To determine the key molecule in breast cancer pathology and clinical prognosis by data analysis as well as surgical specimens immunohistochemical staining analysis. TCGA and GTEx databases were used to screen key molecules in the urea cycle with differential expression in breast, and their relationship with the prognosis of breast cancer patients was also analyzed. Then, the surgical specimens of 97 breast cancer patients and 54 non-neoplastic (mammary gland disease) patients who underwent surgical treatment in Xijing Hospital from November 2010 to December 2016 were collected to produce breast cancer tissue chips. Immunohistochemical staining was employed to determine the expression of ASS1 (argininosuccinate synthase 1) in breast cancer and adjacent normal tissues, and to verify its relationship with pathological features and prognosis of breast cancer. TCGA and GTEx database analysis showed that the expression of ASS1 decreased in breast cancer, significantly correlated with the prognosis of patients (p < 0.05). Immunohistochemical results demonstrated that ASS1 is mainly located in cytoplasm. Its expression decreased in breast cancer, and significantly correlated with Ki-67 level and molecular typing (p = 0.0215, p = 0.0005). The expression of ASS1 significantly decreased in breast cancer, and closely related to molecular typing and Ki-67 level, suggesting that ASS1 plays an important role in the occurrence and development of tumor. Therefore, low ASS1 expression can be used as a potential indicator to evaluate the prognosis of breast cancer.
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Antimicrobial resistance (AMR) of bacteria has increased worldwide dramatically and the development of new antibiotics has been slowed down. Therefore, it is urgent to explore new anti-infective drugs or therapeutics. Quorum sensing (QS) system of pathogen is closely related to its pathogenicity. QS system inhibitors could significantly reduce the pathogenicity of pathogen. QS system is mainly composed of las, rhl, and pqs systems and Sargentodoxae Caulis extracts mainly containing caffeic acid which has shown QSI activity. In this study, we proved the antivirulence and antipathogenicity of caffeic acid against Pseudomonas aeruginosa at the transcript and product level, then we further investigate the target of caffeic acid in QS system by using molecular docking combining the mutant strains determination. The results indicated that caffeic acid could reduce the expression of QS-related genes rhlR, rhlI, pqsA, pqsR as well as virulence related genes such as phzA 1、lasB. Motility ability and biofilm were also suppressed obviously by caffeic acid. Chinese cabbage and fruit fly infection model analysis verified the antipathogenicity of caffeic acid. Caffeic acid might inhibit QS system by targeting the pqs system based on the docking analysis and gene mutant strains evaluation on caffeic acid.
Burns are a common medical problem globally, and wound infection is one of the major causes of inducing related complications. Although antibiotics effectively prevent wound infections, the misuse of antibiotics has created a new problem of superbugs. Herein, we propose a new strategy to obtain pH-responsive antimicrobial P-ZIF (ZIF: zeolitic imidazolate framework) by loading polyhexamethylenebiguanide (PHMB) into the framework of ZIF-8 nanoparticles. This will enable PHMB to be released in the weak acid environment of an infected wound. To address burn infections, P-ZIF nanoparticles were loaded into a hydrogel system made of sodium alginate (SA) and 3-aminophenylboronic acid modified human-like collagen (H-A) through borate ester bonds. The resulting H-A/SA/P-ZIF (HASPZ) hydrogel dressing not only possesses antibacterial and wound healing properties but also has dual pH responsiveness to prevent the overuse of medication while effectively treat deep second-degree burns. Therefore, P-ZIF nanoparticles and the corresponding HASPZ hydrogel dressing are considered of significant importance in antimicrobial, drug delivery, and wound repair.
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