•Optimization of chestnut shells extraction using response surface methodology.•Subcritical water extraction is a clean method for antioxidants extraction.•Optimum extraction conditions: temperature ...220 °C and extraction time 30 min.•Caffeoylquinic acid isomers were the main phenolic compounds.
The objective of this study was to evaluate the optimal Subcritical Water Extraction (SWE) conditions of antioxidants and polyphenols from chestnut shells using Response Surface Methodology (RSM). A central composite design (CCD) was conducted to analyse the time (6–30 min) and temperature (51–249 °C) effects in antioxidant activity (ABTS, DPPH and FRAP) and Total Phenolic Compounds (TPC). TPC ranged from 315.21 to 496.80 mg gallic acid equivalents (GAE)/g DW; the DPPH from 549.23 to 1125.68 mg Trolox equivalents (TE)/g DW; ABTS varied between 631.16 and 965.45 mg ascorbic acid equivalents (AAE)/g DW and FRAP from 2793.95 to 11393.97 mg ferrous sulphate equivalents (FSE)/g DW. The optimal extraction conditions were 30 min/220 °C, revealing excelling scavenging efficiencies against HOCl (IC50 = 0.79 µg/mL) and O2− (IC50 = 12.92 µg/mL) without toxicity on intestinal cells (0.1 µg/mL). The phenolic composition revealed high amounts of pyrogallol and protocatechuic acid. SWE can be a useful extraction technique for the recovery of polyphenolics from chestnut shells.
Chestnut processing industry generates large amounts of by-products, including leaves, burs and shells that are a source of bioactive compounds. The purpose of this study was to establish an ...ultrasound-assisted extraction (UAE) of phenolic and antioxidant compounds from industrial chestnut shells. A central composite design (CCD) was conducted to analyze the effects of time (4-46 min) and temperature (34-76 °C) in the antioxidant activity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP)) and total phenolic compounds (TPC) of chestnut shells extracts. The optimal extraction conditions were obtained at 70 °C for 40 min. The optimal extract was characterized regarding phenolic profile, radical scavenging capacity, and effects on intestinal and dermal cell lines. The optimal extract revealed high amounts of ellagic acid (40.4 µg/mg dw), followed by caffeic acid derivative (15.4 µg/mg dw) and epigallocatechin (15.3 µg/mg dw). Indeed, the extract exhibited the highest scavenging efficiencies against NO● (IC
= 0.1 µg/mL) and HOCl (IC
= 0.7 µg/mL) and did not conducted to a decrease on HaCaT and HFF-1 viability up to 100 μg/mL. Oppositely, a decrease on Caco-2 and HT29-MTX viability was observed. This study suggests that UAE could be a sustainable option to valorize chestnut shells as raw material for different industries.
Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The ...biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.
Halloysite nanotubes (HNTs) were functionalized with several organosilanes with different functional groups, by a post-grafting methodology, in aprotic and anhydrous conditions: ...3-aminopropyltriethoxysilane (APTES), N-2-aminoethyl-3-aminopropyltrimethoxysilane (AEAPTMS), (3-mercaptopropyl)trimethoxysilane (MPTMS), (3-bromopropyl)-trimethoxysilane (BrTMS), vinyltrimethoxysilane (VTMS) and phenyltriethoxysilane (PhTES).
The pristine and silylated clay minerals were characterized by transmission and scanning electron microscopy, energy-dispersive X-ray spectroscopy, powder X-ray diffraction, nitrogen adsorption-desorption isotherms at −196 °C, bulk elemental analysis, X-ray photoelectron spectroscopy, thermogravimetry, Fourier transform infrared spectroscopy-attenuated total reflectance and 13C, 29Si and 27Al solid-state nuclear magnetic resonance.
The techniques identified pristine HNTs as halloysite-7Å (dehydrated form) and proved their successful silylation without the disruption of the nanotubes structure. The silylated HNTs showed bulk Si and C contents up to 7.30 and 1.92 mmol/g, respectively, with the APTES functionalized material containing the highest bulk and surface Si and C loadings, confirming its highest silylation efficiency. Some insights into the silylation reaction and mechanism were also provided by the techniques used. Combination of 29Si and 27Al MAS NMR and XRD data suggested that silylation reaction occurred at Al–OH groups from the inner lumen surface, as well as the Al–OH and Si–OH groups at the edges or external surface defects; no evidence was found for the existence of functionalization in the interlayer Al–OH groups. The silylation mechanism was found to proceed through reaction of the alkoxy moieties from the organosilane with the referred surface groups from the HNTs in a 3-fold (for VTMS and BrTMS), or 2-fold covalent grafting (for MPTMS) or a mixture of both approaches (for APTES, AEAPTMS and PhTES); in the case of APTES- and AEAPTMS-functionalized HNTs, a polymerization side-reaction was also evidenced, as a parallel functionalization pathway.
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•Halloysite nanotubes (HNTs) were silylated successfully with several organosilanes.•The silylation mechanism proceeded through reaction of alkoxy moieties from organosilane.•Aminopropyltrimethoxysilane grafted into HNTs with the highest efficiency.•Aminosilanes showed polymerisation side-reaction via NH2-silicon oligomerization as a parallel functionalisation pathway.
Wine production generates large amounts of vine-canes, a devalued by-product that could be used for the recovery of bioactive compounds. In this work, two vine-canes varieties, namely Touriga ...Nacional (TN) and Tinta Roriz (TR), were submitted to different ultrasound-assisted extraction (UAE) conditions. The highest phenolic and flavonoid content was observed for TR extract obtained at lab-scale without an ice bath and pilot-scale after 60 min of extraction (32.6 ± 2.1 and 26.0 ± 1.5 mg gallic acid equivalent/g dry weight (dw) and 9.5 ± 0.6 and 8.3 ± 0.8 mg epicatechin equivalents/g dw, respectively). Further, all extracts demonstrated a high antioxidant activity to scavenge DPPH free radicals with the best value reached by TR at the lab-scale without an ice bath after 30 min and pilot-scale extraction after 60 min (34.2 ± 2.4 and 33.4 ± 2.1 mg trolox equivalents/g dw, respectively). Extracts phenolic composition were also evaluated by HPLC, demonstrating that resveratrol, myricetin and catechin were the main compounds. According to our knowledge, this is the first time that a pilot scale of UAE of phenolic compounds from vine-canes was performed. This paper represents an important step to the use of UAE as an industrial process to recover bioactive compounds.
Pd(II) and Pt(II) composites with activated carbon (AC), graphene oxide, and multiwalled carbon nanotubes were prepared by ball milling and used as catalysts for the Suzuki-Miyaura reaction, under ...several energy inputs (mechanical grinding, conventional heating, and microwave irradiation). The catalytic composites were characterized by ICP-MS, BET, XPS analyses, TEM, and SEM. The average particle size of the prepared composites was estimated to be in the range of 6-30 nm, while the loadings of Pd and Pt did not significantly affect the surface area of the AC support due to the tendency to agglomerate as observed by the TEM analysis. The Pd/AC composites exhibit high mechanochemical catalytic activity in cross-coupling of bromobenzene and phenylboronic acid with molar yields up to 80% with TON and TOF of 222 and 444 h
, respectively, achieved with Pd(4.7 wt%)-AC catalyst under the liquid assisted grinding for 0.5 h at ambient conditions, using cyclohexene as an additive.
This work focused on evaluating the possibility of using vineyard pruning wastes from two Portuguese Vitis vinifera varieties; Touriga Nacional (TN) and Tinta Roriz (TR), as new potential ingredients ...for the nutraceutical industry. An environmentally friendly extraction technique; namely subcritical-water extraction (SWE), was employed. The overall results indicate that phenolic acids were the major class of compounds quantified; being gallic acid the principal one. The highest value for total phenolic content (TPC) was obtained for the TR extract at 250 °C (181 ± 12 mg GAE/g dw). In terms of antioxidant activity; the DPPH values for the extracts obtained at 250 °C were approximately 4-fold higher than the ones obtained at 125 °C; with TR extract presenting the highest value (203 ± 22 mg TE/g dw). Thus, the TR extract obtained through SWE at 250 °C was selected to evaluate the scavenging activity and the in vitro effects on cells due to the best results achieved in the previous assays. This extract presented the ability to scavenge reactive oxygen species (O2●-, HOCl and ROO●). No adverse effects were observed in HFF-1 viability after exposure to extract concentrations below 100 μg/mL. This work demonstrated that vine-canes extracts could be a potential ingredient to nutraceutical industry
Organosulfonic acid functionalized montemorillonite-MMT (K10 and cloisite Na+) were prepared by different methodologies: (a) one-pot organosilylation or sulfonation, and (b) two-step organosilylation ...followed by sulfonation or oxidation. The physicochemical characterization ensured the success of the selected methodologies to promote HSO3-functionalization including high S contents (2.84 mmol S/g) and acidities up to 6.03 mmol H+/g (K10_PhSO3H).
All the organosulfonic acid functionalized MMT were tested as acid catalyst in the esterification of free fatty acids in a hybrid feedstock model. Conversions of 100% were obtained after 60 min for K10_PhTESO3H, K10_SO3H, Cloi_PhTESO3H and Cloi_H2SO4, in accordance with the acid character of these catalysts, prepared by one-pot and two-step methodologies involving a sulfonation step. The MMT catalysts obtained by direct sulfonation exhibited the highest TOF whereas those obtained by two-step organosilylation-sulfonation showed the highest stability and reusability. The increase of FFA carbon chain length led to higher conversions, showing the prevalence of inductive effect and absence of steric effects on the esterification mechanism using these organosulfonic acid functionalized catalysts. Moreover, K10-PhSO3H was applied as solid acid catalyst in a simultaneous (trans) esterification of different feedstock types for biodiesel production giving up to 100% of FAMEs under moderate conditions.
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•Sulfonic-acid montmorillonites prepared by one-pot and two-step methodologies.•Efficient catalysts for esterification of hybrid feedstocks to biodiesel.•K10_PhSO3H catalyst allows trans (esterification), giving 100% of FAMEs.
Digestive tract tumors are among the most common and deadliest malignancies worldwide, mainly due to late diagnosis and lack of efficient therapeutics. Current treatments essentially rely on surgery ...associated with (neo)adjuvant chemotherapy agents. Despite an upfront response, conventional drugs often fail to eliminate highly aggressive clones endowed with chemoresistant properties, which are responsible for tumor recurrence and disease dissemination. Synthetic drugs also present severe adverse systemic effects, hampering the administration of biologically effective dosages. Nanoencapsulation of chemotherapeutic agents within biocompatible polymeric or lipid matrices holds great potential to improve the pharmacokinetics and efficacy of conventional chemotherapy while reducing systemic toxicity. Tagging nanoparticle surfaces with specific ligands for cancer cells, namely monoclonal antibodies or antibody fragments, has provided means to target more aggressive clones, further improving the selectivity and efficacy of nanodelivery vehicles. In fact, over the past twenty years, significant research has translated into a wide array of guided nanoparticles, providing the molecular background for a new generation of intelligent and more effective anti-cancer agents. Attempting to bring awareness among the medical community to emerging targeted nanopharmaceuticals and foster advances in the field, we have conducted a systematic review about this matter. Emphasis was set on ongoing preclinical and clinical trials for liver, colorectal, gastric and pancreatic cancers. To the best of our knowledge this is the first systematic and integrated overview on this field. Using a specific query, 433 abstracts were gathered and narrowed to 47 manuscripts when matched against inclusion/exclusion criteria. All studies showed that active targeting improves the effectiveness of the nanodrugs alone, while lowering its side effects. The main focus has been on hepatocarcinomas, mainly by exploring glycans as homing molecules. Other ligands such as peptides/small proteins and antibodies/antibody fragments, with affinity to either tumor vasculature or tumor cells, have also been widely and successfully applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few solutions have been presented for pancreatic tumors. To this date only three nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine-functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid tumors; and iii) MBP-426, a transferrin–liposome–oxaliplatin conjugate, also for advanced stage tumors. Still, none has been approved for clinical use. However, based on the high amount of pre-clinical studies showing enthusiastic results, the number of clinical trials is expected to increase in the near future. A more profound understanding about the molecular nature of chemoresistant clones and cancer stem cell biology will also contribute to boost the field of guided nanopharmacology towards more effective solutions.
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Rivastigmine is a drug commonly used in the management of Alzheimer's disease that shows bioavailability problems. To overcome this, the use of nanosystems, such as nanostructured lipid carriers ...(NLC), administered through alternative routes seems promising. In this work, we performed a double optimization of a rivastigmine-loaded NLC formulation for direct drug delivery from the nose to the brain using the quality by design (QbD) approach, whereby the quality target product profile (QTPP) was the requisite for nose to brain delivery. The experiments started with the optimization of the formulation variables (or critical material attributes-CMAs) using a central composite design. The rivastigmine-loaded NLC formulations with the best critical quality attributes (CQAs) of particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were selected for the second optimization, which was related to the production methods (ultrasound technique and high-pressure homogenization). The most suitable instrumental parameters for the production of NLC were analyzed through a Box-Behnken design, with the same CQAs being evaluated for the first optimization. For the second part of the optimization studies, were selected two rivastigmine-loaded NLC formulations: one produced by ultrasound technique and the other by the high-pressure homogenization (HPH) method. Afterwards, the pH and osmolarity of these formulations were adjusted to the physiological nasal mucosa values and in vitro drug release studies were performed. The results of the first part of the optimization showed that the most adequate ratios of lipids and surfactants were 7.49:1.94 and 4.5:0.5 (%,
/
), respectively. From the second part of the optimization, the results for the particle size, PDI, ZP, and EE of the rivastigmine-loaded NLC formulations produced by ultrasound technique and HPH method were, respectively, 114.0 ± 1.9 nm and 109.0 ± 0.9 nm; 0.221 ± 0.003 and 0.196 ± 0.007; -30.6 ± 0.3 mV and -30.5 ± 0.3 mV; 97.0 ± 0.5% and 97.2 ± 0.3%. Herein, the HPH was selected as the most suitable production method, although the ultrasound technique has also shown effectiveness. In addition, no significant changes in CQAs were observed after 90 days of storage of the formulations at different temperatures. In vitro studies showed that the release of rivastigmine followed a non-Fickian mechanism, with an initial fast drug release followed by a prolonged release over 48 h. This study has optimized a rivastigmine-loaded NLC formulation produced by the HPH method for nose-to-brain delivery of rivastigmine. The next step is for in vitro and in vivo experiments to demonstrate preclinical efficacy and safety. QbD was demonstrated to be a useful approach for the optimization of NLC formulations for which specific physicochemical requisites can be identified.
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