Tricarbonyl rhenium(i) complexes with 8-hydroxyquinolines: structural, chemical, antibacterial, and anticancer characteristics.

Twelve tricarbonyl rhenium(i) complexes in the '2 + 1' system with the anionic bidentate N,O-donor ligand (deprotonated 8-hydroxyquinoline (HQ) or its 2-methyl (MeHQ) or 5-chloro (ClHQ) derivative) and neutral N-donor diazoles (imidazole (Him), 2-methylimidazole (MeHim), 3,5-dimethylpyrazole (Hdmpz), and 3-phenylpyrazole (HPhpz)) were synthesized: [Re(CO)3(LN,O)LN] (LN,O = Q-, MeQ-, ClQ-; LN = Him, MeHim, Hdmpz, HPhpz). Their crystal structures were determined by the scXRD method, compared with the DFT-calculated ones, and characterized by analytical (EA) and spectroscopic techniques (FT-IR, NMR, and UV-Vis) interpreted with DFT and TD-DFT calculations. Most of the Re(i) complexes did not show relevant antibacterial activity against Gram-negative and Gram-positive bacterial strains. Only [Re(CO)3(MeQ)Him] demonstrated significant action 4-fold better against Gram-negative Pseudomonas aeruginosa than the free MeHQ ligand. The cytotoxicity of the compounds was estimated using human acute promyelocytic leukemia (HL-60), ovarian (SKOV-3), prostate (PC-3), and breast (MCF-7) cancer, and breast non-cancerous (MCF-10A) cell lines. Only HQ and ClHQ ligands and [Re(CO)3(Q)Hdmpz] complex had good selectivity toward MCF-7 cell line. HL-60 cells were sensitive to all complexes (IC50 = 1.5-14 µM). Still, pure HQ and ClHQ ligands were slightly more active than the complexes.

Salmonellosis in Poland in 2021. / Salmonelozy w Polsce w 2021 roku.

AIM: The aim of the article is to present and assess the epidemiological situation of salmonellosis in Poland in 2021, in relation to previous years. MATERIAL AND METHODS: The assessment of the epidemiological situation of salmonellosis in Poland was made on the basis of individual data on salmonellosis cases, entered by sanitary-epidemiological stations into the EpiBaza System, data on outbreaks caused by Salmonella bacilli from the Registry of Epidemic Outbreaks System (ROE), as well as on the basis of aggregated data published in the annual bulletins "Infectious Diseases and Poisoning in Poland" (NIPH NIH - NRI, GIS, Warsaw), including information sent by laboratories of sanitary-epidemiological stations, data from the article on the epidemiological situation of salmonellosis in Poland in 2020 and data from the Demographic Research Department of the Central Statistical Office. RESULTS: In 2021, in Poland sanitary-epidemiological stations registered 8,294 cases of salmonellosis - 8,014 cases of intestinal salmonellosis and 280 extra-intestinal salmonellosis, including 190 cases of salmonellosis septicemia. The incidence rate for total salmonellosis was 21.7/100,000 population, for intestinal salmonellosis 21.0, for salmonellosis septicemia 0.50, and 0.23 per 100,000 population for other extra-intestinal infections of salmonellosis etiology. The reported 7,988 cases were classified as confirmed and 306 as probable. There were 5,127 hospitalizations due to salmonellosis, mainly children and the elderly. The peak of the incidence was registered in July. The highest incidence rate of salmonellosis in 2021 was recorded in the Podkarpackie voivodeship (39.8/100,000 population), the lowest in the Swietokrzyskie voivodeship (10.7/100,000 population). The highest incidence of intestinal salmonellosis was registered in the age group 0-4 years, accounting for 44.2% of the total number of cases. Among extra-intestinal infections, almost 62% of cases occurred in people aged 60+. In 2021, sanitary-epidemiological stations were detected and reported 229 outbreaks of food poisoning caused by Salmonella bacilli, 75% of them was Enteritidis serotype. In 2021, the most frequently isolated serotypes were S. Enteritidis 72%, S. Typhimurium (2%) and S. Infantis (0.5%). The serotype was not determined in 24.3% of cases. There were 24 imported cases of salmonellosis from different regions of the world. Due to Salmonella infection 11 people died in 2021. Laboratories of sanitary-epidemiological stations performed 438,183 tests for the presence of Salmonella and Shigella bacilli among humans, 92% of these tests concerned people working in contact with food. CONCLUSIONS: In 2021, there was an increase in the number of salmonellosis cases in Poland, compared to 2020. It can therefore be concluded that the COVID-19 pandemic did not have a long-term impact on reducing the number of Salmonella infections. At the same time, despite the increase, the situation of salmonellosis in Poland has not fully returned to the state before the COVID-19 pandemic.The area where we observe a significant difference, is the percentage of hospitalizations, which is the lowest in 2021 since 1998. It can be assumed, that one of the reasons for this, could be a stricter qualification of people with milder symptoms for hospital treatment, in favour of outpatient care.

An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil's Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer.

Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4'-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration.

Healthcare workers highly affected during the COVID-19 epidemic wave in Poland prior to vaccination availability: seroprevalence study.

BACKGROUND: The aim of the study was to assess seroprevalence of anti-SARS-CoV-2 antibodies among healthcare workers (HCW) before introduction of vaccination, in selected areas in Poland as well as to identify potential risk factors and estimate the cumulative incidence of COVID-19 infections in this population. MATERIAL AND METHODS: The authors conducted a sero-epidemiological, cross-sectional study among HCW of 5 non-COVID-19 hospitals in Poland. The recruitment took place in December 1-23, 2020, all HCW at selected hospitals could volunteer into the study. All persons were screened with rapid SARS-CoV-2 IgM/IgG tests in capillary blood. In case of positive result, 5 ml of venous blood was drawn for confirmatory testing with ELISA assay. The authors estimated prevalence of laboratory confirmed anti-SARS-CoV-2 antibody presence and examined factors associated with positive result. Cumulative incidence was estimated applying 2-source capture-recapture method to serology results and self-report of past infection. RESULTS: Out of 1040 HCW included in the analysis, one-fourth (25.2%) received a positive result for anti-SARS-CoV-2 antibodies by ELISA test, the prevalence among women was 25.3% (95% CI: 22.5-28.4) and 24.6% (95% CI: 19-31.2) among men. The prevalence of anti-SARS-CoV-2 antibodies was the highest among respondents who declared home contact with a confirmed COVID-19 case, 43.9% (95% CI: 32.4-56.1). It was also elevated among those who indicated contact with patients with COVID-19, 32.5% (95% CI: 26.7-38.8) and business contacts, including at the workplace, 28.9% (95% CI: 22.5-36.3). The estimated cumulative incidence of COVID-19 infections in the population, using the capture-recapture method was 41.2% (95% CI: 38.1-44.2). CONCLUSIONS: Healthcare workers remained at increased risk of infection largely due to work-related contacts with infected patients, although home exposure was also common. Estimated cumulative incidence is higher than the antibody prevalence, which indicates the need to monitor HCW for possible immunity waning, also post-immunization immunity. Med Pr. 2022;73(2):109-23.

Salmonellosis in Poland in 2020.

AIM: The aim of the study is to assess the epidemiological situation of salmonellosis in Poland in 2020 compared with previous years. MATERIAL AND METHODS: The epidemiological situation was assessed on the basis of data provided to the Department of Epidemiology of Infectious Diseases and Surveillance of the NIPH NIH-NRI by sanitary-epidemiological stations through the EpiBaza System and the Registry of Epidemic Outbreaks System (ROE), as well as on the basis of data published in the annual bulletin "Infectious Diseases and Poisoning in Poland in 2020" (NIPH NIH-NRI, GIS, Warsaw, 2021) and from information received from laboratories of sanitary-epidemiological stations and data from the Demographic Research Department of the Statistics Poland. RESULTS: In Poland in 2020, in the sanitary-epidemiological surveillance registered a total of 5,470 cases of salmonellosis, 5,302 cases of intestinal salmonellosis, and the remaining 168 cases of extra-intestinal salmonellosis. The incidence per 100,000 population was 14.3 for total salmonellosis, 13.8 for intestinal salmonellosis and 0.44 for extra-intestinal salmonellosis. Sanitary-epidemiological stations registered 5,349 confirmed cases and 121 probable cases of salmonellosis. Due to intestinal salmonellosis, 63.9% of all patients were hospitalized, while for extra-intestinal salmonellosis 153 patients or 91.1% of cases, were hospitalized. The increase in the number of salmonellosis cases in 2020 started in June, while the peak of the incidence was in August. Among the voivodeships, the highest incidence of salmonellosis was registered in the Podkarpackie voivodeship 33.3/100,000 population, the lowest in Zachodniopomorskie 6.1/100,000 population. Cases in the 0-4 age group accounted for 45.2% of all salmonellosis cases in 2020. Among extra-intestinal salmonellosis, 63.1% were people aged 60+. Sanitary-epidemiological stations registered 131 food poisoning outbreaks caused by Salmonella bacilli in the ROE system, 108 of these outbreaks were caused by the Enteritidis serotype. In 2020, the most common serotypes were S. Enteritidis 70% of all recorded salmonellosis, S. Typhimurium 1.9%, and S. Infantis 0.54%. There were 9 deaths due to Salmonella infection. CONCLUSIONS: The COVID-19 pandemic and the associated restrictions introduced in the country, as well as increased hygiene through more frequent washing and disinfection of hands, could have contributed to a reduction of almost 69% in the number of salmonellosis cases registered in 2020, in Poland, compared to 2019. This is a 82% decrease in relation to 2018. There was also a decrease in the number of food poisoning outbreaks caused by Salmonella bacilli, while at the same time their percentage in the total number of outbreaks increased. On the one hand, the implemented restrictions could have had an impact on the decrease in the number of cases and outbreaks, on the other hand, worse access to medical care and diagnostics, most likely deepened the underestimation of these cases in the country observed for years, and distorted the real picture of the situation.

The Mode of SN38 Derivatives Interacting with Nicked DNA Mimics Biological Targeting of Topo I Poisons.

The compounds 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (2) and 7-ethyl-9-(N-morpholino)methyl-10-hydroxycamptothecin (3) are potential topoisomerase I poisons. Moreover, they were shown to have favorable anti-neoplastic effects on several tumor cell lines. Due to these properties, the compounds are being considered for advancement to the preclinical development stage. To gain better insights into the molecular mechanism with the biological target, here, we conducted an investigation into their interactions with model nicked DNA (1) using different techniques. In this work, we observed the complexity of the mechanism of action of the compounds 2 and 3, in addition to their decomposition products: compound 4 and SN38. Using DOSY experiments, evidence of the formation of strongly bonded molecular complexes of SN38 derivatives with DNA duplexes was provided. The molecular modeling based on cross-peaks from the NOESY spectrum also allowed us to assign the geometry of a molecular complex of DNA with compound 2. Confirmation of the alkylation reaction of both compounds was obtained using MALDI-MS. Additionally, in the case of 3, alkylation was confirmed in the recording of cross-peaks in the 1H/13C HSQC spectrum of 13C-enriched compound 3. In this work, we showed that the studied compounds-parent compounds 2 and 3, and their potential metabolite 4 and SN38-interact inside the nick of 1, either forming the molecular complex or alkylating the DNA nitrogen bases. In order to confirm the influence of the studied compounds on the topoisomerase I relaxation activity of supercoiled DNA, the test was performed based upon the measurement of the fluorescence of DNA stain which can differentiate between supercoiled and relaxed DNA. The presented results confirmed that studied SN38 derivatives effectively block DNA relaxation mediated by Topo I, which means that they stop the machinery of Topo I activity.

Synergistic Interaction between 5-FU and an Analog of Sulforaphane-2-Oxohexyl Isothiocyanate-In an In Vitro Colon Cancer Model.

Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.

New camptothecin derivatives for generalized oncological chemotherapy: Synthesis, stereochemistry and biology.

Derivatives of SN38 were synthesized that were either monosubstituted at C-5 or C-9 or disubstituted at both C-5 and C-9. Substitution to C-5 led to the generation of pairs of diastereomers (2c-2 h) in a one-pot reaction and was readily separable by HPLC. The absolute configurations of C-5 were established by electronic circular dichroism experiments. Compounds were tested in vitro against human cancer cell lines as well as a normal cell line. The impact of compounds 2a-2j on cancer cells is significant and the IC50 values against the normal cell line are several times higher than that of SN38. Using the Mannich reaction we obtained a new innovative group of derivatives with unique biological properties that preserves the high cytotoxicity in cancer cells and eliminates the acute toxicity to non-neoplastic cells, which can be considered a breakthrough in chemotherapy with the use of topoisomerase I inhibitors from the camptothecin family.

Salmonellosis in Poland in 2018 and 2019.

AIM: The aim of this study is to assess the epidemiological situation of salmonellosis in Poland, in 2018 and 2019 compared with previous years. MATERIAL AND METHODS: The assessment of the epidemiological situation was performed on the basis of data provided to the Department of Epidemiology Infectious Diseases and Surveillance of NIPH NIH - NRI by sanitary-epidemiological stations through the Epidemiological Case Reporting System (SRWE) and the Registry of Epidemic Outbreaks (ROE), as well as on the basis of data from the annual bulletins "Infectious Diseases and Poisonings in Poland" 2018 and 2019 (NIPH NIH - NRI, GIS, Warsaw, 2019 and 2020) and from information received from laboratories of sanitary-epidemiological stations and data from the Demographic Research Department of Statistics Poland (GIS). RESULTS: In Poland in 2018 a total of 9,957 cases of salmonellosis were reported in the sanitaryepidemiological surveillance, among these infections 9,651 were cases of intestinal salmonellosis, 306 were cases of extraintestinal salmonellosis. The incidence rate for total salmonellosis was 25.9 per 100,000 population, for parenteral salmonellosis alone was 0.80 per 100,000 population. There were 9,370 cases of confirmed and 587 cases of probable salmonellosis registered. Hospital treatment was given to 65% of patients with intestinal salmonellosis and 88.6% of patients with extraintestinal forms of the disease. The increase in salmonellosis cases in 2018 occurred during the summer months with a peak in cases in August. The highest incidence of salmonellosis nationwide was in the Podkarpackie voivodeship 42.2/100,000, the lowest in the Lubuskie voivodeship 9.4/100,000. More cases were registered in urban areas - 5,866 salmonellosis cases. Cases in the age group 0-4 constituted 37.7% of all cases. Among parenteral salmonellosis 64.7% were people over 60 years of age. In ROE system there were 351 food poisoning outbreaks with Salmonella spp. as the etiological agent, mainly Enteritidis serotype. The most frequently isolated serotypes in Poland in 2018 were S. Enteritidis, S. Typhimurium and S. Infantis, the first of which was responsible for 76.3% of all Salmonella infections. There were 1,719 cases registered in which the serotype was not determined, most of them came from the Pomorskie voivodeship. Sanitary-epidemiological stations performed 547,976 bacteriological tests for Salmonella and Shigella, 0.2% of people working in contact with food had a positive result. There were 43 cases imported from abroad. Due to Salmonella infection 4 people died in 2018. In 2019 a total of 9,234 cases of salmonellosis were registered in Poland, including 8,919 food poisoning and 315 parenteral salmonellosis. The incidence for total salmonellosis in Poland was 24.1 per 100,000 population. There were 8,687 confirmed and 547 probable cases of salmonellosis reported. Due to food poisoning 63.1% of patients were hospitalized, while due to parenteral salmonellosis 87.6% of patients were hospitalized. The peak incidence in 2019 occurred in August. The highest incidence per 100,000 population of total salmonellosis by voivodeship was recorded in the Podkarpackie voivodeship 55.1, the lowest in the Zachodniopomorskie voivodeship 8.8. Almost 40% of all salmonellosis cases in the country were among children aged 0-4; as far as parenteral salmonellosis is concerned, the main group of patients 68.6%, were people over 60 years old. Sanitaryepidemiological stations reported in the ROE system 303 outbreaks of food poisoning of salmonellosis etiology. The most commonly isolated serotype in 2019 in Poland was Salmonella Enteritidis 75.6% of all recorded salmonellosis cases, followed by Salmonella Typhimurium 3% and Salmonella Infantis 1%. The serotype was not determined in 1,692 cases, the highest number in the Pomorskie and Kujawsko-Pomorskie voivodeships - 51% of undetermined isolates each. Laboratories of sanitary-epidemiological stations carried out 610,164 bacteriological tests for Salmonella and Shigella. Among people working in contact with food 0.2% had a positive test result. 71 cases of imported intestinal salmonellosis were registered. Nine deaths due to Salmonella infection were reported. CONCLUSIONS: The salmonellosis situation in Poland in 2018 and 2019 remains at a high but stable level. The significant increase in the number of laboratory tests performed for Salmonella in 2018-2019 and the decrease in the number of people refusing the carrier exclusion test, is an important step in the process of enhancing salmonellosis surveillance.

The Premature Senescence in Breast Cancer Treatment Strategy.

Cellular senescence is a permanent blockade of cell proliferation. In response to therapy-induced stress, cancer cells undergo apoptosis or premature senescence. In apoptosis-resistant cancer cells or at lower doses of anticancer drugs, therapy-induced stress leads to premature senescence. The role of this senescence in cancer treatment is discussable. First of all, the senescent cells lose the ability to proliferate, migrate, and invade. In addition, the senescent cells secrete a set of proteins (inflammatory cytokines, chemokines, growth factors) known as the senescence-associated secretory phenotype (SASP), which influences non-senescent normal cells and non-senescent cancer cells in the tumor microenvironment and triggers tumor promotion and recurrence. Recently, many studies have examined senescence induction through breast cancer therapy and potentially using this phenomenon to treat this cancer. This review summarizes the recent in vitro, in vivo, and clinical studies investigating senescence in breast cancer treatments. Senescence inductors, senolytics, as well as their action mechanism are discussed herein. Potential SASP-modulating treatment strategies are also described.

In the triple-negative breast cancer MDA-MB-231 cell line, sulforaphane enhances the intracellular accumulation and anticancer action of doxorubicin encapsulated in liposomes.

A new combination of sulforaphane (a natural compound obtained from Brassicaceae vegetables) and the cytostatic drug doxorubicin was entrapped in nanometer-sized liposomes. In vitro experiments were performed to investigate the cytotoxicity of these structures on the human breast cancer cell line MDA-MB-231. Confocal microscopy studies revealed enhanced cellular endocytotic internalization, followed by the release of the examined combination from the lysosomes. The in vitro interaction analysis using the Chou-Talalay approach showed high synergistic activity of the examined combination. This synergistic activity enables a considerable reduction in cytostatic dosage and an increase in cancer treatment efficiency.

Salmonellosis in Poland in 2017

AIM: The aim of the study is to assess the epidemiological situation of salmonellosis in 2017 in Poland compared to the previous years. MATERIAL AND METHODS: The assessment of the epidemiological situation was performed on the basis of data submitted to the Department of Epidemiology of Infectious Diseases and Surveillance NIPH-NIH by sanitaryepidemiological stations by means of the Epidemiological Case Reporting System (SRWE) and the Registry of Epidemic Outbreaks (ROE), along with data from the annual bulletin "Infectious diseases and poisonings in Poland in 2017" (NIPH-NIH, CSI, Warsaw 2018), and information from the laboratories of Sanitary epidemiological Stations as well as data from the Department of Demographic Studies of the Central Statistical Office. RESULTS: In 2017, 10 000 cases of Salmonella infection were registered in Poland, 9 710 were cases of intestinal salmonellosis, 290 were forms of extraintestinal salmonellosis. The incidence rate per 100 thousand population was 26.0. The hospitalization rate for all salmonellosis cases was 63.3%. Confirmed cases accounted for 92,1% of all cases, the remaining 7.9% were probable cases. Peak incidence occurred, as in previous years, in the summer months. The voivodships with the largest number of cases caused by Salmonella were the Mazowieckie and Malopolskie voivodeships, the least was recorded in the Lubuskie voivodeship. The age group in which the highest percentage of food poisonings was recorded were children aged 0-4, while extraintestinal forms most often concerned people aged over 60. 278 food poisoning outbreaks were recorded, in which Salmonella Enteritidis was the most frequently isolated serotype. This serotype was most often isolated in foodborne outbreaks and in sporadic cases, it is responsible for 92% of all salmonellosis. Salmonella infection was found in 0.2% of people working with food and in 8.1% of contacts of the cases. According to data from the Central Statistical Office, 10 people died of salmonellosis in 2017. CONCLUSIONS: In 2017, the number of people infected with Salmonella was as high as in 2016, the reason for the persistence of such a high number of cases may be the association of some infections with an international salmonellosis outbreak, the peak of which was in 2016. The high incidence of salmonellosis may also be a consequence of legal changes introduced in 2014 regarding the reporting of positive test results by laboratories for epidemiological surveillance.

Giardiasis (lambliasis) in Poland in 2017

OBJECTIVE: To assess the epidemiological situation of giardiasis in Poland in 2017. MATERIAL AND METHOD: The assessment of the epidemiological situation of giardiasis in Poland was carried out on the basis of the results of the analysis of data from the annual bulletins "Infectious diseases and poisoning in Poland", information from forms on individual cases provided by PSSE employees through the Epidemiological Case Reporting System (SRWE), information on outbreaks transferred by PSSE employees through the Registry of Epidemic Outbreaks (ROE), as well as data on deaths from the Department of Demographic Studies of the Central Statistical Office. RESULTS: This is the first epidemiological report on giardiasis in Poland published in the epidemiological Chronicle. The number of new giardiasis cases registered in Poland in 2017 was 1 229 cases, incidence rate 3.2 per 100 000 population. Compared to previous years, the number of registered cases decreased. There were no deaths. Hospitalizations accounted for around 24.5% of all cases. All giardiasis cases met the criteria for the definition of a confirmed case. In 2017, there were 4 outbreaks of giardiasis. CONCLUSIONS: The long-term decline in the number of cases and incidence in Poland indicates an improvement of the epidemiological situation. In comparison with epidemiological data for EU / EEA countries, Poland does not stand out significantly in terms of the number of cases, incidence or seasonality distribution of cases.

In Vitro Evaluation of Sulforaphane and a Natural Analog as Potent Inducers of 5-Fluorouracil Anticancer Activity.

Isothiocyanates (R-NCS) are sulphur-containing phytochemicals. The main source are plants of the Brassicaceae family. The best known plant-derived isothiocyanate is sulforaphane that has exhibited anticancer activity in both in vivo and in vitro studies. Recent attempts to expand their use in cancer therapy involve combining them with standard chemotherapeutics in order to increase their therapeutic efficacy. The aim of this paper is to determine the impact of sulforaphane and its natural analog alyssin on the anticancer activity of the well-known anticancer drug 5-fluorouracil. The type of drug-drug interactions was determined in prostate and colon cancer cell lines. Confocal microscopy, western blot and flow cytometry methods were employed to determine the mechanism of cytotoxic and cytostatic action of the combinations. The study revealed that additive or synergistic interactions were observed between 5-fluorouracil and both isothiocyanates, which enhanced the anticancer activity of 5-fluorouracil, particularly in colon cancer cell lines. An increased cytostatic effect was observed in case of alyssin while for sulforaphane the synergistic interaction with 5-fluorouracil involved an intensification of apoptotic cell death.

Autophagic cell death and premature senescence: New mechanism of 5-fluorouracil and sulforaphane synergistic anticancer effect in MDA-MB-231 triple negative breast cancer cell line.

In view of the need for new, more effective therapies for the triple negative breast cancer treatment, the aim of the study was to evaluate the anticancer activity and mechanism of action of the sulforaphane and 5-fluorouracil combination in the triple negative breast cancer cell line MDA-MB-231. Changes in the number of live cells after alone and sequential treatment were determined by the MTT test. The Chou and Talaly method was used to identify the type of interaction. Confocal microscopy, flow cytometry, western blot and spectrophotometry were used to examine apoptosis, autophagy and premature senescence. The western blot method was applied to measure the level of enzymes that are crucial for the 5-fluorouracil activity. Sulforaphane and 5-fluorouracil have been shown to interact synergistically in the breast cancerMDA-MB-231 cell line, resulting in a significant reduction of the number of live cells compared to alone treatments. Sulforaphane has decreased the level of thymidylate synthetase, which was also observed in the case of the sequential sulforaphane and 5-fluorouracil treatment. Studies of the interaction mechanism have revealed that sulforaphane and 5-fluorouracil act synergistically in the MDA-MB-231 cells by inducing autophagic cell death and premature senescence.

Salmonellosis in Poland in 2015 and 2016

THE AIM: The aim of the study is to assess the epidemiological situation of salmonellosis in 2015-2016 in Poland, compared to the previous years. MATERIAL AND METHODS: The assessment of the epidemiological situation was performed on the basis of data from bulletins "Infectious diseases and poisonings in Poland", information from the laboratories of Sanitaryepidemiological Stations and data from epidemiological investigations of outbreaks which were provided by Sanitary-epidemiological Stations through the Register of Epidemic Outbreaks (ROE) to the Department of Epidemiology of Infectious Diseases and Surveillance as well as data from the Department of Demographic Studies of the Central Statistical Office. Cases were classified according to the implemented case definitions. RESULTS: In 2015, a total of 8 650 cases salmonellosis were reported. Among them 8 418 were cases of intestinal salmonellosis and 232 of extraintestinal one. Total incidence was 22.5/100 000. 8235 (95,2%) cases met the criteria for confirmed case and 415 cases were classified as probable. In comparison to 2014, the percentage of hospitalized persons increased slightly and remained at a high level of 71.8%. The increase of salmonellosis cases, as in previous years, occurred in the summer months. In 2015 he highest incidence was recorded in the Malopolskie and Mazowieckie voivodeships, and the lowest in the Lubuskie. Children 0-4 were most often affected, especially at the age of 2 and 3 years old. Number of reported foodborne outbreaks caused by Salmonella was 190. Among them 154 were caused by Salmonella Enteritidis. This serotype, as in previous years was the most frequently isolated. Out of the 433 571 tested people who were working with food, 0.2% were infected with Salmonella. In 2016, the total number of reported cases of salmonellosis was 10,027 cases, which was close to 16% increase in cases compared to the previous year and over 19% increase compared to 2014. There were registered 9,701 cases of intestinal and 326 extraintestinal infections. 9,713 cases were classified as confirmed, accounting for 96.9% of all and 314 cases were classified as probable ones. The percentage of hospitalizations in 2016 remained at a similar level as in previous years (71.1%). The peak of incidence as in the previous year was in July. The highest numbers of cases were recorded in the Malopolskie and Mazowieckie voivodeships, which accounted for 23% of all reported cases. As in previous years, most often affected were children at the age 0-4. In 2016 number of reported outbreaks of foodborne infections caused by Salmonella sp. was 240. In 85% of them S. Enteritidis serotype was isolated, which as in previous years was the serotype most frequently isolated in outbreaks and sporadic diseases. Among 443 419 people working with food who were tested for Salmonella 0,2% were positive, as in the previous year. CONCLUSIONS: The increase in the incidence of salmonellosis in 2015-2016 in Poland may be related to the outbreak detected in 2016, covering more than a dozen EU countries, associated with eggs originating in Poland. Observed in the last several years high percentage of hospitalizations due to salmonellosis is a consequence of rare laboratory testing for salmonellosis by GPs of patients with gastroenteritis. It also results in the low sensitivity of salmonella surveillance in Poland.

Organofluorine Isoselenocyanate Analogues of Sulforaphane: Synthesis and Anticancer Activity.

A series of previously unknown sulforaphane analogues with organofluorine substituents bonded to the sulfinyl sulfur atom, an isoselenocyanate moiety in place of the isothiocyanate group, the central sulfur atom in various oxidation states, and different numbers of methylene groups in the central alkyl chain were synthesized and fully characterized. All new compounds were tested for their biological properties in vitro and demonstrated much higher anticancer activity against two breast cancer cell lines than that shown by native sulforaphane; at the same time, the compounds were less toxic for normal cells. The influence of the particular structural changes in the molecules on the cytotoxicity is discussed.

Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells.

Sulforaphane (SFN), a naturally occurring chemopreventive and anticancer agent, is a nuclear factor, erythroid 2-like 2 (NFE2L2/Nrf2) inducer. Nrf2 plays a critical role in coordinating the cell defense system by initiating the transcription of cytoprotective genes, including detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 (NQO1) and transport proteins such as ATP-binding cassette, subfamily C (CFTR/MRP). Recently, the essential role of Nrf2 in tumor development and progression and in the development of multidrug resistance in cancer cells has been highlighted. The aim of this study was to compare the effect of SFN on the Nrf2 system and the Nrf2-target enzymes NQO1 and MRP in human untransformed epithelial colon CRL-1790 cells and in HT-29 and Caco-2 colorectal cancer cells to elucidate the role of SFN in cancer prevention and treatment. We have demonstrated that SFN has excellent cytoprotective properties in CRL-1790 cells, as it induced Nrf2-dependent expression of MRP1 and NQO1. SFN induced Nrf2 target enzyme activity in HT-29 and Caco-2 cancer cells but regulated the Nrf2/ARE signaling pathway differently in cancer and untransformed cells.

The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions.

Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining) assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs) and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS) level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC) or false positive (Selol) results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound.