The arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.
To determine the oxidant-scavenging activities and antiproliferative activity of (2E)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), an arylidene indanone derivative.
Jurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.
The antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI50) of 341.5 nM, being 12- and 9-fold less than GI50 concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G0/G1 cells after MLT-401 treatment. Mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase activities were inhibited by MLT-401 in a dose-dependent manner.
MLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.
Pulmonary alveolar proteinosis (PAP) is a rare disease, certainly underdiagnosed, characterised by the intra-alveolar accumulation of a milky fluid rich in phospholipids and lipoproteins derived from alveolar surfactant, positive in periodic acid-Schiff staining. The alveolar macrophage plays a major role in the pathogenesis of PAP, and its role in the turn-over of alveolar surfactant is being altered by various mechanisms.
More than 90% of cases of PAP are primary autoimmune, characterised by the presence in serum of circulating autoantibodies against granulocyte-macrophages colony-stimulating factor. Other causes of PAP are genetic, secondary to other diseases or to exposure to different agents.
The evolution of the disease is unpredictable, from spontaneous remission to progression despite treatment towards pulmonary fibrosis and chronic severe respiratory failure. The gold standard of therapy is the whole lung lavage, other treatments are being still in evaluation.
The article presents a few cases that illustrate different patterns in the evolution of PAP.
Chronic obstructive pulmonary disease (COPD) continues to cause a heavy health and economic burden in the Europe and around the world. Arterial hypertension (AH) is considered as one of the principal COPD-associated comorbidi-ties. However, no data for association between gene polymorphism and AH in patients with COPD in Ukraine have ever been internationally published. We assessed the genotype and allele frequencies of angiotensinogen (AGT) M235T polymorphisms in patients with COPD and comorbid AH.
The study group consisted of 96 patients: Group 1 (25 individuals with COPD), Group 2 (23 individuals with AH) and Group 3 (28 individuals with COPD and AH). The control group consisted of 20 healthy subjects. M/T genotypes of AGT were determined by polymerase chain reaction amplification.
The results of the study have not demonstrated any significant impact of alleles of AGT genes on the occurrence of diseases such as COPD, AH and combinations thereof. However, analysis of odds ratio has demonstrated the presence of a trend towards a protective role of the M allele of the AGT gene concerning occurrence of COPD, AH and their combinations. At the same time, the presence of the T allele of the AGT gene may increase the risk for occurrence of the above-mentioned diseases.
The study that we have conducted suggests that the presence of T allele of the AGT gene at position 235 of the peptide chain both in homozygous and heterozygous states may increase the risk for AH in patients with COPD.
The prevalence of asthma is still high in many countries. However, the asthma mortality rate has been significantly decreased after the epidemic of asthma death in the 1970s. The epidemic was occurred in New Zealand and was associated with the use of high-dose inhaled fenoterol at that time. The increased use of inhaled corticosteroids (ICS) in asthma management is proposed as the key factor in the declining trend of asthma mortality rate. The risk factors of asthma-related deaths included history of near-fatal asthma requiring intubation and mechanical ventilation, hospitalisation or emergency care visit for asthma in the past year, currently using or having recently stopped using oral corticosteroids, not currently using ICS, overuse of short-acting b2-agonists, history of psychiatric disease or psychosocial problems, poor adherence with asthma medications and/or poor adherence with (or lack of) a written asthma action plan, food allergy in a patient with asthma, and air pollution.
Quit-smoking support is provided to Romanian smokers since 2007 through a network of stop-smoking centres. The study aimed to collect up-to-date information about the availability of psychological counselling and medication for smoking cessation at the existing specialised centres.
Materials and methods
All the stop-smoking centres listed on the program’s official website were contacted by phone by a trained evaluator introducing himself as a smoker in need of professional support.
Of the 41 counties listed on the website, only 70.7% provided a contact phone number for the stop-smoking centre. While 56.1% of the centres answered the first or second call, the actual availability of quit support was confirmed by only 41.5% of the centres. The time till the first appointment varied between 1 day and 1 month. Psychological support and free medication for treating nicotine addiction were available in 36.6% and 14.6% of the centres, respectively.
The availability of stop-smoking support at the time of the assessment was significantly limited.
We present the case of a male patient, 34 years old, non-smoker, presenting repeatedly in the past 2 years in emergency and cardiology departments for episodes of palpitation accompanied by faitness. One of the electrocardiograms recorded in emergency department captures bigeminated ventricular premature heartbeats. A cardiac magnetic resonance imaging (MRI) examination in May 2019 showed increased thickness of left ventricle during systole and contrast enhancement in the middle of cardiac wall at the base of the heart, considered initially as hypertrophic non-obstructive cardiomyopathy. The reinterpretation of MRI suggested that the changes were typical for cardiac sarcoidosis. Investigations performed later showed increased angiotensin-converting enzyme (ACE); thoracic computed tomography (CT) scan showed nodules and micronodules bilateral in upper lobes with moderate mediastinal lymph node enlargement and bronchoalveolar lavage (BAL) showed lymphocytic alveolitis with normal CD4/CD8 ratio, normal lung function with normal diffusing capacity. Even without biopsy, but based on CT scan, BAL and ACE, the patient was diagnosed as sarcoidosis with lung and cardiac involvement and was started on oral corticosteroids (methylprednisolone 32 mg/day). The diagnosis of cardiac involvement as initial presentation of sarcoidosis is difficult, due to limited knowledge about the disease among cardiologists and radiologists. Though, a recurrent arrhythmia, potentially severe, in a young patient in the absence of an alternative cause, should raise the suspicion for sarcoidosis with cardiac involvement, with a potential severe outcome in the absence of treatment.
Serum starvation is mostly considered as a standard preparatory method in many cellular and molecular experiments. However, recent studies give some evidence that serum starvation is a major event that triggers various cell responses and has therefore great potential to change and interfere with the experimental results. In this study, the behavior of breast cancer cells in serum-starved condition was examined.
To focus on the role of serum starvation on cell migration and also the possible changes in the expression and secretion of genes and cytokines mostly involved in migration and chemotaxis of breast cancer cells.
MDA-MB-231 cells were cultured under serum-starved condition. Transwell migration assay was performed to evaluate the effect of serum starvation on cell migration after 24, 48, and 72 h. The transcriptional expression of migration-related genes was evaluated using real-time polymerase chain reaction. The cytokine secretion was also analyzed using enzyme-linked immunosorbent assay.
Serum starvation suppressed cell migration in breast cancer cells. Additionally, the gene expression of markers involved in migration including β-catenin, twist, zinc finger E-box binding homeobox 1, vimentin, fibronectin, intercellular adhesion molecule 1, and vascular endothelial growth factor were downregulated. Moreover, cytokines of transforming growth factor, beta 1, matrix metallopeptidase 9, interleukin 8, and nitric oxide were differentially secreted.
Serum deprivation causes significant changes in cancer cell migration and also the expression of migration-related genes and cytokines, special care needs to be taken when this practice is used as preparatory method especially in migration and chemotaxis experiments on cancer cells.
E-cigarette has a long history. From 1965 until now, we accepted the promotional campaigns of the tobacco industry and now a new epidemic disease EVALI is generated with an explosion of deaths and pulmonary lesions. We need now to learn more about the algorithm of diagnosis and treatment. This article is updating for 2019 the guideline of diagnosis and treatment of this new disease.
The аim is to study family influence on formation of eating and weight disorders. The concept of an “alimentary family” is defined as a family with dysfunctional, disharmonious relationships, which is a prerequisite for emergence and support of distorted patterns of eating behaviour, leading in the future to children’s eating and weight disorders.
Methods: The research was carried out using the method of a thematic retrospective analysis (MTRA)-food, which is a variant of the narrative method, the questionnaire "Parental convictions and control tactics as for eating behaviour of their children during food taking". The data was processed by the content analysis method; Fisher's φ-criterion was used to compare differences between the groups.
Results: The research has allowed us to clarify eating behavioural characteristics and to identify the “roots” of eating disorders. Various forms of forcing at eating, direct and indirect ways of making children to eat or blocking of eating are manifested in ignoring of children’s taste preferences, their desire and readiness to eat. Parents often use manipulative techniques influencing children’s eating behaviour (encouragement, inducement, reward promises, approval, recognition, warning, or switching attention), direct means of influence (coercion: prohibition, restriction, rejection, destructive criticism, intimidation, deprivation from various pleasures). There is the statistical confirmation that parents’ use of manipulative means and / or direct coercion towards their children during eating predetermines formation of pathological processes of corporeality, attitudes and psychological mechanisms stipulating eating disorders.
Conclusions: The research results indicate necessity to develop psychotherapeutic programs for people with eating disorders, as well as programs to help parents improve family relationships and, accordingly, to apply correctional effects on their children.