP-ALI. This study aims to define the role of miR-339-3p in SAP-ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR-339-3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF-α, IL-6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT-qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP-ALI mice had decreased survival rate, increased levels of TNF-α, IL-6, AMS, MPO, and Schmidt scores. miR-339-3p was poorly expressed in lung tissue of SAP-ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR-339-3p. miR-339-3p inhibited the relative expression of the Akt/mTOR signaling pathway-related proteins, alleviated inflammation and edema of SAP-ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR-339-3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP-ALI mice.

Protective role of licochalcone B against ethanol-induced hepatotoxicity through regulation of Erk signaling.

OBJECTIVES: Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study. MATERIALS AND METHODS: An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay. Cell apoptosis were quantified by flow cytometric analysis. The intracellular oxidative level was evaluated by reactive oxidative species, malondialdehyde and glutathione detection. Furthermore, the expression level of Erk, p-Erk, Nrf-2 were assessed using Western blot. RESULTS: Treatment with ethanol induced marked cell injury and cell apoptosis in BRL cells. Licochalcone B significantly attenuated ethanol-induced cell injury, and inhibited cell apoptosis. Furthermore, licochalcone B significantly inhibited ethanol-induced intracellular oxidative level, upregulated the expression of p-Erk, and promoted nuclear localization of Nrf2. Additionally, this hepatoprotective role was significantly abolished by inhibition of Erk signaling. However, no apparent effects of Erk inhibition were observed on ethanol-induced hepatotoxicity. CONCLUSION: This study demonstrates that licochalcone B protects hepatocyte from alcohol-induced cell injury, and this hepatoprotective role might be attributable to apoptosis reduction, inhibition of oxidative stress, and upregulation of Erk-Nrf2. Therefore, licochalcone B might possess potential as a novel therapeutic drug candidate for alcohol-related liver disorders.

[Effects of enhanced-efficiency nitrogen fertilizers on nitrous oxide emissions from cotton field under plastic mulched drip irrigation in Xinjiang,China]. / 高效氮肥对新疆膜下滴灌棉田土壤氧化亚氮排放的影响.

The effect of enhanced-efficiency nitrogen (N) fertilizers on emissions of nitrous oxide (N2O) from the grey desert agricultural soils of Xinjiang is uncertain. In this study, the enhanced-efficiency fertilizers, polymer-coated urea (ESN), and stabilized urea with urease and nitrification inhibitors (U+I) were compared to conventional urea (U) for N2O emissions from cotton under plastic mulch drip irrigation near Urumqi, Xinjiang. ESN was added once at planting but the other treatments were added multiple times with drip irrigation during the growing season. Gas samples were collected and analyzed twice per week during the growing season, using the static chamber-chromatography methodology. The results showed that generally, ESN significantly increased soil cumulative N2O emissions during the growing season by 47%-73% compared to other treatments. In the first four months after fertilization, soil ammonium (NH4+-N) and nitrate (NO3--N) concentrations under ESN treatment were generally higher than under other treatments. Thereafter, NH4+-N and NO3--N concentrations under all treatments gradually decreased to similar levels. ESN all added at planting was likely responsible for high NH4+-N and NO3--N concentrations and highest N2O emissions. The U+I treatment reduced soil N2O emission by 9.9% in comparison with U, whereas the difference was not statistically significant. In addition, soil NO3--N contents of the U+I treatments were generally lower than those of the ESN and the U treatments. The cumulative N2O emissionsover the growing season ranged from 300 to 500 g N2O-N·hm-2, generally lower than emissions reported for other agricultural ecosystems. Drip irrigation successfully kept moisture conditions below levels for appreciable N2O emissions. Multiple applications of N via drip irrigation seemed to be effective to lower emissions than all N applied at planting. Therefore, for cotton field under plastic mulch drip irrigation in arid land of Northwest China, the benefit of enhanced efficiency N ferti-lizers on N2O mitigation is limited.