Antiplatelet Drugs Use in Pregnancy—Review of the Current Practice and Future Implications

When clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological state of the pregnant woman’s body, which can influence the pharmacokinetics of the drug, its ability to traverse the placental barrier, and its potential teratogenic effects on the fetus. While the efficacy and safety of aspirin during pregnancy have been relatively well-established through numerous clinical studies, understanding the effects of newer, more potent antiplatelet agents has primarily stemmed from individual clinical case reports necessitating immediate administration of potent antiplatelet therapy during pregnancy. This review consolidates the collective experiences of clinicians confronting novel thrombotic complications during pregnancy, often requiring the use of dual antiplatelet therapy. The utilization of potent antiplatelet therapy carries inherent risks of bleeding, posing threats to both the pregnant woman and the fetus, as well as the potential for teratogenic effects on the fetus. In the absence of official guidelines regarding the use of potent antiplatelet drugs in pregnancy, a plethora of cases have demonstrated the feasibility of preventing recurrent thrombotic complications, mitigating bleeding risks, and successfully managing pregnancies, frequently culminating in cesarean deliveries, through meticulous selection and dosing of antiplatelet medications

Inkluzivni pristup zaštiti manjinskog nematerijalnog kulturnog nasleđa u Srbiji iz perspektive standarda ljudskih prava

Zaštita nematerijalnog kulturnog nasleđa predstavlja značajan aspekt zaštite prava nacionalnih manjina, a u našem kontekstu dobija poseban značaj s obzirom na osetljivo nasleđe međuetničkih konflikata i potrebu za prevencijom bilateralne kondicionalnosti pri pristupanju Republike Srbije Evropskoj Uniji. Iako se na nju obično ne gleda na taj način, pristupanjem Konvenciji o zaštiti nematerijalnog kulturnog nasleđa UNESCO Republika Srbija je dobila još jedan značajan instrument za unapređenje položaja pripadnika nacionalnih manjina. U prethodnim godinama, uprkos nepostojanju adekvatnog zakonskog okvira, uspostavljen je originalan i uspešan institucionalni mehanizam za realizaciju ovog režima u nacionalnim okvirima, čiji su značajni rezultati već primetni. U članku se analizira aktuelni pravni okvir zaštite manjinskih prava iz perspektive zaštite nematerijalnog kulturnog nasleđa i razmatraju dosadašnji pravno relevantni rezultati zajedničkog pravno-etnoantropološkog istraživanja. Analiza sadrži i primenjeno-naučne preporuke kojima se sugerišu moguća pravna rešenja usmerena na prevenciju instrumentalizacije pitanja manjinskog kulturnog nasleđa i izostanka njegove zaštite u kontekstu procesa evropskih integracija i kulturalizovane bilaternalne kondicionalnosti

In silico analiza utjecaja toksičnih metala na komplikacije bolesti COVID-19: molekularni uvidi

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.COVID-19 može izazvati niz komplikacija, uključujući kardiovaskularnu, bubrežnu i/ili respiratornu insuficijenciju, ali se malo zna o njegovim potencijalnim učincima u osoba koje su izložene toksičnim metalima. Cilj ovog istraživanja bio je odgovoriti na to pitanje pomoću in silico toksikogenomske metode, koja može pružiti molekularni uvid u komplikacije bolesti COVID-19 uslijed izloženosti arsenu, kadmiju, olovu, živi, niklu i kromu. U tu su svrhu korišteni Komparativna toksikogenomska baza podataka (CTD), GeneMANIA i ToppGene Suite portal te je identificirana skupina od pet zajedničkih gena (IL1B, CXCL8, IL6, IL10, TNF) za šest metala i COVID-19, koji svi kodiraju proinflamatorne i antiinflamatorne citokine. Lista je proširena s dodatnih 20 srodnih gena. Fizičke interakcije dominirale su između gena na koje utječe kombinacija ispitivanih metala (77,64 %), a koekspresija je dominantna interakcija između gena na koje djeluju pojedinačni metali (As 56,35 %, Cd 64,07 %, Pb 71,5 %, Hg 81,91 %, Ni 64,28 %, Cr 88,51 %). Biološki procesi, molekulske funkcije i putovi u kojima sudjeluje tih 25 gena blisko su povezani s citokinima i citokinskom olujom, koja je uključena u razvoj komplikacija bolesti COVID-19. Drugim riječima, ovi rezultati potvrđuju da izloženost toksičnim metalima, bilo pojedinačno ili u kombinaciji, može dovesti do razvoja težih oblika bolesti COVID-19

Supplementary data for the article: Kašanin-Grubin, M.; Štrbac, S.; Antonijević, S.; Djogo Mračević, S.; Randjelović, D.; Orlić, J.; Šajnović, A. Future Environmental Challenges of the Urban Protected Area Great War Island (Belgrade, Serbia) Based on Valuation of the Pollution Status and Ecosystem Services. Journal of Environmental Management 2019, 251. https://doi.org/10.1016/j.jenvman.2019.109574

Supplementary material for: [https://doi.org/10.1016/j.jenvman.2019.109574]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3510

Supplementary data for the article: Kašanin-Grubin, M.; Štrbac, S.; Antonijević, S.; Djogo Mračević, S.; Randjelović, D.; Orlić, J.; Šajnović, A. Future Environmental Challenges of the Urban Protected Area Great War Island (Belgrade, Serbia) Based on Valuation of the Pollution Status and Ecosystem Services. Journal of Environmental Management 2019, 251. https://doi.org/10.1016/j.jenvman.2019.109574

Supplementary material for: [https://doi.org/10.1016/j.jenvman.2019.109574]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3510

In silico analiza utjecaja toksičnih metala na komplikacije bolesti COVID-19: molekularni uvidi

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.COVID-19 može izazvati niz komplikacija, uključujući kardiovaskularnu, bubrežnu i/ili respiratornu insuficijenciju, ali se malo zna o njegovim potencijalnim učincima u osoba koje su izložene toksičnim metalima. Cilj ovog istraživanja bio je odgovoriti na to pitanje pomoću in silico toksikogenomske metode, koja može pružiti molekularni uvid u komplikacije bolesti COVID-19 uslijed izloženosti arsenu, kadmiju, olovu, živi, niklu i kromu. U tu su svrhu korišteni Komparativna toksikogenomska baza podataka (CTD), GeneMANIA i ToppGene Suite portal te je identificirana skupina od pet zajedničkih gena (IL1B, CXCL8, IL6, IL10, TNF) za šest metala i COVID-19, koji svi kodiraju proinflamatorne i antiinflamatorne citokine. Lista je proširena s dodatnih 20 srodnih gena. Fizičke interakcije dominirale su između gena na koje utječe kombinacija ispitivanih metala (77,64 %), a koekspresija je dominantna interakcija između gena na koje djeluju pojedinačni metali (As 56,35 %, Cd 64,07 %, Pb 71,5 %, Hg 81,91 %, Ni 64,28 %, Cr 88,51 %). Biološki procesi, molekulske funkcije i putovi u kojima sudjeluje tih 25 gena blisko su povezani s citokinima i citokinskom olujom, koja je uključena u razvoj komplikacija bolesti COVID-19. Drugim riječima, ovi rezultati potvrđuju da izloženost toksičnim metalima, bilo pojedinačno ili u kombinaciji, može dovesti do razvoja težih oblika bolesti COVID-19

Zagađivači životne sredine igojaznost: od uzročnoposledičnih dokaza do otvorenih pitanja

The link between environmental pollution and obesity is of high importance, because understanding the relationship between the two can provide valuable insights into the complex factors contributing to the obesity epidemic. These chemicals, termed “obesogens,” are believed to disrupt lipid metabolism processes, therefore promoting the development of obesity. Human activities such as industrialization, urbanization, agriculture, and transportation have significantly contributed to environmental pollution. Therefore, the main identified obesogens are BPA found in plastics, food packaging, and thermal paper receipts, phthalates, commonly used in plastics, personal care products, and food packaging, toxic metal(oid)s, determined in non-stick cookware, water-resistant fabrics, and food packaging, pesticides, used in agriculture, as well as other persistent organic pollutants (POPs), and pharmaceuticals (waste). Addressing environmental pollution not only has the potential to improve environmental quality, but also to promote public health and prevent obesity-related diseases. Addressing the causality between pollutants and obesity could be a new and challenging road map for health professionals.Veza između zagađenja životne sredine i gojaznosti je od velikog značaja, jer razumevanje ovog odnosa može pružiti vredan uvid u složeni set faktora koji doprinose epidemiji gojaznosti. Veruje se da ove hemikalije, zagađujuće supstance, nazvane "obesogeni", ometaju procese metabolizma lipida, čime podstiču razvoj gojaznosti. Antropogene aktivnosti kao što su industrijalizacija, urbanizacija, poljoprivreda i transport značajno su doprinele zagađenju životne sredine. Shodno tome, najznačajniji identifikovani obesogeni su bisfenol A, koji se nalazi u plastici, ambalaži za hranu i termalnom papiru za račune, ftalati, koji se obično koriste u plastici, proizvodima za ličnu negu i ambalaži za hranu, toksični metal(oid)i, pesticidi, koji se koriste u poljoprivredi, kao i perzistentne organske zagađujuće supstance (POPs) i farmaceutski proizvodi (otpad). Rešavanje pitanja zagađenja životne sredine ne samo da ima potencijal da poboljša kvalitet životne sredine, već i da unapredi javno zdravlje i spreči bolesti povezane sa gojaznošću. Rešavanje uzročno-posledične veze između zagađujućih supstanci i gojaznosti moglo bi biti nova i izazovna mapa puta za zdravstvene profesionalce

Hematotoxicity of lead, cadmium, mercury and arsenic low dosed mixtures relevant to environmental exposure: the Adverse Outcome Pathway framewor

Lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) are toxic metals/metalloids placed at the top of the list of the most significant environmental pollutants from the public aspect of health. The literature showed that exposure to individual metals, as well as their mixtures, could influence the development of numerous health disorders, including changes in hematological parameters, which mostly result in anemia. In the current study, in silico and in vivo analysis was performed to determine hematotoxicity of low dosed toxic metals mixture (Pb, Cd, Hg and As) relevant for exposure from life environment. AOP framework was applied to elucidate the mechanisms of hematotoxicity through: in silico approach – Comparative Toxicogenomics Database (CTD), GeneMANIA Gene Ontology tools, and in vivo approach – orally exposed male Wistar rats divided into control group and group treated with a mixture (MIX) of aqueous solutions of lead-acetate (1 mg/kg b.w.), cadmium-chloride (3 mg/kg b.w.), mercury(II)-chloride (0,06 mg/kg b.w.), arsenic(III)-oxide (0,6 mg/kg b.w.). Rats were euthanized after 28 days and hematological parameters were measured. CTD analysis showed connected genes for MIX and the development of: hematological diseases – FAS and ALAD; anemia – ACHE, GSR, TNF; thrombocytosis – JAK2, CALR, MPL, THPO. Further analysis singled out changes in protein and mRNA expression, as well as protein activity of the selected genes as 3 clusters of molecular initiating events (MIEs). These molecular changes, along with the main interactions among the related genes in each cluster (GeneMANIA) (physical interactions), led to the further macromolecular alterations. Cluster-specific subsequent key events (KEs) were obtained by Gene Ontology tools: hematological diseases – The FAS protein signaling pathways, apoptosis and heme synthesis; anemia – oxidative stress, glutathione metabolism, ROS induced apoptosis; thrombocytosis – activation of JAK and THPO, binding of THPO to receptors and their activation. Identified molecular pathways (KEs) could converge to the development of Disruption of Hematological Homeostasis as the final organ-specific adverse outcome (AO). In vivo approach showed statistically significant changes compared to the control in values of RCB, Hb, Hct, MCV, MCH, MCHC, strengthening the weight of evidence for anemia development, while an increase in platelets suggested the thrombocytosis development. This AOP framework provides an insight into the better mechanistic understanding of environmental metal mixture mode of action and its relation to hematotoxicity. Also, it suggested KEs useful for future biomarkers identification and enabled grouping the metals with similar toxicity (451-03-68/2020–14/200161).Abstracts of the 57th congress of the European Societies of Toxicology (EUROTOX 2023) TOXICOLOGY – MULTIDISCIPLINARY SCIENCE LEADING TO SAFER AND SUSTAINABLE LIFE Ljubljana, Slovenia, September 10–13, 202

Actual contamination of the Danube and Sava Rivers at Belgrade (2013)

This study was focussed on a comprehensive investigation on the state of pollution of the Danube and Sava Rivers in the region of Belgrade. Different complementary analytical approaches were employed covering both i) organic contaminants in the river water by target analyses of hormones and neonicotinoids as well as non-target screening analyses and ii) heavy metals in the sediments. Finally, some common water quality parameters were analysed. The overall state of pollution is on a moderate level. Bulk parameters did not reveal any unusual observations. Moreover, quantification of preselected organic contaminants did not indicate to elevated pollution. More significant contaminations were registered for chromium, nickel, zinc and partially copper in sediments with values above the target values according to Serbian regulations. Lastly, non-target screening analysis revealed a wider spectrum of organic contaminants comprising pharmaceuticals, technical additives, personal care products and pesticides. The study presented a comprehensive view on the state of pollution of the Sava and Danube Rivers and is the base for setting up further monitoring programs. As a superior outcome, it was illustrated how different chemical analyses can result in different assessments of the river quality. A comparison of target and non-target analyses pointed to potential misinterpretation of the real state of pollution

Predicting sulforaphane-induces adverse effects in prostatic cancer patients via in silico investigation

Prostate cancer is a major cause of death in men. Traditional therapies have limited efficacy, leading to the increased interest in phytochemicals like sulforaphane (SFN), found in cruciferous vegetables. Literature data indicate numerous beneficial effects of SFN as an antioxidant, immunomodulator and antitumor agent, but the toxicity and thus safety of its use has not been sufficiently investigated. Also, SFN may selectively accumulate in prostate tissue. The aim of this work was to predict the positive and negative influence of SFN on gene expression in patients with prostate cancer by conducting in silico analysis. Publicly available database, Gene expression omnibus (GEO, https://www. ncbi.nlm.nih.gov/geo/) was used to obtain gene profiles of malignantly changed tissues and healthy tissues and then analyzed with GEO2R tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/) which identify differentially expressed genes between tumor and healthy tissue. Interactivenn tool (http://www.interactivenn.net/) helped with obtaining sets of genes that are consistently up- and down-regulated in prostate cancer. Toppgene tool (https://toppgene.cchmc.org/) was used to explore the role of the selected genes in gene ontology processes that could affect cancer progression, while GeneMania (https://genemania.org/) determined genes related to the set of genes and the type of interaction between all of them. To determine whether SFN has an effect on selected sets of genes, the Comparative Toxicogenomic Database (CTD, http://ctdbase.org/) was used. In prostate cancer, a total of 13 genes were consistently down-regulated, and 37 genes up-regulated. Down- regulated genes are involved in molecular functions, biological processes and pathways of muscle contraction and channel and enzyme functions, while up-regulated genes regulate processes at the level of the kidneys and the renin-angiotensin-aldosterone system. Network analysis showed that the type of interaction that dominated between downstream or upstream regulated genes and their related genes, was co-expression. Finally, SFN interacted with 21 dysregulated genes and reduced the expression of ERG and TMEFF2, while increased the expression of GSTM3, ACTG2 and CNN1 genes which can lead to positive effects such as improving antioxidant protection, suppressing expansion of tumor tissue and risk of developing bone metastases. In addition, SFN could contribute to the development of prostate cancer, by interacting with the genes already expressed in the tumor tissue. The conducted study indicates that the genomic signature of patients suffering from prostate cancer could be an important factor which determines the benefits and risks of SFN as an adjunctive therapy. It could be suggested that prostate cancer patients with increased expression of ABCC4 and ENTPD5 and decreased expression of MAMDC2, MYLK, PGM5, PPP1R3C and SYNM might not be the best candidates for SFN administration. (Serbia-China project: 451-03-1203/2021-09)Abstracts of the 57th congress of the European Societies of Toxicology (EUROTOX 2023) TOXICOLOGY – MULTIDISCIPLINARY SCIENCE LEADING TO SAFER AND SUSTAINABLE LIFE Ljubljana, Slovenia, September 10–13, 202