Background: Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common conditions of microcytic hypochromic anemia (MHA) in pregnant women. We used the BC-6800Plus analyzer to study the utility of erythrocyte and reticulocyte parameters for distinguishing TT from IDA in pregnant women.Methods: A total of 454 anemic pregnant women, including 340 with IDA, 66 with β-thalassemia trait (β-TT) and 48 with α-thalassemia trait (α-TT), were included. Multiple comparisons among groups were performed, and diagnostic performance of parameters was determined using receiver operating characteristic (ROC) curve analysis, with P<0.05 indicating statistical significance.Results: Reticulocyte production index (RPI) and the average volume of mature red blood cells (MCVm) in the IDA group were significantly higher than in the β-TT and α-TT groups. Red blood cell (RBC), reticulocyte percentage (Ret%), and RPI in the IDA group were significantly lower than in the α-TT and β-TT groups. We devised MHA 1=0.42× MCH −0.57× RPI −0.08× %MICROr −9.38 to distinguish IDA from α-TT. With a cut-off value of 0.61, the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were 0.868, 90.9%, and 68.5%, respectively. We devised MHA 2=0.04× %MICROr +0.12
Heterotopic ossification (HO) is a common disease characterized by pain, dysfunction and calcification. The mechanisms underlying HO have not been completely elucidated. Palovarotene, a retinoic acid receptor γ agonist, significantly inhibits the formation of HO in vivo. However, its specific mechanism of action remains unclear. Therefore, we aimed to evaluate the signalling pathways related to the formation of HO as well as the mechanism of palovarotene action. We constructed in vitro and in vivo models of HO. Osteogenic differentiation of bone mesenchymal stem cells (BMSCs) was observed by alizarin red and alkaline phosphatase staining assays in vitro. X‐ray and haematoxylin–eosin staining were performed in vivo. Western blots and reverse transcription‐polymerase chain reaction were performed to determine the levels of osteogenic‐ and inflammation‐related genes. Immunofluorescence and immunocytochemistry were used to assess the levels of p65, the core molecule of the nuclear factor κ‐B (NF‐κB) signalling pathway. We demonstrated that, in vitro, under inflammatory stimulation, pathological calcium deposition increased in BMSCs. The levels of osteogenesis‐ and inflammation‐related genes were also upregulated, along with an enhanced expression of p65. Immunofluorescence assays revealed that p65 entered the nucleus, thereby stimulating the downstream effectors of the NF‐κB pathway. The above trends were reversed after palovarotene treatment. In conclusion, the NF‐κB signalling pathway played an important role in HO, and palovarotene could alleviate HO by blocking the NF‐κB cascade. Our results may provide a theoretical basis for palovarotene in the treatment of HO. Further studies on the side effects of palovarotene are warranted in the future.
Heterotopic ossification (HO) occurs when bone forms within non-ossifying tissues, such as in muscle. Palovarotene, an activator of retinoic acid receptor γ (RAR-γ), has been shown to inhibit the formation of ectopic bone in HO model mice, but its specific mechanism of action remains unclear. This study will explore the target and molecular mechanism of Palovarotene's action on HO by network pharmacology study. We collected the relevant targets of Palovarotene and HO from the database, obtained the potential targets of Palovarotene acting on HO through Venn analysis, and constructed the protein-protein interaction (PPI) network. Then, Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment Analysis and Module-based Network Analysis were performed for potential targets, and in addition, PPI Network Topology Analysis and Gene-Phenotype Correlation Analysis were performed. The results suggested that MAPK1, MDM2, and other targets as well as P53 signaling pathway and PI3K–Akt signaling pathway may be closely related to Palovarotene treatment of HO. We carried out verification experiments to confirm our finding, alkaline phosphatase and alizarin red staining in vitro and Micro-CT as well as hematoxylin-eosin staining in vivo were performed to verify treatment for HO of Palovarotene, reverse transcription polymerase chain reaction was also used to explore the transcription changes of MAPK1, MDM2, and osteogenic genes. This study systematically elucidated the possible mechanism of Palovarotene in the treatment of HO through network pharmacology study, revealing a new direction for the further application of Palovarotene in the treatment of HO.
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