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The treatment of ovarian cancer remains a medical challenge and its malignant progression is connected with obvious changes in both tissue and cell stiffness. However, the accurate mechanical-responsive molecules and mechanism remains unclear in ovarian cancer. Based on our previous results combined with the crucial regulatory role of STAT3 in the malignant progression of various cancer types, we want to investigate the relationship between STAT3 and matrix stiffness in ovarian cancer and further explore the potential mechanisms. Collagen-coated polyacrylamide gels (1, 6, and 60 kPa) were prepared to mimic soft or hard matrix stiffness. Western blotting, qRT-PCR, flow cytometry, IHC, EdU assays, and TEM were used to evaluate the effect of STAT3 in vitro under different matrix stiffnesses. Furthermore, a BALB/c nude mouse model was established to assess the relationship in vivo. Our results confirmed the differential expression of STAT3/p-STAT3 not only in normal and malignant ovarian tissues but also under different matrix stiffnesses. Furthermore, we verified that STAT3 was a mechanically responsive gene both in vitro and in vivo, and the mechanical response was carried out by altering the migration-related molecules (TNFAIP1) and adhesion-related molecules (LPXN, CNN3). The novel findings suggest that STAT3, a potential therapeutic target for clinical diagnosis and treatment, is a mechanically responsive gene that responds to matrix stiffness, particularly regulation in migration and adhesion in the progression of ovarian cancer.
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Cellular dysfunction caused by vesicle transport is associated with a variety of diseases.The trans-Golgi network(TGN)to endosome transport is an important pathway of vesicle transport,and its defects leading to protein balance disorders has been linked to many diseases such as cancer,neurodegenerative diseases and diabetes mellitus.Gol-gi-associated gamma-adaptin ear-containing ADP-ribosylation factor-binding protein 2(GGA2)is a crucial protein in-volved in TGN-endosomal transport.It plays a significant role in the regulation of several diseases,including cancer,Al-zheimer disease,type 2 diabetes mellitus and cerebral ischemia,by mediating protein transport with important biological significance.This article provides an overview of the molecular structure of GGA2,its role in regulating clathrin-mediated protein transport between TGN and endosomes,and its potential implications for a variety of diseases.
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Lipedema is secondary to local fat deposition, a disease characterized by the symmetric thickening of lower limbs, mostly occurs in women, especially in adolescence and pregnancy. In its early stage, it could be easily confused with lymphedema. Extensive literature review on primary fat edema in recent years, as well as a summary of the clinical symptoms and signs and diagnosis and treatment of lipedema were conducted, so as to provide a useful reference for clinicians.
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Objective To evaluate the effect of sevoflurane preconditioning on autophagy in the operated lung tissues of the patients undergoing one-lung ventilation.Methods Forty patients of both sexes,with American Society of Anesthesiologists physical status Ⅰ-Ⅲ,aged 30-80 yr,weighing 45-84 kg,scheduled for elective radical operation for lung cancer performed via video-assisted thoracoscope under general anesthesia,were divided into control group (C group) and sevoflurane preconditioning group (SP group),with 20 patients in each group.In SP group,sevoflurane was inhaled for 30 min with the final concentration of 2.0%,followed by washout.The normal lung tissues (the distance from the edge of the lump>2 cm) around the lump were obtained for detection of the expression of microtubule-associated protein 1 light chain 3 Ⅱ by Western blot.Results Compared with C group,the expression of microtubule-associated protein 1 light chain 3 Ⅱ in lung tissues was significantly up-regulated in SP group (P<0.05).Conclusion Sevoflurane preconditioning can enhance autophagy in the operated lung tissues of the patients undergoing one-lung ventilation,which may be related to the lung protective effect.
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A rapid and sensitive method based on ultrafast liquid chromatography-tandem mass spectrometry was developed and validated for simultaneous determination of Sudan Ⅰ, Sudan Ⅱ, Sudan Ⅲ, and Sudan Ⅳ levels in rat whole blood. Cleanert C18 mixed-mode polymeric sorbent was used for effective solid-phase extraction cleanup. Separation was carried out on a reversed-phase C18 column (100 mm × 2.1 mm, 1.8 μm) using 0.1% (v/v) formic acid in water/0.1% (v/v) formic acid in acetonitrile as the mobile phase in gradient elution. Quantification was performed by an electrospray ionization source in the positive multiple reaction monitoring mode using D5-Sudan I as the internal standard. Calibration curves showed good linearity between 0.2 and 20.0 μg/L, with correlation coefficients higher than 0.9990. The average recovery rates were between 93.05% and 114.98%. The intra- and inter-day relative standard deviations were within 6.2%. The lower limit of quantification was 0.2 μg/L. All the analytes were found to be stable in aseries of stability studies. The proposed method was successfully applied to a pharmacokinetic study of four Sudan dyes after oral administration to rats.
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The development of renal transplantation from living relative donors relives the shortage of transplanted organs,and benefits patients with end-stage renal diseases.However,when seen from the aspect of donors,implementing a non-therapeutic invasive surgical treatment on a healthy person still violates the absolute sound principle of medical ethics.To reduce the harm to the minimum,a comprehensive assessment should be conducted before the transplantation,and long-term follow-up observations after transplantation should also be strengthened.