Human epidermal growth factor receptor 2 (HER2) regulates cell mitosis, proliferation, and apoptosis. Trastuzumab is a HER2-targeted monoclonal antibody (mAB), which can prolong the overall survival rate of patients with HER2 overexpression in later periods of gastric cancer and breast cancer. Although anti-HER2 monoclonal antibody has a curative effect, adjuvant chemotherapy is still necessary to upgrade the curative effect maximumly. Antibody-drug conjugate (ADC) is a kind of therapeutic drug that contains antigen-specific antibody and cytotoxic payload, which can improve the survival time of tumor patients. To date, there are several HER2-ADC products on the market, for which two anti-HER2 ADC (trastuzumab emtansine and trastuzumab deruxtecan) have been authorized by the FDA for distinct types of HER2-positive carcinoma in the breast. Disitamab vedotin (RC48) is a newly developed ADC drug targeting HER2 that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker. This paper aims to offer a general insight and summary of the mechanism of action and the currently completed and ongoing clinical studies of RC-48 in HER-2 positive solid tumors.

The aim of this study was to estimate the prevalence of tooth wear in the aging population of northwest China and to investigate the factors associated with such tooth wear. Cross-sectional analytic clinical and questionnaire study was performed in 704 participants who had a mean age of 46.5 ± 0.2 SD and of which 367(52.13%) were males and 337(47.87%) female. These participants were invited when they attended the hospital which located in northwest China for routine oral examination. In the maxilla of the examined patients, the rate of tooth wear varied from 85.51% for molar group, 89.77% for premolar group, 100.0% for canine group to 87.22% for incisor group. In the mandible, the rates were 86.36%, 88.92%, 100.0% and 91.19% for the four groups respectively. Moreover, both the incisor and canine groups of these patients showed median scores of 3, the premolar group showed a median score of 1, and the molar group had a median score of 2. Additionally, multiple factors were considered to contribute to these patterns of tooth wear, especially the habitual consumption of a hard or sour diet (P < 0.05,odds ratio 1.21, 95% confidence intervals 1.04-1.49). Tooth wear is a common disease in which the anterior teeth exhibit greater wear than posterior teeth. The data support an association between tooth wear and dietary patterns.

Our previous studies have shown that hydrostatic pressure can serve as an active regulator for bone marrow mesenchymal stem cells (BMSCs). The current work further investigates the roles of cytoskeletal regulatory proteins Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) in hydrostatic pressure-related effects on BMSCs. Flow cytometry assays showed that the hydrostatic pressure promoted cell cycle initiation in a RhoA- and Rac1-dependent manner. Furthermore, fluorescence assays confirmed that RhoA played a positive and Rac1 displayed a negative role in the hydrostatic pressure-induced F-actin stress fiber assembly. Western blots suggested that RhoA and Rac1 play central roles in the pressure-inhibited ERK phosphorylation, and Rac1 but not RhoA was involved in the pressure-promoted JNK phosphorylation. Finally, real-time polymerase chain reaction (PCR) experiments showed that pressure promoted the expression of osteogenic marker genes in BMSCs at an early stage of osteogenic differentiation through the up-regulation of RhoA activity. Additionally, the PCR results showed that pressure enhanced the expression of chondrogenic marker genes in BMSCs during chondrogenic differentiation via the up-regulation of Rac1 activity. Collectively, our results suggested that RhoA and Rac1 are critical to the pressure-induced proliferation and differentiation, the stress fiber assembly, and MAPK activation in BMSCs.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H₂O₂-treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the function of nuclear factor-erythroid 2-related factor 2 (Nrf2). We demonstrated that with upregulated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), the effect of oxidative stress was obvious under H₂O₂ treatment. Oxidative molecules were altered after the H₂O₂ exposure, whereby the signaling of Nrf2 was activated with an increase in its downstream effectors, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and γ-glutamyl cysteine synthetase (γ-GCS). Additionally, the apoptosis levels gradually increased with oxidative stress by the upregulation of caspase-9, caspase-3, Bax and c-Fos levels in addition to the downregulation of Bcl-2. However, there was no alterations in levels of caspase-8. The enhanced antioxidant effect could not mitigate the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, Bax and c-Fos, but not that of caspase-8. In contrast, silencing the expression of Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on regulating oxidative stress and anti-intrinsic apoptosis by the activation of oxidative enzymes.

Periodontitis can cause irreversible defects in the periodontal ligament (PDL), the regeneration of which is the major obstacle to the clinical treatment of periodontitis. Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration. However, existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium, which may have been shown as an important role in tissue regeneration. Meanwhile, the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive. In this study, we developed a bi-crosslinking viscoelastic hydrogel (Alg-PBA/Spd) by integrating phenylboronic acid-modified alginate with anti-inflammatory agent (spermidine) through borate ester and B–N coordination bonds, where spermidine will be released with the degradation of the hydrogel. Alg-PBA/Spd hydrogel is biocompatible, injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking. We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage. Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.