The prevalence of EIM is similar to that reported from Europe and USA, albeit higher than that previously reported in Asian patients. Female sex, religion, severe disease, and steroid use were associated with EIM.
Background:
Breast cancer is one of the most common cancers diagnosed among women. It
is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha
(ERα) correlates with better prognosis and the likelihood of response to hormonal therapy. ERα is
an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast
cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour
completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not
exhibit any high toxic effects against normal cells.
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Objectives: To identify the potential natural inhibitors for BCa through an optimised in silico approach.
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Methods: Structural modification and molecular docking-based screening approaches were imposed to
identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used
for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the
compounds was evaluated by MTT assay against MCF-7 Cell lines.
Results:
From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin,
Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1
respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 ± 4.0 and 58.3 ±
4.4 µM, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated
to find the drug-likeness and pharmacokinetic parameters.
We mainly focused on in silico study to dock the compounds into the human estrogen receptor
ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens.
Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising
among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell
line. These findings may provide basic information for the development of anti-breast cancer agents.
It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri, a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae (p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups (p = 0.04–0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri (p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.
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