Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.     

Distinct Ca2+- and cAMP-dependent anion conductances in the apical membrane of polarized T84 cells

Monolayers of the human colonic epithelial cell line T84 exhibitelectrogenic Cl secretionin response to the Ca²⁺ agonistthapsigargin and to the cAMP agonist forskolin. To evaluate directlythe regulation of apical Clconductance by these two agonists, we have utilized amphotericin B topermeabilize selectively the basolateral membranes of T84 cellmonolayers. We find that apical anion conductance is stimulated by bothforskolin and thapsigargin but that these conductances aredifferentially sensitive to the anion channel blocker DIDS. DIDSinhibits thapsigargin-stimulated responses completely but forskolinresponses only partially. Furthermore, the apical membrane anionconductances elicited by these two agonists differ in anion selectivity(for thapsigargin, I > Cl; for forskolin,Cl > I). However, theDIDS-sensitive component of the forskolin-induced conductance responseexhibits anion selectivity similar to that induced by thapsigargin(I > Cl). Thusforskolin-induced apical anion conductance comprises at least twocomponents, one of which has features in common with that elicited bythapsigargin.

     

Evaluation of pomegranate (Punica granatum L. var. Gabsi) peel extract for control of root-knot nematode Meloidogyne javanica on tomato

The present study was carried out to assess the nematicidal potential of Punica granatum L. against the root-knot nematode Meloidogyne javanica responsible for yield losses in tomato. Varied concentrations of methanolic, ethanolic and aqueous extracts from pomegranate peels were investigated for activity against eggs and juveniles of M. javanica in in vitro assays. All extracts used significantly inhibited egg hatch by over than 75%, but viability of second-stage juveniles (J2) was not significantly inhibited by ethanolic extract. Aqueous extract was assessed at the concentration of 10, 25 and 50% against M. javanica on tomato in greenhouse trials; pomegranate peels powder was also tested at the rate of 3, 6 and 9 g as a soil amendment. Both extracts significantly reduced nematode infestations; aqueous extract enhanced plant growth but powder amendment exhibited a phytotoxicity compared to the untreated plants. The reduction in number of galls, egg masses and nematode reproduction rate was recorded.     

Nanoparticle Fullerene (C60) demonstrated stable binding with antibacterial potential towards probable targets of drug resistant Salmonella typhi – a computational perspective and in vitro investigation

Salmonella typhi, a Gram negative bacterium, has become multidrug resistant (MDR) to wide classes of antibacterials which necessitate an alarming precaution. This study focuses on the binding potential and therapeutic insight of Nano-Fullerene C60 towards virulent targets of Salmonella typhi by computational prediction and preliminary in vitro assays. The clinical isolates of Salmonella typhi were collected and antibiotic susceptibility profiles were assessed. The drug targets of pathogen were selected by rigorous literature survey and gene network analysis by various metabolic network resources. Based on this study, 20 targets were screened and the 3D structures of few drug targets were retrieved from PDB and others were computationally predicted. The structures of nanoleads such as Fullerene C60, ZnO and CuO were retrieved from drug databases. The binding potential of these nanoleads towards all selected targets were predicted by molecular docking. The best docked conformations were screened and concept was investigated by preliminary bioassays. This study revealed that most of the isolates of Salmonella typhi were found to be MDR (p < .05). The theoretical models of selected drug targets showed high stereochemical validity. The molecular docking studies suggested that Fullerene C60 showed better binding affinity towards the drug targets when compared to ZnO and CuO. The preliminary in vitro assays suggested that 100 μg/L Fullerene C60 posses significant inhibitory activities and absence of drug resistance to this nanoparticle. This study suggests that Fullerene C60 can be scaled up as probable lead molecules against the major drug targets of MDR Salmonella typhi.     

Chromium Exposure in the Adult Population,Consuming Different Types of Smokeless Tobacco Products in Pakistan

The pervasive smokeless tobacco (SLT) consumption and diseases related to its use is a hot topic for the public discussion. In this study, concentrations of chromium (Cr) were measured in different SLT products [snuff (dry and moist), mainpuri, and gutkha] offered and used in Pakistan. The current study was also designed to assess the Cr levels in the biological (scalp hair and blood) samples of male and female subjects, age ranged from 25 to 60 years, chewing different SLT products. For comparative purpose, the healthy persons of the same age group, who did not consume any SLT products, were selected as referents. The concentrations of Cr in SLT products and biological samples were measured by electrothermal atomic absorption spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked by certified reference materials (CRMs). The resulted data indicated that the adult persons, who consumed different SLT products, have 2–3 fold higher levels of Cr in biological samples as compared to referent subjects (p < 0.01). The persons, who chew/sniff different SLT products, have 50–80 and 42–82 % higher levels of Cr in their scalp hair and blood samples as related to referents. The daily intake of Cr is lower as compared to the recommended value of 50–200 μg/day. It was expected that 10 g consumption of various kinds of SLT products (snuff, mainpuri, and gutkha) may subsidize 21.2–220, 17.7–122, and 18.4–273 % of the recommended daily intake of Cr, respectively.     

NutriTRAILomics in prostate cancer: time to have two strings to one’s bow

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype. The purpose of this review is to significantly inspect results from current research concerning the mechanisms of action of phytonutrients and potential effects on prostate cancer. Substantial emerging data supports the synergistic adiministration of nutraceuticals with TRAIL in prostate cancer progression to circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods for discovery, validation, characterization and standardization of these multicomponent phyto-therapeutics is vital to their recognition into mainstream medicine. The key to interpret a personalized response is a greater comprehension of nutrigenomics, proteomics and metabolomics.     

How could thermal stratification affect horizontal distribution of depth-integrated metazooplankton communities in the Gulf of Gabes (Tunisia)?

The spatial and temporal variability of metazooplankton communities in relation to environmental and trophic factors were studied in the Gulf of Gabes during three periods of increasing thermal stratification in June, July and September. Non-metric multi-dimensional scaling (NMDS) revealed the time and space succession of three zooplankton communities in relation to the degree of thermal stratification. A co-inertia analysis showed the association between these communities and the trophic conditions (abundance and composition of microplankton) driven by stratification. Three divergent communities were evident. The first, characterized by annelid larvae and coastal copepods, was associated with shallow mixed and microplankton-rich water (June, coastal). The second, characterized by euphausiids, amphipods, doliolids and several deep-water copepods, corresponded to highly stratified microplankton-poor water (September). The third, characterized by the most ubiquitous and abundant species, was linked to intermediate water (June deep and July). Temperature and salinity conditions also explained the distribution of key species. Clausocalanus furcatus, Oithona plumifera and Triconia conifera were clearly associated with warm and highly stratified water (September). Enhanced thermal stratification led to higher surface salinity, explaining the emergence of euryhaline taxa such as Oithona plumifera.     

Comparative Study on Chemical Composition of Green and Black Table Olives Brines of the Endemic ′′Sigoise′′ Cultivar: Recovery of high-Added Values Compounds

The effluents derived from the processing of table olives stand for a serious environmental problem. The study aims to valorize the brine water of table olives at different stages of ripening (green and black) of the Algerian variety Sigoise of Bejaia (East) and Mascara (West). The physico-chemical characterization revealed that these samples display have a high acid pH and salinity. The comparative study of phenolic levels exhibited showed very significant differences between the brine waters of green olives from Bejaia and Mascara, while the brines of black olives presented showed comparable levels. A high strong antioxidant potential was confirmed by DPPH (CI₅₀=0.35 μg/100 ml–0.50 μg/100 ml) and FRAP (CI₅₀=626.89 μg/100 ml–875.54 μg/100 ml) tests. Chemical screening by HPLC-DAD of the four samples identified high concentrations of hydroxytyrosol (HT) (390.4 mg/100 ml–360.8 mg/100 ml) and tyrosol (202.2 mg/100 ml–101.4 mg/100 ml). This study provided a deeper insight into the phenolic profile and the antioxidant potential of these brines.