Search

A20 acts as a tumor suppressor in hepatocellular carcinoma, especially inhibiting metastasis of the malignant cells. However, the mechanisms whereby A20 plays the inhibitory roles are not understood completely. Rac1 signaling is essential for cell migration in hepatocellular carcinoma metastasis. Nevertheless, it is not known whether and how A20 inhibits Rac1 signaling to suppress the migration of hepatocellular carcinoma cell. Thereby, we analyzed the relationship between A20 and Rac1 activation, as well as the activity of Akt and mTORC2, two signaling components upstream of Rac1, using gain and loss of function experiments. We found that the overexpression of A20 repressed, while the knockdown or knockout of A20 promoted, the activation of Rac1, Akt and mTORC2 in hepatocellular carcinoma cells. Moreover, the inhibitory effect of A20 on the mTORC2/Akt/Rac1 signaling axis was due to the interaction between A20 and mTORC2 complex. The binding of A20 to mTORC2 was mediated by the ZnF7 domain of A20 and M1 ubiquitin chain in the mTORC2 complex. Furthermore, A20 inhibited metastasis of hepatocellular carcinoma cells via restraining mTORC2 in a hepatocellular carcinoma xenograft mouse model. These findings revealed the relationship between A20 and mTORC2, and explained the molecular mechanisms of A20 in inhibition of hepatocellular carcinoma metastasis.

Endometrial carcinoma is one of the most common malignancies in the female reproductive system. Interleukin-37 (IL-37) is a newly discovered anti-inflammatory factor belonging to the IL-1 family. IL-37 has five different isoforms, and IL-37b is the most biologically functional subtype. In recent years, the protective roles of IL-37 in different cancers, including lung and liver cancers, have been successively reported. IL-37 also plays an important role in some gynecological diseases such as endometriosis, adenomyosis, and cervical cancer. However, the role and mechanism of IL-37b, especially the mature form of IL-37b, in endometrial carcinoma have not been elucidated. The present study demonstrated that IL-37 protein was downregulated in endometrial carcinoma cells compared with the control endometrium. IL-37b did not affect the proliferation and colony-forming ability of endometrial cancer cells. A mature form of IL-37b (IL-37bΔ1-45) effectively suppressed the migration and invasion of endometrial cancer cells by decreasing the expression of matrix metalloproteinase 2 (MMP2) via Rac1/NF-κB signal pathway. However, it did not affect epithelial–mesenchymal transition (EMT) or filamentous actin (F-actin) depolymerization of endometrial cancer cells. IL-37bΔ1-45 attenuated tumor metastasis in a peritoneal metastatic xenograft model of endometrial cancer. To sum up, these results suggested IL-37b could be involved in the pathogenesis of endometrial carcinoma and provide a novel target for the diagnosis and treatment of endometrial carcinoma.

Aim:The bacterial persisters have emerged as a huge threat to human health. Here, we investigated the role of L-tryptophan in bacterial persister killing by aminoglycoside antibiotics (AGs). Materials & methods:The relevance to the antibiotic susceptibility of Escherichia coliincluding transcriptional sequencing, gene expression, intracellular ATP, Nicotinamide adenine dinucleotide (NAD/NADH), reactive oxygen species and membrane depolarization were determined. Results & conclusion:We found that exogenous L-tryptophan efficiently inhibited AGs-enabled persisters. The flagellar genes were almost significantly downregulated. Besides, the AGs uptake was obviously increased as the result of elevation in proton motive force (PMF) in response to L-tryptophan-mediated NADH production. Taken together, these data supported a novel role of L-tryptophan in eradicating AGs persisters against E. coli.

ABSTRACTIntroduction: Toxoplasma gondiiis an intracellular parasitic protozoan that infects almost all warm-blooded animals and humans, resulting in threats to public health and economic losses. Despite continuous research efforts, there are still very few effective strategies against toxoplasmosis. In the past few years, numerous vaccination experiments have been performed to control T. gondiiinfection.Areas covered: In this review, the authors summarize the development of T. gondiivaccines with proper adjuvants, ranging from live or live-attenuated vaccines to protein vaccines, DNA vaccines, epitope vaccines and novel vaccines. They also highlight the challenges involved in the development of T. gondiivaccines, including specific impediments and shortcomings.Expert opinion: Moving towards the development of effective vaccines against T. gondiiis not only a tedious mission but also a difficult challenge. Future studies should consider new approaches and strategies for vaccine development, particularly novel vaccines and genetic adjuvants, as well as optimizing immunization protocols and evaluation criteria.

Among the family of nitrogen-containing heterocycles, quinoxalinone (or quinoxalin-2-one) core, characterized by pyrazin-2(1H)-one fused to benzene ring at two adjacent carbon atoms, has been frequently found in a variety of pharmacologically active compounds with biological or pharmaceutical applications. It was gratifying that a larger part of these bioactive quinoxalinone-based derivatives has entered various clinical trials, which in turn hastens the synthetic versatility and also initiates various derivatization of quinoxalinone scaffold. In this review, we highlighted the newly emerged quinoxalinone- based derivatives or analogues, with the emphasis of their biological applications and structure-activity analysis covering literatures in recent years.

In this work, we consider a class of Hardy–Sobolev differential equations and systems involving the fractional Laplacian on the unit ball. We first show the differential equations and systems are equivalent to some integral equations and systems, respectively. Then applying the method of moving planes in the integral forms, we prove the radial symmetry of positive solutions.

Toxoplasma gondiiinfection occurs commonly in humans and other warm-blooded animals. Its serious impact on public health and livestock sectors makes the development of an effective vaccine particularly important. In the current study, we constructed a multiantigenic DNA vaccine expressing ROP16 and GRA7 of T. gondiiand evaluated the protective efficacy of these two fragments with or without a plasmid encoding murine costimulatory molecule B7-2. These recombinant eukaryotic expression plasmids were termed pROP16, pGRA7, pROP16-GRA7 and pB7-2, respectively. After intramuscular immunization in Kunming mice, we assessed the immune response using cytokine and antibody determinations, T lymphocyte subsets analysis, and the survival times of mice post acute T. gondiichallenge. The results showed that mice immunized with the multiantigenic DNA vaccine pROP16–GRA7 gained higher levels of IgG titers and IgG2a subclass titers, production of IFN-γ, percentage of CD8+T cells and median survival times against the acute infection of T. gondiicompared with those of mice administered with pROP16 or pGRA7 and those in control groups. Moreover, the adjuvant pB7-2 formulated with DNA vaccine boosted these humoral and cellular (Th1, CD8+T cell) immune responses. Therefore, it might be a promising genetic adjuvant to DNA vaccine against T. gondiifor further investigation.

Toxoplasma gondiiis a ubiquitous protozoan parasite that can infect a wide range of animals including humans. This single known species in the genus Toxoplasmais considered as one of the most successful eukaryotic pathogens which is of major medical and veterinary importance. Effective vaccines may contribute toward preventing and controlling the spread of toxoplasmosis. The present communication addresses the current status of development of vaccines against T. gondii. Further discussion is made on the difficulties along with challenges, such as vaccine construct, mode of vaccine administration and standardization of immunization evaluation. Finally suggestions are made on possible directions for future research on the development of vaccines against T. gondii.