Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis.

This review aims to evaluate the adjunctive clinical effectiveness of diode laser (DL) to scaling and root planing (SRP) in the treatment of periodontitis, and identify the optimal combination of usage mode and application regimen of DL. Eight electronic databases were searched up to January 2021. Probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), plaque index (PI), and gingival index (GI) were assessed at short-term (4-6 weeks), 3-month, and 6-month follow-ups. Based on DL usage mode, studies were divided into three groups: inside, outside pocket, and combined modes. As for application regimen, studies in each group were further subdivided into single- and multiple-session subgroups. Thirty randomized controlled trials with 825 participants were included. For inside mode, single-session DL showed significant improvements for PPD (short-term, and 3-month, p < 0.05), CAL (short-term, and 3-month, p < 0.05), PI (3- and 6-month, p < 0.05), and GI (short-term, 3-month, and 6-month, p < 0.05). For outside mode, multiple-session DL showed notable improvements for most clinical outcomes (p < 0.05). The effect of combined mode was still uncertain. Adjunctive DL had additional clinical benefits in the treatment of periodontitis. One session laser treatment is suggested when DL is applied inside pocket in future clinical practice. Meanwhile, more than one session laser treatment presents better outcomes when DL is used outside pocket. PROSPERO: CRD42020156162.

Functionalized 3D-Printed ST2/Gelatin Methacryloyl/Polcaprolactone Scaffolds for Enhancing Bone Regeneration with Vascularization.

Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/ß-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair.

HIV testing behaviors and willingness to receive oral rapid HIV testing among dental patients in Xi'an, China.

INTRODUCTION: HIV testing is an important strategy for controlling and ultimately ending the global pandemic. Oral rapid HIV testing (ORHT) is an evidence-based strategy and the evidence-based shows is favored over traditional blood tests in many key populations. The dental setting has been found to be a trusted, convenient, and yet untapped venue to conduct ORHT. This study assessed the HIV testing behaviors and willingness to receive ORHT among dental patients in Xi'an, China. METHODS: A cross-sectional survey of dental patients from Xi'an was conducted from August to September 2017. Dental patients were recruited using a stratified cluster sampling. A 44-item survey was used to measure HIV/AIDS knowledge, HIV testing behaviors, and willingness to receive ORHT. RESULTS: Nine hundred and nine dental patients completed the survey with a mean HIV/AIDS knowledge score of 10.7/15 (SD 2.8). Eighty-four participants (9.2%) had previously received an HIV test. Participants would have a high rate of HIV testing if they had higher monthly income (OR = 1.982, 95% CI: 1.251-3.140) and a higher HIV/AIDS knowledge score (OR = 1.137, 95% CI: 1.032-1.252). Five hundred and eighty-two participants (64.0%) were willing to receive ORHT before a dental treatment, 198 (21.8%) were not sure, and 129 (14.2%) were unwilling. Logistic regression showed that age (OR = 0.970, 95% CI: 0.959-0.982), HIV/AIDS knowledge score (OR = 1.087, 95% CI: 1.031-1.145), previous HIV test (OR = 2.057, 95% CI: 1.136-3.723), having advanced HIV testing knowledge (OR = 1.570, 95% CI: 1.158-2.128), and having advanced ORHT knowledge (OR = 2.074, 95%: CI 1.469-2.928) were the factors affecting the willingness to receive ORHT. CONCLUSIONS: The majority of dental patients had not previously received an HIV test, although many were receptive to being tested in the dental setting. The dental setting as a venue to screen people for HIV needs further exploration, particularly because many people do not associate dentistry with chairside screenings. Increasing awareness of ORHT and reducing testing price can further improve the patient's willingness to receive ORHT.

A multifunctional-targeted nanoagent for dual-mode image-guided therapeutic effects on ovarian cancer cells.

PURPOSE: Nanomedicine has emerged as a novel therapeutic modality for cancer treatment and diagnosis. Lipid-polymer hybrid nanoparticles (LPHNPs) are core-shell nanoparticle (NP) structures comprising polymer cores and lipid shells, which exhibit complementary characteristics of both polymeric NPs and liposomes. However, it is difficult to wrap perfluoropentane (PFP) into core-shell NPs in the existing preparation process, which limits its application in the integration of diagnosis and treatment. METHODS: The folate-targeted LPHNPs-loaded indocyanine green/PFP-carrying oxygen (TOI_HNPs) using a combination of two-step method and solution evaporation technique for the first time. The essential properties and dual-mode imaging characteristics of developed NPs were determined. The cellular uptake of TOI_HNPs was detected by confocal microscopy and flow cytometry. The SKOV3 cell viability and apoptosis rate were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. The ROS was demonstrated by fluorescence microplate reader and the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and IL-6 was detected by Western blot. RESULTS: TOI_HNPs showed spherical morphology with particle size about (166.83±5.54) nm and zeta potential at -(30.57±1.36) mV. It exhibited better stability than lipid NPs and higher encapsulation efficiency as well as active targeting ability than poly (lactic-co-glycolic acid) (PLGA) NPs. In addition, the novel NPs could also act as the contrast agents for ultrasound and photoacoustic imaging, providing precision guidance and monitoring. Furthermore, TOI_HNPs-mediated photo-sonodynamic therapy (PSDT) caused more serious cell damage and more obvious cell apoptosis, compared with other groups. The PSDT mediated by TOI_HNPs induced generation of intracellular ROS and downregulated the expression of HIF-1α and IL-6 in SKOV3 cells. CONCLUSION: This kind of multifunctional-targeted nanoagent may provide an ideal strategy for combination of high therapeutic efficacy and dual-mode imaging guidance.

[Effect of oral intervention on matrix metalloproteinase-2, 9 expression in carotid arteries and serum interleukin-6 in rats with chronic periodontitis].

OBJECTIVE: To establish chronic periodontitis model in SD rats, and to investigate the effect of oral intervention on atherosclerosis. METHODS: Fifty male SD rats were randomly divided into three groups, group A (normal control), group B (atherosclerosis,As) and group C (chronic periodontitis, CP). Group C was further divided into group C1 (natural process), group C2 (simple mechanical treatment), group C3 (systemic antibiotics), group C4-1 (teeth extraction) and group C4-2 (teeth extraction+systemic antibiotics), each group consisted of 7 rats. Every group received oral intervention. Serum interleukin (IL)- 6 levels were detected in five different time points (1, 3, 5, 7, 9 weeks after a successful modeling) by enzyme linked immunosorbent assay. All animals were killed after 24 weeks. Matrix metalloproteinase (MMP)- 2, 9 in the proximal aorta was detected by immuno histochemistry. RESULTS: The levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that in group A (P < 0.01). Levels of serum IL-6 were increased gradually in each intervention group (C2, C3, C4-1, C4-2) and reached its peak at 5 weeks after modeling [C2:(62.3 ± 14.3) ng/L, C3:(58.2 ± 8.7) ng/L, C4-1:(127.0 ± 29.9) ng/L, C4-2:(120.6 ± 23.1) ng/L]. Compared with group B, group C4- 1 and C4- 2 increased most significantly (P < 0.01). Levels of serum IL- 6 decreased gradually. Eventually, group C2 [(28.6 ± 8.1) ng/L], C3 [(40.8 ± 15.1) ng/L] and C4-2 [(32.7 ± 11.1) ng/L] were significantly lower than group B (P < 0.05), and in group C2 IL- 6 was the lowest. Although levels of serum of IL-6 significantly decreased in group C4-1 [(72.8 ± 16.4) ng/L], but remained the highest. Immunohistochemistry showed that MMP-2, 9 were expressed in group B, C1 and C4-1, and significantly higher than in group A (183.0 ± 2.0, 181.3 ± 2.0), the gray value differences were statistically significant (P < 0.01). Group C4-1 (123.1 ± 2.9, 121.0 ± 3.2) was the strongest, group B (126.4 ± 2.0, 124.8 ± 2.8) and C1 (140.0 ± 2.2, 139.7 ± 3.2) were decreased (P < 0.01). While group C2(169.3 ± 3.4, 169.7 ± 2.3), C3 (149.0 ± 1.7, 145.1 ± 2.5) and C4-2 (157.7 ± 1.2, 155.8 ± 2.7) were significantly lower than group C1 (P < 0.01), and group C2 was close to normal. CONCLUSIONS: Periodontitis could increase the risk of atherosclerosis in rats with chronic periodontitis. Periodontal mechanical treatment and teeth extraction may increase the risk of As in the short time. However, the risk would gradually reduce in a long time.

[Influence of periodontal therapy on serum interleukin-6 and carotid metalloproteinases in animals with chronic periodontitis associated with atherosclerosis].

OBJECTIVE: To investigate the effect of periodontal mechanical treatment on serum interleukin-6 (IL-6) and carotid artery matrix metalloproteinase (MMP)-2 and MMP-9 expression in chronic periodontitis (CP) SD rats with atherosclerosis (As). METHODS: Forty-four six-week-old male SD rats were randomly divided into three groups: control group (group A), As group (group B), As+CP group(group C). According to different periodontal interventions, group C was randomly subdivided into four groups: natural process group (C1), the periodontal mechanical treatment group (C2), the periodontal mechanical treatment+ local drugs group (C3), and the periodontal mechanical treatment+local and system drugs group (C4). Each group received the appropriate treatment and periodontal interventions. Serum IL-6 levels were determined by enzyme linked immunosorrbent assay (ELISA). MMP-2 and MMP-9 levels in the proximal aorta were examined by immunohistochemistry. RESULTS: The gray value of MMP-2 and MMP-9 was basically the same in all groups. Compared with group A, the gray value of MMP-2 and MMP-9 of group B and C were decreased. C1 group showed the formation of atherosclerotic plaque and fibrous cap. Compared with group B (126.4 ± 2.0, 124.8 ± 2.8) , the gray value of group C1 (101.3 ± 2.4, 101.2 ± 4.1) was significantly weaker (P < 0.05). The staining depth of MMP-2 and MMP-9 of groups C1, C2, C3 and C4 were sequentially decreased, and the differences of gray value were statistically significant(P < 0.05). The levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that of group A (P < 0.01). The levels of serum IL-6 in groups C2, C3, and C4 increased gradually and reached the peak 5 weeks after the establishment of model (P < 0.001). After that, the levels of serum IL-6 decreased gradually and was lower than baseline. The levels of serum IL-6 in groups C3 and C4 were significantly lower than that in group C2 7 weeks after the establishment of model(P < 0.01). CONCLUSIONS: In rats with periodontitis and cardiovascular diseases, chronic periodontal inflammation may significantly increase the severity of As and promote the formation of atherosclerotic plaque. Mechanical periodontal therapy may cause short-term systemic inflammation and then reduce vascular inflammation in long term.With supplement use of local and systemic antibiotics, the mechanical periodontal therapy may get the vascular disease and systemic inflammation improved.