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Artificial catalytic synthesis of ammonia has become a hot research frontier in recent years. It is regarded as a promising approach that may replace the Haber-Bosch process and reduce global carbon dioxide emission. However, it is extremely difficult for the cleavage of nitrogen molecules under ambient conditions. Thus the ammonia yield rate is still low and the study is still limited in lab scale. If nitrites or nitrates are used as nitrogen sources, rather than nitrogen gas, the catalytic efficiency can be significantly improved, and the residual nitrate and nitrite contaminations in water systems can be efficiently eliminated and converted to energy sources at the same time. It is an emerging alternative for artificial ammonia synthesis, while there is not enough focus on the reduction of nitrate and nitrite. Herein, we systematically compared the differences between the reduction of nitrogen and nitrates, as well as listed the challenges in this area. The total conversion rate and energy efficiency of catalytic nitrate reduction are much higher than nitrogen gas reduction due to the much higher solubility and better converting pathway, which might be further enhanced by employing catalysts improvement strategies. Further, we also proposed suitable materials as well as a few future researches needs that may help boost the development of artificial ammonia synthesis using nitrate.

Despite significant research progress on the pathogenesis, molecular biology, diagnosis, treatment, and prevention of cancer, its morbidity and mortality are still high around the world. The emerging resistance of cancer cells to anticancer drugs remains still a significant problem in oncology today. Furthermore, an important challenge is the inability of anticancer drugs to selectively target tumor cells thus sparing healthy cells. : One of the new potential options for efficient and safe therapy can be provided by opioid growth factor (OGF), chemically termed Met-enkephalin. It is an endogenous pentapeptide (Tyr-Gly-Gly-Phe-Met) with antitumor, analgesic, and immune-boosting properties. Clinical trials have demonstrated that OGF therapy alone, as well as in combination with standard chemotherapies, is a safe, non-toxic anticancer agent that reduces tumor size. : In this paper, we review the structure-activity relationship of OGF and its analogues. We highlight also OGF derivatives with analgesic, immunomodulatory activity and the ability to penetrate the blood-brain barrier and may be used as safe agents enhancing chemotherapy efficacy and improving quality of life in cancer patients. : The reviewed papers indicate that Met-enkephalin and its analogues are interesting candidates for the development of novel, non-toxic, and endowed with an analgesic activity anticancer drugs. More preclinical and clinical studies are needed to explore these opportunities.

Background: Alzheimer’s disease (AD) is progressive and irreversible neurodegenerative disorder. Current pharmacotherapy is not able to stop progression of the disease and can only improve cognitive functions. Therefore, new drugs are being sought that will slow down the development of the disease. Objective: Novel phosphorus and thiophosphorus tacrine derivatives 7-14 were designed, synthesized and their biological activity and molecular modeling was investigated as a new potential anti- Alzheimer’s disease (AD) agents. Methods: 9-Chlorotacrine was treated with propane-1,3-diamine in the presence of sodium iodide to yield N1-(1,2,3,4-tetrahydroacridin-9-yl)propane-1,3-diamine 6. Finally, it was treated with corresponding acid ester or thioester to give phosphorus or thiophosphorus tacrine derivative 7-14. All of the obtained final structures were characterized by 1H NMR, 13C NMR, 31P NMR and MS. Results: The results of the docking studies showed that the newly designed phosphorus and thiophosphorus tacrine analogs, theoretically possess AChE and BChE-binding ability. Kinetic study showed that 8 and 12 in the series proved to be more potent electric eel AChE (eeAChE) and human (hAChE) inhibitors than tacrine, where 8 inhibited eeAChE three times more than the referenced drug. The highest BChE inhibition revealed 11 and 13. The most active compounds against eeAChE, hAChE and BChE showed mixed type of inhibition. Conclusion: All new synthesized compound exhibited lower toxicity against neuroblastoma cell line (SH-SY5Y) in comparison with tacrine. Two analogues in the series, 7 and 9, demonstrated lack of cytotoxicity against hepatocellular cells (hepG2).

In this work, we report a stepwise formation method of a chitosan/sodium alginate polyelectrolyte complex (CS/SA PEC) membrane. The proposed method aiming at the utilization of the ultrasonic treatment of chitosan and sodium alginate solution allowed us to obtain a highly homogeneous hybrid membrane for electrochemical usage. The CS/SA PEC membrane saturated in a 2 M Li2SO4 aqueous solution was used in electrochemical double layer capacitor (EDLC) cell to study its applicability as quasi-solid electrolyte. Electrochemical characteristic of EDLC cells was determined by electrochemical impedance spectroscopy, cyclic voltammetry and galvanostatic charge/discharge methods. The results show that the EDLC cell with CS/SA PEC quasi-solid electrolyte exhibit a comparable specific capacitance (102 F g-1 for 0–0.8 V) to CS reference (100 F g-1 for 0–0.8 V) and commercial separator (99 F g-1 for 0–0.8 V) cells. Thus, the CS/SA PEC membrane can be considered as an alternative modification for chitosanbased materials of electrochemical purpose.

Calorimetric titration studies of carbendazim and thiabendazole solutions with α-cyclodextrin solutions were performed. The study involved the determination stoichiometry of the resulting inclusion...

Isolated hypothyroxinemia (IH) unfavorably affects reproduction. This study aimed to evaluate retrospectively if any routinely measured clinical/laboratory parameters are associated with IH among women of childbearing age hospitalized in the endocrine department. A group of 466 female non-pregnant inpatients (age range 13–57 years) was considered. IH (decreased free thyroxine (FT4) with normal TSH) was found in 8/466 patients (1.72%). Vitamin D deficiency (&lt, 30 ng/mL) was found in all patients with IH, whereas severe Vitamin D deficiency (&lt, 20 ng/mL) was found in 5/6. Vitamin D concentration was lower in IH females. FT4 concentration was lower in patients with severe vitamin D deficiency and correlated positively with vitamin D concentration. Insulin resistance index (IRI) was increased (&gt, 1.25) in 5/6 patients with IH. IRI was higher in IH patients and it was the only independent linear factor for IH in the univariate regression. FT4 concentration was lower in patients with increased IRI and correlated negatively with IRI. FT4 concentration correlated negatively with body mass index (BMI) and LDL cholesterol or triglycerides, and positively with HDL cholesterol or HDLC/cholesterol ratio. Vitamin D deficiency, insulin resistance and increased BMI (as potential causative factors), and abnormal lipid profile (as a possible consequence), are associated with IH in women of childbearing age. Eliminating risk factors for hypothyroxinemia may improve reproductive health.

Iron excess in tissues results in increased oxidative damage. Among different tissues, the skin can particularly be severely damaged by oxidative stress, as it is exposed not only to endogenous but also directly to exogenous pro-oxidants. The skin is especially vulnerable to harmful oxidative stress. Melatonin and indole-3-propionic acid (IPA), two indole substances, are efficient antioxidants. This study aims to evaluate the potential protective effects of melatonin and IPA against oxidative damage to membrane lipids (lipid peroxidation (LPO)), induced in porcine skin homogenates by the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO4 (2400, 1200, 600, 300, 150 and 75 µM) + H2O2 (5 mM) with/without melatonin or IPA. LPO level (MDA + 4-HDA/mg protein) was measured spectrophotometrically. Melatonin, in its highest used concentration (5.0 mM), prevented FeSO4 (1200 mM)-induced LPO, whereas it was effective in concentrations as low as 2.5 mM against all lower iron concentrations. IPA was protective in concentrations as low as 2.5 mM independently of FeSO4 concentration. In conclusion, melatonin and IPA effectively protect against oxidative damage to membrane lipids induced by high concentrations of iron in porcine skin; therefore, both can be considered pharmacological agents in the case of disorders associated with excessive iron accumulation in the skin.

Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin is an effective antioxidant, which protects against KIO3-induced LPO in the thyroid. This study aimed to compare the protective effects of melatonin, used in the highest achievable in vitro concentration, against KIO3-induced oxidative damage to membrane lipids in various porcine tissues (thyroid, ovary, liver, kidney, brain, spleen, and small intestine). Homogenates were incubated in the presence of KIO3 (20, 15, 10, 7.5, 5.0, 0.0 mM) without/with melatonin (5 mM). The malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased the LPO in all examined tissues, in the thyroid, the damaging effect of KIO3 (10, and 7.5 mM) was lower than in other tissues and was not observed for the lowest concentration of 5 mM. Melatonin reduced LPO induced by KIO3 (10, 7.5, and 5 mM) in all tissues, and in the thyroid it was also protective against as high a concentration of KIO3 as 15 mM, the LPO level resulting from KIO3 + melatonin treatment was lower in the thyroid than in other tissues. In conclusion, the thyroid is less sensitive tothe pro-oxidative effects of KIO3 compared to other tissues. The strongest protective effect of melatonin was observed in the thyroid, but beneficial effects were significant also in other tissues. Melatonin should be considered to avoid the potential damaging effects of iodine compounds applied in iodine prophylaxis.

It has long been observed that thyroid diseases are more prevalent in women than in men. However, there are limited experimental data demonstrating mechanisms by which sex differences in thyroid diseases may occur and exact molecular mechanisms involved are still far from clear. The aim of the study was to evaluate if there are sex differences concerning oxidative damage to membrane lipids in thyroid homogenates in response to Fenton reaction substrates, i.e., Fe

Tacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and butyrylcholinesterase) that shows limiting clinical application by liver toxicity. In spite of this, analogues of tacrine are considered as a model inhibitor of cholinesterases in the therapy of Alzheimer’s disease. The interest in these compounds is mainly related to a high variety of their structure and biological properties. In the present review, we have described the role of cholinergic transmission and treatment strategies in Alzheimer’s disease as well as the synthesis and biological activity of several recently developed classes of multifunctional tacrine analogues and hybrids, which consist of a new paradigm to treat Alzheimer’s disease. We have also reported potential of these analogues in the treatment of Alzheimer’s diseases in various experimental systems.

A series of substituted piperazinium, piperidinium, and pyrrolidinium acetates were synthesized. Highly effective cellulose solvents have been designed by mixing an aprotic polar solvent, dimethyl sulfoxide (DMSO), with synthesized ionic liquids (ILs). Different weight ratios of corresponding IL/DMSO mixed solvents were prepared to investigate the effect of cosolvent on cellulose solubility. Cellulose solubility in IL/DMSO solvent systems was measured at 25, 50 and, 80 °C. The effect of factors such as solvent composition, process temperature, type of IL’s cation, and alkyl chain length of IL’s cation on cellulose solubility was investigated. Amongst all tested solvents, N,N’-dimethyl-N-ethylpiperazinium acetate ([DMEPpz][Ac]/DMSO) mixed solvent exhibits the best performance in the dissolution of cellulose, reaching up to 13.5 wt% at 80 °C. The dissolved cellulose was regenerated using water as an antisolvent. The structure and morphology of the regenerated cellulose material were characterized by SEM, XRD, and FTIR, respectively.

Background Poplar leaf-buds (Populi gemmae) are used traditionally as anti-inflammatory agents to the treatment of skin injuries or cough. They differ in their diverse chemical composition and different types of activities, whose mechanisms are not fully recognized. Purpose Evaluation and comparison of anti-inflammatory activity of leaf-buds extracts from Populus nigra, P. × berolinensis and P. lasiocarpa and flavanones - pinocembrin and pinostrobin towards human gingival fibroblasts (HGF-1) pro-inflammatory stimulated by silver nanoparticles (AgNPs). Determination of antioxidant activity associated with anti-inflammatory properties by means of bioautographic TLC tests. Methods Phytochemical analysis was performed by TLC and videodensitometry analysis. The extracts were standardized on the pinocembrin and pinostrobin content. Bioautography was performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and riboflavin-light blue tetrazolium chloride (riboflavin-light-NBT) radicals to assess the extracts and both flavanones radical scavenging properties as well as potential inhibition of xanthine oxidase (XO) activity. The protective effects of poplar buds extract and flavanones – pinocembrin and pinostrobin on HGF-1 line exposured to AgNPs were investigated by analysis of interleukin 6 (IL-6) and interleukin IL-1β (IL-1β) level measured by ELISA kit. The messenger ribonucleic acid (mRNA) of both cytokines was determined by real-time quantitative PCR. The involvement of cyclooxygenase 2 protein (COX-2) was studied using Western blot analysis. Results The presence of several flavanones and phenolic acids, which have radical scavenging properties, was revealed in all of the bud poplar extracts analyzed. Treatment with particular flavanones or extracts from buds of P. × berolinensis and P. nigra decreased the IL-6 and IL-1β release in HGF-1 cells and down-regulation of mRNA for both cytokines was observed. The COX-2 protein expression was demonstrated for pinocembrin and P. × berolinensis buds. These effects were not observed for buds from P. lasiocarpa not containing of flavonoids. Conclusion The potential protective role of pinocembrin and pinostrobin and extracts from buds P. nigra and P. × berolinensis against AgNPs induced inflammation and cytotoxicity in HGF-1 cells is disclosed. In addition, the antioxidant properties of poplar bud extracts have been demonstrated. P. × berolinensis buds showed the highest activity in both the in vitro model and in the bioautographic tests.

Discovering that metals are essential for the structure and function of biomolecules has given a completely new perspective on the role of metal ions in living organisms. Nowadays, the design and synthesis of new metal-based compounds, as well as metal ion binding components, for the treatment of human diseases is one of the main aims of bioinorganic chemistry. One of the areas in vanadium-based compound research is their potential anticancer activity. In this review, we summarize recent molecular and cellular mechanisms in the cytotoxic activity of many different synthetic vanadium complexes as well as inorganic salts. Such mechanisms shall include DNA binding, oxidative stress, cell cycle regulation and programed cell death. We focus mainly on cellular studies involving many type of cancer cell lines trying to highlight some new significant advances.

Despite significant progress in the pathogenesis, diagnosis, treatment, and prevention of cancer and neurodegenerative diseases, their occurrence and mortality are still high around the world. The resistance of cancer cells to the drugs remains a significant problem in oncology today, while in the case of neuro-degenerative diseases, therapies reversing the process are still yet to be found. Furthermore, it is important to seek new chemotherapeutics reversing side effects of currently used drugs or helping them perform their function to inhibit progression of the disease. Carnosine, a dipeptide constisting of β-alanine and l-histidine, has a variety of functions to mention: antioxidant, antiglycation, and reducing the toxicity of metal ions. It has therefore been proposed to act as a therapeutic agent for many pathological states. The aim of this paper was to find if carnosine and its derivatives can be helpful in treating various diseases. Literature search presented in this review includes review and original papers found in SciFinder, PubMed, and Google Scholar. Searches were based on substantial keywords concerning therapeutic usage of carnosine and its derivatives in several diseases including neurodegenerative disorders and cancer. In this paper, we review articles and find that carnosine and its derivatives are potential therapeutic agents in many diseases including cancer, neurodegenerative diseases, diabetes, and schizophrenia. Carnosine and its derivatives can be used in treating neurodegenerative diseases, cancer, diabetes, or schizophrenia, although their usage is limited. Therefore, there's an urge to synthesize and analyze new substances, overcoming the limitation of carnosine itself.

High-normal TSH can be associated with metabolic abnormalities and infertility. Aims of this study are to analyze retrospectively if routinely measured blood laboratory and anthropometric parameters differ between women of reproductive age with TSH &lt, 2.5 mIU/L and with TSH &ge, 2.5 mIU/L. Retrospective analysis was performed in 466 female inpatients, aged 13&ndash, 51, hospitalized in an endocrine department. The group of 280 patients with normal thyroid tests (TSH 0.27-4.2 mIU/L, normal FT3 and FT4) was selected and it was divided into two subgroups, i.e., with TSH &lt, 2.5 mIU/L and TSH &ge, 2.5 mIU/L (n = 66, 23.6%). After excluding patients on L-thyroxine treatment (n = 240), those with TSH &ge, 2.5 mIU/L constituted 22.92% (n = 55). In the group of 280 patients with normal thyroid tests, an abnormally high concentration of triglycerides and an abnormally low HDLC/cholesterol ratio occurred more frequently in women with TSH &ge, 2.5 mIU/L than those with TSH &lt, 2.5 mIU/L (17% vs. 7%, p = 0.017, 14% vs. 5%, p = 0.015, respectively). Increased concentration of thyroid antibodies, i.e., TPOAb, occurred more frequently in patients with TSH &ge, 2.5 mIU/L (27% vs. 9%, p = 0.001). The same differences were found in the group of 240 patients after excluding those on L-thyroxine treatment. Blood lymphocyte concentration was the only independent linear parameter associated with TSH &ge, 2.5 mIU/L (OR = 1.551, p = 0.024) but only in the group of 280 patients with normal thyroid tests. TSH concentration correlated positively with blood lymphocyte (r = 0.129, p = 0.031) and TPOAb (r = 0.177, p = 0.005) concentrations but only in the group of 280 patients with normal thyroid tests. Less favorable lipid profiles and a higher prevalence of thyroid antibodies in women of reproductive age with high-normal TSH suggests that L-thyroxine treatment should be considered in such patients. The significance of a positive association between high-normal TSH and blood lymphocytes requires further evaluation.

Background: At the present time, there is a growing interest in metal-based anticancer agents. Metal complexes exhibit many valuable clinical properties, however, due to toxicity, only a few clinically useful complexes have been discovered. It has been demonstrated that synthetic vanadium complexes exhibit many biological activities, including anti-cancer properties, however, cellular and molecular mechanisms still are not fully understood. Objective: This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells. Methods: We measured cytotoxicity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, antiproliferative activity by bromodeoxyuridine assay and necrosis as well as late apoptosis by lactate dehydrogenase assay. Reactive oxygen species generation, apoptosis and mitochondrial membrane potential were determined by a flow cytometry technique. Cell morphology was evaluated by using a transmission electron microscope. Results: The results showed that oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2) over the concentration range of 12.5-200μM, following 48h incubation. Additionally, the cellular mechanism of cytotoxic activity of [2-NH2-3-OH(py)H]4[V2O2(pmida)2]·6H2O (V3) complex was dependent on ROS generation, induction apoptosis with simultaneous disruption of mitochondrial membrane potential. Conclusion: We have proven that oxidovanadium (IV) complexes show therapeutic potential in pancreatic cancer therapy. The results of our research will help to understand the cellular mechanisms of the cytotoxic activity of the vanadium complexes and will allow a more effective design structure of new vanadium-based compounds in the future.

Three-dimensional (3D) biopolymer-based scaffolds including chitinous matrices have been widely used for tissue engineering, regenerative medicine and other modern interdisciplinary fields including extreme biomimetics. In this study, we introduce a novel, electrochemically assisted method for 3D chitin scaffolds isolation from the cultivated marine demosponge Aplysina aerophoba which consists of three main steps: (1) decellularization, (2) decalcification and (3) main deproteinization along with desilicification and depigmentation. For the first time, the obtained electrochemically isolated 3D chitinous scaffolds have been further biomineralized ex vivo using hemolymph of Cornu aspersum edible snail aimed to generate calcium carbonates-based layered biomimetic scaffolds. The analysis of prior to, during and post-electrochemical isolation samples as well as samples treated with molluscan hemolymph was conducted employing analytical techniques such as SEM, XRD, ATR–FTIR and Raman spectroscopy. Finally, the use of described method for chitin isolation combined with biomineralization ex vivo resulted in the formation of crystalline (calcite) calcium carbonate-based deposits on the surface of chitinous scaffolds, which could serve as promising biomaterials for the wide range of biomedical, environmental and biomimetic applications. © 2020, The Author(s). Politechnika PoznaÅ ska, PUT: 0911/SBAD/0380/2019 Deutsche Forschungsgemeinschaft, DFG: HE 394/3 Deutscher Akademischer Austauschdienst, DAAD Russian Science Foundation, RSF: 18-13-00220 PPN/BEK/2018/1/00071 03/32/SBAD/0906 Sächsisches Staatsministerium für Wissenschaft und Kunst, SMWK: 02010311 This work was performed with the financial support of Poznan University of Technology, Poland (Grant No. 0911/SBAD/0380/2019), as well as by the Ministry of Science and Higher Education (Poland) as financial subsidy to PUT No. 03/32/SBAD/0906. Krzysztof Nowacki was supported by the Erasmus Plus program (2019). Also, this study was partially supported by the DFG Project HE 394/3 and SMWK Project No. 02010311 (Germany). Marcin Wysokowski is financially supported by the Polish National Agency for Academic Exchange (PPN/BEK/2018/1/00071). Tomasz Machałowski is supported by DAAD (Personal Ref. No. 91734605). Yuliya Khrunyk is supported by the Russian Science Foundation (Grant No. 18-13-00220).

Background Mannan-binding lectin (MBL) is a main component of the lectin pathway of the complement system. Lower MBL levels are associated with, among other conditions, hypothyroidism and adverse pregnancy outcomes. In turn, adverse pregnancy outcomes and infertility may result from hypothyroidism, even in patients with high normal Thyroid-stimulating hormone (TSH). The aim of this study was to determine if MBL level differs between women of reproductive age with low normal ( Methods Ninety five (95) patients with normal thyroid tests (TSH 0.27–4.2 mIU/l), aged 18–48 years, were prospectively enrolled. Several laboratory parameters were measured, including MBL level, thyroid tests and lipid profile. Results Serum MBL level was lower in women with TSH ≥ 2.5 mIU/l than with TSH Conclusion In women of reproductive age with normal thyroid tests, lower MBL is associated with high normal TSH and with less favourable lipid profile. Therefore treatment with L-thyroxine should be considered in women of reproductive age with TSH ≥ 2.5 mIU/l.

The development of novel and effective methods for the isolation of chitin, which remains one of the fundamental aminopolysaccharides within skeletal structures of diverse marine invertebrates, is still relevant. In contrast to numerous studies on chitin extraction from crustaceans, mollusks and sponges, there are only a few reports concerning its isolation from corals, and especially black corals (Antipatharia). In this work, we report the stepwise isolation and identification of chitin from Cirrhipathes sp. (Antipatharia, Antipathidae) for the first time. The proposed method, aiming at the extraction of the chitinous scaffold from the skeleton of black coral species, combined a well-known chemical treatment with in situ electrolysis, using a concentrated Na2SO4 aqueous solution as the electrolyte. This novel method allows the isolation of &alpha, chitin in the form of a microporous membrane-like material. Moreover, the extracted chitinous scaffold, with a well-preserved, unique pore distribution, has been extracted in an astoundingly short time (12 h) compared to the earlier reported attempts at chitin isolation from Antipatharia corals.

Abstract. Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p 3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.

Several acetate and lactate ionic liquids (ILs) based on pyrrolidinium, piperidinium, or piperazinium cation were synthesized and characterized. Two of these compounds, N-methyl-N-propylpyrrolidinium acetate ([MPPyrr][Ac]) and N-methyl-N-propylpyrrolidinium lactate ([MPPyrr][L]) have been proved to be room temperature ionic liquids (RTILs). Temperature dependencies of conductivity and electrochemical stability of RTILs were determined. The conductivities of these compounds were of the order of ca. 6 mS cm−1 at ambient temperature. The Vogel-Tammann-Fulcher (VTF) equation was used to describe the dependence of conductivity on temperature with high precision. Electrochemical stability ranges were estimated on platinum and a glass-like carbon electrode. Electrochemical properties of all synthesized ILs in a form of mixtures with acetonitrile (AN) were also determined. Acetonitrile concentration dependencies of conductivity as well as the electrochemical stability of IL/AN mixtures were measured. Additionally, neat RTILs, as well as IL/AN mixtures, were tested as electrolytes in EDLC devices with commercial carbon cloth as the electrode material. The specific capacitances of these devices shown values of 34–57 F g−1, with 2 V of maximum operating voltage. The addition of AN increases conductivity significantly and distinctly improves the electrochemical properties of the capacitor cells by changing wettability and the charge relocation speed of the electrolytes in the selected electrode material.

In the present work, the cellulose-based materials were manufactured and used as components of electrochemical double layer capacitors (EDLCs). The preparation method of cellulose membranes as well as composite electrodes containing cellulose as a binder was presented. These materials were prepared using for the first time ionic liquid/dimethyl sulfoxide (IL/DMSO) mixture solvent. Obtained components displayed a uniform structure, thermal stability, and good electrochemical properties. The electrochemical performances of these materials were studied in 2-electrode EDLC cells by common electrochemical techniques as cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), and electrochemical impedance spectroscopy (EIS). The composite electrodes were investigated in three types of electrolytes: aqueous, organic, and ionic liquids. The cellulose membranes were, however, soaked in an aqueous electrolyte and tested as hydrogel polymer electrolytes. All investigated materials show high efficiency in terms of specific capacity. The studied cellulose-based capacitors exhibited specific capacitance values in the range of 20–22 F g−1, depending on the type of applied electrolyte.

Introduction and objective Protective antioxidative effects of melatonin have been repeatedly documented in experimental and clinical studies. One of the most spectacular exogenous prooxidative agents is cigarette smoking. The aim of the study was to evaluate the level of oxidative damage to membrane lipids (lipid peroxidation; LPO) in blood serum, and in epidermis exfoliated during microdermabrasion collected from former-smokers who were treated with melatonin. Material and methods The study was performed in postmenopausal women. Ninety (90) female volunteers, aged 46-67 years, were enrolled. Two major groups, i.e. never-smokers (n=44) and former-smokers (n=46), were divided into: Control, melatonin topical skin application, Restructurer (containing antioxidants) topical skin application, and melatonin oral treatment. Microdermabrasion was performed at point '0', after 2 weeks, and after 4 weeks of treatment. The following parameters were measured: LPO in blood serum, LPO in epidermis exfoliated during microdermabrasion, and skin biophysical characteristics, such as sebum, moisture, elasticity, and pigmentation. Malondialdehyde+4-hydroxyalkenals level (LPO index) was measured spectrophotometrically. Results Melatonin oral treatment significantly reversed the increased serum LPO level in former-smokers already after 2 weeks of treatment. In a univariate regression model, LPO blood level constituted the only independent factor negatively associated with melatonin oral treatment. After 4 weeks of treatment, melatonin given orally increased skin sebum, moisture and elasticity levels, and melatonin applied topically increased sebum level. Conclusions Exogenous melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers.

Tegafur (TF) is a 5-fluorouracil (FU) derivative used in cancer therapy with the hydrogen atom substituted by a tetrahydrofuran ring. The results of solubility measurements, equilibrium dialysis, 1H NMR titration and isothermal calorimetric titration (ITC) indicate that the surface of a PPI G4 macromolecule binds approximately 30 TF particles with the constant l o g K = 2.7 in an exothermic and thermodynamically spontaneous fashion in an aqueous environment at room temperature. The comparison of obtained parameters of TF binding by PPI G4 dendrimer with the literature data describing FU binding by PPI G4 dendrimer allowed to draw conclusions regarding the influence of hydrophobic tetrahydrofuran ring in the TF molecule on the stoichiometry, affinity and thermodynamics of the ligand binding by PPI G4 macromolecule in an aqueous medium.

The crystal and molecular structures of a new dinuclear oxidovanadium(IV) complex with the N-(phosphonomethyl)iminodiacetate (pmida) ligand and the 4-amino-2-methylquinolinium ([amqH]+) cation of the molecular formula [amqH]4[V2O2(pmida)2]6H2O have been determined. The phosphonate groups in the two pmida4− ligands form two bridges between adjacent V4+ atoms, resulting in the formation of a [V2O2(pmida)2]4− dimer with a V2O4P2 eight-membered ring. This is the first example of a quinoline derivative complex containing the [V2O2(pmida)2]4− ion. The susceptibility curve for the complex exhibits a maximum at approximately 10 K, indicating the presence of antiferromagnetic interactions transmitted in the crystal lattice. Furthermore, the biological properties of the complex in the concentration range 1–100 μM were investigated in relation to its cytoprotective activity against oxidative damage generated exogenously using hydrogen peroxide in the hippocampal neuronal HT22 cell line (MTT tests). The obtained results were subsequently referred to the [amqH][VO(nta)(H2O)]H2O analogue as well as trolox and ascorbic acid, used as known antioxidants. It has been established that the title compound effectively protects HT22 from oxidative damage and is a potentially good candidate for further evaluation of the mechanism of its action.

Water soluble amphiphilic anion receptors based on urea-substituted β-cyclodextrin were synthesized via a copper(I) mediated azide-alkyne coupling reaction. The synthetic route was designed to minimize the number of operations of cyclodextrins. Stable products were obtained in 90% yield. They were successfully tested as amino acid receptors, showing excellent affinity constants (103-104M-1) in a highly competitive environment (pH 8 phosphate-buffered water solution). Isothermal titration calorimetry indicated that complex formation strongly depends on the hydrophobic nature of the guest and that the urea moiety of the receptor is necessary to efficiently bind amino acids.

According to current recommendations, a TSH value of

Muscleblind-like proteins (MBNLs) are regulators of RNA metabolism. During tissue differentiation the level of MBNLs increases, while their functional insufficiency plays a crucial role in myotonic dystrophy (DM). Deep sequencing of RNA molecules cross-linked to immunoprecipitated protein particles (CLIP-seq) revealed that MBNL1 binds to MBNL1 exon 1 (e1) encoding both the major part of 5΄UTR and an amino-terminal region of MBNL1 protein. We tested several hypotheses regarding the possible autoregulatory function of MBNL1 binding to its own transcript. Our data indicate that MBNLs induce skipping of e1 from precursor MBNL1 mRNA and that e1 exclusion may impact transcript association with polysomes and translation. Furthermore, e1-deficient protein isoform lacking the first two zinc fingers is highly unstable and its EGFP fusion protein has severely compromised splicing activity. We also show that MBNL1 can be transcribed from three different promoters and that the transcription initiation site determines the mode of e1 regulation. Taken together, we demonstrate that MBNL proteins control steady-state levels of MBNL1 through an interaction with e1 in its precursor mRNA. Insights from our study open a new avenue in therapies against DM based on manipulation of the transcription initiation site and e1 splicing of MBNL1 mRNA.

Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and high-performance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast- hFOB1.19, breast cancer cells - MCF7, breast epithelial cells - MCF10A, pancreatic cancer cells - PANC-1, and pancreatic cells - hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

In this paper, we discuss the effect sewage sludge (SS) application has on the contamination of polycyclic aromatic hydrocarbons in fertilized soils and groundwater. Morver, the contents of these compounds in plant biomass was analyzed. For six months, composted sewage sludge was introduced into sandy soil. The research was conducted under lysimetric experiment conditions with the possibility of collecting soil leachate in natural conditions. The following doses of sewage sludge were used: 0, 10, 20, 30, and 40 t/ha calculated per experimental object containing 10 kg of sandy soil. The examinations were carried out within a three-year time frame. Dactylis glomerata grass was grown on the fertilized soils. Every year, the content of polycyclic aromatic hydrocarbons (PAHs) was collected from fertilized objects and analyzed in soil leachate, which can contaminate surface water. The following six polycylic aromatic hydrocarbons defined by Polish standards were determined: benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, dibenz(a,h)anthracene, and benzo(g,h,i)perylene, indeno(1,2,3-cd)pyrene. Further, the content of PAHs in soils and the bioaccumulation of these compounds in cultivated plants were evaluated after each year. The results of the study showed that the increase in the dose of sewage sludge used for soil fertilization led to the rise in the amount of polycyclic aromatic hydrocarbons analyzed in the soil. The compounds migrated to cultivated plants. This phenomenon was observed especially in the first year following soil fertilization with sewage sludge. Excessive accumulation of PAHs (especially benzo(a)pyrene) was observed in plant biomass in the first year of a lysimetric experiment after sewage sludge fertilization with doses greater than 10 t/ha. The increase in bioaccumulation of this compound in plant biomass compared to control objects was 138%, 288%, and 505% after application of 20, 30, and 40 t/ha, respectively. Fertilization with sewage sludge did not cause contamination with PAHs in water leachates from the soils.

Pancreatic cancer is characterized by one of the lowest five-year survival rates. In search for new treatments, some studies explored several metal complexes as potential anticancer drugs. Therefore, we investigated three newly synthesized oxidovanadium(IV) complexes with 2-methylnitrilotriacetate (bcma3−), N-(2-carbamoylethyl)iminodiacetate (ceida3−) and N-(phosphonomethyl)-iminodiacetate (pmida4−) ligands as potential anticancer compounds using pancreatic cancer cell lines. We measured: Cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) assay, antiproliferative activity by bromodeoxyuridine BrdU assay, reactive oxygen species (ROS) generation and cell cycle analysis by flow cytometry, protein level by Western blot and cellular morphology by confocal laser scanning microscopy. The results showed that these oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2), but not on non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE) over the concentration range of 10–25 μM, following 48 h incubation. Furthermore, molecular mechanisms of cytotoxicity of [4-NH2-2-Me(Q)H][VO(bcma)(H2O)]2H2O (T1) were dependent on antiproliterative activity, increased ROS generation, cell cycle arrest in G2/M phase with simultaneous triggering of the p53/p21 pathway, binucleation, and induction of autophagy. Our study indicates that oxidovanadium(IV) coordination complexes containing 2-methylnitrilotriacetate ligand are good candidates for preclinical development of novel anticancer drugs targeting pancreatic cancer.

The aim of the present study was to evaluate the thermodynamic parameters of the formation of supramolecular complexes of the flavonoid quercetin, a plant polyphenol with high therapeutic activity, and the molecular containers, β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD), as well as to assess the effects of quercetin and the quercetin - HPβСD complex on the functional activity of isolated rat liver mitochondria. The formation of the complex (stoichiometry 1:1) resulted in a marked elevation of quercetin water solubility: more than 5-fold in the case of 16 mM βCD (the association constant was equal to 300±45 М−1 as determined by the method of phase solubility diagram), and more than 50-fold in the case of 16 mM HPβCD (the association constant was equal to 3275±450 М−1), which reflects increased bioavailability of quercetin. In comparison, the association constant of the polyphenol sesamin - HPβСD complex formation (stoichiometry 1:1 and 1:2) was 2500 ± 350 М−1, and the solubility of sesamin in the complex increased more than 60-fold in the case of 10 mM HPβСD. The inclusion complex formation was spontaneous and exothermic, and both the enthalpic and entropic effects competed during complexation of polyphenol molecules with HPβCD, but the enthalpic factor was dominating in the bounding process in the case of quercetin and the entropic factor – in the case of sesamin. Quercetin and the quercetin - HPβCD complex considerably inhibited the respiratory activity of mitochondria, and uncoupled the oxidation and phosphorylation reactions, whereas quercetin alone, and not the complex, enhanced the mitochondria susceptibility to Ca2+-induced mitochondrial permeability transition (MPT). The complex quercetin - HPβCD (10–50 μM) was much more effective in preventing mitochondrial reduced glutathione depletion and α-ketoglutarate dehydrogenase impairment during mitochondria exposure to hypochlorous acid in comparison with the quercetin water solution due to enhanced availability of mitochondria matrix components to the antioxidant (quercetin). The decrease of quercetin lipophilicity after the complexation with HPβCD attenuated the effects on mitochondrial respiration and changed the direction of the effect on the MPT process owing to the quercetin redistribution between water and lipid phases.

The enthalpies of dilution of glycyl-L-α-alanine, glycyl-L-α-leucine and glycyl-L-glutamine have been measured in water at T = 298.15 K. The experimental results were used to calculate the enthalpic coefficients of the interactions between dipeptides molecules in water based on McMillan–Mayer's model. The values of the interaction parameters were interpreted in terms of the hydrophobic or hydrophilic properties of the amino acid side chins in the examined dipeptide molecules and the influence on their interactions with each other in water.

The influence of the oxydiacetate (ODA) and thiodiacetate (TDA) ligands on the physicochemical and biological properties of the oxidovanadium(IV) ternary complexes of the VO(L)(B) type, where L denotes ODA or TDA and B denotes 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen), has been investigated. The stability of the complexes in aqueous solutions, assessed based on the potentiometric titration method, increases in the following direction: VO(TDA)(bipy)

We report the synthesis of both macrocyclic and linear derivatives of pyrrole-2,5-diacetic bisamides, and the studies of their anion binding properties, which are further compared with the properties of similar derivatives bearing dipicolinic or isophthalic moieties. The new macrocyclic compound built on pyrrole-2,5-diacetic bisamide was found to be an efficient receptor for H2PO4− and PhCOO−, even in DMSO-d6 + 0.5% H2O (v/v), with changed relative selectivity toward a series of anions with respect to its parental analogues. The anion binding properties of the linear derivatives of pyrrole-2,5-diacetic bisamide, in turn, were found to strongly depend on the pKa of the amide NH protons, which can be modulated through the introduction of various substituents.

Objectives: In dentistry, silver nanoparticles (AgNPs) have drawn particular attention because of their wide antimicrobial activity spectrum. However, controversial information on AgNPs toxicity limited their use in oral infections. Therefore, the aim of the present study was to evaluate the antibacterial activities against a panel of oral pathogenic bacteria and bacterial biofilms together with potential cytotoxic effects on human gingival fibroblasts of 10 nm AgNPs: non-functionalized - uncapped (AgNPs-UC) as well as surface-functionalized with capping agent: lipoic acid (AgNPs-LA), polyethylene glycol (AgNPs-PEG) or tannic acid (AgNPs-TA) using silver nitrate (AgNO3) as control. Methods: The interaction of AgNPs with human gingival fibroblast cells (HGF-1) was evaluated using the mitochondrial metabolic potential assay (MTT). Antimicrobial activity of AgNPs was tested against anaerobic Gram-positive and Gram-negative bacteria isolated from patients with oral cavity and respiratory tract infections, and selected aerobic Staphylococci strains. Minimal inhibitory concentration (MIC) values were determined by the agar dilution method for anaerobic bacteria or broth microdilution method for reference Staphylococci strains and Streptococcus mutans. These strains were also used for antibiofilm activity of AgNPs. Results: The highest antimicrobial activities at nontoxic concentrations were observed for the uncapped AgNPs and the AgNPs capped with LA. It was found that AgNPs-LA and AgNPs-PEG demonstrated lower cytotoxicity as compared with the AgNPs-TA or AgNPs-UC in the gingival fibroblast model. All of the tested nanoparticles proved less toxic and demonstrated wider spectrum of antimicrobial activities than AgNO3 solution. Additionally, AgNPs-LA eradicated Staphylococcus epidermidis and Streptococcus mutans 1-day biofilm at concentration nontoxic to oral cells. Conclusions: Our results proved that a capping agent had significant influence on the antibacterial, antibiofilm activity and cytotoxicity of AgNPs. Clinical significance: This study highlighted potential usefulness of AgNPs against oral anaerobic Gram-positive and Gram-negative bacterial infections and aerobic Staphylococci strains provided that pharmacological activity and risk assessment are carefully performed.

A new chitosan/sponge chitin – based membrane (CS/CH membrane) was prepared via the casting method for the first time. We used the demineralized skeleton of the marine demosponge Ianthella basta as a source for a chitinous network. The obtained membrane was immersed in 1 M LiOAc (lithium acetate) solution and tested in an Electric Double Layer Capacitor (EDLC) cell. For comparison, chitosan (CS) with LiOAc solution was also tested. The studies performed indicated good properties of the CS/CH membrane. Very good mechanical stability (for use in electrochemical capacitors) and electrochemical properties of the CS membrane were achieved by the addition of chitin isolated from the sponge to the polymer matrix. Their electrochemical performances were tested in EDLC cells by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and galvanostatic charge/discharge. The specific capacitances of the tested capacitor cells were found to be approximately 97 F g−1 and 88 F g−1 with CS/CH and CS membranes (in the voltage range 0–0.8 V), respectively.

Estrogens, with their principle representative 17β-estradiol, contribute to the redox state of cells showing both pro- and antioxidative properties. In the ovary, being the main source of estrogens, maintaining balance between the production and detoxification of ROS is crucial. Whereas ovary estrogen concentration is difficult to estimate, its circulating concentration in women may reach the nanomolar level. The aim of the study was to evaluate the effects of 17β-estradiol on oxidative damage to membrane lipids (lipid peroxidation, LPO) and to nuclear DNA in the porcine ovary under basal conditions and in the presence of Fenton reaction (Fe(2+)+H2O2→Fe(3+)+(•)OH + OH(-)) substrates. Ovary homogenates and DNA were incubated in the presence of 17β-estradiol (1 mM-1 pM), without/with FeSO4 (30 μM) + H2O2 (0.5 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. The concentration of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) (DNA damage index) was measured by HPLC. We observed that 17β-estradiol did not alter the basal level of oxidative damage, but reduced Fe(2+)+H2O2-induced oxidative damage to membrane lipids when ≥10 nM and to DNA at concentrations ≥1 nM. In the ovary at near physiological concentration, 17β-estradiol prevents experimentally induced oxidative damage. This suggests that under physiological conditions this hormone may contribute to protecting the ovary against oxidative damage.

In order to assess the effect of β-cyclodextrin (β-CD) on the tebuconazole (TEB) solubility in water, UV–VIS spectroscopic measurements of the tebuconazole solutions with β-cyclodextrin were examined, followed by a VP-ITC calorimetric titration of the solutions of tebuconazole with β-cyclodextrin. The stoichiometry of the tebuconazole–β-cyclodextrin inclusion complex formed and the physical and chemical parameters describing the complex were determined. The effect of fungicide included inside the macromolecule of β-cyclodextrin on the fungal culture (hyphae) of Aspergillus fumigatus was also assessed.

The Fenton reaction (Fe2++H2O2→Fe3++•OH+OH-) results in strong oxidative damage to macromolecules when iron (Fe) or hydrogen peroxide (H2O2) are in excess. This study aims at comparing Fe2++H2O2-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and protective effects of 17β-estradiol (a potential antioxidant) in porcine ovary and thyroid homogenates. Iron, as one of the Fenton reaction substrates, was used in the highest achievable concentrations. Thyroid or ovary homogenates were incubated in the presence of: (1st) FeSO4+H2O2 with/without 17β-estradiol (1 mM; 100, 10.0, 1.0 µM; 100, 10.0, 1.0 nM; 100, 10.0, 1.0 pM); five experiments were performed with different FeSO4 concentrations (2400, 1200, 600, 300, 150 µM); (2nd) FeSO4 (2400, 1200, 600, 300, 150 µM)+H2O2 with/without 17β-estradiol; three experiments were performed with three highest 17β-estradiol concentrations; (3rd) FeSO4 (2400, 1200, 1100, 1000, 900, 800, 700, 600, 300, 150, 75 µM)+H2O2 (5 mM). LPO level [MDA+4-HDA/mg protein] was measured spectrophotometrically. The basal LPO level is lower in ovary than in thyroid homogenates. However, experimentally-induced LPO was higher in the former tissue, which was confirmed for the three highest Fe2+ concentrations (2400, 1200, 1100 µM). Exogenous 17β-estradiol (1 mM, 100, and 10 µM) reduced experimentally-induced LPO independently of iron concentration and that protective effect did not differ between tissues. The ovary, compared to the thyroid, reveals higher sensitivity to prooxidative effects of iron, however, it showed similar responsivity to protective 17β-estradiol activity. The therapeutic effect of 17β-estradiol against iron overload consequences should be considered with relation to both tissues.

The thermodynamic and spectroscopic parameters of the betulin/2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex and its hepatoprotective activity were investigated in rats with nonalcoholic steatohepatitis (NASH). The pentacyclic triterpene betulin was isolated from birch bark and complexed with HPβCD. The parameters of inclusion complex formation were evaluated by infrared spectroscopy and differential scanning and isothermal titration calorimetries. The aqueous solubility and stability of betulin were significantly increased due to the formation of a stable inclusion complex with a stoichiometry of 1:1. The determined changes in molar enthalpy (ΔH 0) and free energy (ΔG

The development of novel oral drug delivery systems is an expanding area of research and both new approaches for improving their efficacy and the investigation of their potential toxicological effect are crucial and should be performed in parallel. Polystyrene nanoparticles (NPs) have been used for the production of diagnostic and therapeutic nanosystems, are widely used in food packaging, and have also served as models for investigating NPs interactions with biological systems. The mucous gel layer that covers the epithelium of the gastrointestinal system is a complex barrier-exchange system that it is mainly constituted by mucin and it constitutes the first physical barrier encountered after ingestion. In this study, we aimed to investigate the effect of polystyrene NPs on mucin and its potential role during NP–cell interactions. For this purpose, we evaluated the interaction of polystyrene NPs with mucin in dispersion by dynamic light scattering and with a deposited layer of mucin using a quartz crystal microbalance with dissipation technology. Next, we measured cell viability and the apoptotic state of three enterocyte-like cell lines that differ in their ability to produce mucin, after their exposure to the NPs. Positive charged NPs showed the ability to strongly interact and aggregate mucin in our model. Positive NPs affected cell viability and induced apoptosis in all cell lines independently of their ability of produce mucin.

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, where the 5-year survival rate is less than 4% worldwide. Successful treatment of pancreatic cancer is a challenge for today’s oncology. Several studies showed that increased levels of oxidative stress may cause cancer cells damage and death. Therefore, we hypothesized that oxidative as well as nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18 nm) as a key factor triggering the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1). Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy. Then, the aim of our study was to evaluate the implication of oxidative and nitro-oxidative stress in this cytotoxic effect of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison purposes. We found that the increase was lower in noncancer cells. Reduction of mitochondrial membrane potential and changes in the cell cycle were also observed. Additionally, we determined the increase in RNS level: nitric oxide (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level. Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3), glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA level. Moreover, we showed cells ultrastructural changes, characteristic for oxidative damage. Summarizing, oxidative and nitro-oxidative stress and mitochondrial disruption are implicated in AgNPs-mediated death in human pancreatic ductal adenocarcinoma cells.

Chitin, poly N-acetylglucosamine, has a great potential for use on an industrial scale as an enzyme carrier but it has an unfavorable particle structure that can be modified using ionic liquids (ILs). Several ionic liquids were investigated that have the same substituents on the ring (methyl- and propyl-) but differed in the type of cationic ring (pyrrolidinium, piperidinium, and piperazinium). Organic acid ions (acetic and lactic) were used as counter ions. 1-ethyl-3-methyl-imidazolium acetate and 1-ethyl-3-methyl-imidazolium lactate were used as a reference. The results confirm that the chitin particle structure or size, or both, simultaneously changes if chitin is dissolved in an IL and then precipitated. Organic acid anions and short substituents on the cationic ring of ILs influenced particle modification substantially, whereas the type of ring played a minor role. Additionally, the ionic liquids [MPpyrr][OAc], [MPpip][OAc] and [DMPpz][OAc] could be reused up to at least 4 times without losing their ability to dissolve chitin.

Studies on the interactions between cucurbituril Q7 and gemcitabine (Gem) hydrochloride in water were carried out using isothermal titration calorimetry (ITC) and electrospray ionization–mass spectrometry (ESI-MS). According to ITC and ESI-MS, the formation of this complex occurs in both the solution containing excess gemcitabine and the solution containing excess cucurbituril Q7. ITC results confirm the formation of a thermodynamically stable supramolecular complex with stoichiometry 1:1. The inclusion mechanism of Gem inside the cucurbituril macromolecule is spontaneous ( $$\Delta G < 0$$ ). This process is exothermic ( $$\Delta H < 0$$ ) and is characterized by the loss of entropy ( $$\Delta S < 0$$ ).

An efficient multigram-scale azide-alkyne coupling of cyclodextrin derivatives mono-6-azido-6-deoxy-β-cyclodextrin, mono-2-O-propargyl-β-cyclodextrin, and mono-2-O-propargyl-α-cyclodextrin with terminal alkynyl aryl ethers or azides, mediated by copper(I) is reported. This process uses a stoichiometric ratio of substrates and 5 mol% of the copper catalyst to give the products with full conversion; thus, no chromatographic purification is necessary. The yields of both α- and β-cyclodextrin derivatives are in the range of 80 to 99%.

Purpose Iodine, bivalent iron (Fe2+), and hydrogen peroxide (H2O2), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10−3 M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff–Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO3), in concentrations corresponding to those typical for Wolff–Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe2++H2O2 → Fe3++·OH + OH−) substrates. Methods Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO3 (2.5–50 mM), without/with FeSO4 (30 µM) + H2O2 (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2′-deoxyguanosine, was measured by HPLC. Results Neither KI nor KIO3 increased the basal level of 8-oxodG in both nDNA and mtDNA. KI—in all used concentrations—completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO3 partially prevented Fe2++H2O2-induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). Conclusions Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO3, seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO3 relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.

Muscleblind-like (MBNL) proteins bind to hundreds of pre- and mature mRNAs to regulate their alternative splicing, alternative polyadenylation, stability and subcellular localization. Once MBNLs are withheld from transcript regulation, cellular machineries generate products inapt for precise embryonal/adult developmental tasks and myotonic dystrophy, a devastating multi-systemic genetic disorder, develops. We have recently demonstrated that all three MBNL paralogs are capable of fine-tuning cellular content of one of the three MBNL paralogs, MBNL1, by binding to the first coding exon (e1) of its pre-mRNA. Intriguingly, this autoregulatory feedback loop grounded on alternative splicing of e1 appears to play a crucial role in delaying the onset of myotonic dystrophy. Here, we describe this process in the context of other autoregulatory and regulatory loops that maintain the content and diverse functions of MBNL proteins at optimal level in health and disease, thus supporting the overall cellular homeostasis.

Introduction Oxidative stress has been implicated in the normal ageing process and the pathogenesis of several diseases, including goitre. The aim of the study was to evaluate the relationship between urine lipid peroxidation (LPO) and anthropometric parameters as well as the parameters associated with goitre formation in children. Material and methods The subjects included 172 healthy children (93 girls and 79 boys) aged 8-15, divided into 4 age groups - group I (8-9 years), group II (10-11 years), group III (12-13 years) and group IV (14-15 years) - and into 2 groups based on the BSA: the BSA-1 group (≤ 0.55 m2) and the BSA-2 group (> 0.55 m2). Results The value of LPO was the highest in group I but the difference between the groups was not statistically significant (p = 0.074). In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 ±6.90 nmol/ml and 10.79 ±4.86 nmol/ml, respectively; p = 0.023). We found a weak, negative linear correlation between LPO and age (r = -0.216; p < 0.005), body mass (r = -0.153; p < 0.05), height (r = -0.152; p < 0.05) and BSA (r = -0.151; p < 0.05). Conclusions Anthropometric parameters of school-age children independently of age are negatively associated with oxidative damage to membrane lipids, whereas factors promoting goitrogenesis do not contribute to this process.