Pub Date : 2023-11-21DOI: 10.1007/s10534-023-00560-3
David A. Geier, Mark R. Geier
Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18–20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15–20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.
{"title":"Reductions in plasma and urine mercury concentrations following N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial","authors":"David A. Geier, Mark R. Geier","doi":"10.1007/s10534-023-00560-3","DOIUrl":"10.1007/s10534-023-00560-3","url":null,"abstract":"<div><p>Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18–20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15–20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, the metabolic adjustments performed by maize (Zea mays L.) seminal roots exposed to 25 µM Cd2+ or 25 µM Cu2+ at pre-emergence are compared, focusing on the proteomic changes after metal exposure. Root width was increased, and root length was decreased after 72 h of metal treatment. Both metals induced H2O2 accumulation and lipid peroxidation in the root tip. These changes were accompanied by increases in lipoxygenase activity and 4-hydroxy-2-nonenal content. NMR spectroscopy revealed that the abundance of 38 water-soluble metabolites was significantly modified by Cd and Cu exposure; this set of metabolites comprised carboxylic acids, amino acids, carbohydrates, and unidentified phenolic compounds. Linoleic acid content significantly decreased in Cu-treated samples. The total amount of proteins detected in maize root apexes was 2,171. Gene ontology enrichment analysis of the differentially accumulated proteins was performed to detect pathways probably affected by metal additions. Both metals altered redox homeostasis, up-regulated oxylipins biosynthetic process, and shifted metabolism towards the oxidative pentose-phosphate in the root apexes. However, the methionine salvage pathway appears as a key metabolic module only under Cd stress. The integrative analysis carried out in this study suggests that most molecular features behind the reprogramming of maize root tips to cope with cadmium and copper toxicity are common, but some are not.
{"title":"Cadmium and copper-induced metabolic and proteomic changes in the root tip during early maize growth","authors":"Carolina Lucila Matayoshi, Odalis Maholi Jiménez Guaman, Marcos Leopoldo Esteso, Micaela Pavoni, Martín Arán, Liliana Beatriz Pena, Susana Mabel Gallego","doi":"10.1007/s10534-023-00557-y","DOIUrl":"10.1007/s10534-023-00557-y","url":null,"abstract":"<div><p>In this study, the metabolic adjustments performed by maize (<i>Zea mays</i> L.) seminal roots exposed to 25 µM Cd<sup>2+</sup> or 25 µM Cu<sup>2+</sup> at pre-emergence are compared, focusing on the proteomic changes after metal exposure. Root width was increased, and root length was decreased after 72 h of metal treatment. Both metals induced H<sub>2</sub>O<sub>2</sub> accumulation and lipid peroxidation in the root tip. These changes were accompanied by increases in lipoxygenase activity and 4-hydroxy-2-nonenal content. NMR spectroscopy revealed that the abundance of 38 water-soluble metabolites was significantly modified by Cd and Cu exposure; this set of metabolites comprised carboxylic acids, amino acids, carbohydrates, and unidentified phenolic compounds. Linoleic acid content significantly decreased in Cu-treated samples. The total amount of proteins detected in maize root apexes was 2,171. Gene ontology enrichment analysis of the differentially accumulated proteins was performed to detect pathways probably affected by metal additions. Both metals altered redox homeostasis, up-regulated oxylipins biosynthetic process, and shifted metabolism towards the oxidative pentose-phosphate in the root apexes. However, the methionine salvage pathway appears as a key metabolic module only under Cd stress. The integrative analysis carried out in this study suggests that most molecular features behind the reprogramming of maize root tips to cope with cadmium and copper toxicity are common, but some are not.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-16DOI: 10.1007/s10534-023-00555-0
Ivana Timková, Lenka Maliničová, Lea Nosáľová, Mariana Kolesárová, Zuzana Lorková, Nikola Petrová, Peter Pristaš, Jana Kisková
The subsurface mine environments characterized by high levels of toxic metals and low nutrient availability represent an extreme threat to bacterial persistence. In recent study, the genomic analysis of the Acinetobacter johnsonii strain RB2-047 isolated from the Rozália Gold Mine in Slovakia was performed. As expected, the studied isolate showed a high level of heavy metal tolerance (minimum inhibitory concentrations were 500 mg/L for copper and nickel, 1,500 mg/L for lead, and 250 mg/L for zinc). The RB2-047 strain also showed noticeable resistance to several antibiotics (ampicillin, kanamycin, chloramphenicol, tetracycline and ciprofloxacin). The genomic composition analysis demonstrated a low number of antibiotic and metal resistance coding genes, but a high occurrence of efflux transporter genes located on the bacterial chromosome. The experimental inhibition of efflux pumps resulted in decreased tolerance to Zn and Ni (but not to Cu and Pb) and to all antibiotics tested. In addition, the H33342 dye-accumulation assay confirmed the high efflux activity in the RB2-047 isolate. These findings showed the important role of efflux pumps in the adaptation of Acinetobacter johsonii strain RB2-047 to metal polluted mine environment as well as in development of multi-antibiotic resistance.
{"title":"Genomic insights into the adaptation of Acinetobacter johnsonii RB2-047 to the heavy metal-contaminated subsurface mine environment","authors":"Ivana Timková, Lenka Maliničová, Lea Nosáľová, Mariana Kolesárová, Zuzana Lorková, Nikola Petrová, Peter Pristaš, Jana Kisková","doi":"10.1007/s10534-023-00555-0","DOIUrl":"10.1007/s10534-023-00555-0","url":null,"abstract":"<div><p>The subsurface mine environments characterized by high levels of toxic metals and low nutrient availability represent an extreme threat to bacterial persistence. In recent study, the genomic analysis of the <i>Acinetobacter johnsonii</i> strain RB2-047 isolated from the Rozália Gold Mine in Slovakia was performed. As expected, the studied isolate showed a high level of heavy metal tolerance (minimum inhibitory concentrations were 500 mg/L for copper and nickel, 1,500 mg/L for lead, and 250 mg/L for zinc). The RB2-047 strain also showed noticeable resistance to several antibiotics (ampicillin, kanamycin, chloramphenicol, tetracycline and ciprofloxacin). The genomic composition analysis demonstrated a low number of antibiotic and metal resistance coding genes, but a high occurrence of efflux transporter genes located on the bacterial chromosome. The experimental inhibition of efflux pumps resulted in decreased tolerance to Zn and Ni (but not to Cu and Pb) and to all antibiotics tested. In addition, the H33342 dye-accumulation assay confirmed the high efflux activity in the RB2-047 isolate. These findings showed the important role of efflux pumps in the adaptation of <i>Acinetobacter johsonii</i> strain RB2-047 to metal polluted mine environment as well as in development of multi-antibiotic resistance.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-16DOI: 10.1007/s10534-023-00554-1
Tao Ke, André Rajoo, Alexey A. Tinkov, Anatoly V. Skalny, Yousef Tizabi, Joao B. T. Rocha, Aaron B. Bowman, Michael Aschner
Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32–47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity. The excretion through feces is a major route in the demethylation of MeHg. Accumulating evidence suggests that the intestinal microbiota plays an important role in the demethylation of MeHg, thereby protecting the host from neurotoxic effects. Here, we discuss recent developments on the role of intestinal microbiota in MeHg metabolism, based on in vitro cell culture experiments, experimental animal studies and human investigations. Demethylation by intestinal bacteria is the rate-limiting step in MeHg metabolism and elimination. The identity of bacteria strains responsible for this biotransformation is currently unknown; however, the non-homogenous distribution of intestinal microbiota may lead to different demethylation rates in the intestinal tract. The maintenance of intestinal barrier function by intestinal microbiota may afford protection against MeHg-induced neurotoxicity, which warrant future investigations. We also discuss studies investigating the effects of MeHg exposure on the population structural stability of intestinal microbiota in several host species. Although this is an emerging area in metal toxicity, current research suggests that a change in certain phyla in the intestinal microbiota may indicate MeHg overexposure.
{"title":"Intestinal microbiota protects against methylmercury-induced neurotoxicity","authors":"Tao Ke, André Rajoo, Alexey A. Tinkov, Anatoly V. Skalny, Yousef Tizabi, Joao B. T. Rocha, Aaron B. Bowman, Michael Aschner","doi":"10.1007/s10534-023-00554-1","DOIUrl":"10.1007/s10534-023-00554-1","url":null,"abstract":"<div><p>Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32–47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity. The excretion through feces is a major route in the demethylation of MeHg. Accumulating evidence suggests that the intestinal microbiota plays an important role in the demethylation of MeHg, thereby protecting the host from neurotoxic effects. Here, we discuss recent developments on the role of intestinal microbiota in MeHg metabolism, based on in vitro cell culture experiments, experimental animal studies and human investigations. Demethylation by intestinal bacteria is the rate-limiting step in MeHg metabolism and elimination. The identity of bacteria strains responsible for this biotransformation is currently unknown; however, the non-homogenous distribution of intestinal microbiota may lead to different demethylation rates in the intestinal tract. The maintenance of intestinal barrier function by intestinal microbiota may afford protection against MeHg-induced neurotoxicity, which warrant future investigations. We also discuss studies investigating the effects of MeHg exposure on the population structural stability of intestinal microbiota in several host species. Although this is an emerging area in metal toxicity, current research suggests that a change in certain phyla in the intestinal microbiota may indicate MeHg overexposure.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-10DOI: 10.1007/s10534-023-00552-3
Ayub Shaik, Vani Kondaparthy, Alia Begum, Ameena Husain, Tejasree Chinnagalla
Drug-protein interactions are essential since most administered drugs bind abundantly and reversibly to serum albumin and are delivered mainly as a complex with protein. The nature and strength of drug-protein interactions have a big impact on how a drug works biologically. The binding parameters are useful in studying the pharmacological response of drugs and the designing of dosage forms. Serum albumin is regarded as optimal model for in vitro research on drug-protein interaction since it is the main protein that binds medicines and other physiological components. In this perspective, binary complex have been synthesized and characterized, from vanadium metal and acetylacetone(4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione). Imidazole, 2-Methyl-imidazole, and 2-Ethyl-imidazole auxiliary ligands were employed for the synthesis of ternary complexes. Additionally, UV absorption and fluorescence emission spectroscopy were used to examine the binding interactions between vanadium complexes and Bovine Serum Albumin. The outcomes of the binding studies and spectral approaches were in strong agreement with one another. These complexes upon inoculation into diabetes-induced Wistar rats stabilized their serum glucose levels within 3 days. From various studies, it was discovered that the ordering of glucose-lowering actions of these metal complexes were equivalent. The vanadium ternary metal complex derived from (4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione) and imidazole as ligands is the best among the other metal vanadium complexes.
{"title":"Novel vanadyl complexes synthesis, characterization and interactions with bovine serum albumin–effects on STZ- diabetes rats","authors":"Ayub Shaik, Vani Kondaparthy, Alia Begum, Ameena Husain, Tejasree Chinnagalla","doi":"10.1007/s10534-023-00552-3","DOIUrl":"10.1007/s10534-023-00552-3","url":null,"abstract":"<div><p>Drug-protein interactions are essential since most administered drugs bind abundantly and reversibly to serum albumin and are delivered mainly as a complex with protein. The nature and strength of drug-protein interactions have a big impact on how a drug works biologically. The binding parameters are useful in studying the pharmacological response of drugs and the designing of dosage forms. Serum albumin is regarded as optimal model for in vitro research on drug-protein interaction since it is the main protein that binds medicines and other physiological components. In this perspective, binary complex have been synthesized and characterized, from vanadium metal and acetylacetone(4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione). Imidazole, 2-Methyl-imidazole, and 2-Ethyl-imidazole auxiliary ligands were employed for the synthesis of ternary complexes. Additionally, UV absorption and fluorescence emission spectroscopy were used to examine the binding interactions between vanadium complexes and Bovine Serum Albumin. The outcomes of the binding studies and spectral approaches were in strong agreement with one another. These complexes upon inoculation into diabetes-induced Wistar rats stabilized their serum glucose levels within 3 days. From various studies, it was discovered that the ordering of glucose-lowering actions of these metal complexes were equivalent. The vanadium ternary metal complex derived from (4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione) and imidazole as ligands is the best among the other metal vanadium complexes.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-08DOI: 10.1007/s10534-023-00546-1
Jai Devi, Binesh Kumar, Amit Dubey, Aisha Tufail, Ankit Boora
Malaria, a relentless and ancient adversary, continues to cast its shadow over vast swathes of the globe, afflicting millions of people and have a heavy toll on human health and well-being. Despite substantial progress in the fight against this parasitic disease in recent decades, malaria still persists as a substantial global health concern, especially in some specific region which have limited resources and vulnerable populations. Thus, to ascertain an combating agent for malaria and its associated dysfunction, 4-(4-ethylphenyl)-3-thiosemicarbazide and benzaldehydes based two new thiosemicarbazone ligands (1–2) and their cobalt(II), nickel(II), copper(II), zinc(II) metal complexes (3–10) were synthesized in the present research work. The synthesized compounds were comprehensive characterized through spectral and physical investigations, demonstrating octahedral stereochemistry of the complexes. Further, the antimalarial and antioxidant potential of the compounds (1–10) were analyzed by micro assay and DPPH assay protocols, respectively, to examine the therapeutic aspect of the compounds. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. The complexes (5), (6), (10) shows significant efficiency for malarial and oxidant dysfunctions whereas Zn(II) complex (6) exhibit highest potency with 1.02 ± 0.07 and 2.28 ± 0.05 µM IC50 value. Furthermore, to support the highest antimalarial potency of the (3–6) complexes and their associated ligand (1), the computational studies like molecular docking, DFT, MESP and ADMET analysis were executed which were supported the biological efficacy of the complex (6) by providing numerous parameters like binding interaction electronegativity, electrophilicity, HOMO value and electron density.
{"title":"Exploring the antimalarial and antioxidant efficacy of transition metal(II) chelates of thiosemicarbazone ligands: spectral investigations, molecular docking, DFT, MESP and ADMET","authors":"Jai Devi, Binesh Kumar, Amit Dubey, Aisha Tufail, Ankit Boora","doi":"10.1007/s10534-023-00546-1","DOIUrl":"10.1007/s10534-023-00546-1","url":null,"abstract":"<div><p>Malaria, a relentless and ancient adversary, continues to cast its shadow over vast swathes of the globe, afflicting millions of people and have a heavy toll on human health and well-being. Despite substantial progress in the fight against this parasitic disease in recent decades, malaria still persists as a substantial global health concern, especially in some specific region which have limited resources and vulnerable populations. Thus, to ascertain an combating agent for malaria and its associated dysfunction, 4-(4-ethylphenyl)-3-thiosemicarbazide and benzaldehydes based two new thiosemicarbazone ligands (1–2) and their cobalt(II), nickel(II), copper(II), zinc(II) metal complexes (3–10) were synthesized in the present research work. The synthesized compounds were comprehensive characterized through spectral and physical investigations, demonstrating octahedral stereochemistry of the complexes. Further, the antimalarial and antioxidant potential of the compounds (1–10) were analyzed by micro assay and DPPH assay protocols, respectively, to examine the therapeutic aspect of the compounds. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. The complexes (5), (6), (10) shows significant efficiency for malarial and oxidant dysfunctions whereas Zn(II) complex (6) exhibit highest potency with 1.02 ± 0.07 and 2.28 ± 0.05 µM IC<sub>50</sub> value. Furthermore, to support the highest antimalarial potency of the (3–6) complexes and their associated ligand (1), the computational studies like molecular docking, DFT, MESP and ADMET analysis were executed which were supported the biological efficacy of the complex (6) by providing numerous parameters like binding interaction electronegativity, electrophilicity, HOMO value and electron density.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-06DOI: 10.1007/s10534-023-00547-0
Emma Baglini, Lorenzo Chiaverini, Iogann Tolbatov, Sabrina Taliani, Federico Da Settimo, Diego La Mendola, Elisabetta Barresi, Tiziano Marzo
Ovarian cancer (OC) is a lethal gynecologic cancer in industrialized countries. Treatments for OC include the surgical removal and chemotherapy. In the last decades, improvements have been made in the surgery technologies, drug combinations and administration protocols, and in diagnosis. However, mortality from OC is still high owing to recurrences and insurgence of drug resistance. Accordingly, it is urgent the development of novel agents capable to effectively target OC. In this respect, tyrosine kinase inhibitors (TKIs) may play an important role. Most of TKIs developed and tested so far are organic. However, owing to their chemical versatility, also metals can be exploited to design selective and potent TKIs. We provide a short and easy-to-read overview on the main organic TKIs with a summary of those that entered clinical trials. Additionally, we describe the potential of metal-based TKIs, focusing on this overlooked family of compounds that may significantly contribute towards the concept of precision-medicine.
{"title":"Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity—a perspective overview","authors":"Emma Baglini, Lorenzo Chiaverini, Iogann Tolbatov, Sabrina Taliani, Federico Da Settimo, Diego La Mendola, Elisabetta Barresi, Tiziano Marzo","doi":"10.1007/s10534-023-00547-0","DOIUrl":"10.1007/s10534-023-00547-0","url":null,"abstract":"<div><p>Ovarian cancer (OC) is a lethal gynecologic cancer in industrialized countries. Treatments for OC include the surgical removal and chemotherapy. In the last decades, improvements have been made in the surgery technologies, drug combinations and administration protocols, and in diagnosis. However, mortality from OC is still high owing to recurrences and insurgence of drug resistance. Accordingly, it is urgent the development of novel agents capable to effectively target OC. In this respect, tyrosine kinase inhibitors (TKIs) may play an important role. Most of TKIs developed and tested so far are organic. However, owing to their chemical versatility, also metals can be exploited to design selective and potent TKIs. We provide a short and easy-to-read overview on the main organic TKIs with a summary of those that entered clinical trials. Additionally, we describe the potential of metal-based TKIs, focusing on this overlooked family of compounds that may significantly contribute towards the concept of precision-medicine.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-02DOI: 10.1007/s10534-023-00549-y
Heloisa F. Frota, Carolline M. A. Lorentino, Pedro F. Barbosa, Lívia S. Ramos, Iuri C. Barcellos, Lucas Giovanini, Lucieri O. P. Souza, Simone S. C. Oliveira, Olufunso O. Abosede, Adeniyi S. Ogunlaja, Matheus M. Pereira, Marta H. Branquinha, André L. S. Santos
Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)2phen(H2O).5H2O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 μg/mL and MFCs from 15.62 to 62.5 μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 μg/mL for 5 days. After 24 h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600 μg/mL), with the 50% cytotoxic concentration calculated as 776.2 μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.
{"title":"Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species","authors":"Heloisa F. Frota, Carolline M. A. Lorentino, Pedro F. Barbosa, Lívia S. Ramos, Iuri C. Barcellos, Lucas Giovanini, Lucieri O. P. Souza, Simone S. C. Oliveira, Olufunso O. Abosede, Adeniyi S. Ogunlaja, Matheus M. Pereira, Marta H. Branquinha, André L. S. Santos","doi":"10.1007/s10534-023-00549-y","DOIUrl":"10.1007/s10534-023-00549-y","url":null,"abstract":"<div><p><i>Candida</i> spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-<i>Candida</i> drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of <i>Candida albicans</i> and <i>Candida tropicalis.</i> Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)<sub>2</sub>phen(H<sub>2</sub>O).5H<sub>2</sub>O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant <i>Candida</i> species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 μg/mL and MFCs from 15.62 to 62.5 μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using <i>Galleria mellonella</i> and <i>Tenebrio molitor</i>. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 μg/mL for 5 days. After 24 h of treatment, <i>G. mellonella</i> larvae exhibited high survival rates even when exposed to high doses of CTP (600 μg/mL), with the 50% cytotoxic concentration calculated as 776.2 μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each <i>Candida</i> species. These findings suggest that CTP could serve as a potential drug to treat infections caused by <i>Candida</i> species resistant to clinically available antifungals.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-02DOI: 10.1007/s10534-023-00548-z
Nasim Rezaeimanesh, Pegah Rafiee, Roghayyeh Saeedi, Pegah Khosravian, Mohammad Ali Sahraian, Sharareh Eskandarieh, Abdorreza Naser Moghadasi, Soodeh Razeghi Jahromi
The prevalence of cognitive impairment in multiple sclerosis (MS) patients is estimated to be approximately 40–60%. There is an increasing body of evidence regarding the impact of both selenium and crocin as antioxidant agents on cognitive function. In the present study, for the first time, we investigated the effect of crocin-selenium nanoparticles (Cor@SeNs) on cognitive function and oxidative stress markers in MS patients. A triple-blind randomized clinical trial was conducted among 60 MS patients. The participants were randomly divided in a 1:1 ratio to either the Cor@SeNs or placebo group, employing block randomization. During the course of 12 weeks, the participants received Cor@SeNs capsules, containing 5.74 mg crocin and 55 mcg Selenium, or placebo capsules. Cognition assessed using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Serum levels of total antioxidant capacity (TAC), glutathione reductase (GR) activity and malondialdehyde (MDA) determined by colorimetric kits. Data analysis was performed in SPSS, version 26. P < 0.05 was considered as the significant range. The mean ± SD of TAC change was 0.03 ± 0.07 mM vs. − 0.03 ± 0.09 mM in intervention and placebo groups, respectively (Time × group effect P: 0.01; effect size: 0.10). The time effect of intervention on the California Verbal Learning Test second edition (CVLT-II) (P < 0.01; effect size: 0.29), CVLT-II-delay (P < 0.01; effect size: 0.29), and the Symbol Digit Modalities Test (SDMT) (P < 0.01; effect size: 0.18) was increasing and significant. In addition, the time effect of intervention on GR activity was significant and decreasing in both groups (P < 0.01; effect size: 0.20). Our results suggested a significant effect of the Cor@SeNs intervention in improving TAC. We also observed a significant improvement in cognitive function in both groups during our study. However, although not statistically significant, a higher amount of change in cognitive function and serum antioxidant markers was noted in the Cor@SeNs group compared to the placebo group. This is the first study on this nano product with low dose of selenium and crocin. More investigations with longer duration and varied doses are suggested.
{"title":"The effect of crocin-selenium nanoparticles on the cognition and oxidative stress markers of multiple sclerosis patients: a randomized triple-blinded placebo-controlled clinical trial","authors":"Nasim Rezaeimanesh, Pegah Rafiee, Roghayyeh Saeedi, Pegah Khosravian, Mohammad Ali Sahraian, Sharareh Eskandarieh, Abdorreza Naser Moghadasi, Soodeh Razeghi Jahromi","doi":"10.1007/s10534-023-00548-z","DOIUrl":"10.1007/s10534-023-00548-z","url":null,"abstract":"<div><p>The prevalence of cognitive impairment in multiple sclerosis (MS) patients is estimated to be approximately 40–60%. There is an increasing body of evidence regarding the impact of both selenium and crocin as antioxidant agents on cognitive function. In the present study, for the first time, we investigated the effect of crocin-selenium nanoparticles (Cor@SeNs) on cognitive function and oxidative stress markers in MS patients. A triple-blind randomized clinical trial was conducted among 60 MS patients. The participants were randomly divided in a 1:1 ratio to either the Cor@SeNs or placebo group, employing block randomization. During the course of 12 weeks, the participants received Cor@SeNs capsules, containing 5.74 mg crocin and 55 mcg Selenium, or placebo capsules. Cognition assessed using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Serum levels of total antioxidant capacity (TAC), glutathione reductase (GR) activity and malondialdehyde (MDA) determined by colorimetric kits. Data analysis was performed in SPSS, version 26. P < 0.05 was considered as the significant range. The mean ± SD of TAC change was 0.03 ± 0.07 mM vs. − 0.03 ± 0.09 mM in intervention and placebo groups, respectively (Time × group effect P: 0.01; effect size: 0.10). The time effect of intervention on the California Verbal Learning Test second edition (CVLT-II) (P < 0.01; effect size: 0.29), CVLT-II-delay (P < 0.01; effect size: 0.29), and the Symbol Digit Modalities Test (SDMT) (P < 0.01; effect size: 0.18) was increasing and significant. In addition, the time effect of intervention on GR activity was significant and decreasing in both groups (P < 0.01; effect size: 0.20). Our results suggested a significant effect of the Cor@SeNs intervention in improving TAC. We also observed a significant improvement in cognitive function in both groups during our study. However, although not statistically significant, a higher amount of change in cognitive function and serum antioxidant markers was noted in the Cor@SeNs group compared to the placebo group. This is the first study on this nano product with low dose of selenium and crocin. More investigations with longer duration and varied doses are suggested.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-02DOI: 10.1007/s10534-023-00542-5
Mohammad Shiraz, Havza Imtiaz, Ameer Azam, Shamsul Hayat
<div><p>Researchers are swarming to nanotechnology because of its potentially game-changing applications in medicine, pharmaceuticals, and agriculture. This fast-growing, cutting-edge technology is trying different approaches for synthesizing nanoparticles of specific sizes and shapes. Nanoparticles (NPs) have been successfully synthesized using physical and chemical processes; there is an urgent demand to establish environmentally acceptable and sustainable ways for their synthesis. The green approach of nanoparticle synthesis has emerged as a simple, economical, sustainable, and eco-friendly method. In particular, phytoassisted plant extract synthesis is easy, reliable, and expeditious. Diverse phytochemicals present in the extract of various plant organs such as root, leaf, and flower are used as a source of reducing as well as stabilizing agents during production. Green synthesis is based on principles like prevention/minimization of waste, reduction of derivatives/pollution, and the use of safer (or non-toxic) solvent/auxiliaries as well as renewable feedstock. Being free of harsh operating conditions (high temperature and pressure), hazardous chemicals and the addition of external stabilizing or capping agents makes the nanoparticles produced using green synthesis methods particularly desirable. Different metallic nanomaterials are produced using phytoassisted synthesis methods, such as silver, zinc, gold, copper, titanium, magnesium, and silicon. Due to significant differences in physical and chemical properties between nanoparticles and their micro/macro counterparts, their characterization becomes essential. Various microscopic and spectroscopic techniques have been employed for conformational details of nanoparticles, like shape, size, dispersity, homogeneity, surface structure, and inter-particle interactions. UV–visible spectroscopy is used to examine the optical properties of NPs in solution. XRD analysis confirms the purity and phase of NPs and provides information about crystal size and symmetry. AFM, SEM, and TEM are employed for analyzing the morphological structure and particle size of NPs. The nature and kind of functional groups or bioactive compounds that might account for the reduction and stabilization of NPs are detected by FTIR analysis. The elemental composition of synthesized NPs is determined using EDS analysis. Nanoparticles synthesized by green methods have broad applications and serve as antibacterial and antifungal agents. Various metal and metal oxide NPs such as Silver (Ag), copper (Cu), gold (Au), silicon dioxide (SiO<sub>2</sub>), zinc oxide (ZnO), titanium dioxide (TiO<sub>2</sub>), copper oxide (CuO), etc. have been proven to have a positive effect on plant growth and development. They play a potentially important role in the germination of seeds, plant growth, flowering, photosynthesis, and plant yield. The present review highlights the pathways of phytosynthesis of nanoparticles, various techniques used for
{"title":"Phytogenic nanoparticles: synthesis, characterization, and their roles in physiology and biochemistry of plants","authors":"Mohammad Shiraz, Havza Imtiaz, Ameer Azam, Shamsul Hayat","doi":"10.1007/s10534-023-00542-5","DOIUrl":"10.1007/s10534-023-00542-5","url":null,"abstract":"<div><p>Researchers are swarming to nanotechnology because of its potentially game-changing applications in medicine, pharmaceuticals, and agriculture. This fast-growing, cutting-edge technology is trying different approaches for synthesizing nanoparticles of specific sizes and shapes. Nanoparticles (NPs) have been successfully synthesized using physical and chemical processes; there is an urgent demand to establish environmentally acceptable and sustainable ways for their synthesis. The green approach of nanoparticle synthesis has emerged as a simple, economical, sustainable, and eco-friendly method. In particular, phytoassisted plant extract synthesis is easy, reliable, and expeditious. Diverse phytochemicals present in the extract of various plant organs such as root, leaf, and flower are used as a source of reducing as well as stabilizing agents during production. Green synthesis is based on principles like prevention/minimization of waste, reduction of derivatives/pollution, and the use of safer (or non-toxic) solvent/auxiliaries as well as renewable feedstock. Being free of harsh operating conditions (high temperature and pressure), hazardous chemicals and the addition of external stabilizing or capping agents makes the nanoparticles produced using green synthesis methods particularly desirable. Different metallic nanomaterials are produced using phytoassisted synthesis methods, such as silver, zinc, gold, copper, titanium, magnesium, and silicon. Due to significant differences in physical and chemical properties between nanoparticles and their micro/macro counterparts, their characterization becomes essential. Various microscopic and spectroscopic techniques have been employed for conformational details of nanoparticles, like shape, size, dispersity, homogeneity, surface structure, and inter-particle interactions. UV–visible spectroscopy is used to examine the optical properties of NPs in solution. XRD analysis confirms the purity and phase of NPs and provides information about crystal size and symmetry. AFM, SEM, and TEM are employed for analyzing the morphological structure and particle size of NPs. The nature and kind of functional groups or bioactive compounds that might account for the reduction and stabilization of NPs are detected by FTIR analysis. The elemental composition of synthesized NPs is determined using EDS analysis. Nanoparticles synthesized by green methods have broad applications and serve as antibacterial and antifungal agents. Various metal and metal oxide NPs such as Silver (Ag), copper (Cu), gold (Au), silicon dioxide (SiO<sub>2</sub>), zinc oxide (ZnO), titanium dioxide (TiO<sub>2</sub>), copper oxide (CuO), etc. have been proven to have a positive effect on plant growth and development. They play a potentially important role in the germination of seeds, plant growth, flowering, photosynthesis, and plant yield. The present review highlights the pathways of phytosynthesis of nanoparticles, various techniques used for","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}