Oral cavity incessantly encounters a plethora of microorganisms. Plaque biofilm-a major cause of caries, periodontitis and other dental diseases-is a complex community of bacteria or fungi that ...causes infection by protecting pathogenic microorganisms from external drug agents and escaping the host defense mechanisms. Antimicrobial nanoparticles are promising because of several advantages such as ultra-small sizes, large surface-area-to-mass ratio and special physical and chemical properties. To better summarize explorations of antimicrobial nanoparticles and provide directions for future studies, we present the following critical review. The keywords "nanoparticle," "anti-infective or antibacterial or antimicrobial" and "dentistry" were retrieved from Pubmed, Scopus, Embase and Web of Science databases in the last five years. A total of 172 articles met the requirements were included and discussed in this review. The results show that superior antibacterial properties of nanoparticle biomaterials bring broad prospects in the oral field. This review presents the development, applications and underneath mechanisms of antibacterial nanoparticles in dentistry including restorative dentistry, endodontics, implantology, orthodontics, dental prostheses and periodontal field.
Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor ...progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic.
Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential.
Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity.
The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.
The selective in vitro expansion and differentiation of multipotent stem cells are critical steps in cell‐based regenerative therapies, while technical challenges have limited cell yield and thus ...affected the success of these potential treatments. The Rho GTPases and downstream Rho kinases are central regulators of cytoskeletal dynamics during cell cycle and determine the balance between stem cells self‐renewal, lineage commitment and apoptosis. Trans‐4‐(1R)‐aminoethyl‐N‐(4‐pyridinyl)cylohexanecarboxamidedihydrochloride (Y‐27632), Rho‐associated kinase (ROCK) inhibitor, involves various cellular functions that include actin cytoskeleton organization, cell adhesion, cell motility and anti‐apoptosis. Here, human periodontal ligament stem cells (PDLSCs) were isolated by limiting dilution method. Cell counting kit‐8 (CCK8), 5‐ethynyl‐2′‐deoxyuridine (EdU) labelling assay, cell apoptosis assay, cell migration assay, wound‐healing assay, alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, Oil Red O staining, quantitative real‐time polymerase chain reaction (qRT‐PCR) were used to determine the effects of Y‐27632 on the proliferation, apoptosis, migration, stemness, osteogenic and adipogenic differentiation of PDLSCs. Afterwards, Western blot analysis was performed to elucidate the mechanism of cell proliferation. The results indicated that Y‐27632 significantly promoted cell proliferation, chemotaxis, wound healing, fat droplets formation and pluripotency, while inhibited ALP activity and mineral deposition. Furthermore, Y‐27632 induced PDLSCs proliferation through extracellular‐signal‐regulated kinase (ERK) signalling cascade. Therefore, control of Rho‐kinase activity may enhance the efficiency of stem cell‐based treatments for periodontal diseases and the strategy may have the potential to promote periodontal tissue regeneration by facilitating the chemotaxis of PDLSCs to the injured site, and then enhancing the proliferation of these cells and maintaining their pluripotency.
Exosomes derived from cells have been found to mediate signal transduction between cells and to act as efficient carriers to deliver drugs and small RNA. Hepatocyte growth factor (HGF) is known to ...promote the growth of both cancer cells and vascular cells, and the HGF‐cMET pathway is a potential clinical target. Here, we characterized the inhibitory effect of HGF siRNA on tumor growth and angiogenesis in gastric cancer. In addition, we showed that HGF siRNA packed in exosomes can be transported into cancer cells, where it dramatically downregulates HGF expression. A cell co‐culture model was used to show that exosomes loaded with HGF siRNA suppress proliferation and migration of both cancer cells and vascular cells. Moreover, exosomes were able to transfer HGF siRNA in vivo, decreasing the growth rates of tumors and blood vessels. The results of our study demonstrate that exosomes have potential for use in targeted cancer therapy by delivering siRNA.
HGF siRNA packed in exosomes can be transported into cancer cells, and down‐regulates HGF expression, and suppress proliferation and migration of both cancer cells and vascular cells.
The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect ...areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes.
Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration.
Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials.
Ferroelectric materials (FEMs), possessing piezoelectric, pyroelectric, inverse piezoelectric, nonlinear optic, ferroelectric‐photovoltaic, and many other properties, are attracting increasing ...attention in the field of biomedicine in recent years. Because of their versatile ability of interacting with force, heat, electricity, and light to generate electrical, mechanical, and optical signals, FEMs are demonstrating their unique advantages for biosensing, acoustics tweezer, bioimaging, therapeutics, tissue engineering, as well as stimulating biological functions. This review summarizes the current‐available FEMs and their state‐of‐the‐art fabrication techniques, as well as provides an overview of FEMs‐based applications in the field of biomedicine. Challenges and prospects for future development of FEMs for biomedical applications are also outlined.
Ferroelectric materials (FEMs), which are able to sense and convert mechanical, thermal, electrical, and optical energy, possess multiple capabilities to interface with various biological processes, thus demonstrating great potential to work for biomedicine.
Oxaliplatin (oxa) is widely used in the treatment of colorectal cancer (CRC), but the development of oxaliplatin resistance is a major obstacle to the therapeutic efficacy in patients. MicroRNAs ...(miRNAs), endogenous noncoding RNAs measuring between 22 and 24 nucleotides, have been shown to be involved in the development of CRC drug resistance. However, the mechanism by which differentially expressed miRNAs induce chemotherapy resistance in CRC has not been fully elucidated to date. Here, we showed the differentially expressed miRNAs in oxaliplatin-sensitive and oxaliplatin-resistant CRC cells through miRNA microarray technology and found that miR-135b-5p was significantly increased in oxaliplatin-resistant cells. And miR-135b-5p was increased in the serum of colorectal cancer patients. More importantly, the miR-135b-5p level in the serum of oxaliplatin-resistant patients was further increased compared to that of oxaliplatin-sensitive patients. Recent studies have shown that protective autophagy is an important mechanism that promotes drug resistance in tumors. The potential role of miR-135b-5p in inducing protective autophagy and promoting oxaliplatin resistance was evaluated in two stable oxaliplatin-resistant CRC cell lines and their parental cells. We further identified MUL1 as a direct downstream target of miR-135b-5p and showed that MUL1 could degrade the key molecule of autophagy, ULK1, through ubiquitination. Mouse xenograft models were adopted to evaluate the correlation between miR-135b-5p and oxaliplatin-induced autophagy in vivo. Furthermore, we also investigated the regulatory factors for the upregulation of miR-135b-5p in CRC cells under oxaliplatin chemotoxicity. These results indicated that miR-135b-5p upregulation in colorectal cancer could induce protective autophagy through the MUL1/ULK1 signaling pathway and promote oxaliplatin resistance. Targeting miR-135b-5p may provide a new treatment strategy for reversing oxaliplatin resistance in CRC.
Hepatocellular carcinoma (HCC) is a common cancer with high incidence and mortality worldwide. The main treatments for HCC include radical hepatectomy, liver transplant, locoregional therapies, and ...systemic therapies. Systemic treatments include targeted agent treatment, chemotherapies, antiviral therapies, and nutritional treatments. According to the results of SHARP and ORIENTAL study, sorafenib became the standard first-line therapy since 2008 because of nearly three months of survival improvement in patients with advanced HCC. Subsequent studies on targeted agents found that neither sunitinib nor brivanib were superior to sorafenib as first-line therapy. After progression or intolerance of sorafenib, brivanib did not improve the overall survival (OS) compared with placebo as second-line therapy. Randomized controlled EACH study and retrospective AGEO study for systemic chemotherapy showed that oxaliplatin-based or gemcitabine-based regimen was effective for advanced HCC patients. Randomized controlled trial for adjuvant chemotherapy in China showed that capecitabine could reduce the risk of recurrence and improve postoperative survival of HCC. Comparing sorafenib with other treatments, several retrospective studies found that other treatments were not inferior to sorafenib in terms of OS. In the systemic treatment of HCC, antiviral treatment can decrease the recurrence of HBV-related HCC postoperation and prolong the survival of patients. Based on the etiology, symptoms, complications, and treatment-related side effects, nutritional treatment is also very important for HCC patients. Systemic chemotherapy, newer targeted agents, and immune therapy are the new directions in future research.
Background and Objectives
Basic fibroblast growth factor (bFGF) promotes cells proliferation and chemotaxis and maintains stemness while inhibits mineralized nodule formation. Bone morphogenetic ...protein 2 (BMP‐2) shows great potential in promoting bone formation. However, sequential application of these two growth factors on periodontal ligament stem cells (PDLSCs) has not been explored. In this study, we aimed to identify the optimal concentration and time of bFGF on PDLSCs proliferation, migration and then investigate the sequential delivery of bFGF and BMP‐2 on osteogenic differentiation of PDLSCs in vitro.
Materials and Methods
Periodontal ligament stem cells were isolated by limiting dilution method. Dose‐dependent additive effects of bFGF and BMP‐2 on PDLSCs were detected. Cell counting assay, cell migration assay, alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis were used to determine different application modalities of bFGF and BMP‐2 on proliferation, migration, and osteogenic differentiation of PDLSCs.
Results
50 ng/mL bFGF significantly promoted PDLSCs proliferation and chemotaxis while time‐dependently inhibited BMP‐2 induced ALP activity. Sequential application of 25 ng/mL bFGF for first 3 days and followed with 50 ng/mL BMP‐2 for another 9, 18, and 25 days significantly promoted PDLSCs osteogenic differentiation. Compared with bFGF and BMP‐2 simultaneous group, sequential application of bFGF and BMP‐2 group significantly enhanced ALP activity, osteogenesis‐related genes and proteins expression and mineral deposition.
Conclusion
Sequential application of bFGF and BMP‐2 synergistically promoted osteogenic differentiation of PDLSCs, and this sequential application modality of growth factors would provide a new strategy for periodontal regeneration.
The biodegradable metals have great potential for the biomedical applications, which could be gradually degraded, absorbed, or excreted in the human body, avoiding the removal though secondary ...surgery. Zinc-based alloys are novel series of degradable metals for medical applications, and they are gaining lots of attention in the research field of absorbable metals. Zinc-silver (Zn-Ag) alloys show superior mechanical strength, good biodegradability, biocompatibility, and antibacterial properties, which render them to be potential candidates for biomedical applications. In this paper, we reviewed the development of Zn-Ag alloys in terms of mechanical properties, degradabilities, biocompatibilities, antibacterial properties, and potential applications in dentistry.
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