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Background: Numerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry. Results: 106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P <0.001). After the administration of probiotics and prebiotics, the composition and metabolic function of the intestinal microbiota were significantly altered and positively related to the beneficial effect on seasonal AR patients. Conclusion: Probiotics combined with prebiotics administered for 90 days significantly attenuated the symptoms of seasonal AR patients, which may related to fluctuations in the composition and metabolic function of the intestinal microbiota and further ameliorating host immunity. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) and type 2 diabetes (T2DM) are closely associated with increased rate of death. C1q/TNF-related protein 6 (CTRP6) is a novel adipocytokine which plays an important role in glucose and lipid metabolism. Little is known about the function of CTRP6 in CAD and T2DM patients. Herein, we aimed to study the association of CTRP6 level with CAD and T2DM. Methods: This study included 51 CAD, 44 CAD+T2DM and 65 non-CAD+T2DM patients from Affiliated Aoyang Hospital of Jiangsu University. Serum CTRP6 concentrations were detected by ELISA. Multiple logistic regression was used to analyze the association of serum CTRP6 with CAD and T2DM. Results: Serum CTRP6 concentrations were significantly lower in CAD patients than controls. However, there is no significant statistical difference between CAD+T2DM patients and non-CAD+T2DM patients. Serum CTRP6 was negatively correlated with low-density lipoprotein cholesterol (LDL-C) (ρ=− 0.2769, p=0.028) in controls. Serum CTRP6 was positively correlated with age (ρ=0.4121, p=0.0027), systolic blood pressure (SBP) (ρ=0.4012, p=0.0035), Creatinine (ρ=0.3295, p=0.0194), uric acid (UA) (ρ=0.3386, p=0.0162), and left ventricular end diastolic diameter (LVD) (ρ=0.4277, p=0.0042) and negatively correlated with ejection fraction (EF) (ρ=− 0.3237, p=0.0342) in CAD patients. Serum CTRP6 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) (ρ=− 0.3164, p=0.0387) in CAD+T2DM patients. Multiple logistic regression showed that the decrease of CTRP6 was significantly related to the increased prevalence of CAD. What is more, CTRP6 increased prevalence of T2DM in CAD patients. Conclusion: Lower serum CTRP6 could be a risk factor of CAD. However, higher circulating CTRP6 associated with the increased prevalence of T2DM in CAD patients. [ABSTRACT FROM AUTHOR]

Anti-PD-L1 therapy exhibits durable efficacy, but only in a small fraction of cancer patients. The immunosuppressive tumor microenvironment (TME) is a crucial obstacle that impedes cancer immunotherapy. Here, we found that anti-PD-L1 therapy coupled with CD4+ T cell depletion induced colorectal tumor regression and vascular normalization, while monotherapy only retarded tumor growth without affecting the tumor vasculature. Moreover, simultaneous PD-L1 blockade and CD4+ T cell depletion eradicated intratumoral PD-L1+ lymphoid and myeloid cell populations, while additively elevating the proportions of CD44+CD69+CD8+, central memory CD44+CD62L+CD8+, and effector memory CD44+CD62L-CD8+ T cells, suggesting a reduction in immunosuppressive cell populations and the activation of CD8+ T cells in the TME. Moreover, anti-PD-L1 therapy reduced the proportions of intratumoral PD-L1+ immune cells and suppressed tumor growth in a CD8+ T cell dependent manner. Together, these results suggest that anti-PD-L1 therapy induces tumor vascular normalization and colorectal tumor regression via CD8+ T cells, which is antagonized by CD4+ T cells. Our findings unveil the positive correlation of tumor regression and vascular normalization in colorectal tumor models upon anti-PD-L1 therapy, providing a potential new strategy to improve its efficacy. [ABSTRACT FROM AUTHOR]

B7-H5, an immune checkpoint molecule, is markedly upregulated in multiple cancers and plays an important role in tumor progression and immune escape. However, the expression and significance of soluble B7-H5 (sB7-H5) in cancer remain unclear. Herein, we generated two novel mouse anti-human B7-H5 monoclonal antibodies (mAbs) 2E5 and 7B10, which had different epitopes. Based on the two mAbs, a sandwich enzyme-linked immunosorbent assay (ELISA) system was developed. Using this ELISA, we found that compared with healthy controls (HCs), sB7-H5 levels were significantly increased in the serum of patients with gastric cancer (GC), colorectal cancer (CRC), and lung cancer (LC) and were associated with TNM stage and metastasis. Receiver operating characteristic (ROC) curve analysis showed that sB7-H5 has diagnostic value for GC, CRC, and LC. Collectively, our findings delineate that sB7-H5 may be used as a predictor for diagnosis of cancer and a potential therapeutic target for cancer treatment. [ABSTRACT FROM AUTHOR]

Background:Asthma is characterized by airway remodeling arising from an increase in airway smooth muscle (ASM) mass. This increase is regulated in part by ASM cell proliferation and migration. MicroRNA (miR)-21 also plays a role in asthma, but the molecular mechanisms underlying its effects are not completely understood. This study investigated the effects and mechanism of miR-21 on the human ASM (HASM) cell proliferation and migration.Materials and Methods:HASM cells were transduced with a miR-21 vector, and the expression of miR-21 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of the miR-21 on HASM cell proliferation and migration was analyzed by CCK8 and transwell assay. The expression level ofPTEN(phosphatase and tensin homolog deleted on chromosome 10) in HASM cells was assessed by qRT-PCR and Western blot analysis. Meanwhile, the activity of PTEN was measured by PTEN malachite green assay kit.Results:Lentivirus-mediated miR-21 overexpression markedly enhanced the proliferation and migration of HASM cells (P< .05), and ablation of miR-21 by anti-miR-21 inhibitor markedly reduced cell proliferation and migration. We demonstrated that miR-21 overexpression significantly reduced the expression of PTEN (P< .05), while PTEN knock-down markedly increased HASM cell proliferation and migration. Furthermore, we found that overexpression of PTEN led to a decrease of HASM cell proliferation and migration. MiR-21 mediated HASM cell proliferation and migration through activation of the phosphoinositide 3-kinase pathway.Conclusions:This study provides the firstin vitroevidence that overexpression of miR-21 in HASM cells can trigger cell proliferation and migration, and the effects of miR-21 depend on the level of PTEN. [ABSTRACT FROM PUBLISHER]

Acinetobacter pittii 44551 was recovered from a patient with gout combined with tuberculosis and was found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM-44551 displayed high self-transferability across multiple bacterial species, while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii receipts. pNDM-44551 was a close variant of the previously characterized pNDM-BJ01, and the blaNDM-1 gene cluster was arranged sequentially as orfA, ISAba14, aphA6, ISAba125, blaNDM-1, bleMBL, ΔtrpF, dsbC, tnpR, and zeta. pOXA58-44551 was a repAci9-containing plasmid, and blaOXA-58 was embedded in a 372F-ISAba3-like-blaOXA-58-ISAba3 structure. The mobile genetic platforms of blaNDM-1 and blaOXA-58 herein showed some differences from their previously characterized variants. The production of NDM-1 in strain 44551 contributed the majority to its high resistance to carbapenems, while the blaOXA-58 stayed silent most likely due to the lack of an upstream promoter to drive its transcription. Increased surveillance of Acinetobacter co-harboring blaNDM-1 (active) and blaOXA-58 (either active or silent) is urgently needed. [ABSTRACT FROM AUTHOR]