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Abstract

Background: Prunella vulgaris L., known as self-healing herb, is a widely spread species in the spontaneous flora with beneficial effects on human health, a fact proven in particular by Asian researchers. The aim of this study was to evaluate the antitumor activity and the antibacterial effect on different bacterial strains, including multidrug-resistant ones, depending on the type of solvent used (aqueous, hydroalcoholic), the plant product taken into consideration (spike inflorescence, leaf), its quantity and the concentration of active principles.

Material and method: For screening of antimicrobial susceptibility, both minimum inhibitory concentration and minimum bactericidal concentration were determined on Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosai, and methicillin-resistant Staphylococcus aureus species, including reference strains and hospital strains. Leaves and flower extracts (aqueous and 70% methanolic) were first assessed, and the one with the best antibacterial potential was further tested as a concentrated extract. The antitumor activity was determined on MDA-MB-231 breast adenocarcinoma cells and on a non-tumor cell line, MCF-10A breast epithelial cells by means of Alamar blue technique and Scratch assay.

Results: Inflorescence extracts showed better bacteriostatic effects than leaf extracts on most bacteria, in both aqueous and hydroalcoholic extracts. The concentrated extract of spike inflorescence showed measurable activity with good effects on Gram-positive bacteria, but also on multidrug-resistant Gram-negative ones. The 70% methanolic extract of the species Prunella vulgaris L. (spike inflorescence) demonstrated a concentration-dependent cytotoxic and anti-migratory activity on MDA-MB-231 breast cancer cells, while affecting the non-tumor cell line less.

Conclusions: The results suggest that Prunella vulgaris extracts present antibacterial potential in the complementary treatment of multidrug-resistant infections. The extract from the spike inflorescence of Prunella vulgaris L. produced a dose and time-dependent reduction in cell viability and migration, eliciting a stronger effect on the breast adenocarcinoma cell line.

Abstract

Introduction: Colorectal cancer (CRC) is the third most common neoplasia in the world. Circulating tumor cells (CTC) have a prognostic value and can be useful in monitoring solid neoplasia. Only one method for CTC identification has received the approval and this is the CellSearch® system based on the immunomagnetic separation. Multiple markers are used in CTC identification, as epithelial markers and cytokeratines. CTC identification in peripheral blood is associated with a worse prognostic and reduced free survival in CRC.

Material and methods: We performed a systematic search in PubMed database for articles that reports the circulating tumor cells in CRC until July 2019. We selected studies in English and French and the main words used for search were ‘circulating tumor cells’, ‘colorectal cancer’, ‘colon cancer’, ‘rectal cancer’, ‘flow cytometry’, ‘peripheral blood’. We included studies with more than 10 patients, where samples were collected from the blood in relation with surgery and flow cytometry was used as analyzing technique.

Results: We included 7 studies in final analysis, that showed in flow cytometry analysis a cut-off value of CTC that can vary from 2-4 CTC/ 7.5 ml peripheral blood with a sensitivity of 50.8% and specificity of 95%. Patients with positive CTC were associated with higher T stage and positive lymph nodes, with a worse overall survival (OS) and disease free survival (DFS) comparing with negative patients.

Conclusion: CTC are considered to be a prognostic factor who needs more validation studies in order to be included in the clinical practice.

Abstract

Bacteremia in the febrile neutropenic patients significantly increases the mortality. It takes a long time to complete the blood culture for the diagnosis of bacteremia. Therefore, quick and specific markers are needed for the prediction of bacteremia. The purpose of this study are to compare the diagnostic value of lactate, procalcitonin, C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) levels in a patient with febrile neutropenia, and to evaluate its usefulness in predicting bacteremia. This study was designed to be prospective case-control study. Forty-eight patients and forty control cases aged 18 years or older who were monitored between May 2016 and May 2017 were included in the study. P-value as <0.05 was accepted to be significant. Significantly increased values were determined by the level of inflammatory markers of patients compared to the control group. The highest diagnostic odds ratio were found to be in MCP-1. For patients with febrile neutropenia, CRP (83.3%), and MCP-1 (81.2%) were the most sensitive markers while lactate (85.0%), MCP-1 (75%), and procalcitonin (75%) were the most specific markers. CRP was the only beneficial biomarker in the estimation of bacteremia. No significant results were observed for any biomarker for the prediction of the gram positive/negative discrimination of bacteria in the blood culture. We believe that CRP, MCP-1, and lactate levels can be taken into consideration for diagnosis, and CRP can be beneficial in the estimation of bacteremia.

Abstract

Purpose: We aimed to find critical biomakers associated with BRCA1-mutation positive breast cancer.

Methods: The data set E-MTAB-982 was downloaded from ArrayExpress database and the data were preprocessed using R package Oligo. Differential expression analysis between BRCA1-mutation positive breast cancer patients and BRCA1-mutation positive healthy subjects were performed using limma package. Then, gene set enrichment analysis was conducted. We constructed the network for BRCA1, its related differentially expressed genes (DEGs), and the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. After that, survival analysis was performed based on the clinical data of breast cancer in TCGA database. Finally, box diagram for key genes was drawn.

Results: The network showed that LSM3, NDUFB3, GNPDA2, and PTGS2 were BRCA1 related DEGs. Furthermore, LSM3 was mainly enriched in RNA degradation pathway and spliceosome pathway. PTGS2 was enriched in arachidonic acid metabolism and VEGF signaling pathway. Survival analysis indicated that high expression of LSM3 indicated a poor prognosis of BRCA1-mutant breast cancer. Besides, box diagram showed that LSM3 was down-regulated in BRCA1-mutation positive breast cancer patients compared with that in BRCA1-mutation positive healthy subjects.

Conclusions: LSM3, NDUFB3, and PTGS2 may be biomarkers in BRCA1-mutant breast cancer, and high expression of LSM3 may indicate a poor prognosis of BRCA1-mutant breast cancer.

Abstract

Introduction: A dramatic increase of infections induced by carbapenemase-producing Enterobacterales (CPE) has been registered worldwide. The aim of this study was to evaluate the molecular epidemiology and the clinical impact of CPE strains isolated from adult inpatients.

Material and methods: A one-year, single-center, retrospective observational study including 34 consecutive patients with 37 non-duplicate CPE strains recovered from clinical specimens was accomplished. The Vitek 2 Compact, M.I.C.Evaluator strips, the modified carbapenem inactivation method (mCIM), and the combination disks test (KPC, MBL, OXA-48 Confirm kit, Rosco Diagnostica) were applied as phenotypic tests. A multiplex polymerase chain reaction (PCR) assay was used for detection of blaKPC, blaNDM, and blaOXA-48-like genes. The clonality was assessed with pulsed-field gel electrophoresis (PFGE).

Results: Klebsiella pneumoniae (n=25) was the most frequent CPE encountered. The carbapenemase types were NDM (n=13), KPC (n=12), and OXA-48-like (n=12). Two distinct clonal clusters were identified among the 12 KPC positive strains. All CPE isolates exhibited non-susceptibility to carbapenems, cephalosporins, ciprofloxacin. Respiratory tract infections (n=16) and hospitalization in the intensive care unit (ICU) (n=14) were dominant. The most common comorbidity was congestive heart failure (n=11). Monotherapy was the main strategy adopted (n=15). Death occurred in 18 patients.

Conclusions: Our analysis underscores the scarcity of antibiotic solutions and high mortality. Monotherapy for urinary tract infections (UTIs) is beneficial. Inter- or intrahospital dissemination of successful epidemic clones is proved. The adequate CPE infections control programs and antimicrobial policies are essential..

Abstract

Background: Ovarian malignant germ cell tumors (OMGCT) that fail to recover with conventional management have a poor prognosis. Several recurrent events after chemotherapy have been found. Programmed death ligand-1 (PD-L1) is expressed in various malignancies and tumor infiltrating lymphocytes (TILs) with a known role as a prognostic factor.

Objective: To determine the role of PD-L1 expression in OMGCT in determining overall survival (OS) and progression-free survival (PFS).

Methods: Expression of PD-L1 was assessed from PD-L1 immunohisto-chemistry in paraffin block preparations from 40 patients diagnosed with OMGCT who met the inclusion criteria. The relationship between clinicopathological characteristics and OS and PFS was analyzed using the Kaplan-Meier method and multivariate analysis using the Cox regression model.

Results: No significant relationship was found between PD-L1 expression in tumor cells with 2-year OS (p=0.275) and PFS (p=0.421) in OMGCT. A significant association was found between histopathologic types with 2-year OS (p=0.002), and cancer stage with 2- year OS (p=0.028) and PFS (p=0.014).

Conclusion: PD-L1 expression in tumor cells was not related to OS and PFS in OMGCT patients. There is a tendency for death and recurrence in patients OMGCTs with low PD-L1 expression in tumor cells.

Abstract

Aim: We evaluated the association between anthropometric parameters and markers of insulin and leptin secretion/resistance in patients with type 2 diabetes mellitus (T2DM).

Material and methods: This post-hoc data analysis from a cross-sectional study included 176 T2DM patients. Laboratory tests (serum leptin, soluble form of leptin receptor (sObR), C peptide, glycemic and lipid parameters) and anthropometric parameters were obtained, adiposity indexes (including body adiposity index (BAI), visceral adiposity index (VAI)), indicators of insulin resistance, β-cell function, and leptin resistance (Free Leptin Index, FLI) were calculated.

Results: The body mass index (BMI), diabetes duration, VAI and leptin correlated independently with HOMA-IR, while BMI, diabetes duration and HbA1c with HOMA-B. The total body fat mass (TBFM), C peptide, diabetes duration, BMI and BAI correlated with leptin concentrations, while the first three with FLI. VAI was an indicator of insulin resistance (β=0.166, p=0.003), while BAI of leptin secretion (β=0.260, p=0.010). TBFM strongly associated with leptin resistance and secretion (β=0.037, r=0.688, p<0.0001, and β=0.521, r=0.667, p<0.0001), and BMI correlated weakly with insulin secretion and resistance. While insulin and leptin secretion increased progressively with BMI, leptin and insulin resistance became significant only in case of obesity. The sObR was significantly associated with C peptide concentrations (β=-0.032; p=0.044), but not with HOMA-B or -IR. A strong positive correlation between the C peptide/leptin ratio and non-fat mass /TBFM ratio was noted (r=0.62 [0.52, 0.71], p<0.0001).

Conclusions: Parameters of peripheral adiposity correlated better with markers of leptin system, and those of visceral adiposity with markers of insulin secretion/resistance. The sObR correlated independently and negatively with C peptide.

Abstract

Carbapenemase-producing Enterobacterales (CPE) have emerged and spread in Romania since 2010. According to the reports of the EuSPACE (European survey of carbapenemase-producing Enterobacteriaceae) the epidemio-logical stage of the CPE expansion in Romania has shifted from sporadic occurrence in 2013 directly to inter-regional spread in 2014-2015. In this study we aimed to provide data from the timeframe when the dissemination of the carbapenemase genes in Romania began, by retrospectively analyzing CPE strains in a tertiary care university hospital. During the period of November 2012 – October 2013 we found 107 CPE (8.78%) out of 1219 non-duplicate Enterobacterales strains. 26 isolates of various Enterobacterales species carried blaNDM-1, 83 Klebsiella pneumoniae strains were positive for blaOXA-48-like and 2 of these co-harboured blaNDM-1. The increased incidence of OXA-48 producing K. pneumoniae was linked to a two-peaked hospital outbreak during February and May 2013. The percentage of 24.3% of NDM-1 producers was alarming due to the diversity of involved species and the higher resistance levels to carbapenems compared with blaOXA-48-like gene carriers. Plasmid replicon typing revealed a great diversity of plasmids in NDM-1-positive strains, belonging to incompatibility groups A/C, FII, FIIk, HI2, L and M. The strong connection between certain plasmid groups and host species suggests that the transfer of broad host-range plasmids through conjugation does not play the main role in the successful spread of blaNDM-1 among Enterobacterales species.