Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells.

Colon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of ALDH1B1 knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer.

Degradation of per- and polyfluoroalkyl substances in landfill leachate by a thin-water-film nonthermal plasma reactor.

Per- and polyfluoroalkyl substances (PFAS) are present in landfill leachate, posing potential challenges to leachate disposal and treatment. This work represents the first study of a thin-water-film nonthermal plasma reactor for PFAS degradation in landfill leachate. Of the 30 PFAS measured in three raw leachates, 21 were above the detection limits. The removal percentage depended on the category of PFAS. For example, perfluorooctanoic acid PFOA (C8) had the highest removal percentage (77% as an average of the three leachates) of the perfluoroalkyl carboxylic acids (PFCAs) category. The removal percentage decreased when the carbon number increased from 8 to 11 and decreased from 8 to 4. The effects of various landfill leachate components, including sodium chloride, acetate, humic acids, pH, and surfactants, had no or minor impacts (<30%) on PFOA mineralization in synthetic samples. This might be explained by the plasma-generation and PFAS-degradation mainly occurring at the gas/liquid interface. Shorter-chain PFCAs were produced as intermediates of PFOA degradation, and shorter-chain PFCAs and perfluorosulfonic acids (PFSAs) were produced as intermediates of perfluorooctanesulfonic acid (PFOS). The concentrations of the intermediates decreased with decreasing carbon number, suggesting a stepwise removal of difluoromethylene (CF2) in the degradation pathway. Potential PFAS species in the raw and treated leachates were identified at the molecular level through non-targeted Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The intermediates did not show accurate toxicity per Microtox bioassay.

Analysis of Isotopically Depleted Proteins Derived from Escherichia coli and Caenorhabditis elegans Cell Lines by Liquid Chromatography 21 T Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry.

Protein mass measurement by mass spectrometry is complicated by wide isotopic distributions that result from incorporation of heavy isotopes of C, H, N, O, and S, thereby limiting signal-to-noise ratio (SNR) and accurate intact mass determination, particularly for larger proteins [Fenselau et al. Anal. Chem. 1983, 55 (2), 353-356]. Observation of the monoisotopic mass-to-charge ratio (m/z) is the simplest and most accurate way to determine intact protein mass, but as mass increases, the relative abundance of the monoisotopic peak becomes so low that it is often undetectable. Here, we used an isotopically depleted growth medium to culture bacterial cells (Escherichia coli), resulting in isotopically depleted proteins. Isotopically depleted proteins show increased sequence coverage, mass measurement accuracy, and increased S/N of the monoisotopic peak by Fourier transform ion cyclotron resonance mass spectrometry analysis. We then grew Caenorhabditis elegans cells in a medium containing living isotopically depleted E. coli cells, thereby producing the first isotopically depleted eukaryotic proteins. This is the first time isotopic depletion has been implemented for four isotopes (1H, 12C, 14N, and 16O), resulting in the highest degree of depletion ever used for protein analysis and further improving MS analysis.

The Efficacy and Tolerability of a Fixed Combination of Perindopril and Indapamide in the Treatment of Unregulated Essential Hypertension - a Postmarketing Study.

OBJECTIVE: The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. PATIENTS AND METHODS: The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥ 140/90 mmHg at baseline. On the basis of the investigator's decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). RESULTS: The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. CONCLUSION: A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

Introduction to verification of the GOHAI instrument for measuring the oral health-related quality of life in patients with dentures using the Serbian preliminary version--A pilot study.

BACKGROUND/AIM: Quality of life related to health should be seen as a multidimensional concept that, in addition to the physical symptoms associated with a disease and treatment, should include physical, psychological and social functioning of a person. The primary objective of this study was to use the Serbian preliminary version of the Geriatric Oral Health Assessment Index (GOHAI) questionnaire in oder to examine the consistency, reliability and stability, as well as an introduction to the verification tool. METHODS: The GOHAI questionnaire with 6-level Likert scale, translated into Serbian, including the relevant oral health characteristics (oral hygiene, required dentures, number of teeth extracted), was filled by five specialists in prosthodontics for 30 randomly selected respondents, before and after the dental prosthetic treatment. Subsequently, in order to measure the reliability of the questionnaire, 27 patients were re-interviewed. RESULTS: The value of Cronbach's Alpha Coefficient (Crα) before the treatment was 0.878, and after the treatment it was 0.788 confirming the internal consistency and stability of the questionnaire. The validity of discriminatory properties of the GOHAI was confirmed by the Spearman's correlation coefficient (r), which was highly significantly associated with oral health characteristics, confirming the high reliability of the measurement. The results of test-retest analysis measured by the individual Pearson's correlation coefficient (r) were in the range of 0.34-0.97, and for the total score r was 0.927, while the Kappa coefficient was 0.63. The correlation analysis of the GOHAI score before the treatment showed that for 10 questions there was a statistically significant correlation of the score with the answers to the questions, and for 6 questions Spearman's r was ≥ 0.7. After the treatment a highly significant correlation of the GOHAI was shown with the answers to 10 questions, while for 5 questions the Spearman's r was > 0.6. The GOHAI average score before the treatment was 19.44 ± 11.12, and after the treatment 2.77 ± 3.83, where the lower value indicates better quality of life. CONCLUSION: The results of this pilot study confirm internal consistency and stability of the Serbian preliminary version of the GOHAI questionnaire and the causal relation between the quality of life and the characteristics of oral health of the patients with dentures. Accordingly, instrument verification is recommended.