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Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. Using three pairs of human disomic and trisomic DS induced pluripotent stem cell (iPSC) isogenic lines, we differentiated neurons and treated them with lithium. Nuclear REST expression and reactive oxygen species (ROS) levels were quantified. Results showed the significantly lower nuclear REST expression in DS neurons was restored after 24 h of 10 mM lithium carbonate treatment. Notably, lithium treatment selectively reduced ROS levels in DS neurons to near-baseline levels. When challenged with hydrogen peroxide, DS neurons exhibited increased vulnerability to oxidative stress. The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is an endocrine and reproductive condition affecting women of reproductive age, although its expression profiles and molecular pathways are not fully understood., Aims: To identify the transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in women with PCOS and controls. To investigate noninvasive diagnostic biomarkers and potential treatment targets to improve women's fertility., Methods: RNA sequencing (RNA-Seq) was conducted on PBMC samples from six patients with PCOS and six healthy controls. qRT-PCR validation was carried out in 68 subjects. Multivariate logistic regression was performed to assess the combined impact of biomarkers., Results: A total of 186 differentially expressed genes (DEG) were found between patients and controls (log 2 FC >1, p < 0.05). Enrichment analysis revealed cytokine-mediated signaling pathways, cytokine activity, and cytokine-cytokine receptor interaction. RNA sequencing showed consistency with qRT-PCR. Women with PCOS had significantly higher levels of AQP9 (p < 0.001), PROK2 (p = 0.001), and S100A12 (p < 0.001) expression compared to controls. AQP9 (AUC = 0.77), PROK2 (AUC = 0.71), and S100A12 (AUC = 0.82) adequately discriminated women with PCOS from healthy controls. In addition, multiple logistic regression on biomarkers resulted in a significant diagnostic power with an AUC = 0.89, 95 % CI: 0.81-0.97, p < 0.0001. Further associations were analyzed between relative gene expression and clinical, anthropometric, hormonal, and ultrasonographic data., Conclusions: Dysregulated RNA expression in PBMCs may contribute to an increased risk of PCOS and serve as a potential diagnostic biomarker. The involvement of inflammatory and cytokine-related pathways supports the notion that PCOS is a chronic inflammatory condition., Competing Interests: Conflict of Interests R.H. has nothing to disclose. M.P. has nothing to disclose. M.B.O. has nothing to disclose. K- H.L. has nothing to disclose. H.A.H. has nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

JAK-STAT signaling cascade has emerged as an ideal target for the treatment of myeloproliferative diseases, autoimmune diseases, and neurological disorders. Ruxolitinib (Rux), is an orally bioavailable, potent and selective Janus-associated kinase (JAK) inhibitor, proven to be effective to target activated JAK-STAT pathway in the diseases previously described. Unfortunately, limited studies have investigated the potential cytotoxic profile of Rux on other cell populations within the heterogenous CNS microenvironment. Two stem and progenitor cell populations, namely the oligodendrocyte precursor cells (OPCs) and neural stem/progenitor cells (NSPCs), are important for long-term maintenance and post-injury recovery response of the CNS. In light of the limited evidence, this study sought to investigate further the effect of Rux on proliferating and differentiating OPCs and NSPCs populations. In the present study, cultured rat OPCs and NSPCs were treated with various concentrations of Rux, ranging from 2 μM to 20 μM. The effect of Rux on proliferating OPCs (PDGF-R-α + ) and proliferating NSPCs (nestin + ) was assessed via a 3-day Rux treatment, whereas its effect on differentiating OPCs (MBP + /PDGF-R-α + ) and differentiating NSPCs (neurofilament + ) was assessed after a 7-day treatment. Cytotoxicity of Rux was also assessed on OPC populations by examining its influence on cell death and DNA synthesis via YO-PRO-1/PI dual-staining and BrdU assay, respectively. The results suggest that Rux at a dosage above 10 μM reduces the number proliferating OPCs, likely via the induction of apoptosis. On the other hand, Rux treatment from 2.5 μM to 20 μM significantly reduces the number of differentiating OPCs by inducing necrosis. Meanwhile, Rux treatment has no observable untoward impact on NSPC cultures within the dosage range tested. Taken together, OPCs appears to be more vulnerable to the dosage effect of Rux, whereas NSPCs are not significantly impacted by Rux, suggesting a differential mechanism of actions of Rux on the cell types., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is one of the most common, most formidable, and deadliest malignant types of primary astrocytoma with a poor prognosis. At present, the standard of care includes surgical tumor resection, followed by radiation therapy concomitant with chemotherapy and temozolomide. New developments and significant advances in the treatment of GBM have been achieved in recent decades. However, despite the advances, recurrence is often inevitable, and the survival of patients remains low. Various factors contribute to the difficulty in identifying an effective therapeutic option, among which are tumor complexity, the presence of the blood-brain barrier (BBB), and the presence of GBM cancer stem cells, prompting the need for improving existing treatment approaches and investigating new treatment alternatives for ameliorating the treatment strategies of GBM. In this review, we outline some of the most recent literature on the various available treatment options such as surgery, radiotherapy, cytotoxic chemotherapy, gene therapy, immunotherapy, phototherapy, nanotherapy, and tumor treating fields in the treatment of GBM, and we list some of the potential future directions of GBM. The reviewed studies confirm that GBM is a sophisticated disease with several challenges for scientists to address. Hence, more studies and a multimodal therapeutic approach are crucial to yield an effective cure and prolong the survival of GBM patients., (Copyright © 2022 IBRO. All rights reserved.)

Breast cancer is the most common cancer among women worldwide and novel therapeutic agents are needed to treat this disease. The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors. This review will discuss recent studies and consider the application of new prospective approaches based on microRNAs and other crucial regulators for use in future studies to define the action of berberine in cancer. The effects of berberine on cancer cell survival and proliferation are also outlined., (Copyright © 2014. Published by Elsevier B.V.)

Staphylococcus aureus biofilm associated infections remains a major clinical concern in patients with indwelling devices. Quantitative real-time PCR (qPCR) can be used to investigate the pathogenic role of such biofilms. We describe qPCRs for 12 adhesion and biofilm-related genes of four S. aureus isolates which were applied during in vitro biofilm development. An endogenous control (16S rRNA) was used for signal normalization. We compared the qPCR results with structural analysis using scanning electron microscopy (SEM). The SEM studies showed different cellular products surrounding the aggregated cells at different times of biofilm formation. Using qPCR, we found that expression levels of the gene encoding fibronectin binding protein A and B and clumping factor B (fnbA/B and clfB), which involves in primary adherence of S. aureus, were significantly increased at 24h and decreased slightly and variably at 48 h when all 4 isolates were considered. The elastin binding protein (ebps) RNA expression level was significantly enhanced more than 6-fold at 24 and 48 h compared to 12h. Similar results were obtained for the intercellular adhesion biofilm required genes type C (icaC). In addition, qPCR revealed a fluctuation in expression levels at different time points of biofilm growth of other genes, indicating that different parameter modes of growth processes are operating at different times., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The dose-dependent effects of the anticholinesterases, neostigmine and mycotoxin territrem-B, were determined on: (i) Cl(-)-responses of voltage clamped Achatina fulica neurons to microperfused acetylcholine; (ii) the 4 K(+)-induced outward currents evoked by an electrogenic sodium pump in the same neuron; and (iii) acetylcholinesterase activity of Achatina fulica ganglionic homogenates. Both compounds at low doses potentiated the peak acetylcholine responses. However, they had different effects at higher (> 1 microM) doses in that neostigmine now antagonized acetylcholine responses, while territrem-B still produced a maximal potentiation. At all doses neostigmine produced a dose-dependent inhibition of acetylcholinesterase activity. The cholinolytic effect of high doses of neostigmine was associated with the inhibition of 4 K(+)-induced current in the same neuron, while territrem-B neither altered the K(+)-induced current nor antagonized acetylcholine responses. The cholinolytic effect of neostigmine was completely antagonized by the inhibition of electrogenic sodium pump by ouabain or by perfusion with K(+)-free solution. These results suggest that neostigmine at high concentrations inhibits the electrogenic sodium pump and that the cholinolytic effect of high doses of neostigmine is secondary to this action. Territrem-B, on the other hand, had no effect on the electrogenic sodium pump and had no effect on the neuronal membrane properties other than to inhibit acetylcholinesterase. Thus, territrem-B may be a useful tool for studying the interaction between acetylcholinesterase and acetylcholine receptors.