Secondary Metabolites of Actinomycetes and their Antibacterial, Antifungal and Antiviral Properties

The growing resistance of microorganisms towards antibiotics has become a serious global problem. Therapeutics with novel chemical scaffolds and/or mechanisms of action are urgently needed to combat infections caused by multidrug resistant pathogens, including bacteria, fungi and viruses. Development of novel antimicrobial agents is still highly dependent on the discovery of new natural products. At present, most antimicrobial drugs used in medicine are of natural origin. Among the natural producers of bioactive substances, Actinobacteria continue to be an important source of novel secondary metabolites for drug application. In this review, the authors report on the bioactive antimicrobial secondary metabolites of Actinobacteria that were described between 2011 and April 2018. Special attention is paid to the chemical scaffolds, biological activities and origin of these novel antibacterial, antifungal and antiviral compounds. Arenimycin C, chromopeptide lactone RSP 01, kocurin, macrolactins A1 and B1, chaxamycin D as well as anthracimycin are regarded as the most effective compounds with antibacterial activity. In turn, the highest potency among selected antifungal compounds is exhibited by enduspeptide B, neomaclafungins A-I and kribelloside D, while ahmpatinin iBu, antimycin A1a, and pentapeptide 4862F are recognized as the strongest antiviral agents

Characterization and Optimization of Biosynthesis of Bioactive Secondary Metabolites Produced by Streptomyces sp. 8812

The nutritional requirements and environmental conditions for a submerged culture of Streptomyces sp. 8812 were determined. Batch and fed-batch Streptomyces sp. 8812 fermentations were conducted to obtain high activity of secondary metabolites. In the study several factors were examined for their influence on the biosynthesis of the active metabolites-7-hydroxy-6-oxo-2,3,4,6-tetrahydroisoquinoline-3-carboxyl acid (C10H9NO4) and N-acetyl-3,4-dihydroxy-l-phenylalanine (C11H13NO5): changes in medium composition, pH of production medium, various growth phases of seed culture, amino acid supplementation and addition of anion exchange resin to the submerged culture. Biological activities of secondary metabolites were examined with the use of dd-carboxypeptidase 64–575 and horseradish peroxidase. Streptomyces sp. 8812 mycelium was evaluated under fluorescent microscopy and respiratory activity of the strain was analyzed. Moreover, the enzymatic profiles of the strain with the use of Api®ZYM test were analyzed and genetic analysis made. Phylogenetic analysis of Streptomyces sp. 8812 revealed that its closest relative is Streptomyces capoamus JCM 4734 (98%), whereas sequence analysis for 16S rRNA gene using NCBI BLAST algorithm showed 100% homology between these two strains. Biosynthetic processes, mycelium growth and enzyme inhibitory activities of these two strains were also compared

Risk factors of pelvic organ prolapsed in women qualified to reconstructive surgery – the Polish multicenter study

To evaluate the prevalence rate of various pelvic floor disorders among patients treated in 8 academic centers in Poland due to pelvic organ prolapse (POP). Results: The mean age of affected women with POP was 61,25 years (median 61), and mean BMI – 27.62 (median – 27.29). 80% of women were menopausal. Mean time of symptoms related to disease was 65,6 months; whereas the time relapsed from first doctor diagnosis of POP to hospital admission was 50.6 months. 97.4% affected women were multiparous. Only 1.21% women with POP were nulliparous. Family history of prolapse was found in 13.4% of patients, whereas familial positive history of urinary incontinence was 10%. Lower urinary tract symptoms (LUTS) among the analyzed group were as follows: frequency – almost 50%, urgency 32.2%, feeling of improper voiding – 29,6% and voiding difficulty – 17.7%. Functional disorders of lower bowel were found in 43% of patients and the most prevalent symptom was constipation (31%), followed by empting difficulty (12%), dyschesia (9%), and urge stool empting (7.7%). Cardiovascular diseases were found among 43% of respondents, whereas pulmonary diseases with chronic coughing were present in 20% of the analyzed population. Subjective POP symptoms reported by women were as follows: feeling of heaviness in lower abdomen – 37.8%, perineal pain – 27.8%, lumbosacral pain – 34.2%, and abdominal pain – 28.4%. Female sexual disorders were reported by 9,8% women and dyspareunia was found in 7.6% of responders. POP was the main reason for sexual abstinence only in 1 out of 10 patients. More than 30% of patients from the study group underwent previously pelvic surgery due to various reasons. POP related quality of life measured by VAS (Visual Analogue Scale) was 61.4 points (median – 60). The most common finding during gynecological examination was cystocele – 96.5%, followed by rectoenterocele – 92.7%, and central defect – 79%. Mean POP quantification was stage III in POP-Q scale. LUTS symptoms (urinary incontinence, urgency and voiding difficulties) were present among 81% of patients whereas lower gastrointestinal disorders (constipation, fecal incontinence, dyschesia) were found in 43% of women affected by POP

The glycolysis influence on regulation of interkeukin 6 level in astrocytoma cells

Metabolizm szybko proliferujących komórek prawidłowych oraz komórek nowotworowych, w przeciwieństwie do komórek prawidłowych zróżnicowanych, oparty jest na glikolizie. Proces ten zachodzi niezależnie od dostępności tlenu i prowadzi do powstania mleczanu, który po wydzieleniu na zewnątrz komórki powoduje zakwaszenie środowiska. Ten typ metabolizmu może przynosić komórkom nowotworowym wiele korzyści, m.in. szybką generację biomasy, wydajny pobór glukozy i glutaminy, upośledzenie odpowiedzi układu immunologicznego oraz aktywację metaloproteinaz. Obecnie wiele terapii przeciwnowotworowych skierowanych jest przeciwko ścieżkom metabolicznym. Niniejsza praca skupia się na badaniu wpływu glikolizy na regulację poziomu interleukiny 6 w komórkach gwiaździaka. Interleukina 6 jest cytokiną prozapalną, która ma również działanie antyapoptotyczne i promujące proliferację, w związku z czym może uczestniczyć w progresji nowotworu. Do badań wykorzystano komórki linii U-373 MG. Na podstawie uzyskanych wyników można stwierdzić, że zahamowanie glikolizy z wykorzystaniem 2 - deoksyglukozy prowadzi do wzrostu poziomu mRNA IL-6 poprzez stabilizację transkryptu. Podczas badania regulacji stabilności mRNA pokazano destabilizujący wpływ białek TTP oraz MCPIP1, który nie jest jednak w stanie zrównoważyć efektu stabilizacji po inkubacji komórek z 2-DG. Na stabilizację mRNA IL-6 może mieć wpływ białko HuR, nie wykazano jednak żadnego efektu nadekspresji ARID5A. Pokazano również, że zahamowanie glikolizy jest sygnałem stresu dla badanych komórek i prowadzi do fosforylacji podjednostki α czynnika eIF2. Podjęto również próbę sprawdzenia wpływu zahamowania glikolizy na poziom interleukiny 6 w pożywce i lizatach komórkowych, jednak zakończyła się ona niepowodzeniem, prawdopodobnie z przyczyn technicznych.Metabolism of highly proliferative normal cells and cancer cells, as opposed to normal, differentiated cells, is based on glycolysis. The process doesn't depend on oxygen availability and leads to lactate production. Cells excrete lactate what causes extracellular environment acidification. This kind of metabolism can be beneficial for cancer cells for many reasons, including rapid biomass generation, efficient intake of glucose and glutamine, impaired immune response and activation of metalloproteinases. Nowadays, many anti-cancer therapies are directed against metabolic pathways. The glycolysis influence on regulation of interleukin 6 level in astrocytoma cells is the topic of this study. Interleukin 6 is a pro-inflammatory cytokine that has also anti-apoptotic effect and promotes proliferation what can contribiute to cancer progession. Human astrocytoma U-373 MG cell line was used for the study. It was showed that inhibition of glycolysis with 2-deoxyglucose leads to the increase in IL-6 mRNA by transcript stabilization. RNA-binding proteins, like TTP and MCPIP1 are responsible for IL-6 destabilization whereas HuR seems to be the stabilizing factor. ARID5A, which should protect IL-6 transcript against degradation, has no effect on IL-6 mRNA half-life in this study. What is more, the data show that glycolysis inhibition induces stress response and leads to increased level of phosphorylated eIF2 subunit α. An attempt was made to investigate if 2-deoxyglucose has any influence on interleukin 6 level in medium and cell lysates, but it failed probably because of technical reasons

Influence of glycolysis inhibition on mRNA IL-6 level

Interleukina 6 jest cytokiną zaangażowaną w regulację procesów zapalnych. W niniejszej pracy badano zależność pomiędzy zahamowaniem glikolizy aerobowej w komórkach nowotworowych, a poziomem mRNA IL-6.Interleukin 6 is a cytokine involved in regulation of inflammatory processes. In this study, the relationship between inhibition of aerobic glycolisis in cancer cells and IL-6 mRNA level has been examinated

Citizens’ Perceptions of Landscape Changes and Their Driving Forces: Evidence from Poland

The main aim of our studies was to explore the driving forces of landscape change and their impact on the landscape as perceived by citizens in our study. We use quantitative tools for unravelling processes of landscape change over time and a qualitative tool aimed at capturing people’s perceptions about those changes. We use the two municipalities of Ostrów Wielkopolski and Kąty Wrocławskie as illustrative examples of urban and urban–rural municipalities in two time periods, 2006–2021 and 2012–2018, in Poland. We apply a three-stage approach: (1) to identify the main landscape changes based on land-cover data, (2) to characterize those changes with the use of orthophoto maps and (3) to identify the driving forces of landscape changes with the use of an online survey and interviews. The results show a large agreement between the perceived and actual level of changes. We identified key landscape change processes in both municipalities, and we conclude that citizens’ perceptions concerning those processes in both municipalities differed depending on the context, the level of changes, and the way this process was planned and implemented. In both municipalities, the respondents pointed out political driving forces of landscape change as key underlying drivers. Future landscape planning should consider citizens’ approaches towards landscape change to achieve better societal approval and improve the quality of life of the inhabitants