Search

Marta Szukalska,1 Bartosz F Grześkowiak,2 Magdalena J Bigaj-Józefowska,2 Marta Witkowska,3,4 Emilia Cicha,5 Patrycja Sujka-Kordowska,6 Izabela Miechowicz,7 Michał Nowicki,6 Radosław Mrówczyński,3,4 Ewa Florek1 1Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland; 2NanoBioMedical Centre, Adam Mickiewicz University, Poznań, Poland; 3Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland; 4Centre for Advanced Technologies, Adam Mickiewicz University, Poznań, Poland; 5Laboratory of Experimental Animals, Poznan University of Medical Sciences, Poznań, Poland; 6Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland; 7Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznań, PolandCorrespondence: Marta Szukalska, Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Rokietnicka 3 Street, Poznan, 60-806, Poland, Email martan@ump.edu.plPurpose: Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT.Methods: Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD).Results: In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%.Conclusion: Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies. Keywords: polydopamine nanoparticles, oxidative stress, liver cancer model, in vivo toxicity, chemo- and photothermal therapy

Endometriosis, the presence of ectopic endometrium, has an unclear etiology and is commonly associated with endocrine, genetic, and immunological imbalance. This study determined whether immunomodulation by the RESAN vaccine could alter the potentially pathogenic gene expression profiles in the cells of the eutopic endometrium in an animal model of endometriosis. Preventing these changes could inhibit the early development of the illness and support the success of surgical treatment. Wistar rats were divided into three groups: prophylaxis (vaccinated before ectopic endometrium implantation, n = 23), therapeutic (vaccinated at the time of the ectopic excision, n = 23) and control (n = 10). During the first laparotomy, autotransplantation of the endometrium to the peritoneum was performed in the prophylaxis and therapeutic groups. The second laparotomy was carried out three months later in all groups to examine endometriotic foci and adhesions. Suspected endometriosis foci were removed. Three months later, the third laparotomy was performed in all animals, followed by suspected foci excision. Fragments of the eutopic endometrium were collected from all animals during the first and third laparotomies. All samples were analysed by real-time PCR to assess the expression of Bcl2, Bax, Bax/Bcl2 ratio, Mki67, and Tert genes. Endometrial foci were found in abdominal peritoneum at the second laparotomy in 1 animal in the prophylaxis group, compared to 16 animals in the therapeutic group. The prophylaxis group showed a high expression of Bax while the therapeutic group showed high expression of Bax, Tert and Mki67 genes. Additional analysis revealed that throughout the six months of the experiment, the expression of the Bax, Tert, and Mki67 genes decreased significantly in the prophylaxis group, Mki67 gene expression decreased in the therapeutic group, and Tert, Mki67, and Bcl2 gene expression decreased in the control group. The results indicate that immunomodulation affects the balance between apoptosis and proliferation in the eutopic endometrium and may prevent the onset and recurrence of endometriosis. [ABSTRACT FROM AUTHOR]

Caffeine and nicotine are some of the most often self-administered substances worldwide. Very often they are taken simultaneously and it seems that this fact is correlated with the amount of caffeine and nicotine administered. The aim of this study is to determine, whether tobacco smoke influences the metabolism of caffeine. The secondary task is to establish whether caffeine has an effect on elimination of cotinine, nicotine's main metabolite. The results showed that tobacco smoke influences the metabolism of caffeine by accelerating its elimination, by the means of induced CYP1A2 activity. As far as cotinine is concerned, no influence of caffeine on its elimination was observed. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.

Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. This review aims to elucidate the relationship between ferroptosis and head and neck cancer treatment by discussing its conceptual framework, mechanism of action, functional aspects, and implications for tumor therapy. In addition, this review consolidates strategies aimed at improving the efficacy of head and neck cancer treatment through modulation of ferroptosis, herein serving as a valuable reference for advancing the treatment landscape for this patient population.

Hepatocellular damage by the harmful effects of xenobiotics, which increase the production of free radicals, is a widespread phenomenon. The extract from the leaves of Cynara scolymus L. available as an artichoke preparation (natural source) of antioxidants may serve as a potential hepatoprotective factor. This study aimed to evaluate the impact of the protective and regenerative properties of artichoke preparation on the liver in three extract doses: 0.5; 1.0; and 1.5 g/kg bw/day. The evaluation was conducted by measuring the levels of oxidative stress parameters, including glutathione (GSH), glutathione S-transferases (GST), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), Trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx), paraoxonase 1 (PON1), SH- group, nitrosylated protein (RSNO), as well as such liver enzymes as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in the plasma and liver homogenate of rats with liver damage induced by CCl 4 (1 mL/kg bw). Measurements were taken in plasma and liver homogenate. The results have demonstrated that the artichoke preparation, owing to its high antioxidative potential, exhibits protective and regenerative effects on the liver. This is supported by the observation of higher GSH levels in the plasma of rats treated with artichoke extract for two weeks before CCl 4 exposure. Furthermore, the artichoke extract has shown regenerative properties, as evidenced by lower ALT, AST, and SOD activity in the group treated with artichoke extract after CCl 4 exposure. These findings suggest that the in vivo administration of artichoke preparation may be beneficial for the protection and regeneration of the liver.

Head and neck cancers (HNC) are among the most common cancers in the world. In terms of frequency of occurrence in the world, HNC ranks sixth. However, the problem of modern oncology is the low specificity of the therapies used, which is why most of the currently used chemotherapeutic agents have a systemic effect. The use of nanomaterials could overcome the limitations of traditional therapies. Researchers are increasingly using polydopamine (PDA) in nanotherapeutic systems for HNC due to its unique properties. PDA has found applications in chemotherapy, photothermal therapy, targeted therapy, and combination therapies that facilitate better carrier control for the effective reduction of cancer cells than individual therapies. The purpose of this review was to present the current knowledge on the potential use of polydopamine in head and neck cancer research.

All treatment modalities for head and neck cancer carry with them a risk of adverse events. Head and neck surgeons are faced with significant challenges to minimize associated morbidity and manage its sequelae. Recognizing situations in which a surgical complication is an adverse event inherent to the procedure can alleviate the psychologic impact a complication might have on the treatment team and minimize external and internal pressures. Focusing on the complications that can be effectively modified, future complications can be avoided. Also, some surgical morbidities may not be preventable, necessitating the option to reconsider whether the incidents should be labeled toxic reactions rather than a complication. This discussion highlights some of the areas in which additional research is needed to achieve the goal of minimizing the impact of surgical morbidity., (© 2022. The Author(s).)

Multi-walled carbon nanotubes (MWCNTs) serve as nanoparticles due to their size, and for that reason, when in contact with the biological system, they can have toxic effects. One of the main mechanisms responsible for nanotoxicity is oxidative stress resulting from the production of intracellular reactive oxygen species (ROS). Therefore, oxidative stress biomarkers are important tools for assessing MWCNTs toxicity. The aim of this study was to evaluate the oxidative stress of multi-walled carbon nanotubes in male rats. Our animal model studies of MWCNTs (diameter ~15-30 nm, length ~15-20 μm) include measurement of oxidative stress parameters in the body fluid and tissues of animals after long-term exposure. Rattus Norvegicus/Wistar male rats were administrated a single injection to the knee joint at three concentrations: 0.03 mg/mL, 0.25 mg/mL, and 0.5 mg/mL. The rats were euthanized 12 and 18 months post-exposure by drawing blood from the heart, and their liver and kidney tissues were removed. To evaluate toxicity, the enzymatic activity of total protein (TP), reduced glutathione (GSH), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), Trolox equivalent antioxidant capacity (TEAC), nitric oxide (NO), and catalase (CAT) was measured and histopathological examination was conducted. Results in rat livers showed that TEAC level was decreased in rats receiving nanotubes at higher concentrations. Results in kidneys report that the level of NO showed higher concentration after long exposure, and results in animal serums showed lower levels of GSH in rats exposed to nanotubes at higher concentrations. The 18-month exposure also resulted in a statistically significant increase in GST activity in the group of rats exposed to nanotubes at higher concentrations compared to animals receiving MWCNTs at lower concentrations and compared to the control group. Therefore, an analysis of oxidative stress parameters can be a key indicator of the toxic potential of multi-walled carbon nanotubes.

Vitamin D (VitD) deficiency has garnered significant attention in contemporary medical research. Although the canonical biological activity of VitD manifests itself mainly in the regulation of calcium-phosphorus metabolism, recent studies show that, thanks to the presence of numerous receptors, VitD may also play an important role in regulating the immune system. VitD deficiency has been demonstrated to impact autoimmune disease, coeliac disease, infections (including respiratory/COVID-19), and patients with cancer. Recent studies also show that VitD plays a significant role in autoimmune thyroid diseases (AITDs). Many studies have shown a correlation between low VitD levels and chronic autoimmune thyroiditis - Hashimoto thyroiditis (HT), Graves' disease (GD), and postpartum thyroiditis (PPT). This review article, therefore, describes the current state of knowledge on the role of VitD in AITDs, including HT, GD, and PTT.

Tobacco smoking is deleterious to the lungs because it exposes them to many toxic substances. These include transition metal ions, such as cadmium. However, there is a lack of information about the influence of endogenous metal-binding peptides, such as His-Leu (HL), on the lung distribution of transition metals in smokers. To address this, we administered HL subcutaneously to rats exposed to tobacco smoke for six weeks, then we measured the concentrations of transition metal ions in the lungs. We found that exposure to tobacco smoke elevates the concentrations of Cd(II) and Cu(II). Administration of the HL peptide, whose elevation is a consequence of angiotensin receptor blocker anti-hypertension therapy, increases the concentration of Fe in the lungs of rats exposed to smoke. These findings suggest that smoking is a risk factor for patients receiving angiotensin receptor blockers to treat hypertension.

Carbon nanotubes are increasingly used in nanomedicine and material chemistry research, mostly because of their small size over a large surface area. Due to their properties, they are very attractive candidates for use in medicine and as drug carriers, contrast agents, biological platforms, and so forth. Carbon nanotubes (CNTs) may affect many organs, directly or indirectly, so there is a need for toxic effects evaluation. The main mechanisms of toxicity include oxidative stress, inflammation, the ability to damage DNA and cell membrane, as well as necrosis and apoptosis. The research concerning CNTs focuses on different animal models, functionalization, ways of administration, concentrations, times of exposure, and a variety of properties, which have a significant effect on toxicity. The impact of pristine CNTs on toxicity in rodent models is being increasingly studied. However, it is immensely difficult to compare obtained results since there are no standardized tests. This review summarizes the toxicity issues of pristine CNTs in rodent models, as they are often the preferred model for human disease studies, in different organ systems, while considering the various factors that affect them. Regardless, the results showed that the majority of toxicological studies using rodent models revealed some toxic effects. Even with different properties, carbon nanotubes were able to generate inflammation, fibrosis, or biochemical changes in different organs. The problem is that there are only a small amount of long-term toxicity studies, which makes it impossible to obtain a good understanding of later effects. This article will give a greater overview of the situation on toxicity in many organs. It will allow researchers to look at the toxicity of carbon nanotubes in a broader context and help to identify studies that are missing to properly assess toxicity.

Alcohol and nicotine (tobacco smoke) are often used together, and taking both addictive substances is associated with an increased risk of certain diseases. It is extremely important to understand the pharmacodynamic and pharmacokinetic mechanisms of the interaction between nicotine and ethanol, which are still not fully understood. The study aimed to evaluate the influence of chronic alcohol consumption on nicotine biotransformation in ethanol-preferring and non-preferring male and female rats. Rats were divided into four groups depending on their alcohol preferences and gender. Nicotine, nornicotine, nicotine N-oxide, cotinine, trans-3'-hydroxycotinine, and cotinine N-oxide in rats plasma were determined by LC-MS/MS after five days of exposure to tobacco smoke. A non-compartmental analysis of nicotine and its metabolites was used for pharmacokinetic parameters calculation. Our experimental results showed that the rate of nicotine elimination depends on gender, regardless of alcohol preferences (significantly slower in females than in males). Mean residence timeof nornicotine, cotinine, and trans-3'-hydroxycotinine were significantly higher in alcohol-preferring male rats than in alcohol preferring female rats. In non-alcohol preferring female rats compared to ethanol-preferring female rats, significantly more nicotine N-oxide (fivefold) and trans-3'-hydroxycotinine (twofold) reached the general circulation unchanged. Drinking ethanol influenced the elimination of nornicotine and cotinine in male rats. Ethanol consumption was identified as a modifier of nicotine pharmacokinetics and this was gender-dependent., (© 2022. The Author(s).)

Introduction: Tobacco smoke contains, among others, polycyclic aromatic hydrocarbons (PAHs), heterocyclic analogues, aromatic amines, N-nitrosamines, volatile hydrocarbons, aldehydes, phenols, miscellaneous organic compounds, metals, and inorganic compounds. Tobacco smoking can harm women's reproductive system and may reduce fertility. The objective of the study was to explore the effect of tobacco smoke on the menstrual cycle due to smoking and second-hand smoke-exposure., Material and Methods: The study was performed on 153 women of reproductive age, who received care at the Gynaecological-Obstetric Clinical Hospital of the Poznan University of Medical Sciences. They were divided into three treatment groups: non-smokers, secondhand smokers, and smokers. Comprehensive assessment of all hormone levels: follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E2), and progesterone (P), in the various phases of the menstrual cycle and with concomitant determinations of serum cotinine concentrations was performed. The menstrual cycle was observed with ultrasonography., Results: Cigarette smoking may be an important factor in disrupting reproduction: 1. The increase in the oestradiol E2 level was accompanied by significantly lowered serum cotinine concentrations in tobacco smokers; 2. In smoking patients, the serum level of LH significantly increased on the first days of the menstrual cycle; 3. The higher levels of P (in the 14th and 21st days) were assumed to be the result of a longer menstrual cycle., Conclusions: Active and passive smoking may be an important contributor to reproductive health issues and deserves greater focus in health education programs directed towards women of reproductive age.

Objectives: Based on the current state of knowledge, elevated levels of oxidative stress markers may be considered as risk factors for pregnancy complications. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the occurrence of foetal chromosomal aberration and congenital malformations., Material and Methods: This retrospective research lasted for two years. The purpose was to determine serum levels of selected oxidative stress markers, including total protein (TP), glutathione (GSH), S-nitrosothiols (RSNO), nitric oxide (NO), trolox equivalent antioxidant capacity (TEAC) and glutathione S-transferase (GST) at 11-13 + 6 gestational weeks in 38 women with confirmed foetal developmental abnormalities and in 34 healthy pregnancies in order to assess their utility as predictors of abnormal foetal development., Results: Serum concentrations of TP (56.90 ± 5.30 vs 69.1 ± 15.30 mg/mL), TEAC (4.93 ± 0.82 vs 5.64 ± 0.74 μM/mL) and GST (15.94 ± 4.52 vs 21.72 ± 6.81 nM/min/mg) were statistically significantly (p < 0.05) lower in the group of patients with developmental abnormalities in the fetus, whereas GSH levels (6.43 ± 1.24 vs 4.98 ± 1.88 nM/mg) were significantly higher, compared to the group of healthy fetuses. There were no differences in the concentration of these markers between chromosomal aberrations and fetal dysmorphia in subjects. A significant difference in odds ratio obtained for GSH (OR = 0.57, 95% CL: 0.40-0.80) indicates that its higher concentration can relate to reduced risk of developmental abnormalities, whereas odds ratio for TP (OR=1.11, 95% CL: 1.04-1.17), TEAC (OR = 3.54, 95% CL: 1.56-8.05) and GST (OR = 1.18, 95% CL: 1.03-1.17) indicate that their elevation may increase the risk of developmental abnormalities CONCLUSIONS: Elevated levels of TP, GST, TEAC and low GSH level may be relevant to predict congenital defects.

Objective: One of the treatment goals in type 1 diabetes and periodontitis is to address chronic inflammation to prevent the development of neurovascular complications. The aim of this study was to assess the local anti-inflammatory effects of chlorhexidine digluconate and cetylpyridine chloride on periodontal status and indicators of oxidative stress in saliva in patients with type 1 diabetes., Materials and Methods: A total of 42 subjects aged 27 (interquartile range, IQR 22-35) years, with type 1 diabetes for a duration of 12 (IQR 9-18) years, and glycated hemoglobin 8.05 (IQR 7.1-9.4)% were included. Patients were examined twice-initially, and after 14 days of using toothpaste with chlorhexidine and cetylpyridine. Clinical examination of gingival tissues was performed. Certain oxidative stress markers (TP, TEAC, TBARS, AOPP) were measured in the saliva samples., Results: There were significant changes in clinical indicators of periodontal status before and after the application of the toothpaste (API before 0.35 (0.24-0.65) vs. API after 0.265 (0.18-0.39), p = 0.03; SBI before 0.07 (0.04-0.15) vs. SBI after 0.035 (0-0.06), p = 0.002; GI before 0.88 (0.46-1) vs. GI after 0.67 (0.25-1), p = 0.0008). The concentration of saliva TBARS decreased ( p = 0.00005) and TEAC increased ( p = 0.09)., Conclusion: Proper oral hygiene supported by antibacterial chemicals may improve the periodontal status and reduce inflammation.

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus . Rats ( n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all of the animals and metabolites were studied using the NMR method. The metabolomic pattern was compared before and after the protoberberine treatment. The performed analysis showed significant changes in the concentrations of metabolites that are involved in energy homeostasis, including glucose, glutamine, and lactate. Histopathological studies showed no recurrence of endometriosis loci after treatment with BBR. The results of the study found that BBR treatment prevents the recurrence of endometriosis in rats. Moreover, metabolomics profiling can be applied to better understand the mechanisms of action of these protoberberine secondary plant metabolites. Our findings provide new insights into the pharmaceutical activity of natural protoberberine plant compounds.

Several reports confirm the deleterious effects of tobacco smoking and exposure to second-hand smoke (SHS) resulting in changes in the composition of breast milk. The aim of our study was to compare the levels of selected essential, as well as, toxic metals found in colostrum (collected at day 1 ± 2 post-birth) and mature milk (1 month ± 7 days post-birth) of nonsmoking women (n = 52) compared to those found in women who smoke tobacco (n = 51) and women exposed to second-hand smoke during pregnancy and lactation (n = 47). Women's non-smoking or smoking status was determined by their responses to a questionnaire, including questions about others who may smoke in the home environment, and confirmed by measurement of cotinine in the blood serum by high performance liquid chromatography with diode array detector (HPLC-DAD). Inductively coupled plasma mass spectrometry (ICP-MS) and flame atomic absorption spectroscopy (F-AAS) techniques were used to determine the metal concentrations in colostrum and mature milk previously digested by a microwave mineralizer. We confirmed that exposure to tobacco smoke increases concentrations of heavy metals (cadmium and lead) in colostrum and mature milk. These increased concentrations of heavy metals may disturb the action of bioactive substances necessary for the optimal growth and development of newborns and infants. These findings support the need for increased concern and information to lactating women about preventing their exposure to cigarette smoking and SHS due to the adverse effects of tobacco smoke on breast milk with added risks to their infants., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Radioiodine therapy (131I) is a standard procedure in the treatment of hyperthyroidism in the course of Graves' disease or toxic nodules. However, the use of 131I in patients with low radioiodine uptake (RAIU) may be controversial., Objectives: To determine the influence of lithium carbonate (Li) on iodine kinetics., Material and Methods: Patients with hyperthyroidism and low RAIU (< 30%) were divided into 2 groups: a Li(-) group of 305 patients not receiving Li adjuvant therapy and a Li(+) group of 264 patients receiving adjuvant therapy. The serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone (TSH) were assessed at baseline, 24 h, 48 h, 72 h and 96 h, and 1, 6 and 12 months after 131I therapy. The RAIU was assessed after 5 h, 24 h, 48 h, 72 h, and 96 h., Results: Levels of fT3 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 48 h, 72 h, 96 h and 1 month, and did not differ significantly after 24 h, 6 months and 12 months. Levels of fT4 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 24 h, 48 h, 72 h, 96 h and 1 month, and not differ significantly after 6 and 12 months. The RAIU in the hyperthyroidism Li(-) and Li(+) groups, respectively, was 11.9 ±5.6% compared to 23.9 ±10.1% (p < 0.001) after 5 h; 25.9 ±8.3% compared to 40.5 ±12.4% (p < 0.05) after 24 h; 7.8 ±8.1% compared to 40.9 ±13.7% (p < 0.05) after 48 h; 26.2 ±10.2% compared to 39.5 ±11.2% (p < 0.01) after 72 h; and 24.7 ±7.1% compared to 37.4 ±10.1% (p < 0.01) after 96 h., Conclusions: Adjuvant therapy with Li in patients with hyperthyroidism caused a significant increase in RAIU and positive changes in the fT3 and fT4 profiles. The use of lithium carbonate prior to the inclusion of 131I in hyperthyroid patients with low RAIU should be considered.

Genetically uniform plant material, derived from Lychnis flos-cuculi propagated in vitro, was used for the isolation of 20-hydroxyecdysone and polypodine B and subjected to an evaluation of the antifungal and antiamoebic activity. The activity of 80% aqueous methanolic extracts, their fractions, and isolated ecdysteroids were studied against pathogenic Acanthamoeba castellani . Additionally, a Microtox ® acute toxicity assay was performed. It was found that an 80% methanolic fraction of root extract exerts the most potent amoebicidal activity at IC 50 of 0.06 mg/mL at the 3rd day of treatment. Both ecdysteroids show comparable activity at IC 50 of 0.07 mg/mL. The acute toxicity of 80% fractions at similar concentrations is significantly higher than that of 40% fractions. Crude extracts exhibited moderate antifungal activity, with a minimum inhibitory concentration (MIC) within the range of 1.25-2.5 mg/mL. To the best of our knowledge, the present report is the first to show the biological activity of L. flos-cuculi in terms of the antifungal and antiamoebic activities and acute toxicity. It is also the first isolation of the main ecdysteroids from L. flos-cuculi micropropagated, ecdysteroid-rich plant material.

The metabolic syndrome is a combination of several metabolic disorders, such as cardiovascular disease, atherosclerosis, and type 2 diabetes. Lifestyle modifications, including quitting smoking, are recommended to reduce the risk of metabolic syndrome and its associated complications. Not much research has been conducted in the field of e-cigarettes and the risk of metabolic syndrome. Furthermore, taking into account the influence of e-cigarettes vaping on the individual components of metabolic syndrome, i.e, abdominal obesity, insulin resistance, dyslipidemia and elevated arterial blood pressure, the results are also ambiguous. This article is a review and summary of existing reports on the impact of e-cigarettes on the development of metabolic syndrome as well as its individual components. A critical review for English language articles published until 30 June 2020 was made, using a PubMed (including MEDLINE), Cochrane, CINAHL Plus, and Web of Science data. The current research indicated that e-cigarettes use does not affect the development of insulin resistance, but could influence the level of glucose and pre-diabetic state development. The lipid of profile an increase in the TG level was reported, while the influence on the level of concentration of total cholesterol, LDL fraction, and HDL fraction differed. In most cases, e-cigarettes use increased the risk of developing abdominal obesity or higher arterial blood pressure. Further research is required to provide more evidence on this topic.

E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.

The pathophysiological mechanism underlying pregnancy complications such as congenital malformations, miscarriage, preeclampsia, or fetal growth restriction is not entirely known. However, the negative impact of the mother's body oxidative imbalance on the fetus and the course of gestation is increasingly discussed. This article is an integrative review of some original studies and review papers on the effects of oxidative stress on the adverse pregnancy outcomes mainly birth defects in fetuses. A systematic search for English language articles published from 2010 until 2020 was made, using MEDLINE data. Additionally, we analyzed the Cochrane and Scopus databases, discussions with experts, and a review of bibliography of articles from scientifically relevant and valuable sources. The main purposes are to assess the contribution of the existing literature of associations of oxidative stress on the etiology of the abovementioned conditions and to identify relevant information and outline existing knowledge. Furthermore, the authors aim to find any gaps in the research, thereby providing grounds for our own research. The key search terms were "oxidative stress in pregnancy," "oxidative stress and congenital malformations," and "oxidative stress and adverse pregnancy outcomes." Studies have confirmed that oxidative stress has a significant impact on pregnancy and is involved in the pathomechanism of adverse pregnancy outcomes., Competing Interests: No conflict of interest regarding this publication., (Copyright © 2020 Kinga Toboła-Wróbel et al.)

Cartilage and bone injuries are prevalent ailments, affecting the quality of life of injured patients. Current methods of treatment are often imperfect and pose the risk of complications in the long term. Therefore, tissue engineering is a rapidly developing branch of science, which aims at discovering effective ways of replacing or repairing damaged tissues with the use of scaffolds. However, both cartilage and bone owe their exceptional mechanical properties to their complex ultrastructure, which is very difficult to reproduce artificially. To address this issue, nanotechnology was employed. One of the most promising nanomaterials in this respect is carbon nanotubes, due to their exceptional physico-chemical properties, which are similar to collagens-the main component of the extracellular matrix of these tissues. This review covers the important aspects of 3D scaffold development and sums up the existing research tackling the challenges of scaffold design. Moreover, carbon nanotubes-reinforced bone and cartilage scaffolds manufactured using the 3D bioprinting technique will be discussed as a novel tool that could facilitate the achievement of more biomimetic structures.

Phytoecdysteroids are natural compounds with therapeutic benefits in both humans and animals. The effectiveness of natural products with health potential is based on the activities and potencies of their active ingredients. In this study, dominant ecdysteroids-ajugasterone C, 20-hydroxyecdysone and polypodine B-from the Serratula coronata ( S. coronata ) herb were separated by column chromatography, identified by spectroscopic data and quantified by high-performance liquid chromatography with a diode array detector (HPLC-DAD). The obtained concentration of ecdysteroids (approximately 23%) in the S. coronatae herb extract enhances the possibility of their use in pharmaceutical and cosmetic products with high levels of phytoecdysteroids. Moreover, this study has shown a positive effect of ecdysteroids-containing cream on changes in quality of life and a beneficial effect in reducing the symptoms of seborrheic dermatitis. It has been demonstrated that the application of the cream with phytoecdysteroids resulted in a statistically significant alleviation of symptoms ( p < 0.05), especially in terms of itching, pain or burning sensations in the affected areas in comparison to previous symptoms.

Flavonoids, a ubiquitous group of naturally occurring polyphenolic compounds, have recently gained importance as anticancer agents. Unfortunately, due to low solubility, absorption, and rapid metabolism of dietary flavonoids, their anticancer potential is not sufficient. Nanocarriers can improve the bioavailability of flavonoids. In this review we aimed to evaluate studies on the anticancer activity of flavonoid nanoparticles. A review of English language articles published until 30 June 2020 was conducted, using PubMed (including MEDLINE), CINAHL Plus, Cochrane, and Web of Science data. Most studies determining the anticancer properties of flavonoid nanoparticles are preclinical. The potential anticancer activity focuses mainly on MCF-7 breast cancer cells, A549 lung cancer cells, HepG2 liver cancer cells, and melanoma cells. The flavonoid nanoparticles can also support the anti-tumour effect of drugs used in cancer therapy by enhancing the anti-tumour effect or reducing the systemic toxicity of drugs.

The presence of dominant active compounds in standardised methanol extract from the leaves of Stizolophus balsamita ( S. balsamita ) was examined using HPLC with a diode-array detector. The extract and three dominant parthenolide derivatives were tested with Serotonin Research ELISA for their ability to inhibit the serotonin release from platelets. The antiserotonin effect of the extract was compared with that of parthenolide, a compound with proven antiserotonin and antimigraine effects. This study aimed to evaluate the ability of natural parthenolide derivatives to inhibit serotonin release from platelets. Izospiciformin, stizolin and stizolicin were analysed along with the standardised alcohol extract of S. balsamita leaves, which also contained four other parthenolide derivatives. All the analysed substances were found to inhibit serotonin release from platelets as compared with the control sample, which had 100% of serotonin released. Izospiciformin had the most significant impact (97.98% serotonin release inhibition). The effect of the methanol extract of S. balsamita on the serotonin release inhibition was also statistically significant.

Background: Many women who smoke tobacco continue to do so during lactation, and many non-smoking women are exposed to second-hand tobacco smoke (SHS) during the period that she wishes to breastfeed. There are reports documenting the adverse effects of maternal smoking during lactation on their infant's health; however, the pathophysiological mechanisms underlying these effects are incompletely understood., Objectives: Our study purpose was to examine the influence of tobacco smoke on biochemical markers reflecting the intensity of oxidative stress using concentration of total protein (TP), trolox equivalent antioxidant capacity (TEAC), S-nitrosothiols (RSNO), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) in the plasma, colostrum, and mature milk of women who smoke, those only exposed to SHS, and non-smokers., Methods: Questionnaire data on the tobacco smoking status were verified based on the determination of cotinine by high performance liquid chromatography with diode array detector (HPLC-DAD). Relevant markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods., Results: We found that tobacco smoking during lactation increases oxidative stress in the mother's plasma, colostrum, and mature milk, and lesser so in those exposed to SHS. Tobacco smoke significantly increase TBARS and decrease TEAC in colostrum and mature milk. In response to ROS generated by tobacco smoke increase the activity of antioxidant enzymes (SOD, GST, GPx and CAT), p < 0.05., Discussion: Such exposure to tobacco smoke influences the antioxidant barrier of human colostrum and mature milk that can adversely affect their infant's health. Greater public health awareness of the adverse effects of tobacco smoking during lactation on breast milk quality and its protective effects is urgently needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Approximately 10% of women report smoking during pregnancy. The number of breastfeeding women who relapse back to smoking is even greater. Smoking may cause adverse changes to the milk's composition by not only reducing its protective properties, but also by affecting the infant's health. The pathophysiological mechanisms underlying these adverse effects are not entirely known. This article is a review of previous reports about the effects of smoking on the lactation process, breast milk composition and infant development. A systematic search for English language articles published until 2015 was made, using a MEDLINE data. The key search terms were "smoking and breastfeeding", "smoking and lactation", "smoking and milk composition", "nicotine and breast milk". Studies have shown that nicotine levels in breast milk of women who smoke are three times higher than those in the plasma levels. Breast milk volume is reduced and the duration of lactation period is shorter. Smoking causes adverse changes to the milk's composition by not only reducing its protective properties, but also affecting infants' response to breastfeeding and to breast milk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study., Results: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns' hair when compared to mothers'. The mean concentrations of diazepam in mothers' hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns' hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers' hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns' hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn's hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers' hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam and temazepam--were detected in very few cases, in low concentrations.

Background: Based on evidence that exposure to smoking in movies is associated with adolescent smoking, the WHO has called on countries to assign a rating that restricts youth access to such movies., Objective: To evaluate youth access to movies that portray smoking in European countries and compare with that in the USA., Methods: The authors identified the most commercially successful movies screened in six European countries (Germany, Iceland, Italy, the Netherlands, Poland and UK) and the USA between 2004 and 2009. The authors coded the 464 movies that were screened in both Europe and the USA according to whether or not they portrayed smoking., Results: 87% of the movies were 'youth' rated in Europe (ratings board classification as suitable for those younger than 16 years) compared to only 67% in the USA (suitable for those younger than 17 years). Smoking was portrayed in 319 (69%) movies. 85% of the movies that portrayed smoking were 'youth' rated in Europe compared with only 59% in the USA (p<0.001)., Conclusions: Tobacco imagery is still common in popular films shown in European countries and the USA. None of the seven countries examined followed the WHO recommendations on restricting youth access to movies that portray smoking. Compared to the USA, European youths have access to substantially more movies in general, and this gives them access to more movies that portray smoking in particular.

Background: Tobacco smoking and alcohol abuse causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Liver is the main organ exposed to alcohol toxic metabolites, whereas tobacco smoke is chiefly harmful to the lungs., Methods: The aim of the current study was the assessment and comparison of selected oxidative stress markers, reduced glutatione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase, nitrites and protein nitrosylation and DNA damage in the livers and in the lungs of alcohol-addicted rats exposed to tobacco smoke alone or in combination with a single dose of ethanol., Results: The highest levels of GSH were measured in the liver of smoke only exposed animals and in the lungs of rats exposed to smoke and alcohol. In the liver of animals treated with a single dose of alcohol or with smoke and alcohol, GST was significantly higher than in the group exposed to smoke only. SOD and catalase showed the highest activities in the livers of rats receiving a single dose of alcohol. High concentration of nitrites was observed in the lungs of animals treated with smoke and alcohol in combination, which corresponded to elevated protein nitrosylation in this group, whereas in the livers of these animals relatively low level of nitrites was accompanied with the lowest concentration of nitrosylated proteins. In the liver of alcohol only treated rats the highest nitrites corresponded to the highest protein nitrosylation. In the lungs of all treatment groups the range of DNA damage was higher, than the respective values in the livers. Although alcohol is not considered a specific toxicant to the lungs it was found to cause oxidative stress in this organ., Conclusions: The obtained results suggest that in the ethanol-addicted rats combined exposure to smoke and alcohol differentially modulate endogenous antioxidant defense system and reactions to oxidative stress.