Antibacterial and Biodegradable Polysaccharide-Based Films for Food Packaging Applications: Comparative Study

One of the major objectives of food industry is to develop low-cost biodegradable food packaging films with optimal physicochemical properties, allowing for their large-scale production and providing a variety of applications. To meet the expectations of food industry, we have fabricated a series of solution-cast films based on common biodegradable polysaccharides (starch, chitosan and alginate) to be used in food packaging applications. Selected biopolymers were modified by the addition of glycerol and oxidized sucrose (starch), glycerol (chitosan), and glycerol and calcium chloride (alginate), as well as being used to form blends (starch/chitosan and starch/alginate, respectively). A chestnut extract was used to provide antibacterial properties to the preformed materials. The results of our studies showed that each modification reduced the hydrophilic nature of the polymers, making them more suitable for food packaging applications. In addition, all films exhibited much higher barrier properties to oxygen and carbon dioxide than commercially available films, such as polylactic acid, as well as exhibiting antimicrobial properties against model Gram-negative and Gram-positive bacteria (Escherichia coli and Staphylococcus epidermidis, respectively), as well as yeast (Candida albicans).     

Dietary Patterns and Metabolic Disorders in Polish Adults with Multiple Sclerosis

Diet plays a major role in the aetiopathogenesis of many neurological diseases and may exacerbate their symptoms by inducing the occurrence of metabolic disorders. The results of research on the role of diet in the course of multiple sclerosis (MS) are ambiguous, and there is still no consensus concerning dietary recommendations for patients with MS. The aim of this study was to analyse the dietary patterns (DPs) of patients with MS and to assess the relationships between these DPs and the metabolic disorders. The study participants were comprised of 330 patients aged 41.9 ± 10.8 years. A survey questionnaire was used to collect data related to diet, lifestyle and health. The DPs were identified using a principal component analysis (PCA). Three DPs were identified: Traditional Polish, Prudent and Fast Food & Convenience Food. An analysis of the odds ratios adjusted for age, gender, smoking and education showed that a patient’s adherence to the Traditional Polish and the Fast Food & Convenience Food DPs increased the likelihood of abdominal obesity and low HDL-cholesterol concentration. Conversely, adherence to the Prudent DP was not significantly associated with any metabolic disorder. The results of this study confirmed that an unhealthy diet in patients with MS is connected with the presence of some metabolic risk factors. There is also an urgent need to educate patients with MS on healthy eating, because the appropriate modifications to their diet may improve their metabolic profile and clinical outcomes.     

Acoustic Performance of Sound Absorbing Materials Produced from Wool of Local Mountain Sheep

Wool of mountain sheep, treated nowadays as a waste or troublesome byproduct of sheep husbandry, was used for the production of sound-absorbing materials. Felts of two different thicknesses were produced from loose fibres. Additionally, two types of yarn, ring spun and core rug, were obtained. The yarns were used for the production of tufted fabric with cut and loop piles. During the examinations, basic parameters of the obtained materials were determined. Then, according to standard procedure with the use of impedance tube, the sound absorption coefficient was measured, and the noise reduction coefficient (NRC) was calculated. It was revealed that felt produced from coarse wool exhibits high porosity, and its sound absorbing capacity is strongly related to the felt thickness. For thicker felt the NRC achieved 0.4, which is comparable with the NRC of commercial ceiling tiles. It was shown that the crucial parameter influencing the sound absorption of the tufted fabrics was the pile height. For both types of yarns, when the height of the pile was increased from 12 to 16 mm, the NRC increased from 0.4 to 0.42. The manufactured materials made from local wool possess good absorption capacity, similar to commercial products usually made from more expensive wool types. The materials look nice and can be used for noise reduction as inner acoustic screens, panels, or carpets.     

Stereoselective Synthesis and Anticancer Activity of 2,6-Disubstituted trans-3-Methylidenetetrahydropyran-4-ones

In this report, we present efficient and stereoselective syntheses of 2,6-disubstituted trans-3-methylidenetetrahydropyran-4-ones and 2-(4-methoxyphenyl)-5-methylidenetetrahydropyran-4-one that significantly broaden the spectrum of the available methylidenetetrahydropyran-4-ones with various substitution patterns. Target compounds were obtained using Horner–Wadsworth–Emmons methodology for the introduction of methylidene group onto the pyranone ring. 3-Diethoxyphosphoryltetrahydropyran-4-ones, which were key intermediates in this synthesis, were prepared by fully or highly stereoselective addition of Gilman or Grignard reagents to 3-diethoxyphosphoryldihydropyran-4-ones. Addition occurred preferentially by axial attack of the Michael donors on the dihydropyranone ring. Relative configurations and conformations of the obtained adducts were assigned using a detailed analysis of the NMR spectra. The obtained methylidenepyran-4-ones were evaluated for cytotoxic activity against two cancer cell lines (HL-60 and MCF-7). 2,6-Disubstituted 3-methylidenetetrahydropyran-4-ones with isopropyl and phenyl substituents in position 2 were more cytotoxic than analogs with n-butyl substituent. Two of the most cytotoxic analogs were then selected for further investigation on the HL-60 cell line. Both analogs induced morphological changes characteristic of apoptosis in cancer cells, significantly inhibited proliferation and induced apoptotic cell death. Both compounds also generated DNA damage, and one of the analogs arrested the cell cycle of HL-60 cells in the G2/M phase. In addition, both analogs were able to inhibit the activity of topoisomerase IIα. Based on these findings, the investigated analogs may be further optimized for the development of new and effective topoisomerase II inhibitors.     

Ultrasensitive profiling of UV-induced mutations identifies thousands of subclinical facial tumors in tuberous sclerosis complex

BackgroundTuberous sclerosis complex (TSC) is a neurogenetic syndrome due to loss-of-function mutations in TSC2 or TSC1, characterized by tumors at multiple body sites, including facial angiofibroma (FAF). Here, an ultrasensitive assessment of the extent and range of UV-induced mutations in TSC facial skin was performed.MethodsA multiplex high-sensitivity PCR assay (MHPA) was developed, enabling mutation detection at extremely low (<0.1%) variant allele frequencies (VAFs).ResultsMHPA assays were developed for both TSC2 and TP53, and applied to 81 samples, including 66 skin biopsies. UV-induced second-hit mutation causing inactivation of TSC2 was pervasive in TSC facial skin with an average of 4.8 mutations per 2-mm biopsy at median VAF 0.08%, generating more than 150,000 incipient facial tumors (subclinical “micro-FAFs”) in the average TSC subject. The MHPA analysis also led to the identification of a refined UV-related indel signature and a recurrent complex mutation pattern, consisting of both a single-nucleotide or dinucleotide variant and a 1- to 9-nucleotide deletion, in cis.ConclusionTSC facial skin can be viewed as harboring a patchwork of clonal fibroblast proliferations (micro-FAFs) with indolent growth, a small proportion of which develop into clinically observable FAF. Our observations also expand the spectrum of UV-related mutation signatures.FundingThis work was supported by the TSC Alliance; the Engles Family Fund for Research in TSC and LAM; and the NIH, National Heart, Lung, and Blood Institute (U01HL131022-04 and Intramural Research Program).     

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

MET receptor is a potential therapeutic target in high grade cervical cancer

Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.     

Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47^phox subunits, elevated level of p47^phox phosphorylation, and enlarged phospho‐p47^phox and p67^phox content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho‐p47^phox and p67^phox. Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.