Diagnostic delays in breast cancer among young women: An emphasis on healthcare providers.

Despite advances in breast cancer care, breast cancer in young women (BCYW) faces unique challenges, diagnostic delays, and limited awareness in many countries. Here, we discuss the challenges and consequences associated with the delayed diagnosis of BCYW. The consequences of delayed diagnosis in young women - which generally varies among developed, developing, or underdeveloped countries - are severe due to a faster breast tumor growth rate than tumors in older women, also contributing to advanced cancer stages and poorer outcomes. Though there are many underlying reasons for diagnostic delays due to age, the article delves explicitly deep into the diagnostic delay of BCYW, focusing on healthcare providers, potential contributing factors, its consequences, and the urgent need to start minimizing such incidences. The article suggests several strategies to address these issues, including increasing awareness, developing educational programs for healthcare providers to identify signs and symptoms in young women, developing clear diagnostic guidelines, and improving screening strategies.

Neuroprotective potential of flavonoid rich Ascophyllum nodosum (FRAN) fraction from the brown seaweed on an Aß42 induced Alzheimer's model of Drosophila.

BACKGROUND: In Alzheimer Disease (AD) pathogenesis, aggregation of Aß42 fibrils strongly correlates with memory dysfunction and neurotoxicity. Till date, no promising cures for AD. Report shows that flavonoids contributed anti-oxidant, anti-cancer and neuroprotection activity by regulating the mitochondrial machinery. Here, we first report the identification of flavonoids from Ascophyllum nodosum as having the ability to dissolve Aß42 fibrils in an AD model of Drosophila. FRAN could be superior anti-AD agents for neuroprotection, their underlying mechanism and how they collectively halted amyloidogenesis is currently being investigated. PURPOSE: This study aimed to investigate the neuroprotective role of FRAN in the Aß42 expressing AD model of Drosophila. METHODS: Drosophila stocks: OregonR+, ey-GAL4/CyO, elavc155-GAL4, UAS-mitoGFP, UAS-mcherry.mito.OMM, UAS-Aß42/CyO were used, cultured at 28±1 °C in a BOD incubator. Ascophyllum extract rich in flavonoids as revealed by LC-MS study and employed against the AD flies. The validation of Aß42 expression was done by immunostaining and q-RT PCR. The eye roughness of AD flies was scored in a dose-dependent manner. Further, In vivo and in silico studies of FRAN extract was executed against Aß42 induced neurotoxicity. RESULTS: In order to determine the most effective lethal dose of FRAN extract concentration 1, 2, 5, 10 mg/ml were screened using OregonR+flies. Extract 1 and 2 mg/ml did not show any lethality. Hence, extract 2 mg/ml was employed on AD flies and a ≥ 50% rescue in the eye phenotype was observed using SEM images. This dose had a strong effect on cell apoptosis, viability, longevity, mitochondrial dysfunction and oxidative stress by regulating mitochondrial dynamic markers in comparable to control. Extract also scavenging free radicals in order to maintain in situ cellular ROS and prevent Aß42-induced neurotoxicity in vivo and in silico. Hence, we suggest its great potential as a future therapeutic agent for AD treatment. CONCLUSION: In conclusion, FRAN extract rich in flavonoids as having largest neuroprotective activity against Aß42 aggregation in eye tissue of Drosophila. Extract shows strong effect against Aß42-induced neurotoxicity by altering the various cellular and molecular events. So, it could be considered as strong anti-AD agents for neuroprotection.

Antimalarial evaluation of copper(II) nanohybrid solids: inhibition of plasmepsin II, a hemoglobin-degrading malarial aspartic protease from Plasmodium falciparum.

A new class of copper(II) nanohybrid solids, LCu(CH(3)COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and plasmepsin II (an aspartic protease and a plausible novel target for antimalarial drug development), which is believed to be essential for hemoglobin degradation by the parasite, have been assayed by UV-vis spectroscopy and inhibition kinetics using Lineweaver-Burk plots. Our results suggest that these two compounds have antimalarial activities, and the IC(50) values (0.025-0.032 microg/ml) are similar to the IC(50) value of the standard drug chloroquine used in the bioassay. Lineweaver-Burk plots for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH(3)COO)(2) and LCuCl(2) were found to be 10 and 13 microM, respectively. The IC(50) values for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) were found to be 14 and 17 microM, respectively. Copper(II) metal capped by a benzimidazole group, which resembles the histidine group of copper proteins (galactose oxidase, beta-hydroxylase), could provide a suitable anchoring site on the nanosurface and thus could be useful for inhibition of target enzymes via binding to the S1/S3 pocket of the enzyme hydrophobically. Both copper(II) nanohybrid solids were found to be nontoxic against human hepatocellular carcinoma cells and were highly selective for plasmepsin II versus human cathepsin D. The pivotal mechanism of antimalarial activity of these compounds via plasmepsin II inhibition in the P. falciparum malaria parasite is demonstrated.