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We conducted an in‐depth exploration of the in vitro activities of the dinuclear Mn2L2Ac and Mn2L2 complexes (where HL=2‐{[di(2‐pyridyl)methylamino]‐methyl}phenol), possessing dual superoxide dismutase (SOD) and catalase (CAT) activity. We investigated these complexes both individually and in conjunction with various Pt(II)‐complexes, either as mixtures or as the Mn2‐Pt adducts. Our findings revealed a notable up to 50 % enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50 % in breast cancer cells upon combined treatments with Mn2 SOD mimics and Pt(II) complexes. Specifically, we synthesized and characterized the self‐assembled Mn2‐Pt adducts (isolated Mn2L2Pt and in situMn2L2Pt'), linking Mn2L2‐core with the carboxylate group of PtDAPCl2 (dichloro(2,3‐diaminopropionic acid) platinum(II)). The SOD activity of the isolated Mn2L2Pt adduct (kSOD=1.7×107 M−1 s−1) remained intact. Through in vitro cell viability assessments, ROS levels, cellular Mn uptake and proteomics measurements, we elucidated key mechanisms underlying the observed biological effects. We demonstrated that Mn2‐containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H2S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is a genetic condition where the person is born with an extra chromosome 21. DS is associated with accelerated aging; people with DS are prone to age-related neurological conditions including an early-onset Alzheimer's disease. Using the Dp(17)3Yey/ + mice, which overexpresses a portion of mouse chromosome 17, which encodes for the transsulfuration enzyme cystathionine β-synthase (CBS), we investigated the functional role of the CBS/hydrogen sulfide (H2S) pathway in the pathogenesis of neurobehavioral dysfunction in DS. The data demonstrate that CBS is higher in the brain of the DS mice than in the brain of wild-type mice, with primary localization in astrocytes. DS mice exhibited impaired recognition memory and spatial learning, loss of synaptosomal function, endoplasmic reticulum stress, and autophagy. Treatment of mice with aminooxyacetate, a prototypical CBS inhibitor, improved neurobehavioral function, reduced the degree of reactive gliosis in the DS brain, increased the ability of the synaptosomes to generate ATP, and reduced endoplasmic reticulum stress. H2S levels in the brain of DS mice were higher than in wild-type mice, but, unexpectedly, protein persulfidation was decreased. Many of the above alterations were more pronounced in the female DS mice. There was a significant dysregulation of metabolism in the brain of DS mice, which affected amino acid, carbohydrate, lipid, endocannabinoid, and nucleotide metabolites; some of these alterations were reversed by treatment of the mice with the CBS inhibitor. Thus, the CBS/H2S pathway contributes to the pathogenesis of neurological dysfunction in DS in the current animal model. [ABSTRACT FROM AUTHOR]

Background: This cross-sectional study aimed to assess the correlation between subjective oral health status and mental health in a group of university students in Serbia. Methods: The study included 948 students, aged between 18 and 27, from the Faculty of Medical Sciences, University of Kragujevac, Serbia, and was conducted in 2020. The World Health Organization's Oral Health Questionnaire for Adults was utilized to evaluate the respondents' self-perceived oral health and oral hygiene practices. The existence of depressive symptoms was evaluated using the Beck Depression Inventory-II (BDI-II), and the Zung self-rating anxiety scale (SAS) was used for determining anxiety symptoms. Results: It is observed that 28.9% of respondents exhibit symptoms of depression and 42.3% showed symptoms of anxiety. Results show that students with severe depression and anxiety symptoms very often reported lower self-perceived oral health and oral health problems. Although the nature of this relationship has not been thoroughly evaluated, several studies have shown a mutually dependent connection between oral health and mental health. Conclusions: The results suggest that some aspects of oral health are associated with higher risks of developing symptoms of depression or anxiety, and vice versa. [ABSTRACT FROM AUTHOR]

The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post‐translational modification of cysteine residues to produce reactive persulfides. A persulfide‐specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by ZnII, O2, and H2S, with intermediates involving oxygen‐ and sulfur‐based radicals detected by mass spectrometry and optical spectroscopies. A small molecule ZnII complex exhibits analogous reactivity with H2S and O2, giving a persulfidated product. These data show that ZnII is not just a biological structural element, but also plays a critical role in mediating H2S‐dependent persulfidation. ZF persulfidation appears to be a general post‐translational modification and a possible conduit for H2S signaling. This work has implications for our understanding of H2S‐mediated signaling and the regulation of ZFs in cellular physiology and development. [ABSTRACT FROM AUTHOR]

Significance: Protein persulfidation (the formation of RSSH), an evolutionarily conserved oxidative posttranslational modification in which thiol groups in cysteine residues are converted into persulfides, has emerged as one of the main mechanisms through which hydrogen sulfide (H2S) conveys its signaling. Recent Advances: New methodological advances in persulfide labeling started unraveling the chemical biology of this modification and its role in (patho)physiology. Some of the key metabolic enzymes are regulated by persulfidation. RSSH levels are important for the cellular defense against oxidative injury, and they decrease with aging, leaving proteins vulnerable to oxidative damage. Persulfidation is dysregulated in many diseases. Critical Issues: A relatively new field of signaling by protein persulfidation still has many unanswered questions: the mechanism(s) of persulfide formation and transpersulfidation and the identification of "protein persulfidases," the improvement of methods to monitor RSSH changes and identify protein targets, and understanding the mechanisms through which this modification controls important (patho)physiological functions. Future Directions: Deep mechanistic studies using more selective and sensitive RSSH labeling techniques will provide high-resolution structural, functional, quantitative, and spatiotemporal information on RSSH dynamics and help with better understanding how H2S-derived protein persulfidation affects protein structure and function in health and disease. This knowledge could pave the way for targeted drug design for a wide variety of pathologies. Antioxid. Redox Signal. 39, 19–39. [ABSTRACT FROM AUTHOR]

The studies about the seven-coordinate iron and manganese complexes with the acyclic and rigid [H.sub.2]dapsox (2,6-diacetylpyridinebis(semioxamazide)) ligand which demonstrate their ability to catalytically decompose superoxide is presented.