Phytochemical composition and antitumor activity of a new arctic lichen Anamylopsora pakistanica.

For the first-time, chemical composition and in vitro antitumor activity was investigated of a newly described lichen Anamylopsora pakistanica Usman & Khalid from the second highest plateau of the world (Deosai Plains, Pakistan). HPLC-UV method was used for identification of secondary metabolites and the acetone extract had higher values of TPC (41.90 mg GA/g) and TFC (75.37 mg RE/g) as compared to methanol extract. As chemical constituents 5,7-dihydroxy-6-methylphthalide, haematommic acid and alectorialic acid, were identified as major compounds. Atranol, alectorialin, gyrophoric acid and usnic acid were detected as minor substances. Acetone and methanol extracts induced a dose-dependent and time-dependent decrease in the viability of three types of tumour cells HeLa, HCT116 and MDA-MB-231. This lichen extract can induce S phase arrest in HeLa as compared to the untreated cells. Extract of this unique lichen, A. pakistanica, can be used safely as a significant source of biologically active compounds.

Antimicrobial treatment in invasive infections caused by Gordonia bronchialis: systematic review.

Background: Corynebacterium, Nocardia, Rhodococcus, Mycobacterium, as well as Gordonia genera belongs to the genus Gordonia, Actinomycetia class. Gordonia bronchialis is a nitrate-reducing, urease-producing, non-motile, force aerobe with a rod-like figure that is known to arrangement into sessile, cord-like groups. This systematic review aimed to establish whether and what invasive infections in humans were caused by Gordonia bronchialis, and to evaluate outcomes of administered antibiotic treatment. Methods: We have registered this systematic review in PROSPERO database of systematic reviews and meta-analyses with the number CRD42022369974. Results: A total of 24 publications were included (22 case reports and two case series) with 28 individual cases. The oldest patients had 92 years, and the youngest patients had 13 years. Clinical signs of infection were present in six patients (21%). All isolates were susceptible to ciprofloxacin, imipenem, and amikacin. Vancomycin was the most frequently used antibiotic with nine cases followed by ciprofloxacin, ceftriaxone, and amoxicillin/clavulanic acid. Conclusion: Although there are no standardized recommendations to date, successful treatment with a favorable outcome has most often been carried out with fluoroquinolones, vancomycin with or without aminoglycosides, as well as carbapenems.

Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units.

Intensive care units (ICUs) are expert hospital areas that provide treatment and 24 h care for people who are very sick. Sepsis represents a serious, severe condition and it can lead to septic shock and multiple organ dysfunction syndromes and is one of the most common reasons for patients' hospitalization in ICUs. We wanted to explore the prognostic values of interleukin (IL) 33, soluble suppression of tumorigenicity 2 (sST2), IL 27, and galectin 3 in critically-ill patients. We assumed that these parameters in combination or alone could predict mortality in ICU patients. This research represents a clinical non-randomized prospective study, performed at the Medical Military Academy, a tertiary care hospital in Belgrade, Serbia. The patients were divided in four groups: patients with sepsis (peritonitis, pancreatitis, trauma) and patients without sepsis (trauma). Total number of patients enrolled in the study was 151 and average years of patients were 56.48. The values greater than the cut-off were the predictors of mortality. The IL-33, IL-27 as well as galectin-3 can successfully predict the outcome of critically-ill patients in ICUs. The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs.

Antimicrobial Treatment of Serratia marcescens Invasive Infections: Systematic Review.

Background: Serratia marcescens (SM) is a Gram-negative pathogen discovered by Italian pharmacist, Bizio, in 1819. According to the literature, S. marcescens is resistant to a wide range of antibiotics, including penicillin, cephalosporin, tetracycline, macrolide, nitrofurantoin, and colistin. We conducted a systematic review of published reports, determined what invasive infections could cause SM, and established the most appropriate antibiotic therapy. Methods: We registered this systematic review on the PROSPERO registry of systematic reviews-meta-analyses before we started our research (registration number CRD42022323159). The online searches of published studies were implemented via MEDLINE, the Cochrane Central Register of Controlled Trials, EBSCO, Scopus, Google Scholar, SCIndex, and the registry of clinical studies of human participants (ClinicalTrials.gov). Results: Our study included 32 published articles (9 case series and 23 case reports). There were 57 individual cases, respectively. The oldest patient was 97 years and the youngest patient was a newborn. S. marcescens was, in most cases, isolated from blood followed by urine and cerebrospinal fluid. In most cases, sensitivity was tested to cotrimoxazole (from 27 isolates, 10 showed resistance) followed by gentamicin (from 26 isolates, 3 showed resistance) as well as amikacin (from 21 isolates, none showed resistance). Patients died from an infection in 21 cases (31%). Conclusions: Treatment of SM infections should include carbapenems or aminoglycosides in combination with third-generation (and eventually fourth-generation) cephalosporin. Cotrimoxazole should be considered in cases of uncomplicated urinary infections.

Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen.

The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8-14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1-7 and 8-14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 µM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.

Validation of the fear of COVID-19 scale in a central Balkan country - Serbia.

Validation of the fear of introduction: High levels of fear of COVID-19 may be associated with increased levels of stress, anxiety, and depression, as well as decreased resilience and life expectancy. Objective: This study aimed to translate and confirm the Serbian version of the Fear of COVID-19 scale as well as to investigate its psychometric properties. Methods: The translation and intercultural adaptation of the Fear of COVID-19 scale was performed by the leading standard of the International Society for Pharmacoeconomics and Outcome Research. When the distribution was normal, the Kolmogorov-Smirnov test was used. The reliability of the Serbian version of FCV-19S was tested by measuring the internal consistency through the value of Cronbach's alpha. Results: The original version of the Fear of COVID-19 scale was tested on a sample of 256 subjects with a mean age of 25.38 ± 12.47. The Cronbach's alpha value was 0.864. We divided the scale by the split-half method (Spearman-Brown), and the value of the coefficient for the questionnaire as a whole was 0.882. Divergent criterion validity was tested through the non-parametric correlation between the scores of the Fear of COVID-19 scale and the Fear of Hospitalization scale. A score of the Fear of COVID-19 scale was calculated as the sum of each question for each of the respondents. Convergent criterion validity was tested through the non-parametric correlation between the scores of the Fear of COVID-19 scale and the Emotional Regulation Questionnaire. Conclusion: The validated version of the scale in Serbia complements versions available in other cultures and other languages and facilitates global studies related to mental health during the COVID-19 pandemic.

Newly synthesized palladium(II) complexes with aminothiazole derivatives: in vitro study of antimicrobial activity and antitumor activity on the human prostate cancer cell line.

Five new complexes of the palladium(II) ion (C1-C5) having the general formula [(PdL2)]Cl2 with some 2-aminothiazoles (L1-L5), where L1 = 2-amino-4-(3,4-difluorophenyl)thiazole, L2 = 2-amino-5-methyl-4-phenylthiazole, L3 = 2-amino-4-phenylthiazole, L4 = 2-amino-4-(4-chlorophenyl)thiazole, and L5 = 2-amino-4-(2,4-difluorophenyl)thiazole, have been synthesized and characterized by elemental microanalysis and infrared, 1H NMR and 13C NMR spectroscopy. The in vitro antimicrobial activity of the five ligands and the corresponding Pd(II) complexes is investigated. Testing is performed by the microdilution method and the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) have been determined. Testing is conducted against 11 microorganisms (nine strains of pathogenic bacteria and two yeast species). The tested ligands and palladium(II) complexes show selective, high and moderate activity. There is a difference in antimicrobial activity between the ligands and the corresponding palladium(II) complexes. The complexes have significant anti-staphylococcal activity and activity on Pseudomonas aeruginosa which is better than the positive control. The interactions of newly synthesized palladium(II) complexes with calf thymus DNA (CT-DNA) were investigated using UV-Vis absorption and fluorescence spectroscopy. Analysis of UV-absorption and fluorescence spectra indicates the formation of a complex between the palladium(II) complexes and DNA. The high values of intrinsic binding constants, Kb, of the order 104 M-1 and Stern-Volmer quenching constants, KSV, of the order 105 M-1 indicated very good binding of all complexes to CT-DNA. Also, the new Pd(II) complexes show high cytotoxic activity towards the human prostate cancer cell line and insignificant activity towards non-cancerous human fibroblasts. Future research could additionally explore the biological activity of Pd(II) complexes presented in this paper and investigate the possibility of their implementation in clinical practice.

Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells.

Endometrial hyperplasia is a condition that may lead to the development of endometrial carcinoma. Initially, changes of the endometrium are caused by the estrogen's hyperstimulation that may lead to the development of an irregular bleeding and the infertility problems. Therapy of endometrial hyperplasia is limited to medical and surgical approaches. During the past decade, the new types of drugs were developed for the treatment of the endometrial hyperplasia. Here, for the first time, we investigated the cytotoxic effects of the various combinations of estrogen, raloxifene, and methotrexate in human ThESC cell line as a possible potential treatment of the endometrial hyperplasia. Our aim was to investigate and to determine the most efficient combination of investigated drugs in ThESC cells during 24-hr period using MTT assay, FACS analysis, and immunofluorescence staining. Our results demonstrated that the combination of raloxifene with methotrexate efficiently induced both the cytotoxicity and apoptosis in ThESC cells when compared to their single effect, as well as to the effect of combined treatment of raloxifene with estrogen. The application of the low doses of methotrexate combined with raloxifene offers all advantages of a potential beneficial antitumor match in cancer chemoprevention and therapy.

Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II) complexes: synthesis, structure, DNA/protein binding, lipophilicity and anticancer activity.

With the aim of assessing how the aromaticity of the inert chelating ligand can influence the activity of ruthenium(II) polypyridyl complexes, two new monofunctional ruthenium(II) complexes, [Ru(Cl-Ph-tpy)(phen)Cl]Cl (1) and [Ru(Cl-Ph-tpy)(o-bqdi)Cl]Cl (2) (where Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, phen = 1,10-phenanthroline, o-bqdi = o-benzoquinonediimine), were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR, XRD). Their chemical behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing that both compounds are relatively labile leading to the formation of the corresponding aqua species 1a and 2a. 1H NMR spectroscopy studies performed on complexes 1 and 2 demonstrated that after the hydrolysis of the Cl ligand, they are capable to interact with guanine derivatives (i.e., 9-methylguanine (9MeG) and 5'-GMP) through the N7, forming monofunctional adduct. The kinetics and the mechanism of the reaction of complexes 1 and 2 with the biologically more relevant 5'-GMP ligand were studied by UV-Vis spectroscopy. DNA/protein interactions of the complexes have been examined by photophysical studies, which demonstrated a bifunctional binding mode of the complexes with DNA and the complexes strongly quench the fluorescence intensity of bovine serum albumin (BSA) through the mechanism of both static and dynamic quenching. Complexes 1 and 2 strongly induced apoptosis of treated cancer cells with high percentages of apoptotic cells and negligible percentage of necrotic cells. In addition, both ruthenium complexes decreased Bcl-2/Bax ratio causing cytochrome c mitochondrial release, the activation of caspase-3 and induction of apoptosis.

Induction of mitochondrial apoptotic pathway by raloxifene and estrogen in human endometrial stromal ThESC cell line.

INTRODUCTION: Endometrial hyperplasia is a condition that occurs as a result of hormonal imbalance between estrogen and progesterone. Morphological disturbance of endometrial cells occurs consequently leading towards endometrial cancer. In therapy of endometrial hyperplasia SERMs are used to supress effects of locally high estrogen level in uterus. There is strong evidence suggesting that estrogen could be involved in cell death - apoptosis. There are no experimental data demstrating the direct apoptotic effect of both raloxifene and estrogen on the ThESC cell line. The aim of our study wa sto investigate both cytotoxic and apototic mechanism of raloxifene and estrogen - induced death in the ThESC cell line. MATERIAL AND METHODS: In order to determine their cytotoxic and apoptotic effects, various doses of raloxifene and estrogen were applied to the ThESC cell line for 24 h. After the treatment MTT assay, FACS analysis and immunofluoroscence method were conducted. RESULTS: The results of this study for the first time demonstrated the cytotoxic and apoptotic effects of raloxifene and estrogen on human endometrial stromal cell line suggesting the involvement of the inner, mitochondrial apoptotic pathway. CONCLUSIONS: Our results demonstrated apoptotic effects of investigated drugs in the ThESC cell line through increasing the Bax/Bcl-2 ratio and activation of caspase 3.

Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy.

OBJECTIVE: Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. MATERIALS: The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective ß-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients' data were collected both from participants' health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. RESULTS: TSH values were significantly higher in the group of patients with selective ß-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. CONCLUSIONS: Our study shows that selective ß-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy.