Thermo-treatment affects Quercus cerris L. wood properties and the antioxidant activity and chemical composition of its by-product extracts

Nowadays, there is an increasing interest on thermo-treatment and its effects on wood structure and extraction processes, connected to the wood use for industrial application and for its use as biorefinery. The present investigation aimed to provide the main changes on wood properties (mass loss, color variation and modulus of elasticity) and a comparative analysis of the antioxidant properties and GC–MS profile of the extracts from Turkey oak (Quercus cerris L.) wood. Untreated and thermo-treated wood (170 °C x 3 h) samples were compared. Thermo-treatment induced a mass loss (5.1%) in wood, a darkening of color surface (ΔE = 7.6) and a decrease of MOE (4.1%). Moreover samples were extracted using different techniques: maceration (ME), ultrasound assisted extraction (UAE) and accelerated solvent extraction (ASE). Extracts were tested to evaluate the content of polyphenols and flavonoids along with the in vitro antioxidant activity. Results showed that extracts obtained from thermo-treated wood reported the highest Relative Antioxidant Capacity Index and extraction techniques affected the value in the following rating: UAE > ME > ASE. Qualitative and quantitative measurements of chemical compounds were carried out by GC–MS system. Taking into account the thermo-treatment and extraction techniques, principal component analysis (PCA) was performed also in order to evaluate the relationships among principal chemical compounds. According to results obtained, thermo-treatment and extraction technique had a determinant role in the antioxidant efficiency and, consequently, on the potential application of extracts

MTOR cross-talk in cancer and potential for combination therapy

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer. Single-agent mTOR targeting, mostly using rapalogs, has so far met limited clinical success; however, due to the extensive cross-talk between mTOR and other pathways, combined approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance. This review provides a brief and up-to-date narrative on the regulation of mTOR function, the relative contributions of mTORC1 and mTORC2 complexes to cancer development and progression, and prospects for mTOR inhibition as a therapeutic strategy

Biological activities of alkaloids: From toxicology to pharmacology

Plants produce many secondary metabolites, which reveal biological activity [...]

Role of mTOR signaling in tumor microenvironment. An overview

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS). CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation

Focus on Olea europaea L. pruning by-products: extraction techniques, biological activity, and phytochemical profile

The Olea europaea L. tree has played a central role in Mediterranean culture since ancient times. Several studies have highlighted the health-promoting properties both of its primary products (olives) and its by-products (leaves, pomace, husk, stone, mill wastes, and wood). In this study, pruning residues from 25-year-old olive trees located in a Mediterranean region (Basilicata, Italy) were analyzed. The antioxidant activity of hydro-alcoholic extracts from wood samples were analyzed through three complementary in vitro assays. The molecular composition of the extracts was thoroughly evaluated using a gas chromatography apparatus coupled with a mass spectrometer (GC–MS). Our study demonstrated that all but three extracts had remarkable antioxidant activity, which was likely due to the meaningful presence of phenolic compounds, mostly derived from lignin. Moreover, the results showed that bark extracts obtained with ultrasound-assisted extraction (UAE) had the highest antioxidant activity. In this extract, several known compounds with demonstrated antioxidant activity were found, including hexylresorcinol, 1-methyl-N-vanillyl-2-phenethamine, and allopurinol. This research suggests that woody olive by-products are a potential natural resource of antioxidants. These compounds could be useful for functional foods and in industry, and could help to solve the problem of pruning residues, increasing their potential economic valu

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity

Phytochemicals of minthostachys diffusa epling and their health-promoting bioactivities

The genus Minthostachys belonging to the Lamiaceae family, and is an important South American mint genus used commonly in folk medicine as an aroma in cooking. The phytochemical-rich samples of the aerial parts of Minthostachys diffusa Epling. were tested for pharmacological and health-promoting bioactivities using in vitro chemical and enzymatic assays. A range of radical scavenging activities of the samples against biological radicals such as nitric oxide and superoxide anion and against synthetic 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, the ferric reducing antioxidant power and the lipid peroxidation inhibition were determined and ranked using the 'relative antioxidant capacity index' (RACI). The ethyl acetate fraction showed the highest RACI of +1.12. Analysis of the various fractions' inhibitory ability against enzymes involved in diabetes (α-amylase and α-glucosidase), and against enzymes associated with Parkinson's or Alzheimer's diseases (acetylcholinesterase and butyrylcholinesterase) also suggested that the ethyl acetate fraction was the most active. Liquid chromatography-tandem mass spectrometry analysis of the ethyl acetate fraction showed more than 30 polyphenolic compounds, including triterpenes. The inhibitory cholinesterase effects of the triterpenes identified from M. diffusa were further analysed by in silico docking of these compounds into 3D-structures of acetylcholinesterase and butyrylcholinesterase. This is the first study on pharmacological activities and phytochemical profiling of the aerial parts of M. diffusa, showing that this plant, normally used as food in South America, is also rich in health-promoting phytochemicals

Identification and antimicrobial activity of most representative secondary metabolites from different plant species

Abstract Background The plant kingdom constitutes an enormous reservoir of bioactive molecules, generally used by plants to prevent or to protect themselves from pathogens' attacks. To date, several primary or secondary plant metabolites have been already proven to exert antibiotic activities; nonetheless, researchers are still continuing to lavish great efforts to identify and characterize new natural molecules one by one. Aiming at the replacement of synthetic chemical products, the bioactivity of plant extracts should be assessed case by case, and active substances should be tested as individuals to obtain accurate information on the real usefulness of plant metabolites. In this work major glycoalkaloids obtained from Solanum nigrum, glucosinolates from Armoracia rusticana, and cannabinoids from Cannabis sativa were identified. The antimicrobial activity of crude extracts and pure components against Gram+ (Bacillus cereus (A1I), Bacillus thuringiensis (B7I2), and Bacillus amyloliquefaciens (A5TI)) and Gram− bacteria (Pseudomonas orientalis (A14-1II), and Stenotrophomonas maltophilia (B9TIII)), employed as model organisms, was tested. Result Major glycoalkaloids, glucosinolates, and cannabinoids were identified in crude plants' extracts using high-resolution LC–ESI-FTICR/MS. From antimicrobial assays useful information towards a few of biological activities of crude extracts and individual components were obtained. Solanum nigrum extracts revealed inhibition activity on all bacteria tested as well as the main active glycoalkaloids, solamargine and solasonine, which were found to be active even when tested individually. At assayed concentrations, A. rusticana extract was active towards a few of the microorganisms tested, confirming that the activity of glucosinolates can be referred only partially to the mother molecules, while biological efficiency of such kind of compounds is mainly due to their enzymatic breaking off, where myrosinase converts them into isothiocyanates and/or thiocyanates. Hemp-type C. sativa extract showed antimicrobial activity only against Gram+ bacteria, but the main individual components tested showed always a limited bioactivity. Conclusion Promising results were obtained, but tests performed in vitro are only the first step of a wider investigation as required for an extensive application. Further research efforts are necessary to demonstrate the efficiency of natural substances in different target environments