Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate.

Background: High-dose methotrexate (HD-MTX) is commonly employed in the treatment of malignant tumors in children and young adults due to its distinctive therapeutic efficacy. Nonetheless, the systemic exposure to MTX often results in liver injury (drug induced liver injury, DILI), thereby imposing limitations on the sustained administration of HD-MTX. Additionally, individual variations including genetic underpinnings attributable to disparities in therapeutic effects and clinical toxicity remain to be elucidated.

Combination of UGT1A1 polymorphism and baseline plasma bilirubin levels in predicting the risk of antipsychotic-induced dyslipidemia in schizophrenia patients.

The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia.

Differential impact of intermittent versus continuous treatment with clozapine on fatty acid metabolism in the brain of an MK-801-induced mouse model of schizophrenia.

Continuous antipsychotic treatment is often recommended to prevent relapse in schizophrenia. However, the efficacy of antipsychotic treatment appears to diminish in patients with relapsed schizophrenia and the underlying mechanisms are still unknown. Moreover, though the findings are inconclusive, several recent studies suggest that intermittent versus continuous treatment may not significantly differ in recurrence risk and therapeutic efficacy but potentially reduce the drug dose and side effects.

Pre-treatment risk predictors of valproic acid-induced dyslipidemia in pediatric patients with epilepsy.

Valproic acid (VPA) stands as one of the most frequently prescribed medications in children with newly diagnosed epilepsy. Despite its infrequent adverse effects within therapeutic range, prolonged VPA usage may result in metabolic disturbances including insulin resistance and dyslipidemia. These metabolic dysregulations in childhood are notably linked to heightened cardiovascular risk in adulthood.

B-GOS alleviates olanzapine-induced lipid disturbances in mice by enriching Akkermansia and upregulation of PGRMC1-Wnt signaling.

Although olanzapine (OLZ) remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability issues related to its metabolic profile such as weight gain and dyslipidemia. Our previous studies have demonstrated that progesterone receptor membrane component 1 (PGRMC1) plays a key role in antipsychotic-induced metabolic side effects. Prebiotics showed positive effects on lipid metabolism, however, limited studies focused on their therapeutic potential and mechanisms in treating antipsychotic-induced lipid metabolic disorders.

The Involvement of PGRMC1 Signaling in Cognitive Impairment Induced by Long-Term Clozapine Treatment in Rats.

Introduction: Progesterone receptor component 1 (PGRMC1) has been identified as a potential target in atypical antipsychotic drug-induced metabolic disturbances as well as neuroprotection in the central nervous system. In our study, we aimed to figure out the essential role of PGRMC1 signaling pathway underlying clozapine-induced cognitive impairment.

Methods: In male SD rats, we utilized recombinant adeno-associated viruses (BBB 2.

Insight into mitochondrial dysfunction mediated by clozapine-induced inhibition of PGRMC1 in PC12 cells.

Clozapine is usually considered as the last resort for treatment-resistant schizophrenia (TRS). However, it shows limited efficacy in cognition improvement. Moreover, the metabolic side effects induced by clozapine can aggravate cognitive impairment, which is closely related to its neurotoxicity.

Olanzapine-induced nonalcoholic fatty liver disease: The effects of differential food pattern and the involvement of PGRMC1 signaling.

Detrimental dietary habits with high-fat food are common in the psychiatric population, leading to higher obesity rate. Olanzapine (OLZ), as one of the mainstream antipsychotic drugs, shows superior efficacy in treating schizophrenia but limited by adverse effects such as obesity, dyslipidemia and liver injury, which are risk factors for the development of nonalcoholic fatty liver disease (NAFLD). Progesterone receptor component 1 (PGRMC1) is a key regulator associated with antipsychotic drug-induced metabolic disorders.