Multifunctional MXene-doped photothermal microneedles for drug-resistant bacteria-infected wound healing.

Skin injuries and drug-resistant bacterial infections pose serious challenges to human health. It is essential to establish a novel multifunctional platform with good anti-infection and wound-healing abilities. In this study, a new MXene-doped composite microneedle (MN) patch with excellent mechanical strength and photothermal antibacterial and ROS removal properties has been developed for infected wound healing. When the MN tips carrying the MXene nanosheets are inserted into the cuticle of the skin, they will quickly dissolve and subsequently release the nanomaterials into the subcutaneous infection area. Under 808 nm NIR irradiation, the MXene, as a "nano-thermal knife", sterilizes and inhibits bacterial growth through synergistic effects of sharp edges and photothermal antibacterial activity. Furthermore, ROS caused by injury and infection can be cleared by MXene-doped MNs to avoid excessive inflammatory responses. Based on the synergistic antibacterial and antioxidant strategy, the MXene-doped MNs have demonstrated excellent wound-healing properties in an MRSA-infected wound model, such as promoting re-epithelialization, collagen deposition, and angiogenesis and inhibiting the expression of pro-inflammatory factors. Therefore, the multifunctional MXene-doped MN patches provide an excellent alternative for clinical drug-resistant bacteria-infected wound management.

Graphene and its derivatives: "one stone, three birds" strategy for orthopedic implant-associated infections.

Orthopedic implants provide an avascular surface for microbial attachment and biofilm formation, impeding the entry of immune cells and the diffusion of antibiotics. The above is an important cause of dental and orthopedic implant-associated infection (IAI). For the prevention and treatment of IAI, the drawbacks of antibiotic resistance and surgical treatment are increasingly apparent. Due to their outstanding biological properties such as biocompatibility, immunomodulatory effects, and antibacterial properties, graphene-based nanomaterials (GBNs) have been applied to bone tissue engineering to deal with IAI, and in particular have great potential application in drug/gene carriers, multi-functional platforms, and coating forms. Here we review the latest research progress and achievements in GBNs for the prevention and treatment of IAI, mainly including their biomedical applications for antibacterial and immunomodulation effects, and for inducing osteogenesis. Furthermore, the biosafety of graphene family materials in bone tissue regeneration and the feasibility of clinical application are critically analyzed and discussed.

Recent advances and trends in the applications of MXene nanomaterials for tissue engineering and regeneration.

MXene, as a new two-dimensional nanomaterial, is endowed with lots of particular properties, such as large surface area, excellent conductivity, biocompatibility, biodegradability, hydrophilicity, antibacterial activity, and so on. In the past few years, MXene nanomaterials have become a rising star in biomedical fields including biological imaging, tumor diagnosis, biosensor, and tissue engineering. In this review, we sum up the recent applications of MXene nanomaterials in the field of tissue engineering and regeneration. First, we briefly introduced the synthesis and surface modification engineering of MXene. Then we focused on the application and development of MXene and MXene-based composites in skin, bone, nerve and heart tissue engineering. Uniquely, we also paid attention to some research on MXene with few achievements at present but might become a new trend in tissue engineering and regeneration in the future. Finally, this paper will also discuss several challenges faced by MXene nanomaterials in the clinical application of tissue engineering.

A Novel circUBR4/miR-491-5p/NRP2 ceRNA Network Regulates Oxidized Low-density Lipoprotein-induced Proliferation and Migration in Vascular Smooth Muscle Cells.

ABSTRACT: Vascular smooth muscle cells (VSMCs) play critical roles in the progression of atherosclerosis. Circular RNA (circRNA) ubiquitin protein ligase E3 component n-recognin 4 (circUBR4) has been shown to regulate VSMC migration and proliferation. In this study, we sought to identify the mechanism in the regulation of circUBR4. CircUBR4, microRNA (miR)-491-5p, and Neuropilin-2 (NRP2) were quantified by quantitative real-time polymerase chain reaction (PCR) and western blot. Cell proliferation was evaluated by Cell Counting Kit-8 and 5-Ethynyl-2'-Deoxyuridine assays. Cell migration was examined by wound-healing and transwell invasion assays. The direct relationship between miR-491-5p and circUBR4 or NRP2 was validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that in VSMCs, ox-LDL induced circUBR4 expression. Silencing endogenous circUBR4 attenuated VSMC proliferation and migration induced by ox-LDL. Mechanistically, circUBR4 targeted miR-491-5p by pairing to miR-491-5p. Moreover, miR-491-5p was identified as a downstream mediator of circUBR4 function in ox-LDL-treated VSMCs. NRP2 was a direct target of miR-491-5p, and circUBR4 acted as a competing endogenous RNA for miR-491-5p to regulate NRP2 expression. In addition, NRP2 was a functionally downstream effector of miR-491-5p in regulating ox-LDL-evoked VSMC proliferation and migration. Our findings identify a new competing endogenous RNA network, the circUBR4/miR-491-5p/NRP2 axis, for the regulation of circUBR4 in VSMC migration and proliferation.

Circ-USP9X Inhibition Reduces Oxidized Low-density Lipoprotein-induced Endothelial Cell Injury via the microRNA 599/Chloride Intracellular Channel 4 Axis.

ABSTRACT: Atherosclerosis (AS) is the common pathological basis of cardiovascular disease. Circular RNA circ-USP9X (hsa_circ_0090231) has been discovered to be upregulated in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs), but the role of circ-USP9X in ox-LDL-induced endothelial cell injury is indistinct. The purpose of the research was to investigate the role and regulatory mechanism of circ-USP9X in ox-LDL--induced endothelial cell injury. Expression of circ-USP9X was examined by quantitative real-time polymerase chain reaction. Loss-of-function experiments were performed to assess the impacts of circ-USP9X inhibition on viability, cell cycle progression, apoptosis, and tube formation, inflammation, and oxidative stress of ox-LDL-induced HUVEC. The regulatory mechanism of circ-USP9X predicted by bioinformatics analysis and verified by dual-luciferase reporter or RNA immunoprecipitation assays. We observed that circ-USP9X was upregulated in AS patients' serum and ox-LDL-induced HUVEC. Inhibition of circ-USP9X elevated viability, promoted cell cycle progression and angiopoiesis, and decreased apoptosis, inflammation, and oxidative stress of ox-LDL-induced HUVEC. Mechanically, circ-USP9X regulated chloride intracellular channel 4 (CLIC4) messenger RNA expression by sponging microRNA (miR)-599. Furthermore, miR-599 inhibitor overturned circ-USP9X silencing-mediated influence on ox-LDL-induced HUVEC injury. Also, CLIC4 overexpression reversed miR-599 elevation-mediated effect on ox-LDL-induced HUVEC injury. In conclusion, circ-USP9X silencing decreased ox-LDL-induced endothelial cell injury via the miR-599/CLIC4 axis, which offered a novel molecular mechanism to comprehend the pathology of AS.

Biomaterial-based strategies for maxillofacial tumour therapy and bone defect regeneration.

Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects. In traditional tumour therapy, the systemic toxicity of chemotherapeutic drugs, invasive surgical resection, intractable tumour recurrence, and metastasis are major threats to the patients' lives in the clinic. Fortunately, biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis, suggesting new promising antitumour therapies. In addition, maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients, and investment in treatment can result in a multitude of burdens to society. Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration. More interestingly, an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option. Herein, we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair. Furthermore, we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.

Correlation Between Maternal Smoking During Pregnancy and Dental Caries in Children: A Systematic Review and Meta-Analysis.

Background: Dental caries is a long-standing oral health problem for children all over the world. The available evidence shows that the association between maternal smoking during pregnancy and childhood caries is still controversial. Therefore, the aim of this systematic review and meta-analysis was to determine whether there was a correlation of prenatal smoking and dental caries in children. Methods: PubMed, EMBASE, Cochrane, Web of Science, and Scopus databases were searched for observational studies assessing the relationship between maternal smoking during the pregnancy and childhood caries. According to the predesigned eligibility criteria and items, studies selection, and data extraction were conducted, respectively. The effect estimates were pooled using a fixed-effect model or a random-effect model. Newcastle-Ottawa Scale (NOS) was adopted to evaluate the methodological quality of the included studies. All analyses were carried out through Stata 12.0 software. Results: Our systematic review included a total of 11 studies, of which 6 cross-sectional studies and 3 longitudinal studies were included in the final meta-analysis. The pooled estimates indicated maternal smoking during pregnancy was significantly associated with dental caries in children both in cross-sectional studies (OR = 1.57, 95% CI = 1.47-1.67) and longitudinal studies (RR = 1.26, 95% CI = 1.07-1.48). Sensitivity analyses confirmed the overall effect estimates were robust. Conclusions: There is a significant correlation of maternal smoking during pregnancy and childhood caries. However, the causal relationship between them cannot be determined. More prospective and extensive studies on this theme is needed for verification. Even so, it is necessary for pregnant women and women of reproductive age to quit smoking. Strategies must be developed to raise public awareness about the impact of prenatal smoking on children's oral health.

Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta-analysis.

BACKGROUND: Increasing studies suggest that antibiotic exposure during pregnancy may increase the risk of childhood allergic diseases; however, controversy still exists. Thus, we conducted this meta-analysis to evaluate the association between antibiotic use during pregnancy and childhood asthma/wheeze, eczema/atopic dermatitis, and food allergy. METHODS: CENTRAL, EMBASE, and PubMed were searched for studies up to July 20, 2020. Cohort studies and case-control studies that estimated the association of antibiotic exposure in pregnancy with the risk of childhood asthma/wheeze, eczema/atopic dermatitis, and food allergy were included. A random-effects model or fixed-effects model was used to calculate the pooled estimates. The quality of the included studies was assessed by the Newcastle-Ottawa Scale (NOS). Stata12.0 software was used to analyze the association through a meta-analysis. RESULTS: A total of 26 studies were included in the meta-analysis. The results showed that maternal antibiotic exposure in pregnancy and the summary OR for the risk of childhood asthma/wheeze was 1.29 (95% CI = 1.16-1.43), the summary OR for eczema/atopic dermatitis was 1.62 (95% CI = 1.16-2.27), and the pooled OR for food allergy was 1.36 (95% CI = 0.94-1.96). CONCLUSIONS: Our results indicated that maternal antibiotic use during pregnancy might increase the risk of asthma/wheeze and eczema/atopic dermatitis but not food allergy in children. Further studies with larger sample size and robust multivariable adjustment are needed to confirm our findings. Nevertheless, the appropriate use of antibiotics during pregnancy is incredibly important, and healthcare professionals should be selective when prescribing antibiotics for pregnant women.