Small nucleolar RNA expression profiles: A potential prognostic biomarker for non-viral Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.

Bioresorbable films of polycaprolactone blended with poly(lactic acid) or poly(lactic-co-glycolic acid).

Recent complications on the use of polypropylene meshes for hernia repair has led to the development of meshes or films, which were based on resorbable polymers such as polycaprolactone (PCL), polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). These materials are able to create suitable bioactive environment for the growth and development of cells. In this research, we mainly focused on the relations among structure, mechanical performance and biocompatiblity of PCL/PLA and PCL/PLGA and blends prepared by solution casting. The films were characterized regarding the chemical structure, morphology, physicochemical properties, cytotoxicity, biocompatibility and cell growth. All the films showed high tensile strength ranging from 9.5 to 11.8 MPa. SAXS showed that the lamellar stack structure typical for PCL was present even in the blend films while the morphological parameters of the stacks varied slightly with the content of PLGA or PLA in the blends. WAXS indicated preferential orientation of crystallites (and thus, also the lamellar stacks) in the blend films. In vitro studies revealed that PCL/PLGA films displayed better cell adhesion, spreading and proliferation than PCL/PLA and PCL films. Further the effect of blending on the degradation was investigated, to understand the significant variable within the process that could provide further control of cell adhesion. The results showed that the investigated blend films are promising materials for biomedical applications.

Chitosan and cellulose-based composite hydrogels with embedded titanium dioxide nanoparticles as candidates for biomedical applications.

Hydrogel based matrices and titanium dioxide (TiO2) nanoparticles (NPs) are well established materials in bone tissue engineering. Nevertheless, there is still a challenge to design appropriate composites with enhanced mechanical properties and improved cell growth. Progressing in this direction, we synthesized nanocomposite hydrogels by impregnating TiO2 NPs in a chitosan and cellulose-based hydrogel matrix containing polyvinyl alcohol (PVA), to enhance the mechanical stability and swelling capacity. Although, TiO2 has been incorporated into single and double component matrix systems, it has rarely been combined with a tri-component hydrogel matrix system. The doping of NPs was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and small- and wide-angle X-ray scattering. Our results showed that incorporation of TiO2 NPs improved the tensile properties of the hydrogels significantly. Furthermore, we performed biological evaluation of scaffolds, swelling degree, bioactivity assessment, and hemolytic tests to prove that all types of hydrogels were safe for use in the human body. The culturing of human osteoblast-like cells MG-63 on hydrogels showed better adhesion of cells in the presence of TiO2 and showed increasing proliferation with increasing amount of TiO2. Our results showed that the sample with the highest TiO2 concentration, CS/MC/PVA/TiO2 (1 %) had the best biological properties.

Theranostics Nanomedicine Applications for Colorectal Cancer and Metastasis: Recent Advances.

Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic CRC is a fatal disease. The CRC-affected tissues show several molecular markers that could be used as a fresh strategy to create newer methods of treating the condition. The liver and the peritoneum are where metastasis occurs most frequently. Once the tumor has metastasized to the liver, peritoneal carcinomatosis is frequently regarded as the disease's final stage. However, nearly 50% of CRC patients with peritoneal carcinomatosis do not have liver metastases. New diagnostic and therapeutic approaches must be developed due to the disease's poor response to present treatment choices in advanced stages and the necessity of an accurate diagnosis in the early stages. Many unique and amazing nanomaterials with promise for both diagnosis and treatment may be found in nanotechnology. Numerous nanomaterials and nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold nanoparticles, metal-organic frameworks, core-shell polymeric nano-formulations, and nano-emulsion systems, among others, can be used for targeted anticancer drug delivery and diagnostic purposes in CRC. Theranostic approaches combined with nanomedicine have been proposed as a revolutionary approach to improve CRC detection and treatment. This review highlights recent studies, potential, and challenges for the development of nanoplatforms for the detection and treatment of CRC.

T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis.

In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells' QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.

Peppermint extract inhibits protein aggregation.

The extracts of 7 herbs were screened and compared for their functional ability to inhibit the aggregation of trypsin as an appropriate model protein for in vitro fibrillation in aqueous ethanol at pH 7.0. Turbidity measurements, total phenolic content determination, aggregation kinetics, Congo red binding assay as well as transmission electron microscopy were used to analyse the inhibition of amyloid fibril formation. This correlated with the total phenolic content of the herb extracts. The peppermint extract proved to be the most potent anti-amyloidogenic agent. Results showed that the peppermint extract exerted dose-dependent inhibitory effect on trypsin fibril formation.

Inhibition of the formation of amyloid-like fibrils with spices, especially cloves.

During the study of inhibition of amyloid fibril formation, α-chymotrypsin protein was developed in 55% ethanol at pH 7.0. We investigated the inhibitory effect of different spices on amyloid fibril formation using turbidity measurements and Congo red binding assays. We found that all spices except the black pepper and caraway seed prevented fibril formation. The highest inhibition was measured with the clove, which reduced the amount of aggregates by 90%. We studied the inhibitory effect of the cloves at different concentrations on aggregation, it was found that the inhibitory activity of clove is dependent on concentration. We have measured the total phenolic content of the spice extracts too. Based on all these findings we have come to the following conclusion: Our results indicate that spices can contain other compounds too - not only phenolic compounds - which influence the formation of amyloid fibrils, and the effectiveness of various phenolic compounds are different.

Inhibition of the formation of amyloid-like fibrils using herbal extracts.

We tested the amyloid fibril formation inhibitory effect of seven teas diluted in 55% ethanol at pH 7.0 at a protein concentration of 0.15 mg/ml α-chymotrypsin. In the experiments we investigated the formation and inhibition of amyloid fibrils by turbidity measurements, aggregation kinetics experiments and Congo red binding assay. The results suggest that the different teas effectively inhibit the formation of amyloidlike fibrils. The two most potent inhibitors were peppermint and melilot, extracts which almost completely inhibited the formation of aggregates in 5-fold dilution. The inhibitory effect on the aggregation formation of melilot and peppermint extracts was concentration dependant. The extent of inhibition was found to be proportional with the total concentration of phenolic compounds.

The Inhibitory Effect of Panax Ginseng Extract on Amyloid-like Fibril Formation of Trypsin in Aqueous Ethanol.

BACKGROUND: In case of several chronic diseases, prevention is could be more effective than treatment. Functional foods that contain significant amounts of bioactive components gained considerable attention not only in traditional but in modern medicine as well. We have investigated how P. ginseng extract inhibits the in vitro formation of amyloid-like fibrils of phenylmethylsulfonyl- trypsin (PMS-trypsin) in 60% ethanol at pH 7.0. The model system used is non-physiological, but it is capable of detecting the anti-amyloidogenic effect of the various agents. OBJECTIVE: The main objective of this study was to examine the possible inhibitory effect of ginseng extract on amyloid-like fibril formation of trypsin in aqueous ethanol. METHODS: The amyloid formation and aggregation kinetics of PMS-trypsin was studied by turbidity measurements, Congo Red (CR) binding assays, size exclusion chromatography and Electronic Circular Dichroism (ECD) measurements and the shapes of amyloid fibrils became visible by Transmission Electron Microscopy (TEM). RESULTS: In the presence of 500-fold diluted P. ginseng extract in the incubation mixture, the absorption at 350 nm decreased to 47.1% after incubation for 24 h, compared relative to the sample which contained no additives. CR binding experiments suggested that the aggregates in our samples have amyloid-like properties, and P. ginseng extract inhibits the amyloid-like fibril formation of PMS-trypsin depending on concentration. Our results show that the ginseng extract does not bind to the fibrils. In the absence of P. ginseng extracts large sized colloid aggregates were abundant. Adding P. ginseng extracts to our samples decreased the light dispersion of the solution. This is due to the decrease of the rate of the aggregation or to the smaller size of the aggregates evolved. Our results show that the presence of ginseng extract helps to maintain the native structure of the protein. In the presence of 500-fold diluted P. ginseng extract, TEM images demonstrated, that P. ginseng extract has inhibitory effect on the formation of amyloid-like fibrils of PMS-trypsin. CONCLUSION: The results indicated that P. ginseng extract significantly inhibits the formation of amyloid-like fibrils of PMS-trypsin in aqueous ethanol, and helps to maintain the native structure of the protein. The rate of inhibition depends on concentration. P. ginseng extract is an efficient antiamyloidogenic agent.

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines.

The aim of the present study was to examine the potential role and applicability of dietary supplements in reducing the risk of development of amyloid diseases associated with the gastrointestinal tract, such as type II diabetes. Trypsin, a well-known serine protease was used as a model protein in our experiments. The effect of various red wines on the formation of amyloid-like fibrils of trypsin was studied in vitro, in aqueous ethanol, at pH 7.0. Turbidity measurements, aggregation kinetics experiments, Congo red binding assays and electronic circular dichroism spectroscopic measurements were used to follow the aggregation process in the presence or absence of various red wines. The results suggest that red wines effectively inhibit the formation of amyloid-like fibrils of trypsin and the inhibitory effect is dose-dependent. The extent of inhibition was found to be proportional to the total concentration of phenolic compounds.