Oral squamous cell carcinoma (OSCC) is the most frequent oral cancer in the world, accounting for more than 90% of all oral cancer diagnosis. Circular RNAs (circRNAs) are large types of non-coding RNAs, demonstrating a great capacity of regulating the expression of genes. However, most of the functions of circRNAs are still unknown. Recent research revealed that circRNAs could serve as a miRNA-sponge, consequently regulating the expression of target genes indirectly, including oncogenes. In this study, we built an apoptotic model with TNF-α, and then we confirmed a circRNA associated with the apoptosis of OSCC cells, circDOCK1 by comparing the expression profile of circRNAs in an apoptotic model with that in untreated OSCC cells. We ascertained the presence of circDOCK1 with qRT‑PCR and circRNA sequencing. The knockdown of the expression of circDOCK1 led to the increase of apoptosis. Utilizing multiple bioinformatics methods, we predicted the interactions among circRNAs, miRNAs and genes, and built the circDOCK1/miR‑196a‑5p/BIRC3 axis. Both the silencing of circDOCK1 with small interfering RNA and the upregulation of the expression of miR‑196a‑5p with mimics led OSCC cells to increase apoptosis and decrease BIRC3 formation. We further confirmed this outcome by comparing the expression of circDOCK1, miR‑196a‑5p and BIRC3 in oral squamous carcinoma tissue with those in para‑carcinoma tissue, and examining the expression profile of circRNAs in oral squamous carcinoma tissue and para‑carcinoma tissue with microarray. Our results demonstrated that circDOCK1 regulated BIRC3 expression by functioning as a competing endogenous RNA (ceRNA) and participated in the process of OSCC apoptosis. Thus, we propose that circDOCK1 could represent a novel potential biomarker and therapeutic target of OSCC.

Bone grafts or prosthetic implant designing for clinical application is challenging due to the complexity of integrated physiological processes. The revolutionary advances of nanotechnology in the biomaterial field expedite and endorse the current unresolved complexity in functional bone graft and implant design. Rare earth (RE) materials are emerging biomaterials in tissue engineering due to their unique biocompatibility, fluorescence upconversion, antimicrobial, antioxidants, and anti‐inflammatory properties. Researchers have developed various RE smart nano‐biomaterials for bone tissue engineering and implantology applications in the past two decades. Furthermore, researchers have explored the molecular mechanisms of RE material‐mediated tissue regeneration. Recent advances in biomedical applications of micro or nano‐scale RE materials have provided a foundation for developing novel, cost‐effective bone tissue engineering strategies. This review attempted to provide an overview of RE nanomaterials' technological innovations in bone tissue engineering and implantology and summarized the osteogenic, angiogenic, immunomodulatory, antioxidant, in vivo bone tissue imaging, and antimicrobial properties of various RE nanomaterials, as well as the molecular mechanisms involved in these biological events. Further, we extend to discuss the challenges and prospects of RE smart nano‐biomaterials in the field of bone tissue engineering and implantology.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear.Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level.Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results.Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal–oral routes.

Infection withHelicobacter pyloriis a major risk factor for development of gastric disease, including gastric cancer. Patients infected withH. pyloristrains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which thecagAcopy number dynamically expands and contracts inH. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers ofcagAcopies; strains carried from zero to four copies ofcagAthat were arranged as direct repeats within the chromosome. Each of the multiple copies ofcagAwas expressed and encoded functional CagA; strains with morecagArepeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed threecagAhomologous areas (CHAs) within thecagArepeats. Of these, CHA-ud flanked each of thecagAcopies and is likely important for the dynamic variation ofcagAcopy numbers. Analysis of a large panel of clinical isolates showed that 7.5% ofH. pyloristrains isolated in the United States harbored multiplecagArepeats, while none of the tested Korean isolates carried more than one copy ofcagA. Finally,H. pyloristrains carrying multiplecagAcopies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction ofcagAcopy numbers may serve as a novel mechanism by whichH. pylorimodulates gastric disease development.IMPORTANCESeverity ofH. pylori-associated disease is directly associated with carriage of the CagA toxin. Though the sequences of the CagA protein can differ across strains, previous analyses showed that virtually allH. pyloristrains carry one or no copies ofcagA. This study showed thatH. pylorican carry multiple tandem copies ofcagAthat can change dynamically. Isolates harboring morecagAcopies produced more CagA, thus enhancing toxicity to host cells. Analysis of 314H. pyloriclinical strains isolated from patients in South Korea and the United States showed that 7.5% of clinical strains in the United States carried multiplecagAcopies whereas none of the South Korean strains did. This study demonstrated a novel molecular mechanism by whichH. pyloridynamically modulatescagAcopy number, which affects CagA expression and activity and may impact downstream development of gastric disease.

During exogenous bone‐graft‐mediated bone defect repair, macrophage inflammation dictates angiogenesis and bone regeneration. Exosomes from different human cells have shown macrophage immunomodulation‐mediated bone regeneration potential. However, the effect of human serum‐derived exosomes (serum‐Exo) on macrophage immunomodulation‐mediated angiogenesis during bone defect repair has not been investigated yet. In this study, we explored the effects of serum‐Exo on macrophage inflammation regulation‐mediated angiogenesis during bone defect repair and preliminarily elucidated the mechanism. Healthy serum‐Exo was isolated by ultracentrifugation. The effect of serum‐Exo on LPS‐induced M1 macrophage inflammation was analysed in vitro. The conditioned medium of serum‐Exo‐treated LPS‐induced M1 macrophage (serum‐Exo‐treated M1 macrophage‐CM) was used to culture human umbilical vein endothelial cells (HUVEC), and the effect on angiogenesis was analysed by western blot, qRT‐PCR, etc. mRNA‐sequencing of HUVECs was performed to identify deferentially expressed genes. Finally, the rat mandibular defect model was established and treated with Bio‐Oss and Bio‐Oss + Exo. The effect of the Bio‐Oss + Exo combination on mandibular bone regeneration was observed by micro‐computed tomography (micro‐CT), haematoxylin and eosin (HE) staining, Masson staining, and immunohistochemical staining. Serum‐Exo promoted the proliferation of RAW264.7 macrophages and reduced the expression of M1‐related genes such as IL‐6, IL‐1β, iNOS, and CD86. Serum‐Exo‐treated M1 macrophage‐CM induced the proliferation, migration, and angiogenic differentiation of HUVEC, as well as the expression of H‐type blood vessel markers CD31 and endomucin (EMCN), compared with M1 macrophage‐CM. Moreover, higher expression of vascular endothelial adhesion factor 1 (VCAM1) in HUVEC cultured with serum‐Exo‐treated M1 macrophage‐CM compared with M1 macrophages‐CM. Inhibition of VCAM1 signalling abrogated the pro‐angiogenic effect of serum‐Exo‐treated M1 macrophage‐CM on HUVEC. Local administration of serum‐Exo during mandibular bone defect repair reduced the number of M1 macrophages and promoted angiogenesis and osteogenesis. Collectively, our results demonstrate the macrophage inflammation regulation‐mediated pro‐angiogenic potential of serum‐Exo during bone defect repair possibly via upregulation of VCAM1 signalling in HUVEC.