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1.
Scand J Clin Lab Invest ; 83(8): 533-539, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38145316

ABSTRACT

Vitamin B12 deficiency and insufficiency can lead to both hematological and neurological impairments. This review examines nondisease causes and risk factors associated with dietary availability, such as eating habits, food processing, cooking techniques, and bioavailability, as well as increased physiological needs and iatrogenic factors linked to medication use or surgical procedures. As a result of these nondisease influences, groups at higher risk include vegans, vegetarians, older adults, individuals with limited diets, breastfed and preterm infants, and those who primarily consume foods prepared or cooked in ways that reduce vitamin B12 content, as well as individuals on certain medications or who have undergone specific surgeries. Recognizing these diverse risk factors helps develop strategies for prevention and intervention to minimize the adverse health effects related to B12 deficiency and insufficiency.


Subject(s)
Vitamin B 12 Deficiency , Vitamin B 12 , Infant, Newborn , Infant , Humans , Aged , Diet, Vegetarian/adverse effects , Infant, Premature , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12 Deficiency/etiology , Risk Factors
2.
Pharmacol Res ; 193: 106806, 2023 07.
Article in English | MEDLINE | ID: mdl-37244387

ABSTRACT

The estrogen receptor-α (ER-α) is a key driver of breast cancer (BC) and the ER-antagonist, tamoxifen, is a central pillar of BC treatment. However, cross-talk between ER-α, other hormone and growth factor receptors enables development of de novo resistance to tamoxifen. Herein, we mechanistically dissect the activity of a new class of anti-cancer agents that inhibit multiple growth factor receptors and down-stream signaling for the treatment of ER-positive BC. Using RNA sequencing and comprehensive protein expression analysis, we examined the activity of di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), on the expression and activation of hormone and growth factor receptors, co-factors, and key resistance pathways in ER-α-positive BC. DpC differentially regulated 106 estrogen-response genes, and this was linked to decreased mRNA levels of 4 central hormone receptors involved in BC pathogenesis, namely ER, progesterone receptor (PR), androgen receptor (AR), and prolactin receptor (PRL-R). Mechanistic investigation demonstrated that due to DpC and Dp44mT binding metal ions, these agents caused a pronounced decrease in ER-α, AR, PR, and PRL-R protein expression. DpC and Dp44mT also inhibited activation and down-stream signaling of the epidermal growth factor (EGF) family receptors, and expression of co-factors that promote ER-α transcriptional activity, including SRC3, NF-κB p65, and SP1. In vivo, DpC was highly tolerable and effectively inhibited ER-α-positive BC growth. Through bespoke, non-hormonal, multi-modal mechanisms, Dp44mT and DpC decrease the expression of PR, AR, PRL-R, and tyrosine kinases that act with ER-α to promote BC, constituting an innovative therapeutic approach.


Subject(s)
Breast Neoplasms , Thiosemicarbazones , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Progesterone/therapeutic use , Androgens/therapeutic use , Receptors, Prolactin , Prolactin/therapeutic use , Tamoxifen/pharmacology , Thiosemicarbazones/pharmacology , Thiosemicarbazones/therapeutic use , ErbB Receptors , Estrogens/therapeutic use
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