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1.
J Clin Med ; 12(23)2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38068358

RESUMO

Incidental pancreatic cysts are highly prevalent, with management dependent on the risk of malignant progression. Serous cystadenomas (SCAs) are the most common benign pancreatic cysts seen on imaging. They have typical morphological patterns but may also show atypical features that mimic precancerous and cancerous cysts. If a confident diagnosis of SCA is made, no further follow-up is warranted. Therefore, a preoperative distinction between SCA and precancerous or cancerous lesions is critically essential. Distinguishing an SCA from other types of pancreatic cysts on imaging remains a challenge, thus leading to misdiagnosis and ramifications. This review summarizes the current evidence on diagnosing and managing SCA.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35895929

RESUMO

In vitro genotoxicity testing plays an important role in chemical risk assessment. The human B-lymphoblastoid cell line TK6 is widely used as a standard cell line for regulatory safety evaluations. Like many other mammalian cell lines, TK6 cells have limited metabolic capacity; therefore, usually require a source of exogenous metabolic activation for use in genotoxicity testing. Previously, we developed a set of TK6-derived cell lines that individually express one of fourteen cytochrome P450s (CYPs). In the present study, we surveyed a panel of major Phase II drug-metabolizing enzymes to characterize their baseline expression in TK6 cells. These results may serve as a reference enzymatic profile of this commonly used cell line.


Assuntos
Dano ao DNA , Mamíferos , Ativação Metabólica , Animais , Linhagem Celular , Humanos , Testes de Mutagenicidade/métodos
3.
J Appl Toxicol ; 42(9): 1491-1502, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35261072

RESUMO

Black cohosh extract (BCE) is one of the most popular botanical products for relieving menopausal symptoms. However, recent studies indicate that BCE is not only ineffective for menopausal therapy but also induces genotoxicity through an aneugenic mode of action (MoA). In this study, the cytotoxicity of five constituents of BCE was evaluated in human lymphoblastoid TK6 cells. Among the five constituents, actein (up to 50 µM) showed the highest cytotoxicity and was thus selected for further genotoxicity evaluations. Actein caused DNA damage proportionally to concentration as evidenced by the phosphorylation of the histone protein H2A.X (γH2A.X) and resulted in chromosomal damage as measured by the increased percentage of micronuclei (%MN) in cells. In addition, actein activated DNA damage response (DDR) pathway through induction of p-ATM, p-Chk1, and p-Chk2, which subsequently induced cell cycle changes and apoptosis. Moreover, both BCE and actein increased intracellular reactive oxygen species (ROS) production, decreased glutathione levels, and activated the mitogen-activated protein kinases (MAPK) signaling pathway. N-acetylcysteine, a ROS scavenger, attenuated BCE- and actein-induced ROS production, apoptosis, and DNA damage. These findings indicate that BCE- and actein-induced genotoxicity is mediated, at least partially, through oxidative stress. Taken together, our data show that actein is likely one of the major contributors to BCE-induced genotoxicity.


Assuntos
Cimicifuga , Cimicifuga/metabolismo , Cimicifuga/toxicidade , Dano ao DNA , Humanos , Extratos Vegetais , Espécies Reativas de Oxigênio/metabolismo , Saponinas , Triterpenos
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