Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

<p>Abstract</p> <p>Background</p> <p>Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells.</p> <p>Methods</p> <p>The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth <it>in vivo </it>were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression.</p> <p>Results</p> <p>BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10.</p> <p>Conclusions</p> <p>These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.</p

The impact of coping on the somatic and mental status of patients with COPD: a cross-sectional study

Ion Papava,1 Cristian Oancea,2 Virgil Radu Enatescu,1 Ana Cristina Bredicean,1 Liana Dehelean,1 Radu Stefan Romosan,1 Bogdan Timar3 1Department of Neurosciences &ndash; Discipline of Psychiatry, 2Department of Infectious Diseases, 3Department of Functional Sciences, &ldquo;Victor Babes&rdquo; University of Medicine and Pharmacy, Timisoara, Romania Background and objectives: Chronic obstructive pulmonary disease (COPD) is one of the most debilitating somatic diseases, having anxiety and depression frequently as comorbidities. The coping style, the way in which the subject manages to control the difficult and stressful situations of life, can influence its evolution and also the existence of the comorbidities. In this study, coping styles in a group of subjects with COPD and their association with the intensity of depressive and anxiety symptoms as well as medical determinants were identified. Materials and methods: In this cross-sectional study, 28 male patients with COPD risk class&nbsp;D were enrolled. The patients performed spirometry tests, Borg scale, 6-minute walking test, Hospital Anxiety and Depression Scale, and COPE Inventory were recorded. Results: According to their higher coping subscale score, the depression score was the highest in patients with avoidance-type coping and the lowest in patients with problem-focused coping (11.0 vs 5.6; P=0.042), respectively, patients with social support-focused coping having the highest anxiety score in contrast to patients with emotion-focused coping, which had the lowest anxiety score (11.6 vs 5.0; P=0.006). Regarding respiratory parameters, significant differences were present for the variation of the medians between the four groups only for forced vital capacity (FVC%) (the&nbsp;lowest FVC% was in patients with predominant social support-focused coping and the highest in patients with problem-focused coping) and 6-minute walking test (%) (the lowest score for patients with social support-focused coping and the highest value in patients with avoidance-type coping). Problem-coping score was significantly and positively associated with FVC% (Spearman&rsquo;s r=0.400; P=0.035), emotion-focused coping score was significantly and positively associated with FVC% (Spearman&rsquo;s r=0.395; P=0.038), and social support-focused coping score was negatively and significantly correlated with forced expiratory volume in 1 second/FVC% ratio (Spearman&rsquo;s r=0.389; P=0.041). A significant, negative correlation was found only between depression score and forced expiratory volume in 1 second (Spearman&rsquo;s r=-0.435; P=0.026) with respect to psychiatric symptoms. Conclusion: Coping styles in patients with COPD affect the intensity of associated depressive and anxiety symptoms as well as medical determinants, thus the coping style should be considered an important part in the multidisciplinary approach of these patients. Keywords: COPD, COPE, Hospital Anxiety and Depression Scale, depression, anxiet

Cadmium nitrate and DNA methylation in gastropods: comparison between ovotestis and hepatopancreas

Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different organismal levels, including major storage organs (liver, kidneys), key organs for species survival (gonads), and epigenetic networks regulating gene expression. 5-methylcytosine (5mC) is the most common and best-characterized epigenetic mark among different modified nucleosides in DNA. This important player in methylation-driven gene expression is impacted by cadmium in sentinel terrestrial vertebrates. However, limited information exists regarding its impact on macroinvertebrates, especially land snails commonly used as (eco)toxicological models. We first investigate the methylomic effects of dietary cadmium given as cadmium nitrate on terrestrial mollusks. Mature specimens of the common brown garden snail, Cornu aspersum, were continuously exposed for four weeks to environmentally-relevant cadmium levels. We determined global genomic DNA methylation in hepatopancreas and ovotestis, as well as changes in the methylation status of CG pairs at the 5′ region close to the transcription site of gene encoding the Cd-selective metallothionein (Cd-MT). Weight gain/loss, hypometabolism tendency, and survival rates were also assessed. Although this exposure event did not adversely affect survival, gastropods exposed to the highest Cd dose revealed a significant reduction in body weight and a significant increase in hypometabolic behavior. The hepatopancreas, but not the ovotestis, displayed significant hypermethylation, but only for the aforementioned specimens. We also found that the 5′ end of the Cd-MT gene was unmethylated in both organs and its methylation status was insensitive to cadmium exposure. Our results are important since they provide scientists, for the first time, with quantitative data on DNA methylation in gastropod ovotestis and refine our understanding of Cd epigenetic effects on terrestrial mollusks

A novel approach to cardiovascular disturbances in patients with schizophrenia spectrum disorders treated with long-acting injectable medication

Minodora Andor,1,* Liana Dehelean,2,* Ana-Maria Romosan,2,* Valentina Buda,3 Gabriela Radu,1 Florina Caruntu,1 Aurora Bordejevic,1 Minodora Marinela Manea,4 Ion Papava,2 Cristina Ana Bredicean,2 Radu Stefan Romosan,2 Mirela Tomescu1 1Medical Semiology II, Department of Internal Medicine I, &ldquo;Victor Babeş&rdquo; University of Medicine and Pharmacy, Timişoara, Romania; 2Discipline of Psychiatry, Department of Neurosciences, &ldquo;Victor Babeş&rdquo; University of Medicine and Pharmacy, Timisoara, Romania; 3Pharmacology and Clinical Pharmacology, 2nd Department, &ldquo;Victor Babeş&rdquo; University of Medicine and Pharmacy, Timişoara, Romania; 4Department of Psychology, Medical Education, &ldquo;Iuliu Haţieganu&rdquo; University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work and thus share first authorship Purpose: This research article assesses the cardiovascular impact of long-term injectable antipsychotic therapy on patients diagnosed with schizophrenia spectrum disorders. In our study, we attempted to quantify the potential causes of cardiovascular damage, assess cardiovascular parameters, and correlate them with the time elapsed from the onset of the psychosis until the initiation of injectable antipsychotic therapy, as well as the duration of long-acting therapy, and finally, to compare two of the most utilized long-acting injectable (LAI) medications (olanzapine vs risperidone).Patients and methods: This cross-sectional study recruited 64 patients of 2 outpatient clinics undergoing treatment with LAI antipsychotics for schizophrenic spectrum disorder. The study reports outpatients&rsquo; clinical data, laboratory blood sample findings, routine echocardiography, as well as speckle tracking echocardiography.Results: Among patients with longer durations of pre-long-acting antipsychotic treatment, body mass indices, mitral velocity wave values (E and A waves), and the global longitudinal strain (GLS) measurements significantly correlated with patients&rsquo; myocardial contractility. The study also found that GLS was significantly lower in the group in which pre-LAI duration was prolonged, and was not influenced by the duration of LAI treatment. Furthermore, patients receiving olanzapine showed significantly improved myocardial contractility as measured by the aforementioned parameters, in comparison with patients treated with risperidone.Conclusion: The results of our study indicate that patients suffering from schizophrenia and who are left untreated or poorly treated for a longer period of time may develop myocardial impairment. The changes may be both secondary to a high prevalence of cardiovascular risk factors and may also be generated by the disease per se. The group who received olanzapine demonstrated improved results for a longer period of time without proper medication. Keywords: schizophrenic patients, speckle tracking echocardiography, myocardial dysfunctio

Untangling the Professional Web: Understanding the Impact of Work-Related Factors on the Mental Health of Healthcare Professionals During the Late Stages of Covid-19 Pandemic

Ruxandra Laza,1 Anca Lustrea,2 Voichita Elena Lazureanu,1 Adelina Raluca Marinescu,1 Narcisa Nicolescu,1 Alexandra Herlo,1 Talida Georgiana Cut,1,3,4 Tamara Mirela Porosnicu,3,5 Ion Papava,6 Radu Stefan Romosan,6 Ana-Maria Romosan,6 Mariana Bondrescu,3,6 Cristian Zoltan Dimeny,7 Cristina Bianca Nica-Bacaiteanu,7 Minodora Andor,8,9 Liana Dehelean6 1Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 2Department of Educational Sciences, University Clinic of Therapies and Psycho-Pedagogical Counseling, West University of Timisoara, Timisoara, Romania; 3Doctoral School Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 4Center for Ethics in Human Genetic Identifications, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 5Intensive Care Unit, Victor Babes Clinical Hospital of Infectious Diseases and Pneumophtisiology Timisoara, Timisoara, Romania; 6Department of Neurosciences-Psychiatry, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 7Department of Psychiatry, Timis County Emergency Clinical Hospital Pius Brinzeu, Timisoara, Romania; 8Department of Medical Semiology II, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 9Multidisciplinary Heart Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaCorrespondence: Anca Lustrea, Department of Educational Sciences, University Clinic of Therapies and Psycho-Pedagogical Counseling, West University of Timisoara, Bd. Vasile Parvan 4, Timisoara, 300223, Romania, Email [email protected]: The COVID-19 pandemic has determined an extraordinary challenge to healthcare systems worldwide. The extraordinary circumstances, characterized by elevated stress levels, prolonged working hours, new medical procedures, media attention, and high population expectations, have created an extremely stressful situation for healthcare professionals. This period has offered a unique opportunity to examine the medical system and the responses of healthcare practitioners to stress. This research aimed to identify the work-related factors that significantly impact the mental health of healthcare professionals.Patients and Methods: Three mental health variables were assessed: anxiety, depression and stress. The work-related factors considered were professional degree, type of medical unit (COVID or non-COVID), the number of hours spent at work in a single shift, type of shifts, monthly on-call frequency, and number of COVID-19 treated patients per month. In the spring of 2022, three inventories and a demographic survey were distributed and completed online by 300 healthcare professionals from Timisoara’s public hospitals in Romania.Results: Among the respondents, 47.7% reported mild symptoms of anxiety, 65.3% reported moderate levels of stress, and 33% of the participants reported mild symptoms of depression. The intensity of anxious, depressive, and stress symptoms varied significantly depending on the professional degree, number of on-calls per month, the type of medical unit where the participants worked, and the number of SARS CoV-2 patients treated in the previous month.Conclusion: Current data underlines the urgency of implementing effective strategies to reduce the stress and anxiety of medical practitioners who work with COVID-19 patients. Possible interventions encompass a variety of approaches, such as improving working conditions, reducing working hours where possible, increasing access to mental health services, and promoting team-building activities to enhance social support among colleagues. Digital mental health interventions, including online counseling and stress management programs, have also shown promise in these challenging times. Sustaining the mental health of medical practitioners is vital to support the continued provision of first-rate care to patients and to build a resilient healthcare workforce capable of navigating future health crises.Keywords: healthcare professionals, SARS-CoV-2, stress, anxiety, depressio