The clinical outcomes of triple-negative breast cancer (TNBC) chemotherapy are unsatisfactory. Water solubility and biosafety of chemo drugs are also major barriers for achieving satisfactory treatment effect. In this study, we have reported a combinational strategy by self-assembly engineering nanodrugs PC NDs, which were composed of paclitaxel (PTX) and curcumin (Cur), for effective and safe TNBC chemotherapy. PC NDs were prepared through reprecipitation method without using any additional carriers. The PC NDs were preferentially taken up by TNBC cells and we also observed pH-related drug release. Compared with free PTX and simple PTX/Cur mixture, PC NDs have shown higher therapeutic efficiency and better prognosis while the metastasis rate was significantly lower than that of either PTX or PTX/Cur mix group. Therefore, the self-assembly engineered PC NDs might be a promising nanodrugs for efficient and safe TNBC chemotherapy.

Depression is a common psychological and mental disorder, characterized by low mood, slow thinking and low will, and even suicidal tendencies in severe cases. It imposes a huge mental and economic burden on patients and their families, and its prevention and treatment have become an urgent public health problem. It is worth noting that there is a significant gender difference in the incidence of depression. Studies have shown that females are far more likely to suffer from depression than males, confirming a close relationship between estrogen and the onset of depression. Moreover, recent studies suggest that the brain-derived neurotrophic factor- (BDNF-) mammalian target of rapamycin complex-1 (mTORC1) signaling pathway is a crucial target pathway for improving depression and mediates the rapid antidepressant-like effects of various antidepressants. However, it is not clear whether the BDNF-mTORC1 signaling pathway mediates the regulation of female depression and how to regulate female depression. Hence, we focused on the modulation of estrogen-BDNF-mTORC1 signaling in depression and its possible mechanisms in recent years.

Protein therapeutics have been considered a promising strategy for cancer treatment due to their highly specific bioactivity and few side effects. Unfortunately, the low physiological stability and poor membrane permeability of most protein drugs greatly limit their clinical application. Furthermore, single-modality protein therapeutics show insufficient efficacy. To address these issues, Janus magnetic mesoporous silica nanoparticles (Janus MSNNPs) were developed to preload ribonuclease A (RNaseA) to simultaneously realize the magnetically enhanced delivery of protein drugs and magnetic hyperthermia-enhanced protein therapy. Janus MSNNPs showed a high RNaseA loading ability and pH-responsive drug release behavior. Furthermore, an external magnetic field could remarkably enhance the therapeutic effect of RNaseA-loaded Janus MSNNPs due to the improved intracellular internalization of RNaseA. Importantly, Janus MSNNPs possessed an outstanding magnetic hyperthermia conversion efficiency, which could generate hyperthermia under an alternating magnetic field, effectively supplementing protein therapy by a combined effect. In vitro and in vivo experiments confirmed the high anticancer outcome and low side effects of this intriguing strategy for breast cancer based on Janus MSNNPs. Hence, Janus MSNNPs might be an effective and safe nanoplatform for magnetically combined protein therapy.

There is an urgent need to identify chemotherapeutic agents with improved efficacy and safety against triple-negative breast cancer (TNBC). Ginsenosides can reportedly induce tumor cell death, invasion, and metastasis; however, poor water solubility, low oral absorption rate, and rapid blood clearance limit their clinical application. Utilizing the amphiphilic property of ginsenosides as building blocks of biomaterials, we fabricated a carrier-free nanodrug composed of ginsenosides Rg3 and Rb1 using a nano-reprecipitation method without any additional carriers. After characterizing and demonstrating their uniform morphology and pH-sensitive drug release properties, we observed that Rg3-Rb1 nanoparticles (NPs) exhibited stronger antitumor and anti-invasive effects on TNBCs in vitro than those mediated by free ginsenosides. Consequently, Rg3-Rb1 NPs afforded superior inhibition of tumor growth and reduction of pulmonary metastasis than the Rg3 and Rb1 mixture, with no obvious systematic toxicity in vivo. Collectively, our results provide a proof-of-concept that self-assembled engineered ginsenoside nanodrugs may be efficient and safe for TNBC therapy.

Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics.