Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound-Amplified Biocatalytic Tumor Nanotherapies.

The external-stimulation-induced reactive-oxygen-species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound-amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate-supported Ru clusterzymes (RuNC/BTO) for ultrasound-amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru-O coordination on BaTiO3 . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O2 - radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10-3 s-1 ) among the state-of-the-art POD-mimics. Moreover, the catalase-like activity of the RuNC/BTO facilitates the decomposition of H2 O2 to produce O2 for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi-modal strategy presents superior tumor cell-killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment-specific catalytic therapy and also provide a new pathway for engineering high-performance ROS production materials across broad therapeutics and biomedical fields.

Curriculum setting and students' feedback of pre-clinical training in different dental schools in China-A national-wide survey.

INTRODUCTION: Adequate time and effective training facilities are essential for undergraduate dental students participating in pre-clinical dental practice to ensure them providing safe treatment for patients in the future. The study aimed to explore the current status of pre-clinical dental training in China in relation to the curriculum setting and students' feedback of pre-clinical training in different dental schools and thus provide information for further standardise curricula. MATERIALS AND METHOD: An online questionnaire was distributed electronically to undergraduates in 44 Chinese dental schools of different levels according to China Discipline Ranking (CDR). The questionnaire collected information in relation to the training hour and student to facility ratio of four main dental courses (cariology and endodontics, periodontology, prosthodontics and oral surgery), as well as the application and effect of virtual reality (VR) simulator in pre-clinical dental practice in different schools. Students' feedback was also collected. RESULTS: A total of 565 valid questionnaires were recruited. Results of this cross-sectional survey show that training hour of periodontology course was the lowest, and oral surgery course showed most prominent shortage of facilities. The application of VR simulator amongst schools is uneven. Students from A and A+ level schools showed higher satisfaction with their pre-clinical courses and reported a more positive attitude towards the use of VR simulator than other students. (p < .05). CONCLUSION: Pre-clinical dental training in China remained imperfect in insufficient training time, training facility and students did not have access to standard pre-clinical training and quality assurance. VR technique has potential values in pre-clinical dental practice in China.

Moringa isothiocyanate-1 mitigates the damage of oxidative stress and apoptosis in diabetic nephropathy mice.

OBJECTIVE: Diabetic nephropathy (DN) is a prevalent cause of end-stage kidney disease worldwide. Moringa isothiocyanate-1 (MIC-1) has shown potential for DN management, however, the exact mechanisms remain unclear. This research intended to evaluate the impact and mechanism of MIC-1 on DN. METHODS: Six C57BLKS/J-db/m mice served as controls. Eighteen C57BLKS/J-db/db mice were randomly separated into three groups: db/db, db/db + irbesartan (IBS), and db/db + MIC-1. Three weeks post-drug administration, the body weight and kidney weight of mice in each group were measured. Concurrently, serum creatinine (Scr), urine albumin, insulin, glycosylated hemoglobin (GHb), oxidative stress-, and inflammatory-related factors were determined. Additionally, the pathological injury, apoptosis, apoptosis-related markers, NLRP3, and ASC levels in the kidney tissues were examined utilizing H&E, Masson, PAS, TUNEL staining, and Western blot. RESULTS: MIC-1 decreased the body weight, kidney weight, the levels of Glu, Scr, and urine albumin in db/db mice. Moreover, MIC-1 significantly suppressed the levels of MDA, insulin, GHb, TNF-α, IL-1ß, and IL-6, while increased the activities of SOD, CAT, and GPX in the serum of db/db mice. MIC-1 also mitigated the kidney tissue injury in db/db mice. Western blot assay showed that MIC-1 enhanced the Bcl-2 level and suppressed the Bax, cleaved caspase-3, cleaved caspase-9, NLRP3, ASC, and caspase-1 levels of the kidney tissues in db/db mice. CONCLUSIONS: MIC-1 ameliorated the kidney injury in DN mice, and its mechanism may be associated with the suppression of renal cell apoptosis, oxidative stress, and inflammatory responses.

Comparative study on the impact-sliding wear behaviour of CAD/CAM resin-ceramic materials and tooth enamel.

OBJECTIVES: To compare the impact-sliding wear of different CAD/CAM resin-ceramic materials and tooth enamel, and explore the corresponding wear damage mechanism. METHODS: Human tooth enamel (EN), Vita ENAMIC (Vita, VE), Lava Ultimate (3 M, LU), and GC CERASMART (GC, CS) were used in this study. The hardness, elastic modulus, and roughness values of the samples were measured. Further, impact-sliding wear tests were performed in a ball-on-flat configuration with spherical zirconia antagonists and the coefficients of friction (CoF) were recorded simultaneously. Additionally, a white light interferometer was used to determine the volume losses and scanning electron microscopy was used to observe the wear morphology of the wear scars and the damage feature in the vertical sections to clarify the damage mechanism during the impact-sliding wear test. RESULTS: EN exhibited the highest elastic modulus and CoF, followed by VE, LU, and CS. The hardness and roughness of EN and VE were similar and were higher than those of LU and CS. Throughout the wear tests, VE exhibited the highest volume loss, whereas CS exhibited the lowest. The wear damage characteristics of VE were similar to those of EN, displaying brittle fractures of inorganic substances and plastic deformation of organic substances in the impact part, exhibiting plough marks in the sliding parts. In the case of LU and CS, the entire wear areas displayed plastic deformation of the resin matrix, exfoliation of the filler particles, and plough marks. SIGNIFICANCE: Enamel and polymer-infiltrated ceramic network materials exhibit similar wear damage modes. Additionally, the high-density nanocomposite resin material is the most resistant to impact-sliding wear from a tribological perspective.

The Effect of Moringa Isothiocyanate-1 on Renal Damage in Diabetic Nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) is the most common clinical complication of diabetes mellitus. Moringa isothiocyanate-1 (MIC-1) is effective in the treatment of diabetes mellitus, but its mechanism of action in DN remains obscure. This research specifically probed the role of MIC-1 in modulating renal injury in DN. METHODS: Six db/m mice were assigned to control group and twelve db/db mice were randomly allocated to the db/db and db/db + MIC-1 groups. The body and kidney weights of the mice were monitored. Renal function indicators and oxidative stress-related markers were assessed by automatic biochemical analyzer and ELISA method. The pathological changes, apoptosis of renal tissues, extracellular regulated protein kinases (ERK) 1/2/ Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related markers, and the positive expressions of podocalyxin (Pod) and synaptopodin (Syn) were measured by H&E, PAS, and TUNEL staining, Western blot, and IHC assay. RESULTS: MIC-1 reduced the body and kidney weights, and increased the kidney organ index (calculated as 100*kidney weight/ body weight) in db/db mice. In addition, MIC-1 improved renal function, kidney tissue injury, and apoptosis of db/db mice. MIC1 noticeably repressed the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) and enhanced the contents of (glutathione) GSH, superoxide dismutase (SOD), and catalase (CAT) in db/db mice. At molecular level, db/db mice showed a decrease in p-ERK/ERK, Nrf2, SOD-1, heme oxygenase 1 (HO-1), and CAT and an increase in p- inhibitor kappa B alpha (IKBα) and p-Nuclear factor-kappa B (P65/P65), which were reversed when MIC-1 was administered. Furthermore, MIC-1 facilitated the positive expressions of Pod and Syn of the kidney tissues in db/db mice. CONCLUSION: MIC-1 reduces oxidative stress and renal injury by activating the ERK/Nrf2/HO-1 signaling and repressing the NFκB signaling in db/db mice.  DOI: 10.52547/ijkd.7515.

Diosmin mitigates high glucose-induced endoplasmic reticulum stress through PI3K/AKT pathway in HK-2 cells.

BACKGROUND: Diosmin has been reported to treat diabetes, but its role in diabetic nephropathy (DN) remains unclear. This research investigated the mechanism by which diosmin alleviated high glucose (HG)-induced HK-2 cell injury. METHODS: First, we used CCK-8 to detect the effect of 0.1, 1, or 10 µg/mL diosmin on the viability of HK-2 cells treated with normal glucose or HG. Next, we used flow cytometry, automatic biochemical analyzer, ELISA, immunofluorescence, and colorimetric assay kit to examine the apoptosis, oxidative stress, inflammatory factors, and Caspase-3 expression in HK-2 cells. Thereafter, we used the western blot and qRT-PCR to examine the expression of the endoplasmic reticulum stress-, oxidative stress-, inflammation-, apoptosis-, and autophagy, and PI3K/AKT pathway-related factors. RESULTS: Diosmin was non-cytotoxic to normal HK-2 cells and enhanced the HK-2 cell viability suppressed by HG. Meanwhile, diosmin restrained apoptosis, the contents of MDA, pro-inflammatory factors, and Caspase-3 but intensified the contents of SOD and CAT induced by HG. We further confirmed that diosmin blunted oxidative stress-, inflammation-, apoptosis-, and autophagy-related factors expression induced by HG via restraining the CHOP and GRP78 expressions. Further, we also discovered that PTEN level was restrained and the ratios of p-PI3K/PI3K and p-AKT/AKT were enhanced in HK-2 cells induced by HG, which was reversed by co-treatment of HG and diosmin. CONCLUSIONS: Our study manifested that diosmin alleviated the HG-mediated endoplasmic reticulum stress injury in HK-2 cells via restraining the PI3K/AKT pathway.

Cobalt nanowire-based multifunctional platform for targeted chemo-photothermal synergistic cancer therapy.

Cobalt nanowires (CoNWs) simultaneously possessing advantages in photothermal effect, targeting drug delivery and photoacoustic imaging property are hopefully promising strategies to further improve the treatment efficiency and reduce the side effects of cancer chemotherapy. Herein, a unique cobalt-based structure decorated with graphene oxide (GO) and polyethylene glycol (PEG) is fabricated through a facile approach. The resultant nanohybrids show relatively low cytotoxicity, favorable biocompatibility as well as inherit the outstanding properties of cobalt. Moreover, CoNWs decorated with GO and PEG (CoNWs-GO-PEG) can load therapeutic drug molecules (e.g., doxorubicin, DOX) with a high drug loading capacity (992.91 mg/g), and simultaneously they are responsive to pH, NIR (near-infrared) irradiation and magnetism stimulation. Accordingly, CoNWs-GO-PEG-DOX shows the satisfactory effect of eliminating cancer cells with synergistic chemo-photothermal therapy in vitro. Current work provides a solid demonstration of the potential of CoNWs-GO-PEG for serving as a targeted antitumor agent in synergistic chemo-photothermal therapy.