作者單位：總醫(yī)院第五醫(yī)療中心腫瘤內(nèi)科、高級腫瘤科

摘要：Background

Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the oncostatic function of melatonin on esophageal squamous cell carcinoma (ESCC) remains elusive. This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.

Methods

ESCC cell lines treated with or without melatonin were used in this study. In vitro colony formation and EdU incorporation assays, and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells. RNA-seq, qPCR, Western blotting, recombinant lentivirus-mediated target gene overexpression or knockdown, plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.

Anti-Fibronectin/FN1 pAb; IF

作者單位：德國肺研究中心，亥姆霍茲慕尼黑，肺健康與免疫研究所和綜合肺病學(xué)中心

文獻引用抗體：bs-3195R

Anti-Phospho-IRF3 (Ser396) pAb; WB

文獻引用抗體：bs-4089R

Anti-phospho-AKT2 (Ser474) pAb; IF

摘要：Early-stage temporomandibular joint osteoarthritis (TMJOA) is characterized by excessive subchondral bone loss. Emerging evidence suggests that TMJ disc displacement is involved, but the pathogenic mechanism remains unclear. Here, we established a rat model of TMJOA that simulated disc displacement with a capacitance-based force-sensing system to directly measure articular surface pressure in vivo. Micro-CT, histological staining, immunofluorescence staining, IHC staining, and Western blot were used to assess pathological changes and underlying mechanisms of TMJOA in the rat model in vivo as well as in RAW264.7 cells in vitro. We found that disc displacement led to significantly higher pressure on the articular surface, which caused rapid subchondral bone loss via activation of the RANTES–chemokine receptors–Akt2 (RANTES-CCRs-Akt2) axis. Inhibition of RANTES or Akt2 attenuated subchondral bone loss and resulted in improved subchondral bone microstructure. Cytological studies substantiated that RANTES regulated osteoclast formation by binding to its receptor CCRs and activating the Akt2 pathway. The clinical evidence further supported that RANTES was a potential biomarker for predicting subchondral bone loss in early-stage TMJOA. Taken together, this study demonstrates important functions of the RANTES-CCRs-Akt2 axis in the regulation of subchondral bone remodeling and provides further knowledge of how disc displacement causes TMJOA.

文獻引用抗體：

bs-0397R; Anti-MMP9 pAb

bs-1313R; Anti-VEGFA pAb

bs-10802R; Anti-TNF alpha pAb

bs-1407R; Anti-HIF1 beta pAb

bs-4593R; Anti-MMP9 pAb

bs-0782R; Anti-IL-6 pAb

bs-6761R; Anti-IL-10 pAb

摘要：In addition to oxidative stress and impaired angiogenesis, the overexpression of metalloproteinases (MMPs) and proinflammatory cytokines, which are promoted by hyperglycemia, causes chronic inflammation in diabetic wounds. Herein, TA-siRNA nanogels are prepared for the first time on the basis of the self-assembling interaction between tannic acid (TA) and short interfering RNA (siRNA). The efficient, biodegradable nanogels are cross-linked with poly(vinyl alcohol) (PVA), human-like collagen (HLC), TA, and borax to prepare adaptive, conductive PHTB (TA-siRNA) hydrogels. In response to high levels of reactive oxygen species (ROS), the ROS-responsive borate ester bonds in the hydrogels are oxidized and broken, and TA-siRNA nanogels are released into cells to reduce the expression of the MMP-9. Moreover, the TA and HLC promote collagen expression, reduce inflammation, and ROS level. It is found that electrical stimulation (ES) promotes the in vivo release of TA-siRNA nanogels from PHTB (TA-siRNA) hydrogels and endocytosis of the nanogels. The combination therapy using ES and PHTB (TA-siRNA) hydrogels accelerates the healing of diabetic wounds by reducing the levels of ROS and MMP-9 and promoting the polarization of macrophages, production of collagen, and angiogenesis. This study provides insights on the design of functional gene-delivery and efficient therapeutic strategies to promote the repair of diabetic chronic wounds.

作者單位：上海交通大學(xué)醫(yī)學(xué)院,上海市第九人民醫(yī)院口腔種植科