Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

The extraction of a glucomannan polysaccharide from konjac corms (elephant yam,Amorphophallus rivierii)

Abstract : A process for the micropropagation of Amorphophallus rivierii (elephant yam or konjac) and for the extraction and purification of the glucomannan polysaccharide from fresh konjac plant corms has been developed. This process involves extraction with 2-propanol, which has the additional benefit of extracting carotenoids as a potentially valuable side-product. Starch granules with an unusually high and homogeneous gelatinisation temperature range are normally present in the corms, particularly immature ones, and this greatly reduces the strength of gels formed using the glucomannan. Therefore, the extraction process also involves the selective hydrolysis of the starch, by α- and β-amylases that have been specially selected for an absence of contaminating β-mannanase or β-glucanase activity that would depolymerise the glucomannan and render it nonfunctional. Bacillus lichenformis α-amylase was preferred. Using this process pure glucomannan could be extracted which, when mixed with K -carrageenan, forms a gel almost twice as strong as locust bean gum-K -carrageenan gels of the same concentration.     

High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.     

Comparison of bioactive phytochemical content and release of isothiocyanates in selected brassica sprouts

The consumption of brassica sprouts as raw vegetables provides a fair amount of glucosinolates (GLs) and active plant myrosinase, which enables the breakdown of GLs into health-promoting isothiocyanates (ITCs). This study reports the determination of the main constituents related to human health found in edible sprouts of two Brassica oleracea varieties, broccoli and Tuscan black kale, and two Raphanus sativus varieties, Daikon and Sango. Radish sprouts exhibited the highest ability to produce ITCs, with Daikon showing the greatest level of conversion of GLs into bioactive ITCs (96.5%), followed by Sango (90.0%). Tuscan black kale gave a value of 68.5%, whereas broccoli displayed the lowest with 18.7%. ITCs were not the exclusive GL breakdown products in the two B. oleracea varieties, since nitriles were also produced, thus accounting for the lower conversion observed. Measuring the release of plant ITCs is a valuable tool in predicting the potential level of exposure to these bioactive compounds after the consumption of raw brassica sprouts.     

Does It Look Cooked? A Review of Factors That Influence Cooked Meat Color

ABSTRACT:  Adequate cooking of meat is necessary to inactivate microbial pathogens. This is particularly important for ground meat products and some variety meats where pathogens can be present internally. Consumers are being advised on appropriate temperatures to which meat products should be cooked, and to use a meat thermometer to ensure these temperatures are reached. However, consumers are more likely to assess cooking status by the color of the meat or juice. This article reviews the factors that can influence the final color of cooked meat. In most instances, these factors influence color by modifying the meat pigment myoglobin prior to and during cooking. Many factors can prolong the pink "uncooked" color in meat, including high pH, modified atmosphere packaging, rapid thawing, low fat content, nitrite, and irradiation. Such factors may lead to overcooking and loss of food quality, and consumer rejection. Alternatively, factors that cause "premature browning" of meat, where the interior of the product looks cooked but a microbiologically safe temperature has not been reached, are food safety issues. Pale, soft exudative meats can prematurely brown, as can meats packaged under oxygenated conditions, frozen in bulk or thawed over long periods, or those that have had salts or lean finely textured beef added. Meats cooked from a frozen state or irradiated in aerobic conditions might also be at risk, but this might depend on meat species. In summary, the color of cooked meat is not a good indicator of adequate cooking, and the use of a food thermometer is recommended.     

Dietary Fish Oil Alters DNA Methylation of Genes Involved in Polyunsaturated Fatty Acid Biosynthesis in Muscle and Liver of Atlantic Salmon (Salmo salar)

Adequate dietary supply of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) is required to maintain health and growth of Atlantic salmon (Salmo salar). However, salmon can also convert α-linolenic acid (18:3n-3) into eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) by sequential desaturation and elongation reactions, which can be modified by 20:5n-3 and 22:6n-3 intake. In mammals, dietary 20:5n-3 + 22:6n-3 intake can modify Fads2 expression (Δ6 desaturase) via altered DNA methylation of its promoter. Decreasing dietary fish oil (FO) has been shown to increase Δ5fad expression in salmon liver. However, it is not known whether this is associated with changes in the DNA methylation of genes involved in polyunsaturated fatty acid synthesis. To address this, we investigated whether changing the proportions of dietary FO and vegetable oil altered the DNA methylation of Δ6fad_b, Δ5fad, Elovl2, and Elovl5_b promoters in liver and muscle from Atlantic salmon and whether any changes were associated with mRNA expression. Higher dietary FO content increased the proportions of 20:5n-3 and 22:6n-3 and decreased Δ6fad_b mRNA expression in liver, but there was no effect on Δ5fad, Elovl2, and Elovl5_b expression. There were significant differences between liver and skeletal muscle in the methylation of individual CpG loci in all four genes studied. Methylation of individual Δ6fad_b CpG loci was negatively related to its expression and to proportions of 20:5n-3 and 22:6n-3 in the liver. These findings suggest variations in dietary FO can induce gene-, CpG locus-, and tissue-related changes in DNA methylation in salmon.     

New piezoelectric polymers

Piezoelectricity and pyroelectricity, traditionally encountered in single crystals and ceramics, have now been documented in a number of polymers. The most successful and widely used polymer is polyvinylidene fluoride (PVF₂) which has been shown to be ferroelectric. The copolymers of PVF₂ with related fluorinated vinyl monomers also exhibit piezoelectric activity and those with trifluoroethylene (VF₃) show enhanced activity over the homopolymer. These particular copolymers crystallize into an intrinsically piezoelectric crystal phase from the melt and thus offer advantages in processing and potential application.

This paper compares piezoelectric constants obtained for commercially available PVF₂ with those for a series of PVF₂/VF₃ copolymers. One copolymer shows a 50 per cent increase in activity over PVF₂ when evaluated as a hydrophone material. The chemistry of alternative piezoelectric polymers is described. Areas of application of these exciting new materials are presented.     

The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.