PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

IL-21 Enhances the Immune Protection Induced by the Vibrio vulnificus Hemolysin A Protein.

We previously reported that the Vibrio vulnificus hemolysin A (VvhA) protein elicited good immune protection and could effectively control V. vulnificus infection in mice. However, its molecular mechanism remains unknown. We hypothesized that hemolysin A induces an immunoprotective response via IL-21 regulation. To demonstrate this, IL-21 expression in mice was regulated by injecting either specific antibodies or rIL-21, and the immune response was evaluated by flow cytometry. Our results suggested that IL-21 enhances immune protection by inducing a T follicular helper cell and germinal center B cell response. We used RNA-seq to explore molecular mechanisms and identified 10 upregulated and 32 downregulated genes involved in IL-21-upregulated protection. Gene Ontology analysis and pathway analysis of the differentially expressed genes were also performed. Our findings indicate that IL-21 can enhance the immune protection effect of the VvhA protein and may serve as a novel strategy for enhancing the immune protection effect of protein vaccines.

SRY-negative 45,X/46,XY adult male with complete masculinization and infertility: A case report and review of literature.

BACKGROUND: 45,X/46,XY mosaicism is a rare chromosomal abnormality with a wide range of phenotypes in both males and females, from normal individuals with different degrees of genital ambiguity to those who show signs of Turner's syndrome. More rarely, cases of 45,X/46,XY mosaicism with a normal-appearing male phenotype are not found until a chromosome test is performed to investigate the cause of male infertility. CASE SUMMARY: In this study, a 29-year-old male patient with complete azoospermia is reported. Chromosomal analyses of his lymphocytes revealed the karyotype 45,X[93%]/46,X,+mar(Y)[7%]. In addition, Y chromosome-specific markers, such as SRY, ZFY, AZFa, AZFb and AZFc, were not observed in his blood DNA according to multiplex polymerase chain reaction test. A literature review identified several 45,X/46,XY cases with a normal-appearing male phenotype, most of whom were diagnosed during infertility investigation. However, the present case is the first SRY-negative 45,X/46,XY male case diagnosed during a premarital medical examination. CONCLUSION: This finding further suggests that sex determination is a complex process regulated by multiple genetic and environmental factors.