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1.
Life Sci ; 310: 121074, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36243120

ABSTRACT

The highly active estrogen metabolism and receptor protein expression are to blame for the elevated breast cancer (BC) rate in post-menopausal women. Letrozole is a powerful endocrine medication that targets and inhibits the aromatase, often known as an aromatase inhibitor (AI). It aids in the adjuvant, neoadjuvant, and metastatic treatment of HR+ breast cancer because it can boost FSH production for ovulation induction. It has recently been used in infertile pre-menopausal women. The main advantages of utilizing letrozole to enhance follicle development may be wasted in current infertility treatments. We went into great length in this review about the pharmacokinetics, pharmacodynamics, and distinct adverse effects of the drug on the heart, kidney, liver, embryo, bone, and ovary. It also causes apoptosis, necrosis, and fibrosis, which all result in the demise of cancer cells. Its central and peripheral effects on follicle formation, estrogen production in the ovaries, and their clinical implications are explored in detail in this work.


Subject(s)
Breast Neoplasms , Infertility, Female , Female , Humans , Letrozole/pharmacology , Letrozole/therapeutic use , Nitriles/therapeutic use , Triazoles/pharmacology , Triazoles/therapeutic use , Aromatase Inhibitors/pharmacology , Aromatase Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Estrogens/metabolism , Infertility, Female/drug therapy
2.
Adv Protein Chem Struct Biol ; 127: 315-342, 2021.
Article in English | MEDLINE | ID: mdl-34340772

ABSTRACT

Lung Emphysema is an abnormal enlargement of the air sacs followed by the destruction of alveolar walls without any prominent fibrosis. This study primarily identifies the differentially expressed genes (DEGs), interactions between them, and their significant involvement in the activated signaling cascades. The dataset with ID GSE1122 (five normal lung tissue samples, five of usual emphysema, and five of alpha-1 antitrypsin deficiency-related emphysema) from the gene expression omnibus (GEO) was analyzed using the GEO2R tool. The physical association between the DEGs were mapped using the STRING tool and was visualized in the Cytoscape software. The enriched functional processes were identified with the ClueGO plugin's help from Cytoscape. Further integrative functional annotation was performed by implying the GeneGo Metacore™ to distinguish the enriched pathway maps, process networks, and GO processes. The results from this analysis revealed the critical signaling cascades that have been either activated or inhibited due to identified DEGs. We found the activated pathways such as immune response IL-1 signaling pathway, positive regulation of smooth muscle migration, BMP signaling pathway, positive regulation of leukocyte migration, NIK/NF-kappB signaling, and cytochrome-c oxidase activity. Finally, we mapped four crucial genes (CCL5, ALK, TAC1, CD74, and HLA-DOA) by comparing the functional annotations that could be significantly influential in emphysema molecular pathogenesis. Our study provides insights into the pathogenesis of emphysema and helps in developing potential drug targets against emphysema.


Subject(s)
Databases, Genetic , Pulmonary Emphysema , Signal Transduction/genetics , Systems Biology , alpha 1-Antitrypsin Deficiency , Humans , Pulmonary Emphysema/genetics , Pulmonary Emphysema/metabolism , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/metabolism
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