Triptolide mitigates the inhibition of osteogenesis induced by TNF-α in human periodontal ligament stem cells via the p-IκBα/NF-κB signaling pathway: an in-vitro study.

BACKGROUND: Triptolide is a widely utilized natural anti-inflammatory drug in clinical practice. Aim of this study was to evaluate effects of triptolide on hPDLSCs osteogenesis in an inflammatory setting and to investigate underlying mechanisms. METHODS: Using the tissue block method to obtain hPDLSCs from extracted premolar or third molar. Flow cytometry, osteogenic and adipogenic induction were carried out in order to characterise the features of the cells acquired. hPDLSC proliferative activity was assessed by CCK-8 assay to determine the effect of TNF-α and/or triptolide. The impact of triptolide on the osteogenic differentiation of hPDLSCs was investigated by ALP staining and quantification. Osteogenesis-associated genes and proteins expression level were assessed through PCR and Western blotting assay. Finally, BAY-117,082 was used to study the NF-κB pathway. RESULTS: In the group treated with TNF-α, there was an elevation in inflammation levels while osteogenic ability and the expression of both osteogenesis-associated genes and proteins decreased. In the group co-treated with TNF-α and triptolide, inflammation levels were reduced and osteogenic ability as well as the expression of both osteogenesis-associated genes and proteins were enhanced. At the end of the experiment, both triptolide and BAY-117,082 exerted similar inhibitory effects on the NF-κB pathway. CONCLUSION: The osteogenic inhibition of hPDLSCs by TNF-α can be alleviated through triptolide, with the involvement of the p-IκBα/NF-κB pathway in this mechanism.

Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration.

Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal-phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of mice bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.

[Application of immunosuppressive agents in crtical coronavirus disease].

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the nucleus raphe magnus to participate in pain modulation.

Hypothalamic paraventricular nucleus (PVN) is one of the main sources of arginine vasopressin (AVP) synthesis and secretion. AVP is the most important bioactive substance in PVN regulating pain process. Our previous study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation. The present study was designed to investigate the source of AVP in the rat NRM during pain process using the methods of nucleus push-pull perfusion and radioimmunoassay. The results showed that pain stimulation increased the AVP concentration in the NRM perfusion liquid, PVN cauterization inhibited the role that pain stimulation induced the increase of AVP concentration in the NRM perfusion liquid, and PVN microinjection of L-glutamate sodium, which excited the PVN neurons, could increase the AVP concentration in the NRM perfusion liquid. The data suggested that AVP in the PVN might be transferred to the NRM to participate in pain modulation.