Hainan Medical University

Epidermal growth factor receptor (EGFR) and histone deacetylase 3 (HDAC3) synergistically drive malignant progression in triple-negative breast cancer (TNBC). In this study, a series of N-benzyl-2-fluorobenzamide derivatives (11-43) were identified as EGFR/HDAC3 dual-target inhibitors. Among them, compound 38 exhibited the most promising activity, with IC₅₀ values of 20.34 nM and 1.09 μM against EGFR and HDAC3, respectively. Molecular modeling revealed that the 2-fluorobenzamide moiety of 38 chelates with Zn²⁺ in the active channel of HDAC3, while the 4-fluorobenzyl group occupies the ATP-binding pocket of EGFR, exercising a dual-target binding function. In vitro experiments demonstrated that 38 exhibited superior anti-proliferative activity (IC₅₀ = 1.98 μM) against MDA-MB-231 cells compared to chidamide (IC₅₀ = 24.37 μM), inducing 74.15 % inhibition of cell migration and 57.4 % late-stage apoptosis. In vivo studies revealed that 38 (30 mg/kg/day) suppressed tumor growth by 34.78 % without significant toxicity. Collectively, 38 represents a novel dual EGFR/HDAC3 inhibitor that shows promising potential for providing new therapeutic insights into TNBC treatment.

Candida albicans is the most prominent conditional fungal pathogen, which can cause systemic candidiasis when an individual becomes immunocompromised. The widespread and long-term use of azoles like fluconazole (FLC) has led to a significant increase in drug resistance, posing substantial challenges to clinical treatment. In our previous study, benzyl isothiocyanate (BITC) was extracted from Carica papaya L. seed, and it exhibited a notable inhibitory effect against C. albicans. However, the application of BITC is restricted by its instability, poor water solubility, volatility, and easy degradation. This study aimed to prepare BITC-loaded nanostructured lipid carrier (BITC-NLC) to address these limitations of BITC and enhance antifungal efficacy in vitro and in vivo against C. albicans. The results of physicochemical properties showed that BITC-NLC had small particle size, good physical stability, and high encapsulation efficiency. In vitro, the antifungal effect of BITC-NLC was better than BITC against both sensitive and resistant C. albicans and better than FLC against resistant C. albicans. Moreover, in the in vivo experiment using systemic candidiasis mice model induced by resistant C. albicans, BITC-NLC was more remarkable than BITC and FLC in the increase of the survival rate and the splenic index, the reduction of the fungal burden, and the alleviation of the pathological damage. These findings may be attributed to the enhanced stability and sustained release of BITC. This study highlights the potential of BITC-NLC as a novel and effective formulation for the clinical treatment of drug-resistant C. albicans infections, thereby expanding the application scope of papaya.

Thalassemia is an endemic genetic disease. The main clinical manifestation of this condition is long-term chronic anemia. In addition, patients may present with jaundice, heart failure, hepatosplenomegaly, skeletal deformities, growth retardation, and cognitive impairment. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment.

Cognitive impairment in patients with thalassemia has received increasing attention, and related studies have confirmed that patients with thalassemia have varying degrees of cognitive dysfunction. Potential contributing factors include white matter damage, ischemia, hypoxia, and systemic iron overload. However, the specific underlying mechanisms remain unclear and require further investigation. This study aimed to systematically integrate the currently fragmented mechanisms of cognitive impairment in patients with thalassemia.

PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were used to search for related literature. The main contents of this review include the latest progress in the diagnosis and treatment of thalassemia and the mechanism of cognitive impairment in patients.

Cognitive impairment in patients with thalassemia includes deficits in spatial memory, computing power, executive operation, emotional communication, and other domains. Several contributing factors have been identified, including white matter damage, ischemia, hypoxia, iron deposition in the brain, and accelerated aging. Iron overload has recently emerged as a research hotspot. However, the exact location, extent, and mechanism of cerebral iron deposition remain unclear. Despite many challenges in the current research, greater breakthroughs are expected in the diagnosis and treatment of cognitive dysfunction in thalassemia, ultimately improving patients' quality of life.