Aging-related decrease of histone methyltransferase SUV39H1 in adipose-derived stem cells enhanced SASP.

Aging-related diseases are closely associated with the state of inflammation, which is known as "inflammaging." Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed the senescence-associated secretory phenotype (SASP). Epigenetic regulation, especially the structural regulation of chromatin, is closely linked to the regulation of SASP. In our previous study, the suppressor of variegation 3-9 homolog 1 (SUV39H1) was elucidated to interact with Lhx8 and determine the cell fate of mesenchyme stem cells. However, the function of SUV39H1 during aging and the underlying mechanism of its epigenetic regulation remains controversial. Therefore, the C57BL/6 J CAG-Cre; SUV39H1fl/fl knockout mice and irradiation-induced cellular senescence model were built in this study to deepen the understanding of epigenetic regulation by SUV39H1 and its relation to SASP. In vivo and in vitro studies demonstrated that SUV39H1 decreased with aging and served as an inhibitor of SASP, especially IL-6, MCP-1, and Vcam-1, by altering H3K9me3 enrichment in their promoter region. These results provide new insights into the epigenetic regulation of SASP.

PCSK9 causes inflammation and cGAS/STING pathway activation in diabetic nephropathy.

Our previous research revealed that an increase in PCSK9 is linked to aggravated inflammation in the kidneys of mice affected by a high-fat diet and streptozotocin (HFD/STZ) or in HGPA-induced HK-2 cells. Furthermore, the cGAS/STING pathway has been reported to be involved in diabetic nephropathy (DN). Therefore, in this study, we aimed to examine the correlation between the proinflammatory effect of PCSK9 and the cGAS/STING pathway in DN. We used PCSK9 mAbs to inhibit PCSK9 in vivo and PCSK9 siRNA in vitro and measured the inflammatory phenotype in HFD/STZ-treated mice or HGPA-induced HK-2 cells, and observed decreased blood urea nitrogen, creatinine, UACR, and kidney injury in response to the PCSK9 mAb in HFD/STZ-treated mice. Moreover, IL-1 ß, MCP-1, and TNF-α levels were reduced by the PCSK9 mAb in vivo and PCSK9 siRNA in vitro. We observed increased mtDNA damage and activation of the cGAS-STING signaling pathway during DN, as well as the downstream targets p-TBK1, p-NF-κB p65, and IL-1ß. In a further experiment with an HGPA-induced DN model in HK-2 cells, we revealed that mtDNA damage was increased, which led to the activation of the cGAS/STING system and its downstream targets. Notably, the cGAS-STING signaling pathway was inhibited by the PCSK9 mAb in vivo and PCSK9 siRNA in vitro. In addition, inhibition of STING with C-176 in HGPA-induced HK-2 cells markedly blocked inflammation. In conclusion, we report for the first time that PCSK9 triggers mitochondrial DNA damage and activates the cGAS-STING pathway in DN, which leads to a series of inflammation cascades. PCSK9-targeted intervention can effectively reduce DN inflammation and delay its progression. Moreover, the inhibition of STING significantly abrogated the inflammation triggered by HGPA in HK-2 cells.

Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus.

PURPOSE: The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients. METHODS: PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 (p < 0.05). The DBP and UACR values were significantly higher in PCSK9 tertile 3 than in PCSK9 tertile 1 and PCSK9 tertile 2 (both p < 0.05). In addition, URCR values were significantly higher in PCSK9 tertile 3 and PCSK9 tertile 2 than in PCSK9 tertile 1 (both p < 0.05). Serum PCSK9 levels were positively correlated with SBP, Scr, BUN, TG, URCR, UαCR and UACR but inversely correlated with eGFR. In STZ + HFD mice, serum PCSK9 levels were positively correlated with Scr, BUN and UACR, which was consistent with the findings in the patients. A logistic regression model revealed that serum PCSK9 is an independent risk factor for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2. The ROC curve showed that 170.53 ng/mL and 337.26 ng/mL PCSK9 were the best cutoff values for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2, respectively. CONCLUSION: Serum PCSK9 levels are associated with renal function impairment in T2DM patients and in some patients lower PCSK9 may be helpful to decrease chronic kidney disease.

Transcriptome analysis of human peri-implant soft tissue and periodontal gingiva: a paired design study.

OBJECTIVES: Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the soft tissue in vivo by using paired samples and compare the differences between peri-implant soft tissue and periodontal gingiva at the transcriptional level. METHODS: Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further verification was done by quantitative real-time PCR. RESULTS: Totally 3549 differentially expressed genes (DEGs) were found between peri-implant and periodontal groups. The Venn diagram further identified 185 DEGs in every pair of samples, of which the enrichment analysis identified significant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokine-cytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9, and SFRP2 were verified to be upregulated in peri-implant soft tissue. CONCLUSIONS: Peri-implant soft tissue showed altered expressions of several genes related to the cell-ECM interaction compared to periodontal gingiva. CLINICAL RELEVANCE: Compared to periodontal gingiva, altered cell-ECM interactions in peri-implant may contribute to the susceptibility of peri-implant diseases. At the transcriptional level, periodontal gingiva is generally considered the appropriate control for peri-implantitis, except regarding the cell-ECM interactions.

Kidney involvement in coronavirus-associated diseases (Review).

Since 2003, coronaviruses have caused multiple global pandemic diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19). Clinical and autopsy findings suggest that the occurrence of kidney injury during infection may negatively affect the clinical outcomes of infected patients. The authoritative model predicts that outbreaks of other novel coronavirus pneumonias will continue to threaten human health in the future. The aim of the present systematic review was to summarize the basic knowledge of coronavirus, coronavirus infection-associated kidney injury and the corresponding therapies, in order to provide new insights for clinicians to better understand the kidney involvement of coronavirus so that more effective therapeutic strategies can be employed against coronavirus infection in the future.

Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19.

OBJECTIVE: To explore ABO blood group distribution and clinical characteristics in patients with COVID-19. METHODS: The clinical data of 187 patients with COVID-19 seen between January 20, 2020 and March 5, 2020 at the First Hospital of Changsha were retrospectively analyzed. The differences in the ABO blood group distribution between COVID-19 patients and the control group (1991 cases) were analyzed. The relationship between blood type and clinical characteristics was analyzed. RESULTS: Of the 187 patients with COVID-19, 69 had type A (36.90%), 63 had type B (33.69%), 41 had type O (21.92%), and 14 had type AB blood (7.49%). The proportion of patients with type A blood in the COVID-19 group was significantly higher than that in the control group (36.90% vs. 27.47%, P = 0.006), while the proportion of patients with type O blood in the COVID-19 group was significantly lower than that in the control group (21.92% vs. 30.19%, P = 0.018). The risk of COVID-19 was higher for individuals with blood group A than for those with blood group O (OR = 1.849, 95% CI = 1.228-2.768, P = 0.003). The risk of COVID-19 was higher for patients with blood group A than for those with a blood group other than A (OR = 1.544, 95% CI = 1.122-2.104, P = 0.006). Patients with blood group O had a lower risk of COVID-19 than non-O blood group patients (OR = 0.649, 95% CI = 0.457-0.927, P = 0.018). The ABO blood group distribution was related to COVID-19 status. CONCLUSIONS: Patients with blood group A had an increased risk for infection with SARS-CoV-2, whereas blood group O was associated with a decreased risk, indicating that certain ABO blood groups were correlated with SARS-CoV-2 susceptibility. Blood type was related to some clinical characteristics of patients with COVID-19.

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release.

Tooth defect and tooth loss are common clinical diseases in stomatology. Compared with the traditional oral restoration treatment, tooth regeneration has unique advantages and is currently the focus of oral biomedical research. It is known that dozens of cytokines/growth factors and other bioactive factors are expressed in a spatial-temporal pattern during tooth development. On the other hand, the technology for spatial-temporal control of drug release has been intensively studied and well developed recently, making control release of these bioactive factors mimicking spatial-temporal pattern more feasible than ever for the purpose of tooth regeneration. This article reviews the research progress on the tooth development and discusses the future of tooth regeneration in the context of spatial-temporal release of developmental factors.

Optogenetic control of mesenchymal cell fate towards precise bone regeneration.

Rationale: Spatial-temporal control of cell fate in vivo is of great importance for regenerative medicine. Currently, there remain no practical strategies to tune cell-fate spatial-temporally. Optogenetics is a biological technique that widely used to control cell activity in genetically defined neurons in a spatiotemporal-specific manner by light. In this study, optogenetics was repurposed for precise bone tissue regeneration. Methods: Lhx8 and BMP2 genes, which are considered as the master genes for mesenchymal stem cell proliferation and differentiation respectively, were recombined into a customized optogenetic control system. In the system, Lhx8 was constitutively expressed, while BMP2 together with shLhx8 expression was driven by blue light. Results: As expected, blue light induced BMP2 expression and inactivated Lhx8 expression in cells infected with the optogenetic control system. Optogenetic control of BMP2 and Lhx8 expression inversely regulates MSC fate in vitro. By animal study, we found that blue light could fine-tune the regeneration in vivo. Blue light illumination significantly promotes bone regeneration when the scaffold was loaded with MSCs infected with adeno-Lhx8, GI-Gal4DBD, LOV-VP16, and BMP2-shLhx8. Conclusions: Together, our study revealed that optogenetic control of the master genes for mesenchymal stem cell proliferation and differentiation would be such a candidate strategy for precise regenerative medicine.

Secreting-lux/pT-ClyA engineered bacteria suppresses tumor growth via interleukin-1ß in two pathways.

Engineered Salmonella typhimurium (S.t-ΔpGlux/pT-ClyA) and attenuated Salmonella typhimurium (SL: Salmonella typhimurium with a defect in the synthesis of guanine 5'-diphosphate-3'-diphosphate) exhibit similar tumor targeting capabilities (Kim et al. in Theranostics 5:1328-1342, 2015; Jiang et al. in Mol Ther 18:635-642, 2013), but S.t-ΔpGlux/pT-ClyA exerts superior tumor suppressive effects. The aim of this study was to investigate whether S.t-ΔpGlux/pT-ClyA inhibits colon cancer growth and recurrence by promoting increased IL-1ß production. The CT26 tumor mouse model was used, and mice were treated in the following ways: PBS, S.t-ΔpGlux/pT-ClyA(+) + IL-1ßAb, SL, S.t-ΔpGlux/pT-ClyA(-), and S.t-ΔpGlux/pT-ClyA(+). Dynamic evaluation of the efficacy of S.t-ΔpGlux/pT-ClyA in the treatment of colon cancer was assessed by MRI. Western blot, immunofluorescence and flow cytometry analysis were used to investigate IL-1ß-derived cells and IL-1ß expression on tumor cells and immune cells to analyze the regulatory mechanism. IL-1ß levels in tumors colonized by S.t-ΔpGlux/pT-ClyA were significantly increased and maintained at high levels compared to control treatments. This increase caused tumors to subside without recurrence. We examined the immune cells mediating S.t-ΔpGlux/pT-ClyA-induced tumor suppression and examined the major cell types producing IL-1ß. We found that macrophages and dendritic cells were the primary IL-1ß producers. Inhibition of IL-1ß in mice treated with S.t-ΔpGlux/pT-ClyA using an IL-1ß antibody caused tumor growth to resume. This suggests that IL-1ß plays an important role in the treatment of cancer by S.t-ΔpGlux/pT-ClyA. We found that in St-ΔpGlux/pT-ClyA-treated tumors, expression of molecules involved in signaling pathways, such as NLRP3, ASC, Caspase1, TLR4, MyD88, NF-kB and IL-1ß, were upregulated, while in ΔppGpp S. typhimurium treated animals, TLR4, MyD88, NF-kB and IL-1ß were upregulated with NLRP3, ASC, and Caspase1 being rarely expressed or not expressed at all. Using S.t-ΔpGlux/pT-ClyA may simultaneously activate TLR4 and NLRP3 signaling pathways, which increase IL-1ß expression and enhance inhibition of colon cancer growth without tumor recurrence. This study provides a novel platform for treating colon cancer.

Effects of Myeloperoxidase on Methicillin-Resistant Staphylococcus aureus-Colonized Burn Wounds in Rats.

Objective: To achieve better therapeutic results in burn wound infections and to examine alternatives to antibiotics, we designed this study to elaborate the role of myeloperoxidase (MPO) on infected burn wounds in rats. Approach: We compared chemical properties as well as bacteriostatic ability of MPO in different concentrations with NeutroPhase. Subsequently, we applied MPO (MPO group), NeutroPhase (NeutroPhase group), NaCl+H2O2 (NaCl+H2O2 group), or NaCl (control group) on rat dorsal burn wounds inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Their effects on MRSA-colonized wounds were evaluated by microscopy, histologic section, and Western blot. Results: MPO produced more H+ and HClO-, leading to a more acidic environment. Moreover, MPO inhibited the growth of MRSA more intensely after 6 h of inoculation ex vivo. In vivo the open wound rate in the MPO group was significantly lower, while the contraction rate and epithelialization rate of MPO group were higher than that of the control group, NaCl+H2O2 group, and NeutroPhase group on day 20. The hematoxylin and eosin staining of MPO group showed better wound healing than other groups. More vascular endothelial growth factor (VEGF) was expressed in wound tissue of MPO group by Western blot. Innovation: This is the first study to use MPO for MRSA-colonized burn wound therapy. Conclusion: MPO displayed more effective bacteriostatic ability, possibly beneficial for MRSA-colonized wound healing.

PLAGL2 and POFUT1 are regulated by an evolutionarily conserved bidirectional promoter and are collaboratively involved in colorectal cancer by maintaining stemness.

BACKGROUND: Our previous study revealed that PLAGL2 or POFUT1 can promote tumorigenesis and maintain significant positive correlations in colorectal cancer (CRC). However, the mechanism leading to the co-expression and the underlying functional and biological implications remain unclear. METHODS: Clinical tumor tissues and TCGA dataset were utilized to analyze the co-expression of PLAGL2 and POFUT1. Luciferase reporter assays, specially made bidirectional promoter vectors and ectopic expression of 3'UTR were employed to study the mechanisms of co-expression. In vitro and in vivo assays were performed to further confirm the oncogenic function of both. The sphere formation assay, immunofluorescence, Western blot and qRT-PCR were performed to investigate the effect of both genes in colorectal cancer stem cells (CSCs). FINDINGS: PLAGL2 and POFUT1 maintained co-expression in CRC (r = 0.91, p < .0001). An evolutionarily conserved bidirectional promoter, rather than post-transcriptional regulation by competing endogenous RNAs, caused the co-expression of PLAGL2 and POFUT1 in CRC. The bidirectional gene pair PLAGL2/POFUT1 was subverted in CRC and acted synergistically to promote colorectal tumorigenesis by maintaining stemness of colorectal cancer stem cells through the Wnt and Notch pathways. Finally, PLAGL2 and POFUT1 share transcription factor binding sites, and introducing mutations into promoter regions with shared transcription regulatory elements led to a decrease in the PLAGL2/POFUT1 promoter activity in both directions. INTERPRETATION: Our team identified for the first time a bidirectional promoter pair oncogene, PLAGL2-POFUT1, in CRC. The two genes synergistically promote the progression of CRC and affect the characteristics of CSCs, which can offer promising intervention targets for clinicians and researchers. FUND: National Nature Science Foundation of China, the Hunan province projects of Postgraduate Independent Exploration and Innovation of Central South University.

Study of Promoter Methylation Patterns of HOXA2, HOXA5, and HOXA6 and Its Clinicopathological Characteristics in Colorectal Cancer.

Research on DNA methylation offers great potential for the identification of biomarkers that can be applied for accurately assessing an individual's risk for cancer. In this article, we try to find the ideal epigenetic genes involved in colorectal cancer (CRC) based on a CRC database and our CRC cohort. The top 20 genes with an extremely high frequency of hypermethylation in CRC were identified in the latest database. Remarkably, 3 HOXA genes were included in this list and ranked at the top. The percentage of methylation in the HOXA5, HOXA2, and HOXA6 genes in CRC were up to 67.62, 58.36, and 31.32%, respectively, and ranked first in CRC among all human tumor tissues. Paired colorectal tumor samples and adjacent non-tumor colorectal tissue samples and four CRC cell lines were selected for MethylTarget™ assays. The results demonstrated that CRC tissues and cells had a stronger methylation status around the 3 HOXA gene promoter regions compared with adjacent non-tumor colonic tissue samples. The Receiver operator characteristic curve (ROC) curves for HOXA genes show excellent diagnostic ability in distinguishing tissue from healthy individuals and CRC patients, especially for Stage I patients (AUC = 0.9979 in HOXA2, 0.9309 in HOXA5, and 0.8025 in HOXA6). An association analysis between the methylation pattern of HOXA genes and clinical indicators was performed and found that HOXA2 methylation was significantly associated with age, N, stage, M, lymphovascular invasion, perineural invasion, lymph node number. HOXA5 methylation was associated with age, T, M, stage, and tumor status, and HOXA6 methylation was associated with age and KRAS mutation. Notably, we found that the highest methylation of HOXA5 and HOXA2 occurs in the early stages of colorectal cancer tissues such as stage I, N0, MO, and non-invasive tissues. The methylation levels declined as tumors progressed. However, methylation level at any stage of the tumor was still significantly higher than in normal tissues (p < 0.0001). The mRNA of the 3 HOXA genes was downregulated in early tumor stages due to hypermethylation of CpG islands adjacent to the promoters of the genes. In addition, hypermethylation of HOXA5 and HOXA6 mainly occurred in patients < 60 years old and with MSI-L, MSS, CIMP.L and non-CIMP tumors. Together, this suggests that epigenetic silencing of 3 adjacent HOXA genes may be an important event in the progression of colorectal cancer.

PLGA-based control release of Noggin blocks the premature fusion of cranial sutures caused by retinoic acid.

Craniosynostosis (CS), the premature and pathological fusion of cranial sutures, is a relatively common developmental disorder. Elucidation of the pathways involved and thus therapeutically targeting it would be promising for the prevention of CS. In the present study, we examined the role of BMP pathway in the all-trans retinoic acid (atRA)-induced CS model and tried to target the pathway in vivo via PLGA-based control release. As expected, the posterior frontal suture was found to fuse prematurely in the atRA subcutaneous injection mouse model. Further mechanism study revealed that atRA could repress the proliferation while promote the osteogenic differentiation of suture-derived mesenchymal cells (SMCs). Moreover, BMP signal pathway was found to be activated by atRA, as seen from increased expression of BMPR-2 and pSMAD1/5/9. Recombinant mouse Noggin blocked the atRA-induced enhancement of osteogenesis of SMCs in vitro. In vivo, PLGA microsphere encapsulated with Noggin significantly prevented the atRA-induced suture fusion. Collectively, these data support the hypothesis that BMP signaling is involved in retinoic acid-induced premature fusion of cranial sutures, while PLGA microsphere-based control release of Noggin emerges as a promising strategy for prevention of atRA-induced suture fusion.

Sodium Fluoride under Dose Range of 2.4-24 µM, a Promising Osteoimmunomodulatory Agent for Vascularized Bone Formation.

Fluoride has essential effects on bone physiological activity and is widely used in bone biomaterials modification. However, this beneficial effect is highly related to the dose range and improper dosing can lead to pathological conditions such as fluorosis of bone. Therefore, this study first investigated the dose dependent effect of fluoride on bone regeneration. In the range of 0.24-240 µM, in vivo vascularized bone formation can be achieved via fine-tuning the fluoride concentration, and the peak osteogenic effect was found at 2.4-24 µM. The underlying mechanism is related to the modulation of the osteoimmune environment. Fluoride elicited significant osteoimmunomodulatory effect in modulation of the inflammatory cytokines and expression of osteogenic factors (BMP2, OSM, spermine/spermidine) and angiogenic factor (VEGF, IGF-1) during the early response. Fluorine with the doses of 2.4 and 24 µM could increase polyamines and IGF-1 production in macrophages, thus promoting osteogenesis of BMSCs and angiogenesis of HUVECs. These doses could also inhibit the inflammatory response of macrophages. In vitro osteogenesis and angiogenesis were both improved by the fluorine (2.4 and 24 µM)/macrophage conditioned medium, which is consistent with the in vivo results. These results collectively imply that fluoride is an effective osteoimmunomodulatory agent that can regulate both osteogenesis and angiogenesis. "Osteoimmune-smart" bone biomaterials can be developed via incorporating fluorine, and the release concentration should be controlled within the range of 2.4-24 µM for improved bone formation.

Involvement of methylation-associated silencing of formin 2 in colorectal carcinogenesis.

AIM: To investigate whether promoter methylation is responsible for the silencing of formin 2 (FMN2) in colorectal cancer (CRC) and to analyze the association between FMN2 methylation and CRC. METHODS: We first identified the expression levels and methylation levels of FMN2 in large-scale human CRC expression datasets, including GEO and TCGA, and analyzed the relationship between the expression and methylation levels. Then, the methylation levels in four CpG regions adjacent to the FMN2 promoter were assessed by MethylTarget™ assays in CRC cells and in paired colorectal tumor samples and adjacent nontumor tissue samples. Furthermore, we inhibited DNA methylation in CRC cells with 5-Aza-2'-deoxycytidine and assessed the expression of FMN2 by qRT-PCR. Last, the association between FMN2 methylation patterns and clinical indicators was analyzed. RESULTS: A statistically significant downregulation of FMN2 expression in large-scale human CRC expression datasets was found. Subsequent analysis showed that a high frequency of hypermethylation occurred in the FMN2 gene promoter in CRC tissues; operating characteristic curve analysis revealed that FMN2 gene methylation had a good capability for discriminating between CRC and nontumor tissue samples (AUC = 0.8432, P < 0.0001). MethylTarget™ assays showed that CRC cells and tissues displayed higher methylation of these CpG regions than nontumor tissue samples. Correlation analysis showed a strong inverse correlation between methylation and FMN2 expression, and the inhibition of DNA methylation with 5-Aza significantly increased endogenous FMN2 expression. Analysis of the association between FMN2 methylation patterns and clinical indicators showed that FMN2 methylation was significantly associated with age, N stage, lymphovascular invasion, and pathologic tumor stage. Notably, the highest methylation of FMN2 occurred in tissues from cases of early-stage CRC, including cases with no regional lymph node metastasis (N0), cases in stages I and II, and cases with no lymphovascular invasion, but the methylation level began to decrease with tumor progression. Additionally, FMN2 promoter hypermethylation was more common in patients > 60 years old and in colon cancer tissue. CONCLUSION: FMN2 promoter hypermethylation may be an important early event in CRC, most likely playing a critical role in cancer initiation, and can serve as an ideal diagnostic biomarker in elderly patients with early-stage colon cancer.

Application of animated cartoons in reducing the pain of dressing changes in children with burn injuries.

BACKGROUND: Nonpharmacological management remains one of the central pain interventional therapies in the burn unit. VR and other distraction treatments for adults have achieved great advantages in pain relief. METHODS: A within-subject study was conducted to evaluate 54 participants aged from 3 to 7. In the control group, a standard analgesic, ibuprofen, was used over the period of dressing change, whereas animated cartoons were played simultaneously in the intervention-group condition. We adopted the Wong-Baker faces pain rating scale, COMFORT scale, FLACC scale and POCIS to assess the pain rating 5 min before, during and 5 min after dressing changes, respectively. RESULTS: Compared with the control group, FLACC scale and POCIS scores in the intervention group were not significantly different (P>0.05) throughout the observation period; outcomes measured using the Wong-Baker faces pain rating scale and COMFORT scale 5 min before and during dressing changes were also not different between the groups (P>0.05). Nevertheless, 5 min after that period, subjects in the intervention group had reduced pain behavior according to scores on the Wong-Baker faces pain rating scale (control-group scores: 7.231±0.403; intervention-group scores: 6.026±0.501, P<0.05) and COMFORT scale (control-group scores: 21.602±1.316; intervention-group scores: 19.040±1.204, P<0.05). CONCLUSION: This study supports that watching animated cartoons appears to be a practical way to ease the pain behavior of children in the burn unit after replacing wound dressings, although its effectiveness remains insufficient before and during the dressing change procedure. SIGNIFICANCE: Conducting a thorough study and exploring the efficacy of animated cartoons in reducing the pain of dressing changes for pediatric patients may surely result in practical value, especially in developing countries.

E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma.

INTRODUCTION: Melanoma is a malignant tumor that seriously affects patients. The pathogenesis of malignant melanoma is complex, and the cell cycle is closely related to tumor progression. Based on the catalog of cancer somatic mutations, we found that overexpression of the E2F3 gene ranked first in percentage increase in not only melanoma but also in all human cancer tissues. However, there are few studies on the high expression of E2F3 and its carcinogenic mechanism in melanoma. METHODS AND RESULTS: We found that E2F3 showed extensive copy number amplification that was positively correlated with the expression level. Patients with high copy number had a significantly poorer prognosis. We also found that E2F3 levels were significantly negatively correlated with promoter methylation. However, we showed that the E2F3 promoter region is hypomethylated, and in normal cells or tumor cells, the methylation level did not correlate with expression. Finally, we knocked down the E2F3 gene in melanoma cells by shRNA. Colony formation, anchorage-dependent growth, and EdU cell proliferation experiments showed a significant decrease in proliferation. Flow cytometry showed a significant increase in the G0/G1 ratio. CONCLUSION: It can be speculated that copy number amplification and other mechanisms result in the high expression of E2F3 in melanoma, which promotes tumor progression by involving the cell cycle. E2F3 is a good target for the treatment of melanoma.

Clinical and Radiologic Outcomes of Submerged and Nonsubmerged Bone-Level Implants with Internal Hexagonal Connections in Immediate Implantation: A 5-Year Retrospective Study.

PURPOSE: To evaluate the 5-year clinical and radiologic outcome of immediate implantation using submerged and nonsubmerged techniques with bone-level implants and internal hexagonal connections and the effects of potential influencing factors. MATERIALS AND METHODS: A total of 114 bone-level implants (XiVE S plus) with internal hexagonal connections inserted into 72 patients were included. Patients were followed up for 5 years. A t-test was used to statistically evaluate the marginal bone loss between the submerged and nonsubmerged groups. The cumulative survival rate (CSR) was calculated according to the life table method and illustrated with Kaplan-Meier survival curves. Comparisons of the CSR between healing protocols, guided bone regeneration, implants with different sites, lengths, and diameters were performed using log-rank tests. RESULTS: The 5-year cumulative implant survival rates with submerged and nonsubmerged healing were 94% and 96%, respectively. No statistically significant differences in terms of marginal bone loss, healing protocol, application of guided bone regeneration, implant site, or length were observed. CONCLUSIONS: High CSRs and good marginal bone levels were achieved 5 years after immediate implantation of bone-level implants with internal hexagonal connections using both the submerged and nonsubmerged techniques. Factors such as implant length, site, and application of guided bone regeneration did not have an impact on the long-term success of the implants.

Differences of treatment outcomes between self-ligating brackets with microimplant and headgear anchorages in adults with bimaxillary protrusion.

INTRODUCTION: Our aim was to determine differences between the outcomes of treatment using microimplant anchorage compared with headgear anchorage in adult patients with bimaxillary protrusion treated with self-ligating brackets. METHODS: Thirty-one adult orthodontic patients (13 men, 18 women; age, 25.87 ± 3.37 years) who were diagnosed with bimaxillary protrusion were selected. All patients were treated with self-ligating brackets and maximum anchorage after extraction of 4 first premolars. Group 1 received microimplant anchorage, and group 2 received headgear. Lateral cephalometric radiographs were obtained before and after treatment. Differences in the skeletal and dental parameters between and within groups were analyzed. RESULTS: No significant difference was observed in the mean treatment times between the groups (21.93 ± 3.10 vs 23.88 ± 2.68 months). There was no significant difference in skeletal measurements before or after treatment in patients who received microimplant anchorage. Patients who received headgear anchorage had an increase of the mandibular plane angle. The microimplant anchorage group had greater anterior tooth retraction and less maxillary molar mesialization than did the headgear group. CONCLUSIONS: In both the anteroposterior and vertical directions, microimplant anchorage achieved better control than did the traditional headgear appliance during the treatment of bimaxillary protrusion.

Impact of malocclusion on oral health-related quality of life in young adults.

OBJECTIVE: To assess oral health-related quality of life (OHRQoL) in young adult patients with malocclusion and to measure the association between orthodontic treatment need and OHRQoL. MATERIALS AND METHODS: The study sample comprised 190 young adults aged 18 to 25 years who were attending orthodontic clinics at the Faculty of Dentistry. The Index of Orthodontic Treatment Need-Dental Health Component was used to measure orthodontic treatment need. Each participant was assessed for OHRQoL before and after treatment by using the Oral Health Impact Profile, Chinese version (OHIP-14). RESULTS: Patients who had little or no, borderline, and actual need for orthodontic treatment represented 21.6%, 50.5%, and 27.9% of the total sample, respectively. OHRQoL (total OHIP-14 score and score for each domain) improved after treatment (P < .05). Significant differences in summary OHIP-14 scores were apparent with respect to orthodontic treatment need. Participants with high treatment need reported a significantly greater negative impact on the overall OHRQoL score. The greatest impact was seen in the psychological discomfort domain and the psychological disability domain. CONCLUSION: Malocclusion has a significant negative impact on OHRQoL. This is greatest for the psychological discomfort and psychological disability domains. The orthodontic treatment of malocclusion improves OHRQoL of patients.