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Introduction: Interpersonal relations significantly impact our well-being and mental health. They are also crucial among students, especially when they start living independently in a new social environment. The study aimed to determine the impact of relations on the occurrence of depression, anxiety, and drowsiness among medical students in Poland. Material and methods: An online questionnaire was created, consisting of four parts: the authors’ questionnaire on interpersonal relations, the Beck Depression Inventory (BDI), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Epworth Sleepiness Scale (ESS). The results were analyzed using STATISTICA software. Results: 2339 completed questionnaires were obtained. 69.75% of the subjects had good/rather good relations with their co-tenants, and 5.04% – had bad/definitely bad. 85% of the participants had good relations with their parents. 65.63% of the respondents were satisfied with their social relationships; in addition, 71.91% of respondents were satisfied with their relationships with their friends. Poor relations with family and co-tenants, and poor social and friend relationships were linked to higher levels of depression, anxiety, and sleepiness. This phenomenon was particularly evident among introverts. Conclusions: Identifying the risk factors could significantly improve the prevention, diagnosis, and treatment of mental disorders in this group. Supporting students and paying greater attention to social competencies equally with medical knowledge acquired by them would be highly recommended.

Introduction: The search for factors influencing the survival of patients with lung cancer is still ongoing. It may potentially be a polymorphism of the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is involved in the process of carcinogenesis. The aim of the study was to assess the distribution of genotypes and alleles of selected polymorphisms of the CLPTM1L gene – rs401681 and rs402710 – in cancerous and healthy lung tissue in patients with lung adenocarcinoma and their relationship with patient survival. Material and methods: The study included 133 patients with an average age of lung cancer diagnosis of 65 years, who had undergone lung adenocarcinoma surgery in the past. Genetic material – deoxyribonucleic acid (DNA) – was isolated from paraffin-protected specimens of cancerous and healthy lung tissue, and genotyping of CLPTM1L polymorphisms was performed. The obtained results were analyzed along with demographic data, history of smoking, family history of cancer, stage of the disease in the tumor, node, metastasis (TNM) classification, clinical stage of the cancer and the survival time of the patients. Results: The mean follow-up period was 44.5 months. The patients who died lived an average of 22.6 months from the time of cancer diagnosis. There were no significant differences between the distribution of genotypes or alleles in the cancerous and healthy tissues and their relationship with the survival of the patients. The age at the time of diagnosis of cancer, category N in the TNM classification and high clinical advancement of the cancer were the only factors influencing the survival of the patients. Conclusions: No relationships between the polymorphic variability of rs401681 and rs402710 in cancerous and healthy lung tissue and the survival of patients were found.

Innovative types of dressings should manifest biodegradability and non-immunogenicity and prevent dehydration. The mentioned technological features are demonstrated by polymeric, nonwoven propolis dressings, which exhibit regenerative properties, produced with the implementation of the electrospinning method. These features are highly needed in the course of burn wound healing. To analyze the dynamics of the changes in content of glycosaminoglycans (GAGs), such as heparan sulfates and hyaluronan, a well-known protocol of burn wound healing (the Hoekstra model) was used. Burn wounds were subsequently treated with nonwoven dressings containing either 5% wt or 10% wt propolis. Control groups were treated with either a saline salt solution or nonwoven dressings without propolis. Statistical differences between groups were determined by a multivariate analysis of variance (ANOVA) and Tukey’s post hoc tests. Evaluation of the effectiveness of nonwoven dressings containing 5% wt and 10% wt propolis in healing burn wounds, based on the dynamics and concentration of GAGs, revealed apitherapeutic positive effects on injured tissue healing. This research underscores the advantageous impact of utilizing nonwoven dressings containing propolis for the treatment of burn wounds.

Background: Fear and anxiety are common psychological responses to unpleasant stimuli, with dental fear being the fourth most prevalent type of fear or phobia. However, not all dental procedures cause the same level of anxiety, with dental surgery and tooth extraction being among the top five most frightening procedures in the field. Tooth extractions are also the most common surgical procedure in dental surgery. It is important to manage anxiety in the dental office by identifying the main factors. Methods: The study was conducted on a group of 250 patients. The survey technique and the Beliefs about Pain Control Questionnaire (BPCQ) were used in the study. Pain and stress intensity on a Visual Analog Scale (VAS) were measured in each patient before and after tooth extraction procedures. Results: Young women and people from small towns had the highest levels of anxiety. The factor causing the highest level of anxiety was fear of complications. Patients undergoing extraction of retained teeth were characterized by higher levels of anxiety. Conclusions: Perioperative stress is strongly dependent on numerous factors. For patient comfort, it may be crucial for dentists to have knowledge about these factors and the ability to utilize them to reduce stress before and after tooth extractions.

Natural origin products are regarded as promising for the development of new therapeutic therapies with improved effectiveness, biocompatibility, reduced side effects, and low cost of production. Betulin (BE) is very promising due to its wide range of pharmacological activities, including its anticancer, antioxidant, and antimicrobial properties. However, despite advancements in the use of triterpenes for clinical purposes, there are still some obstacles that hinder their full potential, such as their hydrophobicity, low solubility, and poor bioavailability. To address these concerns, new BE derivatives have been synthesized. Moreover, drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. The aim of this manuscript is to summarize the recent achievements in the field of delivery systems of BE and its derivatives. This review also presents the BE derivatives mostly considered for medical applications. The electronic databases of scientific publications were searched for the most interesting achievements in the last ten years. Thus far, it is mostly nanoparticles (NPs) that have been considered for the delivery of betulin and its derivatives, including organic NPs (e.g., micelles, conjugates, liposomes, cyclodextrins, protein NPs), inorganic NPs (carbon nanotubes, gold NPs, silver), and complex/hybrid and miscellaneous nanoparticulate systems. However, there are also examples of microparticles, gel-based systems, suspensions, emulsions, and scaffolds, which seem promising for the delivery of BE and its derivatives.

In the original publication [...]

Tumor cells stimulate local angiogenesis, resulting in their further multiplication and spread. Angiogenesis is a multifaceted process in which angiopoietins parti- cipate. Angiopoietin-1 (Ang-1) through its receptor Tie2 stimulates endothelial cell survival and the maintenance of the endothelial barrier. These phenomena can support tumour growth by promoting angiogenesis. On the other hand, overproduction of Ang-1 triggers endothelium stability and can lead to angiogenesis inhibition. Because of the ambiguous role of Ang-1, we decided to determine its clinical significance in patients with resectable NSCLC. In a group of 47 patients, tumours and the adjacent non-cancerous tissues were assessed for ANG-1 mRNA expression (using Q-RT-PCR analysis) and Ang-1 concentration (by enzyme-linked immunosorbent assay) together with clinical parameters and the five-year survival rate. ANG-1 expression and Ang-1 concentration were higher in tumour-free tissue, showing no differences between histological types of NSCLC, clinical stage or grading and seemed not to determine the five-year survival. ANG-1 expression and Ang-1 concentration in tumour and tumour-free tissues in patients with NSCLC seem not to be useful as factors supporting either diagnostics or prognosis.

Introduction Stress is ubiquitous and has a multidirectional impact on our health. One of the most visible problems caused by stress is sleep disturbance. The aim of the study was to evaluate the impact of subjectively assessed stress on objectively and subjectively measured sleep quality and somnolence. Material and methods 179 healthy adults aged 25–60 were examined using survey and actigraphy methods. The Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and MotionWatch 8 dream recorders with MotionWare software were used. The data were analysed using Statistica 13.3 software. Results Increased sleepiness was observed in 7.8% of the population, moderate in 15.1%, poor sleep quality in 29.7%. The average intensity of stress oscillated around 3.1 pts on a 5-point scale. 27.4% had difficult and depressing problems in life, which only 45.5% of people could cope with. Stress significantly worsened the quality of sleep (PSQI) and the results of the actigraphy tests; difficult problems in life translated into a deterioration of sleep quality (PSQI), somnolence (ESS) and deterioration of the actigraphy record. The ability to cope with stress positively influenced the quality of sleep, the actigraphy record and reduced sleepiness. Conclusions Stress significantly worsens the quality of sleep, with a slight impact on daytime sleepiness. Questionnaire methods seem to be better than actigraphy to monitor the impact of stress on sleep quality. Due to the significant impact on sleep quality, it would be advisable to promote stress-coping methods as an effective method to prevent sleep disorders, especially among the working population.

Aripiprazole (ARP) is an atypical neuroleptic used in the therapy of mental diseases such as schizophrenia. The lack of optimal adherence to an oral therapy regime creates the basis for designing ARP long-acting injections. This study aimed to use 105 °C hot melt extrusion (HME) as a formulation method for rods based on poly(d,l-lactide-co-glycolide-co-trimethylene carbonate) with a molecular weight (Mn) of 21 kDa (Td,l 21), poly(l-lactide-co-glycolide-co-trimethylene carbonate) with a Mn of 59 kDa (Tl 59), and with a Mn of 77 kDa (Tl 77). The following methods were involved in the research: NMR, DSC, XRD, HSM, FTIR, GPC, SEM, and mechanical tests. HME at 105 °C (i) ensured flow behavior for terpolymers, (ii) did not influence the terpolymers’ composition and (iii) the polymorph changes of ARP, and (iv) resulted in the changes in terpolymers’ Mn. For the rods with ARP based on Td,l 21 (Td,l 21 rod-ARP) and Tl 59 (Tl 59 rod-ARP), plasticization was noted. No drug–terpolymer interactions were revealed. No pores were observed on the surface. Due to its high flexibility and rubber character, Td,l 21 rod-ARP may be proposed for intramuscular administration, whereas Tl 59 rod-ARP, due to its higher strength and moderate stiffness, is proposed for subcutaneous administration.

Latanoprost (LTP) is a prostaglandin F2α analog used to lower intraocular pressure in glaucoma treatment administered daily as eye drops. In this study, a universal model based on poly(l-lactide-co-glycolide-co-trimethylene carbonate) with shape memory was proposed for the development of a solid biodegradable formulation with prolonged release administered intraconjunctivally, intravitreally, subconjunctivally, and subcutaneously. Solution casting and electron beam (EB) irradiation were applied to the matrix formulation. The properties of the native matrix and matrices degraded in a PBS buffer (pH 7.4) were monitored by NMR, DSC, GPC, and SEM. Water uptake (WU) and weight loss (WL) were also analyzed. LTP was released over 113 days in a tri-phasic and sigmoidal pattern without a burst effect and with a relatively long second release phase, in which changes were observed in the glass transition temperature, molecular weight (Mn), WU, and WL. EB irradiation decreased the initial Mn, increased WU, and accelerated LTP release with a shortened lag phase. This provides the opportunity to partially eliminate the use of drops at the start of treatment. SEM observations indicated that surface erosion is the prevalent degradation mechanism. The proposed model is an interesting solution during a preliminary study to develop final medicinal products that provide high adherence.

PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm.The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs. Keywords: Bioresorbable, Hydrogels, Poly(trimethylene carbonate), Drug release, Doxorubicin, Biocompatibility, Cyto-toxicity

Ischemic heart disease (IHD) is one of the main focuses in today’s healthcare due to its implications and complications, and it is predicted to be increasing in prevalence due to the ageing population. Although the conventional pharmacological and interventional methods for the treatment of IHD presents with success in the clinical setting, the long-term complications of cardiac insufficiency are on a continual incline as a result of post-infarction remodeling of the cardiac tissue. The migration and involvement of stem cells to the cardiac muscle, followed by differentiation into cardiac myocytes, has been proven to be the natural process, though at a slow rate. SDF-1α is a novel candidate to mobilize stem cells homing to the ischemic heart. Endogenous SDF-1α levels are elevated after myocardial infarction, but their presence gradually decreases after approximately seven days. Additional administration of SDF-1α-releasing microspheres could be a tool for the extension of the time the stem cells are in the cardiac tissue after myocardial infarction. This, in turn, could constitute a novel therapy for more efficient regeneration of the heart muscle after injury. Through this practical study, it has been shown that the controlled release of SDF-1α from biodegradable microspheres into the pericardial sac fourteen days after myocardial infarction increases the concentration of exogenous SDF-1α, which persists in the tissue much longer than the level of endogenous SDF-1α. In addition, administration of SDF-1α-releasing microspheres increased the expression of the factors potentially involved in the involvement and retention of myocardial stem cells, which constitutes vascular endothelial growth factor A (VEGFA), stem cell factor (SCF), and vascular cell adhesion molecules (VCAMs) at the site of damaged tissue. This exhibits the possibility of combating the basic limitations of cell therapy, including ineffective stem cell implantation and the ability to induce the migration of endogenous stem cells to the ischemic cardiac tissue and promote heart repair.

Prostate cancer is the second most common cancer in males. In the case of locally advanced prostate cancer radical prostatectomy is one of the first-line therapy. However, recurrence after resection of the tumor can appear. Drug-eluting bioresorbable implants acting locally in the area of the tumor or the resection margins, that reduce the risk of recurrence would be advantageous. Electrospinning offers many benefits in terms of local delivery so fiber-forming polyesters and polyestercarbonates which are suitable to be drug-loaded were used in the study to obtain CTX or DTX-loaded electrospun patches for local delivery. After a fast verification step, patches based on the blend of poly(glycolide-ε-caprolactone) and poly(lactide-glycolide) as well as patches obtained with poly(lactide-glycolide- ε-caprolactone) were chosen for long-term study. After three months, 60% of the drug was released from (PGCL/PLGA) + CTX and it was selected for final, anticancer activity analysis with the use of PC-3 and DU145 cells to establish its therapeutic potential. CTX-loaded patches reduced cell growth to 53% and 31% respectively, as compared to drug-free patches. Extracts from drug-free patches showed excellent biocompatibility with the PC-3 cell line. Cabazitaxel-loaded bioresorbable patches are a promising drug delivery system for prostate cancer therapy.

Stem cell treatment is a promising method of therapy for the group of patients whose conventional options for treatment have been limited or rejected. Stem cells have the potential to repair, replace, restore and regenerate cells. Moreover, their proliferation level is high. Owing to these features, they can be used in the treatment of numerous diseases, such as cancer, lung diseases or ischemic heart diseases. In recent years, stem cell therapy has greatly developed, shedding light on stromal-derived factor 1α (SDF-1α). SDF-1α is a mobilizing chemokine for application of endogenous stem cells to injury sites. Unfortunately, SDF-1α presented short-term results in stem cell treatment trials. Considering the tremendous benefits of this therapy, we developed biodegradable polymeric microspheres for the release of SDF-1α in a controlled and long-lasting manner. The microspheres were designed from poly(L-lactide/glycolide/trimethylene carbonate) (PLA/GA/TMC). The effect of controlled release of SDF-1α from microspheres was investigated on the migration level of bone marrow Mesenchymal Stromal Cells (bmMSCs) derived from a pig. The study showed that SDF-1α, released from the microspheres, is more efficient at attracting bmMSCs than SDF-1α alone. This may enable the controlled delivery of selected and labeled MSCs to the destination in the future.

Introduction: The number of people refusing to vaccinate their children is growing in Poland every year. Anti-vaccine organisations lead very fierce disinformation campaigns. The incidence of vaccine preventable diseases is on the rise. Monitoring of parents’ attitudes towards preventive vaccinations and gauging the level of their understanding of the issue may enable more effective actions of organisations responsible for public health. Aim: The objectives of the study included finding out about parents’ opinions and views as well as evaluating their knowledge about vaccinations in Poland. The study was also to define a parents’ assessment of the range of campaigns promoting vaccination and actions of anti-vaccine movements. Material and method: The studies were carried out with a survey conducted among 233 parents or legal guardians of the children being under the obligation of vaccinations. Results: Nearly 90% of respondents are proponents of vaccinations, one-third of them consider some vaccinations unnecessary, and almost 7% of the surveyed describe themselves as opponents of vaccinations. 78% among the parents surveyed encountered campaigns promoting the Childhood Immunisation Programme, and most of them regard such campaigns as useful. Anti-vaccine movements were heard of by 62.4% of all the surveyed parents or legal guardians. 60% of respondents regard their own knowledge of the issue of vaccinations as sufficient. However, only 35% of respondents provided correct answers to the control questions about preventive vaccinations. People with higher education have better knowledge on vaccinations, whereas those with primary education have the best opinion on their own knowledge. Conclusions: Parents’ knowledge in terms of preventive vaccinations seems inadequate. The number of opponents of preventive vaccinations is systematically growing. The paediatrician being the main source of information on the issue of vaccinations for the parents. Monitoring of parents’ attitudes and opinions about the issue of preventive vaccination will be useful in better directing promoting campaigns in social media, and in adjusting healthcare workers’ activities to specific social groups.

A growing interest in the use of a combination of chemosensitizers and cytostatics for overcoming cancer resistance to treatment and the development of their delivery systems has been observed. Resveratrol (Res) presents antioxidant, anti-inflammatory and chemopreventive properties but also limits multidrug resistance against docetaxel (Dtx), which is one of the main causes of failure in cancer therapy with this drug. However, the use of both drugs presents challenges, including poor bioavailability, the unfavourable pharmacokinetics and chemical instability of Res and the poor water solubility and dose-limiting toxicity of Dtx. In order to overcome these difficulties, attempts have been made to create different forms of delivery for both agents. This review is focused on the latest developments in nanoparticles for the delivery of Dtx, Res and for the combined delivery of those two drugs. The aim of this review was also to summarize the synergistic mechanism of action of Dtx and Res on cancer cells. According to recent reports, Dtx and Res loaded in a nano-delivery system exhibit better efficiency in cancer treatment compared to free drugs. Also, the co-delivery of Dtx and Res in one actively targeted delivery system providing the simultaneous release of both drugs in cancer cells has a chance to fulfil the requirements of effective anticancer therapy and reduce limitations in therapy caused by multidrug resistance (MDR).

Co-delivery of epothilone B (EpoB) and rapamycin (Rap) increases cytotoxicity against various kinds of cancers. However, the current challenge is to develop a drug delivery system (DDS) for the simultaneous delivery and release of these two drugs. Additionally, it is important to understand the release mechanism, as well as the factors that affect drug release, in order to tailor this process. The aim of this study was to analyze PLA–PEG micelles along with several types of microspheres obtained from PLA or a mixture of PLA and PLA–PEG as carriers of EpoB and Rap for their drug release properties and cytotoxicity against breast cancer cells. The study showed that the release process of EpoB and Rap from a PLA-based injectable delivery systems depends on the type of DDS, morphology, and polymeric composition (PLA to PLA–PEG ratio). These factors also affect the biological activity of the DDS, because the cytotoxic effect of the drugs against MDA-MB-231 cells depends on the release rate. The release process from all kinds of DDS was well-characterized by the Peppas–Sahlin model and was mainly controlled by Fickian diffusion. The conducted analysis allowed also for the selection of PLA 50/PLA–PEG 50 microspheres and PLA–PEG micelles as a promising co-delivery system of EpoB and Rap.

Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.

Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise.

The selection of dressing is crucial for the wound healing process. Traditional dressings protect against contamination and mechanical damage of an injured tissue. Alternatives for standard dressings are regenerating systems containing a polymer with an incorporated active compound. The aim of this research was to obtain a biodegradable wound dressing releasing propolis in a controlled manner throughout the healing process. Dressings were obtained by electrospinning a poly(lactide-co-glycolide) copolymer (PLGA) and propolis solution. The experiment consisted of in vitro drug release studies and in vivo macroscopic treatment evaluation. In in vitro studies released active compounds, the morphology of nonwovens, chemical composition changes of polymeric material during degradation process, weight loss and water absorption were determined. For in vivo research, four domestic pigs, were used. The 21-day experiment consisted of observation of healing third-degree burn wounds supplied with PLGA 85/15 nonwovens without active compound, with 5 wt % and 10 wt % of propolis, and wounds rinsed with NaCl. The in vitro experiment showed that controlling the molar ratio of lactidyl to glycolidyl units in the PLGA copolymer gives the opportunity to change the release profile of propolis from the nonwoven. The in vivo research showed that PLGA nonwovens with propolis may be a promising dressing material in the treatment of severe burn wounds.

Background: Oxidative stress is involved in lead toxicity. This suggests that some antioxidants may play a role in the treatment of lead poisoning. In the light of this, the aim of the study was to determine whether β-carotene administration reduces oxidative stress and homocysteine level in workers chronically exposed to lead. Material and Methods: The exposed population included healthy male workers exposed to lead who were randomly divided into 2 groups (mean blood lead level ca. 44 μg/dl). Workers in the 1st group (N = 49, reference group) had no antioxidants, drugs, vitamins or dietary supplements administered, while workers in the 2nd group (N = 33) had β-carotene administered in a dose of 10 mg per day for 12 weeks. Biochemical analysis included markers of lead-exposure and the level of malondialdehyde (MDA), an oxidative stress biomarker. We also measured the level of homocysteine (Hcy) and thiol groups as well as the activity of superoxide dismutase (SOD) and its isoenzyme EC-SOD in serum. Results: After supplementation, the level of MDA significantly decreased, compared to baseline, by 16%, and to the reference group. When compared to the reference group, Hcy level was also significantly decreased. However, the level of thiol groups was significantly higher after supplementation with β-carotene compared to the reference group. Analogically, the activity of SOD and EC-SOD was significantly higher compared to the baseline and to the reference group. Conclusions: Despite some controversies over antioxidant properties of β-carotene, our results indicate that its antioxidant action could provide some beneficial effects in lead poisoning independent of chelation. Med Pr 2014;65(3):309–316

To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.