The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of interleukin-1 (IL-1), IL-10 and tumor necrosis factor (TNF)-a polymorphisms with Behcet's disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta-analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above-mentioned three cytokine genes and susceptibility to BD. Meta-analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF-a -308A/G: OR = 0.73, 95% CI: 0.61-0.88, P = 0.001; IL-10 -819C/T: OR = 0.72, 95% CI: 0.66-0.78, P < 0.001; IL-10 -592C/A: OR = 0.74, 95% CI: 0.64-0.86, P < 0.001); the dominant model (TNF-a -308A/G: OR = 0.77, 95% CI: 0.64-0.92, P = 0.004; IL-10 -1082G/A: OR = 1.64, 95% CI: 1.10-2.44, P = 0.014); the recessive model (TNF-a -308A/G: OR = 0.27, 95% CI: 0.12-0.65, P = 0.003; IL-10 -819C/T: OR = 0.71, 95% CI: 0.57-0.90, P = 0.004). However, no significant evidence for the associations of IL-1a -889C/T, IL-1b -551C/T, IL-1b -3962C/T polymorphisms with BD susceptibility was detected. The present study might suggest that TNF-a -308A/G, IL-10 -1082G/A, -819C/T, -592C/A polymorphisms are associated with BD susceptibility.

Abstract. Liver cancer stem cells (LCSCs) have important roles in the occurrence, development, recurrence, therapy resistance and metastasis of hepatocellular carcinoma (HCC). Therefore, intensive studies are undergoing to identify the mechanisms by which LCSCs contribute to HCC invasion and metastasis, and to design more efficient treatments for this disease. With continuous efforts in LCSC research over the years, therapies targeting LCSCs are thought to have great potential for the clinical treatment and prognosis of liver cancer. Novel LCSC surface markers are continuously discovered and several have been used in targeted therapies to reduce HCC recurrence, metastasis, and drug resistance following tumor resection. The present review describes the surface markers characterizing LCSCs and the recent progress in therapies targeting these markers, including antibodies and polypeptides.

Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT).

Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (μR), one of the major opioid receptors, strongly influences memory processing in that alterations in μR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether μR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective μR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal μR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal μRs were significantly activated during acute stress. Blockage of hippocampal μRs, non-selective deletion of μRs or selective deletion of μRs on GABAergic neurons (μR GABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a μR GABA-dependent manner. Pharmaceutically enhancing hippocampal GABA A receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate μR GABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.

The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.

This study attempted to use collagen–Matrigel as extracellular matrix (ECM) to supply cells with three-dimensional (3D) culture condition and employ alginate-poly-l-lysine-alginate (APA) microcapsules to control the formation of alveolus-like structure in vitro. We tested mice foetal pulmonary cells (FPCs) by immunohistochemistry after 2D culture. The alveolus-like structure was reconstructed by seeding FPCs in collagen–Matrigel mixed with APA microcapsules 1.5 ml. A self-made mould was used to keep the structure from contraction. Meanwhile, it provided static stretch to the structure. After 7, 14 and 21 days of culture, the alveolus-like structure was analysed histologically and immunohistochemically, or by scanning transmission electron microscopy (TEM). We also observed these structures under inverted phase contrast microscope. The expression of pro-surfactant protein C (SpC) was detected by reverse transcription-polymerase chain reaction (RT-PCR). We obtained fibroblasts, epithelial cells and alveolar type II (AE2) cells in FPCs. In the reconstructed structure, seeding cells surrounding the APA microcapsules constructed alveolus-like structures, the size of them ranges from 200 to 300 μm. In each reconstructed lung tissue sheet, microcapsules had integrity. Pan-cytokeratin, vimentin and SpC positive cells were observed in 7- and 14-day cultured structures. TEM showed lamellar bodies of AE2 cells in the reconstructed tissues whereas RT-PCR expressed SpC gene. Primary mice FPCs could form alveolus-like structures in collagen–Matrigel/APA microcapsules engineered scaffolds, which could maintain a differentiated state of AE2 cells.

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Background: Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed.Methods: Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pretreatment, in-treatment plasma samples and available matched tissue samples were collected. Targetedcapture sequencing of 1,021 genes that are frequently mutated in solid tumors.Results: Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001).Conclusions: ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy.