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Chemical & Pharmaceutical Bulletin 2023Chiral lithium binaphtholates prepared from the corresponding binaphthols and lithium tert-butoxide effectively catalyze the asymmetric Michael additions of ketones to...
Chiral lithium binaphtholates prepared from the corresponding binaphthols and lithium tert-butoxide effectively catalyze the asymmetric Michael additions of ketones to poorly reactive acrylamides. The lithium binaphtholate catalyst mediates ketone deprotonation and enantioselective carbon-carbon bond formation to the acrylamide to deliver the Michael adduct in good yield and enantioselectivity. A small excess of lithium tert-butoxide relative to the binaphthol successfully enolizes the ketone in the initial stage of the reaction to promote the Michael reaction. Computational analysis of the transition state suggested that the 3- and 3'-phenyl groups of the binaphtholate catalyst regulate the orientation of the lithium enolate and the subsequent approach of the acrylamide, leading to superior enantioselectivity.
Topics: Lithium; Acrylamides; Acrylamide; Stereoisomerism; Ketones; Catalysis
PubMed: 37779082
DOI: 10.1248/cpb.c23-00435 -
Translational Psychiatry Apr 2021Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized b-y recurrent and distinctive obsessions and/or compulsions. The etiologies remain... (Review)
Review
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized b-y recurrent and distinctive obsessions and/or compulsions. The etiologies remain unclear. Recent findings have shown that oxidative stress, inflammation, and the glutamatergic pathway play key roles in the causes of OCD. However, first-line therapies include cognitive-behavioral therapy but only 40% of the patients respond to this first-line therapy. Research for a new treatment is mandatory. This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on OCD and some of the presumed mechanisms by which lithium provides its benefit properties. Lithium medication downregulates GSK-3β, the main inhibitor of the WNT/β-catenin pathway. The activation of the WNT/β-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway. Future prospective clinical trials could focus on lithium and its different and multiple interactions in OCD.
Topics: Compulsive Behavior; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Obsessive-Compulsive Disorder; Wnt Signaling Pathway
PubMed: 33828076
DOI: 10.1038/s41398-021-01329-3 -
International Journal of Molecular... Feb 2021Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder... (Review)
Review
Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder (BD). Molecular biology studies have indicated an involvement of the immune system in the pathogenesis of mood disorders, and showed their correlation with altered levels of inflammatory markers and energy metabolism. Previous reports, including meta-analyses, also suggested the role of microglia activation in the M1 polarized macrophages, reflecting the pro-inflammatory phenotype. Lithium is an effective mood stabilizer used to treat both manic and depressive episodes in bipolar disorder, and as an augmentation of the antidepressant treatment of depression with a multidimensional mode of action. This review aims to summarize the molecular studies regarding inflammation, microglia activation and energy metabolism changes in mood disorders. We also aimed to outline the impact of lithium on these changes and discuss its immunomodulatory effect in mood disorders.
Topics: Animals; Biomarkers; Cytokines; Disease Management; Disease Susceptibility; Energy Metabolism; Humans; Immunomodulation; Inflammation; Inflammation Mediators; Lithium; Mood Disorders
PubMed: 33546417
DOI: 10.3390/ijms22041532 -
The Primary Care Companion For CNS... Aug 2021
Topics: Humans; Lithium
PubMed: 34416101
DOI: 10.4088/PCC.20l02782 -
Chemosphere Nov 2022The rising use of lithium (Li) in industrial processes, modern technology and medicine has generated concerns in the scientific community, in particular its potential...
The rising use of lithium (Li) in industrial processes, modern technology and medicine has generated concerns in the scientific community, in particular its potential impact on the environment. Unfortunately, there is only scarce information concerning the toxicity of lithium in marine organisms. The objective of this study is to determine the toxicity of Li using Mytilus galloprovincialis as model organism, based on acute and sublethal toxicity tests. In the first experiment, mussels were exposed for 9 days to a range of acute concentrations of Li (0, 2, 5, 13, 34, 89, 233 and 610 mg/L Li) in order to find the median lethal concentration. In the sublethal experiment, mussels were exposed to environmentally relevant concentrations of Li (0, 0.1, 1, 10 mg/L Li) for 21 days. Digestive gland and gonad samples were taken at day 0, 1, 7 and 21 for histopathological analysis. Samples of the whole mussels were taken for chemical analysis at day 0 and after 21 days. Results showed that M. galloprovincialis had a LC50 value of 153 mg/L Li after 9 days of exposure. Lower concentrations (environmentally relevant), led to Li bioaccumulation in a dose-dependent manner and histopathological effects in a time-dependent manner. Atrophy of the digestive alveoli epithelium and degeneration of the digestive gland were observed after 21 days of exposure. These findings open new perspectives for the understanding of the toxic effects of Li on marine organisms and evidence the need for further long-term research at different levels of biological organizations.
Topics: Animals; Lithium; Mytilus; Water Pollutants, Chemical
PubMed: 36002063
DOI: 10.1016/j.chemosphere.2022.136022 -
Psychopharmacology Bulletin Feb 2022To determine if enhanced flow cytometry () can identify intracellular proteins of lithium responsiveness in monocytes and CD4 lymphocytes from patients with bipolar...
Protein Biomarkers in Monocytes and CD4 Lymphocytes for Predicting Lithium Treatment Response of Bipolar Disorder: a Feasibility Study with Tyramine-Based Signal-Amplified Flow Cytometry.
PURPOSE
To determine if enhanced flow cytometry () can identify intracellular proteins of lithium responsiveness in monocytes and CD4 lymphocytes from patients with bipolar disorder.
METHODS
Eligible bipolar I or II patients were openly treated with lithium for 16-weeks. Baseline levels of Bcl2, BDNF, calmodulin, Fyn, phospho-Fyn/phospho-Yes, GSK3β, phospho-GSK3αβ, HMGB1, iNOS, IRS2, mTor, NLPR3, PGM1, PKA C-α, PPAR-γ, phospho-RelA, and TPH1 in monocytes and CD4 lymphocytes of lithium responders and non-responders were measured with . Their utility of discriminating responders from non-responders was explored. Protein-protein network and pathway enrichment analyses were conducted.
RESULTS
Of the 24 intent-to-treat patients, 12 patients completed the 16-week study. Eleven of 13 responders and 8 of 11 non-responders were available for this analysis. The levels of the majority of analytes in lithium responders were lower than non-responders in both cell types, but only the level of GSK3β in monocytes was significantly different (p = 0.034). The combination of GSK3β and phospho-GSK3αβ levels in monocytes correctly classified 11/11 responders and 5/8 non-responders. Combination of GSK3β, phospho-RelA, TPH1 and PGM1 correctly classified 10/11 responders and 6/7 non-responders, both with a likelihood of ≥ 85%. Prolactin, leptin, BDNF, neurotrophin, and epidermal growth factor/epidermal growth factor receptor signaling pathways are involved in the lithium treatment response. GSK3β and RelA genes are involved in 4 of 5 these pathways.
CONCLUSION
CellPrint™ flow cytometry was able to detect differences in multiple proteins in monocytes and CD4 lymphocytes between lithium responders and non-responders. A large study is warranted to confirm or refute these findings.
Topics: Biomarkers; Bipolar Disorder; Brain-Derived Neurotrophic Factor; CD4-Positive T-Lymphocytes; Feasibility Studies; Flow Cytometry; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Lithium Compounds; Monocytes; Tyramine
PubMed: 35342205
DOI: No ID Found -
Drug Development Research Nov 2020The pandemic of respiratory illness caused by a novel coronavirus (SARS-nCoV-2) is a global health crisis. Despite numerous preliminary results, there is as yet no...
The pandemic of respiratory illness caused by a novel coronavirus (SARS-nCoV-2) is a global health crisis. Despite numerous preliminary results, there is as yet no treatment of proven efficacy for this condition. In this context, the pharmacological properties of lithium, better known as a treatment for mood disorders, merit closer examination. Lithium has shown in vitro efficacy at inhibiting the replication of coronaviruses responsible for gastrointestinal and respiratory diseases in animals. It has immunomodulatory properties that may be of additional benefit in moderating the host inflammatory response to the novel coronavirus (SARS-CoV-2). Furthermore, there is evidence that lithium may exert a protective action against upper respiratory infections and influenza-like illnesses in patients taking it for other indications. These promising reports must be balanced against the narrow therapeutic index and high risk of toxicity associated with lithium therapy, its documented interactions with several commonly used drugs, and the absence of evidence of its efficacy against coronaviruses responsible for human disease. Nevertheless, naturalistic studies of the risk of COVID-19 in patients already receiving lithium could provide indirect evidence of its efficacy, and understanding the putative antiviral and immune-regulatory mechanisms of lithium in models of SARS-CoV-2 infection may provide leads for the development of safer and more effective treatments with a specific action against COVID-19.
Topics: Animals; Antiviral Agents; Lithium; Pragmatic Clinical Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32524646
DOI: 10.1002/ddr.21701 -
Canadian Family Physician Medecin de... Apr 2020
Topics: Humans; Lithium; Systems Analysis
PubMed: 32273410
DOI: No ID Found -
Molecular Biology of the Cell Apr 2023Ciliary length is highly regulated, but can be disrupted by lithium, which causes ciliary elongation across cell types and organisms. We used the algal system to...
Ciliary length is highly regulated, but can be disrupted by lithium, which causes ciliary elongation across cell types and organisms. We used the algal system to investigate the mechanism behind lithium-induced ciliary elongation. Protein synthesis is not required for lengthening, and the target of lithium, GSK3, has substrates that can influence membrane dynamics. Further, ciliary assembly requires a supply of ciliary membrane as well as protein. Lithium-treated cilia elongate normally with brefeldin treatment, but dynasore treatment produced defective lengthening suggesting a source of membrane from the cell surface rather than the Golgi. Genetic or chemical perturbation of the Arp2/3 complex or dynamin, required for endocytosis, blocks lithium-induced ciliary lengthening. Finally, we found an increase in Arp2/3 complex- and endocytosis-dependent actin filaments near the ciliary base upon lithium treatment. Our results identify a mechanism for lithium-mediated cilium lengthening and demonstrate the endocytic pathway for cilium membrane supply in algae is likely a conserved mechanism given lithium's conserved effects across organisms.
Topics: Lithium; Actin-Related Protein 2-3 Complex; Glycogen Synthase Kinase 3; Cilia; Endocytosis
PubMed: 36753380
DOI: 10.1091/mbc.E22-06-0219 -
International Journal of Molecular... Feb 2020Lithium salt is the first-line therapeutic option for bipolar disorder and has been proposed as a potential antitumoral drug. The effects of LiCl treatment were...
Lithium salt is the first-line therapeutic option for bipolar disorder and has been proposed as a potential antitumoral drug. The effects of LiCl treatment were investigated in SH-SY5Y, a human neuroblastoma cell line and an in vitro model of dopaminergic neuronal differentiation. LiCl, at the dosage used in psychiatric treatment, does not affect cell proliferation, while at higher doses it delays the SH-SY5Y cell division cycle and for prolonged usage reduces cell viability. Moreover, the ion treatment affects DNA integrity as demonstrated by accumulation of p53 and γH2AX (the phosphorylated form of H2AX histone), two important markers of genome damage. p57, a CIP/Kip protein, is required for proper neuronal maturation and represents a main factor of response to stress including genotoxicity. We evaluated the effect of lithium on p57 levels. Unexpectedly, we found that lithium downregulates the level of p57 in a dose-dependent manner, mainly acting at the transcriptional level. A number of different approaches, mostly based on p57 content handling, confirmed that the CKI/Kip reduction plays a key role in the DNA damage activated by lithium and suggests the unanticipated view that p57 might be involved in DNA double-strand break responses. In conclusion, our study identified novel roles for p57 in the molecular mechanism of lithium at high concentration and, more in general, in the process of DNA repair.
Topics: Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p57; DNA Damage; Humans; Lithium; Neurons
PubMed: 32050593
DOI: 10.3390/ijms21031169