The effects of nano-silver loaded zirconium phosphate on antibacterial properties, mechanical properties and biosafety of room temperature curing PMMA materials

Polymethyl methacrylate (PMMA) frequently features in dental restorative materials due to its favorable properties. However, its surface exhibits a propensity for bacterial colonization, and the material can fracture under masticatory pressure. This study incorporated commercially available RHA-1F-II nano-silver loaded zirconium phosphate (Ag-ZrP) into room-temperature cured PMMA at varying mass fractions. Various methods were employed to characterize Ag-ZrP. Subsequently, an examination of the effects of Ag-ZrP on the antimicrobial properties, biosafety, and mechanical properties of PMMA materials was conducted. The results indicated that the antibacterial rate against Streptococcus mutans was enhanced at Ag-ZrP additions of 0%wt, 0.5%wt, 1.0%wt, 1.5%wt, 2.0%wt, 2.5%wt, and 3.0%wt, achieving respective rates of 53.53%, 67.08%, 83.23%, 93.38%, 95.85%, and 98.00%. Similarly, the antibacterial rate against Escherichia coli registered at 31.62%, 50.14%, 64.00%, 75.09%, 86.30%, 92.98%. When Ag-ZrP was introduced at amounts ranging from 1.0% to 1.5%, PMMA materials exhibited peak mechanical properties. However, mechanical strength diminished beyond additions of 2.5%wt to 3.0%wt, relative to the 0%wt group, while PMMA demonstrated no notable cytotoxicity below a 3.0%wt dosage. Thus, it is inferred that optimal antimicrobial and mechanical properties of PMMA materials are achieved with nano-Ag-ZrP (RHA-1F-II) additions of 1.5%wt to 2.0%wt, without eliciting cytotoxicity

MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression

Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis of OSCC. However, the potential mechanisms have not been clarified yet. This study aimed to evaluate the role of miR-378 in the migration and invasion of OSCC in vitro and in vivo. According to our results, the migration and invasion abilities were increased in miR-378-overexpressing cells, while decreased in miR-378-3p/5p-silencing cells. In addition, overexpression of miR-378 suppressed the expressions and activities of MMP-9 and MMP-2. Epithelial-mesenchymal transition (EMT) was restrained by overexpression of miR-378 as evidenced by increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, the miR-378-3p/5p knockdown groups had the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed miR-378 overexpression-induced decrease in migration and invasion via upregulating MMP-9, MMP-2, and N-cadherin levels, while downregulating E-cadhrin level. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the metastasis nodule number was raised by miR-378 knockdown. Taken together, our study suggests that miR-378/KLK4 axis is involved in the mechanisms of the migration and invasion of OSCC cells. Targeting miR-378/KLK4 axis may be an effective measure for treating OSCC.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

TBC1D15 deficiency protects against doxorubicin cardiotoxicity via inhibiting DNA-PKcs cytosolic retention and DNA damage

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15CKO) or Tbc1d15 knockin (Tbc1d15CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography–tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594–624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594–624, deletion of segment 594–624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity

Inhibiting Matrix Metalloproteinase-2 Activation by Perturbing Protein-Protein Interactions Using a Cyclic Peptide.

We report on a cyclic peptide that inhibits matrix metalloproteinase-2 (MMP2) activation with a low-nM-level potency. This inhibitor specifically binds to the D570-A583 epitope on proMMP2 and interferes with the protein-protein interaction (PPI) between proMMP2 and tissue inhibitor of metalloproteinases-2 (TIMP2), thereby preventing the TIMP2-assisted proMMP2 activation process. We developed this cyclic peptide inhibitor through an epitope-targeted library screening process and validated its binding to proMMP2. Using a human melanoma cell line, we demonstrated the cyclic peptide's ability to modulate cellular MMP2 activities and inhibit cell migration. These results provide the first successful example of targeting the PPI between proMMP2 and TIMP2, confirming the feasibility of an MMP2 inhibition strategy that has been sought after for 2 decades

Effects of intravenous hydration on risk of contrast induced nephropathy and in-hospital mortality in STEMI patients undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

Abstract Background The role of intravenous hydration at the time of primary percutaneous intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains unclear. Guidelines are vague, supported by low level evidence, and hydration is used less often than other clinical settings.To perform a systematic review and meta-analysis of all randomized controlled trials assessing intravenous hydration compared with non-hydration for prevention of contrast induced nephropathy (CIN) and In-hospital mortality in patients with STEMI undergoing primary PCI. Methods Medline, EMBASE and the Cochrane Register were searched to September 2018. Included studies reported the incidence of CIN, In-hospital mortality, requirement for dialysis and heart failure. Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using a random effects model. Results Three moderate quality trials were identified including 1074 patients. Overall, compared with no hydration, intravenous hydration significantly reduced the incidence of CIN by 42% (RR 0.58; 95% CI: 0.45 to 0.74, p < 0.001). The estimated effects upon all-cause mortality (RR 0.56; 95% CI: 0.30 to 1.02, p = 0.057) and the requirement for dialysis (RR 0.52, 95% CI 0.14–1.88, p = 0.462) were not statistically significant. The outcome of heart failure was not consistently reported. Conclusions Intravenous hydration likely reduces the incidence of CIN in patients with STEMI undergoing primary PCI. However, for key clinical outcomes such as mortality, heart failure and dialysis the effect estimates were imprecise. Further high quality studies are needed to clarify the appropriate volume of fluid and effects on outcomes