Oxidative Stress in Xenograft Mouse Model Exposed to Dendrimers Decorated Polydopamine Nanoparticles and Targeted Chemo- and Photothermal Therapy.

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.

Polydopamine-Based Material and Their Potential in Head and Neck Cancer Therapy-Current State of Knowledge.

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.

Iron, Ferroptosis, and Head and Neck Cancer.

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.

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide.

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.

Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models.

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.

Toxic metals in human milk in relation to tobacco smoke exposure.

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.

Two Ecdysteroids Isolated from Micropropagated Lychnis flos-cuculi and the Biological Activity of Plant Material.

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 IC50 of 0.06 mg/mL at the 3rd day of treatment. Both ecdysteroids show comparable activity at IC50 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.

Vitamin D in Head and Neck Cancer: a Systematic Review.

PURPOSE OF REVIEW: Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. RECENT FINDINGS: The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.

Molecular and health effects in the upper respiratory tract associated with tobacco smoking other than cigarettes.

The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

The effect of maternal tobacco smoking and second-hand tobacco smoke exposure on human milk oxidant-antioxidant status.

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.

The Anti-Serotonin Effect of Parthenolide Derivatives and Standardised Extract from the Leaves of Stizolophus balsamita.

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.

Ecdysteroids: production in plant in vitro cultures.

Ecdysteroids are secondary metabolites, widely distributed in the animal and plant kingdoms. They have a wide range of pharmacological effects in vertebrates, including mammals, most of which are beneficial for humans. Therefore, they have become compounds of interest for the pharmaceutical industry due to their adaptogenic, anabolic, hypoglycaemic, hypocholesterolaemic and antimicrobial activities, which are still being researched. Nowadays, ecdysteroids are present as active ingredients in bodybuilding supplements. Because of their complex structures, their chemical synthesis seems unprofitable and impractical. Due to high content of ecdysteroids in many plants, they are primarily obtained by extraction of the plant material. Plant in vitro cultures provide an alternative source of these compounds, helping to avoid problems associated with field production-such as variable yield or dependence on environmental factors, as well as limited availability of natural resources. Plant cell and tissue cultures may be suggested as alternatives for the production of plant biomass rich in pharmaceutically active ecdysteroids. Moreover, the use of common biotechnological strategies, such as elicitation or precursor feeding, may further increase the yield and improve production of these compounds. In this paper, we describe general information about ecdysteroids: their structure, biosynthesis, distribution, role in plants, and we review recent studies on micropropagation of ecdysteroid-producing plants and cell cultures, and potential ability of ecdysteroids enhancement in in vitro cultures.

Metal concentrations in hair of patients with various head and neck cancers as a diagnostic aid.

Head and neck cancers are one of the most frequent cancers worldwide. This paper attempts to evaluate disturbances of homeostasis of the necessary elements (calcium, magnesium, zinc, copper, iron, manganese) and changes in the levels of toxic metals (lead, cadmium, cobalt, chromium VI) in hair of patients with head and neck cancers, as well as people without a diagnosed neoplastic disease. In order to quantify the necessary elements and toxic metals, a method using ICP-MS and ICP-OES techniques had been developed and validated. The studies have shown that patients with head and neck cancer used to drink alcohol and smoked much more frequently than healthy individuals, both in the past and presently. Statistically significant differences in concentrations of average metal content in the group of patients with head and neck cancers compared to the control group were confirmed. Significant differences in metal content between the group of patients with head and neck cancers and healthy individuals were found which enabled distinguishing between the study groups. To this end, a more advanced statistical tool, i.e. chemometrics, was used. The conducted research analyses and the use of advanced statistical techniques confirm the benefits of using alternative material to distinguish the patients with head and neck cancers from the healthy individuals.

Tobacco smoking and breastfeeding: Effect on the lactation process, breast milk composition and infant development. A critical review.

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.

Cytological evaluation of the nasal mucosa in neonates exposed to tobacco smoke during fetal life.

OBJECTIVES: The objective of this study is to assess the cytological picture of the nasal mucosa of neonates born to mothers who are active smokers, passive smokers and non-smokers. METHODS: A prospective study was conducted in a group of 86 neonates born between 23 and 41 weeks of gestation. The assignation of neonates to one of the three aforementioned groups was based on a questionnaire concerning exposure to tobacco smoke, and on the concentration of cotinine in maternal urine. A cytological examination was performed using exfoliative cytology with a semi-quantitative evaluation of the cells present in the specimens. Hematological summation equipment was used to assess the number of neutrophils, eosinophils, columnar, goblet, basal and squamous cells out of 500 cells counted. The number of specific cells was expressed as a percentage and a cytogram was created. RESULTS: The most common type of cytogram contained neutrophils, columnar cells, and squamous cells. No significant differences were observed between the subgroups. Similarly, there was no correlation between the median of each type of cell and the cotinine concentration in the mothers' urine. CONCLUSION: Active and passive smoking during pregnancy do not influence the cytological picture of the nasal mucosa of neonates.

[Qualitative and quantitative determination of caffeine in saliva by high performance liquid chromatography].

The European Union drew attention to the increased consumption and the reports of adverse reactions to caffeine in recent years. The EU Commission in Regulation No. 536/2013 dated 11 June 2013 expressed concern about the caffeine content in the products. It is important to develop a simple and accurate methods for determining the level of caffeine in the biological material for accurate exposure assessment, as well as in the caffeinated products. The use of saliva as a diagnostic material is painless, non-invasive and does not require the participation of professional medical personnel. The compounds identified in saliva showed relatively high durability. The developed method for the determination of caffeine by high performance liquid chromatography with diode array detection (HPLC-DAD) after extraction of caffeine from saliva by solid phase extraction (SPE) is characterized by the linearity in the concentration range 50 - 2000 ng/mL. This method have low detection (12 ng/mL) and quantification (40 ng/mL) limits and high intra-day (4.87% for low concentration and 2.10% for high concentration) and inter-day (5.84% for low concentration and 2.43% for high concentration) repeatability.

[Nicotine and caffeine: influence on dopaminergic transmission].

Dopamine plays an important role in the neuronal regulation of motivation / reward, voluntary movements, cognitive processes and the process of addiction. Disorders of the production and release of dopamine can be the base of the pathomechanism of many diseases. Both nicotine and caffeine are psychomotor stimulants. Caffeine, through inhibition of adenosine, increases the activity of the dopaminergic system, and it shows the reinforcing and the psychomotor effect. Nicotine gets its reinforcing and psychostimulant effects from blocking dopamine uptake and increasing synaptic dopamine release. Nicotine and caffeine affect the release of the dopamine. It is believed that the interaction of these substances may be a synergistic effect on pain perception, voluntary movement functions or behavioral traits.

[The impact of cannabinoids on the endocrine system].

Cannabinoids are naturally occurring compounds, derivatives of Indian hemp, in which tetrahydrocannabinol (THC) is the most important. Marijuana, hashish and hash oil are among those most commonly used in the group. Cannabinoids (marjhuana and hashish) have been used throughout recorded history as effective drugs in treating various diseases and conditions such as: malaria, hypertension, constipation, bronchial asthma, rheumatic pains, and as natural pain relief in labour and joint pains. Marijuana acts through cannabinoid receptors CB 1 and CB2. Both receptors inhibit cAMP accummulation (through Gi/o proteins) and stimulate mitrogen- activated protein kinase. CB1 rceptors are located in CNS and in adipose tissue, digestive tract, muscles, heart, lungs, liver, kidneys, gonads, prostate gland and other peripheral tissues. CB2 cannabinoid receptors are located in the peripheral nervous system (at the ends of peripheral nerves), and on the surfaces of the cells of the immunological system. The discovery of endogenous cannabinoids has contributed to a better understanding of their role in the regulation of the intake of food, energetic homeostasis and their significant influence on the endocrine system.

[Interaction between cigarette smoking and glucocorticoids therapy and therapeutic doses of radioiodine (131I) in patients with Graves' disease].

The present study evaluated the effects of smoking on the amount of therapeutic doses of radioiodine ((131)I) given to patients with Graves' disease (GB). The study also retrospectively analyzed the relationship between the onset of symptoms of thyroid ophthalmopathy (OT) after treatment with (131)I within 2 years and changes of TSHR-Abs levels, and the impact of prednisone administration before and after the therapy on OT development in both smoking and non-smoking patients. Materials and Methods: The study group included 116 patients, 97 women and 19 men, aged 28 ÷ 77 years (average 51 years) who were diagnosed with GB and treated with therapeutic doses of (131)I. Of the 116 patients treated, 85 patients were given a single dose of (131)I, whereas in 31 patients, due to recurrent hyperthyroidism, there was a need for a second dose of (131)I. In the group of 85 studied patients who received a single therapeutic dose of (131)I, 34 patients were smokers, including 27 women and 7 men, whereas in the group of 31 patients with recurrent hyperthyroidism who received repeated doses of 131I, 21 patients were smokers, 17 women and 4 men. Patients qualified for the therapy with (131)I and diagnosed with mild OT, were given prednisone, administered orally with an initial dose of 0.4 - 0.5 mg/kg daily tapering within 4-6 weeks. Results: The results of the study demonstrated that there was a statistically significant relationship (p<0.05) between cigarette smoking and the number of administered therapeutic doses of (131)I in patients with GD. Smoking patients needed to be given the second therapeutic dose of (131)I more frequently. The relationship between the onset of symptoms of OT in patients with GD and the TSHRAb in serum within two years after (131)I administration was highly significant (p<0.0001). The results obtained in our study showed that efficacy of therapy was lower in smokers with GD when compared with non-smokers Since the increased titer of TSHR-Ab was associated with higher risk of OT development, especially in smokers, its routine measurement after (131)I administration could be considered in all treated patients with GD. Steroid prophylaxis should be recommended for each smoking GD patient with mild OT qualified for (131)I therapy.

[Historical trends in prevalence of tobacco smoking among women]. / Historyczne trendy rozpowszechnienia palenia tytoniu wsród kobiet.

The paper contain a brief historical introduction about tobacco and smoking trends among women over the years--from cigarettes introduction to the present (years 1840-2014). Particular attention was paid to the historical backgrounds and marketing strategies of tobacco companies, which tried to reach each of women. Moreover, this paper described the dangers of smoking, which have been proven by scientists over the years and the impact of this knowledge on the tobacco industry and cigarettes consumption by women.