Chronic rhinosinusitis (CRS) is a prevalent, multifaceted inflammatory condition affecting the nasal cavity and the paranasal sinuses, frequently accompanied by formation of nasal polyps (CRSwNP). ...This apparently uniform clinical entity is preceded by heterogeneous changes in cellular and molecular patterns, suggesting the presence of multiple CRS endotypes and a diverse etiology. Alterations of the upper airway innate defense mechanisms, including antimicrobial and antioxidant capacity, have been implicated in CRSwNP etiology. The aim of this study was to investigate mRNA expression patterns of antioxidative enzymes, including superoxide dismutase (SOD) and peroxiredoxin-2 (PRDX2), and innate immune system defense players, namely the bactericidal/permeability-increasing fold-containing family A, member 1 (BPIFA1) and PACAP family members, particularly adenylate-cyclase-activating polypeptide receptor 1 (ADCYAP1) in nasal mucosa and nasal polyps from CRSwNP patients. Additional stratification based on age, sex, allergic comorbidity, and disease severity was applied. The results showed that ADCYAP1, BPIFA1, and PRDX2 transcripts are differentially expressed in nasal mucosa and scale with radiologically assessed disease severity in CRSwNP patients. Sinonasal transcriptome is not associated with age, sex, and smoking in CRSwNP. Surgical and postoperative corticosteroid (CS) therapy improves endoscopic appearance of the mucosa, but variably reverses target gene expression patterns in the nasal cavity of CRSwNP patients. Transcriptional cross-correlations analysis revealed an increased level of connectedness among differentially expressed genes under inflammatory conditions and restoration of basic network following CS treatment. Although results of the present study imply a possible engagement of ADCYAP1 and BPIFA1 as biomarkers for CRSwNP, a more profound study taking into account disease severity and CRSwNP endotypes prior to the treatment would provide additional information on their sensitivity.
Background/Aims: Tff3 protein plays a well recognized role in the protection of gastrointestinal mucosa. The role of Tff3 in the metabolism is a new aspect of its function. Tff3 is one of the most ...affected liver genes in early diabetes and fatty liver rodent models. The aim of this study was to investigate the effect of Tff3 deficiency on lipid and carbohydrate metabolism and on markers of oxidative stress that accompanies metabolic deregulation. Methods: Specific markers of health status were determined in sera of Tff3 deficient mice, including glucose level, functional glucose and insulin tolerance. Composition of fatty acids (FAs) was determined in liver and blood serum by using gas chromatography. Oxidative stress parameters were determined: lipid peroxidation level via determination of lipid hydroperoxide and thiobarbituric acid reactive substances (TBARS), antioxidative capacity (FRAP) and specific antioxidative enzyme activity. The expression of several genes and proteins related to the metabolism of lipids, carbohydrates and oxidative stress (CAT, GPx1, SOD2, PPARα, PPARγ, PPARδ, HNF4α and SIRT1) was determined. Results: Tff3 deficient mice showed better glucose utilization in the glucose and insulin test. Liver lipid metabolism is affected and increased formation of small lipid vesicles is noticed. Formation of lipid droplets is not accompanied by increased liver oxidative stress, although expression/activity of monitored enzymes is deregulated when compared with wild type mice. Tff3 deficient mice exhibit reduced expression of metabolism relevant SIRT1 and PPARγ genes. Conclusion: Tff3 deficiency affects the profile and accumulation of FAs in the liver, with no obvious oxidative stress increase, although expression/activity of monitored enzymes is changed as well as the level of SIRT1 and PPARγ protein. Considering the strong downregulation of liver Tff3 in diabetic/obese mice, presence in circulation and regulation by food/insulin, Tff3 is an interesting novel candidate in metabolism relevant conditions.
Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the ...development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of
and
were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (
= 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty,
= 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6).
mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while
was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with
isolated from sinus swabs showed upregulation of
in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of
genes in the development of CRSwNP.
Seawater is an environment in which numerous microorganisms have evolved, some with a great potential for biotechnology. In recent years, many scientists have moved away from the assumption that the ...origin of life was in pools of water, and instead propose that life on Earth probably originated in accumulations of warm, nutrient-rich mud. This mud, also called peloid is a rich source of organisms that, due to their adaptation to this unique environment, produce a wide variety of primary and secondary metabolites with numerous and diverse activities, including anti-cancer, anti-inflammatory, antiviral, and immunomodulatory ones. In this research, two questions were addressed using collected samples of a peloid with demonstrated healing properties. Firstly biodiversity in this ecological niche was explored in order to assess microbial communities present and secondly natural products were screened for in order to assess whether predicted activities could be linked to healing properties of the peloid. The use of peloids in medical therapy dates back to ancient times. Abiotic components such as clay and mineral water are believed to be the main contributors of the healing properties of natural peloids. The places where peloids are usually found are characteristically shallow and enclosed lagoons. The constant UV exposure and increased salt concentration classify peloid as an extreme environment. The spectrum of relief’s peloid therapy is claimed to provide ranges from purely cosmetic and skin-related to musculoskeletal and immunological problems. These claims can hardly be supported by mineral content and heat-retaining properties alone. However, organic compounds from present microorganisms as well as secondary metabolites could help explain the observed range of health benefits. The fact that the relationship between the therapeutic activity of peloids and their composition besides mineral and physicochemical properties has not been extensively studied indicates untapped biotechnological potential.
The aim of this study was to compare the organismal responses of farmed and wild-caught turbot, Scophthalmus maximus, based on analyses of biochemical plasma parameters, leukocyte profile, and ...histological tissue profile of gills, kidney, liver, intestine, and spleen, as well as gene expression of stress proteins in kidney and liver tissue. The results revealed significant differences in plasma triglycerides (TRIG), total protein (TP), albumin (ALB), globulin (GLOB), bilirubin (TBIL), creatinine (CRE) levels, creatine kinase (CK), and superoxide dismutase (SOD) activities that were higher, and A/G ratio, calcium (Ca) and phosphorus (P) concentrations, alkaline phosphatase (ALP), and glutathione peroxidase (GPx) activity, which were lower in farmed population. The neutrophil-leukocyte (N:L) ratio and gene expression of HSP70, HSP90, and WAP65-2 were increased in the wild-caught turbot. The wild-caught turbot were infested with the gill digenean parasite Dactylogyrus sp. and tapeworm Bothriocephalus scorpii. The obtained results provide valuable data for the assessment of the physiological responses of turbot for future comparative studies of the effects of various endogenous and exogenous factors on homeostasis of this species.
Hydroxyurea has been used for decades and it is still valuable for the treatment of some types of cancer. It inhibits ribonucleotide reductase (RNR) enzyme known to be crucial in the conversion of ...ribonucleotides into deoxyribonucleotides. However, nowadays the main focus has shifted to structurally similar hydroxamic acid derivatives that target specific enzymes involved in cancer progression such as histone deacetylases, matrix metalloproteinases and also RNR.
Bacteria from the genus
Shewanella
are inhabitants of marine and freshwater ecosystems, recognized fish spoilage bacteria, but less known as fish disease agents.
Shewanella
spp. isolated from fish ...living in waters close to effluents of a wastewater treatment plant (WWTP) were not previously characterized. We have tested
Shewanella
isolates from WWTP-affected waters and related fish. Genotypic characterization identified most strains as
S. baltica
and
S. oneidensis
. In order to investigate the sensibility and accuracy of their MALDI-TOF MS identification, they were grown on two culture media enriched by various NaCl concentrations, incubated at different temperatures and duration. We analyzed their antimicrobial susceptibility on a panel of antimicrobial drugs and capacity for biofilm production. With a view to demonstrate their capacity to produce fatty acids, we assessed the impact of different culture media on their lipid profile. We performed zebrafish embryotoxicity tests to simulate the environmental infection of the earliest life stages in
S. baltica
-contaminated waters. The best MALDI-TOF MS identification scores were for strains cultivated on TSA for 24 h at 22 °C and with supplementation of 1.5% NaCl. Less than 17% of isolates demonstrated antimicrobial resistance. Most isolates were weak biofilm producers. Strain-to-strain variation of MIC and MBC was low. The major fatty acids were C15:0, C16:0, C16:1, C17:1, and iC15:0. Exposure of
Danio rerio
to different
S. baltica
concentrations induced severe effects on zebrafish development: decreased heartbeat rate, locomotor activity, and melanin pigmentation.
S. baltica
passed through chorionic pores of zebrafish.
•High frequency of p53 mutations in renal cell cancer was found by functional assay.•Full-length p53 was the most expressed isoform in renal cell cancer.•Δ133p53 isoforms were down-regulated in ...cancer compared to normal tissue.•Expression of all examined p53 isoforms was higher in tumors harboring mutant p53.•p53 function might be lost either by specific p53 isoform expression or by mutation.
To analyze p53 mutations and gene expression of p53, ∆40p53, and ∆133p53 isoforms in renal cell cancer (RCC) tissues and normal adjacent tissue (NAT) and to associate them to clinical features and outcome.
Forty-one randomly selected patients, with primary, previously untreated RCC, with complete clinicopathohistological data were analyzed. NAT samples were available for 37 cases. Expression of p53, ∆40p53 and ∆133p53 was determined using RT-qPCR. A functional yeast-based assay was performed to analyze p53 mutations.
More than half (56.1%) of patients harbored functional p53 mutations, and they were significantly younger than those with wild type (WT) p53 (P = 0.032). Expression of p53, ∆40p53, and ∆133p53 was upregulated in mutant (MT) p53 RCC compared to WT p53 RCC tissues. However, there was no difference in expression of these isoforms between MT p53 RCC tissues and NAT. Expression of ∆133p53 was significantly downregulated in WT p53 tissues compared to NAT (P = 0.006). Patients that harbored functional p53 mutation had better overall survival (hazard ratio 4.32, 95% confidence interval 1.46–18.82, P = 0.006). Multivariate analysis demonstrated that tumor stage and p53 mutation might be used as independent prognostic marker for overall survival in RCC patients.
Our findings support the specific events in the carcinogenesis of RCC. p53 isoforms can be differentially expressed depending on p53 mutational status.
The aim of the study was to compare bacterial composition and load in waters and fish related to the wastewater treatment plant (WWTP), particularly waters and wild fish affected by sugarplant ...processing (sugar cane and sugar beet). Aeromonads were the most frequently isolated group from water and fish. A. hydrophila was a prevailing species in isolates from water, followed by A. veronii, Rheinheimera soli and Ochrobactrum anthropi. Of indicator bacteria for aquatic contamination from fish tissues, the most prominent were V. cholerae, Enterobacter cloacae and E. sakazakii. Sugar cane processing contributed to high viable cell counts at 37 °C while sugar beet processing contributed to high bacterial counts at 22 °C. Heterotrophs from gills of effluent fish were highest during sugar cane processing. Counts retrieved from fish skin were more uniform between effluent fish and fish from downstream waters. Antimicrobial resistance of bacteria isolated from water was high against amoxicillin, sulfamethoxazole, flumequine, norfloxacin and oxolinic acid in samples from the inflow of raw municipal wastewaters to WWTP, while resistance found in bacteria from the inflow of sugarplant mostly related to sulfamethoxazole and amoxicillin. The PCA analysis associated the occurrence of high heterotroph counts, P. aeruginosa, and intestinal enterococci on skin and gills with sugar cane, and yeasts and molds with sugar beet processing. Fish living in treated wastewaters and related water bodies could pose a microbial hazard if fished for human consumption, possibly causing infection when being handled and processed, as a risk of human pathogens penetrating fish tissues.
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•We evaluated microbiological impact of sugarplant effluent on wild fish.•Ubiquitous and pathogenic bacteria were retrieved from tissues; mostly aeromonads.•63% of fish aeromonads showed resistance against tested antimicrobials.•Gill and kidney histopathology showed an increased number of bacterial cells.•Multivariate tools correlated effectively microbiological data, tissues and seasons.
DNA intercalating and minor groove binding compounds are new weapons in the battle against malignant diseases. These antineoplastic agents target the DNA molecule and interfere with the cell cycle ...leading to rapidly proliferating cell death. They are mainly derivates of a naturally occurring organic compound derived from a microorganism or plant. Intercalators usually act as topoisomerase I and/or II poisons, while the mechanisms of DNA minor groove binders are a combination of several steps including topoisomerase poisoning. This paper gives an overview of some of the developed DNA intercalating and minor groove binding compounds, as well as an explanation of their chemical structures, origins, and application in chemotherapy.
Novo oružje u borbi protiv zloćudnih bolesti su spojevi koji se umeću u dvolančanu strukturu deoksiribonukleinskih kiselina (DNA) ili se vezuju na mali utor DNA. Navedene skupine kemoterapeutika primarno ciljaju molekulu DNA te utječu na stanični ciklus što vodi do smrti brzo dijelećih stanica. Uglavnom su derivati organskih spojeva prirodnog podrijetla, izoliranih iz mikroorganizama ili biljaka. DNA umetnuti spojevi uglavnom djeluju kao otrovi enzima topoizomeraza I i/ili II a spojevi koji se vezuju na mali utor DNA imaju kombinirani mehanizam djelovanja pri čemu je jedan od koraka i otrovanje topoizomeraza. U ovom preglednom članku dajemo pregled nekih od spojeva koji se umeću u molekulu DNA ili vezuju na mali utor DNA, a koji se primjenjuju u kemoterapiji, njihova podrijetla i kemijske strukture.
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