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1.
Echocardiography ; 40(3): 174-179, 2023 03.
Article in English | MEDLINE | ID: mdl-36545784

ABSTRACT

BACKGROUND: Takotsubo syndrome (TTS) is characterized by transient abnormalities of myocardial contractility. Noninvasive tests are currently being sought to differentiate TTS from acute coronary syndrome (ACS). THE AIM OF THE STUDY: To evaluate the prevalence of TTS and echocardiographic parameters to distinguish apical TTS from acute anterior wall infarction. MATERIAL AND METHODS: The medical records of patients with suspected TTS, hospitalized in the Department of Cardiology (TTS group n = 18) were analyzed. The control group included patients with STEMI of the left ventricle anterior wall and anterior and lateral wall (STEMI group n = 17). Standard transthoracic echocardiography (TTE) was supplemented with segmental longitudinal strain (LS) assessment with the use of acoustic marker tracking. RESULTS: A statistically significant difference was observed in the second cardiac troponine I (CTNI) measurement (TTS: 3241.2 ng/L vs. STEMI: 12032.6 ng/L; p < 0.05). A significant difference in left and right ventricular size was observed on TTE. Left ventricular end-diastolic and end-systolic volumes were considerably smaller in TTS group; (86.1 vs. 104 ml and 48.1 vs. 74.1 ml, respectively). LS were significantly higher (in absolute values) in patients with TTS than in those with STEMI in the apical and middle lateral segments, LS in the apical four-chamber view (apSept -14.9 vs. -8.9; apLat -14.8 vs. -6.84; midLat -13.26 vs. -9.11). CONCLUSIONS: Patients with TTS are characterized by a different LS pattern in the apical segments of the left ventricle compared to patients with STEMI. TTE examination with LS remains insufficient to distinguish TTS from ACS at the early stage of diagnosis.


Subject(s)
Acute Coronary Syndrome , Anterior Wall Myocardial Infarction , ST Elevation Myocardial Infarction , Takotsubo Cardiomyopathy , Humans , Echocardiography , Myocardium
2.
Biol Sport ; 38(1): 71-79, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33795916

ABSTRACT

The study was designed to assess the usefulness of routine electrocardiography (ECG) as well as transthoracic echocardiography (TTE) in screening top level endurance athletes. An additional goal was to attempt to identify factors determining occurrence of adaptive and abnormal changes in ECG and TTE. The retrospective analysis included basic medical data, ECG and TTE results of 262 athletes (123 rowers, 32 canoeists and 107 cyclists), members of the Polish National Team. The athletes were divided into two age groups: young (≤ 18 years; n = 177) and elite (> 18 years; n = 85). ECG and TTE measurements were analysed according to the International Recommendations from 2017 and 2015, respectively. Adaptive ECG changes were found in 165 (63%) athletes. Abnormal ECG changes were identified in 10 (3.8%) athletes. 98% of athletes exceeded TTE norms for the general population and 26% exceeded norms for athletes. The occurrence of both adaptive ECG findings and abnormalities in the TTE (in norms for athletes) was strongly associated with the years of training, hours of training per week and the age of the athlete. Male gender and the years of training were independent predictors of the ECG and TTE findings. Abnormal ECG changes were not related to the time of sport. Among 10 athletes with ECG changes, only 3 had changes in TTE and no relationship was found between abnormal finding in ECG and TTE (p = 0.45). ECG and TTE screening complement each other in identifying endurance athletes requiring treatment or verification. Unlike abnormal ECG changes, adaptive ECG changes and TTE abnormalities are strongly related to the training duration, which reflects physiological adaptation of the heart to physical exertion in high endurance athletes.

3.
Neurol Neurochir Pol ; 53(2): 156-161, 2019.
Article in English | MEDLINE | ID: mdl-31020990

ABSTRACT

INTRODUCTION: One of the leading causes of death in Poland is stroke. Cardiogenic stroke is known to be one of the most important reasons for acute ischaemic stroke (AIS), comprising 25-30% of all AISs. AIM OF STUDY: Assessment of the prevalence of different risk factors of cardiogenic causes of AIS using transthoracic echocardiography (TTE). MATERIAL AND METHODS: Transthoracic echocardiograms performed in patients with AIS admitted to a single neurological ward between October 2013 and September 2017 were analysed. Patients were assigned, based on the results of their TTE and their previous medical history of atrial fibrillation (AF), to one of three groups depending on the level of the risk of occurrence of cardiogenic causes of AIS. ETHICAL PERMISSION: According to Dz.U.2001, no. 126, 1381 no ethical permission was needed. RESULTS: 663 patients with AIS were included in the study. Patients with high risk of cardiogenic cause of AIS: 26.7% (N = 177 patients [p]). Of these, 64.4% (114 p) were diagnosed with AF. 31.6% (56 p) with sinus rhythm during hospitalisation had a history of paroxysmal AF (PAF). In 11.9% (21 p) of the patients qualified to the high risk group, factors other than AF were found. Patients with moderate risk of cardiogenic cause of AIS: 10.1% (67 p). Patients with low risk of cardiogenic cause of AIS: 25.9% (172 p). Echocardiographic results led to a change in therapy in 1.21% of cases. CONCLUSIONS: 1. Transthoracic echocardiography performed routinely in all AIS patients affects the treatment in a very low percentage of cases. 2. The group that could benefit the most from TTE examination includes people without established indications for chronic anticoagulant therapy, in particular patients after myocardial infarction and people with additional clinical symptoms. 3. In patients with AIS, the diagnostic sensitivity of TTE in the detection of PFO is low. Young people with a cryptogenic ischaemic stroke should undergo a transoesophageal assessment.


Subject(s)
Atrial Fibrillation , Stroke , Anticoagulants , Echocardiography , Humans , Ischemia , Poland
4.
Int J Mol Sci ; 18(6)2017 Jun 06.
Article in English | MEDLINE | ID: mdl-28587286

ABSTRACT

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) was identified as a powerful activator of apoptosis in tumor cells and one of the most promising candidates for cancer therapy with no toxicity against normal tissues. However, many tumor cells are resistant to TRAIL-induced apoptosis. The aim of this work was to analyze the improvement of the anticancer effect of rhsTRAIL (recombinant human soluble TRAIL) by nine flavones: 5-Hydroxyflavone, 6-Hydroxyflavone, 7-Hydroxyflavone and their new synthetic derivatives 5-acetoxyflavone, 5-butyryloxyflavone, 6-acetoxyflavone, 6-butyryloxyflavone, 7-acetoxyflavone and 7-butyryloxyflavone. We examined the cytotoxic and apoptotic effects of rhsTRAIL enhanced by novel structurally-related flavones on SW480 and SW620 colon cancer cells using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, the lactate dehydrogenase assay and annexin V-FITC fluorescence staining. We observed a slight difference in the activities of the flavones that was dependent on their chemical structure. Our study indicates that all nine flavones significantly augment cell death by rhsTRAIL (cytotoxicity range 36.8 ± 1.7%-91.4 ± 1.7%; apoptosis increase of 33.0 ± 0.7%-78.5 ± 0.9%). Our study demonstrates the potential use of tested flavones in TRAIL-based anticancer therapy and prevention.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Colonic Neoplasms/drug therapy , Flavones/chemistry , Flavones/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Cell Line, Tumor , Colonic Neoplasms/pathology , Drug Synergism , Humans , Recombinant Proteins/pharmacology
5.
Int J Mol Sci ; 17(6)2016 Jun 22.
Article in English | MEDLINE | ID: mdl-27338375

ABSTRACT

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and lactate dehydrogenase assay (LDH). The expression of death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2) and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm) by DePsipher reagent using fluorescence microscopy. The intracellular expression of proteins was evaluated by Western blotting. Our study showed that xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of death receptors was not changed. The findings suggest that xanthohumol is a compound of potential use in chemoprevention of prostate cancer due to its sensitization of cancer cells to TRAIL-mediated apoptosis.


Subject(s)
Adenocarcinoma/metabolism , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Flavonoids/toxicity , Plant Extracts/toxicity , Propiophenones/toxicity , Prostatic Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Flavonoids/pharmacology , Humans , Humulus/chemistry , Ligands , Male , Plant Extracts/pharmacology , Propiophenones/pharmacology , Receptors, Death Domain/metabolism , Tumor Necrosis Factor-alpha/metabolism
6.
Cent Eur J Immunol ; 41(3): 229-235, 2016.
Article in English | MEDLINE | ID: mdl-27833438

ABSTRACT

INTRODUCTION: It is well known that the presence of Helicobacter pylori in the stomach induces gastritis and causes an immune response. Exposure of gastric epithelial cell lines to this germ induces the secretion of interleukin-8 (IL-8), which is a potent PMN-activating chemotactic cytokine. Interleukin-8 is usually elevated in gastric biopsy samples of patients with H. pylori-associated gastritis and significantly increases in the supernatant of in vitro cultivated biopsy samples of gastric mucosa with active H. pylori gastritis. Interleukin-8 is an activating factor for leucocytes and other pro-inflammatory factors, free radicals, and proteolytic enzymes. That is why natural compounds potentially useful in therapy are still investigated - among them flavonoids. They reveal anti-oxidative and anti-inflammatory activities and significantly inhibit the gastric mucosa damage. THE AIM OF THE STUDY: Was the estimation of the anti-inflammatory effects of flavonoids on H. pylori-induced activation of human gastric adenocarcinoma cells (AGS). After infection of AGS cells by cag PAI (+) H. pylori in vitro, secretion of IL-8, effects of flavonoids on viability of AGS cells, and effects of flavonoids on increase of H. pylori were determined. Such flavones as chrysin, quercetin, kaemferide, flavanone, galangin, and kaempferol were examined. RESULTS: This study has shown an inhibitory effect of flavonoids on the release of IL-8 through infected AGS cells (except chrysin), and no toxic effects to AGS cells were observed. Galangin revealed antibacterial effects against H. pylori. Flavonoids limit the inflammatory process through the inhibition of IL-8 release in infected AGS cells with H. pylori. The strongest inhibitor of IL-8 was galangin.

7.
Int J Mol Sci ; 16(11): 27433-49, 2015 Nov 17.
Article in English | MEDLINE | ID: mdl-26593898

ABSTRACT

Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.


Subject(s)
Neoplastic Stem Cells/metabolism , Prostatic Neoplasms/etiology , Prostatic Neoplasms/metabolism , Animals , Biomarkers , Cell Transformation, Neoplastic , Gene Expression Regulation, Neoplastic , Humans , Male , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Signal Transduction , Stem Cell Niche
8.
Molecules ; 20(1): 1610-25, 2015 Jan 19.
Article in English | MEDLINE | ID: mdl-25608043

ABSTRACT

Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities.


Subject(s)
Triterpenes/toxicity , Animals , Cell Death/drug effects , Cell Line, Tumor , Humans , Triterpenes/chemistry , Triterpenes/classification
9.
Molecules ; 20(1): 900-12, 2015 Jan 08.
Article in English | MEDLINE | ID: mdl-25580686

ABSTRACT

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R) are an important factor of apoptosis in cancer cells. There are no data about the effect of flavonols on the receptor expression on a surface of macrophage like cells. In this study, the expression level of TRAIL-R1 on murine RAW264.7 macrophages in the presence of selected flavonols: galangin, kaempferol, kaempferide and quercetin, which differ from their phenyl ring substituents, were studied. The expression of TRAIL-R1 death receptors on non-stimulated and lipopolysaccharide (LPS)-stimulated macrophages was determined using flow cytometry. The results suggested that compounds being tested can modulate TRAIL-R1 expression and can enhance TRAIL-mediated apoptosis.


Subject(s)
Flavonols/pharmacology , Macrophage Activation/drug effects , Macrophages/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Apoptosis/drug effects , Cell Line , Flavonols/chemistry , Macrophages/drug effects , Mice , TNF-Related Apoptosis-Inducing Ligand/pharmacology
10.
Pneumonol Alergol Pol ; 83(5): 401-8, 2015.
Article in English | MEDLINE | ID: mdl-26379004

ABSTRACT

Patients with diabetes mellitus (DM) are likely to develop many types of infections, which affect the transport of glucose into tissues. Diabetes increases the susceptibility to different kinds of respiratory infections, is often identified as an independent risk factor for developing lower respiratory tract infections. Pulmonary infections caused by Mycobacterium tuberculosis, Staphylococcus aureus, gram-negative bacteria and fungi may occur with an increased frequency, whereas infections due to Streptococcus pneumonia or influenza virus may be associated with increased morbidity and mortality. During lung infection, there are changes in the local and ciliary epithelial lining. Increased susceptibility to pneumococcal infection by people with diabetes is the result of reduced defense capability of antibodies to protein antigens. The relationship between diabetes and pulmonary tuberculosis is well known, and the incidence of tuberculosis in diabetic individuals is 4-5 times greater than among the non-diabetic population. It is thought that malfunction of monocytes in patients with diabetes may contribute to the increased susceptibility to tuberculosis and/or a worse prognosis. Hospitalization of patients with diabetes due to influenza virus or flu-like infections is up to 6 times more likely to occur compared to healthy individuals, also diabetic patients are more likely to be hospitalized due to infection complications. Immunization with influenza and anti-pneumococcal vaccines is recommended to reduce hospitalizations, deaths, and medical expenses. Diabetes, especially the uncontrolled one, predisposes to fungal infection, the most common candidiasis and mucormycosis.


Subject(s)
Community-Acquired Infections/etiology , Diabetes Complications , Respiratory Tract Infections/etiology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Diabetes Complications/microbiology , Diabetes Complications/prevention & control , Diabetes Mellitus/immunology , Female , Hospitalization , Humans , Immunization , Influenza, Human/prevention & control , Influenza, Human/virology , Male , Monocytes/pathology , Pneumonia/etiology , Prognosis , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/etiology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/prevention & control
11.
Int J Mol Sci ; 15(7): 11510-22, 2014 Jun 27.
Article in English | MEDLINE | ID: mdl-24979133

ABSTRACT

Expression level of Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.


Subject(s)
Apigenin/pharmacology , Flavones/pharmacology , Flavonoids/pharmacology , Macrophages/drug effects , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Cell Line , Macrophages/metabolism , Mice , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics
12.
Biochim Biophys Acta Rev Cancer ; 1878(5): 188944, 2023 09.
Article in English | MEDLINE | ID: mdl-37356738

ABSTRACT

The Growth and Differential Factor 11 (GDF11) is a recently discovered representative of Transforming Growth Factor ß superfamily. The highest expression of GDF11 is detected in the nervous system, bladder, seminal vesicles and muscles whereas the lowest in the testis, liver or breast. GDF11 role in physiology is still not clear. GDF11 is a crucial factor in embryogenesis, cell cycle control and apoptosis, inasmuch it mainly targets cell retain stemness features, managing to the cell differentiation and the maturation. GDF11 is entangled in lipid metabolism, inflammatory processes and aging. GDF11 is strongly related to carcinogenesis and its expression in tumors is intruded. GDF11 can promote cancer growth in the colon or inhibit the cell proliferation in breast cancer. The aberrated expression is probably allied with the impaired maturation. In this article we summarized an impact of GDF11 on the tumor cells and review the all attitudes connecting GDF11 with carcinogenesis.


Subject(s)
Bone Morphogenetic Proteins , Neoplasms , Male , Humans , Bone Morphogenetic Proteins/metabolism , Bone Morphogenetic Proteins/pharmacology , Factor XI , Growth Differentiation Factors/metabolism , Growth Differentiation Factors/pharmacology , Cell Differentiation , Biology
13.
Anal Chem ; 84(13): 5574-81, 2012 Jul 03.
Article in English | MEDLINE | ID: mdl-22724537

ABSTRACT

Detection of new designer drugs remains an analytical challenge because of the ability of manufacturers to rapidly substitute closely related analogs for banned substances. Traditional targeted mass spectrometry methods rely on library searches, known masses, or multiple reaction monitoring (MRM) transitions and are therefore often unable to detect or identify recently discovered or yet unreported designer drug analogs. Here, high-resolution mass spectrometry in conjunction with mass defect filtering is presented as a method for nontargeted analysis to detect both known and novel analogs of designer drugs. The technique is applied in depth to a family of designer drugs composed of indole-derived synthetic cannabinoids closely related to JWH-018, a substance recently controlled in the United States. A single mass defect filter with a 50 mDa window encompasses over 80% of all currently published structures in this family. Searching for precursor ions of common fragment ions enables detection of compounds with mass defects that fall outside the range of mass defect filter parameters. Application of a mass defect filter to fragment ions prior to precursor ion searching increases the breadth of analogs that can be detected. The combined approach defines a broad-spectrum search for related molecules.


Subject(s)
Cannabinoids/analysis , Designer Drugs/analysis , Mass Spectrometry/methods , Plants, Medicinal/chemistry , Substance Abuse Detection/methods , Indoles/analysis , Ions/chemistry , Naphthalenes/analysis
14.
Med Sci Monit ; 18(1): BR47-53, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22207109

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) is an attractive, emerging therapeutic procedure suitable for the treatment of non-muscle-invasive bladder cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that belongs to the TNF superfamily of cytokines. The ability of TRAIL to selectively induce apoptosis in cancer cells but not in normal cells promotes the development of TRAIL-based cancer therapy. However, many tumor cells are resistant to TRAIL-induced apoptosis. The purpose of the study was to overcome TRAIL-resistance in bladder cancer cells by photodynamic therapy (PDT). MATERIAL/METHODS: Three human bladder transitional cancer cell lines - T24, 647V and SW780 - were treated with TRAIL and/or chlorin-based PDT. The cytotoxicity was measured by MTT and LDH assays and apoptosis was detected using annexin V by flow cytometry. RESULTS: Our test confirmed that T24 and 647V bladder cancer cells are resistant to TRAIL, whereas SW780 cells are sensitive to TRAIL. Then we examined the cytotoxic and apoptotic effects of TRAIL in combination with chlorin e6-polyvinylpyrrolidone (Ce6-PVP)-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with a low dose of PDT significantly sensitizes bladder cancer cells to TRAIL-induced apoptosis. Chlorin-based PDT augments the effect of TRAIL on bladder cancer cells. CONCLUSIONS: PDT with Ce6-PVP photosensitizer enhances the cytotoxic and apoptotic effects of TRAIL on bladder cancer cells. The obtained results suggest that combined treatment by TRAIL and PDT may provide the basis for a new therapeutic approach to induce cell death in bladder cancer.


Subject(s)
Apoptosis/drug effects , Photochemotherapy/methods , Porphyrins/therapeutic use , TNF-Related Apoptosis-Inducing Ligand/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Analysis of Variance , Annexin A5 , Cell Line, Tumor , Flow Cytometry , Humans , L-Lactate Dehydrogenase/metabolism , Porphyrins/pharmacology , Statistics, Nonparametric , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Tetrazolium Salts , Thiazoles
15.
Int J Mol Sci ; 13(11): 15343-59, 2012 Nov 20.
Article in English | MEDLINE | ID: mdl-23203129

ABSTRACT

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.


Subject(s)
Apoptosis/drug effects , Chalcone/pharmacology , Neoplasms/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/antagonists & inhibitors , Cell Line, Tumor , Chalcone/toxicity , Drug Synergism , HeLa Cells , Humans , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/pharmacology , TNF-Related Apoptosis-Inducing Ligand/toxicity
16.
Molecules ; 17(6): 6449-64, 2012 May 29.
Article in English | MEDLINE | ID: mdl-22643355

ABSTRACT

Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Benzofurans/pharmacology , Coumarins/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Antineoplastic Combined Chemotherapy Protocols/chemistry , Apoptosis/drug effects , Benzofurans/chemistry , Coumarins/chemistry , Drug Synergism , Gene Expression/drug effects , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Receptors, Death Domain/genetics , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , TNF-Related Apoptosis-Inducing Ligand/chemistry
17.
Molecules ; 17(10): 11693-711, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-23027370

ABSTRACT

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new therapeutic strategies to overcome this resistance. Flavonoids have been shown to sensitize cancer cells to TRAIL-induced apoptosis. The aim of this study was to examine the cytotoxic and apoptotic activities of TRAIL on HeLa cancer cells in combination with two synthetic compounds: 6-hydroxyflavanone (6-HF) and its derivative 6-propionoxy-flavanone (6-PF) and to determine the mechanism by which the flavanones overcome the TRAIL-resistance. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected by annexin V-FITC fluorescence staining in flow cytometry and microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression were analysed using flow cytometry. Mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. The synthetic flavanones enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and reduction of mitochondrial membrane potential. Our study indicates that the 6-HF and 6-PF augmented the anticancer effects of TRAIL and confirm a potential use of flavanones in TRAIL-based anticancer therapy and prevention.


Subject(s)
Antineoplastic Agents/pharmacology , Flavanones/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Drug Synergism , Flavanones/chemical synthesis , Flavanones/toxicity , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Receptors, Death Domain/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Signal Transduction/drug effects , TNF-Related Apoptosis-Inducing Ligand/toxicity
18.
Acta Pol Pharm ; 69(6): 1149-52, 2012.
Article in English | MEDLINE | ID: mdl-23285676

ABSTRACT

Antimicrobial activity in vitro of a series of novel azaphenothiazine derivatives containing a quinoline moiety was investigated using Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains as well as in Candida albicans yeast. The examined compounds showed the highest activity against Enterococcus faecalis and Escherichia coli whereas activity against Pseudomonas aeruginosa was the lowest. Compound 1d demonstrates the highest activity against all tested bacterial strains. Compounds 1c, 1h and 1k with various substituents (CH3, OH, NH2) at C11 position of the quinobenzothiazine ring, did not exhibit activity against any tested bacterial strain. Only compounds 1m and 1n with long aliphatic chains at the quinoline nitrogen atom showed antifungal activity. Correlations between antimicrobial activity and chemical structure of the tested compounds were observed.


Subject(s)
Anti-Infective Agents/pharmacology , Phenothiazines/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Microbial Viability/drug effects , Structure-Activity Relationship
19.
J Cardiovasc Echogr ; 32(2): 116-118, 2022.
Article in English | MEDLINE | ID: mdl-36249436

ABSTRACT

Primary tumors of the heart are extremely rare. The most common is the left atrial myxoma. This article presents a case of large asymptomatic left atrial myxoma in an 80-year-old woman. The patient was admitted to the hospital emergency department after a traffic accident. After a performed trauma scan and an echocardiographic examination, a diagnosis of asymptomatic left atrial myxoma was made. The patient was discharged from the hospital with a referral for a consultation at a cardiac surgery center, which the patient did not attend. The treatment of choice for myxomas is surgical removal. The detection of a myxoma usually is considered as an emergency however the tumor described here has the characteristics of myxoma in the complication-free phase. Given the patient's age, reluctance to undergo invasive surgery, and tumor characteristics, it seems that abandoning invasive management in favor of monitoring the patient's condition may be the preferred therapy.

20.
J Ultrason ; 22(90): e153-e160, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36482923

ABSTRACT

Background: The assessment of elite athletes after SARS-CoV-2 infection gives rise to doubts concerning return-to-play decisions: what period of convalescence is needed and what diagnostic measures are appropriate. While cardiovascular protocols have been widely discussed in the literature, lung parenchyma imaging was only briefly mentioned, and the usefulness of lung ultrasound has been not considered yet. Materials and methods: A total of 31 elite Caucasian male athletes (mean age: 26.03 ± 5.62), recovered from COVID-19 were assessed after SARS-COV-2 infection. Medical data was collected. Lung ultrasonography and high-resolution computed tomography were performed. Results: Normal lung parenchyma dominated on CT scans. A total of 25 athletes (80.6%) presented abnormalities on high-resolution computed tomography; changes typical for COVID-19 were detected in five cases (16.1%), and less specific abnormalities were identified in 20 athletes (64.5%). Despite the prevalence of ultrasound abnormalities, A-line pattern was dominant in 23 athletes (74.2%): for 434 ultrasound-scans, it was visible in = 265 (61.1%). In 93.2% of the subjects, it corresponded to a normal lung parenchyma pattern visible on high-resolution computed tomography. The sensitivity of lung ultrasonography in comparison to high-resolution computed tomography was 74.65%, while the specificity was 68.56%. Conclusion: Lung changes are frequent, but not extensive. Ultrasound A-line pattern was associated with normal lung parenchyma findings revealed on high-resolution computed tomography. The negative predictive value for lung ultrasonography (93.2%) points towards its suitability in return-to-play protocols.

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