HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Navigation-Guided Nasal Endoscopy to Remove the Cavernous Venous Malformation of the Orbital Apex Through the Sphenoid Approach.

OBJECTIVE: To explore the feasibility of navigation-guided sinus endoscopy to remove the cavernous vascular malformation of the orbital apex through the sphenoid approach. METHODS: A retrospective series of non-control cases were collected. From May 2012 to December 2019, patients with imaging findings of cavernous venous malformation in the orbital apex were collected at the Eye Hospital Affiliated to Nanchang University. All patients underwent navigation guided sinusoscopy through the sphenoid approach to remove the cavernous venous malformation of the orbital apex. Analyze the changes of visual function and postoperative complications before and after operation. RESULTS: Twelve patients were collected, including 3 males and 9 females aged between 32 and 59. In 3 patients without visual impairment, the postoperative visual function was still normal. The remaining 9 patients all had visual impairment. Among them, 3 patients had fully recovered normal visual function after operation, 2 patients had improved visual function compared with preoperative, and 4 patients had no change in postoperative visual acuity. There were no complications in 3 of the 12 patients, and 9 patients had transient limited intraocular rotation with mild limitation of diplopia after operation, and all returned to normal within 1 month after surgery. CONCLUSION: Navigation-guided sinus endoscopy through the sphenoid approach to remove the cavernous venous malformation of the orbital apex is an effective and feasible surgical method.

Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways.

Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1ß production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.

Changes in protein composition of epidermal mucus in turbot Scophthalmus maximus (L.) under high water temperature.

To explore the skin mucous of juvenile turbot (Scophthalmus maximus) protein under thermo-treatment in different temperatures (20, 23, 25, and 27 °C), the corresponding proteome maps were constructed by two-dimensional gel electrophoresis (2-DE), from which the peptide mass map with MALDI-TOF-TOF was obtained, and a novel protein of polypeptide was identified by database retrieval. Results show that the proteome maps varied remarkably with temperature, indicating the increase or decrease in protein spot. Totally, 209 protein spots were matched in five maps in temperature using ImageMaster 2D Platinum 6.0. In addition, six unique protein spots were selected and identified with MALDI-TOF-TOF. By searching database for protein identification and function prediction, five proteins were confirmed, of which lectin and cytokeratin are highly potential as protein marker for further research. The information should be useful for better understanding the role of mucus as a component of innate immune system and for identifying genotypes that suit best to the aquiculture environment. These proteins could be used as potential biomarkers to environmental stressors in mucus for providing early warning when fish suffers in a dangerous situation.

Protein expression of mesenchymal stem cells after transfection of pcDNA3.1⁻-hVEGF165 by ultrasound-targeted microbubble destruction.

Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new technique for organ-specific gene transfer and drug delivery. This study was performed to investigate the effect of UTMD on marrow mesenchymal stem cells (MSCs) transfected with pcDNA3.1⁻-hVEGF165.pcDNA3.1⁻-hVEGF165 were transfected into the third passage of MSCs, with or without UTMD under different ultrasound conditions. Protein expression was quantified by hVEGF165-ELISA kit after transfection for 24, 48, and 72 hours. UTMD-mediated transfection of MSCs yielded a significant protein expression. UTMD of mechanic index (MI) 0.6 for 90 seconds led to the highest level of protein expression.