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Osteoporosis (OP) is a systemic bone disease with loss of bone mass and destruction of the microscopic structure. Many antiosteoporosis drugs have been used for OP therapy, but the therapeutic efficiency remains limited. Therefore, there is an urgent need to develop new drugs for antiosteoporosis treatment. Selenium (Se) is one kind of essential trace element for humans and displays pivotal roles in maintaining bone homeostasis. However, the modulation roles of Se are greatly affected by its chemical forms. Herein, Se containing protein derived from Se-enriched Spirulina platensis (Se-SP) were extracted and used for the treatment of OP in an ovariectomized mice model. The results showed that Se-SP showed enhanced potential in promoting excretion of calcium and alkaline phosphatase (ALP) expression than that of SP in MC3T3-E1 cells. Micro-CT revealed that Se-SP administration in vivo effectively alleviated bone loss as indicated by the upregulated BV, Tb.Th, Bv/TV, Tb.N, and BMD as well as the decreased Tb.Sp. Se-SP in vivo also significantly suppressed inflammatory response through restricting the expression of proinflammatory cytokines expression and upregulating the secretion of anti-inflammatory cytokines. Additionally, Se-SP effectively inhibited ovariectomy-induced osteoblast inactivation and osteoclastogenesis by upregulating BMP2, RUNX2, COL-I, OCN and OPG pression and downregulating RANKL expression. Together, these findings suggested that Se-SP was a new form of Se in therapy of human OP. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C‐termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene‐recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O‐sulfation at C‐terminus. Experimental Approach An integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein‐engineered hirudins. Key Results: Molecular dynamic analysis showed that modifications of the C‐termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C‐termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased Ki and IC50 values. In the in vivo experiments, mutations at C‐termini of HV1 and HM2 significantly changed partial thromboplastin time, prothrombin and thrombin time Conclusion and Implications: The study indicated that the anticoagulant effects of gene‐engineered HM2 are stronger than gene‐engineered HV1 and HM2‐E60D‐I62D has the strongest effects and could be an antithrombotic with better therapeutic effects. [ABSTRACT FROM AUTHOR]