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• High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment compromise clinical efficacy. • Adding Panax notoginseng saponin (PNS) to ASA potentiates platelet inhibition without increased bleeding. • PNS alleviates ASA-related dyspepsia symptoms and mitigates ASA-induced gastric mucosal injury. • These effects are associated with intraplatelet and gastric arachidonic acid metabolism modulation by lipidomic analysis. High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment are associated with poor compliance and an increased risk of cardiovascular events. Panax notoginseng saponins (PNS) have been widely used for the treatment of coronary heart disease (CHD) in addition to antiplatelet drugs in China; however, the joint effect and possible mechanism of PNS in addition to ASA on platelet activation and gastric injury remain unclear. This study was designed to investigate the combinational effects of PNS with ASA, and to explore the underlying mechanism via arachidonic acid (AA) metabolism pathway using lipidomic analysis. In a randomized, assessor-blinded trial, 42 patients with stable coronary heart disease (SCHD) and chronic gastritis were randomly assigned to receive ASA (n = 21) or PNS + ASA (n = 21) for 2 months. Compared with ASA alone, PNS + ASA further inhibited CD62p expression, GPIIb-IIIa activation and platelet aggregation and led to increased platelet inhibition rate. PNS + ASA suppressed the activity of platelet cyclooxygenase (COX)-1, and decreased the production of TXB 2 , PGD 2 , PGE 2 , 11-HETE, the downstream oxylipids of AA/COX-1 pathway in platelets, compared with ASA alone. The severity of dyspepsia assessment (SODA) results showed that patients in PNS + ASA group exhibited relieved dyspeptic symptoms as compared with those in ASA group, which might be associated with enhanced secretion of gastrin and motilin. In vivo study of myocardial infarction rats demonstrated that PNS attenuated ASA-induced gastric mucosal injury, which was related to markedly boosted gastric level of 6,15-diketo-13,14-dihydro-prostaglandin (PG)F1α, 13,14-dihydro-15-keto-PGE 2 and PGE 2 from AA/PG pathway in response to PNS + ASA compared with ASA alone. In summary, our study demonstrated that the combination of PNS and ASA potentiated the antiplatelet effect of ASA via AA/COX-1/TXB 2 pathway in platelets, and mitigated ASA-related gastric injury via AA/PG pathway in gastric mucosa. [ABSTRACT FROM AUTHOR]

Tremendous progress has been seen in the study of the role of sialic acid binding im-munoglobulin type lectins (Siglecs) in osteoimmunology in the past two decades. Interest in Siglecs as immune checkpoints has grown from the recognition that Siglecs have relevance to human disease. Siglecs play important roles in inflammation and cancer, and play key roles in immune cell signaling. By recognizing common sialic acid containing glycans on glycoproteins and glycolipids as regulatory receptors for immune cell signals, Siglecs are expressed on most immune cells and play important roles in normal homeostasis and self-tolerance. In this review, we describe the role that the siglec family plays in bone and bone homeostasis, including the regulation of osteoclast differentiation as well as recent advances in inflammation, cancer and osteoporosis. Particular emphasis is placed on the relevant functions of Siglecs in self-tolerance and as pattern recognition receptors in immune responses, thereby potentially providing emerging strategies for the treatment of bone related diseases. [Display omitted] • Siglec-15 is involved in osteoclast differentiation and maturation. • Siglecs significantly influence cancer progression. • CD22 and Siglec-G may be novel therapeutic targets for rheumatoid arthritis. • Siglecs as pattern recognition receptors engage the bone innate immune system. [ABSTRACT FROM AUTHOR]

To uncover the role of microRNA-200a-3p in regulating osteogenic differentiation of MSCs via targeting glutaminase, thus influencing the progression of OP. Serum level of microRNA-200a-3p in OP patients and healthy controls was determined by qRT-PCR. MicroRNA-200a-3p level in MSCs undergoing osteogenic differentiation for different days was examined as well. ALP activity, calcification nodules and relative levels of Bglap, Runx2 and OPN in MSCs overexpressing microRNA-200a-3p undergoing osteogenic differentiation were detected. Relative l -glutaminase uptake in MSCs undergoing osteogenic differentiation for different days was determined. After transfection of si-GLS in MSCs undergoing osteogenic differentiation, l -glutaminase uptake, ALP activity and relative levels of Bglap, Runx2 and OPN were detected. The potential binding relationship between microRNA-200a-3p and GLS was tested by dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to elucidate the role of microRNA-200a-3p/GLS in osteogenic differentiation of MSCs. MicroRNA-200a-3p level was higher in serum of OP patients relative to controls. Its level in MSCs gradually decreased with the prolongation of osteogenic differentiation. Overexpression of microRNA-200a-3p reduced cell viability, ALP activity, number and volume of calcification nodule. The mRNA levels of Bglap, Runx2 and OPN were downregulated by overexpressed microRNA-200a-3p. The cell viability, ALP activity, number and volume of calcification nodule were reduced when microRNA-200a-3p was knocked down. The mRNA levels of Bglap, Runx2 and OPN were upregulated when transfected microRNA-200a-3p inhibitor. l -glutaminase uptake increased with the prolongation of osteogenic differentiation in MSCs. Knockdown of GLS attenuated l -glutaminase uptake and ALP activity, as well as downregulated Bglap, Runx2 and OPN. Besides, GLS was verified to directly bind to microRNA-200a-3p. GLS overexpression reversed the inhibitory effects of overexpressed microRNA-200a-3p on osteogenic differentiation of MSCs. MicroRNA-200a-3p suppresses osteogenic differentiation of MSCs via targeting glutaminase, thereafter accelerating the progression of OP. [ABSTRACT FROM AUTHOR]

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L. [ABSTRACT FROM AUTHOR]