The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Regrettably, there has been no comprehensive review of the role of magnesium in cancer therapy to date. Therefore, this article provides a comprehensive scrutiny of the relationship between magnesium ions and tumors, aiming to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

Pyrroline-5-carboxylate reductase (PYCR) is pivotal in converting pyrroline-5-carboxylate (P5C) to proline, the final step in proline synthesis. Three isoforms, PYCR1, PYCR2, and PYCR3, existed and played significant regulatory roles in tumor initiation and progression. In this study, we first assessed the molecular and immune characteristics of PYCRs by a pan-cancer analysis, especially focusing on their prognostic relevance. Then, a kidney renal clear cell carcinoma (KIRC)-specific prognostic model was established, incorporating pathomics features to enhance predictive capabilities. The biological functions and regulatory mechanisms of PYCR1 and PYCR2 were investigated by in vitro experiments in renal cancer cells. The PYCRs’ expressions were elevated in diverse tumors, correlating with unfavorable clinical outcomes. PYCRs were enriched in cancer signaling pathways, significantly correlating with immune cell infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI). In KIRC, a prognostic model based on PYCR1 and PYCR2 was independently validated statistically. Leveraging features from H&E-stained images, a pathomics feature model reliably predicted patient prognosis. In vitro experiments demonstrated that PYCR1 and PYCR2 enhanced the proliferation and migration of renal carcinoma cells by activating the mTOR pathway, at least in part. This study underscores PYCRs’ pivotal role in various tumors, positioning them as potential prognostic biomarkers and therapeutic targets, particularly in malignancies like KIRC. The findings emphasize the need for a broader exploration of PYCRs’ implications in pan-cancer contexts.

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO₄), (3) Parkinson’s disease (PD), and (4) Parkinson’s disease with magnesium sulfate (PD/MgSO₄). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats’ anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO₄ group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO₄ group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO₄ group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients.

Background: Parkinson’s disease (PD) is characterized by progressive dopaminergic neurodegeneration. Melatonin (MLT) is implicated in neuroprotection, yet the effects of modulating its receptors remain unclear. This study investigated the impact of the MLT receptor agonist agomelatine (AG) and antagonist luzindole (LU) on motor behavior, serum MLT levels, and dopaminergic neuron survival in a 6-hydroxydopamine (6-OHDA) rat model of PD. Methods: A PD model was induced by stereotaxic injection of 6-OHDA into the medial forebrain bundle. Rats received intraperitoneal AG or LU for 2 or 4 weeks. Motor function was assessed using the apomorphine-induced rotation test. Tyrosine hydroxylase (TH) and MLT receptor (MEL-1A/B) expression in the substantia nigra and striatum were evaluated by immunohistochemistry and Western blot. Serum MLT concentrations were measured using ELISA. Pearson’s correlation analysis was performed to examine associations among serum MLT levels, TH expression, and motor performance. Results: AG significantly improved motor function, increased serum MLT levels, and enhanced TH expression in PD rats. LU also mitigated motor deficits and preserved dopaminergic neurons, despite reducing serum MLT levels. Correlation analysis revealed a dynamic temporal relationship between MLT levels, behavioral outcomes, and dopaminergic neuron survival, indicating that MLT signaling may differentially influence PD pathology at various stages. Conclusions: Both AG and LU demonstrated neuroprotective potential in 6-OHDA–induced PD rats. AG may exert its effects by enhancing endogenous MLT signaling, while LU may protect neurons by modulating excessive MLT activity. These findings highlight the complex regulatory role of the MLT pathway in PD progression and suggest stage-dependent therapeutic benefits of MLT receptor modulators.

The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Therefore, this article provides a comprehensive review of the relationship between magnesium ions and tumors, the mechanisms by which magnesium ions regulate mitochondrial function, and the theoretical basis and prospects of magnesium ion regulation of mitochondrial function for tumor treatment. This review aims to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

Magnesium ions and their transport proteins are increasingly recognized for their critical roles in tumor progression. However, their specific mechanisms in endometrial cancer (EC) remain poorly understood. This study investigated the role of Mitochondrial RNA Splicing 2 protein (MRS2), a key mitochondrial magnesium transporter, and its associated genes, in regulating mitochondrial function and the invasive and metastatic capabilities of EC cells. Using a combination of experimental approaches including lactate detection, flow cytometry, immunofluorescence, CCK8 assays, and Transwell migration assays, along with bioinformatics analysis, we investigated the relationship between lactate levels and MRS2 expression in endometrial cancer cells (KLE). Our findings suggest that elevated lactate levels are associated with increased MRS2 expression in mitochondria. This correlation was further linked to enhanced reactive oxygen species (ROS) production and altered expression of mitochondrial-related genes. Notably, MRS2 knockdown resulted in reduced proliferation of KLE cells, supporting a potential functional role of MRS2 in endometrial cancer progression. These findings provide new insights into the molecular mechanisms underlying EC progression and highlight MRS2 as a potential therapeutic target.