Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

• MeSH
• Antioxidants metabolism   MeSH
• Bioaccumulation MeSH
• Environmental Pollutants toxicity   MeSH
• Humans MeSH
• Oxidative Stress * drug effects   MeSH
• Metals, Heavy * toxicity   MeSH
• Environmental Exposure adverse effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The growth and accumulation of active ingredients of Angelica sinensis were affected by rhizosphere soil microbial communities and soil environmental factors. However, the correlationship between growth and active ingredients and soil biotic and abiotic factors is still unclear. This study explored rhizosphere soil microbial community structures, soil physicochemical properties, enzyme activities, and their effects on the growth and active ingredient contents of A. sinensis in three principal cropping areas. Results indicated that the growth indices, ligustilide, ferulic acid contents, and soil environmental factors varied in cropping areas. Pearson correlation analysis revealed that the growth of A. sinensis was affected by organic matter, total nitrogen, total phosphorus, and available phosphorus; ferulic acid and ligustilide accumulation were related to soil catalase and alkaline phosphatase activities, respectively. Illumina MiSeq sequencing showed that the genera Mortierella and Conocybe were the dominant fungal communities, and Sphingomonas, Pseudomonas, Bryobacter, and Lysobacter were the main bacterial communities associated with the rhizosphere soil. Kruskal-Wallis one-way ANOVA and Spearman correlation conjoint analysis demonstrated a significant positive correlation (p < 0.001) among the composition of the rhizosphere microbial communities at all three sampling sites. The growth and active ingredient accumulation of A. sinensis not only was significantly susceptible to the bacterial communities of Sphingomonas, Epicoccum, Marivita, Muribaculum, and Gemmatimonas but also were significantly influenced by the fungal communities of Inocybe, Septoria, Tetracladium, and Mortierella (p < 0.05). Our findings provide a scientific basis for understanding the relationship between the growth and active ingredients in A. sinensis and their corresponding rhizosphere soil microbial communities, soil physicochemical properties, and enzyme activities.

• MeSH
• Angelica sinensis * growth & development   chemistry   microbiology   MeSH
• Bacteria classification   genetics   isolation & purification   MeSH
• Nitrogen analysis   MeSH
• Phosphorus analysis   MeSH
• Fungi classification   genetics   isolation & purification   MeSH
• Microbiota * MeSH
• Soil chemistry   MeSH
• Soil Microbiology * MeSH
• Rhizosphere * MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• China MeSH

Developing bioinspired materials to convert sunlight into electricity efficiently is paramount for sustainable energy production. Fluorescent proteins are promising candidates as photoactive materials due to their high fluorescence quantum yield and absorption extinction coefficients in aqueous media. However, developing artificial bioinspired photosynthetic systems requires a detailed understanding of molecular interactions and energy transfer mechanisms in the required operating conditions. Here, the supramolecular self-assembly and photophysical properties of fluorescent proteins complexed with organic dyes are investigated in aqueous media. Supercharged mGreenLantern protein, mutated to have a charge of +22, is complexed together with anionic zinc phthalocyanines having 4 or 16 carboxylate groups. The structural characterization reveals a strong electrostatic interaction between the moieties, accompanied by partial conformational distortion of the protein structure, yet without compromising the mGreenLantern chromophore integrity as suggested by the lack of emission features related to the neutral form of the chromophore. The self-assembled biohybrid shows a total quenching of protein fluorescence, in favor of an energy transfer process from the protein to the phthalocyanine, as demonstrated by fluorescence lifetime and ultrafast transient absorption measurements. These results provide insight into the rich photophysics of fluorescent protein-dye complexes, anticipating their applicability as water-based photoactive materials.

• MeSH
• Anions chemistry   MeSH
• Fluorescent Dyes chemistry   MeSH
• Spectrometry, Fluorescence MeSH
• Indoles * chemistry   metabolism   MeSH
• Isoindoles MeSH
• Luminescent Proteins * chemistry   metabolism   MeSH
• Organometallic Compounds * chemistry   metabolism   MeSH
• Energy Transfer MeSH
• Zinc Compounds MeSH
• Publication type
• Journal Article MeSH

Vitamin B12, cobalamin, is indispensable for humans owing to its participation in two biochemical reactions: the conversion of l-methylmalonyl coenzyme A to succinyl coenzyme A, and the formation of methionine by methylation of homocysteine. Eukaryotes, encompassing plants, fungi, animals and humans, do not synthesise vitamin B12, in contrast to prokaryotes. Humans must consume it in their diet. The most important sources include meat, milk and dairy products, fish, shellfish and eggs. Due to this, vegetarians are at risk to develop a vitamin B12 deficiency and it is recommended that they consume fortified food. Vitamin B12 behaves differently to most vitamins of the B complex in several aspects, e.g. it is more stable, has a very specific mechanism of absorption and is stored in large amounts in the organism. This review summarises all its biological aspects (including its structure and natural sources as well as its stability in food, pharmacokinetics and physiological function) as well as causes, symptoms, diagnosis (with a summary of analytical methods for its measurement), prevention and treatment of its deficiency, and its pharmacological use and potential toxicity.

• MeSH
• Diet, Vegetarian MeSH
• Diet MeSH
• Food, Fortified MeSH
• Humans MeSH
• Vitamin B 12 Deficiency * diagnosis   prevention & control   drug therapy   etiology   MeSH
• Vitamin B 12 * pharmacokinetics   chemistry   metabolism   therapeutic use   physiology   adverse effects   administration & dosage   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cieľom štúdie je overenie psychometrických vlastností škály CAV, určenej na mapovanie skúseností s kyberagresiou a kyberviktimizáciou. Nástroj je tvorený 24 položkami rozdelenými do dvoch subškál: Kyberagresia (CAV-CB; 12 položiek) a Kyberviktimizácia (CAV-CV; 12 položiek). Výskumný súbor pozostával z N = 5 159 respondentov/tiek vo veku od 14 do 18 rokov (M = 16,06; SD = 1,159), pričom 51,3 % tvorili chlapci a 48,7 % dievčatá. Na overenie faktorovej štruktúry bola použitá konfirmačná faktorová analýza (CFA), aplikovaná metódou DWLS s robustnou korekciou, pričom posudzované boli štandardné indexy zhody. Na základe výsledkov analýz bol podporený dvojfaktorový model: χ2 (251) = 530,064; p < 0,001; CFI = 0,993; TLI = 0,992; RMSEA = 0,016 (90% CI: 0,014 – 0,018). Analýza invariancie merania bola vykonaná vzhľadom na rod a vek, pričom testované boli konfigurálna, metrická, skalárna a striktná invariancia. Hodnoty testov invariancie merania pri porovnaní podľa rodu a veku boli konzistentné so všetkými modelmi invariancie, čo umožňuje porovnávanie skóre medzi skupinami. Reliabilita škály bola hodnotená pomocou Cronbachovho α a McDonaldovho ω, pričom faktory mali uspokojivú vnútornú konzistenciu (CAV-CB: α = 0,907, ω = 0,908; CAV-CV: α = 0,920, ω = 0,921). Kyberagresia signifikantne korelovala s kyberviktimizáciou (r = 0,699; p < 0,001), čo naznačuje vzájomnú súvislosť medzi oboma faktormi. Percentilová distribúcia skóre v populácii dospievajúcich umožnila stanoviť orientačné normo-referenčné hranice pre subškály CAV-CB a CAV-CV, na základe ktorých bola vytvorená trojstupňová klasifikácia úrovne expozície určená na výskumné a preventívne účely.

The aim of this study was to evaluate the psychometric properties of the Cyber-Aggression and Cyber- Victimization Scale (CAV), which was developed to assess adolescents’ experiences with cyber-aggression and cyber-victimisation. The instrument consists of 24 items divided into two subscales: Cyber-aggression (CAV-CB; 12 items) and Cyber-victimization (CAV-CV; 12 items). The research sample comprised N = 5,159 adolescents aged 14 to 18 years (M = 16.06; SD = 1.159), with 51.3%boys and 48.7%girls. Confirmatory factor analysis (CFA) was used to assess the factor structure, employing the DWLS method with robust corrections and evaluating standard goodness-of-fit indices. The analysis supported a two-factor model: χ2 (251) = 530.064; p < .001; CFI = .993; TLI = .992; RMSEA = .016 (90% CI: .014–.018). Measurement invariance was tested across gender and age groups, including configural, metric, scalar, and strict invariance. Invariance testing results indicated acceptable fit for all models, supporting the comparability of scores across groups. Reliability was assessed using Cronbach’s alpha and McDonald’s omega, both indicating satisfactory internal consistency (CAV-CB: α = .907, ω = .908; CAV-CV: α = .920, ω = .921). Cyberaggression showed a significant correlation with cybervictimization (r = .699; p < .001), indicating a substantial relationship between the two constructs. The percentile distribution of scores in the adolescent population made it possible to establish provisional norm-referenced cut-off points for the CAV-CB and CAV- CV subscales, based on which a three-level classification of exposure was created for research and preventive purposes.

In this study, lactic acid bacteria (LAB) isolation from fermented foods and molecular identification using magnetic bead technology were performed. And then exopolysaccharide (EPS) production possibility was tested in agar medium, and the positive ones were selected for the next step. The bacteria that could produce higher carbohydrate level were grown in MRS medium fortified with whey and pumpkin waste. In our study, 19 different LAB species were identified from fermented products collected from different places in Hatay (Türkiye) province. In molecular identification, universal primer pairs, p806R/p8FPL, and PEU7/DG74 were used for PCR amplification. After that, PCR products purified using paramagnetic bead technology were sequenced by the Sanger sequencing method. The dominant species, 23.8% of the isolates, were identified as Lactiplantibacillus plantarum. As a technological property of LAB, exopolysaccharide production capability of forty-two LAB isolate was tested in agar medium, and after eleven isolates were selected as positive. Two LAB (Latilactobacillus curvatus SHA2-3B and Loigolactobacillus coryniformis SHA6-3B) had higher EPS production capability when they were grown in MRS broth fortified with pumpkin waste and whey. The highest EPS content (1750 mg/L glucose equivalent) was determined in Loigolactobacillus coryniformis SHA6-3B grown in MRS broth fortified with 10% pumpkin waste. Besides the produced EPS samples were validated with FTIR and SEM methods.

• MeSH
• Polysaccharides, Bacterial * biosynthesis   metabolism   MeSH
• Cucurbita microbiology   MeSH
• Fermentation MeSH
• Fermented Foods * microbiology   MeSH
• Phylogeny MeSH
• Culture Media chemistry   MeSH
• Lactobacillales * isolation & purification   classification   genetics   metabolism   MeSH
• Waste Products * analysis   MeSH
• Food Microbiology * MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Whey MeSH
• Publication type
• Journal Article MeSH

L eishmaniasis is a prevalent disease that impacts 98 countries and territories, mainly in Africa, Asia, and South America. It can cause substantial illness and death, particularly in its visceral manifestation that can be specifically targeted in the development of medications to combat leishmaniasis. This study has found natural compounds with possible inhibitory activity against APX using a reliable and accurate QSAR model. Despite the severe side effects of current treatments and the absence of an effective vaccination, these compounds show promise as a potential treatment for the disease. Nine hit compounds were found, and subsequent molecular docking was performed. Estradiol cypionate showed the lowest binding energy (- 10.5 kcal/mol), thus showing the strongest binding, and also had the strongest binding affinity, with a ΔGTotal of - 26.31 ± 3.01 kcal/mol, second only to the control molecule. Additionally, three hits viz. cloxacillin-sodium (- 16.57 ± 2.89 kcal/mol), cinchonidine (- 16.04 ± 3.27 kcal/mol), and quinine hydrochloride dihydrate (13.38 ± 1.06 kcal/mol) also showed significant binding affinity. Multiple interactions between drugs and active site residues demonstrated a substantial binding affinity with the target protein. The identified compounds exhibited drug-like effects and were orally bioavailable based on their ADME-toxicology features. Overall, estradiol cypionate, cloxacillin sodium, cinchonidine, and quinine hydrochloride dihydrate all exhibited inhibitory effects on the APX enzyme of Leishmania donovani. These results suggest that further investigation is needed to explore the potential of developing novel anti-leishmaniasis drugs using these compounds.

• MeSH
• Antiprotozoal Agents * pharmacology   chemistry   MeSH
• Enzyme Inhibitors * pharmacology   chemistry   MeSH
• Quantitative Structure-Activity Relationship MeSH
• Leishmaniasis * drug therapy   MeSH
• Humans MeSH
• Molecular Docking Simulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.

• MeSH
• Apoptosis * drug effects   MeSH
• Cell Cycle drug effects   MeSH
• Histone Deacetylases metabolism   MeSH
• Histone Deacetylase Inhibitors * pharmacology   chemical synthesis   chemistry   MeSH
• Hydroxamic Acids * pharmacology   chemical synthesis   chemistry   MeSH
• Coumaric Acids * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemical synthesis   chemistry   MeSH
• Drug Screening Assays, Antitumor MeSH
• Molecular Docking Simulation MeSH
• THP-1 Cells MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Introduction: The ability to self-care is considered essential in heart failure management. One of the valid and reliable instruments that allow the measurement of heart failure self-care behaviour is the European Heart Failure Self-Care Behaviour Scale (EHFScBS-9). Objective: To adapt and assess psychometric properties of the Slovak version of the EHFScBS-9. Methods: In this descriptive validation study, 122 Slovak heart failure patients completed the EHFScBS-9, the Cardiac Self-Efficacy Questionnaire (CSEQ), and Personal Well-being Index (PWI). Item analysis, confirmatory factor analysis (CFA), and convergent and discriminant validity were evaluated. Cronbach's alpha was calculated to assess reliability. Results: The results of CFA confirmed a good fit of the two- respectively three-factor structure of the Slovak EHFScBS-9. Convergent validity was confirmed by positive correlation between the Slovak EHFScBS-9 and the CSEQ. Discriminant validity was supported by poor correlation between EHFScBS-9 and PWI. Cronbach's alpha coefficient for the total EHFScBS-9 instrument of Slovak version was 0.77. Conclusion: The Slovak version of the EHFScBS-9 instrument is valid and reliable to measure self-care behaviour in heart failure patients.

• MeSH
• Factor Analysis, Statistical MeSH
• Middle Aged MeSH
• Humans MeSH
• Self Care methods   psychology   MeSH
• Surveys and Questionnaires MeSH
• Psychometrics * methods   MeSH
• Reproducibility of Results MeSH
• Aged MeSH
• Heart Failure * psychology   MeSH
• Statistics as Topic MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Validation Study MeSH
• Geographicals
• Slovakia MeSH

Medical research is at the forefront of addressing pressing global challenges, including preventing and treating cardiovascular, autoimmune, and oncological diseases, neurodegenerative disorders, and the growing resistance of pathogens to antibiotics. Understanding the molecular mechanisms underlying these diseases, using advanced medical approaches and cutting-edge technologies, structure-based drug design, and personalized medicine, is critical for developing effective therapies, specifically anticancer treatments. Background/Objectives: One of the key drivers of cancer at the cellular level is the abnormal activity of protein enzymes, specifically serine, threonine, or tyrosine residues, through a process known as phosphorylation. While tyrosine kinase-mediated phosphorylation constitutes a minor fraction of total cellular phosphorylation, its dysregulation is critically linked to carcinogenesis and tumor progression. Methods: Small-molecule inhibitors, such as imatinib or erlotinib, are designed to halt this process, restoring cellular equilibrium and offering targeted therapeutic approaches. However, challenges persist, including frequent drug resistance and severe side effects associated with these therapies. Nanomedicine offers a transformative potential to overcome these limitations. Results: By leveraging the unique properties of nanomaterials, it is possible to achieve precise drug delivery, enhance accumulation at target sites, and improve therapeutic efficacy. Examples include nanoparticle-based delivery systems for TKIs and the combination of nanomaterials with photothermal or photodynamic therapies to enhance treatment effectiveness. Combining nanomedicine with traditional treatments holds promise and perspective for synergistic and more effective cancer management. Conclusions: This review delves into recent advances in understanding tyrosine kinase activity, the mechanisms of their inhibition, and the innovative integration of nanomedicine to revolutionize cancer treatment strategies.

• Publication type
• Journal Article MeSH
• Review MeSH