Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.

Bone is a dynamic organ continuously undergoing shaping, repairing and remodeling. The homeostasis of bone is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts (OCs) are specialized multinucleated cells derived from hematopoietic stem cells (HSCs) or monocytes/macrophage progenitor cells. There are different stages during osteoclastogenesis, and one of the most important steps to form functional osteoclasts is realized by cell-cell fusion. In our study, microarray was performed to detect the expression profiles of lncRNA, mRNA, circRNA and miRNA at different stages during osteoclastogenesis of RAW264.7 cells. Often changed RNAs were selected and clustered among the four groups with Venn analysis. The results revealed that expressions of 518 lncRNAs, 207 mRNAs, 24 circRNAs and 37 miRNAs were often altered at each stage during OC differentiation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis were performed to predict the functions of differentially expressed lncRNAs and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed RNAs. The present study provided a systematic perspective on the potential function of non-coding RNAs (ncRNAs) during osteoclastogenesis.

Natural bone is a complex material with well-designed architecture. To achieve successful bone integration and regeneration, the constituent and structure of bone-repairing scaffolds need to be functionalized synergistically based on biomimetics. In this study, a hybrid membrane composed of chitosan (CS), sodium carboxymethyl cellulose (CMC), and nano-hydroxyapatite (n-HA) was curled in a concentric manner to generate an anisotropic spiral-cylindrical scaffold, with compositional and structural properties mimicking natural bone. After optimization in terms of morphology, hydrophilicity, swelling and degradation pattern, the osteoblast cells seeded on the membrane of 60 wt% n-HA exhibited the highest cell viability and osteocalcin expression. In vivo osteogenesis assessment revealed that the spiral-cylindrical architecture played a dominant role in bone regeneration and osseointegration. Newly formed bone tissue grew through the longitudinal direction of the cylinder-shaped scaffold bridging both ends of the defect, bone marrow penetrated the entire scaffold and formed a medullary cavity in the center of the spiral cylinder. This study for the first time demonstrates that the spiral-cylindrical scaffold can promote complete infiltration of bone tissues in vivo, leading to successful osteointegration and functional reconstruction of bone defects. It suggests that the biomimetic spiral-cylindrical scaffold could be a promising candidate for bone regeneration applications.

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